Результаты поиска

Energy metabolism in health and diseases.

Energy metabolism is indispensable for sustaining physiological functions in living organisms and assumes a pivotal role across physiological and pathological conditions. This review provides an extensive overview of advancements in energy metabolism research, elucidating critical pathways such as glycolysis, oxidative phosphorylation, fatty acid metabolism, and amino acid metabolism, along with their intricate regulatory mechanisms. The homeostatic balance of these processes is crucial; however, in pathological states such as neurodegenerative diseases, autoimmune disorders, and cancer, exten

Targeting the p53 signaling pathway in cancers: Molecular mechanisms and clinical studies.

Tumor suppressor p53 can transcriptionally activate downstream genes in response to stress, and then regulate the cell cycle, DNA repair, metabolism, angiogenesis, apoptosis, and other biological responses. p53 has seven functional domains and 12 splice isoforms, and different domains and subtypes play different roles. The activation and inactivation of p53 are finely regulated and are associated with phosphorylation/acetylation modification and ubiquitination modification, respectively. Abnormal activation of p53 is closely related to the occurrence and development of cancer. While targeted t

Unveiling the role of histone deacetylases in neurological diseases: focus on epilepsy.

Epilepsy remains a prevalent chronic neurological disease that is featured by aberrant, recurrent and hypersynchronous discharge of neurons and poses a great challenge to healthcare systems. Although several therapeutic interventions are successfully utilized for treating epilepsy, they can merely provide symptom relief but cannot exert disease-modifying effect. Therefore, it is of urgent need to explore other potential mechanism to develop a novel approach to delay the epileptic progression. Since approximately 30 years ago, histone deacetylases (HDACs), the versatile epigenetic regulators re

Совпадение в полном тексте источника
… However, there are some indirect evidences supporting that inhibition of HDAC by VPA can enable methylated DNA to be more accessible to DNA demethylase, leading to DNA demethylation [ 135 ], which suggests that the induction of the methylation of Scn3a promoter by VPA is likely to be affected by the …

Targeting Protein Degradation Pathways in Tumors: Focusing on their Role in Hematological Malignancies.

Cells must maintain their proteome homeostasis by balancing protein synthesis and degradation. This is facilitated by evolutionarily-conserved processes, including the unfolded protein response and the proteasome-based system of protein clearance, autophagy, and chaperone-mediated autophagy. In some hematological malignancies, including acute myeloid leukemia, misfolding or aggregation of the wild-type p53 tumor-suppressor renders cells unable to undergo apoptosis, even with an intact p53 DNA sequence. Moreover, blocking the proteasome pathway triggers lymphoma cell apoptosis. Extensive studie

Посттрансляционные изменения в нейроиммунных клетках во время нейроинфламмации: комплексные сети регулирования и терапевтические возможности.

Нейроинфламмация представляет собой общий патологический механизм, лежащий в основе широкого спектра нарушений центральной нервной системы (КНС), включая нейродегенеративные расстройства (НДД), ишемический инсульт (ИС), травматическое повреждение мозга (ТБИ) и демиелионирующие заболевания, такие как множественный склероз (МС). Этот процесс начинается с организованной реакции микроглий, астроцитов, олигодендроцитов, нейронов, эндотелиальных клеток головного мозга и проникновения в периферийные иммунные клетки. Нейроинфламмация может облегчить ремонт тканей или, наоборот, увековечить хроническое

Menin inhibitors for the treatment of acute myeloid leukemia: challenges and opportunities ahead.

The AML treatment landscape has significantly changed in recent years with the approval of targeted therapies in the front-line and relapsed/refractory settings, including inhibitors of FLT3 and IDH1/2 mutations. More importantly, approval of the combination of the BCl-2 inhibitor, venetoclax, and hypomethylating agents or low dose cytarabine provided unprecedented breakthrough for the frontline treatment of older, unfit AML patients. Even with all this exciting progress, more targeted therapies for AML treatment are needed. Recent development of menin inhibitors targeting AML with KMT2A rearr

The Crystalline Nephropathies.

