Search Results (2,157)

Skin aging and wound healing are the result of intricate and interconnected processes involving chronic inflammation, oxidative stress, cellular senescence and extracellular matrix degradation. Mesenchymal stem cell (MSC)-derived exosomes are rich in bioactive components, particularly microRNAs (miRNAs), which play a crucial role in regulating gene expression and key signaling pathways critical for maintaining skin homeostasis. This article reviews the current evidence regarding the roles of MSC-derived exosomal miRNAs (MSC-Exo-miRNAs) in cutaneous repair and rejuvenation. Specific exosomal miRNAs are analyzed for their ability to modulate inflammatory responses, promote fibroblast proliferation and collagen synthesis, enhance angiogenesis, and facilitate keratinocyte migration and re-epithelialization. Their roles in regulating key signaling pathways are discussed in the context of skin regeneration and aging, including nuclear factor-κB (NF-κB), PI3K/Akt, TGF-β/Smad, Wnt/β-catenin, and nuclear factor erythroid 2-related factor 2 (Nrf2). Additionally, emerging engineering strategies aimed at optimizing miRNA cargo loading, improving delivery efficiency, and advancing clinical translation are highlighted. Overall, MSC-Exo-miRNAs represent a promising cell-free therapeutic strategy for skin repair and rejuvenation; however, further mechanistic investigations and rigorous clinical studies are necessary to fully realize their translational potential. Full article

Background: Prostate cancer (PCa) arises from complex interactions among host genetics, androgen signaling, and microbial communities. Emerging genomic evidence supports the presence of microbial consortia within prostate tissue, suggesting that microbial genes, metabolites, and host–microbe interactions may contribute to chronic inflammation, oncogenic signaling, and therapeutic resistance. Methods: We conducted a narrative review using targeted searches of PubMed and Google Scholar for studies published between 2020 and 2025, complemented by selected mechanistic reports published in March 2026. Human studies and experimental research providing mechanistic insights into prostate models were prioritized. Due to the heterogeneous methodologies, evidence was synthesized qualitatively, with an emphasis on genomic and signaling perspectives. Results: Low-biomass microbial DNA is consistently detected in prostate tissue. Proteomic analyses of Corpora amylacea suggest a “fossil record” of past infections through sequestered microbial DNA and antimicrobial proteins, potentially priming tissue for long-term carcinogenic processes, although contamination remains a key limitation. Recurrent bacterial and viral signals, including Cutibacterium acnes, Escherichia coli, Pseudomonas, Acinetobacter, human papillomavirus, Epstein–Barr virus, and cytomegalovirus, appear to converge on a restricted set of tumor-relevant pathways, including TLR–NF-κB, MAPK, PI3K/AKT/mTOR, cGAS–STING, and p53/pRb disruption. These interactions may promote cytokine production, oxidative stress, DNA damage, epithelial–mesenchymal transition, extracellular matrix remodeling, immune evasion, and resistance to therapy. The gut–prostate axis further links intestinal dysbiosis and microbial metabolites with systemic IGF-1 signaling and castration resistance. Conclusions: Microbial genomic consortia in the prostate and gut may shape inflammatory, metabolic, and immune networks that influence PCa initiation and progression. However, most available data remain correlative and are limited by low-biomass sampling, contamination risk, and heterogeneous study designs. Future research should prioritize rigorous contamination control, longitudinal and prostate-specific mechanistic studies, and integrated multi-omic approaches to clarify causality and identify actionable microbial targets for prevention, diagnosis, and therapy. Full article

