Search Results (369)

High-Mobility Group B (HMGB) proteins are conserved non-histone nuclear proteins involved in DNA replication, transcription, recombination, repair; plant growth and development; and stress responses. In this study, we identified nine ClHMGB genes in watermelon using genome-wide search. Phylogenetic and homology analyses classified them into four distinct classes. Synteny analysis revealed that ClHMGB genes share closer evolutionary relationships with dicots than with monocots. Tissue-specific expression profiling showed that eight ClHMGB members exhibit higher transcript levels in female and/or male flowers, suggesting that they play essential roles in floral organ development. Under drought, low-temperature, and salt stresses, ClHMGB members displayed distinct expression patterns. For instance, ClHMGB4 and ClHMGB8 were downregulated under drought and low-temperature stress but upregulated under salt stress, indicating potential functional specialization in response to different abiotic stresses. The highly virulent Fusarium oxysporum f. sp. niveum race 2 (Fon R2) induced the upregulation of more ClHMGB genes than the less virulent race 1 (Fon R1). Four members (ClHMGB1, 4, 6, and 7) were consistently upregulated by both races, suggesting that they may play fundamental roles in disease resistance. This study provides a foundation for further investigation into the roles of ClHMGB genes in growth, development, and stress responses of watermelon. Full article

Studies in human medicine have demonstrated that rotavirus infection can also affect extraintestinal sites due to its systemic effects. However, in veterinary medicine, the injury caused by rotavirus diarrhea is limited to the intestines, and its effects on various systemic structures remain poorly understood. In this observational case–control study, we aimed to determine the effects of HSP-27, Caspase-3, IL-2, γ-H2AX, HMGB-1, SP-D, and GDH (or GLDH) on the pathogenesis of rotavirus infection by using biomarkers for diagnostic purposes in lung and liver injury in neonate diarrheic calves naturally infected with rotavirus, both alive and post-mortem. Fifty-two Simmental calves (1–28 days old) of both sexes, 40 infected with rotavirus and 12 healthy, were studied. Twenty-eight out of 40 survived, while the remainder underwent necropsy for histopathological and immunopathological (HSP-27, Caspase-3, IL-2, γ-H2AX) examination of the lungs and livers. Lung and liver-specific serum E-selectin, glutamate dehydrogenase, surfactant protein-D, and high mobility group box-1 were analyzed by a bovine-specific ELISA kit (Shanghai Coon Koon Biotech Co., Ltd., China). Histopathological and immunohistochemical analyses confirmed lung and liver injury in naturally infected calves. HMGB-1, SP-D, and GDH concentrations were significantly higher in naturally infected calves than in the control group (p < 0.001, p < 0.001, and p < 0.05, respectively), showing an excellent diagnostic predictive capacity for lung and liver injury. Also, IL-2, HSP-27, CASP-3, and γ-H2AX were significantly expressed in the lungs (p < 0.001, p < 0.001, p < 0.001, and p < 0.05, respectively) and liver (p < 0.001, p < 0.001, p < 0.01, and p < 0.01, respectively). All these observations led us to hypothesize that oxidative stress, apoptosis, and DNA damage may underlie the pathogenesis of this condition. Nevertheless, further studies on large populations of rotavirus-infected calves are needed to confirm the data reported in the current study. Full article

