Search Results (8,735)

In recent decades, the novel role of Galectin-3 (Gal-3) in both physiological and pathological conditions has emerged. Gal-3 is a key protein involved in immunity, inflammation, cell adhesion, proliferation, differentiation, and apoptosis. Its physiological role is crucial for the regulation of these cellular functions. In pathological settings, elevated levels of Gal-3 are associated with diseases such as cancer, heart failure, and fibrotic diseases, making it an important diagnostic and prognostic biomarker in these conditions. It seems that Gal-3 acts as a bridge between different diseases. Because of its pro-inflammatory and pro-tumorigenic properties, it connects atherosclerosis and cancer, regulating inflammation, cell proliferation, immune evasion, angiogenesis and survival in both diseases. Specifically, in atherosclerosis, Gal-3 promotes plaque formation by driving inflammation, oxidative stress, lipid deposition, and vascular cell migration. In cancer, Gal-3 influences tumor growth and metastasis by modulating an immunosuppressive tumor microenvironment, increasing cell survival, and enhancing cell–matrix and cell–cell interactions. Moreover, by stimulating fibroblasts, Gal-3 favors matrix deposition and tissue fibrosis that together with the inflammatory properties contributes to adverse ventricular remodeling leading to heart failure. Finally, taking into account its role in pathogen recognition and immune cells (B and T cells) modulation, Gal-3 might be a critical factor in host defense, disease progression, and the development of autoimmune conditions. Thus, targeting Gal-3 might be a promising therapeutic strategy to pursue for management of different pathological scenarios. Full article

Pharyngeal cartilage, derived from neural crest cells (NCCs), undergoes complex morphogenesis driven by signals from the pharyngeal endoderm. However, the molecular mechanisms governing NCC proliferation and differentiation in response to endoderm-derived signals remain poorly understood. Here, we investigate the role of klf5a, a zinc-finger transcription factor expressed in pharyngeal endodermal pouches, in zebrafish pharyngeal cartilage development. Knockdown of klf5a using morpholinos minimally affected cranial NCC specification and migration but significantly impaired their proliferation and differentiation in the pharyngeal region. Notably, klf5a deficiency reduced expression of fgfbp2b, a modulator of FGF signaling, in the pharyngeal endoderm. Co-injection of klf5a mRNA rescued the cartilage defects, but injection of fgfbp2b mRNA alone failed to restore normal cartilage morphogenesis, suggesting that fgfbp2b is not the sole mediator of klf5a’s effects. These findings indicate that klf5a regulates endodermal signaling to direct NCC-derived pharyngeal cartilage formation, likely through multiple downstream targets including fgfbp2b. This study provides insights into the complex molecular network underlying craniofacial development and highlights potential therapeutic targets for craniofacial disorders. Full article

The current known data on the involvement of the peptidergic systems in breast cancer progression is overwhelmingly vast. Peptidergic systems are useful tools for imaging, diagnosis, prognosis and treatment of breast cancer. These systems play a crucial role in both basic and clinical breast cancer research by enabling the exploration of novel molecular mechanisms, signaling pathways, and the development of effective drug design strategies. Breast cancer cells overexpress peptide receptors; at the same time they are known to interact with peptides that (a) exert an oncogenic action (adrenomedullin 2, endothelin, gastrin-releasing peptide, neurokinin A, neuromedin, neuropeptide Y, neurotensin, substance P, vasoactive intestinal peptide), (b) exert an anticancer action (angiotensin (1–7), ghrelin, peptide YY) or (c) exert dual oncogenic and anticancer effects (adrenomedullin, angiotensin II, bradykinin, corticotropin-releasing factor, β-endorphin, glucagon-like peptide 1, gonadotropin-releasing hormone, kisspeptin, methionine-enkephalin, oxytocin). This indicates that peptides, as well as peptide receptor agonists and antagonists, may serve as antitumor agents due to their diverse actions against breast cancer development, including the inhibition of cell proliferation, migration and invasion, induction of apoptosis, and anti-angiogenesis. Multiple strategies have been developed to combat breast cancer, including peptide receptor silencing; antibodies conjugated to specific signaling proteins; antibodies targeting specific peptide receptors or oncogenic peptides; and the use of peptides or peptide receptor agonists/antagonists loaded with antitumor cargo. Future lines of research are suggested in breast cancer using promising anti-breast-cancer peptide receptor antagonists (HOE-140, exendin (9–39), bosentan, macitentan, PD168,368, CGP71,683A, SR48,692, aprepitant) or agonists (FR190,997, semaglutide, exendin 4, goserelin) mentioned in this review. Peptidergic systems have tremendous anti-breast-cancer clinical potential which must be exploited and developed. Taken together, the available data highlight the enormous promise of translational research into breast cancer and peptidergic systems for the development of effective treatments. A full understanding of the roles played by the peptidergic systems in breast cancer will serve to improve diagnosis and treatment. Full article

