Abstract: The cyclic GMP‐AMP synthase–stimulator of interferon genes (cGAS–STING) pathway has emerged as a critical cytosolic DNA‐sensing mechanism that orchestrates innate immune activation in response to cellular stress. In the central nervous system (CNS), this pathway demonstrates highly context‐specific and cell‐type‐dependent functions, ranging from promoting neuroinflammation in neurodegenerative diseases such as Alzheimer's disease (AD) and Parkinson's disease (PD), to modulating immune surveillance and therapeutic responsiveness in glioma. This review systematically delineates the molecular mechanisms, activation patterns, and regulatory networks of cGAS–STING signaling in the CNS. We highlight its dualistic roles in both inflammatory exacerbation and antitumor immunity, and further discuss recent advances in therapeutic strategies, including pharmacological modulators, blood–brain barrier (BBB)‐penetrating delivery platforms, and nanotechnology‐based precision interventions. Finally, we propose future directions focused on decoding tissue‐specific immunodynamics and developing spatiotemporally controlled, multiorgan immunoregulatory frameworks. Together, this review underscores cGAS–STING as a promising therapeutic axis in the evolving landscape of neuroimmunology.

Abstract: Advanced oxidation protein products (AOPP) are generated from oxidation that is mainly promoted by the action of hypochlorous acid (HOCl) on proteins, such as albumin. However, new pathways and targets associated with AOPP formation must be identified and thoroughly evaluated. Non‐enzymatic post‐translational modifications (NEPTMs), such as protein carbamylation, are relevant in chronic kidney disease and other inflammation‐related processes. Therefore, the aim of this study was to determine whether incubating HOCl with gamma globulins promotes AOPP formation and whether potassium cyanate (KOCN)‐induced carbamylation of albumin and gamma globulins is a new pathway for AOPP formation. Solutions comprising 451 and 86 μM of albumin and gamma globulins, respectively, were incubated with HOCl (2 and 4 mM) and KOCN (150 nM and 150 μM) for 30 min, and then AOPP formation and the concentrations of protein carbonyl and homocitrulline were monitored. Notably, HOCl‐induced oxidation of gamma globulins and albumin increased AOPP production. Gamma globulins also generated a higher amount of AOPP than albumin. Exposure of albumin and gamma globulins to HOCl resulted in a significant increase in protein carbonyl content, whereas exposure to KOCN led to a significant increase in homocitrulline. These findings suggest that gamma globulins are a new target of AOPP and KOCN participates in an alternate pathway of AOPP formation, thereby providing a new hypothesis regarding the pathways of AOPP formation during inflammation.

Abstract: ABSTRACT Gastric cancer remains the primary cause of cancer‐related deaths worldwide, where gastric cancer stem cells play an essential role in tumor growth and resistance to various gastric cancer therapies. Emerging evidence suggests that the interaction between Epstein‐Barr virus and Helicobacter pylori may affect the regulation of gastric cancer stem cells, although the exact mechanism remains to be explored. This mini‐review aims to explore the potential interaction between Epstein‐Barr virus and Helicobacter pylori in modifying the characteristics of gastric cancer stem cells, emphasizing their respective roles in the inflammatory tumor microenvironment and the synergistic effects on gastric carcinogenesis. This review article presents the impact of Epstein‐Barr virus‐induced immune evasion and Helicobacter pylori ‐induced gastric inflammation on the maintenance and differentiation of gastric cancer stem cells. We seek alterations in numerous signaling pathways related to stemness induced by microbial factors. Based on current understanding, several crucial signaling pathways, including the Notch, Hippo pathway, Nuclear factor‐κB, wingless‐related integration site, and autophagy pathways, have been found to be implicated in Epstein‐Barr virus‐ and Helicobacter pylori‐induced gastric cancer stem cells. Understanding this interplay may reveal novel treatment targets for gastric cancer, particularly in patients with chronic infection by these two pathogens. Further research is needed to clarify the mechanistic interactions driving the synergy between Epstein‐Barr virus and Helicobacter pylori , which alters the biology of gastric cancer stem cells. This may provide further insights into early diagnosis and treatment approaches for gastric cancer.