Crystalline nephropathies are a unique form of kidney disease characterized by the histologic finding of intrarenal crystal deposition. The intrinsic nature of some molecules and ions combined with a favorable tubular fluid physiology leads to crystal precipitation and deposition within the tubular lumens. Crystal deposition promotes kidney injury through tubular obstruction and both direct and indirect cytotoxicities. Further kidney injury develops from inflammation triggered by these crystals. From a clinical standpoint, the crystalline nephropathies are associated with abnormal urinalysis a

Marine Natural Products, Multitarget Therapy and Repurposed Agents in Alzheimer's Disease.

Alzheimer's disease (AD) is a multifactorial disease characterized by the presence of amyloid plaques, neurofibrillary tangles, and nerve cell death that affects, mainly, older people. After decades of investigation, the search for an efficacious treatment for AD remains and several strategies can be and are being employed in this journey. In this review, four of the most promising strategies, alongside with its most promising agents under investigation or development are highlighted. Marine natural products (MNP) are a source of unique chemical structures with useful biological activities for

Interplay of non-coding RNAs and approved antimetabolites such as gemcitabine and pemetrexed in mesothelioma.

Gemcitabine and pemetrexed are clinically approved antimetabolites for the therapy of mesothelioma diseases. These drugs are often applied in combination with platinum complexes and other drugs. The activity of antimetabolites depended on the expression levels of certain non-coding RNAs, in particular, of small microRNAs (miRNAs) and long non-coding RNAs (lncRNAs). The development of tumor resistance towards antimetabolites was regulated by non-coding RNAs. An overview of the interplay between gemcitabine/pemetrexed antimetabolites and non-coding RNAs in mesothelioma is provided. Further to th

Targeting Histone Deacetylases: Opportunities for Cancer Treatment and Chemoprevention.

The dysregulation of gene expression is a critical event involved in all steps of tumorigenesis. Aberrant histone and non-histone acetylation modifications of gene expression due to the abnormal activation of histone deacetylases (HDAC) have been reported in hematologic and solid types of cancer. In this sense, the cancer-associated epigenetic alterations are promising targets for anticancer therapy and chemoprevention. HDAC inhibitors (HDACi) induce histone hyperacetylation within target proteins, altering cell cycle and proliferation, cell differentiation, and the regulation of cell death pr

Targeting Abnormal Hematopoietic Stem Cells in Chronic Myeloid Leukemia and Philadelphia Chromosome-Negative Classical Myeloproliferative Neoplasms.

Myeloproliferative neoplasms (MPNs) are unique hematopoietic stem cell disorders sharing mutations that constitutively activate the signal-transduction pathways involved in haematopoiesis. They are characterized by stem cell-derived clonal myeloproliferation. The key MPNs comprise chronic myeloid leukemia (CML), polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF). CML is defined by the presence of the Philadelphia (Ph) chromosome and BCR-ABL1 fusion gene. Despite effective cytoreductive agents and targeted therapy, complete CML/MPN stem cell eradication is r

Natural anti-cancer products: insights from herbal medicine.

Herbal medicine exhibits a broad spectrum of potent anti-cancer properties, including the enhancement of tumor immune responses, reversal of multidrug resistance, regulation of autophagy and ferroptosis, as well as anti-proliferative, pro-apoptotic, and anti-metastatic effects. This review systematically explores recent advances (primarily documented since 2019) in research on key anti-cancer compounds derived from herbal medicine, such as apigenin, artemisinin, berberine, curcumin, emodin, epigallocatechin gallate (EGCG), ginsenosides, icariin, resveratrol, silibinin, triptolide, and ursolic

Цель METTL3/m6A/SOCS3 перепрограммирует макрофажную поляризацию, связанную с опухолью, с тем чтобы повысить эффективность анти-PD-1-терапии в множестве миеломы.

ИССЛЕДОВАНИЯ: В ходе этого исследования были изучены функции иммуномодулятора подавителя цитокина, сигнализирующего 3 (SOCS3) в макрофаге поляризации и активации цитотоксичных Т-клеток в микроопухоли (TME) множественной миэломы (MM). МЕТОДЫ: Выражение SOCS3 оценивалось в клинических образцах MM и здоровом контроле. Для разъяснения воздействия SOCS3 на злокачественное развитие клеток MM и поляризацию макрофага были разработаны анализы эффективности и потери функций, а также система кокультуры MM-камер. В рамках механистических исследований основное внимание было уделено модуляции SOCS3 при помо

Management and Clinical Outcomes of Scleredema Diabeticorum: A Scoping Review.