This paper presents a K-band four-channel phased array beamformer with temperature compensation in 65 nm CMOS for 5G and satellite communications. The beamformer includes a four-way power divider/combiner, four RF channels, and digital control circuits. Each RF channel comprises a receive chain, a transmit chain, and a pair of receive/transmit (TX/RX) single-pole double-throw (SPDT) switches. The receive chain consists of a low-noise amplifier (LNA), a six-bit reflective-type phase shifter (RTPS), a drive amplifier (DA), two temperature-compensation attenuators (TCAs), and a six-bit attenuator (ATT); the transmit chain integrates a power amplifier (PA), two TCAs, a six-bit RTPS, a DA, and a six-bit ATT. Measurements show the chip exhibits 0–4.5 dB gain, noise figure (NF) < 7.8 dB, root mean square (RMS) phase error < 3.5°, and RMS gain error < 0.4 dB in receive mode operating in 19–23 GHz. In transmit mode operating in 21–23 GHz, it provides 6–10 dB gain range, RMS phase error < 3.4°, RMS gain error < 0.25 dB, and output power at 1 dB compression point (OP1dB) > 6.5 dBm. In addition, the receive and transmit gain variations are within 0.8 dB and 0.4 dB, respectively, when temperature ranges from −55 °C to 85 °C. With a compact footprint of 3.5 × 4.8 mm², the beamformer consumes 110 mW (receive) and 190 mW (transmit) DC power per channel. Full article

Objectives: This study aimed to investigated the role of Giardia extracellular vesicles (EVs) in intercellular communication and to evaluated their potential as vaccine candidates. Methods: The immunomodulatory effects of Giardia EVs were assessed in mouse macrophages and human monocyte-derived dendritic cells (Mo-DCs), with a particular focus on key inflammatory signaling pathways. In vivo immunogenicity was evaluated following EV administration, and the antigenic composition of EV cargo was characterized by proteomic analysis. Results: Giardia EVs activated pro-inflammatory signaling pathways in mouse macrphages, including SAPK/JNK, ERK1/2, and NF-κB. This activation was associated with IκB-α degradation and nuclear translocation of p65. Furthermore, EV stimulation significantly upregulated the expression of pro-inflammatory genes, including Il1β, Il6, Il4, Ptgs2, Nos2, and Tnf, with log₂ fold changes ranging from 3.9 to 15.8. Consistently, EVs increased iNOS protein expression (28–45%) and nitrite production (9.6–12.3-fold). In human Mo-DCs, Giardia EVs promoted cellular maturation, as evidenced by increased expression of MHC-II, CD80, and CD86, and enhanced T-cell proliferation with a Th1-skewed profile. In vivo immunization induced antigen-specific antibody responses, with IgG subclass distribution indicative of a balanced Th1/Th2 response. Proteomic analysis identified immunoreactive EV-associated proteins, including elongation factor 1-alpha, α-7.3 giardin, tubulin, and variant surface proteins (VSPs), which are well-established antigens in Giardia infection, with prominent bands observed at approximately 22 kDa and 50 kDa. Conclusions: Collectively, these findings demonstrate that Giardia EVs modulate innate immune responses in vitro, elicit antigen-specific humoral immunity in vivo, and contain conserved immunogenic proteins. These properties support their potential as a promising cell-free vaccine platform against giardiasis. Full article

Serglycin (SRGN) has been found overexpressed and secreted in glioblastoma (GBM), associated with tumorigenic signaling and poor prognosis. In this study, we aimed to elucidate the involvement of SRGN in the unfolded protein response (UPR), an oncogenic signaling pathway implicated in protein recycling and cell fate. Herein, we developed stably transduced LN-18^shSCR GBM cells, expressing high levels of SRGN, and SRGN-depleted LN-18^shSRGN cells. We observed significantly attenuated expression and activity of all UPR mediators upon SRGN suppression, in particular PERK, IRE1, ATF6 and downstream effectors. SRGN-expressing cells possessed a constitutively active UPR, as indicated by its active phosphorylation status and accumulated pool of nuclear ATF4 in LN-18^shSCR cells. Constitutive activation of the caspase-dependent apoptotic pathway was apparent in LN-18^shSRGN cells. Induction of endoplasmic reticulum (ER) stress pointed out that LN-18^shSRGN cells were predisposed to ER stress-associated cell death, whereas LN-18^shSCR cells activated adaptive UPR signaling and displayed resistance to apoptosis. The evaluation of TLRs, TNFRs, ILs and NF-kB also underscored that SRGN is essential for their expression and active inflammatory signaling. We concluded that SRGN-expressing cells acquire a pro-survival UPR mechanism, highlighting the novel regulatory role of SRGN in the adaptation and survival of GBM cells. Full article