Abstract: In Alzheimer's disease (AD), the interaction between many AD‐relevant proteins, including amyloid precursor protein (APP) and tau, with the cysteine protease caspase‐3 (Cas3) enhances AD pathogenesis. Searching for effective Cas3 inhibitors, we turned to the sensor calbindin‐D28K (D28K) which specifically inhibits Cas3. The specific D28K conformation that elicits Cas3 inhibition remains elusive. To shed more light on this D28K conformation, we investigated likely environmental regulators. Recently, evidence of pH imbalance in aging brains has been implicated in AD pathologies. Using pull‐down assays, Cas3 inhibition assays, and molecular docking, we identified pH as a critical regulator for tuning the strength of D28K's inhibitory actions and subsequently identified Loop4 in Cas3 as the structural element targeted by D28K.

Abstract: ABSTRACT Reactive oxygen species (ROS) cause oxidative stress and contribute to cancer genesis and progression. Metastasis‐associated in colon cancer 1 (MACC1) is a key metastasis‐mediating transcription factor in colorectal cancer (CRC). Whether ROS epigenetically regulated MACC1 expression and increased tumor progression in CRC have not been elucidated so far. We applied oxidative stress in two CRC cell lines with differential MACC1 expression (HCT116 and SW480) and analyzed the distribution of the histone marks H3K4me3 (active) and H4K20me3 (repressive), as well as the expression of MACC1. Alteration in cell motility by ROS was assayed with Boyden chambers. Abundance of H4K20me3 on the MACC1 promoter was determined by ChIP‐seq. Induced oxidative stress in SW480 and HCT116 cells increased MACC1 mRNA and protein expression and enhanced cell migration. In the low MACC1 expression SW480 cells, oxidative stress resulted in a higher abundance of the active histone mark H3K4me3, and a lower abundance of repressive mark H4K20me3, both overall and specifically on the MACC1 promoter, compared with the medium MACC1 expression HCT116 cells. Analysis of histological abundances of H3K4me3 and H4K20me3 marks in a small panel of human CRC tumors showed an inverse correlation of H4K20me3 with MACC1. Experimentally, inhibition of H4K20me3 formation caused increased MACC1 mRNA expression in HCT116 cells. Conclusions, we reported a potential ROS‐mediated epigenetic regulation of MACC1 expression in CRC through altered histone methylation, as our data suggested an initial epigenetic silencing of MACC1, which was later partially reactivated under oxidative stress.

Abstract: Triple‐negative breast cancer (TNBC) signifies an enormous risk to women's health globally. TNBC is characterized by its aggressive nature, resistance to existing therapies, and poor prognosis. Understanding the molecular pathogenesis of breast cancer is crucial for identifying screening markers and therapeutic targets. In order to find commonly expressed differentially expressed genes (DEGs) in a variety of TNBC cell lines treated with docetaxel (GSE70690), paclitaxel (GSE86839), doxorubicin (GSE202536), and cisplatin (GSE77515), as well as untreated TNBC cell lines (GSE38959), bioinformatics approaches were used. The R software was utilized, and the cutoff criteria for the analysis were set at p < 0.01 and |log2FC| > ±1. A Venn diagram was used to identify the shared DEGs across TNBC cell lines treated with and without the targeted chemotherapeutic drugs. The DEGs that were found were analyzed to determine their involvement in specific biological processes and pathways using gene ontology and Reactome pathway enrichment analysis. Protein–protein interactions (PPI) were subsequently established, and the hub genes were discovered. Through data analysis, the study identified a set of DEGs associated with the response to chemotherapy drugs in TNBC. The GO analysis revealed that the DEGs identified were primarily associated with cell cycle regulation, cell population proliferation, and microtubule‐related functions. Reactome pathway analysis showed enrichment in cell cycle processes, mitotic phases, and DNA damage checkpoints. Hub genes, such as CDK2, PLK4, and BIRC5, were identified based on their high degree of connectivity in the PPI network. The identified DEGs and pathways in this study shed light on possible therapeutic targets and reducing drug resistance. These findings contribute to the development of personalized and targeted therapies for TNBC, ultimately leading to improved patient outcomes.