Background/objectivesThe objective of this scoping review was to systematically map the available evidence for the management of scleredema diabeticorum (SD) to summarize the documented clinical outcomes with the aim to inform clinical practice and identify research gaps.MethodsWe conducted a scoping review identifying studies published in English from January 2005 to July 2025 through a comprehensive search of Scopus, MEDLINE, and the Cochrane Library. Eligible studies included randomized controlled trials, observational studies, case series, and case reports on treatment interventions and cl

Использование естественных экзоцитозных везикул для борьбы с возрастными заболеваниями: от возрастных драйверов до терапевтических возможностей.

Старение — это сложный биологический процесс, приводящий к увеличению нагрузки возрастных заболеваний (ARD). Клеточная старость, включающая необратимое остановку клеточного цикла и выделение фенотипа секреторной активности при старении (SASP), играет центральную роль в старении и развитии ARD. Естественные экзоцитические везикулы (NEVs) — это везикулы, полученные из клеток, органов и тканей без искусственных вмешательств. В последние годы NEVs привлекли внимание как медиаторы межклеточной коммуникации, и показали многофункциональный потенциал в регулировании клеточной старости и ARD. С одной с

Biomimetic materials for medical applications.

AbstractRecent advances in biomedical research have facilitated the exploration of biomimetic materials and their potential for diagnosing and treating diseases. This review synthesizes reports of recent research into biomimetic materials and provides a focused analysis of their therapeutic and diagnostic efficacy across multiple physiological systems, including the locomotor, digestive, respiratory, urinary, endocrine, nervous, integumentary, hematopoietic, and circulatory systems. These findings highlight the transformative potential of these materials in the management of systemic diseases.

Bone Metastasis of Breast Cancer: Molecular Mechanisms and Therapeutic Strategies.

Bone metastasis is a common complication of many types of advanced cancer, including breast cancer. Bone metastasis may cause severe pain, fractures, and hypercalcemia, rendering clinical management challenging and substantially reducing the quality of life and overall survival (OS) time of breast cancer patients. Studies have revealed that bone metastasis is related to interactions between tumor cells and the bone microenvironment, and involves complex molecular biological mechanisms, including colonization, osteolytic destruction, and an immunosuppressive bone microenvironment. Agents inhibi

Emerging therapeutic strategies in glioblastsoma: drug repurposing, mechanisms of resistance, precision medicine, and technological innovations.

Glioblastoma (GBM) is an aggressive Grade IV brain tumor with a poor prognosis. It results from genetic mutations, epigenetic changes, and factors within the tumor microenvironment (TME). Traditional treatments like surgery, radiotherapy, and chemotherapy provide limited survival benefits due to the tumor's heterogeneity and resistance mechanisms. This review examines novel approaches for treating GBM, focusing on repurposing existing medications such as antipsychotics, antidepressants, and statins for their potential anti-GBM effects. Advances in molecular profiling, including next-generation

2018 Ежегодное совещание СНГ: Североамериканская конференция по вопросам неадекватности и регулирования.

Аннотация не предоставлена источником. Откройте карточку для перехода к публикации.

Interplay Between Poly(ADP-ribosyl)ation and Specific Inner Cellular Events That Suggest Combination Strategies for Overcoming PARP Inhibitor Resistance.

Therapeutic resistance remains a major obstacle to durable cancer control, with functional reprogramming of the DNA damage response (DDR) network playing a central role. The poly(ADP-ribose) polymerase (PARP) family, particularly PARP1 and PARP2, is crucial for maintaining genomic integrity. By exploiting synthetic lethality, PARP inhibitors (PARPi) selectively target tumors with homologous recombination deficiency (HRD) and are integral to precision therapy in ovarian, breast, and prostate cancers. However, over 40% of patients with BRCA1/2 alterations develop resistance, and patient eligibil