Chlorogenic acid (CGA) is a dietary polyphenol with well-documented anti-inflammatory property. However, its effects on cholinergic signaling during inflammation remain under-explored.

This study aimed to investigate the cytotoxic, morphological, and molecular effects of Tamoxifen (TMX) and Chlorambucil (CHL) on breast cancer (MDA-MB-231) and cervical cancer (HeLa) cell lines. The impact of these agents on metastatic behavior, apoptotic mechanisms, and gene expression profiles was examined in both two-dimensional (2D) and three-dimensional (3D) cell culture models.

Gastric cancer is the fifth most prevalent malignancy worldwide. Atranorin is a polyphenol with significant anti-tumor activities. This study was conducted to evaluate the effect of atranorin on proliferation, apoptosis, and metastasis in two different human gastric cancer cell lines, AGS and HGC-27.

Primary ovarian insufficiency (POI) is characterized by the loss of normal ovarian function and depletion of the ovarian reserve before the age of 40. Approximately 4-30% of reported POI cases are familial, indicating a genetic cause. The Newborn Ovary Homeobox (NOBOX) gene, an oocyte-specific transcription factor, plays an essential role in ovarian development and oogenesis in vertebrates. Pathogenic variants in the NOBOX gene are reported to cause autosomal dominant premature ovarian failure (OMIM 610934).

Dendritic cell (DC) maturation is critical for antitumor immunity. Interferon-alpha 2b (IFNα2b) enhances dendritic cell function; however, its effects on monocyte-derived DCs (Mo-DCs) from NSCLC patients remain unclear. This in vitro experimental study investigates IFNα2b-mediated Mo-DC maturation and immune function in both healthy individuals and NSCLC patients.

Chronic kidney disease (CKD) progression is linked to renal fibrosis, influenced by profibrotic factors like transforming growth factor-beta 1 (TGF-β1) and fibroblast growth factor-2 (FGF-2). Despite advancements in synthetic drugs like enalapril, evidence for plant-derived candidates that slow kidney fibrosis remains limited, underscoring the need for rigorous preclinical evaluation.

A serious side effect of allogeneic hematopoietic cell transplantation (HCT) is known as graft-versus-host disease (GvHD), in which the recipient's body is attacked by donor immune cells, leading to a high rate of morbidity and death. Although there are several therapies available for GvHD, their efficacy is limited, and they sometimes have serious adverse effects. Recently, one of the most interesting research in the field of cell therapy is the use of mesenchymal stromal cells (MSCs), which have been investigated in the treatment of HCT and its consequences such as GvHD, due to their potential in tissue repair and immunomodulatory activities. The potential negative consequences of direct cell transplantation are avoided by using MSC-EVs, which are micro vesicles packed with physiologically active materials like proteins, microRNAs, and other nucleic acids. One of the biggest advantages of MSC-EVs is their ability to dramatically alter immune cell responses in GvHD by delivering immunomodulatory chemicals and anti-inflammatory drugs to recipient cells. Some of the significant discoveries include encouraging the differentiation of pro-inflammatory macrophages into tissue-reparative macrophages, inhibiting the generation of inflammatory cytokines, and improving the function of regulatory T-cells. This study details the effects of MSC-EVs on the multiple alterations that occurred inside host cells as well as immunomodulation mediated by both T cells and antigen-presenting cells in terms of the immunopathology of GvHD and direct regenerative effects on damaged tissues.

Cancer cells are well equipped with plasma membrane repair to survive mechanical tension, chemical stress, immune assaults and therapeutic interventions. Maintaining plasma membrane integrity is quintessential for tumor cells as it plays a pivotal role in communication between the internal environment of the tumor cell and the extracellular surroundings. Therefore, tumor cells achieve plasma membrane repair by several dynamic repair pathways such as calcium (Ca) guided lysosomal exocytosis, annexins (ANXs) mediated membrane repair and shedding, damaged oriented membrane repair via endocytosis, ESCRT (Endosomal Sorting Complex Required for Transport) mediated plasma Membrane repair and LC-3 Associated Macropinocytosis (LAM) to survive persistent membrane damage inflicted by immune attack, mechanical stress especially during metastasis and chemotherapy induction. These processes rapidly restore membrane integrity, maintaining cellular homeostasis and conferring survival advantages during metastasis and immune evasion. Notably, key repair proteins such as ANXs, synaptotagmin VII (Syt VII), ESCRT components, and autophagy-related factors (ATGs, rubicon and LC-3) are often upregulated in various cancers including breast, pancreatic, bladder, liver, and aggressive solid tumors, highlighting their clinical relevance and potential as therapeutic targets. Moreover, an understanding of the mechanistic interplay among different pathways unveils a new therapeutic window to selectively disrupt these repair pathways, sensitizing cancer cells to persistent damage while sparing normal tissues. This review elucidates the mechanisms of plasma membrane repair in cancer, highlights the differential regulation of their key mediators across multiple tumor types, and briefly explores their therapeutic potential.