Alpha-mangostin (AM), a xanthone from Garcinia mangostana, has shown promising nephroprotective properties, but its mechanisms in acute kidney injury (AKI) remain incompletely defined. In this study, we applied an integrative network pharmacology pipeline combined with molecular docking to clarify AM’s multi-target mechanisms in AKI. We identified 128 predicted AM targets and intersected them with AKI-related genes, yielding 122 shared targets. Protein–protein interaction analysis identified ten hub genes—TNF, AKT1, IL6, SRC, CTNNB1, HSP90AA1, NFKB1, HIF1A, PPARG, and PTGS2—implicating inflammatory, hypoxia, and cell-survival pathways. KEGG enrichment highlighted HIF-1 signaling, PI3K–Akt signaling, chemokine signaling, AGE–RAGE signaling, and pathways related to cellular senescence and oxidative stress, while GO terms emphasized responses to chemical/oxygen-containing compounds, kinase activity, signal transduction, and apoptosis. Molecular docking against the ten hub proteins showed favorable binding energies across multiple targets. The strongest predicted affinities were observed for PTGS2 (−11.13 kcal/mol), TNF (−9.74 kcal/mol), and AKT1 (−9.48 kcal/mol). Docking positioned AM within the COX-2 catalytic pocket, engaging key catalytic and hydrophobic residues similar to known inhibitors. MD simulation interaction analysis confirmed that AM maintained stable contacts with key human PTGS2 residues, characterized by dominant hydrogen bonds and water-bridge interactions with SER353, TYR355, ARG513, and SER530, along with consistent hydrophobic contacts, and persistent interactions sustained throughout the 200 ns trajectory. Collectively, these results suggest that AM modulates interconnected inflammatory, hypoxic, and survival pathways relevant to AKI, acting as a multi-target ligand with notable interaction involving COX-2, TNF, and AKT1. Further experimental validation and formulation strategies to improve bioavailability are recommended for the advancement of AM toward therapeutic evaluation in AKI. Full article

Interleukin-10 (IL-10) is a key immunoregulatory cytokine that suppresses inflammatory gene transcription in myeloid cells through signal transducer and activator of transcription 3 (STAT3). In Alzheimer’s disease and neuroinflammation, microglia express IL10ra and exhibit STAT3 Tyr705 phosphorylation following IL-10 stimulation, indicating IL-10 receptor-dependent STAT3 activation. Recent studies demonstrate that IL-10 induces promoter-selective STAT3-dependent transcriptional regulation in microglia through chromatin-associated mechanisms, whereas gp130-dependent cytokines activate STAT3 to induce transcription of defined target genes, including Socs3 and Ccl5. Following IL-10 receptor activation, STAT3 binds regulatory regions of inflammatory genes, including Il1b, Tnf, Il6, and Nlrp3, with reduced RNA polymerase II and NF-κB binding. IL-10-dependent transcriptional repression involves formation of a nuclear SHIP1–STAT3 complex, localization of histone deacetylase (HDAC)1 and HDAC2 to H3K4me1-enriched enhancer regions, reduced H3K27ac, and decreased chromatin accessibility at regulatory regions of inflammatory genes. IL-10-activated STAT3 induces Socs3, which regulates JAK1 and TYK2 activity and STAT3 phosphorylation. Impairment of IL-10 receptor signaling in microglia is associated with increased inflammatory gene expression, enhanced inflammasome-related transcription, demyelination, and amyloid accumulation. This review focuses on IL-10–STAT3-dependent transcriptional regulation in microglia, including receptor signaling, chromatin-associated mechanisms, and disease-associated gene expression in Alzheimer’s disease and neuroinflammation. Full article

