Ageing is a complex biological process marked by gradual functional decline, reduced cellular resilience, and increased vulnerability to chronic diseases. Maintaining cell health has become a crucial strategy for extending life span and promoting healthy ageing. Nutrition at the cellular level plays a vital role in the increasing recognition of bioactive compounds from functional foods for their ability to influence pathways related to ageing. The water-soluble tomato concentrate (WSTC), known as Fruitflow®, contains a variety of bioactive compounds, including polyphenols, nucleosides, and phenolic conjugates, that support cardiovascular, metabolic, and immune health. Preclinical and clinical research suggest that Fruitflow® may help reduce platelet hyperactivity, support healthy blood pressure, and improve blood vessel function. Emerging evidence also indicates that it could have broader cellular effects, such as helping reduce oxidative stress and inflammation, supporting mitochondrial activity, promoting cellular growth, and contributing to a balanced gut microbiota. These potential benefits are relevant to several aspects of cellular ageing, including oxidative imbalance, mitochondrial dysfunction, chronic inflammation, and changes in cellular communication. Over the last two decades, various authors have published their research work on the potential health benefits of WSTC/Fruitflow®. This review summarises current evidence on the cellular effects of bioactive compounds present in Fruitflow® and explores the potential molecular mechanisms through which these bioactive constituents may influence cellular processes associated with health benefits.

Chronic inflammatory disorders and cancer remain major global health challenges driven by persistent immune activation and tissue damage. The human umbilical cord-derived mesenchymal stem cell (hUC-MSC) secretome has emerged as a promising cell-free therapeutic alternative owing to its potent anti-inflammatory, immunomodulatory, and regenerative properties. Comprising of cytokines, chemokines, growth factors, and extracellular vesicles enriched with bioactive miRNAs, the hUC-MSC secretome exerts its effects primarily through paracrine signaling. For this review, relevant literature was collected from established databases, including ScienceDirect, PubMed, and Google Scholar, using key terms such as “hUC-MSC secretome,” “chronic inflammation,” “exosomes,” “tumor microenvironment,” and “preconditioning.” The search focused on studies published within the last five years, emphasizing in vitro and in vivo preclinical studies, original research, and review articles. Only studies specifically exploring hUC-MSC-derived secretomes were included, whereas those addressing cell-based therapies or secretomes from other MSC sources were excluded. Cumulative findings indicate that the hUC-MSC secretome alleviates chronic inflammation by releasing anti-inflammatory cytokines such as IL-10 and TGF-β, as well as regulatory miRNAs such as miR-29a-3p, miR-100-5p, and miR-125b-5p, which act via key signaling pathways including PI3K/AKT, Wnt/β-catenin, and JAK/STAT. These mechanisms collectively mediate anti-inflammatory responses, suppress epithelial-mesenchymal transition, enhance chemosensitivity, and promote tissue repair. This review aims to consolidate the emerging evidence that positions the hUC-MSC secretome as a next-generation cell-free therapeutic strategy for chronic inflammatory diseases, including major cancers, inflammatory bowel disease, rheumatoid arthritis, and neurodegenerative disorders, while highlighting current limitations and strategies to enhance the therapeutic efficacy and clinical applicability of the hUC-MSC secretome.

A new mononuclear Hg(II) complex, [Hg(9BuA)2Cl2] (1), was synthesized via a one-pot reaction employing the 9-butyladenine (9BuA) and characterized by using elemental analysis, spectroscopic methods (FT-IR, UV-Vis, 1H NMR), and single-crystal X-ray diffraction analysis. The complex 1 exhibits a distorted tetrahedral geometry, with two 9BuA ligands and two chloride ions coordinating to the mercury center. The supramolecular architecture of 1 is stabilized by directional hydrogen bonds, including N-H & sdot;& sdot;& sdot;N and C-H & sdot;& sdot;& sdot;(Cl/N). Hirshfeld surface analysis indicates that H & ctdot;H interactions are the most prevalent, while Cl & ctdot;H and N & ctdot;H interactions are statistically significant. Notably, C & ctdot;H interactions display the highest enrichment ratio, underscoring their critical role in supramolecular stabilization. Theoretical studies based on DFT analysis have also been employed to demonstrate complex 1's electronic property. The in vitro antibacterial study of complex 1 against four bacterial strains-Gram-positive bacterial strain (Staphylococcus aureus) and Gram-negative bacterial strains (Klebsiella pneumoniae, Pseudomonas aeruginosa, and Escherichia coli)-reveals selective and potent activity, specifically towards Pseudomonas aeruginosa. Moreover, a molecular docking study has been conducted to identify the biomolecular interactions and potential protein binding sites of 1 against Pseudomonas aeruginosa.