The influence of lactic acid bacteria (LAB) strains of various species isolated from Chinese traditional sourdough on the properties of rice sourdough and the textural and flavor qualities of steamed rice bread (SRB) was investigated. Lactiplantibacillus plantarum-fermented rice sourdough had a higher total titratable acidity (13.10 mL) than the other groups. Strains Lacticaseibacillus paracasei PC1 (LPC), Lactobacillus helveticus H1 (LH), Lactobacillus crustorum C1 (LC), Lactobacillus paralimentarius PA1 (LPA), and Lactiplantibacillus plantarum P1 (LP) showed marked protein hydrolysis during rice sourdough fermentation and increased free amino acid levels in rice sourdoughs relative to the control. The Fourier Transform Infrared Spectroscopy results indicated that LAB fermentation could promote the strengthening of inter-intramolecular hydrogen bonds and cause modifications in protein structures; however, these effects varied among the different strains. The LC and LPC strains had the most significant effect on improving the specific volume and textural properties of SRBs. Gas chromatography-mass spectrometry (GC-MS) and GC-ion mobility spectrometry (IMS) identified 33 and 35 volatile compounds, respectively, in the LAB-fermented SRBs, and differentiation was observed in the volatile profiles of SRBs made using different LAB strains. The differential impacts of LAB strains during rice sourdough fermentation can assist in the selection of candidate microorganisms for the production of high-quality gluten-free rice products. Full article

High mobility group A1 (HMGA1) is a chromatin-associated protein that regulates transcription and drives cancer progression. In this pan-cancer study, we analyzed multi-omics data to comprehensively characterize HMGA1’s expression patterns, prognostic significance, epigenetic regulation, and immunotherapy roles. We found that HMGA1 was markedly upregulated in most cancers, mainly driven by promoter hypomethylation and copy number alterations. Elevated HMGA1 expression was consistently associated with unfavorable patient survival, stemness features, and the activation of oncogenic signaling pathways. Crucially, HMGA1 expression correlated with an immune-excluded tumor microenvironment, characterized by suppressed stromal and immune scores. Even in tumors with immune infiltration, high HMGA1 predicted poor prognosis, likely mediated by enhanced regulatory T-cell (Treg) recruitment and impaired effector immune function. Moreover, HMGA1 levels were positively correlated with tumor mutational burden (TMB), and microsatellite instability (MSI), and immunotherapy-related checkpoints including PD-1, CTLA-4, and TIGIT. Drug sensitivity analysis further revealed that HMGA1 predicted resistance to AKT inhibitors, which was experimentally validated in breast cancer cells treated with Capivasertib. Collectively, our findings establish HMGA1 as a pivotal oncogenic regulator and a promising biomarker for prognosis and for guiding strategies in immunotherapy and overcoming targeted therapy resistance. Full article

The hypoxic, cold, and high-ultraviolet radiation environments at high altitude pose severe challenges to mammalian immune and metabolic systems. However, little is known about how captive forest musk deer adapt to high-altitude environments and their seasonal variations. This study analyzed peripheral blood transcriptomes of 33 captive forest musk deer (Moschus berezovskii) at high altitude (~3900 m) and low altitude (~1450 m) during autumn-winter and spring-summer seasons. Results revealed comprehensive immune suppression in the high-altitude group during autumn-winter (downregulation of complement system CFB/C2/C3, interferon pathway genes including FLT3, with only natural killer (NK) cell PRKCQ upregulated), coupled with energy-conserving metabolic reprogramming (altered carbohydrate metabolism, inhibited lipid synthesis, fat mobilization, suppressed protein degradation). During spring-summer, neutrophil antimicrobial responses (SLPI/NCF1/ELANE) and humoral immunity (B cell differentiation genes PAX5/RUNX1; class-switch enzyme AICDA) partially recovered while cellular immunity (IL15/B2M) remained suppressed, accompanied by enhanced anabolic metabolism and adipocyte differentiation. Notably, NK cell-mediated cytotoxicity showed selective enhancement despite comprehensive immune suppression, representing an energy-efficient innate defense strategy. This study provides the first characterization of seasonal immune dynamics in a high-altitude cervid species. These findings reveal persistent immune constraints in high-altitude populations and provide theoretical foundations for disease prevention and health management in captive forest musk deer at high altitudes. Full article