Immune dysregulation is a critical driver of various pathological processes. Fish maw (FM) serves as a traditional immunomodulatory food. However, the immunomodulatory properties and mechanisms of fish maw hydrolysate (FMH) remain unclear. Here, low-molecular-weight FMH was prepared from Perca fluviatilis, exhibiting a major molecular weight distribution of 73–580 Da (83.89%), enriched in charged and hydrophobic amino acids (28.61% and 67.33%, respectively). Moreover, high-resolution mass spectrometry (HRMS) analysis identified 5 small peptides, including Asp-Leu and Gly-Pro-Ala, alongside 7 collagen-derived polypeptides with characteristic Gly-X-Y repetitive motifs. In cyclophosphamide (CTX)-induced immunosuppressed C57BL/6J mice, FMH significantly ameliorated alterations in peripheral blood cell parameters, regulated cytokine homeostasis, attenuated splenic histopathological lesions, and enhanced splenic lymphocyte proliferation. Mechanistically, thymic transcriptomic profiling identified 2237 DEGs in the CTX vs. CON comparison and 212 DEGs in the CTX+FMH vs. CTX comparison, with the NF-κB signaling pathway significantly enriched. Furthermore, qRT-PCR validated the expression of key NF-κB-related genes, including IκBα, P50, P65, CHUK, IL-1β, and IL-6, while immunohistochemical analysis confirmed reduced PI3K and P65 expression, thereby partly restoring immune homeostasis. These findings support FMH as a potential dietary immunomodulator. Full article

Background: Chronic kidney disease (CKD) is characterized by irreversible structural damage and functional deterioration of the kidneys. Esculetin (ES), with its anti-inflammatory, antioxidant, and immunomodulatory activities, shows potential in delaying renal function decline. This study aimed to investigate the protective effect of ES on adenine-induced CKD in mice and its underlying molecular mechanism, with a focus on its role in preventing the transition from acute kidney injury (AKI) to CKD. Methods: A AKI-to-CKD transition mice model was established by feeding mice a 0.2% adenine diet, and ES (30, 60 mg/kg) was co-administered for 4 weeks as a prophylactic intervention. Serum creatinine (SCr), blood urea nitrogen (BUN), and renal histopathology (HE, Masson, IHC) were evaluated to assess renal injury. Network pharmacology and transcriptomics were combined to screen the targets, and Western blot was used to verify the signaling pathways. Results: ES significantly reduced SCr and BUN levels in CKD mice and alleviated renal tubular dilation and inflammatory infiltration. ES decreased pro-inflammatory factors (IL-1β, IL-6, TNF-α) and MDA levels and enhanced SOD activity. Additionally, ES inhibited renal interstitial collagen deposition and reversed epithelial–mesenchymal transition (EMT) by upregulating E-cadherin and downregulating α-SMA levels. Mechanism studies confirmed that ES significantly inhibited the phosphorylation levels of p-EGFR, p-SRC, p-PI3K, p-AKT, and p-p65 in renal tissues. Conclusions: ES effectively inhibits inflammation, oxidative stress, and fibrosis by modulating the EGFR/SRC/PI3K/AKT/NF-κB signaling axis, thereby preventing the AKI-to-CKD transition in the adenine-induced renal injury model and alleviating the progression of chronic renal damage. Full article

Interleukin (IL)-1β is a pro-inflammatory cytokine implicated in sterile inflammation and tumor development. Investigating the role of MAPKAP kinase 2 (MK2) in IL-1β processing, we found that Il1b mRNA and IL-1β protein levels were elevated in resting MK2-knockout (KO) macrophages and in the serum of MK2/3 double-KO mice. This was linked to activation of the non-canonical NF-κB pathway in the absence of MK2 or its activator, p38α. Rescue by MK2, its kinase-inactive mutant MK2K79R, or p38α suppressed this pathway and reduced Il1b expression. We also observed decreased basal protein levels of tumor suppressor p53 in MK2- or p38α-deficient cells. Mechanistically, p53 interacts with caspase-3, promoting cleavage of RelB, thereby inhibiting non-canonical NF-κB signaling and subsequent Il1b and TP53 expression. These findings explain elevated basal IL-1β levels in MK2-KO macrophages and uncover a new autoregulatory mechanism of TP53 expression. Additionally, they reveal a new mechanism that contributes to the long-discussed link between cancer and inflammation, wherein the tumor suppressor p53 inhibits cytokine production in parallel. Full article