Abstract: Tumor invasion and metastasis, the leading causes of cancer‐related mortality, are critically driven by cytoskeletal remodeling, a process extensively hijacked by oncoviruses to promote malignant progression. This review comprehensively examines how oncoviruses—including Epstein‐Barr virus (EBV), Kaposi's sarcoma herpesvirus (KSHV), hepatitis B virus (HBV), hepatitis C virus (HCV), human papillomavirus (HPV), and others—remodel key cytoskeletal components such as actin microfilaments, intermediate filaments (IFs), and microtubules (MTs). These virus‐induced alterations facilitate epithelial‐mesenchymal transition (EMT), enhance cell migration, and enable extracellular matrix degradation, thereby fostering tumor spread. We discuss specific mechanisms, including viral protein interactions and the deregulation of signaling pathways such as Rho GTPases and mTOR, which collectively orchestrate cytoskeletal dynamics to support invasion and metastasis. Furthermore, this review highlights emerging therapeutic opportunities, including targeting FSCN1 (Fascin Actin‐bundling Protein 1, FSCN1) inhibition or using small‐molecule inhibitors to disrupt oncovirus‐mediated cytoskeletal changes and impede tumor progression. By bridging virology and cancer biology, this review provides novel insights for developing precision antimetastatic strategies and underscores the pivotal role of viral‐cytoskeletal interplay in oncology.

Abstract: Bronchopulmonary dysplasia (BPD) is a prevalent chronic lung disease in preterm infants, characterized by dysregulated macrophage polarization and oxidative stress. While mesenchymal stem cell‐derived exosomes (MSC‐Exos) have shown protective effects against BPD, the role of exosomes derived from hypoxia‐preconditioned MSCs (Hypo‐Exos) remains unclear. This study aimed to investigate whether Hypo‐Exos alleviate BPD by modulating alveolar macrophage (AM) polarization and oxidative stress via the mitochondrial transporter SLC25A3. We utilized in vitro models of LPS‐induced M1 polarization and H2O2‐induced oxidative stress in AMs, as well as an in vivo rat model of BPD induced by intermittent hypoxia. Our data demonstrate that hypoxic preconditioning enhanced exosome secretion from MSCs. Furthermore, hypoxic preconditioning promoted the packaging of SLC25A3 into these exosomes. Hypo‐Exos significantly suppressed M1 polarization, reduced oxidative stress, and ameliorated lung injury and dysfunction in BPD rats. Silencing SLC25A3 in MSCs abolished these protective effects. Mechanistically, SLC25A3 interacted with PTEN, leading to inhibition of PTEN expression and activation of the PI3K/AKT signaling pathway. Overexpression of PTEN reversed the beneficial effects of SLC25A3 on macrophage polarization and oxidative stress. These findings reveal that Hypo‐Exos deliver SLC25A3 to AMs, thereby downregulating PTEN, activating PI3K/AKT signaling, promoting M2 polarization, attenuating oxidative damage, and ultimately mitigating BPD progression. This study provides important mechanistic insights and suggests potential therapeutic avenues for exosome‐based treatment of BPD.

Abstract: Botryosphaeran is an exocellular (1 → 3)(1 → 6)-β-d-glucan that promotes significant metabolic effects in male rats, as antiobesogenic and hypoglycemic effects. This study aimed to investigate its metabolic effects in female Wistar rats subjected to a high-fat high-sucrose diet. Obesity induction resulted in increased body weight, accumulation of adipose tissue, glucose intolerance, insulin resistance, hepatomegaly and high levels of TBARS (oxidative stress marker) in the liver, compared with the controls; all differences were statistically significant (p ˂0.05). Treatment with botryosphaeran (12 mg/kg/day; 15 days) significantly reduced the weight gain (p ˂0.01), the retroperitoneal adipose tissue (-29.7%, p ˂0.05), and corrected glucose intolerance with a 8.32% reduction in the area under the curve (AUC, p ˂0.05), relative to untreated obese rats. Furthermore, botryosphaeran reduced the levels of TBARS (-45.4%, p ˂0.05) in liver, reducing oxidative stress. Additionally, no differences were observed in the liver for protein carbonyls, superoxide dismutase, catalase, glutathione peroxidase, and ascorbic acid. In conclusion, botryosphaeran was observed to promote a significant antiobesogenic effect, promoting an expressive loss in body-weight, reduction of adipose tissue, correction of glucose intolerance and promoting an antioxidant effect in the female rats.

