Результаты поиска

Раскрывая причинно-следственную связь между ожирением и множественным склерозом: систематический обзор литературы.

Множественный склероз (MS) представляет собой многогранное нейродегенеративное расстройство под влиянием генетики и образа жизни. В рамках этого систематического обзора литературы изучается роль six Гены, связанные с ожирением, включая жировую массу и ожирение (FTO), ингибиторную молекулу FAS 2 (FAIM2), тип болезни Ньеманн-пиков C1-like 1 (НПК-1), glucosamine-6-phosphate daminase 2 (ВНПДА2), melanocortin-4 Рецептор (MC4R) и нейротрофический коэффициент, полученный из мозга (BDNF) в контексте MS. МЕТОДЫ: Поиск литературы осуществлялся с использованием баз данных Embase, Scopus, Cochrane, Web of

Computational Analysis of miR-140 and miR-135 as Potential Targets to Develop Combinatorial Therapeutics for Degenerative Tendinopathy.

BackgroundDegenerative tendinopathy, a condition causing movement restriction due to high pain, highly impacts productivity and quality of life. The healing process is a complex phenomenon and involves a series of intra-cellular and inter-cellular processes. Proliferation and differentiation of the tenocyte is a major and essential process to heal degenerative tendinopathy. The recent development in microRNA (miRNA)-mediated reprogramming of the cellular function through specific pathways opened door for the development of new regenerative therapeutics. Based on information about gene expressi

Biological Evaluation of Naproxen-Dehydrodipeptide Conjugates with Self-Hydrogelation Capacity as Dual LOX/COX Inhibitors.

The use of peptide-drug conjugates is emerging as a powerful strategy for targeted drug delivery. Previously, we have found that peptides conjugated to a non-steroidal anti-inflammatory drug (NSAID), more specifically naproxen-dehydrodipeptide conjugates, readily form nanostructured fibrilar supramolecular hydrogels. These hydrogels were revealed as efficacious nano-carriers for drug delivery applications. Moreover, the incorporation of superparamagnetic iron oxide nanoparticles (SPIONs) rendered the hydrogels responsive to external magnetic fields, undergoing gel-to-solution phase transition

Integration of circadian rhythms and immunotherapy for enhanced precision in brain cancer treatment.

Circadian rhythms significantly impact (patho)physiological processes, with disruptions linked to neurodegenerative diseases and heightened cancer vulnerability. While immunotherapy has shown promise in treating various cancers, its efficacy in brain malignancies remains limited. This review explores the nexus of circadian rhythms and immunotherapy in brain cancer treatment, emphasising precision through alignment with the body's internal clock. We evaluate circadian regulation of immune responses, including cell localisation and functional phenotype, and discuss how circadian dysregulation af

TECH-VER: A Verification Checklist to Reduce Errors in Models and Improve Their Credibility.

BackgroundIn health economic literature, checklists or best practice recommendations on model validation/credibility always declare verification of the programmed model as a fundamental step, such as 'is the model implemented correctly and does the implementation accurately represent the conceptual model?' However, to date, little operational guidance for the model verification process has been given. In this study, we aimed to create an operational checklist for model users or reviewers to verify the technical implementation of health economic decision analytical models and document their ver

Safety and efficacy of antigen-specific therapeutic approaches for multiple sclerosis: Systematic review.

INTRODUCTION: The objective of this systematic review is to evaluate the efficacy and safety of antigen-specific tolerance-inducing therapeutic approaches (products based on peptides, DNA and T cells) versus placebo or other comparators, where possible, in adult multiple sclerosis (MS) patients. METHODS: PubMed, CINAHL, Web of Science, Cochrane and International Clinical Trials Registry Platform, ClinicalTrials.gov were searched for published and unpublished studies. Screening, critical appraisal, and data extraction for included studies were carried out by two independent reviewers. For effi

Research on RNA modification in disease diagnosis and prognostic biomarkers: current status and challenges.

RNA modification, as a crucial post-transcriptional regulatory mechanism, plays a pivotal role in normal physiological processes and is closely associated with the onset and progression of various human diseases. Recent studies have highlighted significant alterations in the level of RNA modifications, including m6A, m6Am, m1A, m5C, m7G, ac4C, Ψ, and A-to-I editing, across multiple diseases. These findings suggest the potential of RNA modifications and their regulatory factors as biomarkers for early disease diagnosis and prognosis. This review provides an overview of statistical methods, mach

Revolutionizing cancer care strategies: immunotherapy, gene therapy, and molecular targeted therapy.

