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CCN proteins in the musculoskeletal system: current understanding and challenges in physiology and pathology.

The acronym for the CCN family was recently revised to represent "cellular communication network". These six, small, cysteine-enriched and evolutionarily conserved proteins are secreted matricellular proteins, that convey and modulate intercellular communication by interacting with structural proteins, signalling factors and cell surface receptors. Their role in the development and physiology of musculoskeletal system, constituted by connective tissues where cells are interspersed in the cellular matrix, has been broadly studied. Previous research has highlighted a crucial balance of CCN prote

Keyword Index for Volume 105

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The dual balance of the cytokine network: key messengers of immune activation and triggers of cytokine storm.

The cytokine network is the central regulatory system for intercellular communication within the immune system. Its proper function depends on the dynamic balance between pro-inflammatory and anti-inflammatory cytokines. Through complex positive and negative feedback loops, this balance precisely regulates the intensity and duration of immune responses, thereby playing a critical role in both physiological and pathological states. This review systematically summarizes the compositional features and classification framework of the cytokine network, as well as the mechanisms by which it maintain

NAT10 Regulates LPS-Induced Inflammation via Stabilization of N4-Acetylated PTX3 mRNA in Human Dental Pulp Stem Cells.

Severe dental pulp inflammation can lead to tissue lysis and destruction, underscoring the necessity for effective treatment of pulpitis. N-acetyltransferase 10 (NAT10)-mediated N4-acetylcytidine (ac4C) modification has recently emerged as a key regulator in inflammatory processes. However, whether NAT10 affects the inflammatory response in human dental pulp stem cells (hDPSCs) remains unelucidated. In this study, elevated NAT10 expression was observed in pulpitis tissues and LPS-stimulated hDPSCs. Knockdown of NAT10 led to reduced inflammatory gene expression and lower reactive oxygen species

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… New insights of epigenetics in vascular and cellular senescence J. Transl. Intern. Med. 2021 9 239 248 10.2478/jtim-2021-0049 PMC8802399 35136723 19. Feng J. Liu Y. Li K. Wu Y. Challenges and opportunities in targeting epigenetic mechanisms for pulmonary arterial hypertension treatment Int. J. …

Daratumumab в Transplan-Negle Dignesed Myeloma: Meta-Analis of Randomized Controled Tests.

Улучшилось качество фонового оборудования для трансплантации (TIE) с недавно диагностированными множественными миеломами (NDMM) anti-CD38 Моноклональные антитела. Среди них Даратумумаб в сочетании со стандартной терапией продемонстрировал многообещающие результаты клинических испытаний. Этот метаанализ объединяет данные об эффективности и безопасности лечения этой группы пациентов на основе daratumumumab из всех имеющихся выборочных контролируемых испытаний (RCTs). MethodsWe систематического поиска PubMed, Emmase, Cochrane Central Register of Controled Tests и клинических пробных реестров с мо

Study of Cinobufagin as a Promising Anticancer Agent in Uveal Melanoma Through Intrinsic Apoptosis Pathway.

Uveal melanoma (UM) is the most common primary intraocular carcinoma in adults. Cinobufagin, secreted by the Asiatic toad Bufo gargarizans, is a traditional Chinese medicine, widely used in tumor treatment. Here, we explored the potential antitumor function of cinobufagin and investigated its biochemical mechanisms in UM cells. The antitumor potential of cinobufagin was determined via cell viability, cell cycle, and apoptosis assays. Colony formation assays confirmed that cinobufagin exerted potent antitumor activity in a dose-dependent manner. We found that cinobufagin could induce cell apopt

Non-coding RNA/microRNA-modulatory dietary factors and natural products for improved cancer therapy and prevention: Alkaloids, organosulfur compounds, aliphatic carboxylic acids and water-soluble vitamins.