Dry Eye Disease (DED) is a multifactorial condition of the ocular surface, with one potential cause being damage from eye drops containing preservatives such as benzalkonium chloride (BAC). Current treatments for DED are unsatisfactory; therefore, it is worth exploring new therapies based on the secretome derived from stem cells. Human stem cells are important sources of growth factors and cytokines that promote tissue regeneration. The secretome of these cells can be obtained in vitro in conditioned medium (CM). The aim of the study was to evaluate the effect of CM derived from adipose-derived stem cells (hADSCs) and amniotic membrane-derived cells expressing mesenchymal and/or epithelial markers on limbal stem cells (LSCs) damaged by BAC, focusing on their regenerative potential. The study used two experimental models: the first focused on neutralizing the toxic effects of BAC when each CM was administered concurrently, and the second on the therapeutic effects of CM after prior cell damage by BAC. The effects of CM on LSCs were assessed, including apoptosis, cell cycle progression, proliferation, migration, and inflammation. CM from ADSCs and amniotic cells were shown to significantly reduce BAC-induced damage to LSCs. All tested CM promoted LSC regeneration, although their efficacy varied among treatments. The application of CM during BAC exposure yielded stronger and more consistent benefits than post-injury treatment. Full article

Heparan sulfate proteoglycans (HSPGs) are essential constituents of the extracellular matrix (ECM) and cell surface, orchestrating a wide range of biological processes, such as cell adhesion, migration, proliferation, and intercellular communication. Through their highly sulfated glycosaminoglycan chains, HSPGs serve as crucial modulators of bioavailability and signaling of growth factors, cytokines, and chemokines, thereby influencing tissue homeostasis. Their dynamic remodeling is mediated by numerous enzymes, with heparanase (HPSE) playing a predominant role as the only known human endo-β-D-glucuronidase that specifically cleaves heparan sulfate chains. Beyond its well-documented enzymatic activity in ECM degradation and the release of HS-bound molecules, HPSE also exerts non-enzymatic functions that regulate intracellular signaling cascades, transcriptional programs, and immune cell behavior. Dysregulated HPSE expression or activity has been implicated in various pathological conditions, including fibrosis, chronic inflammation, cancer progression, angiogenesis, metastasis, and immune evasion, positioning this enzyme as a pivotal driver of ECM plasticity in both health and disease. This review provides an updated overview of HSPG biosynthesis, structure, localization, and functional roles, emphasizing the activity of HPSE and its impact on tissue remodeling and disease pathogenesis. We further explored its involvement in the hallmark processes of cancer, the inflammatory tumor microenvironment, and its contribution to fibrosis. Finally, we summarize current therapeutic strategies targeting HPSE, outlining their potential to restore ECM homeostasis and counteract HPSE-driven pathological mechanisms. A deeper understanding of the HSPG/HPSE axis may pave the way for innovative therapeutic interventions in cancer, inflammatory disorders, and fibrotic diseases. Full article

Mesenchymal stem cells (MSCs) are multipotent cells capable of self-renewal and differentiation into specialized cell types, which play an important role in maintaining homeostasis and tissue regeneration in humans. The effectiveness of MSCs depends largely on their immunomodulatory properties and ability to regenerate damaged tissues. Biological activity of MSCs is modulated by environmental factors, including dietary components such as vitamins, minerals, and phytochemicals which influence their proliferation, aging, inflammatory response and resistance to oxidative stress. The article aims to highlight the importance of micronutrients and phytochemicals in modulating the MSCs’ performance and therapeutic potential, with a focus on the role of bioactive food components in regulating metabolism, regenerative efficacy and protective mechanisms of stem cells. Vitamins and trace elements are essential for antioxidant protection by eliminating reactive oxygen species, maintaining mitochondrial function and preserving cell viability under stressful conditions. Micronutrients and phytochemicals can modulate the immunomodulatory activity of MSCs by altering the cytokine secretion profile, reducing pro-inflammatory mediators while enhancing anti-inflammatory factors. However, both deficiency and excessively high concentrations of natural compounds can impair stem cell function. Interdisciplinary knowledge about the impact of micronutrients on the functioning of mesenchymal stem cells creates new opportunities in personalized medicine and nutrition. Understanding the mechanisms regulating MSCs activity under the influence of diet components may contribute to the development of individualized therapeutic strategies aimed at supporting tissue regeneration, delaying aging processes, and improving the prevention and treatment of chronic diseases. This knowledge is applicable in the design of functional foods and dietary supplements, making it particularly valuable for specialists in personalized nutrition and functional food development. Full article

