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Gut microbiota and microbial metabolites for osteoporosis.

Osteoporosis is an age-related bone metabolic disease. As an essential endocrine organ, the skeletal system is intricately connected with extraosseous organs. The crosstalk between bones and other organs supports this view. In recent years, the link between the gut microecology and bone metabolism has become an important research topic, both in preclinical studies and in clinical trials. Many studies have shown that skeletal changes are accompanied by changes in the composition and structure of the gut microbiota (GM). At the same time, natural or artificial interventions targeting the GM can

Epigenetic Mechanisms Involved in the Cardiovascular Toxicity of Anticancer Drugs.

The cardiovascular toxicity of anticancer drugs promotes the development of cardiovascular diseases. Therefore, cardiovascular toxicity is an important safety issue that must be considered when developing medications and therapeutic applications to treat cancer. Among anticancer drugs, members of the anthracycline family, such as doxorubicin, daunorubicin and mitoxantrone, are known to cause cardiotoxicity and even heart failure. Using human-induced pluripotent stem cell-derived cardiomyocytes in combination with "Omic" technologies, we identified several cardiotoxicity mechanisms and signal t

Peroxisome Proliferator-Activated Receptors (PPAR)γ Agonists as Master Modulators of Tumor Tissue.

In most clinical trials, thiazolidinediones do not show any relevant anti-cancer activity when used as mono-therapy. Clinical inefficacy contrasts ambiguous pre-clinical data either favoring anti-tumor activity or tumor promotion. However, if thiazolidinediones are combined with additional regulatory active drugs, so-called 'master modulators' of tumors, i.e., transcriptional modulators, metronomic low-dose chemotherapy, epigenetically modifying agents, protein binding pro-anakoinotic drugs, such as COX-2 inhibitors, IMiDs, etc., the results indicate clinically relevant communicative reprogram

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… Nuclear receptor coactivators: Master regulators of human health and disease. Ann. Rev. Med. 2014;65:279–292. doi: 10.1146/annurev-med-051812-145316. 22. Akbiyik F., Ray D.M., Gettings K.F., Blumberg N., Francis C.W., Phipps R.P. …

Proteoglycans as Molecular Regulators of Bone Metastasis: Extracellular Matrix Remodeling, Tumor-Bone Crosstalk, Dormancy, and Therapeutic Opportunities.

Background: Bone metastasis is a frequent and debilitating complication of advanced cancer, particularly in breast and prostate cancer, and is driven by complex interactions among tumor cells, bone-resident cells, immune populations, vascular components, and the extracellular matrix. Within this specialized microenvironment, proteoglycans have emerged as key molecular regulators of tumor-bone crosstalk, matrix remodeling, metastatic niche formation, dormancy, and therapeutic resistance. Methods: We conducted a narrative review using targeted searches of PubMed and Google Scholar for studies pu

Protein breakdown in muscle wasting: role of autophagy-lysosome and ubiquitin-proteasome.

Skeletal muscle adapts its mass as consequence of physical activity, metabolism and hormones. Catabolic conditions or inactivity induce signaling pathways that regulate the process of muscle loss. Muscle atrophy in adult tissue occurs when protein degradation rates exceed protein synthesis. Two major protein degradation pathways, the ubiquitin-proteasome and the autophagy-lysosome systems, are activated during muscle atrophy and variably contribute to the loss of muscle mass. These degradation systems are controlled by a transcription dependent program that modulates the expression of rate-lim

Возможная роль метаформы и фибробластного роста Factor-21 В Multical Sclerosis Neuropathology: Birds of a Feather Flock Common.

Множественный склероз (MS) — прогрессивное демиелинизирующее заболевание CNS, характеризующееся воспалением, образованием CNS-клеров и повреждением нейронной миелинской оболочки (graphical abstract). Фактор роста фибробласта 21 (FGF21) занимается различными метаболическими расстройствами и нейродегенеративными заболеваниями. FFF21 и его корецептор β-Kloth имеют существенно важное значение для процесса ремиелиции MS. Метформин, инсулин-сенсибилизирующее лекарство, которое является первой линией лечения для типа 2 Мэлитус диабета (T2DM) может оказывать потенциальное нейрозащитное воздействие, ре

Triple‑negative breast cancer cell‑derived piR‑31115 promotes the proliferation and migration of endothelial cells via METTL3‑mediated m6A modification of YAP1.

