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Регулярная молекула-а регулирует ответные реакции, связанные с нейтрофильом TH17 в CNS автоиммунитет.

МЯСО И АЙМ: Отталкивающая молекула наведения-А (RGMA) хорошо известна своей ролью в нейро-воспалении и ремонте CNS с помощью Т-образных клеток. Врожденные иммунные взаимодействия, особенно между нейтрофилами и клетками TH17, становятся критическими движущими силами нейроинфламматической патологии в множестве склерозов (MS). Вопрос о том, регулирует ли РГМ эти связанные с нейтрофильом ответы TH17, остается в значительной степени неизвестным. Уточнение этого механизма может выявить новые терапевтические цели для НР. МЕТОДЫ: Уровни сера РГМ, БМП4, нейтрофильная эластаза (NE), IL-17A, и подстрекат

The Polyphenols α-Mangostin and Nordihydroguaiaretic Acid Induce Oxidative Stress, Cell Cycle Arrest, and Apoptosis in a Cellular Model of Medulloblastoma.

Medulloblastoma is a common malignant brain tumor in the pediatric age. The current therapeutics present serious collateral effects. Polyphenols α-mangostin and nordihydroguaiaretic acid (NDGA) exert potent antitumoral activity in different cancer models, although their antitumoral effects have not been described in medulloblastoma cells yet. This study aimed to examine the proapoptotic effects of these polyphenols on human medulloblastoma cells. Medulloblastoma cell line Daoy was incubated with increasing concentrations of α-mangostin or NDGA for 24 h. The cell viability was analyzed using cr

A probiotic approach identifies a Treg-centred immunoregulation via modulation of gut microbiota metabolites in people with multiple sclerosis and healthy individuals.

BACKGROUND: Modulation of the gut microbiota composition has been suggested as a potential disease modifying therapy in immune-mediated diseases such as multiple sclerosis (MS). However, a conclusive mechanism linking gut microbiota modulation to peripheral immune responses has remained elusive so far. METHODS: In this exploratory cohort study, people with MS (pwMS) and healthy controls (HC) supplemented a lactobacilli-rich probiotic for two or six weeks and were additionally investigated six weeks after the last intake. Immune cell phenotyping was performed in blood samples, complemented by

The progress and perspective of nanomedicine in modulating the tumor immune microenvironment.

The widespread application of nanomedicine in oncology is reshaping cancer treatment paradigms. Using the precise targeting mechanisms and the rapid advancements in nanoscale materials, nanomedicine is driving progress in cancer therapy, particularly within the complex landscape of the tumor immune microenvironment (TIM). This review provides a comprehensive overview of recent studies elucidating the critical role of nanomedicine in modulating the TIM, augmenting the efficacy of immunotherapies, and overcoming therapeutic resistance. Emphasis is placed on the significance of targeted drug deli

Recent advances in precision oncology research.

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A Systematic Pan-Cancer Analysis of YY1 Aberrations and their Relationship with Clinical Outcome, Tumor Microenvironment, and Therapeutic Targets.

Yin-Yang 1 (YY1) has a crucial function in the development of several malignancies, according to recent research. However, nothing is known about its aberrant expression and prognostic significance in human pan-cancer. We first explored the potential carcinogenic effect of YY1 in 33 cancers using the cancer genome atlas (TCGA) project and gene expression omnibus (GEO) datasets in this research. Then, we contained a variety of elements, for instance, gene expression, the state of survival, gene alterations, protein phosphorylation, immune infiltration, and related cellular pathways, and used a

The nutrigenomic-epigenetic axis in cancer: from dietary bioactives to precision oncology.

Cancer development and progression are increasingly understood to arise from dynamic interactions between genetic alterations and environmentally driven epigenetic regulation, with dietary exposures representing one of the most biologically influential and modifiable factors. Given the expanding evidence linking nutrition to epigenomic remodeling, a comprehensive synthesis of how specific dietary components influence cancer-relevant epigenetic mechanisms is needed to clarify their preventive and therapeutic relevance. This review brings together mechanistic, epidemiologic, and translational fi

Long Non-Coding RNAs: Role in Testicular Cancers.