The rapid proliferation of e-commerce has reshaped the spatial logic and facility typologies of urban logistics. While the literature on logistics facility location selection is extensive, there is limited understanding of how the relative importance of location criteria varies across facility types shaped by e-commerce. This study addresses this gap by analyzing the location criteria of logistics facilities of different sizes using a multi-criteria decision-making (MCDM) approach. Twenty-five criteria, identified through a literature review and feedback from seven experts in the Istanbul e-commerce logistics sector, were analyzed using the Fuzzy Simple Additive Weighting (SAW) method. The relative weights of criteria were calculated for three facility scales, macro-, meso-, and micro-scales, to reveal how location priorities vary across scales. Proximity to main arteries ranks first across all scales (macro: 0.317, meso: 0.431, micro: 0.409). Land rental values are highly prioritized at both the macro- and meso-scale, while population density ranks prominently at the macro- and micro-scale. At the meso-scale, shopping mall proximity gains notable weight, whereas intermediate arteries stand out as a key factor at the micro scale. These findings advance the understanding of scale-sensitive dynamics in urban logistics and provide a framework for more adaptable and sustainable logistics planning. Full article

Endometriosis involves oestrogen-dependent chronic inflammation and the abnormal proliferation of ectopic endometrial tissue. Conventional hormonal therapies suppress systemic oestrogen, but do not fully address local oxidative and inflammatory signalling. This review provides a mechanistic synthesis of recent molecular evidence. This evidence is on four FDA-recognized (Food and Drug Administration) medicinal plants. These are Curcuma longa, Zingiber officinale, Glycyrrhiza glabra, and Silybum marianum. The review highlights their capacity to modulate key intracellular pathways. These pathways are implicated in endometriosis. The review covers the integration of phytochemical-specific actions within NF-κB- (nuclear factor kappa-light-chain-enhancer of activated B cells), COX-2-(Cyclooxygenase-2), PI3K/Akt-(PI3K/Akt signaling pathway), Nrf2/ARE-(Nuclear factor erythroid 2–related factor 2) and ERβ-(Estrogen receptor beta) mediated networks, which jointly regulate cytokine secretion, apoptosis, angiogenesis and redox balance in endometrial lesions. Curcumin downregulates COX-2 and aromatase while activating Nrf2 signalling, shogaol from ginger suppresses prostaglandin synthesis and induces caspase-dependent apoptosis, isoliquiritigenin from liquorice inhibits HMGB1-TLR4–NF-κB (High Mobility Group Box 1, Toll-like receptor 4) activation, and silymarin from milk thistle reduces IL-6 (Interleukin-6) and miR-155 (microRNA-155) expression while enhancing antioxidant capacity. Together, these phytochemicals demonstrate pharmacodynamic complementarity with hormonal agents by targeting local inflammatory and oxidative circuits rather than systemic endocrine axes. This mechanistic framework supports the rational integration of phytotherapy into endometriosis management and identifies redox-inflammatory signalling nodes as future translational targets. Full article

Granulocyte-macrophage colony-stimulating factor (GM-CSF) has emerged as a key cytokine in the pathogenesis of rheumatoid arthritis, an autoimmune disease distinguished by synovial inflammation and progressive joint destruction. GM-CSF orchestrates the activation, proliferation, and differentiation of myeloid cells (mainly macrophages and neutrophils) thereby sustaining the pro-inflammatory synovial milieu. Recent advances in monoclonal antibody immunotherapy have enabled selective inhibition of GM-CSF or its receptor. Clinical data on several monoclonal antibodies are presented, focusing on their pharmacodynamic properties and efficacy results documented in phase II and III clinical studies. Cumulative evidence supports GM-CSF inhibition as a compelling strategy for modulating inflammation and improving clinical outcomes in rheumatoid arthritis. Full article

