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JAK inhibition in PD-1 immunotherapy and tumor microenvironment.

Targeting the programmed cell death 1 (PD-1)/PD-L1 axis has revolutionized cancer therapy; however, the durability of clinical responses is frequently compromised by chronic inflammation and an immunosuppressive tumor microenvironment (TME). The Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling pathway serves as a central intracellular node integrating cytokine signals that drive these resistance mechanisms. While physiological JAK/STAT signaling is essential for antitumor immunity, its persistent aberrant activation promotes malignant progression, upregulates

Поврежденное когнитивное и поведенческое функционирование в детском возрасте и экономические результаты взрослой жизни.

Метформин был назван следующим: one :: из наиболее важных медицинских агентов первой линии в управлении типом 2 Болит диабет. Поскольку метформин является главным образом антигипергликемическим агентом, он также оказывает огромное влияние на различные системы и процессы. Он действует главным образом путем активации AMPK (Adenosine Monophosphate-Activated Protein Kinase) в клетках и сокращения выхода глюкозы из печени. Кроме того, она сокращает производство современных продуктов гликации и реактивных видов кислорода в эндотелии, помимо регулирования глюкозы и липидного метаболизма в кардиомиоки

A Route for Investigating Psoriasis: From the Perspective of the Pathological Mechanisms and Therapeutic Strategies of Cancer.

Psoriasis is an incurable skin disease that develops in about two-thirds of patients before the age of 40 and requires lifelong treatment; its pathological mechanisms have not been fully elucidated. The core pathological process of psoriasis is epidermal thickening caused by the excessive proliferation of epidermal keratinocytes, which is similar to the key feature of cancer; the malignant proliferation of cancer cells causes tumor enlargement, suggesting that there is a certain degree of commonality between psoriasis and cancer. This article reviews the pathological mechanisms that are common

Intravenous vitamin C for reduction of cytokines storm in acute respiratory distress syndrome.

The recent outbreak of Covid19 has required urgent treatments for numerous patients. No suitable vaccines or antivirals are available for Covid19. The efficiency against Covid19 of WHO therapies of choice, that are two antivirals developed for other pathologies, is controversial. Therefore, alternative approaches are required. Intravenous (IV) Vitamin C (Vit-C) has emerged as one of the other alternatives for this purpose. Here we review the effects of IV Vit-C on the immune system response, the antiviral properties of IV Vit-C, and finally the antioxidant properties of IV Vit-C to specificall

Identifying novel genes and biological processes relevant to the development of cancer therapy-induced mucositis: An informative gene network analysis.

Mucositis is a complex, dose-limiting toxicity of chemotherapy or radiotherapy that leads to painful mouth ulcers, difficulty eating or swallowing, gastrointestinal distress, and reduced quality of life for patients with cancer. Mucositis is most common for those undergoing high-dose chemotherapy and hematopoietic stem cell transplantation and for those being treated for malignancies of the head and neck. Treatment and management of mucositis remain challenging. It is expected that multiple genes are involved in the formation, severity, and persistence of mucositis. We used Ingenuity Pathway A

Epigenetic regulation in gynecological cancers: a paradigm shift in immunotherapy strategies.

Recent advances in immunotherapy have transformed the therapeutic landscape of gynecological cancers; however, durable responses remain limited by tumor heterogeneity and immune evasion mechanisms. Emerging evidence highlights epigenetic modifications comprising of DNA methylation, histone modifications, and RNA methylation as pivotal regulators of the tumor immune microenvironment and immunotherapy efficacy. This review comprehensively explores how these epigenetic alterations modulate immune cell infiltration, antigen presentation, immune checkpoint expression, and tumor immunogenicity acros

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… This process, driven by histone acetyltransferases (HATs), adds acetyl groups, loosening chromatin structure and enhancing gene accessibility at promoter or enhancer regions, thereby promoting gene expression. … Notably, the downregulation of EP300, a histone acetyltransferase, in cervical cancer reduces histone lactylation, stabilizing cancer cell proliferation and inhibiting anti-tumor immune responses [ 119 ]. …

Mesenchymal stromal cells in bone marrow niche of patients with multiple myeloma: a double-edged sword.

Multiple myeloma (MM) is a hematological malignancy defined by the abnormal proliferation and accumulation of plasma cells (PC) within the bone marrow (BM). While multiple myeloma impacts the bone, it is not classified as a primary bone cancer. The bone marrow microenvironment significantly influences the progression of myeloma and its treatment response. Mesenchymal stromal cells (MSCs) in this environment engage with myeloma cells and other bone marrow components via direct contact and the secretion of soluble factors. This review examines the established roles of MSCs in multiple facets of

Оценка двунаправленных причинно-следственных последствий болезни Альцгеймера в различных условиях: систематический обзор и мета-анализ Мендельских исследований в области рандомизации.

