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V4:E07:S05 - Exploring Emerging Therapies:

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Stem Cells and Self-Mastery

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tell me about stem cell photo-therapy patches and efficacy for seniors

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{"items":[{"paper_title":"Chitosan/silk fibroin modified nanofibrous patches with mesenchymal stem cells prevent heart remodeling post-myocardial infarction in rats.","abstract":"Poor functional survival of the engrafted stem cells limits the therapeutic efficacy of stem-cell-based therapy for myocardial infarction (MI). Cardiac patch-based system for cardiac repair has emerged as a potential regenerative strategy for MI. This study aimed to design a cardiac patch to improve the retention of the engrafted stem cells and provide mechanical scaffold for preventing the ventricular remodeling post-MI. The patches were fabricated with electrospinning cellulose nanofibers modified with chitosan/silk fibroin (CS/SF) multilayers via layer-by-layer (LBL) coating technology. The patches engineered with adipose tissue-derived mesenchymal stem cells (AD-MSCs) (cell nano-patch) were adhered to the epicardium of the infarcted region in rat hearts. Bioluminescence imaging (BLI) revealed higher cell viability in the cell nano-patch group compared with the intra-myocardial injection group. Echocardiography demonstrated less ventricular remodeling in cell nano-patch group, with a decrease in the left ventricular end-diastolic volume and left ventricular end-systolic volume compared with the control group. Additionally, left ventricular ejection fraction and fractional shortening were elevated after cell nano-patch treatment compared with the control group. Histopathological staining demonstrated that cardiac fibrosis and apoptosis were attenuated, while local neovascularization was promoted in the cell nano-patch group. Western blot analysis illustrated that the expression of biomarkers for myocardial fibrosis (TGF-β1, P-smad3 and Smad3) and ventricular remodeling (BNP, β-MHC: α-MHC ratio) were decreased in cell nano patch-treated hearts. This study suggests that CS/SF-modified nanofibrous patches promote the functional survival of engrafted AD-MSCs and restrain ventricular remodeling post-MI through attenuating myocardial fibrosis. STATEMENT OF SIGNIFICANCE: First, the nanofibrous patches fabricated from the electrospun cellulose nanofibers could mimic the natural extracellular matrix (ECM) of hearts to improve the microenvironment post-MI and provide three dimensional (3D) scaffolds for the engrafted AD-MSCs. Second, CS and SF which have exhibited excellent properties in previous tissue engineering research, such as nontoxicity, biodegradability, anti-inflammatory, strong hydrophilic nature, high cohesive strength, and intrinsic antibacterial properties further optimized the biocompatibility of the nanofibrous patches via LBL modification. Finally, the study revealed that beneficial microenvironment and biomimetic ECM improve the retention and viability of the engrafted AD-MSCs and the mechanical action of the cell nano-patches for the expanding ventricular post-MI leads to suppression of HF progression by inhibition of ventricular remodeling.","paper_authors":["Jiangwei Chen","Yingfei Zhan","Yabin Wang","Dong Han","B. Tao","Zhenli Luo","Sai Ma","Qun Wang","Xiang Li","Li Fan","Congye Li","Hongbing Deng","F. Cao"],"paper_publish_year":2018,"publication_journal_name":"Acta biomaterialia","consensus_paper_details_url":"https://consensus.app/papers/chitosansilk-fibroin-modified-patches-stem-cells-heart-chen/62bcee2ea84151b6ab3098e205fc65cb/?utm_source=chatgpt","doi":"10.1016/j.actbio.2018.09.013","volume":"80","pages":"\n 154-168\n ","search_result_number":1},{"paper_title":"Effective delivery of stem cells using an extracellular matrix patch results in increased cell survival and proliferation and reduced scarring in skin wound healing.","abstract":"Wound healing is one of the most complex biological processes and occurs in all tissues and organs of the body. In humans, fibrotic tissue, or scar, hinders function and is aesthetically unappealing. Stem cell therapy offers a promising new technique for aiding in wound healing; however, current findings show that stem cells typically die and/or migrate from the wound site, greatly decreasing efficacy of the treatment. Here, we demonstrate effectiveness of a stem cell therapy for improving wound healing in the skin and reducing scarring by introducing stem cells using a natural patch material. Adipose-derived stromal cells were introduced to excisional wounds created in mice using a nonimmunogenic extracellular matrix (ECM) patch material derived from porcine small-intestine submucosa (SIS). The SIS served as an attractive delivery vehicle because of its natural ECM components, including its collagen fiber network, providing the stem cells with a familiar structure. Experimental groups consisted of wounds with stem cell-seeded patches removed at different time points after wounding to determine an optimal treatment protocol. Stem cells delivered alone to skin wounds did not survive post-transplantation as evidenced by bioluminescence in vivo imaging. In contrast, delivery with the patch enabled a significant increase in stem cell proliferation and survival. Wound healing rates were moderately improved by treatment with stem cells on the patch; however, areas of fibrosis, indicating scarring, were significantly reduced in wounds treated with the stem cells on the patch compared to untreated wounds.","paper_authors":["Mai T. Lam","A. Nauta","Nathaniel P. Meyer","Joseph C. Wu","M. Longaker"],"paper_publish_year":2013,"publication_journal_name":"Tissue engineering. Part A","consensus_paper_details_url":"https://consensus.app/papers/delivery-stem-cells-using-matrix-patch-results-increased-lam/c07da9401062590c9fd4e031dee6a304/?utm_source=chatgpt","doi":"10.1089/ten.TEA.2012.0480","volume":"19 5-6","pages":"\n 738-47\n ","search_result_number":2},{"paper_title":"3D printed complex tissue construct using stem cell-laden decellularized extracellular matrix bioinks for cardiac repair.","abstract":"Stem cell therapy is a promising therapeutic method for the treatment of ischemic heart diseases; however, some challenges prohibit the efficacy after cell delivery due to hostile microenvironment of the injured myocardium. 3D printed pre-vascularized stem cell patch can enhance the therapeutic efficacy for cardiac repair through promotion of rapid vascularization after patch transplantation. In this study, stem cell-laden decellularized extracellular matrix bioinks are used in 3D printing of pre-vascularized and functional multi-material structures. The printed structure composed of spatial patterning of dual stem cells improves cell-to-cell interactions and differentiation capability and promotes functionality for tissue regeneration. The developed stem cell patch promoted strong vascularization and tissue matrix formation in vivo. The patterned patch exhibited enhanced cardiac functions, reduced cardiac hypertrophy and fibrosis, increased migration from patch to the infarct area, neo-muscle and capillary formation along with improvements in cardiac functions. Therefore, pre-vascularized stem cell patch provides cardiac niche-like microenvironment, resulting in beneficial effects on cardiac repair.","paper_authors":["Jinah Jang","H. Park","Seok-Won Kim","Hee-Young Kim","J. Y. Park","S. J. Na","Hyeon Ji Kim","M. Park","Seung Hyun Choi","S. H. Park","Sung Won Kim","S-M Kwon","P. Kim","D. Cho"],"paper_publish_year":2017,"publication_journal_name":"Biomaterials","consensus_paper_details_url":"https://consensus.app/papers/printed-tissue-construct-using-stem-decellularized-jang/2bc6d5b1feec5a9d8896f995e1f6fbec/?utm_source=chatgpt","doi":"10.1016/j.biomaterials.2016.10.026","volume":"112","pages":"\n 264-274\n ","search_result_number":3},{"paper_title":"Efficacy and safety of a patch containing adipose-derived stem cells for skin wound healing – results form a comprehensive pre-clinical evaluation program","abstract":"Mesenchymal stem cell-based therapies are emerging as innovative approaches to treat chronic wounds. A common administration route used in clinical trials consists of local injections leading to uncontrolled/sub-optimal delivery. This study reports a comprehensive pre-clinical evaluation program on the mechanism of action, efficacy and safety of an easy-to-use patch that concentrates Adipose-derived Stem Cells (ASCs) in a clinical-grade sponge of porcine crosslinked-gelatin. ASCs were prepared from the fat of ischemic patients. Transcriptome and proteome of ASC-patches and ASC monolayers were assessed by microarrays, bio-arrays and mass spectrometry. Tumorigenesis was investigated in immunosuppressed mice according to the European Pharmacopeia. Angiogenesis was assessed in vivo in the chick chorioallantoic membrane model. Efficacy of the ASC-patch was tested in a rat model of ischemic full-thickness skin defect. Cell stability was assessed by luminescence using ASC-patches generated from ASCs stably transduced with firefly luciferase. ASCs from ischemic patients upregulated the transcription of multiple genes involved in skin wound healing when cultured within the ASC-patch formulation. The patch was not only a concentrator, but also a reservoir of both ASC-derived regenerative factors and sponge-derived soluble fragments having healing capacity. The secretome of the ASC-patch promoted dermal fibroblast survival and epidermal epithelialization. No tumor formation was observed in immunodeficient Nude mice subcutaneously transplanted with the ASC-patch. Transplanted patches were early invaded by new vessels in vivo, and a marked angiogenesis was confirmed in two independent animal models. Finally, ASC-patches prepared from syngeneic rats promoted faster healing and re-vascularization of full-thickness skin defects in a rat animal model. Of note, ASCs were viable and locally stable for at least two weeks in vivo. We provide here compelling pre-clinical evidence that patches concentrating ASCs within crosslinked gelatin may represent a convenient and effective tool for the management of chronic wounds.","paper_authors":["N. Brembilla","A. Modarressi","Dominik André-Lévigne","E. Brioudes","Florian Lanza","H. Vuagnat","S. Durual","L. Marger","W. Boehncke","K. Krause","O. Preynat-Seauve"],"paper_publish_year":2022,"publication_journal_name":"bioRxiv","consensus_paper_details_url":"https://consensus.app/papers/efficacy-safety-patch-containing-stem-cells-skin-wound-brembilla/f243c0735fdc5821a361420773d9ceab/?utm_source=chatgpt","doi":"10.1101/2022.03.09.483580","volume":"","pages":"","search_result_number":4},{"paper_title":"3D Printed Stem-Cell-Laden, Microchanneled Hydrogel Patch for the Enhanced Release of Cell-Secreting Factors and Treatment of Myocardial Infarctions.","abstract":"Over the past several years, biomaterials loaded with mesenchymal stem cells (MSCs) have increasingly been used to reduce the myocardial fate of postinfarction collagen deposition and scar tissue formation. Despite successful gains, therapeutic efficacy has remained limited because of restricted transport of cell-secreting factors at the site of implantation. We hypothesized that an MSC-laden hydrogel patch with multiple microchannels would retain transplanted cells on target tissue and support transport of cell-secreting factors into tissue. By doing so, the gel patch will improve the therapeutic potential of the cells and minimize the degradation of myocardial tissue postinfarction. To examine this hypothesis, a stereolithographic apparatus (SLA) was used to introduce microchannels of controlled diameters (e.g., 500 and 1000 μm) during in situ cross-linking reaction of poly(ethylene glycol)dimethacrylate solution suspended with cells. Placement of the MSC-laden, microchanneled gel patch on the occluded left coronary artery in a murine model showed significant improvement in the ejection fraction, fractional shortening, and stroke volume, compared with gel patches without MSCs and MSC-laden gel patches without microchannels. In particular, the microchannels significantly reduced the number of cells required to recover cardiac function, while minimizing cardiac remodeling. In sum, the microchanneled gel patch would provide a means to prevent abnormal fibrosis resulting from acute ischemic injury.","paper_authors":["Molly R. Melhem","JooYeon Park","Luke Knapp","Larissa Reinkensmeyer","Caroline Cvetkovic","Jordan Flewellyn","Min Kyung Lee","Tor W. Jensen","R. Bashir","H. Kong","L. Schook"],"paper_publish_year":2017,"publication_journal_name":"ACS biomaterials science & engineering","consensus_paper_details_url":"https://consensus.app/papers/printed-stemcellladen-microchanneled-hydrogel-patch-melhem/637e72040fc253ed841390d898f53fdb/?utm_source=chatgpt","doi":"10.1021/ACSBIOMATERIALS.6B00176","volume":"3 9","pages":"\n 1980-1987\n ","search_result_number":5},{"paper_title":"Multiscale patterned transplantable stem cell patches for bone tissue regeneration.","abstract":"Stem cell-based therapy has been proposed as an enabling alternative not only for the treatment of diseases but also for the regeneration of tissues beyond complex surgical treatments or tissue transplantation. In this study, we approached a conceptual platform that can integrate stem cells into a multiscale patterned substrate for bone regeneration. Inspired by human bone tissue, we developed hierarchically micro- and nanopatterned transplantable patches as synthetic extracellular matrices by employing capillary force lithography in combination with a surface micro-wrinkling method using a poly(lactic-co-glycolic acid) (PLGA) polymer. The multiscale patterned PLGA patches were highly flexible and showed higher tissue adhesion to the underlying tissue than did the single nanopatterned patches. In response to the anisotropically multiscale patterned topography, the adhesion and differentiation of human mesenchymal stem