Triple‑negative breast cancer (TNBC), a highly malignant breast cancer subtype with a pronounced metastatic propensity, forms the focus of the present investigation. MDA‑MB‑231, a prevalently utilized TNBC cell line in cancer research, was employed. In accordance with the tumour angiogenesis theory, cancer cells are capable of instigating angiogenesis and the formation of a novel vascular system within the tumour microenvironment, which subsequently sustains malignant proliferation and metastasis. Consequently, impeding the growth of tumour blood vessels holds substantial significance in suppr

Pilot study of lithium to restore intestinal barrier function in severe graft-versus-host disease.

UNLABELLED: Severe intestinal graft-vs-host disease (GVHD) after allogeneic hematopoietic cell transplantation (HCT) causes mucosal ulceration and induces innate and adaptive immune responses that amplify and perpetuate GVHD and the associated barrier dysfunction. Pharmacological agents to target mucosal barrier dysfunction in GVHD are needed. We hypothesized that induction of Wnt signaling by lithium, an inhibitor of glycogen synthase kinase (GSK3), would potentiate intestinal crypt proliferation and mucosal repair and that inhibition of GSK3 in inflammatory cells would attenuate the deregula

Targeting Reactive Oxygen Species Capacity of Tumor Cells with Repurposed Drug as an Anticancer Therapy.

Accumulating evidence shows that elevated levels of reactive oxygen species (ROS) are associated with cancer initiation, growth, and response to therapies. As concentrations increase, ROS influence cancer development in a paradoxical way, either triggering tumorigenesis and supporting the proliferation of cancer cells at moderate levels of ROS or causing cancer cell death at high levels of ROS. Thus, ROS can be considered an attractive target for therapy of cancer and two apparently contradictory but virtually complementary therapeutic strategies for the regulation of ROS to treat cancer. Desp

RSK inhibitor BI-D1870 inhibits acute myeloid leukemia cell proliferation by targeting mitotic exit.

The 90 kDa Ribosomal S6 Kinase (RSK) drives cell proliferation and survival in cancers, although its oncogenic mechanism has not been well characterized. Phosphorylated level of RSK (T573) was increased in acute myeloid leukemia (AML) patients and associated with poor survival. To examine the role of RSK in AML, we analyzed apoptosis and the cell cycle profile following treatment with BI-D1870, a potent inhibitor of RSK. BI-D1870 treatment increased the G2/M population and induced apoptosis in AML cell lines and patient AML cells. Characterization of mitotic phases showed that the metaphase/an

Insights into the role of RNA m6A modification in the metabolic process and related diseases.

According to the latest consensus, many traditional diseases are considered metabolic diseases, such as cancer, type 2 diabetes, obesity, and cardiovascular disease. Currently, metabolic diseases are increasingly prevalent because of the ever-improving living standards and have become the leading threat to human health. Multiple therapy methods have been applied to treat these diseases, which improves the quality of life of many patients, but the overall effect is still unsatisfactory. Therefore, intensive research on the metabolic process and the pathogenesis of metabolic diseases is imperati

Molecular Mechanisms Underlying Curcumin-Mediated Therapeutic Effects in Type 2 Diabetes and Cancer.

The growing prevalence of age-related diseases, especially type 2 diabetes mellitus (T2DM) and cancer, has become global health and economic problems. Due to multifactorial nature of both diseases, their pathophysiology is not completely understood so far. Compelling evidence indicates that increased oxidative stress, resulting from an imbalance between production of reactive oxygen species (ROS) and their clearance by antioxidant defense mechanisms, as well as the proinflammatory state contributes to the development and progression of the diseases. Curcumin (CUR; diferuloylmethane), a well-kn

Спасение гиппокампальной синаптической пластичности и эффективности памяти Финголимода (FTY720) в модели APP/PS1 болезни Альцгеймера сопровождается коррекцией метаболизма финголипидов, полиаминов и фосфолипидного насыщенного состава.

Ранее, наши метаболомические, транскриптомные и геномные исследования характеризовали путь церамида/шфингомилена как терапевтическую цель в болезни Альцгеймера, и мы показали, что FTY720, фингозин-1-фосфахатный рецептор, утвержденный для лечения множественных склерозов, восстанавливает синаптическая пластичность и память в мышах APP/PS1. Для дальнейшего изучения того, как FTY720 спасает патологию, мы провели метаболический анализ мозга, плазмы и печени обученных APP/PS1 и диких мышей. APP/PS1 мыши продемонстрировали локальные нарушения мозга в полиаминах, фосфолипидах и сфинголипидах. Большинс

МикроРНК-219 в центральной нервной системе: потенциальный тераностический подход.