A high-fat diet (HFD) is associated with low fertility in male mice, characterized by reduced sex hormone levels and impaired sperm quality. The epididymis is crucial for sperm maturation, yet its vulnerability to metabolic disturbances remains poorly understood. METHODS AND RESULTS: Twelve C57BL/6J mice were randomly assigned to either a HFD (60% kcal from fat; Research Diets, D12492) or a standard diet group. The dietary intervention started at 5 weeks of age and was maintained for 10 weeks. Epididymal tissues from both groups were studied using immunofluorescence and Western blotting. Compared to the control group, HFD-fed mice exhibited significant increases in body weight, epididymal fat pad weight, serum lipids, along with decreased serum testosterone. Epididymal tissues from the HFD group showed marked lipid droplet accumulation and elevated oxidative stress. Consistently, the activity and expression of key lipolytic enzymes-hormone-sensitive lipase (HSL) and adipose triglyceride lipase (ATGL)-were significantly downregulated. Furthermore, HFD feeding disrupted mitochondrial dynamics, as indicated by reduced levels of fusion proteins (MFN1/MFN2) and altered expression of fission markers (p-DRP1(Ser616) and FIS1). Moreover, autophagy-particularly mitophagy and lipophagy-was impaired, evidenced by a significant reduction in autophagosomes and dysregulation of autophagy-related proteins.

Helicobacter pylori (H. pylori) is a common pathogen that causes serious pathologies such as gastritis, ulcers, and gastric cancer. This study evaluates the therapeutic effects of melittin on H. pylori induced gastric injury, oxidative stress, and tissue damage in an in vivo model.

The differentiation of skin dermal fibroblast into myofibroblast is a critical process in tissue repair and granulation tissue formation, directly affecting the progression of wound healing. While autophagy has been implicated in regulating dermal fibroblast differentiation during wound repair, the underlying molecular mechanisms remain incompletely defined.

Programmed cell death 4 (PDCD4) is a tumor suppressor characterized by its MA3 domain-mediated binding to eIF4A, which suppresses protein synthesis. Its primary functions include inhibiting cell proliferation, invasion, and metastasis, as well as promoting apoptosis. Leukemia is a clonally hematologic malignancy whose pathogenesis is driven primarily by the aberrant activation of key signaling pathways. These dysregulated signals promote enhanced self-renewal, uncontrolled proliferation, impaired differentiation, and blocked apoptosis, collectively arresting leukemic cells at various stages of development. Recent studies have demonstrated a close association between PDCD4 and leukemia development, indicating that PDCD4 regulates this process mainly by participating in abnormally activated signaling pathways. This review examines the expression and regulation of PDCD4 in leukemia, with a focus on its role as a molecular hub that connects the JAK/STAT, PI3K/AKT, and MAPK signaling pathways into a comprehensive network of leukemia pathways. Furthermore, the potential value of PDCD4 in the treatment of leukemia is discussed.

The maintenance of lens transparency depends on the structural stability and functional integrity of crystallin, and post-translational modification (PTM) is the core link in regulating the conformation, solubility, and molecular chaperone activity of crystallin. This article systematically reviews the molecular mechanisms of key PTM types in crystallin, analyzes the synergistic and antagonistic effects among different PTMs, and clarifies that PTM imbalance promotes the occurrence and development of cataracts by inducing denaturation and aggregation of crystallin. Meanwhile, summarize the research progress of PTM as a diagnostic marker and therapeutic target for cataracts, providing a comprehensive theoretical reference for the study of cataract mechanisms and their application in diagnosis and treatment.