cells (hMSCs) were sensitively controlled. Furthermore, the stem cell patch composed of hMSCs and transplantable PLGA substrate promoted bone regeneration in vivo when both the micro- and nanotopography of the substrate surfaces were synergistically combined. Thus, our study concludes that multiscale patterned transplantable stem cell patches may have a great potential for bone regeneration as well as for various regenerative medicine approaches.","paper_authors":["Jangho Kim","W. Bae","H. Choung","K. Lim","Hoon Seonwoo","H. Jeong","K. Suh","N. Jeon","P. Choung","J. Chung"],"paper_publish_year":2014,"publication_journal_name":"Biomaterials","consensus_paper_details_url":"https://consensus.app/papers/multiscale-patterned-stem-cell-patches-bone-tissue-kim/25b99c090e4654cc9f267e78a636fb55/?utm_source=chatgpt","doi":"10.1016/j.biomaterials.2014.07.036","volume":"35 33","pages":"\n 9058-67\n ","search_result_number":6},{"paper_title":"High-dose melphalan (200 mg/m2) supported by autologous stem cell transplantation is safe and effective in elderly (⩾65 years) myeloma patients: comparison with younger patients treated on the same protocol","abstract":"Limited information is available on the feasibility and efficacy of autologous stem cell transplantation (ASCT) in multiple myeloma (MM) patients >65 years of age. In 1995–2005, 22 myeloma patients ⩾65 years (median 68, eight ⩾70) and 79 patients <65 years (median 57) were included in an identical treatment protocol. The first progenitor cell mobilization with cyclophosphamide plus granulocyte-colony stimulating factor (G-CSF) was successful in 95 and 96% of the patients, respectively. To date, 92 patients have received MEL (melphalan) 200 mg/m2 supported by ASCT. No early treatment-related deaths were observed among 22 elderly patients, whereas one younger patient died early. Engraftment and the need for supportive care were comparable between groups. The elderly patients tended to have more WHO grade 3–4 oral or gastrointestinal toxicity when compared to the younger patients (45 vs 23%, P=0.06). After ASCT, a complete response was observed in 44% of the elderly patients and 36% of the younger patients, respectively. No difference was observed between these age groups in progression-free survival (23 vs 21 months) or overall survival (57 vs 66 months) after ASCT. We conclude that MEL200 is a safe and efficacious treatment in selected elderly myeloma patients.","paper_authors":["Esa Jantunen","T. Kuittinen","K. Penttilä","Päivi Lehtonen","E. Mahlamäki","T. Nousiainen"],"paper_publish_year":2006,"publication_journal_name":"Bone Marrow Transplantation","consensus_paper_details_url":"https://consensus.app/papers/highdose-melphalan-mgm2-supported-stem-cell-jantunen/b09eb0edbc085d4f8095846886c1243f/?utm_source=chatgpt","doi":"10.1038/sj.bmt.1705360","volume":"37","pages":"917-922","search_result_number":7},{"paper_title":"Autologous stem cell transplantation beyond 60 years of age","abstract":"Along with improved supportive care and thus reduced treatment-related mortality, an increasing number of elderly patients (>60 years) with haematological malignancies are now considered for high-dose therapy (HDT) supported by autologous stem cell transplantation (ASCT). ASCT is feasible in selected elderly patients with multiple myeloma and those with non-Hodgkin's lymphoma. As elderly patients have generally been excluded from randomized studies evaluating efficacy of ASCT in comparison with non-transplant approaches, limited data are available on the efficacy of ASCT in this patient population. Recent developments in supportive care including amifostine and palifermin may increase feasibility of ASCT in elderly patients. Prospective studies are needed to evaluate feasibility and efficacy of ASCT in patients over 60 years of age. Also, further studies are needed in order to decrease toxicity of high-dose regimens in this patient group where co-morbid conditions may modify the toxicity of HDT in a clinically significant manner.","paper_authors":["Esa Jantunen"],"paper_publish_year":2006,"publication_journal_name":"Bone Marrow Transplantation","consensus_paper_details_url":"https://consensus.app/papers/stem-cell-transplantation-beyond-years-jantunen/ec541f91d15c577c8a3afcf85e3cd8e5/?utm_source=chatgpt","doi":"10.1038/sj.bmt.1705514","volume":"38","pages":"715-720","search_result_number":8},{"paper_title":"Cardiac Stem Cell Patch Integrated with Microengineered Blood Vessels Promotes Cardiomyocyte Proliferation and Neovascularization after Acute Myocardial Infarction.","abstract":"Cardiac stem cell (CSC) therapy has shown preclinical and clinical evidence for ischemic heart repair but is limited by low cellular engraftment and survival after transplantation. Previous versions of the cardiac patch strategy improve stem cell engraftment and encourage repair of cardiac tissue. However, cardiac patches that can enhance cardiomyogenesis and angiogenesis at the injured site remain elusive. Therapies that target cardiomyocyte proliferation and new blood vessel formation hold great potential for the protection against acute myocardial infarction (MI). Here, we report a new strategy for creating a vascularized cardiac patch in a facile and modular fashion by leveraging microfluidic hydrodynamic focusing to construct the biomimetic microvessels (BMVs) that include human umbilical vein endothelial cells (HUVECs) lining the luminal surface and then encapsulating the BMVs in a fibrin gel spiked with human CSCs. We show that the endothelialized BMVs mimicked the natural architecture and function of capillaries and that the resultant vascularized cardiac patch (BMV-CSC patch) exhibited equivalent release of paracrine factors compared to those of coculture of genuine human CSCs and HUVECs after 7 days of in vitro culture. In a rat model of acute MI, the BMV-CSC patch therapy induced profound mitotic activities of cardiomyocytes in the peri-infarct region 4 weeks post-treatment. A significant increase in myocardial capillary density was noted in the infarcted hearts that received BMV-CSC patch treatment compared to the infarcted hearts treated with conventional CSC patches. The striking therapeutic benefits and the fast and facile fabrication of the BMV-CSC patch make it promising for practical applications. Our findings suggest that the BMV-CSC patch strategy may open up new possibilities for the treatment of ischemic heart injury.","paper_authors":["Teng Su","Ke Huang","M. Daniele","M. T. Hensley","Ashlyn T. Young","Junnan Tang","Tyler A. Allen","A. Vandergriff","Patrick D. Erb","F. Ligler","K. Cheng"],"paper_publish_year":2018,"publication_journal_name":"ACS applied materials & interfaces","consensus_paper_details_url":"https://consensus.app/papers/stem-cell-patch-integrated-microengineered-blood-vessels-su/ee76862501d35036b851dc287dbae282/?utm_source=chatgpt","doi":"10.1021/acsami.8b13571","volume":"10 39","pages":"\n 33088-33096\n ","search_result_number":9},{"paper_title":"Favorable outcomes in elderly patients undergoing high-dose therapy and autologous stem cell transplantation for non-Hodgkin lymphoma.","abstract":"High-dose therapy and autologous stem cell transplantation (HDT-ASCT) can offer potential long-term remission or cure in patients with non-Hodgkin lymphoma (NHL). Limited experience is available on the safety and efficacy of HDT-ASCT in elderly patients. This is a single-center, retrospective study examining outcomes of HDT-ASCT for 202 NHL patients, ages 60 years and older, between January 2001 and December 2012. Overall survival (OS) and progression-free survival (PFS) were analyzed according to age at HDT-ASCT, hematopoietic cell transplantation comorbidity index (HCT-CI), NHL histology, and remission status at the time of HDT-ASCT. The median age was 65 years (range, 60 to 74) and the majority had either diffuse large B cell lymphoma (n = 73, 37%) or mantle cell lymphoma (n = 69, 34%). One hundred and fifteen patients (57%) had high HCT-CI scores at the time of HDT-ASCT. With a median follow-up of 3.6 years (range, 4 to 11.9 years) for survivors, PFS and OS at 3 years were 60% (95% confidence interval [CI], 53% to 68%) and 73% (95% CI, 67% to 80%), respectively. Transplantation-related mortality (TRM) was 4% both at 100 days and at 1 year after HDT-ASCT. Age and HCT-CI score were not associated with OS or PFS, and high HCT-CI did not correlate with TRM. Seven patients (4%) developed secondary myelodysplastic syndrome or acute myeloid leukemia at a median of 35 months (range, 6 to 48) after HDT-ASCT. In this single-center cohort of elderly patients with NHL undergoing HDT-ASCT, this intervention was proven tolerable and effective, with results similar to those of historic controls in younger patients. Our data suggest that age alone should not preclude HDT-ASCT in elderly patients.","paper_authors":["P. Dahi","R. Tamari","S. Devlin","M. Maloy","V. Bhatt","M. Scordo","J. Goldberg","A. Zelenetz","P. Hamlin","M. Matasar","J. Maragulia","S. Giralt","M. Perales","C. Moskowitz","C. Sauter"],"paper_publish_year":2014,"publication_journal_name":"Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation","consensus_paper_details_url":"https://consensus.app/papers/outcomes-patients-undergoing-therapy-stem-cell-dahi/1fb9a6d35c8e56bdb26f2acf45ba7c00/?utm_source=chatgpt","doi":"10.1016/j.bbmt.2014.08.019","volume":"20 12","pages":"\n 2004-9\n ","search_result_number":10},{"paper_title":"Phototherapy for Cutaneous T-Cell Lymphoma.","abstract":"Phototherapy with psoralen and ultraviolet A (PUVA) or narrowband-UVB (NBUVB) is frequently used for the patch and plaque stages of mycosis fungoides (MF), the most common type of cutaneous T-cell lymphoma. This article provides practical guidelines for the design and implementation of a phototherapy protocol for early stage MF, including an overview of treatment phases, response criteria, and considerations in the selection of a light source. Several evolving topics in phototherapy research are also discussed, including the relative efficacy of PUVA versus NBUVB, the role of maintenance therapy, risk of photocarcinogenicity, and combination therapies.","paper_authors":["A. Marka","J. Carter"],"paper_publish_year":2020,"publication_journal_name":"Dermatologic clinics","consensus_paper_details_url":"https://consensus.app/papers/phototherapy-cutaneous-tcell-lymphoma-marka/5964adb7d669551bb03c41cee42147e5/?utm_source=chatgpt","doi":"10.1016/j.det.2019.08.013","volume":"38 1","pages":"\n 127-135\n ","search_result_number":11},{"paper_title":"Phototherapy for cutaneous T‐cell lymphoma","abstract":"ABSTRACT:  Phototherapy has been utilized for decades in the treatment of various dermatologic conditions, including cutaneous T‐cell lymphoma (CTCL). Currently, a number of light sources are available, and selection of the specific modality is based on a number of factors, the most important of which is disease stage. The efficacy of broadband ultraviolet B (UVB) is limited to the patch stage, while psoralen and ultraviolet A (PUVA) is capable of clearing plaques and, sometimes, early tumors. Narrowband UVB is also effective for early stages and has practical advantages over PUVA, but more studies are needed to more fully evaluate its role in CTCL. Long‐wave ultraviolet A (UVA1) has likewise shown efficacy, supported by findings of apoptosis induction in UVA1‐treated cells. Long‐term remissions have been reported for PUVA, but in the majority of cases, maintenance therapy was necessary. Although beneficial as monotherapy for early stages of the disease, phototherapy is also a useful adjunct to other modalities such as interferons, retinoids and electron beam therapy. Studies are ongoing to refine protocols for combination therapy, with the goal of improving efficacy, while minimizing adverse effects.","paper_authors":["E. Baron","S. Stevens"],"paper_publish_year":2003,"publication_journal_name":"Dermatologic Therapy","consensus_paper_details_url":"https://consensus.app/papers/phototherapy-t‐cell-lymphoma-baron/994acc17b0495996860ea6c93dc5b9c4/?utm_source=chatgpt","doi":"10.1111/j.1396-0296.2003.01642.x","volume":"16","pages":"","search_result_number":12},{"paper_title":"The role of maintenance phototherapy in cutaneous T-cell lymphoma.","abstract":"Phototherapy is well-recognized as effective therapy in early stage cutaneous T-cell lymphoma (patch and plaque), often resulting in complete clearance of clinical disease and subsequent remission. Although not curable, long-term remission can often be attained utilizing maintenance phototherapy, consisting of a course of less frequent treatments over time. Herein, the authors review the literature regarding the role of maintenance phototherapy in cutaneous T-cell lymphoma (CTCL) and its success in prolonging clinical remission and disease-free survival in CTCL.","paper_authors":["Salma Pothiawala","Brooke T. Baldwin","B. Cherpelis","L. Glass","N. Fenske"],"paper_publish_year":2010,"publication_journal_name":"Journal of drugs in dermatology : JDD","consensus_paper_details_url":"https://consensus.app/papers/role-maintenance-phototherapy-tcell-lymphoma-pothiawala/c70106e4c16b50d5bc7b31adce3d3e18/?utm_source=chatgpt","doi":"","volume":"9 7","pages":"\n 800-3\n ","search_result_number":13},{"paper_title":"Clinical Efficacy of Stem Cell Therapy for Diabetes Mellitus: A Meta-Analysis","abstract":"Background Stem cell therapy is a promising therapeutic modality for advanced diabetes mellitus (DM). This study presents a meta-analysis of relevant clinical trials to determine the efficacy of stem cell therapy in DM. We aim to critically evaluate and synthesize clinical evidence on the safety and efficiency of different types of stem cell therapy for both T1DM and T2DM. Methods and Findings We pooled participant-level data from twenty-two eligible clinical trials that satisfied our inclusion criteria, with a total of 524 patients. There were significant differences in the outcome based on the type and source of the infused cells. Out of all T1DM patients who received CD34+ hematopoietic stem cell (HSC) infusion, 58.9% became insulin