Breast cancer progression and resistance to therapy are strongly influenced by immune evasion within the tumor microenvironment. Immune checkpoint signaling is a major mechanism by which cancer cells evade immune surveillance, thereby promoting tumor progression and reducing the effectiveness of immunotherapy. Recent evidence suggests that extracellular vesicles (EVs) are important mediators of communication between tumor, stromal, and immune cells, enabling the transfer of proteins, nucleic acids, lipids, and other bioactive molecules that regulate immune responses. This review discusses current knowledge on the role of EVs in immune checkpoint regulation in breast cancer, with an emphasis on both programmed death-ligand 1 (PD-L1)-dependent and additional immunosuppressive pathways that collectively contribute to immune escape. A literature review was conducted using PubMed, Google Scholar, and Web of Science, focusing on studies from the past decade related to EV biology, immune checkpoints, and breast cancer. Findings from multiple studies indicate that tumor-derived EVs contribute to immunosuppression by impairing T-cell function, promoting immune tolerance, facilitating metastatic progression, and supporting resistance to immunotherapy. Importantly, EV-mediated effects are different for the breast cancer subtypes, which may play a role in treatment response, disease progression, and clinical outcomes. EVs also show potential as minimally invasive biomarkers for disease monitoring and as therapeutic targets or delivery systems for precision medicine. Overall, this review highlights current evidence on EV-mediated immune checkpoint regulation in breast cancer, highlighting PD-L1 and CTLA-4associated mechanisms as key drivers of immune evasion and promising targets for precision immunotherapy.

Metabolic reprogramming plays a crucial role in cancer progression, therapeutic resistance, and tumor-microenvironment remodelling. Monoamine oxidase-B (MAO-B), a mitochondrial enzyme involved in oxidative deamination, has recently been identified as a metabolic regulator that influences reactive oxygen species (ROS) production, mitochondrial homeostasis, and redox-dependent signaling in tumors. Selegiline, an MAO-B inhibitor traditionally used in neurological disorders, is now gaining attention for its potential role in modulating tumor metabolism. Elevated MAO-B activity contributes to oxidative stress, genomic instability, immune suppression, and metabolic adaptations that support tumor survival. By inhibiting MAO-B, selegiline reduces ROS generation, alters mitochondrial respiration, regulates glycolytic flux, and disrupts hypoxia-associated pathways, making it a promising modulator of metabolic checkpoints in oncology. Relevant literature was collected from PubMed, Google Scholar, and ScienceDirect using keywords such as Selegiline, MAO-B inhibitor, tumor metabolism, oxidative stress, and drug repurposing in cancer. Relevant studies from the past 5 years, with inclusion criteria focusing on mechanistic, preclinical, and translational evidence related to MAO-B and selegiline-mediated metabolic regulation. Recent findings indicate that selegiline not only modulates cancer cell metabolism but also influences the tumor microenvironment by reducing inflammatory cytokine production, altering macrophage polarization, and enhancing susceptibility to therapeutic stress. Additionally, combination approaches with chemotherapeutics, metabolic inhibitors, and immunotherapies show synergistic potential. This review summarizes current insights into selegiline’s role in metabolic reprogramming, highlights existing challenges, and discusses future opportunities for repositioning selegiline as a targeted metabolic modulator in cancer therapy.

Climatic changes and coastal pollution emphasize the need for a better understanding of their impact on human health. The present study investigates the impact of coastal pollution on human health by comparing hematological and biochemical parameters and microbial analysis in the coastal population compared to the non-coastal population. A prospective study was conducted involving 508 participants from coastal areas and 92 participants from non-coastal areas. Blood samples were analyzed for hemoglobin, platelet count, renal function, lipid profile, liver function, protein profile, and thyroid function. Feces, urine, and skin swabs were also analyzed for microbial culture analysis. The coastal population showed significant increases in hemoglobin, platelet count, and HDL, while non-coastal participants showed elevated BUN, Serum creatinine, Cholesterol, Triglycerides, and LDL levels. The coastal participants showed a decrease in ALT, AST, Alkaline phosphatase, and levels of thyroid-stimulating hormone. The coastal population had higher rates of hypertension, diabetes, eczema, and other skin lesions, whereas non-coastal participants had higher tinea cases. Microbial analysis revealed differences in fecal, urine, and skin communities, with a higher prevalence of Escherichia coli and other pathogenic bacteria, such as Acinetobacter and Enterobacter species, in coastal samples. The present investigations revealed significant differences in health parameters between coastal and non-coastal participants, which may be attributed to the influence of coastal pollution. Further research with a larger sample size is required to confirm these findings and better understand the impact of coastal pollution on human health.