In the last few years lncRNAs have gained increasing attention among the scientific community, thanks to the discovery of their implication in many physio-pathological processes. In particular, their contribution to tumor initiation, progression, and response to treatment has attracted the interest of experts in the oncologic field for their potential clinical application. Testicular cancer is one of the tumors in which lncRNAs role is emerging. Said malignancies already have very effective treatments, which although lead to the development of quite serious treatment-related conditions, such a

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… B2 RNA and Alu RNA repress transcription by disrupting contacts between RNA polymerase II and promoter DNA within assembled complexes . …

Role of Dietary Antioxidants in p53-Mediated Cancer Chemoprevention and Tumor Suppression.

Cancer arises through a complex interplay between genetic, behavioral, metabolic, and environmental factors that combined trigger cellular changes that over time promote malignancy. In terms of cancer prevention, behavioral interventions such as diet can promote genetic programs that may facilitate tumor suppression; and one of the key tumor suppressors responsible for initiating such programs is p53. The p53 protein is activated by various cellular events such as DNA damage, hypoxia, heat shock, and overexpression of oncogenes. Due to its role in cell fate decisions after DNA damage, regulato

Генетическая основа болезни.

Генетика в той или иной степени играет определенную роль во всех заболеваниях. Изменения в нашей ДНК и различия в том, как эта ДНК функционирует (одиночка или комбинация), наряду с окружающей средой (которая включает образ жизни), способствуют болезнетворным процессам. В рамках этого обзора изучается генетическая основа человеческих заболеваний, включая однородные генетические расстройства, хромосомные диспропорции, эпигенетические, раковые и сложные расстройства, и рассматривается вопрос о том, каким образом наше понимание и технологические достижения могут быть использованы для обеспечения н

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… This then leads to several epigenetic changes along the coated chromosome, including depletion of RNA polymerase II, loss of histone acetylation and an increase in histone ubiquitination and repressive methylation to silence gene expression on Xi. …

Novel therapeutic agents in clinical trials: emerging approaches in cancer therapy.

Novel therapeutic agents in clinical trials offer a paradigm shift in the approach to battling this prevalent and destructive disease, and the area of cancer therapy is on the precipice of a trans formative revolution. Despite the importance of tried-and-true cancer treatments like surgery, radiation, and chemotherapy, the disease continues to evolve and adapt, making new, more potent methods necessary. The field of cancer therapy is currently witnessing the emergence of a wide range of innovative approaches. Immunotherapy, including checkpoint inhibitors, CAR-T cell treatment, and cancer vacc

Update on Classic and Novel Approaches in Metastatic Triple-Negative Breast Cancer Treatment: A Comprehensive Review.

Triple-negative breast cancer (TNBC) accounts for almost 15% of all diagnosed breast cancers and often presents high rates of relapses and metastases, with generally poor prognosis despite multiple lines of treatment. Immunotherapy has radically changed the approach of clinicians towards TNBC in the last two to three years, even if targeted and specific therapeutic options are still missing; this unmet need is further justified by the extreme molecular and clinical heterogeneity of this subtype of breast cancer and by the weak response to both single-agent and combined therapies. In March 2023

Regulating the regulators: long non-coding RNAs as autophagic controllers in chronic disease management.

The increasing prevalence of chronic diseases and their associated morbidities demands a deeper understanding of underlying mechanism and causative factors, with the hope of developing novel therapeutic strategies. Autophagy, a conserved biological process, involves the degradation of damaged organelles or protein aggregates to maintain cellular homeostasis. Disruption of this crucial process leads to increased genomic instability, accumulation of reactive oxygen species (ROS), decreased mitochondrial functions, and suppression of ubiquitination, leading to overall decline in quality of intrac

Respiratory syncytial virus in hematopoietic cell transplant recipients and patients with hematologic malignancies.