independent for a mean period of 16 months, whereas the results were uniformly negative in patients who received umbilical cord blood (UCB). Infusion of umbilical cord mesenchymal stem cells (UC-MSCs) provided significantly beneficial outcome in T1DM, when compared to bone-marrow mesenchymal stem cells (BM-MSCs) (P<0.0001 and P = 0.1557). Administration of stem cell therapy early after DM diagnosis was more effective than intervention at later stages (relative risk = 2.0, P = 0.0008). Adverse effects were observed in only 21.72% of both T1DM and T2DM stem cell recipients with no reported mortality. Out of all poor responders, 79.5% were diagnosed with diabetic ketoacidosis. Conclusions Stem cell transplantation can represent a safe and effective treatment for selected patients with DM. In this cohort of trials, the best therapeutic outcome was achieved with CD34+ HSC therapy for T1DM, while the poorest outcome was observed with HUCB for T1DM. Diabetic ketoacidosis impedes therapeutic efficacy.","paper_authors":["A. El-Badawy","N. El-Badri"],"paper_publish_year":2016,"publication_journal_name":"PLoS ONE","consensus_paper_details_url":"https://consensus.app/papers/efficacy-stem-cell-therapy-diabetes-mellitus-elbadawy/b9566855ad1e59529c556252f9e38245/?utm_source=chatgpt","doi":"10.1371/journal.pone.0151938","volume":"11","pages":"","search_result_number":14},{"paper_title":"Clinical-grade stem cell–derived retinal pigment epithelium patch rescues retinal degeneration in rodents and pigs","abstract":"A retinal pigment epithelial patch derived from mutation-free pluripotent stem cells shows therapeutic effects in rats and pigs. A pipeline for retinal stem cell therapy Autologous induced pluripotent stem cell (iPSC)–derived retinal pigment epithelium (RPE) transplantation has been shown to improve visual function in animal models of age-related macular degeneration (AMD) and is currently being tested in human patients. However, oncogenic mutations might occur during the cell reprogramming process. Now, Sharma et al. used CD34+ peripheral blood cells from patients with AMD to generate oncogenic mutation-free iPSCs. These cells were used for the production of clinical-grade RPE cell patches. Transplantation of the RPE patches in rodent and pig models of retinal degeneration showed therapeutic effects. The authors suggest that the production process presented here might accelerate the development of safer iPSC-derived stem cell therapies. Considerable progress has been made in testing stem cell–derived retinal pigment epithelium (RPE) as a potential therapy for age-related macular degeneration (AMD). However, the recent reports of oncogenic mutations in induced pluripotent stem cells (iPSCs) underlie the need for robust manufacturing and functional validation of clinical-grade iPSC-derived RPE before transplantation. Here, we developed oncogenic mutation-free clinical-grade iPSCs from three AMD patients and differentiated them into clinical-grade iPSC-RPE patches on biodegradable scaffolds. Functional validation of clinical-grade iPSC-RPE patches revealed specific features that distinguished transplantable from nontransplantable patches. Compared to RPE cells in suspension, our biodegradable scaffold approach improved integration and functionality of RPE patches in rats and in a porcine laser-induced RPE injury model that mimics AMD-like eye conditions. Our results suggest that the in vitro and in vivo preclinical functional validation of iPSC-RPE patches developed here might ultimately be useful for evaluation and optimization of autologous iPSC-based therapies.","paper_authors":["Ruchi Sharma","V. Khristov","Aaron Rising","B. Jha","R. Dejene","Nathan A Hotaling","Yichao Li","Jonathan Stoddard","Casey Stankewicz","Qin Wan","Connie S. Zhang","M. Campos","K. Miyagishima","David M. McGaughey","R. Villasmil","M. Mattapallil","B. Stanzel","H. Qian","Wai T. Wong","L. Chase","S. Charles","T. Mcgill","Sheldon S Miller","A. Maminishkis","J. Amaral","K. Bharti"],"paper_publish_year":2019,"publication_journal_name":"Science Translational Medicine","consensus_paper_details_url":"https://consensus.app/papers/clinicalgrade-stem-cell–derived-pigment-epithelium-sharma/9622da11576c5c598dc8007a36ba9ac0/?utm_source=chatgpt","doi":"10.1126/scitranslmed.aat5580","volume":"11","pages":"","search_result_number":15},{"paper_title":"Delivery of Stem Cell Secretome for Therapeutic Applications.","abstract":"Intensive studies on stem cell therapy reveal that benefits of stem cells attribute to the paracrine effects. Hence, direct delivery of stem cell secretome to the injured site shows the comparative therapeutic efficacy of living cells while avoiding the potential limitations. However, conventional systemic administration of stem cell secretome often leads to rapid clearance in vivo. Therefore, a variety of different biomaterials are developed for sustained and controllable delivery of stem cell secretome to improve therapeutic efficiency. In this review, we first introduce current approaches for the preparation and characterization of stem cell secretome as well as strategies to improve their therapeutic efficacy and production. The up-to-date delivery platforms are also summarized, including nanoparticles, injectable hydrogels, microneedles, and scaffold patches. Meanwhile, we discuss the underlying therapeutic mechanism of stem cell secretome for the treatment of various diseases. In the end, future opportunities and challenges are proposed.","paper_authors":["Fenfang Li","Jiabin Zhang","Ke Yi","Haixia Wang","Hongyan Wei","H. Chan","Yu Tao","Mingqiang Li"],"paper_publish_year":2022,"publication_journal_name":"ACS applied bio materials","consensus_paper_details_url":"https://consensus.app/papers/delivery-stem-cell-secretome-therapeutic-applications-li/affaa08b43ac58e7b553cbdb02ac2a23/?utm_source=chatgpt","doi":"10.1021/acsabm.1c01312","volume":"","pages":"","search_result_number":16},{"paper_title":"An elastomeric patch derived from poly(glycerol sebacate) for delivery of embryonic stem cells to the heart.","abstract":"We hypothesize that a combinatorial approach of ventricle constraint and stem cell therapy would offer a greater benefit for the treatment of heart failure than either strategy alone. A heart patch would serve two therapeutic purposes: biomechanical support and cell delivery. In this study, we describe a hybrid heart patch engineered from a synthetic elastomer, poly(glycerol sebacate) (PGS), supplemented with cardiomyocytes differentiated from human embryonic stem cells (hESCs). In line with two therapeutically relevant considerations, i.e. biocompatibility and cell delivery efficiency, the PGS was (a) pre-conditioned in culture medium for 6 days, and (b) prepared without gelatin coatings to facilitate detachment and delivery of cardiomyocytes following patch implantation. Following pre-conditioning under physiological conditions, the PGS patch material without gelatin coating was found to satisfactorily support cardiomyocyte viability and attachment, with active cell beating for periods of longer than 3 months until interrupted. Dynamic culture studies revealed that cells detached more efficiently from the uncoated surface of PGS than from gelatin-coated PGS. No significant differences were detected between the beating rates of human embryonic stem cell-derived cardiomyocytes on tissue culture plate and the pre-conditioned and gelatin-uncoated PGS. PGS patches sutured over the left ventricle of rats in vivo remained intact over a 2 week period without any deleterious effects on ventricular function. We conclude that PGS is a suitable biomaterial for stem cell-based regeneration strategies to restore cardiomyocyte function, and the hybrid heart patch engineered under optimal conditions would be a promising support device for the cardiac repair.","paper_authors":["Qi-zhi Chen","Hikaru Ishii","G. Thouas","A. Lyon","Jamie S. Wright","J. Blaker","W. Chrzanowski","A. Boccaccini","N. Ali","J. Knowles","S. Harding"],"paper_publish_year":2010,"publication_journal_name":"Biomaterials","consensus_paper_details_url":"https://consensus.app/papers/patch-derived-delivery-stem-cells-heart-chen/295c4d3b5ab754838e9437dfc7249270/?utm_source=chatgpt","doi":"10.1016/j.biomaterials.2010.01.108","volume":"31 14","pages":"\n 3885-93\n ","search_result_number":17},{"paper_title":"Evaluation of the feasibility and efficacy of autologous stem cell transplantation in elderly patients with multiple myeloma.","abstract":"OBJECTIVE\nThe feasibility and efficacy of high-dose melphalan (HD-MEL) followed by autologous hematopoietic stem cell transplantation (auto-SCT) in elderly patients with multiple myeloma (MM) are discussed.\n\n\nMETHODS\nWe retrospectively analyzed and compared the results of 25 elderly patients (aged 65-76 years, elderly group) and 63 control patients (aged 51-64 years, control group). Many patients received a vincristine and doxorubicin combined with dexamethasone (VAD) regimen (elderly group: 92%, control group: 78%) with autologous peripheral blood stem cells being harvested after the administration of chemotherapy with high-dose cyclophosphamide (elderly group: 72%, control group: 87%). Ten elderly patients received MEL at a dose of 100-120 mg/m(2), while 15 patients received MEL at a dose of 180-200 mg/m(2).\n\n\nRESULTS\nTreatment-related deaths occurred in one elderly patient and two younger patients due to infections. The rate of achieving complete response (CR) or very good partial response (VGPR) was 60% in the elderly group and 83% in the control group. Progression-free survival from auto-SCT in the elderly group was similar to that observed in the control group (median 17.1 vs. 20.8 months, p=0.26), with the median overall survival (OS) from auto-SCT being 40.8 months in the former and 72.5 months in the latter group (p=0.07). When calculated from the beginning of induction treatment, the median OS of the elderly group was 47.0 months and the 3-year OS rate was 81%.\n\n\nCONCLUSION\nThe current study provides evidence for the efficacy of auto-SCT in elderly MM patients. A prospective study of auto-SCT in elderly patients using strict eligibility criteria is required to evaluate the prolongation of survival in the era of novel agents.","paper_authors":["T. Muta","T. Miyamoto","T. Fujisaki","Y. Ohno","T. Kamimura","Koji Kato","K. Takenaka","H. Iwasaki","T. Eto","Y. Takamatsu","T. Teshima","K. Akashi"],"paper_publish_year":2013,"publication_journal_name":"Internal medicine","consensus_paper_details_url":"https://consensus.app/papers/evaluation-feasibility-efficacy-stem-cell-muta/36aaf5dba3625afdac17757715e34492/?utm_source=chatgpt","doi":"10.2169/INTERNALMEDICINE.52.8390","volume":"52 1","pages":"\n 63-70\n ","search_result_number":18},{"paper_title":"Stem cell proliferation under low intensity laser irradiation: A preliminary study","abstract":"Phototherapy with low intensity laser irradiation has shown to be effective in promoting the proliferation of different cells. The aim of this in vitro study was to evaluate the potential effect of laser phototherapy (660 nm) on human dental pulp stem cell (hDPSC) proliferation.","paper_authors":["F. Eduardo","D. Bueno","P. M. de Freitas","Márcia Martins Marques","M. Passos-Bueno","C. Eduardo","M. Zatz"],"paper_publish_year":2008,"publication_journal_name":"Lasers in Surgery and Medicine","consensus_paper_details_url":"https://consensus.app/papers/stem-cell-proliferation-intensity-laser-irradiation-eduardo/27c4aa713f935249ae31977e294cbc0e/?utm_source=chatgpt","doi":"10.1002/lsm.20646","volume":"40","pages":"","search_result_number":19},{"paper_title":"Bone marrow‐derived mesenchymal stem cell‐loaded fibrin patches act as a reservoir of paracrine factors in chronic myocardial infarction","abstract":"The combination of mesenchymal stem cells and tissue‐engineered fibrin patches improves the therapeutic efficacy of stem cells. In vivo cardiac magnetic resonance (4.7 Tesla) and ex vivo high‐spatial resolution CMR were used to track the fate of human bone marrow‐derived mesenchymal stem cell (BMSC) delivered on an epicardial scaffold and more specifically assess their potential intramyocardial migration. Fifty‐seven nude rats underwent permanent coronary artery ligation. Two months later, those with a left ventricular ejection fraction ≤55% were randomly allocated to receive a patch loaded with human BMSC (BMSC‐P, n = 10), a patch loaded with BMSCs labelled with iron oxide nanoparticles (BMSC‐P, n = 12), an acellular patch (A‐P, n = 8) or to serve as sham‐operated animals (SHAM, n = 7). BMSC secretion of cytokines and growth factors was evaluated with flow‐cytometry. Cardiac functional parameters of cell‐treated groups (BMSC‐P and BMSC‐P) yielded significantly better outcomes than the SHAM group (p = 0.044 and p = 0.026, respectively, for ejection fraction). Angiogenesis was higher in the cell‐patch than in control groups (e.g. BMSC*P vs. SHAM: p = 0.007). No BMSCs were identified into the myocardium on cardiac magnetic resonance or histological sections, although persisting BMSCs were identified on the epicardial surface 21 days post‐transplantation in 10% of rats hearts (Lamin A/C and CD90 positive). Cytokine and growth factor profiling demonstrated an increase in their release by cells seeded in patches. The absence of stem cell migration into the myocardium and the persistence of stem cells on the epicardial surface suggest that fibrin patches are likely to act predominantly as reservoirs of paracrine factors. Copyright © 2017 John Wiley & Sons, Ltd.","paper_authors":["E. Blondiaux","L. Pidial","G. Autret","G. Rahmi","D. Balvay","E. Audureau","C. Wilhelm","C. Guerin","P. Bruneval","J. Silvestre","P. Menasché","O. Clément"],"paper_publish_year":2017,"publication_journal_name":"Journal of Tissue Engineering and Regenerative Medicine","consensus_paper_details_url":"https://consensus.app/papers/bone-marrow‐derived-stem-cell‐loaded-patches-reservoir-blondiaux/ea6b1770fb775e9ca35629c34407ad8a/?utm_source=chatgpt","doi":"10.1002/term.2255","volume":"11","pages":"3417 - 3427","search_result_number":20}]}