Abstract: ABSTRACT Individuals with type 1 diabetes mellitus (T1DM) experience an increased risk of cardiovascular disease (CVD). To improve early detection and prevention strategies, a better understanding of early vascular changes is needed. Although coronary artery (CA) damage is a known T1DM complication, its underlying proteomic basis remains unclear. This study used a proteomic approach to identify differentially expressed proteins in the CAs of T1DM rat models, with the goal of identifying novel proteins and pathways associated with early diagnosis and prevention of CA complications. We established a streptozotocin‐induced T1DM model in male Sprague–Dawley rats and conducted tandem mass tag‐based quantitative proteomics and bioinformatics analyses to investigate protein expression profiles in CAs. The analyses identified 443 differentially expressed proteins, with 229 upregulated and 214 downregulated proteins. Functional annotation and pathway enrichment analyses revealed that these proteins primarily participate in lipid metabolism, the peroxisome proliferator‐activated receptor (PPAR) signaling pathway, peroxisome function, and butanoate metabolism. Validation experiments using Western blotting analysis and quantitative real‐time PCR confirmed significant upregulation of 3‐hydroxy‐3‐methylglutaryl coenzyme A synthase 2 (HMGCS2), fatty acid‐binding protein 4 (FABP4), and platelet glycoprotein 4 (CD36) at the protein and mRNA levels in diabetic rat CAs, consistent with the proteomic results. Our findings indicate that HMGCS2, FABP4, and CD36 may serve as important molecular markers for the early diagnosis or therapeutic targeting of CA damage in T1DM. The observed molecular changes appear to be linked to the PPAR signaling pathway. Clinical trial registration . Not applicable.

Abstract: Spinal muscular atrophy (SMA) is the most common genetic disease leading to infant mortality, primarily characterized by the deficiency of survival motor neuron (SMN) protein. The effects of SMA are not limited to the nervous system but also encompass multiple cell types. Fibroblasts have been extensively employed as primary disease model cells in SMA pathophysiological studies. Here, we present a comprehensive summary of the pivotal roles fibroblasts play in SMA research, focusing on how SMN deficiency modulates the response characteristics of fibroblasts. Our findings reveal distinct reactivity patterns in fibroblasts, which serve as representative Non-neuronal cells, compared to motor neurons in SMA. This review underscores the crucial roles of fibroblasts in elucidating mechanistic changes, advancing drug discovery, and identifying reliable biomarkers for SMA. These insights underscore the indispensable potential of fibroblasts in future SMA research endeavors.

Abstract: The essential trace element zinc is a well‐known modulator of T cell activation. There have been contradictory findings for the impact of zinc supplementation on T cell activation. In our study, we aimed to analyze IL‐2 production in Jurkat T cells during zinc supplementation in response to different stimuli. We found that zinc strongly suppresses IL‐2 production in Jurkat cells stimulated with phorbol 12‐myristate 13‐acetate (PMA)/calcimycin or phytohemagglutinin (PHA)/calcimycin. In contrast, zinc had no impact on IL‐2 production after PHA stimulation alone, suggesting the inhibitory zinc‐effect was linked to high calcium influx. To distinguish if the observed IL‐2 suppression is due to either potential competing effects of zinc influx or simple elevation of intracellular zinc levels, we pretreated the Jurkat cells with the zinc ionophore pyrithione for an increase of intracellular zinc before the stimulation. It was sufficient to suppress IL‐2 expression even when the cells were not further supplemented with zinc during stimulation. We propose that zinc's inhibitory effects on phosphatases stabilize the phosphorylated NFAT and thus block IL‐2 expression. Our findings underline the importance of a balanced zinc status for proper immune functions and suggest a supporting effect of zinc during immunosuppressive treatments.