Background: Microglial cells are the resident immune cells in the central nervous system (CNS) and constitute the brain’s innate immune system. They are the smallest of the glial cells and are derived from phagocytic white blood cells, fetal monocytes, which migrate from the blood into the brain during development. On the other hand, epilepsy is a chronic condition defined as recurrent unprovoked seizures, with at least two seizures occurring over 24 h apart. Methods: To determine the role of microglial activation in the pathogenesis of drug-resistant epilepsy, we systematically searched published data for biomarkers of microglial activation from main databases including PubMed, PubMed Central, Scopus, Embase, Google Scholar, and Medline. Two research registries were also searched: the Cochrane Registry and clinicaltrial.gov. Data was collected after applying inclusion and exclusion criteria and studies were appraised critically. Both Medical Subject Headings (MeSH) and regular keyword search strategies were employed. Results: Our systematic review shows significant elevation of biomarkers of microglial activation in patients with drug-resistant epilepsy, suggesting its role in the disease’s pathogenesis. Conclusions: Microglia cells are therefore considered as a special type of mononuclear phagocytes found in the CNS that plays important roles in both the brain’s immunity and homeostatic functions. The role of microglial activation in the pathogenesis of drug-resistant epilepsy is an active area of study, with potential therapies for drug-resistant epilepsy that target microglia currently being investigated. Full article

High Mobility Group Box 1 (HMGB1) is a central pro-inflammatory mediator released from damaged or stressed cells, where it activates receptors such as the Receptor for Advanced Glycation Endproducts (RAGE). Dendritic polyglycerol sulfate (dPGS), a hyperbranched polyanionic polymer, is known for its anti-inflammatory activity. In this study, we examined how dPGS modulates HMGB1-driven signaling in RAW 264.7 macrophages and human microglia. Recombinant human HMGB1 expressed in Escherichia coli (E. coli) was purified by nickel-nitrilotriacetic acid (Ni-NTA) and heparin chromatography. Proximity ligation assays (PLA) revealed that dPGS significantly disrupted HMGB1/RAGE interactions, particularly under lipopolysaccharide (LPS) stimulation, thereby reducing inflammatory signaling complex formation. This correlated with reduced activation of the nuclear factor kappa B (NF-κB) pathway, demonstrated by decreased nuclear translocation and transcriptional activity. Reverse transcription polymerase chain reaction (RT-PCR) and quantitative real-time PCR (RT-qPCR) showed that dPGS suppressed HMGB1- and LPS-induced transcription of tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6), monocyte chemoattractant protein-1 (MCP-1), cyclooxygenase-2 (COX-2), and inducible nitric oxide synthase (iNOS). Enzyme-linked immunosorbent assay (ELISA) and Griess assays confirmed reduced TNF-α secretion and nitric oxide production. Electron paramagnetic resonance (EPR) spectroscopy further showed that dPGS altered HMGB1/soluble RAGE (sRAGE) complex dynamics, providing mechanistic insight into its receptor-disruptive action. Full article

This article reviews the research progress for high-mobility group protein B1 (HMGB1) and its signaling pathway in osteosarcoma (OS) and discusses its application potential in targeted therapy. A large number of domestic and foreign studies were reviewed to summarize the research results on the the biological function, signal pathway regulation mechanism, and intervention strategy of HMGB1 in recent years. HMGB1 promotes OS cell proliferation, invasion, and immune escape by activating RAGE, TLR4, and downstream MAPK, NF-κB, and PI3K/AKT signaling pathways. Interfering with HMGB1 or its signaling axis shows good antitumor potential in in vitro and in vivo models, but clinical transformation is still limited by its dual biological effects and tumor heterogeneity. HMGB1 and its related signaling pathways are important targets for the treatment of osteosarcoma. In the future, the development of a multi-channel combined intervention and efficient delivery system will provide a new direction for improving the therapeutic effect. Full article