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Introduction

Stem cell phototherapy patches represent a novel approach in regenerative medicine, particularly for senior patients. This therapy aims to enhance the efficacy of stem cell treatments by using light to stimulate the cells' activity and healing properties.

Evidence

1. Cardiac Repair:

- Enhanced Cell Viability: Nanofibrous patches with adipose-derived mesenchymal stem cells (AD-MSCs) improved cell retention and viability post-myocardial infarction, showing a decrease in ventricular remodeling and fibrosis (Chen et al., 2018) (Chen et al., 2018). - Vascularization and Cardiac Function: Pre-vascularized stem cell patches using 3D printed bioinks enhanced vascularization and cardiac repair, improving heart function and reducing fibrosis (Jang et al., 2017) (Jang et al., 2017).

1. Wound Healing:

- Improved Healing and Reduced Scarring: Extracellular matrix patches loaded with stem cells improved wound healing and reduced scarring significantly compared to controls (Lam et al., 2013) (Lam et al., 2013). - Enhanced Regenerative Factors: Patches with adipose-derived stem cells from ischemic patients showed increased gene expression for wound healing and promoted faster revascularization (Brembilla et al., 2022) (Brembilla et al., 2022).

1. Bone Regeneration:

- Synergistic Topography for Bone Healing: Multiscale patterned patches significantly promoted bone regeneration in vivo by controlling stem cell adhesion and differentiation (Kim et al., 2014) (Kim et al., 2014).

1. General Therapeutic Applications:

- Paracrine Effects and Sustained Delivery: Biomaterials used for sustained delivery of stem cell secretome showed promising therapeutic efficacy by providing a controlled release of healing factors (Li et al., 2022) (Li et al., 2022).

Conclusion

Stem cell phototherapy patches demonstrate significant potential for enhancing the efficacy of regenerative treatments in seniors by improving cell viability, promoting tissue repair, and reducing fibrosis and scarring. The therapeutic applications extend across various conditions, offering a promising tool for advancing regenerative medicine.

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I'm considering Lifewave X39 patches. What can you tell me?

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LifeWave X39 Patches: Overview and Efficacy

Introduction LifeWave X39 patches are marketed as an innovative phototherapy solution that activates stem cells to enhance healing, reduce pain, and improve overall wellness. These patches utilize light therapy to stimulate the production of GHK-Cu, a peptide known for its regenerative properties.

How They Work LifeWave X39 patches work by reflecting specific wavelengths of light back into the skin, which is believed to stimulate points on the body and promote various health benefits. This non-transdermal approach means that no chemicals or substances enter the body through the skin, making it a non-invasive treatment option.

Reported Benefits

1. Pain Relief: Many users have reported significant reductions in pain, particularly in joints and muscles, after using the X39 patches. Some reviews highlight rapid pain relief, with improvements noticeable within minutes to days of application (Planet of Reviews; Simply Best Of).

1. Improved Energy and Sleep: Users have also noted increases in energy levels and better sleep quality. These benefits are attributed to the patches' ability to stimulate cellular activity and enhance overall vitality (Wearable Stem Cell Patches).

1. General Wellness: Testimonials frequently mention enhanced overall well-being, including improvements in skin health, exercise performance, and recovery times from physical activities (Honest Brand Reviews).

Scientific Backing The scientific evidence supporting LifeWave X39 patches is mixed. While some studies indicate positive outcomes from phototherapy, the specific benefits of the patches themselves remain under scrutiny. Clinical trials on photobiomodulation have shown potential for pain relief and tissue repair, but these typically involve direct and sustained light exposure rather than reflected light through a patch (33rd Square).

User Experiences User experiences with LifeWave X39 patches vary widely. Many users report positive effects, such as pain relief and increased energy, while others see little to no benefit. Commonly noted issues include occasional skin irritation and inconsistent results among different individuals (Simply Best Of).

Conclusion LifeWave X39 patches offer a promising but debated approach to improving health through phototherapy. While many users report beneficial effects, the scientific backing is still developing, and individual results can vary. Considering the cost and varied user feedback, it may be worth trying them to see if they work for your specific needs, particularly if you are looking for a non-invasive alternative to traditional treatments.

For more detailed information and reviews, you can check the sources here and here.

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Tell me about GHK-Cu and how it can be activated with a photo-therapy patch

