599 PPARg signaling modulation protects from hair follicle bulge stem cell damage and cyclophosphamide-induced hair follicle cytotoxicity

In oncology, permanent chemotherapy-induced alopecia (pCIA) remains an unfulfilled clinical need. Irreversible hair loss may result from permanent damage of hair follicle bulge epithelial stem cells (HFeSCs), some of which may undergo epithelial-mesenchymal transition (EMT). To prove our hypothesis, we treated ex vivo full-length HFs with 4HC, a cyclophosphamide metabolite 4HC, which routinely induces reversible CIA and sometimes pCIA. PPAR γ signaling is known to have a protective role in eSCs biology.
Source: Journal of Investigative Dermatology - Category: Dermatology Authors: Tags: Stem Cells, Skin Appendages and Tissue Regeneration Source Type: research

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In this study, we hypothesized that moderately and chronically reducing ACh could attenuate the deleterious effects of aging on NMJs and skeletal muscles. To test this hypothesis, we analyzed NMJs and muscle fibers from heterozygous transgenic mice with reduced expression of the vesicular ACh transporter (VAChT), VKDHet mice, which present with approximately 30% less synaptic ACh compared to control mice. Because ACh is constitutively decreased in VKDHet, we first analyzed developing NMJs and muscle fibers. We found no obvious morphological or molecular differences between NMJs and muscle fibers of VKDHet and contro...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
In conclusion, a polypharmacology approach of combining established, prolongevity drug inhibitors of specific nodes may be the most effective way to target the nutrient-sensing network to improve late-life health. Deletion of p38α in Neurons Slows Neural Stem Cell Decline and Loss of Cognitive Function in Mice https://www.fightaging.org/archives/2019/10/deletion-of-p38%ce%b1-in-neurons-slows-neural-stem-cell-decline-and-loss-of-cognitive-function-in-mice/ Researchers here provide evidence for p38α to be involved in the regulation of diminished neural stem cell activity with age. It is thought...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
The SENS Research Foundation should need no introduction to this audience, but, just in case, this is one of the few non-profit organizations dedicated to advancing the state of the art in rejuvenation research and development. The focus of the SENS Research Foundation staff is on unblocking lines of research that are presently moving too slowly, rather than on reinforcing success. The co-founder, Aubrey de Grey, assembled the Strategies for Engineered Negligible Senescence (SENS) going on twenty years ago. It was, and is, a synthesis of what is known in the research community regarding the root causes of aging. In the SEN...
Source: Fight Aging! - Category: Research Authors: Tags: Medicine, Biotech, Research Source Type: blogs
SummaryHair loss is a common dermatosis symptom and side-effect in cancer chemotherapeutics. Imiquimod application at mid and late telogen activated the hair follicle stem cells leading to premature hair cycle entry. Based on quinoline structure, a newly synthesized compound 6b displayed proliferation activity in vitro and in vivo through branch chain replacement and triazole ring cyclization. Toll-like receptors (TLRs) are also critical mediators of the immune system, and their activation is linked to various diseases. The present study aimed to expand new agonists within co-crystallization of TLR7 (PDB code: 5GMH); howev...
Source: Investigational New Drugs - Category: Drugs & Pharmacology Source Type: research
UCLA researchers have discovered a new way to activate the stem cells in hair follicles that are responsible for hair growth.Research led by three UCLA faculty members —Heather Christofk, an associate professor of biological chemistry;William Lowry, a professor of molecular, cellular and developmental biology; andMichael Jung, a distinguished professor of chemistry and biochemistry — led to the discovery of compounds that, in research in mice, enabled hair follicle stem cells to promote lactate production and, consequently, hair growth.The compounds and the technology have been exclusively licensed by UCLA to P...
Source: UCLA Newsroom: Health Sciences - Category: Universities & Medical Training Source Type: news
Discussion MDSCs violently emerge in pathological conditions in an attempt to limit potentially harmful immune and inflammatory responses. Mechanisms supporting their expansion and survival are deeply investigated in cancer, in the perspective to reactivate specific antitumor responses and prevent their contribution to disease evolution. These findings will likely contribute to improve the targeting of MDSCs in anticancer immunotherapies, either alone or in combination with immune checkpoint inhibitors. New evidence indicates that the expansion of myeloid cell differentiation in pathology is subject to fine-tuning, as its...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
Hui Zhou, Xiaoyan Fu, Qian Li and Ting Niu* Department of Hematology and Research Laboratory of Hematology, West China Hospital, Sichuan University, Chengdu, China Background: Immune checkpoint inhibition therapy with monoclonal antibody against programmed cell death protein 1 (PD-1), including nivolumab and pembrolizumab, has demonstrated powerful clinical efficacy in the treatment of advanced cancers. However, there is no evidence-based systematic review on the safety and efficacy of anti-PD-1 antibody in treating lymphoma. Methods: To evaluate the safety and efficacy of nivolumab/pembrolizumab, we analyzed clin...
Source: Frontiers in Pharmacology - Category: Drugs & Pharmacology Source Type: research
Permanent chemotherapy-induced alopecia (pCIA) remains a major unmet medical need in clinical oncology. We hypothesized that irreversible hair loss may result from permanent destruction of hair follicle epithelial stem cells (HFeSCs) in the bulge some of which may undergo epithelial-mesenchymal transition (EMT). Here, we investigated whether this is the case by treating full length HFs ex vivo with the cyclophosphamide metabolite, 4HC, which routinely induces reversible CIA and sometimes pCIA. Given the known protective role of PPAR γ signaling in eSCs biology, we also explored whether the PPARγ modulator, NAC-...
Source: Journal of Investigative Dermatology - Category: Dermatology Authors: Tags: Skin, Appendages, and Stem Cell Biology Source Type: research
Conclusions: The CBT therapies Ipi and Nivo, in combination with BV, are overall both well tolerated over time, although BV/Ipi has a higher overall AE burden. Neither regimen has significant cumulative immune toxicity. Results of this analysis should be interpreted in the context of limited number of pts in both cohorts. A larger scale examination of this analysis is planned to incorporate both phase 1 and the ongoing phase 2 components of E4412. Compared with conventional tox analysis, ToxT delineated important additional and clinically relevant depictions of AEs over time and adds a more comprehensive assessment of the ...
Source: Blood - Category: Hematology Authors: Tags: 904. Outcomes Research-Malignant Conditions: Outcomes in Lymphoid Malignancies and Stem Cell Transplant Source Type: research
In this study, we aim to  characterize the types of hair changes that occur in patients after HSCT and to determine whether these changes are associated with chemotherapy or other factors.
Source: Journal of the American Academy of Dermatology - Category: Dermatology Source Type: research
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