Background: Human adipose-derived mesenchymal stem cells (hADMSCs) are widely used in regenerative medicine due to their ability to proliferate and differentiate. Bone tissue engineering represents an innovative alternative to traditional grafts by combining biomimetic materials, stem cells, and bioactive factors to promote bone regeneration. Gellan gum (GG) is a promising scaffold material owing to its excellent biocompatibility and favorable physicochemical characteristics; however, chemical modifications such as methacrylation are necessary to enhance its mechanical strength and long-term stability. In this in vitro study, osteoprogenitor cells are cultured for 21 days on three 3D-printed GGMA-based scaffolds to evaluate their biological response: (i) neat GGMA, (ii) GGMA functionalized with hydroxyapatite (HAp), and (iii) GGMA functionalized with eumelanin derived from black soldier fly (BSF-Eumelanin). Methods: Cell adhesion, viability, proliferation and osteogenic differentiation are evaluated using MTT assays, histological staining (H&E and Alizarin Red S), alkaline phosphatase (ALP) activity, and gene expression analysis of key osteogenic markers. Results: Our results show that all GGMA-based scaffolds support cell adhesion, growth, and proliferation, while BSF-Eumelanin and HAp notably enhance osteogenic differentiation compared to neat GGMA. Conclusions: These findings highlight the potential of embedding bioactive factors into GGMA scaffolds to improve osteoconductive and osteoinductive performance, offering a promising strategy for bone repair. Full article

Metabolic immune evasion is a major factor limiting the long-term efficacy of intravesical Bacillus Calmette–Guérin (BCG) therapy in non-muscle-invasive bladder cancer (NMIBC). TIA1 is a stress granule RNA-binding protein with liquid–liquid phase separation (LLPS) capacity. Its role in tumor metabolism and immunotherapy response has been unclear. Here, we demonstrated that high TIA1 expression was independently associated with favorable survival across multiple cohorts. Full-length TIA1 formed cytoplasmic condensates, repressed LDHA/PKM2/HK2, reduced lactate, and lowered extracellular acidification. A condensate-defective ΔLCD (deletion of the low-complexity domain) mutant was inactive. TIA1 showed physical association with these glycolytic mRNAs in human cells, consistent with mRNA-linked control. Condensate-competent TIA1 promoted CD8⁺ T-cell proliferation, increased CD69 and Granzyme-B, and reduced PD-1 in co-culture. TIMER (Tumor Immune Estimation Resource) and spatial-omics supported co-localization with tumoral CD8A. BCG induced this metabolic–immune signature in cell lines, murine models, and patient explants, but the effects were abolished by TIA1 knock-down. Conversely, TIA1 over-expression alone limited tumor growth and recapitulated BCG-mediated glycolytic restraint and T-cell activation. Together, these results support an LLPS-linked, mRNA-associated regulation of tumor glycolysis. BCG-driven glycolytic suppression and CD8⁺ T cell activation track with the condensate-forming capacity of TIA1. TIA1 emerges as a prognostic biomarker and a potential therapeutic axis to improve intravesical immunotherapy in NMIBC. Full article

Upon an organism’s death, enzymatic DNA repair ceases, exposing the genome to destructive factors such as free cellular nucleases and proliferating microorganisms, which can cause DNA loss. DNA preservation is highly dependent on environmental conditions, and less favorable environments accelerate degradation. Despite this, advanced extraction and analytical methods now enable the study of poorly preserved and degraded DNA. DNA typing is a foundation of forensic genomics, enabling the identification of individuals and the individualization of biological evidence through the generation of unique genetic profiles. Although DNA is relatively stable, environmental exposure initiates its degradation into progressively shorter fragments, complicating analysis. The extent of DNA preservation in biological evidence depends on numerous factors, and this review focuses on the environmental factors—including temperature, humidity, ultraviolet radiation, pH, chemical agents, and microbial activity—as the most influential variables. In samples with degraded DNA, the maximum amplicon length achievable through polymerase chain reaction (PCR) is inherently limited. This review discusses genetic markers and analytical strategies improvements that enable the examination of highly degraded samples, particularly when conventional short tandem repeat (STR) typing fails. In these situations, successful identification requires targeting short DNA fragments, which are more likely to persist. Single-nucleotide polymorphisms (SNPs) are a valuable alternative, as their high allelic variability and short amplicon requirements make them more amenable to amplification from fragmented templates than STRs. Advances in next-generation sequencing (NGS) technologies have further enhanced this capacity by enabling high-resolution SNP profiling, thereby improving outcomes in challenging forensic cases. Full article