В этом исследовании проводится систематическая оценка и мета-анализ менделианских случайных исследований причинно-следственной связи между болезнью Альцгеймера (АБ) и системными заболеваниями. Мы искали five - базы данных, оценка качества исследований и получение данных. Болезни были классифицированы с использованием ICD-11, и метаанализ был проведен с RevMan 5.4. Всего 56 В ходе исследований были выявлены генетические связи между уязвимостью и системными заболеваниями. В частности, генетические прокси для бедра остеоартрита (OR = 0.80; p = 0.007) и ревматоидный артрит (OR = 0.97; p = 0.004) б

The anti-PD-1 era of cervical cancer: achievement, opportunity, and challenge.

Cervical cancer is one of the three major female gynecological malignancies, becoming a major global health challenge. Although about 90% of early-stage patients can be cured by surgery, advanced-stage patients still need new treatment methods to improve their efficacy, especially for those with recurrence and metastasis tumors. Anti-PD-1 is currently the most widely used immune checkpoint inhibitor, which has revolutionized cancer therapy for different types of cancer. Pembrolizumab has been approved for second-line treatment of R/M CC but has a modest overall response rate of about 15%. Ther

Beyond regulations at DNA levels: A review of epigenetic therapeutics targeting cancer stem cells.

In the past few years, the paramount role of cancer stem cells (CSCs), in terms of cancer initiation, proliferation, metastasis, invasion and chemoresistance, has been revealed by accumulating studies. However, this level of cellular plasticity cannot be entirely explained by genetic mutations. Research on epigenetic modifications as a complementary explanation for the properties of CSCs has been increasing over the past several years. Notably, therapeutic strategies are currently being developed in an effort to reverse aberrant epigenetic alterations using specific chemical inhibitors. In thi

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… As a consequence, aberrant acetylation is believed to be relevant to various cellular events in cancer pathologies; notably, the global hypoacetylation of H4 is one of the most common hallmarks of cancer. 38 The level of histone acetylation is mainly regulated by HDACs and histone acetyltransferases …

From Cellular Stress to Systemic Adaptation: The Circadian Clock and Stress Response at Cellular and Systemic Levels.

The stress response is essential for cellular and organismal survival as it acts as a protective and adaptive mechanism to maintain homeostasis. At the organismal level, physical stressors induce responses in mammals that are mediated primarily by the hypothalamic-pituitary-adrenal (HPA) axis, which regulates glucocorticoid secretion. The HPA axis functions as a circadian-regulated, multi-oscillator system, in which the paraventricular nucleus, the pituitary, and the adrenal gland exhibit intrinsic rhythmicity while remaining coordinated by the output from the suprachiasmatic nucleus. Glucocor

Modulation of Lonp1 Activity by Small Compounds.

The Lon protease homolog 1 (LONP1) is an ATP-dependent mitochondrial protease essential for maintaining proteostasis, bioenergetics, and cellular homeostasis. LONP1 plays a pivotal role in protein quality control, mitochondrial DNA maintenance, and oxidative phosphorylation system (OXPHOS) regulation, particularly under stress conditions. Dysregulation of LONP1 has been implicated in various pathologies, including cancer, metabolic disorders, and reproductive diseases, positioning it as a promising pharmacological target. This review examines compounds that modulate LONP1 activity, categorizin

Exosomes to exosome-functionalized scaffolds: a novel approach to stimulate bone regeneration.

Bone regeneration is a complex biological process that relies on the orchestrated interplay of various cellular and molecular events. Bone tissue engineering is currently the most promising method for treating bone regeneration. However, the immunogenicity, stable and cell quantity of seed cells limited their application. Recently, exosomes, which are small extracellular vesicles released by cells, have been found to effectively address these problems and better induce bone regeneration. Meanwhile, a growing line of research has shown the cargos of exosomes may provide effective therapeutic an

Targeting dorsal root ganglia for chemotherapy-induced peripheral neuropathy: from bench to bedside.