Mesenchymal stem cells (MSCs) isolated from peripheral blood (PB) are gaining increasing attention among both researchers and clinicians, representing a promising alternative to traditional stem cell sources such as bone marrow and adipose tissue. Their therapeutic use offers key advantages like high accessibility, minimally invasive collection and autologous nature of the graft. Together with the ability to differentiate into multiple cell types, PB-MSC features make them ideal candidates for a wide range of clinical applications in the fields of regenerative medicine, tissue engineering and immunotherapy. While the therapeutic potential of PB-derived MSCs is more and more acknowledged, several challenges still need to be overcome regarding, for example, their isolation, expansion, and differentiation efficiency. For clinical translation, PB-MSC administration may be specifically indicated when minimally invasive autologous cell therapies are required, especially when bone marrow harvest is not recommended due to age, comorbidity, or prior surgeries. Conversely, PB-MSC auto-transplant should be avoided in patients suffering from hematological malignancies, active infections, or bone marrow disorders, where circulating stem cell populations may be altered, or their isolation poses safety risks. In this Perspective, we highlight recent advances in PB-MSC isolation and characterization, discuss their bioengineering integration into osteochondral repair strategies, and examine their immunomodulatory potential in osteoarthritis (OA). We propose that PB-MSCs integrate regenerative and immunomodulatory properties, positioning them as a promising, autologous cell source for next-generation personalized regenerative therapies. However, their clinical translation critically depends on the development of reproducible, GMP-compliant expansion protocols and validated potency assays.

The present study investigates the potential role of microRNA-10b (miR-10b) in the proliferation and apoptosis of colon cancer cells, with possible associations with WW and C2-domain containing-2 (WWC2) and phosphatase and tensin homolog (PTEN). Bioinformatics analyses were performed using the UALCAN database, TargetScan, and RNAcofold webserver. In vitro experiments were performed to determine the effects of miR-10b inhibition on primary (SW480) and metastatic (SW620) colon cancer cell lines. 2,3-Bis (2-methoxy-4-nitro-5-sulfophenyl)-2 H-tetrazolium-5-carboxanilide (XTT) assay, senescence-associated β-galactosidase assay, dual acridine-orange/ethidium-bromide apoptosis assay, quantitative real-time PCR (qRT-PCR), immunofluorescence and western blot experiments were performed. UALCAN database analysis showed elevated miR-10b expression in colon cancer patients, but no significant association with overall survival was observed (P = 0.51). TargetScan identified WWC2 and PTEN as important miR-10b targets, and RNAcofold demonstrated the lowest minimum free energy (MFE) values between miR-10b and WWC2 and PTEN. Transfection with miR-10b inhibitor reduced miR-10b expression, decreased cell viability, and increased cellular senescence in both SW480 and SW620 colon cancer cell lines, with higher apoptosis in SW480 cells, while tumor-suppressor miRNAs, namely miR-34a and miR-124a, were upregulated in both the cell lines. MiR-10b inhibition led to increased WWC2 and large tumor suppressor kinases-1/2 (LATS1/2) expression and decreased Yes-associated protein-1 (YAP1) and WW-domain-containing transcription regulator-1 (WWTR1) in SW480 cells, while TEA-domain transcription factor-1 (TEAD1), connective-tissue growth factor (CTGF), and GLI-family zinc finger-2 (GLI2) were decreased in both cell lines. BCL2-associated-X-protein (BAX), BCL2-associated death-promoter (BAD), and Caspase-3 (CASP3) were elevated, whereas B-cell-lymphoma-2 (BCL2) was reduced in SW480 cell line, with no significant differences between the cell lines. Increased PTEN and decreased cyclin-dependent kinase-6 (CDK6) and cyclin D1 (CCND1) expressions were found in SW480 cells, while proliferating cell nuclear antigen (PCNA) expression was reduced in SW620 cells. Immunofluorescence analysis showed reduced nuclear localization of YAP1 and WWTR1; with increased BAX and reduced BCL2 intensity following miR-10b inhibition in both the cell lines. Western blot analysis showed increased WWC2 and PTEN protein expression and decreased BCL2 and WWTR1 protein expression in SW480 cell line. miR-10b possibly promote the proliferation and inhibit the apoptosis of colon cancer cell lines. Not applicable.