Secondary peritonitis is a life-threatening intra-abdominal condition arising from gastrointestinal perforation, chemical injury, or catheter-related infections, characterized by marked heterogeneity in presentation and progression. Major subtypes include stercoraceous peritonitis with fecal contamination, fibrinous peritonitis triggered by bile or gastric contents, peritoneal dialysis-associated infections, and pancreatitis-associated chemical peritonitis. Regardless of etiology, these conditions share profound local and systemic inflammatory responses, contributing to high morbidity and mortality. Biomarkers such as procalcitonin (PCT), interleukin-6 (IL-6), high mobility group box 1 (HMGB1), C-reactive protein (CRP), lipopolysaccharide (LPS), neutrophil-to-lymphocyte ratio (NLR), and neutrophil gelatinase-associated lipocalin (NGAL) have emerged as tools for early diagnosis, subtype stratification, and monitoring of therapeutic response. Their prognostic value is particularly relevant in peritoneal dialysis and postoperative intensive care. Advances in multi-omics, patient-derived organoids, peritoneum-on-chip models, and microbiota profiling are reshaping understanding of peritoneal pathophysiology, revealing cellular heterogeneity, immune-microenvironment interactions, and mechanisms of fibrotic remodeling. Key translational challenges include assessing whether omics-derived signatures can predict the need for early re-laparotomy or the risk of abdominal compartment syndrome. Integration of high-dimensional biomarker profiling with mechanistic and functional studies promises a new era of precision medicine in secondary peritonitis, enabling risk-adapted interventions, complication prevention, and tailored strategies to improve outcomes. Full article

Background/Objectives: Obesity increases reactive oxygen species (ROS), thereby triggering oxidative stress. Coriander seeds contain polyphenolic compounds that act as natural antioxidants to reduce oxidative stress. Coriander seed ethanolic extract has been proven to decrease malondialdehyde and increase catalase activity in the liver of high-fat-diet-fed rats. Thus, coriander seeds are thought to protect against obesity-induced oxidative liver damage; however, their molecular mechanism has not been revealed. Nuclear factor erythroid 2-related factor 2 (Nrf2) and Forkhead Box O3 (FOXO3) are transcription factors involved in cellular antioxidant regulation (e.g., superoxide dismutase/SOD, glutathione peroxidase/GPx expression, and reduced glutathione/GSH) that are negatively regulated by Kelch-like ECH-associated Protein 1 (Keap1) and 14-3-3 protein to maintain cellular homeostasis. This study aimed to analyze the regulation of antioxidant expression through in silico and in vivo experiments. Methods: The in silico study assessed the potential of coriander seed ethanolic extract to inhibit Keap1 and 14-3-3 using molecular docking. Then, the drug-likeness, pharmacokinetics, and toxicity of the top three compounds were analyzed. Meanwhile, the in vivo study investigated how the coriander seed ethanolic extract impacted the level of Nrf2, FOXO3, and their downstream effectors (T-SOD, MnSOD, GPx, and GSH). The in vivo study involved five groups of rats with obesity induced by a high-fat diet that were fed with 100 mg/kgBW coriander seed ethanolic extract for 12 weeks. Results: The in silico tests revealed that shionoside b had the highest potential to inhibit Keap1 (ΔG = −8.90 kcal/mol; Ki = 298.01 nM) and 14-3-3 protein (ΔG = −6.85 kcal/mol; Ki = 9.46 µM). The in vivo tests showed that the Nrf2, FOXO3, MnSOD, and GPx mRNA expression was significantly different between the groups (p < 0.05). Meanwhile, T-SOD, MnSOD, GPx, and GSH activity were not significantly different between the groups (p > 0.05). Nrf2 was significantly correlated with FOXO3 as well as the T-SOD, MnSOD, and GPx activity, and FOXO3 was significantly correlated with the T-SOD, MnSOD, GPx, and GSH activity. Conclusions: In obese rats, coriander seeds tend to increase Nrf2 and FOXO3 expression, which is positively correlated with their downstream enzymatic and nonenzymatic antioxidant activity. This is possibly due to the interaction between the coriander seed phytoconstituents and protein inhibitors (Keap1 and 14-3-3), which contribute to the stability and nuclear mobilization of Nrf2 and FOXO3. Full article