Non-coding small RNA molecules, the microRNAs (miRNAs), contribute decisively to the epigenetic regulation processes in cancer cells. Problematic pathogenic properties of cancer cells and the response of cancers towards anticancer drugs are highly influenced by miRNAs. Both increased drug activity and formation of tumor resistance are regulated by miRNAs. Further to this, the survival and proliferation of cancer cells and the formation of metastases is based on the modulated expression of certain miRNAs. In particular, drug-resistant cancer stem-like cells (CSCs) depend on the presence and abs

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… In breast cancer cells (MDA-MB-231, MCF-7), NaB induced cellular senescence via increased expression of miR-31 leading to suppression of BMI1 [115] . … MicroRNA-31 is a transcriptional target of histone deacetylase inhibitors and a regulator of cellular senescence J. Biol. Chem. 290 2015 10555 10567 25737447 10.1074/jbc.M114.624361 PMC4400362 116 Patnaik A. Rowinsky E.K. Villalona M.A. Hammond L.A. Britten C.D. Siu L.L. Goetz A. Felton S.A. …

The Roadmap of RANKL/RANK Pathway in Cancer.

The receptor activator of the nuclear factor-κB ligand (RANKL)/RANK signaling pathway was identified in the late 1990s and is the key mediator of bone remodeling. Targeting RANKL with the antibody denosumab is part of the standard of care for bone loss diseases, including bone metastases (BM). Over the last decade, evidence has implicated RANKL/RANK pathway in hormone and HER2-driven breast carcinogenesis and in the acquisition of molecular and phenotypic traits associated with breast cancer (BCa) aggressiveness and poor prognosis. This marked a new era in the research of the therapeutic use o

Oroxylin A: A Promising Flavonoid for Prevention and Treatment of Chronic Diseases.

There have been magnificent advancements in the understanding of molecular mechanisms of chronic diseases over the past several years, but these diseases continue to be a considerable cause of death worldwide. Most of the approved medications available for the prevention and treatment of these diseases target only a single gene/protein/pathway and are known to cause severe side effects and are less effective than they are anticipated. Consequently, the development of finer therapeutics that outshine the existing ones is far-reaching. Natural compounds have enormous applications in curbing seve

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… For example, in a study, OA was found to reduce the number of SA-β-gal-positive LO2 cells and inhibited cellular senescence in ethanol-treated hepatocytes via the activation of the YAP pathway and decreasing the expression of p16, p12, and HMGA1, which are important senescence markers [ 169 ]. …

Screening the Active Phytochemicals From Eclipta prostrata and Unraveling Their Molecular Insight Into Human Malignancies.

Current drugs against multiple human malignancies are limited, and developing new treatment strategies is improbable within a short time. So, considering the current situation, phytochemicals could be a viable option for developing chemotherapeutic agents for managing numerous types of malignancies. Therefore, we aimed to locate all phytochemicals of Eclipta prostrata and unravel their chemotherapeutic mechanisms and strategies individually. We defined 25 active compounds based on their anticancer activities after filtering through IMPPAT and literature search, and these compounds have chemoth

Metabolic Cooperation and Competition in the Tumor Microenvironment: Implications for Therapy.

The tumor microenvironment (TME) is an ensemble of non-tumor cells comprising fibroblasts, cells of the immune system, and endothelial cells, besides various soluble secretory factors from all cellular components (including tumor cells). The TME forms a pro-tumorigenic cocoon around the tumor cells where reprogramming of the metabolism occurs in tumor and non-tumor cells that underlies the nature of interactions as well as competitions ensuring steady supply of nutrients and anapleoretic molecules for the tumor cells that fuels its growth even under hypoxic conditions. This metabolic reprogram

Baseline immunonutritional status drives CAR T-cell efficacy, survival, and safety in R/R lymphoma: validation of a pre-lymphodepletion PNI threshold.

Chimeric antigen receptor (CAR) T-cell therapy has revolutionized the treatment landscape for relapsed/refractory (R/R) lymphoma. However, heterogeneous responses and treatment-related toxicities remain significant challenges. The prognostic nutritional index (PNI), reflecting both nutritional status and systemic immune competence, has emerged as a potential biomarker in various malignancies. This study aimed to evaluate the predictive value of the PNI assessed specifically prior to lymphodepletion in patients with R/R lymphoma receiving CAR T-cell therapy. We retrospectively analyzed 449 pati

NRF2: A crucial regulator for mitochondrial metabolic shift and prostate cancer progression.