Leishmaniases, neglected tropical diseases comprising diverse clinical forms and manifestations depending upon the causative Leishmania species, remain a major public health concern globally. Broadly, the diseases are classified into cutaneous (CL), mucocutaneous (MCL) and visceral (VL) forms based on tissue invasion and pathogenesis. Conventional therapeutic agents, including antimonial compounds, amphotericin B, miltefosine, pentamidine, and paromomycin, are limited by high toxicity, emerging resistance, and poor bioavailability. Leishmania amastigotes proliferate within macrophages of the reticuloendothelial system, posing a significant challenge for effective drug delivery. Recent advancements in novel drug delivery systems (NDDS) incorporating diverse nano-formulations offer promising solutions by enhancing targeting efficiency and reducing systemic side effects. This review evaluates current literature (2000-2025) regarding NDDS applications against CL (including MCL) and VL. While formulations like AmBisome are clinically established, many others remain in preclinical stages. This paper critically analyzes the transition from conventional to novel therapies, the mechanisms of intracellular delivery, and the regulatory hurdles delaying clinical translation.

Mitochondria are membrane-bound cell organelles that undertake the majority of the energetic and metabolic processes within the cell. They are also responsible for mediating multiple apoptotic pathways, balancing redox charges, and scavenging reactive oxygen species. MicroRNAs, which are short, non-coding RNAs widely known for regulating gene expression at the post-transcriptional level, regulate many of these processes. The specific microRNAs that directly or indirectly control mitochondrial dynamics are called mitochondrial miRNAs (mitomiRs). The broadest classification of this type of ncRNA encompasses nuclear-encoded miRNAs that interact with cytoplasmatic mRNAs associated with mitochondrial activity. At the same time, a more specific subset comprises nuclear-encoded miRNAs that translocate into the mitochondria to interact with mRNAs inside of this organelle. Finally, the smallest group of mitomiRs includes those codified by mtDNA and can regulate endogenous mitochondrial transcripts or be transported into the cytoplasm to modulate circulating mRNAs. Regardless of the origin or action mechanism, mitomiRs have been recently recognized to have a key role in the progression of a variety of chronic disorders, such as neurodegenerative and cardiovascular diseases, diabetes, asthma, depression, and even cancer. All of these progressive pathologies have been tightly linked to mitochondrial dysregulation. They are further associated with an aberrant expression of specific miRNAs that regulate cellular metabolism, positioning mitomiRs as reliable biomarkers for diagnosing several chronic diseases. These molecular indicators have also provided insights into how these conditions progress, allowing for the development of different miRNA-based treatment strategies that target dysregulated mitochondrial-related genes, reestablishing their baseline activity and restricting further disease progression.

Cytokine-mediated inflammation is increasingly recognized for playing a vital role in the pathophysiology of a wide range of brain disorders, including neurodegenerative, psychiatric, and neurodevelopmental problems. Pro-inflammatory cytokines such as interleukin-1 (IL-1), tumor necrosis factor-alpha (TNF-α), and interleukin-6 (IL-6) cause neuroinflammation, alter brain function, and accelerate disease development. Despite progress in understanding these pathways, effective medicines targeting brain inflammation are still limited. Traditional anti-inflammatory and immunomodulatory drugs are effective in peripheral inflammatory illnesses. Still, they face substantial hurdles when applied to the central nervous system (CNS), such as the blood–brain barrier (BBB) and unwanted systemic effects. This review highlights the developing treatment techniques for modifying cytokine-driven neuroinflammation, focusing on advances that selectively target critical cytokines involved in brain pathology. Novel approaches, including cytokine-specific inhibitors, antibody-based therapeutics, gene- and RNA-based interventions, and sophisticated drug delivery systems like nanoparticles, show promise with respect to lowering neuroinflammation with greater specificity and safety. Furthermore, developments in biomarker discoveries and neuroimaging techniques are improving our ability to monitor inflammatory responses, allowing for more accurate and personalized treatment regimens. Preclinical and clinical trial data demonstrate the therapeutic potential of these tailored techniques. However, significant challenges remain, such as improving delivery across the BBB and reducing off-target effects. As research advances, the creation of personalized, cytokine-centered therapeutics has the potential to alter the therapy landscape for brain illnesses, giving patients hope for better results and a higher quality of life.