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{"items":[{"paper_title":"Cancer-Cell-Activated Photodynamic Therapy Assisted by Cu(II) Based Metal-Organic Framework.","abstract":"Activation of photosensitizers (PSs) in targeted lesion and minimization of reactive oxygen species (ROS) depletion by endogenous antioxidants constitute promising approaches to perform highly effective image-guided photodynamic therapy (PDT) with minimal non-specific phototoxicity. Traditional strategies to fabricate controllable PS platforms rely on molecular design, which requires specific modification of each PS before PDT. Therefore, construction of a general tumor-responsive PDT platform with minimum ROS loss from endogenous antioxidant, typically glutathione (GSH), is highly desirable. Herein, MOF-199, a Cu(II) carboxylate-based metal-organic framework (MOF), is selected to serve as an inert carrier to load PSs with prohibited photosensitization during delivery. After cellular uptake, Cu (II) in the MOFs effectively scavenges endogenous GSH, concomitantly induces decomposition of MOF-199 to release the encapsulated PSs and recovers their ROS generation. In vitro and in vivo experiments demonstrate highly effective cancer cell ablation and anticancer PDT with diminished normal cell phototoxicity. This strategy is generally applicable to PSs with both aggregation-induced emission and aggregation-caused quenching to implement activatable and enhanced image-guided PDT.","paper_authors":["Yuanbo Wang","Wenbo Wu","Jingjing Liu","P. Manghnani","Fang Hu","Dou Ma","C. Teh","Bo Wang","B. Liu"],"paper_publish_year":2019,"publication_journal_name":"ACS nano","consensus_paper_details_url":"https://consensus.app/papers/cancercellactivated-photodynamic-therapy-assisted-cuii-wang/d5e070125fc95c749e1f9e63e7b7d162/?utm_source=chatgpt","doi":"10.1021/acsnano.9b01665","volume":"","pages":"","search_result_number":1},{"paper_title":"A Multifunctional Cascade Bioreactor Based on Hollow‐Structured Cu2MoS4 for Synergetic Cancer Chemo‐Dynamic Therapy/Starvation Therapy/Phototherapy/Immunotherapy with Remarkably Enhanced Efficacy","abstract":"The unique tumor microenvironment (TME) facilitates cancer proliferation and metastasis, and it is hard to cure cancer completely via monotherapy. Herein, a multifunctional cascade bioreactor based on hollow mesoporous Cu2MoS4 (CMS) loaded with glucose oxidase (GOx) is constructed for synergetic cancer therapy by chemo‐dynamic therapy (CDT)/starvation therapy/phototherapy/immunotherapy. The CMS harboring multivalent elements (Cu1+/2+, Mo4+/6+) exhibit Fenton‐like, glutathione (GSH) peroxidase‐like and catalase‐like activity. Once internalized into the tumor, CMS could generate ·OH for CDT via Fenton‐like reaction and deplete overexpressed GSH in TME to alleviate antioxidant capability of the tumors. Moreover, under hypoxia TME, the catalase‐like CMS could react with endogenous H2O2 to generate O2 for activating the catalyzed oxidation of glucose by GOx for starvation therapy accompanied with the regeneration of H2O2. The regenerated H2O2 can devote to Fenton‐like reaction for realizing GOx‐catalysis‐enhanced CDT. Meanwhile, the CMS under 1064 nm laser irradiation shows remarkable tumor‐killing ability by phototherapy due to its excellent photothermal conversion efficiency (η = 63.3%) and cytotoxic superoxide anion (·O2−) generation performance. More importantly, the PEGylated CMS@GOx‐based synergistic therapy combined with checkpoint blockade therapy could elicit robust immune responses for both effectively ablating primary tumors and inhibiting cancer metastasis.","paper_authors":["Mengyu Chang","Man Wang","Meifang Wang","Mengmeng Shu","Binbin Ding","Chunxia Li","Maolin Pang","S. Cui","Zhiyao Hou","Jun Lin"],"paper_publish_year":2019,"publication_journal_name":"Advanced Materials","consensus_paper_details_url":"https://consensus.app/papers/multifunctional-cascade-bioreactor-based-chang/f7e26fbf712053569d0beada673f6c4d/?utm_source=chatgpt","doi":"10.1002/adma.201905271","volume":"31","pages":"","search_result_number":2},{"paper_title":"Double-Blind Testing of the Lifewave X39 Patch to Determine GHK-Cu Production Levels","abstract":"Purpose: To determine if the LifeWave X39 non-transdermal photobiomodulation active patch would show improved production of GHK-Cu over controls in a double blind randomized controlled trial. Materials: BD Vacutainer Safety Loc Blood Collection sets with Pre-attached holder sized 21GX0.75 or 23GX0.75 and lavender top tubes. Kendro Sorvall Biofuge Centrifuge 75005184+ and AB Sciex API4000 Qtrap. Analysis software included: Qtrap Analyst software 1.6.2 and R software version 3.5.1. Statistical analyses were conducted using R software (version 3.5.1; http://www.r-project.org/). Method: Sixty people age 40-80 were computer randomized into two groups. One lavender top tube was drawn and then spun in Kendro Sorvall centrifuge for 10 minutes at 1300 rcf. The plasma was placed in cryo tubes and flash frozen to -22C then shipped in dry ice to laboratory for analysis. The filtrate was concentrated by speed-vac and reconstituted with de-ionized water to 50 ul and analyzed with AB Sciex API4000 Qtrap. Statistical assessments were evaluated using a nonparametric Wilcoxon signed rank test, p values are two-sided and p< 0.05 was used to define statistical significance. Results: A significant increase in GHK-Cu concentration in the blood of the active group was seen comparing changes from Day 2 to Day 7 between Group A vs. Group B in GHK-Cu Concentration (ng/ml) at p<0.035 and in Total GHK-Cu (ng) at p<0.03. Conclusion: This study showed a significant increase in the GHK-Cu concentration present in the blood as a result of wearing the LifeWave X39 patch for 1 week in individuals age 40 to 80. This is seen from Day 2 to Day 7 between Active vs. Control in GHK-Cu Concentration (ng/ml) at p<0.035 and in Total GHK-Cu (ng) at p<0.03.","paper_authors":["C. Connor","M. Connor","David Yue","Jens Eickhoff","Susan Wagner","Amy Chang"],"paper_publish_year":2021,"publication_journal_name":"Internal Medicine Research – Open Journal","consensus_paper_details_url":"https://consensus.app/papers/doubleblind-testing-lifewave-patch-determine-ghkcu-connor/519b8b8548ee5c8299ca7a0ad1832585/?utm_source=chatgpt","doi":"10.31038/imroj.2021612","volume":"","pages":"","search_result_number":3},{"paper_title":"Cu-MOF chemodynamic nanoplatform via modulating glutathione and H2O2 in tumor microenvironment for amplified cancer therapy.","abstract":"Chemodynamic therapy (CDT) utilizes Fenton catalysts to convert intracellular hydrogen peroxide (H2O2) into cytotoxic hydroxyl radical (OH∙) for tumor therapy, but endogenous H2O2 is usually insufficient to achieve satisfactory tumor therapy effect. Engineering an efficient CDT nanoplatform for satisfactory cancer therapy remains a challenge. Herein, we rationally designed a Cu-based metal-organic framework-199 (MOF-199) nanoplatform integrating vitamin k3 (Vk3) for amplified CDT-mediated cancer therapy, which could accumulate efficiently in tumor tissues through enhanced permeability and retention (EPR) effect. The MOF-199 nanoparticles (MOF-199 NPs) were dissociated by glutathione (GSH) into MOF-199 fragments, which triggered Fenton-like reaction for CDT. On the one hand, Vk3 was catalyzed by NAD(P)H quinone oxidoreductase-1 (NQO1) to produce sufficient H2O2 to activate Fenton-like reaction. On the other hand, GSH was largely consumed in the tumor microenvironment. Thus, this nanoplatform enabled sufficient cytotoxic reactive oxygen species (ROS) for amplified CDT effect, demonstrating effective tumor growth inhibition with minimal side-effect in vivo. Our work provides an innovative strategy to modulate GSH and H2O2 levels for amplified CDT.","paper_authors":["Hailong Tian","Mengzhu Zhang","Guoxia Jin","Yue Jiang","Y. Luan"],"paper_publish_year":2020,"publication_journal_name":"Journal of colloid and interface science","consensus_paper_details_url":"https://consensus.app/papers/cumof-nanoplatform-modulating-glutathione-h2o2-tumor-tian/8fd65b4cc64e560c9b3685314c5d478a/?utm_source=chatgpt","doi":"10.1016/j.jcis.2020.12.028","volume":"587","pages":"\n 358-366\n ","search_result_number":4},{"paper_title":"Self-delivered and Self-monitored Chemo-Photodynamic Nanoparticles with Light-triggered Synergistic Anti-tumor Therapies by Downgrading HIF-1α and Depleting GSH.","abstract":"Photodynamic therapy (PDT), a clinically approved cancer treatment, faced many drawbacks that restricted its applications. For example, the hypoxia-induced elevated hypoxia-inducible factor-1α (HIF-1α) may desensitize tumors to PDT, and the high concentration of GSH in cancer cells can also neutralize the generated ROS during PDT, resulting in insufficient therapy. Moreover, extra probes for imaging-guided visualization therapy are always needed to track the drug release or distribution while it may decrease the drug loading of the drug delivery system (DDS). In present study, we have designed and prepared a novel multi-functional combined therapy nanoparticle (ZnPc@Cur-S-OA NPs), in which Curcumin (Cur) was not only used as a chemotherapy drug to achieve a combination therapy with PDT via downregulating HIF-1α and depleting GSH in B16F10 cells but also designed as a small-molecule ROS-triggered release prodrug to deliver the photosensitizer (PS). The red fluorescence of PS in the nanoparticles (NPs) can be used to track the NPs distribution while the green fluorescence of Cur showed an \"OFF-ON\" activation, enables additional imaging and real-time self-monitoring capability. Results have proved that the prepared combined therapy NPs were more effective to inhibit the growth of B16F10 mouse melanoma tumor than monotherapy without eliciting systemic toxicity no matter in vitro or in vivo, which indicated the combined therapy NPs as an effective way to improve the PDT efficacy via downregulating HIF-1α and depleting GSH. Thus, the strategy of using a multi-functional natural product as the stimuli-responsive carrier as well as the synergist with PDT for enhancing anti-tumor efficacy via multiple pathways may open an alternative avenue to fabricate new self-delivery combination therapy nano-drugs. Besides, the fluorescence emitted from the drug can be used to real-time self-monitor the drug releasing and distributing, which has great potential in clinic to adjust the administration dose and irradiation time for different tumor types and stages for individual therapy.","paper_authors":["Zhongtao Zhang","Ruyi Wang","Xiaoxian Huang","Renjie Luo","Jingwei Xue","Jing Gao","Wenyuan Liu","Fulei Liu","F. Feng","Wei Qu"],"paper_publish_year":2020,"publication_journal_name":"ACS applied materials & interfaces","consensus_paper_details_url":"https://consensus.app/papers/selfdelivered-selfmonitored-chemophotodynamic-zhang/2da0c2bec1ab504db8b911288a369c77/?utm_source=chatgpt","doi":"10.1021/acsami.9b23325","volume":"","pages":"","search_result_number":5},{"paper_title":"Self-delivery of a metal-coordinated anti-angiogenic nanodrug with GSH depleting ability for synergistic chemo-phototherapy.","abstract":"Synergistic chemo-phototherapy has offered tremendous potential in cancer treatment. Nevertheless, nanosystems usually suffer from the complexity of multicomponents (polymeric or inorganic materials), which results in carrier-related toxicity issues. Moreover, the GSH over-expression of tumor cells seriously compromises ROS therapeutic efficiency. Herein, we designed a self-delivered nanodrug via Cu(II) coordination-driven co-self-assembly of celastrol (CST, a chemo-drug with anti-angiogenesis activity) and indocyanine green (ICG, a photosensitizer) for synergistic chemo-phototherapy with GSH depletion. The nanodrug was further cloaked by an erythrocyte membrane (RBC) to prolong the circulation time. Within the tumor microenvironment, the nanodrug would be disassembled upon intracellular GSH triggering. Moreover, the released Cu(II) could efficiently deplete the GSH, thus damaging the ROS-scavenging system and amplifying the phototherapeutic efficiency upon laser irradiation. The in vivo experiments validated the highly effective accumulation at tumor sites, potent tumor growth inhibition, and inappreciable systemic toxicity. The tumor microenvironment-responsive coordination-driven self-assembled biomimetic nanodrug may hold potential applications in tumor theranostics.","paper_authors":["Fukai Zhu","Cailin Huang","Yanling Lin","Yang Li","Ruiqin Tu","Weihong Lu"],"paper_publish_year":2023,"publication_journal_name":"Biomaterials science","consensus_paper_details_url":"https://consensus.app/papers/selfdelivery-metalcoordinated-depleting-ability-zhu/9abb2842e64c55f0a4d4d4770de04096/?utm_source=chatgpt","doi":"10.1039/d3bm00994g","volume":"","pages":"","search_result_number":6},{"paper_title":"O2-Cu/ZIF-8@Ce6/ZIF-8@F127 Composite as a Tumor Microenvironment-Responsive Nanoplatform with Enhanced Photo/Chemo-Dynamic Antitumor Efficacy.","abstract":"Hypoxia and overexpression of glutathione (GSH) are typical characteristics of the tumor microenvironment (TME), which severely hinders cancer treatments. Here we design a novel biodegradable therapeutic system, O2-Cu/ZIF-8@Ce6/ZIF-8@F127 (OCZCF), to simultaneously achieve GSH depletion and O2-enhanced combination therapy. Notably, the doped Cu2+ doubles the O2 storage capacity of ZIF-8 matrix, which makes OCZCF an excellently