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Advances in α-Lipoic Acid for Disease Prevention: Mechanisms and Therapeutic Insights.

α-Lipoic acid (ALA) is a naturally occurring compound with diverse biological functions, widely distributed in animal and plant tissues. It has attracted considerable attention due to its versatile therapeutic potential. However, despite these promising prospects, the clinical application of ALA remains limited by its low bioavailability and chemical instability and an incomplete understanding of its multifaceted mechanisms across various diseases. This review provides a comprehensive overview of the biochemical properties of ALA, including its direct free-radical-scavenging activity, regenera

Advances of HDAC inhibitors in tumor therapy: potential applications through immune modulation.

Histone deacetylase inhibitors (HDAC inhibitors, HDACi) have garnered considerable attention due to their potential in treating various types of malignant tumors. Histone deacetylases (HDACs) not only influence chromatin structure and gene transcription by regulating histone acetylation status but also acetylate various non-histone proteins. They are widely involved in several key biological processes, such as cell cycle regulation, apoptosis induction, and immune responses. HDACi exert their effects by inhibiting HDAC activity; however, these effects are highly concentration-dependent and non

Treatment Considerations for Severe Osteoporosis in Older Adults.

Osteoporosis, a chronic metabolic bone disease, increases the predisposition to fragility fractures and is associated with considerable morbidity, high health care cost as well as mortality. An elevation in the rate of incident fragility fractures will be observed proportional with the increase in the number of older people worldwide. Severe osteoporosis is currently defined as having a bone density determined by dual-energy X-ray absorptiometry that is more than 2.5 standard deviations (SD) below the young adult mean with one or more past fractures due to osteoporosis. Nutrition, physical act

Sepsis in multimorbidity: a domain-based framework for systemic vulnerability and precision care.

Sepsis is a leading cause of morbidity and mortality, amplified by multimorbidity. This narrative review synthesizes epidemiological, pathophysiological, and immunological evidence to show how prevalent conditions-type 2 diabetes and obesity, heart failure and cerebrovascular disease, COPD, chronic kidney disease, cancer/HIV, and severe mental illness-reshape sepsis biology and outcomes. Convergent mechanisms include low-grade inflammation, impaired innate and adaptive immunity, endothelial injury with immunothrombosis/NETosis, barrier disruption with dysbiosis, and neuroendocrine maladaptatio

Unraveled role of TLR7-mediated interferon signaling activation in COVID-19.

Emerging evidence underscores the critical role of Toll-like receptor 7 (TLR7)-mediated interferon (IFN) signaling in host defense against viral infections including SARS-CoV-2, through the modulation of both innate and adaptive immunity. However, the specific mechanisms by which TLR7 activation shapes SARS-CoV-2-specific immune responses, particularly via IRF-IFN pathways, remain incompletely elucidated. This review synthesizes current findings on how intrinsic TLR7-driven IFN signaling influences viral clearance, modulates adaptive immunity, and contributes to autoantibody production in COVI

EP300 as a Molecular Integrator of Fibrotic Transcriptional Programs.

Fibrosis is a condition characterized by the excessive accumulation of extracellular matrix proteins in tissues, leading to organ dysfunction and failure. Recent studies have identified EP300, a histone acetyltransferase, as a crucial regulator of the epigenetic changes that contribute to fibrosis. In fact, EP300-mediated acetylation of histones alters global chromatin structure and gene expression, promoting the development and progression of fibrosis. Here, we review the role of EP300-mediated epigenetic regulation in multi-organ fibrosis and its potential as a therapeutic target. We discuss

Mitochondrial metabolism as a potential therapeutic target in myeloid leukaemia.

While the understanding of the genomic aberrations that underpin chronic and acute myeloid leukaemia (CML and AML) has allowed the development of therapies for these diseases, limitations remain. These become apparent when looking at the frequency of treatment resistance leading to disease relapse in leukaemia patients. Key questions regarding the fundamental biology of the leukaemic cells, such as their metabolic dependencies, are still unresolved. Even though a majority of leukaemic cells are killed during initial treatment, persistent leukaemic stem cells (LSCs) and therapy-resistant cells

Reactive oxygen species (ROS) in cancer: from mechanism to therapeutic implications.