Glioblastoma cells sustain tumor growth by releasing inflammatory cytokines that modulate the tumor microenvironment (TME). Targeting the cytokine expression profile of glioblastoma multiforme (GBM) and tumor-supportive cells represents a promising therapeutic strategy. Lactoferrin, a natural compound with recognized anticancer properties, has been poorly investigated regarding its role in modulating GBM cytokine profiles and TME cellular activity. This study evaluated lactoferrin’s ability to modulate GBM inflammatory signaling and pro-tumorigenic functions of tumor-associated astrocytes. U87MG glioblastoma cells were treated with human lactoferrin (10 μg/mL) for 72 h, and DI-TNC1 astrocytes were exposed to conditioned medium from treated and untreated U87MG cells for 24 h. Results demonstrate that lactoferrin inhibits GBM cell proliferation, migration, and stemness-related pathways while modulating inflammatory profiles through NF-κB pathway interference, downregulating pro-tumorigenic cytokines IL-6, IL-1β, IL-4, and IL-10. Increased TGF-β expression in lactoferrin-treated cells likely reflects a compensatory mechanism rather than enhanced malignancy. Furthermore, lactoferrin attenuates pro-tumorigenic effects of tumor-associated astrocytes by reducing NF-κB activation and expression of TGF-β, TNF-α, IL-4, and IL-10. This innovative study provides evidence supporting non-cytotoxic approaches targeting GBM-TME interactions, highlighting lactoferrin’s potential to attenuate glioblastoma malignancy and astrocyte inflammatory signaling, suggesting its therapeutic potential for GBM treatment. Full article

Graphene oxide (GO) is a promising nanocarrier for the delivery of oligonucleotides. It offers a high loading capacity, efficient cellular uptake, and surface functionalization. MicroRNA-21 (miR-21) is a well-characterized oncomiR commonly overexpressed in hepatocellular carcinoma (HCC). In HCC, miR-21 contributes to tumor progression, inflammation, and angiogenesis. In a previous in vitro study, we showed that GO alone induces the upregulation of pro-inflammatory and tumor-related genes in HepG2 cells. However, conjugation with an antisense miR-21 (GO-antisense miRNA 21) reverses this effect, suggesting a potential therapeutic application. This study aims to evaluate the antitumor and anti-angiogenic efficacy of the GO-antisense miR-21 nanosystem in ovo using the chick embryo chorioallantoic membrane (CAM) model. Fertilized chicken eggs (n = 4 per group) were randomized into untreated, GO-treated, and GO–antisense miR-21-treated cohorts. A dose of 200 μL (GO 10.0 µg/mL: antisense miR-21 5.0 pmol/mL) was administered intratumorally. Tumor size, volume, and vascularization were monitored through stereomicroscopy and histological analysis. The expression of inflammatory and tumor-associated genes (IL-8, MCP-1, TIMP-2, ICAM-1 and NF-kB) was assessed by quantitative PCR. Given its prominent response, IL-8 protein expression was further analyzed via immunofluorescence. To evaluate tumor-specific delivery, FITC-labeled GO was tracked by confocal microscopy. Our data revealed that treatment with unfunctionalized graphene oxide (GO) unexpectedly promoted tumor vascularization and led to a significant increase in tumor weight. This was accompanied by upregulation of inflammatory markers. In contrast, GO-antisense miR-21 significantly reduced the tumor volume and vessel density. It also successfully downregulated all target genes. Confocal imaging demonstrated preferential accumulation of the nanosystem within the tumor mass. Our results highlight the dual anti-inflammatory and anti-angiogenic effects of GO-antisense miRNA 21 in ovo and support its potential as a targeted nanoplatform for HCC treatment. Full article