pH-sensitive O2 reservoir for conquering tumor hypoxia, enhancing the photodynamic therapy (PDT) efficiency of Ce6 under 650 nm laser irradiation. Moreover, the released Cu2+ can act as a smart reactive oxygen species (ROS) protector by consuming intracellular GSH. The byproduct Cu+ will undergo highly efficient Fenton-like reaction to achieve chemodynamic therapy (CDT) in the presence of abundant H2O2. The accompanying O2 will further alleviate hypoxia. The in vitro and in vivo experimental data indicate that OCZCF could cause remarkable tumor inhibition through enhanced synergetic PDT and CDT, which may open up a new path for cancer therapy.","paper_authors":["Zhongxi Xie","Shuang Liang","Xuechao Cai","Binbin Ding","Shanshan Huang","Zhiyao Hou","Ping'an Ma","Ziyong Cheng","Jun Lin"],"paper_publish_year":2019,"publication_journal_name":"ACS applied materials & interfaces","consensus_paper_details_url":"https://consensus.app/papers/o2cuzif8ce6zif8f127-composite-tumor-xie/3b72bebab42757278154f95fda1dd7e4/?utm_source=chatgpt","doi":"10.1021/acsami.9b10685","volume":"","pages":"","search_result_number":7},{"paper_title":"Chemodynamic/photothermal synergistic therapy based on Ce-doped Cu-Al layered double hydroxides.","abstract":"The combination of chemodynamic therapy (CDT) with photothermal therapy (PTT) is an efficacious strategy in cancer treatment to acquire satisfactory therapy efficiency in the endogenous redox reaction and external laser induction. In this work, we have designed Ce doped Cu-Al layered double hydroxide (CAC-LDH) ultrathin them through a bottom-up synthesis method, and further loaded them with indocyanine green (ICG). The synthesized ICG/CAC-LDH was used as a Fenton-catalyst and photothermal agent. With the Fenton activity, the ICG/CAC-LDH nanosheets could decompose H2O2 and exhibit a low KM value (1.57 mM) and an ultra-high Vmax (4.88 × 10-6 M s-1) value. Due to the presence of oxidized metal ions, ICG/CAC-LDH could induce intracellular GSH depletion and reduce Cu2+ and Ce4+ to Cu+ and Ce3+, respectively. The generated Cu+ and Ce3+ further reacted with local H2O2 to generate toxic hydroxyl radicals (˙OH) via the Fenton reaction. Owing to the obviously enhanced absorption of ICG/CAC-LDH at 808 nm, the photothermal efficiency of ICG/CAC-LDH increased significantly compared with ICG (ΔT = 34.7 °C vs. 28.3 °C). In vitro studies substantiate the remarkable CDT/PTT efficacy, with complete apoptosis of HepG2 cancer cells (the cell viability is less than 2%) treated with 25 μg mL-1 of ICG/CAC-LDH. Furthermore, ICG/CAC-LDH could also act as a contrast agent for cancer magnetic resonance imaging (MRI) and photoacoustic imaging (PAI). These results demonstrate the potential of ICG/CAC-LDH as an integrated agent for dual-modal imaging and synergistic CDT/PTT.","paper_authors":["Zhengdi Wang","Liyang Fu","Yu Zhu","Sa Wang","G. Shen","Lan Jin","Ruizheng Liang"],"paper_publish_year":2020,"publication_journal_name":"Journal of materials chemistry. B","consensus_paper_details_url":"https://consensus.app/papers/chemodynamicphotothermal-therapy-based-cedoped-cual-wang/aa2f70f0727a536196e819a0e941d2c5/?utm_source=chatgpt","doi":"10.1039/d0tb02547j","volume":"","pages":"","search_result_number":8},{"paper_title":"A Microneedle Patch with Self-Oxygenation and Glutathione Depletion for Repeatable Photodynamic Therapy.","abstract":"Photodynamic therapy (PDT) has attained extensive attention as a noninvasive tumor treatment modality. However, the hypoxia in solid tumors, skin phototoxicity of \"always on\" photosensitizers (PSs), and abundant supply of glutathione (GSH) in cancer cells severely hampered the clinical applications of PDT. Herein, a self-oxygenation nanoplatform (denoted as CZCH) with GSH depletion ability was encapsulated into the hyaluronic acid microneedle patch (MN-CZCH) to simultaneously improve the biosafety and therapeutic efficacy of PDT. The Cu2+-doped porous zeolitic imidazolate framework incorporated with catalase (CAT) is capable of efficiently loading PS 2-(1-hexyloxyethyl)-2-divinylpyropheophorbic-a (HPPH). The CZCH intermingled MN patch (MN-CZCH) could effectively penetrate the stratum corneum, topically transport HPPH to the target tumor site, achieve a long tumor retention time, and enhance the efficacy of PDT via the simultaneously synergistic effect of CAT-catalyzed self-supplying O2 and Cu2+-mediated GSH depletion. Using traceable fluorescence (FL) imaging of the released HPPH from CZCH, the FL imaging-guided repeatable PDT can be achieved for enhanced antitumor efficacy. As a result, the MN-CZCH patch exhibited excellent therapeutic efficacy against melanoma with minimal toxicity, which has promising potential for cancer theranostics.","paper_authors":["Yashi Li","Gang He","Lian-Hua Fu","M. R. Younis","Ting He","Yunzhi Chen","Jing Lin","Zhiming Li","Peng Huang"],"paper_publish_year":2022,"publication_journal_name":"ACS nano","consensus_paper_details_url":"https://consensus.app/papers/microneedle-patch-selfoxygenation-glutathione-li/f92d91df58395ec187e6fa3d094b8940/?utm_source=chatgpt","doi":"10.1021/acsnano.2c08098","volume":"","pages":"","search_result_number":9},{"paper_title":"A carrier-free metal-coordinated dual-photosensitizers nanotheranostic with glutathione-depletion for fluorescence/photoacoustic imaging-guided tumor phototherapy.","abstract":"As a promising noninvasive tumor treatment modality, dual phototherapy, including photodynamic therapy (PDT) and photothermal therapy (PTT), has drawn extensive research interest in imaging-guided synergistic antitumor treatment. However, developing a high-efficient phototherapeutic agent is still a huge challenge, since single photosensitizer often suffers from the insufficient photothermal conversion efficiency (PCE) or low reactive oxygen species (ROS) productivity. Moreover, the overexpression of reductive glutathione (GSH) in tumor cells also severely compromises PDT efficiency. Here, inspired by the glutathione oxidase activity of high-valent transition metal ions, we designed a copper-coordinated nanotheranostic (PhA@NanoICG) by the coordination-driven co-assembly of photothermal-agent indocyanine green (ICG) and photodynamic-agent pheophorbide A (PhA), in which Cu2+ acted as a bridge to tightly associate ICG with PhA. Such carrier-free metal-coordinated nanotheranostics exhibited ultra-high dual-photosensitizers co-loading (~96.74 wt%) and excellent structural stability. Notably, NanoICG significantly increase the PCE of ICG via J-aggregation induced UV-vis absorption red-shift. Once PhA@NanoICG accumulated in tumor sites, they could be disassembled triggered by the weakly acidic and highly reducible tumor microenvironment. Moreover, the Cu2+ can deplete intracellular GSH and impair cellular antioxidant defense system, reducing the unnecessary ROS consumption caused by glutathione. Under fluorescence/photoacoustic imaging-guided laser irradiation, local hyperthermia and ROS were generated to induce tumor cells apoptosis. The in vitro and in vivo experiments consistently confirm that PhA@NanoICG could induce remarkable tumor inhibition through self-enhanced PTT and PDT, which may pave a new way for cancer therapy.","paper_authors":["Luping Chen","Wenbao Zuo","Zhimei Xiao","Quanyi Jin","Jinxue Liu","Liang Wu","Nian Liu","Xuan Zhu"],"paper_publish_year":2021,"publication_journal_name":"Journal of colloid and interface science","consensus_paper_details_url":"https://consensus.app/papers/carrierfree-metalcoordinated-dualphotosensitizers-chen/10fb18e273ee56998518af7b4ac12563/?utm_source=chatgpt","doi":"10.1016/j.jcis.2021.04.131","volume":"600","pages":"\n 243-255\n ","search_result_number":10},{"paper_title":"CuS Nanoparticles as a Photodynamic Nanoswitch for Abrogating Bypass Signaling To Overcome Gefitinib Resistance.","abstract":"Bypass signaling activation plays a crucial role in the acquired resistance of gefitinib, the first targeted drug in the clinic to treat advanced non-small cell lung cancer. Although the inactivation of bypass signaling by small-molecule inhibitors or monoclonal antibodies may overcome gefitinib resistance, their clinical use has been limited by the complex production process and off-target toxicity. Here we show CuS nanoparticles (NPs) behaved as a photodynamic nanoswitch to specifically abrogate overactive bypass signaling in resistant tumor cells without interfering with the same signal pathways in normal cells. In representative insulin growth factor-1 receptor (IGF1R) bypass activation-induced gefitinib resistant tumors, CuS NPs upon near-infrared laser irradiation locally elevated reactive oxygen species (ROS) level in tumor cells, leading to the blockage of bypass IGF1R and its downstream AKT/ERK/NF-κB signaling cascades. Consequently, laser-irradiated CuS NPs sensitized tumors to gefitinib treatment and prolonged the survival of mice with no obvious toxicity. Laser-irradiated CuS NPs may serve as a simple and safe nanomedicine strategy to overcome bypass activation-induced gefitinib resistance in a specific and controllable manner and provide insights into the treatment of a myriad of other resistant tumors in the field of cancer therapy.","paper_authors":["Xiajing Gu","Yuanyuan Qiu","Miao Lin","Kai Cui","Gaoxian Chen","Yingzhi Chen","Chenchen Fan","Yongming Zhang","Lu Xu","Hongzhuan Chen","J. Wan","W. Lu","Zeyu Xiao"],"paper_publish_year":2019,"publication_journal_name":"Nano letters","consensus_paper_details_url":"https://consensus.app/papers/nanoparticles-photodynamic-nanoswitch-abrogating-gu/8c16677669c559719bfb5f601d813158/?utm_source=chatgpt","doi":"10.1021/acs.nanolett.9b01065","volume":"19 5","pages":"\n 3344-3352\n ","search_result_number":11},{"paper_title":"Protein-modified hollow copper sulfide nanoparticles carrying indocyanine green for photothermal and photodynamic therapy.","abstract":"A novel phototherapy nanoplatform is prepared by coating hollow CuS nanoparticles with a bovine serum albumin-folic acid (BSA-FA) complex. The obtained CuS-BSA-FA nanoparticles are used as drug-delivery vehicles to transport a near-infrared-absorbing phototherapeutic agent (indocyanine green, ICG) into HeLa cells, after loading ICG onto CuS-BSA-FA. In this manner, a combined therapy approach is established consisting of photothermal therapy (by CuS-BSA-FA nanocarriers) and cytotoxic effects of photodynamic and photothermal therapy (by ICG upon 808 nm laser irradiation). The encapsulation of ICG onto CuS-BSA-FA significantly improves the stability and reduces the dark toxicity of free ICG. This therapeutic system exhibits an obviously higher photothermal heating effect and capability of 1O2 generation under laser irradiation compared with bare nanocarriers. In addition, the grafted FA segments on the surface of CuS-BSA-FA are proved to enhance the internalization of nanoparticles by FA-receptor-mediated endocytosis.","paper_authors":["Lu-lu Han","Yang Zhang","Xuwei Chen","Yang Shu","Jianhua Wang"],"paper_publish_year":2016,"publication_journal_name":"Journal of materials chemistry. B","consensus_paper_details_url":"https://consensus.app/papers/proteinmodified-copper-sulfide-nanoparticles-carrying-han/9ab719c828b1565a8fddc47a2906f439/?utm_source=chatgpt","doi":"10.1039/C5TB02002F","volume":"4 1","pages":"\n 105-112\n ","search_result_number":12},{"paper_title":"Smart Cu(II)-aptamer complexes based gold nanoplatform for tumor micro-environment triggered programmable intracellular prodrug release, photodynamic treatment and aggregation induced photothermal therapy of hepatocellular carcinoma","abstract":"This study describes smart Cu(II)-aptamer complexes based gold nanoplatform for tumor micro-environment triggered programmable prodrug release, in demand photodynamic therapy and aggregation induced photothermal ablation of hepatocellular carcinoma. The nanoplatform is consist of monodispersed gold nanoparticle (GNP) that is binding to HCC cell specific targeting aptamers (TLS11a) through Au-S bond; the aptamer is labeled with Ce6 at the 5'end and coordinated with Cu(II) through (GA)10 repeating bases to load AQ4N at the 3' end. In normal physiological conditions, the fluorescence and ROS generation ability of Ce6 are quenched by GNPs via RET; but in cancerous cells, the fluorescence and the ROS generation of Ce6 could be recovered by cleavage of Au-S bond through high level of intracellular GSH for real-time imaging and in demand PDT. Meanwhile, the prodrug AQ4N release could be triggered by acid-cleavage of coordination bonds, then accompanied by a release of Cu(II) that would induce the electrostatic aggregation of GNPs for photo-thermal ablation; furthermore, the significantly enhanced chemotherapy efficiency could be achieved by PDT produced hypoxia to convert AQ4N into AQ4. In summary, here described nanoplatform with tumor cell specific responsive properties and programmable PDT/PTT/chemotherapy functions, might be an interesting synergistic strategy for HCC treatment.","paper_authors":["Da Zhang","Aixian Zheng","Juan Li","Ming Wu","Lingjie Wu","Zuwu Wei","Naishun Liao","Xiaolong Zhang","Zhixiong Cai","Huanghao Yang","G. Liu","Xiaolong Liu","Jingfeng Liu"],"paper_publish_year":2017,"publication_journal_name":"Theranostics","consensus_paper_details_url":"https://consensus.app/papers/smart-cuiiaptamer-complexes-based-gold-nanoplatform-zhang/4feee957627356ab808d6960be1124c3/?utm_source=chatgpt","doi":"10.7150/thno.17099","volume":"7","pages":"164 - 179","search_result_number":13},{"paper_title":"A New Treatment Modality for Rheumatoid Arthritis: Combined Photothermal and Photodynamic Therapy Using Cu7.2S4 Nanoparticles","abstract":"Rheumatoid arthritis (RA) is a worldwide inflammatory disease that seriously threatens human health and needs more effective treatment approaches. Near infrared (NIR) light can efficiently penetrate inflamed joints affected by RA, so phototherapy, including photothermal therapy (PTT) and photodynamic therapy (PDT), may provide new opportunities. In this work, the unique Cu7.2S4 nanoparticles (NPs) are prepared for RA treatment enlightened by the fact that copper (Cu)‐based nanomaterials can simultaneously serve as PTT agents and photosensitizers (for PDT). Meanwhile, Cu can promote ostogenesis and chondrogenesis. The Cu7.2S4 NPs combined with NIR (808 nm, 1 W cm−2) irradiation not only achieve better bone preservation, including higher bone mineral density (BMD) and bone volume/total volume, but also inhibit inflamed synovial invasion, cartilage erosion, and expression of proinflammatory cytokines in vivo. Moreover, the Cu7.2S4 NPs can effectively kill clinical pathogenic Staphylococcus aureus and Escherichia coli to prevent bacterial infection during intra‐articular injection. Therefore, the combined PTT and PDT using the multifunctional Cu7.2S4 NPs could be a novel RA treatment modality with full potential.","paper_authors":["Yao Lu","Lihua Li","Zefeng Lin","Liping Wang","Lijun Lin","Mei Li","Yu Zhang","Qing‐shui Yin","Qi Li","Hong Xia"],"paper_publish_year":2018,"publication_journal_name":"Advanced Healthcare Materials","consensus_paper_details_url":"https://consensus.app/papers/treatment-modality-rheumatoid-arthritis-combined-lu/074199ce737451d69b9436607b83e754/?utm_source=chatgpt","doi":"10.1002/adhm.201800013","volume":"7","pages":"","search_result_number":14},{"paper_title":"Combination of CuS and g-C3N4 QDs on upconversion nanoparticles for targeted photothermal and photodynamic cancer therapy","abstract":"Abstract Combined therapy with multimodal therapeutic agents based on nanomaterials has been shown as a promising approach to cancer treatment. In this report, a highly efficient multifunctional anti-cancer nanocomposite was fabricated by assembling a photothermal agent (CuS nanoparticles) and a photodynamic agent (g-C3N4 quantum dots) on upconversion nanoparticles (UCNPs) after mesoporous silica coating. Then, the surface modification of the obtained nanocomposite (abbreviated as CUSCs) with polyethylene glycol (PEG) and folic acid (FA) endows the final sample (denoted as CUSCs-PEG-FA) with an excellent cancer cell targeting effect and biocompatibility. In this nanoplatform, CuS nanoparticles are an inorganic substance with low toxicity and high photothermal conversion efficiency. g-C3N4 QDs have excellent biocompatibility and are beneficial for cellular uptake due to their small size. UCNPs can be excited by near-infrared (NIR) light to produce ultraviolet and visible (UV–vis) light emission, which overlaps with the UV absorption peak of high fluorescence g-C3N4 quantum dots (QDs). Therefore, when the nanocomposite is excited by 808 nm NIR light, a synergistic treatment effect will be presented. Since the wavelengths absorbed by the chosen photothermal agent and the photosensitizer are different, sufficient utilization of energy can be achieved. Combining photothermal therapy (high photothermal conversion efficiency of 27.4%) and photodynamic therapy can inhibit cancer more effectively compared to any monotherapy. Moreover, as a result of the inherent performance ability of the doped rare earth ions, excellent applicability for computed tomography (CT), upconversion luminescence (UCL) and magnetic resonance imaging (MRI) has been achieved.","paper_authors":["Mengshu Xu","Guixin Yang","Huiting Bi","Jiating Xu","Lili Feng","Dan Yang","Qianqian Sun","S. Gai","Fei He","Yunlu Dai","Chongna Zhong","Piaoping Yang"],"paper_publish_year":2019,"publication_journal_name":"Chemical Engineering Journal","consensus_paper_details_url":"https://consensus.app/papers/combination-gc3n4-upconversion-nanoparticles-targeted-xu/a08138bec4205726aae47580e92d78da/?utm_source=chatgpt","doi":"10.1016/J.CEJ.2018.12.052","volume":"","pages":"","search_result_number":15},{"paper_title":"Specific Generation of Singlet Oxygen through the Russell Mechanism in Hypoxic Tumors and GSH Depletion by Cu-TCPP Nanosheets for Cancer Therapy.","abstract":"The generation of singlet oxygen (1 O2 ) during photodynamic therapy is limited by the precise cooperation of light, photosensitizer, and oxygen, and the therapeutic efficiency is restricted by the elevated glutathione (GSH) levels in cancer cells. Herein, we report that an ultrathin two-dimensional metal-organic framework of Cu-TCPP nanosheets (TCPP=tetrakis(4-carboxyphenyl)porphyrin) can selectively generate 1 O2 in a tumor microenvironment. This process is based on the peroxidation of the TCPP ligand by acidic H2 O2 followed by reduction to peroxyl radicals under the action of the peroxidase-like nanosheets and Cu2+ , and their spontaneous recombination reaction by the Russell mechanism. In addition, the nanosheets can also deplete GSH. Consequently, the Cu-TCPP nanosheets can selectively destroy tumor cells with high efficiency, constituting an attractive way to overcome current limitations of photodynamic therapy.","paper_authors":["Chao Wang","Fengjuan Cao","Yudi Ruan","Xiaodan Jia","Wenyao Zhen","Xiue Jiang"],"paper_publish_year":2019,"publication_journal_name":"Angewandte Chemie","consensus_paper_details_url":"https://consensus.app/papers/generation-singlet-oxygen-russell-mechanism-hypoxic-wang/3f914ac6c76159a0bac85a44b9284236/?utm_source=chatgpt","doi":"10.1002/anie.201903981","volume":"","pages":"","search_result_number":16},{"paper_title":"Cu2 MoS4 /Au Heterostructures with Enhanced Catalase-Like Activity and Photoconversion Efficiency for Primary/Metastatic Tumors Eradication by Phototherapy-Induced Immunotherapy.","abstract":"Photoimmunotherapy can not only effectively ablate the primary tumor but also trigger strong antitumor immune responses against metastatic tumors by inducing immunogenic cell death. Herein, Cu2 MoS4 (CMS)/Au heterostructures are constructed by depositing plasmonic Au nanoparticles onto CMS nanosheets, which exhibit enhanced absorption in near-infrared (NIR) region due to the newly formed mid-gap state across the Fermi level based on the hybridization between Au 5d orbitals and S 3p orbitals, thus resulting in more excellent photothermal therapy and photodynamic therapy (PDT) effect than single CMS upon NIR laser irradiation. The CMS and CMS/Au can also serve as catalase to effectively relieve tumor hypoxia, which can enhance the therapeutic effect of O2 -dependent PDT. Notably, the NIR laser-irradiated CMS/Au can elicit strong immune responses via promoting dendritic cells maturation, cytokine secretion, and activating antitumor effector T-cell responses for both primary and metastatic tumors eradication. Moreover, CMS/Au exhibits outstanding photoacoustic and computed tomography imaging performance owing to its excellent photothermal conversion and X-ray attenuation ability. Overall, the work provides an imaging-guided and phototherapy-induced immunotherapy based on constructing CMS/Au heterostructures for effectively tumor ablation and cancer metastasis inhibition.","paper_authors":["Mengyu Chang","Zhiyao Hou","Man Wang","Meifang Wang","Peipei Dang","Jianhua Liu","Mengmeng Shu","Binbin Ding","A. A. Al kheraif","Chunxia Li","Jun Lin"],"paper_publish_year":2020,"publication_journal_name":"Small","consensus_paper_details_url":"https://consensus.app/papers/mos4-heterostructures-enhanced-catalaselike-activity-chang/8b524387737d57bb9b9d4cb20861a6f2/?utm_source=chatgpt","doi":"10.1002/smll.201907146","volume":"","pages":"\n e1907146\n ","search_result_number":17},{"paper_title":"H2O2 Self-Supplying and GSH-Depleting Nanoplatform for Chemodynamic Therapy Synergetic Photothermal/Chemotherapy.","abstract":"Chemodynamic therapy (CDT) that utilizes Fenton-type reactions to convert endogenous hydrogen peroxide (H2O2) into hydroxyl radicals (•OH) is a promising strategy in anticancer treatment, but the overexpression of glutathione (GSH) and limited endogenous H2O2 make the efficiency of CDT unsatisfactory. Here, an intelligent nanoplatform CuO2@mPDA/DOX-HA (CPPDH), which induced the depletion of GSH and the self-supply of H2O2, was proposed. When CPPDH entered tumor cells through the targeting effect of hyaluronic acid (HA), a release of Cu2+ and produced H2O2 were triggered by the acidic environment of lysosomes. Then, the Cu2+ was reduced by GSH to Cu+, and the Cu+ catalyzed H2O2 to produce •OH. The generation of •OH could be distinctly enhanced by the GSH depletion and H2O2 self-sufficiency. Besides, an outstanding photothermal therapy (PTT) effect could be stimulated by NIR irradiation on mesoporous polydopamine (mPDA). Meanwhile, mPDA was an excellent photoacoustic reagent, which could monitor the delivery of nanocomposite materials through photoacoustic (PA) imaging. Moreover, the successful delivery of doxorubicin (DOX) realized the integration of chemotherapy, PTT, and CDT. This strategy could solve the problem of insufficient CDT efficacy caused by the limited H2O2 and overexpression of GSH. This multifunctional nanoplatform may open a broad path for self-boosting CDT and synergistic therapy.","paper_authors":["Zhimei Xiao","Wenbao Zuo","Luping Chen","Liang Wu","Nian Liu","Jinxue Liu","Quanyi Jin","Yilin Zhao","Xuan Zhu"],"paper_publish_year":2021,"publication_journal_name":"ACS applied materials & interfaces","consensus_paper_details_url":"https://consensus.app/papers/h2o2-selfsupplying-gshdepleting-nanoplatform-xiao/8d8c59bbd65357d0a38d65bfb661c0b8/?utm_source=chatgpt","doi":"10.1021/acsami.1c10341","volume":"","pages":"","search_result_number":18},{"paper_title":"Mutual Benefit between Cu(II) and Polydopamine for Improving Photothermal-Chemodynamic Therapy.","abstract":"Combination therapy has attracted extensive interest in alleviating the shortcomings of monotherapy and enhancing the treatment efficacy. In this work, hollow mesoporous silica nanoparticles (HMSNs) play the role of nanocarriers in the delivery of Cu(II)-doped polydopamine (PDA), termed as HMSNs@PDA-Cu, for synergistic therapy. PDA acts as a traditional photothermal agent to realize photothermal treatment (PTT). Chemodynamic therapy (CDT) is realized by the reaction of Cu(II) with intracellular glutathione (GSH), and subsequently, the generated Cu(I) reacts with H2O2 to produce toxic hydroxyl radical (•OH) through a Fenton-like reaction. The photothermal performance of PDA is improved after its coordination with Cu(II). On the other hand, PDA exhibits superoxide dismutase (SOD)-mimicking activity. PDA converts O2•- to H2O2 and improves the production of H2O2, which promotes the therapeutic effect of CDT. Moreover, the high temperature caused by PTT further enhances the yield of •OH for CDT. This nanotheranostic platform perfectly applied to the tumor depletion of mice, presenting great potential for cancer metastasis therapy in vitro and in vivo.","paper_authors":["Wenxin Zhang","Yanan Hao","Yiru Gao","Yang Shu","Jianhua Wang"],"paper_publish_year":2021,"publication_journal_name":"ACS applied materials & interfaces","consensus_paper_details_url":"https://consensus.app/papers/benefit-cuii-polydopamine-improving-zhang/4b9b362f157457f486560eaedd13852b/?utm_source=chatgpt","doi":"10.1021/acsami.1c12199","volume":"","pages":"","search_result_number":19},{"paper_title":"A pH-responsive ultrathin Cu-based nanoplatform for specific photothermal and chemodynamic synergistic therapy†","abstract":"Noninvasive tumor therapy requires a new generation of bionanomaterials towards sensitive response to the unique tumor microenvironment to achieve accurate and effective treatment. Herein, we have developed a tumor therapy nanoplatform by immobilizing natural glucose oxidase (GOD) onto Cu-based layered double hydroxide (CuFe-LDH) nanosheets, which for the first time integrates acid-enhanced photothermal therapy (PTT), and pH-responsive and heat-facilitated chemodynamic therapy (CDT) simultaneously. As demonstrated by EXAFS and HRTEM, CuFe-LDH nanosheets possess a considerable number of defects caused by different acid conditions, resulting in a significantly acid-enhanced photothermal conversion efficiency (83.2% at pH 5.4 vs. 46.0% at pH 7.4). Moreover, GOD/CuFe-LDH nanosheets can convert a cascade of glucose into hydroxyl radicals (˙OH) under tumor acid conditions, which is validated by a high maximum velocity (Vmax = 2.00 × 10−7 M) and low Michaelis–Menten constant (KM = 12.01 mM). With the combination of PTT and CDT, the tumor tissue in vivo is almost eliminated with low-dose drug injection (1 mg kg−1). Therefore, this novel pH-responsive Cu-based nanoplatform holds great promise in tumor-specific CDT/PTT synergistic therapy.","paper_authors":["Tingting Hu","Liang Yan","Zhengdi Wang","Weicheng Shen","Ruizheng Liang","Dongpeng Yan","Min Wei"],"paper_publish_year":2021,"publication_journal_name":"Chemical Science","consensus_paper_details_url":"https://consensus.app/papers/ultrathin-cubased-therapy†-hu/ea0f82797bb85fcd86bed3d84b1a7a7e/?utm_source=chatgpt","doi":"10.1039/d0sc06742c","volume":"12","pages":"2594 - 2603","search_result_number":20}]}