Reactive oxygen species (ROS) act as critical secondary messengers in various intracellular signaling pathways that regulate cellular proliferation, differentiation, and survival under normal physiological conditions. However, dysregulation of redox signaling-driven by genetic mutations, epigenetic alterations, and posttranscriptional or posttranslational modifications-plays a central role in malignant transformation and cancer progression. Cancer cells typically exhibit elevated basal ROS levels due to increased metabolic activity, mitochondrial dysfunction, and oncogene activation. This mode

MicroRNA-7: a versatile player and core target in brain disorders.

OBJECTIVE: This article provides a systematic review of the biological characteristics, regulatory mechanisms, and roles of MicroRNA-7 (miR-7) in the nervous system, as well as explores its clinical translation potential and challenges. METHODS: A review analysis integrating the progress of basic and clinical research related to miR-7. RESULTS: Characteristics and Regulation: miR-7 is highly expressed in mammalian brain tissues, with its function finely regulated by ceRNA networks (such as ciRS-7 and lncRNA SNHG1) and epigenetic modifications, forming a multi-layer dynamic regulatory system.

Prominent Role of Histone Modifications in the Regulation of Tumor Metastasis.

Tumor aggressiveness and progression is highly dependent on the process of metastasis, regulated by the coordinated interplay of genetic and epigenetic mechanisms. Metastasis involves several steps of epithelial to mesenchymal transition (EMT), anoikis resistance, intra- and extravasation, and new tissue colonization. EMT is considered as the most critical process allowing cancer cells to switch their epithelial characteristics and acquire mesenchymal properties. Emerging evidence demonstrates that epigenetics mechanisms, DNA methylation, histone modifications, and non-coding RNAs participate

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… Furthermore, HDAC6 and Sirtuin 1 (SIRT1) have been shown to counteract the p300-mediated acetylation on cortactin and thus enhance its ability to bind F-actin, leading to induction of EMT and tumor progression [ 42 ]. 2.3. …

Organoids as Innovative Models for Bone and Joint Diseases.

Bone is one of the key components of the musculoskeletal system. Bone and joint disease are the fourth most widespread disease, in addition to cardiovascular disease, cancer, and diabetes, which seriously affect people's quality of life. Bone organoids seem to be a great model by which to promote the research method, which further could improve the treatment of bone and joint disease in the future. Here, we introduce the various bone and joint diseases and their biology, and the conditions of organoid culture, comparing the in vitro models among 2D, 3D, and organoids. We summarize the differin

Circadian clocks and adaptive immune function: from mechanisms to therapeutic applications.

The circadian clock exerts profound regulatory control over adaptive immunity, particularly affecting T and B lymphocyte development, trafficking, activation, and effector function. These immune cells possess autonomous molecular clocks governed by core genes such as Bmal1, Clock, Per1/2, and Cry1/2, which influence transcriptional programs related to receptor expression, cytokine signaling, and metabolism. Circadian regulation shapes the daily oscillation of lymphocyte recirculation through lymphoid organs, modulates antigen responsiveness, and fine-tunes subset differentiation-most notably s

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… Variations in energy substrate availability (e.g., glucose, fatty acids) affect the clock via Adenosine Monophosphate-Activated Protein Kinase (AMPK), mTOR, and Sirtuin 1 (SIRT1) pathways, which also regulate the molecular clock in T cells ( 52 ). …

Acute kidney injury: pathogenesis and therapeutic interventions.

Acute kidney injury (AKI) is a prevalent clinical condition that is associated with unacceptably high morbidity and mortality, as well as the development of chronic kidney disease (CKD). The pathogenesis of AKI is highly complex and heterogeneous, primarily attributed to metabolic disturbances arising from the disease itself and the administration of medications related to treatment. In recent years, AKI in cancer patients is highly concerned. The emergence of AKI caused injuries and dysfunction of remote organs but also enhanced the health-care costs. It's essential for early recognition of A

Targeting Autophagy with Natural Products as a Potential Therapeutic Approach for Cancer.