Abstract: Nonalcoholic steatohepatitis (NASH), a highly prevalent metabolic‐related fatty liver disease, has become a major global health issue with limited therapeutic options. Recent studies indicated that ostreolysin (Oly), a protein derived from oyster mushrooms, could be a potential therapeutic agent for NASH. In this study, recombinant Oly (rOly) was expressed in E. coli BL21 (DE3) and purified using Q Sepharose and TOYOPEARL chromatography, with its identity confirmed by SDS‐PAGE and mass spectrometry. Indb/db mice, subcutaneous injection of rOly at 0.5 and 1 mg/kg every 2 days for 30 days significantly reduced body weight by 14.1% in the high‐dose group (p < 0.01), improved insulin resistance (insulin resistance index decreased by 35%, p < 0.05), and alleviated hepatic steatosis as shown by HE and Oil Red O staining.In vitro, rOly induced browning of 3T3‐L1 preadipocytes, evidenced by 1.8‐fold upregulation of UCP1 (p < 0.05) and 2.3‐fold upregulation of ATGL (p < 0.01). Mechanistic studies revealed that rOly inhibited Hedgehog signaling pathway genes Gli1 and Ptch1 by 70% and 65% (p < 0.0001), respectively, promoting beige adipocyte differentiation. These findings demonstrate that rOly enhances energy metabolism by promoting preadipocyte browning via Hedgehog pathway inhibition, providing a promising basis for treating obesity and metabolic diseases.

Abstract: ABSTRACT The biosynthesis of silver nanoparticles (AgNPs) using cyanobacteria has gained significant attention due to its cost‐effective and eco‐friendly advantages in green synthesis. Additionally, biogenic AgNPs show great potential for biological applications, particularly in combating infections caused by drug‐resistant bacteria and fungi. This study synthesized using the cyanobacterium Oscillatoria salina ( Os ‐AgNPs). The Os ‐AgNPs were characterized by a UV‐vis spectral absorption peak at 447 nm, and their functional groups were identified through X‐ray diffraction analysis, revealing a crystal structure with a 2θ value of 38°. Transmission electron microscopy (TEM) analysis showed an average nanoparticle size of 9.81 nm. The Os ‐AgNPs demonstrated remarkable antioxidant, antibacterial, and antifungal properties. Their antibacterial activity was tested against multidrug‐resistant (MDR) Gram‐positive bacteria, including Staphylococcus aureus , Streptococcus pyogenes , and Enterococcus faecalis , as well as Gram‐negative bacteria such as Escherichia coli , Klebsiella pneumoniae , and Pseudomonas aeruginosa , all isolated from clinical samples. The inhibition zones for bacterial strains ranged from 15 to 20 mm, as measured by the agar‐well diffusion method. Similarly, the Os ‐AgNPs exhibited antifungal activity, with 20–30 mm inhibition zones against pathogenic fungi Trichophyton rubrum and Candida tropicalis . Additionally, the antiproliferative effects of the Os ‐AgNPs were evaluated on human cancer cell lines, including HeLa (cervical adenocarcinoma) and MD‐AMB‐231 (breast adenocarcinoma). In vivo toxicity studies were conducted using Swiss mouse models to assess the cytotoxic effects. Overall, the results suggest that Os ‐AgNPs, biosynthesized using O. salina , hold promise as potential antimicrobial and anticancer agents for pharmaceutical applications.

Abstract: The choice of appropriate analytical methods for determining methylation patterns at specific loci across the genome is essential for identifying novel diagnostic and prognostic markers for subsequent clinical implementation. Various methods exist for determining methylation status using different technologies. In this study, we compared two distinct digital polymerase chain reaction (PCR) platforms: the nanoplate-based Qiagen QIAcuity Digital PCR (dPCR) System and the droplet-based Bio-Rad QX-200 Droplet Digital PCR (ddPCR) System. By assessing their efficacy and other attributes, we aimed to elucidate each platform's strengths and limitations in the sensitive detection of DNA methylation, thus contributing valuable insights to the field of molecular diagnostics. We analyzed the methylation status of the CDH13 gene in 141 formalin-fixed, paraffin-embedded breast cancer tissue samples using our in-house developed methylation-specific labeled assay. The specificity and sensitivity of the CDH13 assay evaluated by dPCR were 99.62% and 99.08%, respectively; ddPCR analysis reached a specificity of 100% and a sensitivity of 98.03%. In addition, our data revealed a strong correlation between the methylation levels measured by both methods (r = 0.954). Although both methods are based on different technologies, they yielded comparable, highly sensitive experimental data in our study. Consequently, the main criteria for selecting an optimal digital PCR platform for methylation analysis may lie in other factors such as workflow time and complexity, instrument requirements, the possibility of temperature gradient, reanalysis, or offline options.