Despite the availability of technological advances in traditional anti-cancer therapies, there is a need for more precise and targeted cancer treatment strategies. The wide-ranging shortfalls of conventional anticancer therapies such as systematic toxicity, compromised life quality, and limited to severe side effects are major areas of concern of conventional cancer treatment approaches. Owing to the expansion of knowledge and technological advancements in the field of cancer biology, more innovative and safe anti-cancerous approaches such as immune therapy, gene therapy and targeted therapy a

Insights into Endothelial Progenitor Cells: Origin, Classification, Potentials, and Prospects.

With the discovery of endothelial progenitor cells (EPCs) in the late 1990s, a paradigm shift in the concept of neoangiogenesis occurred. The identification of circulating EPCs in peripheral blood marked the beginning of a new era with enormous potential in the rapidly transforming regenerative field. Overwhelmed with the revelation, researchers across the globe focused on isolating, defining, and interpreting the role of EPCs in various physiological and pathological conditions. Consequently, controversies emerged regarding the isolation techniques and classification of EPCs. Nevertheless, th

Combination Cancer Therapy and Reference Models for Assessing Drug Synergy in Glioblastoma.

Glioblastoma is currently an incurable disease despite the development of a wide variety of therapeutic approaches, from surgical methods to immunotherapy. In current clinical practice, treatment typically involves a combination of existing methods, often comprising three stages: tumor resection, radiotherapy, and chemotherapy. Modern research offers improved chemotherapy strategies, as well as combinations of chemotherapy with immunotherapy. However, the efficacy of these therapies is profoundly influenced by factors such as tumor and peritumoral heterogeneity, alongside complex molecular sig

Prospects and Advances in Adoptive Natural Killer Cell Therapy for Unmet Therapeutic Needs in Pediatric Bone Sarcomas.

Malignant bone tumors are aggressive tumors, with a high tendency to metastasize, that are observed most frequently in adolescents during rapid growth spurts. Pediatric patients with malignant bone sarcomas, Ewing sarcoma and osteosarcoma, who present with progressive disease have dire survival rates despite aggressive therapy. These therapies can have long-term effects on bone growth, such as decreased bone mineral density and reduced longitudinal growth. New therapeutic approaches are therefore urgently needed for targeting pediatric malignant bone tumors. Harnessing the power of the immune

Олептические рецепторы в нейронной регенерации в центральной нервной системе.

Олептические рецепторы имеют решающее значение для обнаружения запахов и играют жизненно важную роль в нашем чувстве запаха, оказывая влияние на поведение, начиная от выбора пищи и кончая эмоциональными воспоминаниями. Эти рецепторы также способствуют нашему восприятию вкуса и могут применяться в медицинской диагностике и экологическом мониторинге. Способность обонятельной системы регенерировать свои сенсорные нейроны обеспечивает уникальную модель для изучения нейронной регенерации — явления, которое в основном отсутствует в центральной нервной системе. Понимание, полученное благодаря тому, к

Genomic Medicine: Lessons Learned From Monogenic and Complex Bone Disorders.

Current genetic studies of monogenic and complex bone diseases have broadened our understanding of disease pathophysiology, highlighting the need for medical interventions and treatments tailored to the characteristics of patients. As genomic research progresses, novel insights into the molecular mechanisms are starting to provide support to clinical decision-making; now offering ample opportunities for disease screening, diagnosis, prognosis and treatment. Drug targets holding mechanisms with genetic support are more likely to be successful. Therefore, implementing genetic information to the

Next-generation immunotherapeutic approaches for blood cancers: Exploring the efficacy of CAR-T and cancer vaccines.

Recent advancements in immunotherapy, particularly Chimeric antigen receptor (CAR)-T cell therapy and cancer vaccines, have significantly transformed the treatment landscape for leukemia. CAR-T cell therapy, initially promising in hematologic cancers, faces notable obstacles in solid tumors due to the complex and immunosuppressive tumor microenvironment. Challenges include the heterogeneous immune profiles of tumors, variability in antigen expression, difficulties in therapeutic delivery, T cell exhaustion, and reduced cytotoxic activity at the tumor site. Additionally, the physical barriers w

Catching Them Early: Framework Parameters and Progress for Prenatal and Childhood Application of Advanced Therapies.