Cancer is one of the major causes of human mortality worldwide. The available cancer therapy is associated with significant adverse effects. Targeted therapies represent a promising approach in drug discovery, focusing on specific pathways involved in cancer growth. Pim kinases play an important role in cancer signal transduction, promoting cell proliferation and inhibiting apoptosis, particularly in prostate and breast cancers. Pim-kinase inhibitors have emerged as an effective targeted therapy to treat cancer. Nitrogen-containing heterocyclic compounds have been reported to bind selectively with a specific Pim kinase enzyme. Various interesting compounds of nitrogen-containing heterocyclic rings, such as pyridine, pyrimidine, thiazole, quinoline, pyrazole, and indole, etc., have shown promising Pim kinase inhibitory potential. This review discusses the design strategies, molecular docking studies, and structure-activity relationships (SAR), including the importance of nitrogen heterocyclic derivatives in the drug discovery of anticancer agents. These developments can further improve the targeted therapy and could help in mitigating the adverse drug effects in cancer treatment. Recent advancements in the development of Pim kinase inhibitors as anti-neoplastic agents could pave the way for the discovery and development of more novel and clinically useful Pim kinase inhibitors for future cancer therapies.

Fibroblast proliferation is influenced by inter alia the cellular transport of glucose and its metabolism. The aim of the study is to confirm whether irisin is involved in the regulation of human cardiac fibroblast proliferation, and whether its effect is dependent on glucose concentration or glucose transporter activity (GLUT1). The study also examines the expression of glucose transporters on the cardiac fibroblast cell membrane.

Tumor-associated extracellular matrix (ECM) remodeling provides a supportive microenvironment for aberrant cellular behaviors and fate, resulting in tumor progression. Concurrently, reprogrammed lipid metabolism, characterized by dysregulated de novo lipogenesis, fatty acid oxidation (FAO), and lipid peroxidation, serves as a metabolic hallmark of cancer. Emerging evidence reveals a bidirectional crosstalk between ECM remodeling and lipid metabolic rewiring, which collectively drive tumorigenesis, survival, metastasis, and drug resistance. However, the mechanistic links connecting ECM dynamics to cellular lipid metabolism remain incompletely elucidated. In this review, we dissect the mechanistic underpinnings of ECM-lipid metabolism crosstalk, focusing on biochemical and biophysical modulation. In general, ECM-lipid metabolism axis form a self-amplifying feedback circuit, wherein ECM remodeling regulates lipid anabolism and catabolism to fuel energy production, membrane biosynthesis, and signaling molecules generation, while lipid metabolites reciprocally promote ECM degradation or deposition. Targeting critical nodes within this circuit-such as ECM-derived cues (e.g., collagen) or intracellular lipid metabolism pathway (e.g., FAO)-represents a promising strategy to disrupt tumor-stroma coevolution and enhance therapeutic efficacy. Notably, this crosstalk is not static but highly dynamic, exhibiting context-dependent dual roles influenced by variables such as cell state, cancer type, tumor site, and disease stage.

Thyroid cancer is now the most commonly diagnosed endocrine malignancy over the past decade, with its incidence having risen sharply. Due to its asymptomatic presentation and poor prognosis when detected at advanced stages, early diagnosis of papillary thyroid cancer (PTC) remains a challenge, even with recent medical advancements. Fortunately, serum-based miRNA testing offers a safe, minimally invasive, and repeatable diagnostic tool. Among promising miRNAs, miRNA-155 has emerged as a potential biomarker for diagnosis and prognosis and, miRNA-429 appears to be more variable and cancer-type specific.

Inflammatory cytokines are crucial for various cellular mechanisms, including differentiation, fibrosis, and proliferation. Cytokine dysregulation provokes pathophysiologic conditions in cholangiocytes, even cholangiocarcinogenesis. Specifically, transforming growth factor-beta (TGF-β) and interleukin-6 (IL-6) are known to be related to cholangiocarcinoma progression. We investigated the pathophysiological signaling in normal cholangiocyte (H69) spheroids mediated by TGF-β1 or/and IL-6.