Несмотря на недавние терапевтические достижения в области неврологических расстройств, лечебная терапия во многих случаях остается серьезной проблемой. Несмотря на то, что в последние годы мы стали свидетелями развития генной терапии из различных терапевтических подходов, влияющих на патофизиологические механизмы, существуют интригующие аспекты, касающиеся эффективности, безопасности и механизма действий генной терапии. Микрорибонуклеиновая кислота (микроRNA-miRNA) в качестве основного генного регулятора регулирует рибонуклеиновую кислоту курьера (mRNA) путем прямого соединения через 3'неперев

The multiple roles of interferon regulatory factor family in health and disease.

Interferon Regulatory Factors (IRFs), a family of transcription factors, profoundly influence the immune system, impacting both physiological and pathological processes. This review explores the diverse functions of nine mammalian IRF members, each featuring conserved domains essential for interactions with other transcription factors and cofactors. These interactions allow IRFs to modulate a broad spectrum of physiological processes, encompassing host defense, immune response, and cell development. Conversely, their pivotal role in immune regulation implicates them in the pathophysiology of v

Novel drug targets for personalized precision medicine in relapsed/refractory diffuse large B-cell lymphoma: a comprehensive review.

Diffuse large B-cell lymphoma (DLBCL) is a clinically heterogeneous lymphoid malignancy and the most common subtype of non-Hodgkin's lymphoma in adults, with one of the highest mortality rates in most developed areas of the world. More than half of DLBLC patients can be cured with standard R-CHOP regimens, however approximately 30 to 40 % of patients will develop relapsed/refractory disease that remains a major cause of morbidity and mortality due to the limited therapeutic options.Recent advances in gene expression profiling have led to the identification of at least three distinct molecular

Proceedings of International Conference on Cell Death in Cancer and Toxicology. February 20-22, 2018. Guest Editors: Kausar M. Ansari, CSIR-IITR, India and Dhyan Chandra, Roswell Park, USA.

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Декодирование GPCR, сигнализирующее перепрограммирование рака: молекулярные механизмы и терапевтические последствия.

G белковые рецепторы (GPCR) представляют собой крупнейшую мембранную группу рецепторов в геноме человека и служат ключевыми регуляторами клеточного сигнала, гомеостаза и фармакологической реакции. Помимо их классической роли в посредничестве внеклеточной стимуляции по зависящим от G-протеина и независимым путям, которые играют ключевую роль при помощи GPCR сигнальных путей, включая CAMP-PKA/EPAC, IP3/PLC, PI3K/Akt/mTOR и ERK/MAPK cascades, в вождении онкогенного распространения, апоптоза и метастаза. Кроме того, ГПХР замешаны в опухоли с помощью различных молекулярных механизмов, в рамках кото

The sirtuin family in health and disease.

Sirtuins (SIRTs) are nicotine adenine dinucleotide(+)-dependent histone deacetylases regulating critical signaling pathways in prokaryotes and eukaryotes, and are involved in numerous biological processes. Currently, seven mammalian homologs of yeast Sir2 named SIRT1 to SIRT7 have been identified. Increasing evidence has suggested the vital roles of seven members of the SIRT family in health and disease conditions. Notably, this protein family plays a variety of important roles in cellular biology such as inflammation, metabolism, oxidative stress, and apoptosis, etc., thus, it is considered a

The Role of Radiosensitizing Drugs in Osteosarcoma Treatment: Mechanisms and Clinical Perspectives.

Osteosarcoma is a highly malignant bone tumor that is resistant to radiotherapy and is associated with poor treatment outcomes and prognoses. Understanding the mechanisms of radioresistance and finding strategies to enhance the radiosensitivity is crucial for improving clinical efficacy. The aim of this review was to address the approaches for enhancing the efficacy of radiotherapy in osteosarcoma, thereby improving patient outcomes. Specifically, we have focused on the mechanisms of radiosensitization and the relationship between drugs that enhance radiosensitivity and cancer. These mechanism