Metabolic alterations are a common survival mechanism for prostate cancer progression and therapy resistance. Oxidative stress in the cellular and tumor microenvironment dictates metabolic switching in the cancer cells to adopt, prosper and escape therapeutic stress. Therefore, regulation of oxidative stress in tumor cells and in the tumor-microenvironment may enhance the action of conventional anticancer therapies. NRF2 is the master regulator for oxidative stress management. However, the overall oxidative stress varies with PCa clinical stage, metabolic state and therapy used for the cancer.

Oral Communication abstracts

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Новые клеточные модели для изучения взаимодействия Мьелин и Микроглиа.

Множественный склероз (MS) характеризуется обезвоживанием и нейроинфламмацией, при этом окислительный стресс играет ключевую роль в патологии поражения. Цель этого исследования заключалась в изучении дифференциальной реакции клеток на миелиновый мусор в различных окислительных состояниях. Окисление Myelin было вызвано с помощью системы Cuperoxid, что подтверждается повышенными уровнями TBARS и автофлюоресценцией. Из-за воздействия миелина на жизнеспособность микроглии BV-2 так и не была затронута. Однако окисленный миелин значительно изменил маркеры окислительного стресса, автофагию и метаболи

Митохондриальная пригодность как функциональная контрольная точка в раке: метаболическая пластичность, эволюция опухолей и иммунотерапия.

Митохондрия все чаще признается в качестве динамичных регуляторов адаптации к раковым клеткам, иммунной функции и терапевтической реакции. Помимо их канонической роли в производстве энергии, митохондриальный метаболизм, динамика, контроль качества и сигнализация стресса влияют на выживание клеток опухоли и способность клеток иммунного эффекта поддерживать антитумберную активность в микроопухоли. В этом обзоре мы рассматриваем митохондриальную пригодность как многоаспектное функциональное достояние, включающее биоэнергетику, метаболическую гибкость, повторное гомеостаз, контроль качества митохо

Strategies to Improve Sensitivity to Radiotherapy in Pediatric Solid Tumors.

The primary goal in the treatment of pediatric malignancies is to maintain effective cancer control while minimizing toxicities and late effects. Radiotherapy is a component of standard therapy against many pediatric cancers, but tumor cell DNA damage repair mechanisms and the hypoxic tumor microenvironment may limit the effectiveness of this modality. Additionally, irradiated cancer cells often acquire resistance to radiotherapy that permits cancer cell survival or stimulates tumor regrowth after treatment, further limiting the efficacy of radiotherapy. Various preclinical studies have invest

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… Camero and colleagues showed that silencing DNMT3A induces cellular senescence via upregulation of p16 and p21, while DNMT3B depletion causes DNA damage and impairs DNA repair mechanisms. …

T-Cell-Based Cellular Immunotherapy of Multiple Myeloma: Current Developments.

T-cell-based cellular therapy was first approved in lymphoid malignancies (B-cell acute lymphoblastic leukemia and large B-cell lymphoma) and expanding its investigation and application both in hematological and non-hematological malignancies. Two anti-BCMA (B cell maturation antigen) CAR (Chimeric Antigen Receptor) T-cell therapies have been recently approved for relapsed and refractory multiple myeloma with excellent efficacy even in the heavily pre-treated patient population. This new therapeutic approach significantly changes our practice; however, there is still room for further investiga

The genetic architecture of bone metastases: unveiling the role of epigenetic and genetic modifications in drug resistance.

Bone metastases represent frequent and severe complications in various cancers, notably impacting prognosis and quality of life. This review article delves into the genetic and epigenetic mechanisms underpinning drug resistance in bone metastases, a key challenge in effective cancer treatment. The development of drug resistance in cancer can manifest as either intrinsic or acquired, with genetic heterogeneity playing a pivotal role. Intrinsic resistance is often due to pre-existing mutations, while acquired resistance evolves through genetic and epigenetic alterations during treatment. These a

Unleashing NK cells for cancer immunotherapy in lung cancer: biologic challenges and clinical advances.

Natural killer (NK) cells are a crucial part of the innate immune system and serve as an important effector for killing tumor cells through direct cytolytic activity or immunomodulatory signaling to T cells and antigen presenting cells. NK cells are correlated with increased tumor control and better overall patient survival across various types of cancers including non-small cell lung cancer (NSCLC). Despite their promising potential for anti-tumor killing, NK cell function is often diminished within the tumor microenvironment. There are many factors that lead to decreased tumor-infiltrating N