Macro-autophagy (autophagy) is a highly conserved eukaryotic intracellular process of self-digestion caused by lysosomes on demand, which is upregulated as a survival strategy upon exposure to various stressors, such as metabolic insults, cytotoxic drugs, and alcohol abuse. Paradoxically, autophagy dysfunction also contributes to cancer and aging. It is well known that regulating autophagy by targeting specific regulatory molecules in its machinery can modulate multiple disease processes. Therefore, autophagy represents a significant pharmacological target for drug development and therapeutic

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… Furthermore, CR stimulates sirtuin 1 (SIRT1), which deacetylates and thereby activates essential autophagic proteins [ 106 ]. …

Navigating the landscape of protein folding and proteostasis: from molecular chaperones to therapeutic innovations.

Protein folding is a fundamental process ensuring that polypeptide chains acquire the correct three-dimensional structures required for biological function. This complex journey from nascent polypeptides to mature proteins is tightly regulated by the cellular proteostasis network-an integrated system of molecular chaperones, folding enzymes, and degradation machineries. Disruptions in this network lead to dysproteostasis, a pathological state implicated in a growing list of human diseases, including neurodegenerative disorders, metabolic syndromes, and cancer. In this review, we provide a comp

What nature has to offer: Opportunities for immuno-oncology.

Recent rapid development of cancer therapy has come about with the paradigm shift from the traditional goal of targeting cancer cells themselves, to reprograming the immune tumor microenvironment. Accumulating evidence shows that compounds that target epigenetic regulation, called epidrugs, play a crucial role in mediating the immunogenicity of cancer cells and in reshaping antitumor immunity. A large body of literature has recognized natural compounds as epigenetic modulators for their immunomodulatory effects and anticancer potential. Unifying our understanding of the role of these biologica

Молекулярные модели, связанные с ущербом от митохондриала: нейроиммуномодуляторы в патофизиологии центральной нервной системы.

Нейроинфламмация способствует широкому спектру нейродегенеративных заболеваний, включая болезнь Альцгеймера, болезнь Паркинсона, болезнь Хантингтона и множественный склероз. Его движут неевропейские глиальные клетки, главным образом микроглии и астроциты. Микроглии являются постоянными иммунными клетками центральной нервной системы, в то время как астроциты являются основными элементами поддержки нейронных функций, но могут также участвовать в нейроиммунной реакции. Оба этих типа глиальных клеток могут стать реактивными при обнаружении определенных внутриклеточных молекул, которые появляются в

Intracellular Pathways and Mechanisms of Colored Secondary Metabolites in Cancer Therapy.

Despite the great advancements made in cancer treatment, there are still many unsatisfied aspects, such as the wide palette of side effects and the drug resistance. There is an obvious increasing scientific attention towards nature and what it can offer the human race. Natural products can be used to treat many diseases, of which some plant products are currently used to treat cancer. Plants produce secondary metabolites for their signaling mechanisms and natural defense. A variety of plant-derived products have shown promising anticancer properties in vitro and in vivo. Rather than recreating

Recent Progress of CircRNAs in Hematological Malignancies.

Circular RNAs (circRNAs) are now recognized as key regulators in the epigenetic control of genetic expression, being involved in a wide range of cellular activities such as proliferation, differentiation, and apoptosis. Their unique closed-loop structure endows them with stability and resistance to exonuclease degradation, making them not only key regulatory molecules within the cell but also promising biomarkers for disease diagnosis and prognosis, particularly in hematological malignancies. This review comprehensively explores the role of circRNAs in the pathogenesis, progression, and therap

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… Most circRNAs are not generated by classical translocation 59 According to research, the downregulation of the mammalian sirtuin 1 (SIRT1) protein during senescence and in vivo ageing was mediated by macroautophagy (henceforth referred to as autophagy), a catabolic membrane trafficking mechanism that …

Membranous nephropathy: pathogenesis and treatments.

Membranous nephropathy (MN), an autoimmune disease, can manifest at any age and is among the most common causes of nephrotic syndrome in adults. In 80% of cases, the specific etiology of MN remains unknown, while the remaining cases are linked to drug use or underlying conditions like systemic lupus erythematosus, hepatitis B virus, or malignancy. Although about one-third of patients may achieve spontaneous complete or partial remission with conservative management, another third face an elevated risk of disease progression, potentially leading to end-stage renal disease within 10 years. The i