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5 result(s) for "Shukla, Lipi"
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Fat Therapeutics: The Clinical Capacity of Adipose-Derived Stem Cells and Exosomes for Human Disease and Tissue Regeneration
Fat grafting is a well-established surgical technique used in plastic surgery to restore deficient tissue, and more recently, for its putative regenerative properties. Despite more frequent use of fat grafting, however, a scientific understanding of the mechanisms underlying either survival or remedial benefits of grafted fat remain lacking. Clinical use of fat grafts for breast reconstruction in tissues damaged by radiotherapy first provided clues regarding the clinical potential of stem cells to drive tissue regeneration. Healthy fat introduced into irradiated tissues appeared to reverse radiation injury (fibrosis, scarring, contracture and pain) clinically; a phenomenon since validated in several animal studies. In the quest to explain and enhance these therapeutic effects, adipose-derived stem cells (ADSCs) were suggested as playing a key role and techniques to enrich ADSCs in fat, in turn, followed. Stem cells - the body's rapid response 'road repair crew' - are on standby to combat tissue insults. ADSCs may exert influences either by releasing paracrine-signalling factors alone or as cell-free extracellular vesicles (EVs, exosomes). Alternatively, ADSCs may augment vital immune/inflammatory processes; or themselves differentiate into mature adipose cells to provide the 'building-blocks' for engineered tissue. Regardless, adipose tissue constitutes an ideal source for mesenchymal stem cells for therapeutic application, due to ease of harvest and processing; and a relative abundance of adipose tissue in most patients. Here, we review the clinical applications of fat grafting, ADSC-enhanced fat graft, fat stem cell therapy; and the latest evolution of EVs and nanoparticles in healing, cancer and neurodegenerative and multiorgan disease.
Radiation therapy attenuates lymphatic vessel repair by reducing VEGFR-3 signalling
Introduction: Surgery and radiotherapy are key cancer treatments and the leading causes of damage to the lymphatics, a vascular network critical to fluid homeostasis and immunity. The clinical manifestation of this damage constitutes a devastating side-effect of cancer treatment, known as lymphoedema. Lymphoedema is a chronic condition evolving from the accumulation of interstitial fluid due to impaired drainage via the lymphatics and is recognised to contribute significant morbidity to patients who survive their cancer. Nevertheless, the molecular mechanisms underlying the damage inflicted on lymphatic vessels, and particularly the lymphatic endothelial cells (LEC) that constitute them, by these treatment modalities, remain poorly understood. Methods: We used a combination of cell based assays, biochemistry and animal models of lymphatic injury to examine the molecular mechanisms behind LEC injury and the subsequent effects on lymphatic vessels, particularly the role of the VEGF-C/VEGF-D/VEGFR-3 lymphangiogenic signalling pathway, in lymphatic injury underpinning the development of lymphoedema. Results: We demonstrate that radiotherapy selectively impairs key LEC functions needed for new lymphatic vessel growth (lymphangiogenesis). This effect is mediated by attenuation of VEGFR-3 signalling and downstream signalling cascades. VEGFR-3 protein levels were downregulated in LEC that were exposed to radiation, and LEC were therefore selectively less responsive to VEGF-C and VEGF-D. These findings were validated in our animal models of radiation and surgical injury. Discussion: Our data provide mechanistic insight into injury sustained by LEC and lymphatics during surgical and radiotherapy cancer treatments and underscore the need for alternative non-VEGF-C/VEGFR-3-based therapies to treat lymphoedema.
The therapeutics of fat grafting and adipose derived stem cells in burn injuries—a comprehensive review of the evidence and challenges
Burn injuries are among the most common types of injuries worldwide, with devastating long-term physical and psychological effects. Recently, adipose-derived stem cells (ADSCs) have shown promise as a potential therapeutic approach for reversing fibrosis, promoting wound healing, and remodeling scars in various types of injuries. ADSCs possess unique features such as multipotency, immunomodulation, and the ability to secrete regenerative factors. These characteristics position them as attractive candidates for enhancing tissue regeneration and reducing inflammation in burn injuries. This overview discusses the current understanding of the biological properties of fat grafts, focusing on ADSCs, in relation to burn injury mechanisms and its clinical manifestations. We examine the role of ADSCs in burn injury and recovery, exploring potential mechanisms of action and future research directions. The aim is to facilitate the clinical application of ADSCs in treating burns and to address the challenges of their clinical use highlighting areas for further research. Level of evidence : Not ratable 
Inhibition of glioblastoma cell proliferation, migration and invasion by the proteasome antagonist carfilzomib
Glioblastoma multiforme is the most aggressive and lethal tumor of the central nervous system with limited treatment strategies on offer, and as such the identification of effective novel therapeutic agents is paramount. To examine the efficacy of proteasome inhibitors, we tested bortezomib, carfilzomib, nafamostat mesylate, gabexate mesylate and acetylsalicylic acid on glioblastoma cell viability, migration and invasion. Both bortezomib and carfilzomib produced significant reduction of cell viability, while nafamostat mesylate, gabexate mesylate and acetylsalicylic acid did not. Subsequent testing showed that carfilzomib significantly reduced cell viability at nM concentrations. Carfilzomib also reduced cell migration, secretion and activation of MMP2 and also cell invasion of all four glioblastoma cells tested. In summary, carfilzomib represents a novel, yet FDA-approved agent for the treatment of glioblastoma multiforme.
From Abstract to Article: Publication Rates of Abstracts Presented at the SHEA Spring Conference 2018 and 2021
Background: Conferences play a crucial role in the early dissemination of significant research to peers and experts within the same field. They provide a platform for receiving feedback, fostering collaborations, and refining groundbreaking findings, which can eventually be developed into full articles for publication in peer-reviewed journals. The transition of presented abstracts to full research journal publications is a key metric for evaluating research productivity, quality, and dissemination. Despite this, there is limited data on the proportion of abstracts that are ultimately published as full articles in peer-reviewed journals. Method: All abstracts (351) presented at the SHEA Spring Conference in 2018 and 2021 were indexed and cataloged from the 2018 online archive and the 2021 Antimicrobial Stewardship & Healthcare Epidemiology journal supplement. We then manually searched the top 20 results of both Google Scholar and PubMed to determine the publication status of each abstract as of Jan 10, 2025. Publication status criteria included: matching at least three keywords between the abstract and any resulting manuscript, having at least one common author, and publication occurring after and inclusive of the year of abstract acceptance. Data was compiled into an Excel spreadsheet, categorizing abstracts as ‘yes’ or ‘no’ for publication. Publication rates were then calculated using Excel formulas based on these categorizations. Factors associated with publication were evaluated, and publication metrics were described. Result: All 351 abstracts were analyzed. Among these, 175 (49.9%) were published as full articles in peer-reviewed journals indexed in Google Scholar or PubMed. Abstracts presented in 2021 and those presented orally had higher publication rates, though the association was statistically nonsignificant (p = 0.06 and p = 0.66, respectively). Abstracts with authors from different institutions and those with more than six authors showed a statistically significant association with higher publication rates (p = 0.002 and p = 0.003, respectively). Infection Control & Hospital Epidemiology was the most common journal in which abstracts were ultimately published, accounting for 51 (29.1%) of the publications. The publication rates surpass those reported in most similar studies of other internal medicine and subspecialty conferences, including IDWeek. Conclusion: Approximately half of the abstracts presented were subsequently published as full articles. Collaborative research, involving more authors and authors from different institutions, was associated with a higher publication rate. These findings highlight the strong academic impact of SHEA-presented research. Further research into the barriers to publication is warranted to improve the dissemination of conference abstracts.