Chemotherapy-induced peripheral neuropathy (CIPN) is a debilitating condition affecting an increasing number of cancer survivors worldwide. However, insights into its pathophysiology and availability of effective therapies remain lacking. Dorsal root ganglia (DRG) have been studied as a key component of chemotherapeutic drug toxicity and a potential therapeutic target for CIPN treatment. This comprehensive review aims to synthesize, summarize, and correlate the results of both preclinical and clinical studies relevant to the pathophysiology and management of CIPN in relation to the DRG. Design

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… the necroptosis of DRG neurons, which has been linked with the development of paclitaxel-induced peripheral neuropathy. 59 Paclitaxel induced the release of high-mobility group box 1 (HMGB1) from macrophages to mediate CIPN through the ROS/p38 mitogen-activated protein kinases (MAPK)/NF-κB/histone acetyltransferases …

Role of Cannabidiol for Improvement of the Quality of Life in Cancer Patients: Potential and Challenges.

There is currently a growing interest in the use of cannabidiol (CBD) to alleviate the symptoms caused by cancer, including pain, sleep disruption, and anxiety. CBD is often self-administered as an over-the-counter supplement, and patients have reported benefits from its use. However, despite the progress made, the mechanisms underlying CBD's anti-cancer activity remain divergent and unclear. Herein, we provide a comprehensive review of molecular mechanisms to determine convergent anti-cancer actions of CBD from pre-clinical and clinical studies. In vitro studies have begun to elucidate the mo

Control of Breast Cancer Pathogenesis by Histone Methylation and the Hairless Histone Demethylase.

Breast cancer is a highly heterogeneous disease, encompassing many subtypes that have distinct origins, behaviors, and prognoses. Although traditionally seen as a genetic disease, breast cancer is now also known to involve epigenetic abnormalities. Epigenetic regulators, such as DNA methyltransferases and histone-modifying enzymes, play essential roles in gene regulation and cancer development. Dysregulation of epigenetic regulator activity has been causally linked with breast cancer pathogenesis. Hairless (HR) encodes a 130-kDa transcription factor that is essential for development and tissue

Treating children with inflammatory bowel disease: Current and new perspectives.

Inflammatory bowel disease (IBD) is a chronic inflammatory condition of the gut characterised by alternating periods of remission and relapse. Whilst the mechanism underlying this disease is yet to be fully understood, old and newer generation treatments can only target selected pathways of this complex inflammatory process. This narrative review aims to provide an update on the most recent advances in treatment of paediatric IBD. A MEDLINE search was conducted using "paediatric inflammatory bowel disease", "paediatric Crohn's disease", "paediatric ulcerative colitis", "treatment", "therapy",

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… The enzymes N-acetyltransferases (NAT1 and NAT2, EC 2.3.1.5) are responsible for the N-acetylation of multiple drugs including the amino-salicylates. Subjects are classified as rapid, intermediate or slow acetylators based on the activity of NAT1 and NAT2 that is genetically determined[ 23 ]. …

Dietary Polyphenols and Their Biological Significance

Dietary polyphenols represent a wide variety of compounds that occur in fruits, vegetables, wine, tea, extra virgin olive oil, chocolate and other cocoa products. They are mostly derivatives and/or isomers of flavones, isoflavones, flavonols, catechins and phenolic acids, and possess diverse biological properties such as antioxidant, antiapoptosis, anti-aging, anticarcinogen, anti-inflammation, anti-atherosclerosis, cardiovascular protection, improvement of the endothelial function, as well as inhibition of angiogenesis and cell proliferation activity. Most of these biological actions have bee

The Impact of Ketogenic Nutrition on Obesity and Metabolic Health: Mechanisms and Clinical Implications.

The ketogenic diet (KD) has recently gained increasing popularity. This high-fat, adequate-protein, and carbohydrate-poor eating pattern leads to nutritional ketosis. The KD has long been known for its antidiabetic and antiepileptic effects and has been used therapeutically in these contexts. Recently, the KD, due to its effectiveness in inducing weight loss, has also been proposed as a possible approach to treat obesity. Likewise, a KD is currently explored as a supporting element in the treatment of obesity-associated metabolic disorders and certain forms of cancer. Here, we discuss the meta

GD2: hopes and challenges for the treatment of pediatric patients with tumors of the central nervous system.

Pediatric Central Nervous System (CNS) tumors are the leading cause of cancer-related death in children, yet effective treatment options remain limited. The tumor-associated antigen GD2 is a promising target for immunotherapeutic approaches aimed at treating pediatric CNS cancers; however, its heterogeneous expression within and between tumors can complicate the development of effective strategies. Here we review different aspects of GD2 biology, including its structure, synthesis pathway, and cellular and tissue expression, focusing on pediatric CNS tumors. We provide a detailed overview of t