Advanced therapy medicinal products (ATMPs) are medicines for human use based on genes, cells or tissue engineering. After clear successes in adults, the nascent technology now sees increasing pediatric application. For many still untreatable disorders with pre- or perinatal onset, timely intervention is simply indispensable; thus, prenatal and pediatric applications of ATMPs hold great promise for curative treatments. Moreover, for most inherited disorders, early ATMP application may substantially improve efficiency, economy and accessibility compared with application in adults. Vindicating t

Инсило-исследования для понимания взаимодействий флавонового ингибитора с nsp12-РНК-зависимой РНК-полимеразой SARS-CoV-2 и его гомологами.

Цель. ВИРУС COVID-19 продолжает быть важной проблемой здравоохранения. РНК-зависимый РНК-полимераза (RdRp) SARS-CoV-2, которая критична для репликации, поэтому является потенциальным объектом для лекарственной терапии. Методология. На основе экспериментальных структур RdRp от SARS-CoV-2 были сгенерированы вычислительные модели его гомологов от SARS-CoV-1, MERS и летучих мышей. SARS-CoV-2 RdRp был использован для виртуального скрининга в нуклеотидном связывающем сайте с молекулами из базы данных COCONUT Natural Products с помощью Glide. Комплексы с верхней ингибиторной молекулой были смоделиров

The Evolving Landscape of Immune Regulation and Immunotherapy in Cholangiocarcinoma and Biliary Tract Cancer.

Cholangiocarcinoma (CCA) is an aggressive and molecularly heterogeneous malignancy characterized by a profoundly immunosuppressive tumor microenvironment (TME) and historically limited therapeutic options. Recent advances have redefined the treatment paradigm, with phase III trials establishing chemoimmunotherapy as a standard of care and multi-omic profiling elucidating the interplay between tumor genomics, stromal architecture, and immune regulation. Despite these gains, durable clinical benefit remains confined to a minority of patients, reflecting convergent mechanisms of primary and acqui

Breaking Therapy Resistance: An Update on Oncolytic Newcastle Disease Virus for Improvements of Cancer Therapy.

Resistance to therapy is a major obstacle to cancer treatment. It may exist from the beginning, or it may develop during therapy. The review focusses on oncolytic Newcastle disease virus (NDV) as a biological agent with potential to break therapy resistance. This avian virus combines, upon inoculation into non-permissive hosts such as human, 12 described anti-neoplastic effects with 11 described immune stimulatory properties. Fifty years of clinical application of NDV give witness to the high safety profile of this biological agent. In 2015, an important milestone was achieved, namely the succ

Immunotherapies for pediatric cancer: current landscape and future perspectives.

The advent of immunotherapy has revolutionized how we manage and treat cancer. While the majority of immunotherapy-related studies performed to date have focused on adult malignancies, a handful of these therapies have also recently found success within the pediatric space. In this review, we examine the immunotherapeutic agents that have achieved the approval of the US Food and Drug Administration for treating childhood cancers, highlighting their development, mechanisms of action, and the lessons learned from the seminal clinical trials that ultimately led to their approval. We also shine a

Endodontic therapy and Medication-related osteonecrosis of the jaw onset: a scoping review and expert opinion-based qualitative meta-synthesis.

INTRODUCTION: Medication-related osteonecrosis of the Jaw (MRONJ) is a serious side effect of bone-modifying agents (BMAs), including bisphosphonates, denosumab, and antiangiogenic drugs. Some dental procedures are recognized as local risk factors for MRONJ. Given the lack of specific guidelines for root canal therapy in patients treated with BMA, this scoping review aimed to investigate the risk of MRONJ associated with failed root canal therapy. Subsequently, a meta-synthesis of expert opinions was performed to identify existing recommendations and pitfalls of root canal therapy in patients

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… Research strategy Records were identified using different search engines (e.g., Medline/PubMed, Scopus and Web of Science) and by scanning reference lists of articles. …