India, home to 4 biodiversity hotspots, hosts 675 wild species used for nutritional and therapeutic purposes. Wild edible fruits are highly valuable for their rich content of health-beneficial compounds, such as polyphenols, carotenoids, and vitamins. The shift in modern lifestyles has increasingly impacted human health. Several factors contribute to heightened oxidative stress, which underpins the development of non-communicable diseases (NCDs). Endometriosis, one of these conditions influenced by oxidative stress, currently lacks a definitive cure, leaving patients reliant on hormonal and surgical treatments. According to the WHO, 10% of girls and women worldwide are affected by endometriosis, often experiencing severe symptoms. This review explores the role of oxidative stress in the progression of endometriosis, its pathophysiology, and the effects of polyphenols found in wild Himalayan fruits, including various phenolic acids, flavonoids, stilbenes, and lignans. It also examines their synergistic effects with other non-polyphenolic compounds in reducing these biomarkers, such as inflammatory enzymes, pro-inflammatory cytokines, and estrogen receptors, and in modulating pathways like NF-κB, PI3K/AKT, among others, based on preclinical and clinical studies. Additionally, the review highlights key wild fruit species native to the Indian Himalayas, details their nutritional and phytochemical profiles, and assesses their potential, individually and synergistically, as functional foods or nutraceuticals for non-invasive treatment options for endometriosis. Full article

Sulfated polysaccharides (SPs), biologically active macromolecules from marine and terrestrial organisms, hold significant potential in revolutionizing cancer therapy. Characterized by their unique sulfate ester groups and structural diversity, SPs exhibit a broad spectrum of bioactivities, including immunomodulation, apoptosis induction, metastasis suppression, and angiogenesis inhibition. Prominent SPs, such as fucoidan from brown algae and carrageenan from red algae, have shown remarkable anticancer properties, either as standalone agents or in synergy with conventional therapies like chemotherapy and radiotherapy. Their mechanisms of action involve targeting critical pathways such as NF-kB, VEGF, and PI3K/Akt, disrupting cancer cell proliferation, invasion, and tumor microenvironment dynamics. SPs also enhance immune system responses, reduce chemotherapy-induced side effects, and exhibit antioxidant properties, making them versatile candidates in cancer treatment. Innovations like SP-based nanoparticles are addressing bioavailability and drug delivery challenges, providing targeted and sustained therapeutic effects while minimizing off-target toxicity. Despite their promise, challenges such as structural complexity, scalability, and clinical validation hinder their widespread adoption. This review provides a comprehensive analysis of SPs’ therapeutic potential, mechanisms, and emerging applications in oncology. It emphasizes the need for advanced extraction, characterization techniques, and clinical research to unlock their full potential, paving the way for novel, efficient, and safer cancer therapies. Full article

Aging is closely linked to oxidative stress and inflammation. This review provides a critical overview of the antioxidant compounds present in apple pomace and explores how they may mitigate age-related oxidative damage and inflammatory responses. We focus on the nutritional profile of apple pomace including its macro- and micronutrients, with particular focus on polyphenols, such as procyanidin tannins, quercetin glycosides (rutin, quercetin-3-glucoside), phloridzin, dietary fiber, vitamins, and lipids alongside current techniques for isolating its bioactive components. Special attention is given to biological pathways through which these compounds influence aging: redox regulation via Nrf2, inflammatory modulation via NF-κB, and metabolic regulation via AMPK, SIRT1 and PI3K/Akt/mTOR. Evidence from in vitro cellular models (HepG2, CCD-986Sk fibroblasts), in vivo rodent studies and limited human pilot trials is summarized, as well as existing and emerging applications of apple pomace in functional foods, cosmeceuticals, and other sectors. Finally, we discuss the challenges and future opportunities in harnessing this by-product of the food industry. Although clinical data remain limited, preclinical findings support the repurposing of apple pomace as a sustainable functional ingredient contributing to healthier aging and circular economy goals. Future long-term randomized controlled trials are necessary to confirm efficacy in humans. Full article