In the USA and other western nations, respiratory syncytial virus is one of the most commonly encountered respiratory viruses among patients who have been diagnosed with a hematologic malignancy or who have undergone a stem cell transplant. Multiple studies have been performed to evaluate the complications associated with respiratory syncytial virus infections. Other studies have evaluated therapeutic agents and strategies in which these agents can be used. There have also been numerous reports of outbreaks in bone marrow transplant units and oncology wards, where infection control measures ha

Targeting HDACs with dacinostat amplifies radiation-induced DNA damage via sustained phosphorylated p53 and repair inhibition in aggressive meningioma.

The lack of standard systemic treatments in meningioma presents a therapeutic challenge, making radiotherapy a crucial intervention for recurrent, high-grade, or inoperable tumours. Nonetheless, the efficacy of radiotherapy is constrained by the inherent radioresistance of meningiomas, attributed to their proficient DNA damage repair and robust cell cycle checkpoint regulation. These biological barriers, along with anatomical constraints of avoiding damage to adjacent neural tissues, restrict dose escalation and therapeutic gains. Histone deacetylases (HDACs) are mediators of radioresistance i

Resveratrol: Molecular Mechanisms, Health Benefits, and Potential Adverse Effects.

Resveratrol (RES), a naturally occurring polyphenolic compound, has garnered significant attention due to its diverse biological activities, which include anti-inflammatory, antioxidant, and antiaging properties. This review synthesizes current evidence concerning the molecular mechanisms, therapeutic efficacy, and safety profile of RES across a variety of pathologies, with an emphasis on the latest research conducted in recent years. Mechanistically, RES is known to modulate critical signaling pathways such as the activation of sirtuin 1. These actions collectively contribute to the attenuati

Systemic Sclerosis: From Pathophysiology to Novel Therapeutic Approaches.

Systemic sclerosis (SSc) is a systemic, immune-mediated chronic disorder characterized by small vessel alterations and progressive fibrosis of the skin and internal organs. The combination of a predisposing genetic background and triggering factors that causes a persistent activation of immune system at microvascular and tissue level is thought to be the pathogenetic driver of SSc. Endothelial alterations with subsequent myofibroblast activation, excessive extracellular matrix (ECM) deposition, and unrestrained tissue fibrosis are the pathogenetic steps responsible for the clinical manifestati

Crosstalk between glucocorticoid and mineralocorticoid receptors boosts glucocorticoid-induced killing of multiple myeloma cells.

The glucocorticoid receptor (GR) is a crucial drug target in multiple myeloma as its activation with glucocorticoids effectively triggers myeloma cell death. However, as high-dose glucocorticoids are also associated with deleterious side effects, novel approaches are urgently needed to improve GR action in myeloma. Here, we reveal a functional crosstalk between GR and the mineralocorticoid receptor (MR) that plays a role in improved myeloma cell killing. We show that the GR agonist dexamethasone (Dex) downregulates MR levels in a GR-dependent way in myeloma cells. Co-treatment of Dex with the

Meibomian Gland Dysfunction Is Associated with Low Levels of Immunoglobulin Chains and Cystatin-SN.

Meibomian gland dysfunction (MGD) is a highly prevalent condition and the most common cause of evaporative dry eye disease. Studying the proteome of MGD can result in important advances in the management of the condition. Here, we collected tear film samples from treatment naïve patients with MGD (n = 10) and age-matched controls (n = 11) with Schirmer filtration paper. The samples were analyzed with label-free quantification nano liquid chromatography-tandem mass spectrometry. The proteins were considered differentially expressed if p < 0.05. A total of 88 proteins were significantly regulate

High-dose intravenous vitamin C, a promising multi-targeting agent in the treatment of cancer.

Mounting evidence indicates that vitamin C has the potential to be a potent anti-cancer agent when administered intravenously and in high doses (high-dose IVC). Early phase clinical trials have confirmed safety and indicated efficacy of IVC in eradicating tumour cells of various cancer types. In recent years, the multi-targeting effects of vitamin C were unravelled, demonstrating a role as cancer-specific, pro-oxidative cytotoxic agent, anti-cancer epigenetic regulator and immune modulator, reversing epithelial-to-mesenchymal transition, inhibiting hypoxia and oncogenic kinase signalling and b