Plant-based compounds have gained significant attention as therapeutic agents for managing infections and facilitating tissue repair. RHRet is a plant-derived product composed of bioactive compounds from the extract of different plant species, like Phyllanthus emblica, Curcuma longa, Terminalia chebula, Swertia chirayita, Azadirachta indica, Pterocarpus santalinus, Adhatoda vasica, and Terminalia bellirica. These medicinal plants are known for their potent antibacterial and immune-modulatory properties. In this study, we evaluated the molecular interactions between major bioactive compounds present in RHRet and bacterial proteins, followed by evaluation of the antibacterial properties of RHRet, its impact on biofilm formation, and oxidative stress responses. Molecular docking was studied to evaluate the interactions of different bioactive compounds potentially present in RHRet with PerR, SodA, and KatG proteins. The antibacterial activity was evaluated using disc diffusion, growth curve analysis, minimum inhibitory concentration analysis, and biofilm formation. Hyaluronidase inhibitory effect was also evaluated to study the potential of RHRet in restricting bacterial growth. The oxidative stress response was analyzed through lipid peroxidation, superoxide dismutase and catalase activity, and measurement of total thiol content. Docking analysis revealed strong binding interactions between compounds potentially present in RHRet and PerR, SodA, and KatG proteins. RHRet inhibits Staphylococcus aureus growth, biofilm formation, and hyaluronidase activity in a concentration-dependent manner. Additionally, RHRet increases lipid peroxidation levels, thiol content, and reducing superoxide dismutase activity. However, no significant changes have been found in catalase activity. RHRet inhibits Staphylococcus aureus growth and biofilm formation and inhibits hyaluronidase activity while modulating oxidative stress and interacting with bacterial proteins. Although RHRet showed promising antibacterial potential, further in vivo studies are necessary to thoroughly evaluate its efficacy and safety profile.

Background Diagnosis and treatment of Tuberculosis (TB), particularly delay in diagnosis of TB poses significant challenges in its eradication. The exploration of new biomarkers is urgently required for TB diagnosis and treatment. This study aimed to investigate the serum levels of Interleukin-2 (IL-2), an important diagnostic parameter in TB; lipoarabinomannan (LAM), a key constituent of the mycobacterial cell wall; and the expression of circulating microRNA-29a (miR-29a) in serum. MiR-29a contributes to increased susceptibility to TB by downregulating interferon-γ expression in T cells through post-transcriptional regulation, thereby exerting an immunosuppressive effect.Materials and methods The study was conducted on pulmonary TB (PTB), extra-pulmonary TB (EPTB), and control groups. Serum from the three groups was isolated, and IL-2 and LAM levels were measured by ELISA. Additionally, q-RT-PCR was conducted to analyse the expression of microRNA-29a in the serum of some TB patients.Result LAM and IL-2 were significantly upregulated in serum samples from both the PTB and EPTB groups compared to the control group. Additionally, the expression of miR-29a was significantly elevated in the EPTB group.Conclusion This study suggests that LAM and IL-2 may be potential diagnostic biomarkers for both PTB and EPTB, while miR-29a may be a promising marker specifically for EPTB. However, further evaluation with larger cohort samples is required to validate the clinical utility of LAM, IL-2, and miR-29a as diagnostic TB markers.

BackgroundMicroRNAs (miRNAs) are small non-coding RNAs that regulate essential cellular functions, such as cell adhesion, proliferation, migration, invasion, and programmed cell death, and therefore, alterations in miRNAs can contribute to carcinogenesis. Previous studies have shown that miRNA-122 is abundant in the liver and regulates cell proliferation, migration, and apoptosis. However, the expression pattern and mechanism of actions of miR-122 remain primarily unknown in colon cancer.MethodsIn this study, we analyzed The Cancer Genome Atlas Colon Adenocarcinoma (TCGA-COAD) database to assess the clinical significance of astrocyte elevated gene-1 (AEG-1)/metadherin (MTDH) and miR-122 in colon cancer. MiR-122 overexpression studies were performed in HCT116, SW480, and SW620 cell lines. Dual-luciferase assay was carried out to confirm the interaction between AEG-1 and miR-122. In vivo-JetPEI-transfection reagent was used for in-vivo transient transfection of miR-122 in the AOM/DSS-induced colon tumor mouse model.ResultsOur results demonstrate that miR-122 was downregulated in colon cancer cells, and it influences the expressions of apoptotic factors and inflammatory cytokines. MiR-122 overexpression in HCT116, SW480, and SW620 cells showed upregulation of Caspase 3, Caspase 9, and BAX and decreased expression of BCL2, which are pro-apoptotic and anti-apoptotic members that maintain a ratio between cellular survival and cell death. In vivo transient transfection of miR-122 mimic in AOM/DSS induced colon tumor mouse model showed less inflammation and disease activity. The TCGA-COAD data indicated that AEG-1 expression was higher in patients with low expression of miR-122 and lower AEG-1 expression in patients with higher expression miR-122.ConclusionOur findings highlight the key role of miR-122 in the high grade of colonic inflammation, and possibly in colon cancer, and the use of miR-122 mimic might be a therapeutic option.