Careya arborea, commonly known as wild guava, is a deciduous tree native to Asia, including Sri Lanka. Traditionally used to treat various ailments such as skin diseases, tumors, gastrointestinal disorders, and inflammation, it is valued for its notable astringent properties. Rich in phytochemicals, including phenolics, terpenes, sterols, tannins, and saponins, Careya arborea exhibits potent antioxidant, anti-inflammatory, and anticancer activities. Its anticancer effects are primarily attributed to the induction of apoptosis and the inhibition of cancer cell proliferation, with several extracts such as chloroform, ethyl acetate, and methanol demonstrating selective cytotoxicity against cancer cell lines. The high phenolic content of Careya arborea underpins its antioxidant potential, which plays a crucial role in mitigating oxidative stress and associated inflammatory conditions. Despite its medicinal potential, Careya arborea remains an underutilized plant in Sri Lanka. Greater attention should be given to promoting its use in both traditional and modern healthcare systems to harness its therapeutic benefits. Given its therapeutic potential, sustainable harvesting and conservation efforts are essential to protect this plant from overexploitation and habitat loss. Taking all these factors into account, this review emphasizes Careya arborea’s potential as a source of natural therapeutic agent, highlighting the importance of further research and conservation to unlock its full medicinal value for clinical applications. Full article

Gallbladder cancer (GBC), an aggressive malignancy of the biliary tract, is characterized by pronounced geographical variation and a poor prognosis, with a five-year survival rate below 20%. Despite its low global incidence, it ranks as the fifth most prevalent gastrointestinal cancer. The aim of this review is to provide a comprehensive understanding of the molecular mechanisms underpinning GBC progression, with a particular focus on the pivotal role of transcription factors (TFs) in its pathogenesis. This review delineates how aberrant regulation of TFs contributes to tumor initiation, progression, and therapeutic resistance, and to discuss the translational potential of targeting these factors for clinical benefit. Tumor suppressor TFs such as p53 and p16 frequently undergo genetic alterations, including mutations, deletions, or epigenetic silencing, leading to impaired cell cycle control, DNA repair, and apoptosis. Conversely, oncogenic TFs including TCF4, MYBL2, NF-kB, AP-1, Snail, c-MYC, SP1, FOXK1, KLF-5, STAT3 and BIRC7 are often upregulated in GBC, promoting unchecked proliferation, epithelial–mesenchymal transition (EMT), metastasis, and therapeutic resistance. This review aims to bridge current molecular insights with emerging therapeutic approaches, with particular emphasis on innovative interventions such as proteolysis-targeting chimeras (PROTACs), RNA-based therapeutics, CRISPR-driven genome editing, and epigenetic modulators, which collectively represent promising strategies for achieving more effective and personalized treatment outcomes in patients with GBC. Full article

This study investigated the effects of vitamin E supplementation on growth performance, antioxidant capacity, and hepatic lipid metabolism in one-year-old juvenile Chinese sturgeon (Acipenser sinensis). A total of 270 fish (initial weight 1.37 ± 0.04 kg) were allocated into 9 fiberglass tanks and fed isonitrogenous and isolipidic diets with graded concentrations of vitamin E (DL-α-tocopherol acetate) including, 0, 1000, and 2000 mg/kg, respectively, for 2 months. Results showed that 1000 mg/kg vitamin E significantly improved growth performance and decreased hepatosomatic index. Dietary vitamin E supplementation significantly reduced the hepatic crude protein and crude lipid levels, withnot significantly affecting moisture and crude ash. Dietary vitamin E led to significant increases in plasma high-density lipoprotein cholesterol and vitamin E levels, while decreasing plasma low-density lipoprotein cholesterol. Additionally, it raised liver vitamin E content and reduced hepatic triglycerides, total cholesterol, crude protein, and crude lipid levels. Vitamin E also significantly downregulated mRNA levels of lipogenesis-related genes (ACC1, acetyl-CoA carboxylase 1; FASN, fatty acid synthase; and PPARγ, peroxisome proliferator activated receptor γ) and inhibited the enzyme activities of ACC1 and FASN, while upregulating lipolysis-related genes (HSL, hormone-sensitive lipase; CPT1, carnitine palmitoyltransferase 1α, and PPARα, peroxisome proliferator activated receptor α) and enhancing the activities of HSL and CPT1α. Furthermore, vitamin E supplementation significantly improved plasma reduced glutathione and superoxide dismutase activities, lowered plasma reactive oxygen species, malondialdehyde levels, and hepatic malondialdehyde contents, and upregulated mRNA levels of hepatic Nrf2 (nuclear factor-erythroid 2 related factor 2), Keap1 (Kelch-like epichlorohydrin associating protein 1), and CuZnSOD (copper/zinc superoxide dismutase). In conclusion, dietary 1000 mg/kg vitamin E supplementation could improve growth performance, enhance antioxidant capacity, and reduce liver fat deposition, indicating its potential as a beneficial dietary additive for promoting health and lipid regulation in juvenile Chinese sturgeon. Full article