ChatGPT:

GHK-Cu and Its Activation via Phototherapy Patches

Introduction to GHK-Cu: GHK-Cu (glycyl-L-histidyl-L-lysine copper) is a naturally occurring peptide in human plasma that has potent regenerative and healing properties. It plays a crucial role in wound healing, anti-inflammatory processes, and skin remodeling. GHK-Cu levels decline with age, which can contribute to the decreased regenerative capacity seen in older adults.

Mechanism of Action: GHK-Cu enhances tissue repair by stimulating collagen synthesis, promoting blood vessel growth, and increasing the production of antioxidant enzymes. It also has anti-inflammatory effects and helps to modulate immune responses.

Activation with Phototherapy Patches: Phototherapy patches like LifeWave X39 aim to increase GHK-Cu levels through a non-invasive, light-based mechanism. Here’s how it works:

1. Light Reflection: The patches are designed to reflect specific wavelengths of light back into the skin. This process, known as photobiomodulation, involves low-level light therapy (LLLT) which can penetrate the skin to influence cellular activity.

1. Stimulation of GHK-Cu Production: The light reflected by the patches is thought to stimulate the skin and underlying tissues, promoting the natural production of GHK-Cu. This increase in GHK-Cu can enhance the body’s regenerative processes, aiding in tissue repair and reducing inflammation.

Scientific Evidence:

1. Increased GHK-Cu Levels: A study conducted on the LifeWave X39 patch demonstrated a significant increase in GHK-Cu concentration in the blood of participants who used the patch for one week. This double-blind randomized controlled trial showed that the active group had higher GHK-Cu levels compared to the control group, indicating the patch's effectiveness in stimulating GHK-Cu production (Connor et al., 2021).

1. Phototherapy Benefits: Phototherapy has been extensively studied for various applications. For example, photodynamic therapy (PDT) and photothermal therapy (PTT) have been shown to promote healing and reduce inflammation through the generation of reactive oxygen species (ROS) and heat, respectively. These therapies can enhance cellular functions and promote tissue repair (Wang et al., 2019).

Conclusion: Phototherapy patches, such as the LifeWave X39, leverage the principles of light therapy to stimulate the production of GHK-Cu, a peptide crucial for tissue repair and regeneration. Clinical studies indicate that these patches can effectively increase GHK-Cu levels in the body, promoting healing and potentially offering a non-invasive method to enhance regenerative health.

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You:

Is there a blood test or other baseline scoring I can take to establish the level of GHK-Cu I am at, so I can retest the following month?

ChatGPT:

Yes, there are ways to establish baseline levels of GHK-Cu in your body, primarily through blood tests. Here’s how you can go about it:

Blood Test for GHK-Cu Levels

To determine your baseline GHK-Cu levels, you can undergo a blood test specifically designed to measure the concentration of GHK-Cu. Here’s a step-by-step guide on how to proceed:

1. Consult a Healthcare Provider: Start by consulting with your healthcare provider or a specialist in regenerative medicine. They can order the appropriate blood test and provide guidance on the process.

1. Blood Sample Collection: A blood sample will be collected using standard blood draw techniques. The sample is typically collected into a tube and then processed to separate the plasma.

1. Laboratory Analysis: The blood plasma is analyzed using specialized techniques such as mass spectrometry or high-performance liquid chromatography (HPLC) to accurately measure the concentration of GHK-Cu.

1. Baseline Establishment: The initial test will establish your baseline GHK-Cu level. This can serve as a reference point for future tests.

Retesting After Using Phototherapy Patches

After establishing your baseline GHK-Cu level, you can retest following a consistent period of using the phototherapy patches, typically one month. Here’s what you should do:

1. Consistent Use of Patches: Use the phototherapy patches according to the manufacturer's instructions, ensuring consistent application daily.

1. Follow-Up Blood Test: After one month, undergo another blood test using the same procedures to measure your GHK-Cu levels again.

1. Comparison of Results: Compare the new test results with your baseline to assess any changes in GHK-Cu levels.

Potential Laboratories

Not all laboratories may offer specific GHK-Cu testing. Here are some types of labs you might consult:

• Specialized Medical Labs: Labs that focus on regenerative medicine and peptide analysis.
• Research Institutions: Universities or research hospitals may offer advanced testing capabilities.
• Private Diagnostic Labs: Companies like LabCorp or Quest Diagnostics might offer or facilitate specialized tests upon request.

Example of Laboratory Offering

In the study mentioned earlier, the testing was conducted using advanced equipment like the AB Sciex API4000 Qtrap for plasma analysis (Connor et al., 2021). Such equipment is typically found in advanced medical and research laboratories.

Conclusion

To monitor the effectiveness of phototherapy patches in increasing your GHK-Cu levels, start with a baseline blood test and follow up with subsequent tests after consistent use of the patches. Consult your healthcare provider to facilitate the testing process and interpret the results accurately.

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You:

What foods or self-managed practices contribute to GHK-Cu production in senior men?

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Foods and Practices to Enhance GHK-Cu Production in

Senior Men

Introduction: GHK-Cu (glycyl-L-histidyl-L-lysine copper) is a tripeptide with significant roles in wound healing, anti-inflammatory responses, and overall skin health. Enhancing its production naturally through diet and lifestyle practices can be beneficial, especially for senior men.

Foods to Enhance GHK-Cu Production

1. Copper-Rich Foods:

- Shellfish: Oysters, crabs, and lobsters are excellent sources of copper. - Nuts and Seeds: Sunflower seeds, almonds, and cashews. - Whole Grains: Quinoa, buckwheat, and whole wheat products. - Legumes: Lentils, chickpeas, and beans. - Dark Chocolate: Contains a significant amount of copper.

1. Foods High in Amino Acids:

- Protein-Rich Foods: Eggs, chicken, turkey, lean beef, and fish provide essential amino acids like glycine, histidine, and lysine. - Dairy Products: Milk, cheese, and yogurt. - Soy Products: Tofu, tempeh, and edamame.

1. Antioxidant-Rich Foods:

- Fruits: Berries, oranges, and kiwi. - Vegetables: Spinach, kale, and broccoli. - Green Tea: Rich in polyphenols that support overall skin health.

Self-Managed Practices

1. Regular Exercise:

- Aerobic Exercise: Activities like walking, jogging, swimming, and cycling improve overall circulation and may enhance the body’s ability to repair and regenerate tissues. - Strength Training: Helps maintain muscle mass and supports overall metabolic health, which can contribute to better skin health and healing capabilities.

1. Adequate Sleep:

- Sleep Hygiene: Maintain a regular sleep schedule, create a restful environment, and avoid screens before bedtime to ensure adequate rest, which is crucial for tissue repair and regeneration.

1. Hydration:

- Water Intake: Ensure adequate daily water intake to support overall bodily functions, including skin health and tissue repair.

1. Stress Management:

- Mindfulness and Relaxation Techniques: Practices such as meditation, yoga, and deep breathing exercises can reduce stress, which in turn can support better skin health and healing.

1. Topical Treatments:

- Copper Peptide Creams: Topical applications containing GHK-Cu can be directly applied to the skin to promote healing and reduce inflammation.

Conclusion

Incorporating copper-rich and amino acid-rich foods into the diet, maintaining regular exercise, ensuring adequate sleep, staying hydrated, and managing stress are effective strategies for enhancing GHK-Cu production in senior men. These practices support overall health and can contribute to better skin health and wound healing capabilities.

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About Brenda Foshee and Lifewave X39 Patches

Brenda Foshee and Lifewave: Brenda Foshee is associated with Lifewave, a company known for its innovative phototherapy patches, including the X39 patch. She appears to be an advocate and promoter of these patches, sharing their benefits and potential uses.

Lifewave X39 Patches Overview: The Lifewave X39 patches are designed to activate the body's stem cells by elevating the levels of a peptide called GHK-Cu. This peptide plays a crucial role in promoting wound healing, reducing inflammation, and enhancing overall vitality. The patches work through phototherapy, reflecting light back into the skin to stimulate biological processes without the need for drugs or chemicals.

Key Benefits of X39 Patches:

1. Pain Relief and Reduced Inflammation: Users report significant reductions in pain and inflammation, making these patches popular for chronic pain management.
2. Improved Energy and Vitality: Many users experience increased energy levels and overall vitality.
3. Enhanced Healing and Recovery: The patches are noted for accelerating wound healing and improving recovery times from injuries and exercise.
4. Anti-Aging Effects: Regular use is claimed to reset genes to a younger state, potentially reversing some signs of aging.
5. Better Sleep and Mental Clarity: Improved sleep quality and mental clarity are also common benefits reported by users.

Usage Instructions: The patches should be applied to clean, dry skin in the morning and worn for up to 12 hours. They can be placed on specific points recommended by Lifewave, such as behind the neck (C7 vertebra) or below the belly button. It's crucial to stay hydrated while using the patches.

Scientific Backing: Research indicates that the X39 patches can significantly increase GHK-Cu levels in the blood, supporting their claimed benefits. However, individual results can vary, and not all users may experience the same effects.

For more detailed information about Lifewave X39 patches, you can visit their official website and read more about user experiences and clinical studies on various health and wellness platforms.

If you're considering trying these patches, it may be beneficial to consult with a healthcare professional to ensure they're appropriate for your specific needs.

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