Antinuclear antibodies, especially anti-DNA antibodies, are known to be a hallmark of systemic lupus erythematosus (SLE) and represent a diverse pool of autoantibodies with different origins, antigenic properties, and physicochemical features. Antibodies with catalytic properties have been found among the antibody repertoire in SLE, but the specific features and clinical associations of such antibodies have not been sufficiently studied. This study showed that chromatographically purified IgG from the serum of SLE patients effectively hydrolyzed DNA and DNA-associated proteins such as histones and high-mobility group box 1 (HMGB1) compared to healthy individuals. Remarkably, the level of hydrolysis of DNA and DNA-associated proteins was closely correlated. At the same time, these antibodies did not hydrolyze the control protein, tumor necrosis factor-α (TNFα), which does not possess DNA-binding properties. IgG DNase activity levels varied significantly, so patients were divided into high- and low-activity subgroups using the DBSCAN algorithm, with the difference between median values being greater than 49 times. The subgroup with high IgG DNase activity was characterized by an increase in anti-DNA antibodies (p < 0.04) than the subgroup with low activity, which had a shorter duration of the disease (p = 0.03) and was more often characterized by a subacute rather than a non-chronic course of the disease (p = 0.048). High catalase-like activity of IgG was also detected in SLE. Thus, the antibody pool in SLE contains not only high-affinity antinuclear autoantibodies but also catalytic antibodies capable of hydrolyzing DNA and DNA-associated proteins. These findings expand our understanding of the heterogeneity of the repertoire of catalytic autoantibodies among SLE patients. Full article

Background/Objectives: Natural products, especially plant metabolites, play a crucial role in drug development and are widely used in medicine, cosmetics, and nutrition. The present review aims to provide a comprehensive overview of the pharmacological profile of Glycyrrhizin (GL), with a specific focus on its molecular targets. Methods: Scientific literature was thoroughly retrieved from reputable databases, including Scopus, Web of Science, and PubMed, up to 30 July 2025. The keywords “glycyrrhizin” and “glycyrrhizic acid” were used to identify relevant references, with a focus on pharmacological applications. Studies on synthetic analogs, non-English publications, non-pharmacological applications, and GL containing crude extracts were largely excluded. Results: Glycyrrhizin, the major bioactive constituent of Glycyrrhiza glabra, exhibits diverse pharmacological activities, including anti-inflammatory, antiviral, hepatoprotective, antitumor, neuroprotective, and immunomodulatory effects. These actions are primarily mediated through the inhibition of high-mobility group box 1 (HMGB1) and the modulation of key signaling pathways, including nuclear factor kappa B (NF-κB), mitogen-activated protein kinase (MAPK), phosphoinositide 3-kinase/protein kinase B (PI3K/Akt), and various cytokine networks. As a result of its therapeutic potential, GL-based formulations, including Stronger Neo-Minophagen C, and GL-rich extracts of G. glabra are commercially available as pharmaceutical preparations and food additives. Conclusions: Despite its therapeutic potential, the clinical application of GL is limited by poor oral bioavailability, metabolic variability, and adverse effects such as pseudoaldosteronism. Hence, careful consideration of pharmacokinetics and safety is essential for translating its therapeutic potential into clinical practice. Full article

Glioblastoma (GBM) remains the most lethal primary brain tumor, owing to profound intratumoral heterogeneity and the limited efficacy of standard treatments. The mesenchymal (MES) molecular subtype is particularly aggressive, exhibiting heightened invasiveness, therapy resistance, and dismal patient survival compared with the proneural (PN) subtype. Emerging evidence implicates the High Mobility Group Box 1 (HMGB1) protein and its cognate receptor, the Receptor for Advanced Glycation End Products (RAGE), as drivers of malignant progression, yet their contribution to the PN-to-MES transition is incompletely defined. We integrated transcriptomic analyses of TCGA-GBM and TCGA-LGG cohorts with immunohistochemistry on in-house patient specimens. Functional studies in patient-derived and established GBM cell lines included migration and invasion assays, tumorsphere formation assays, shRNA knockdowns, and Seahorse XF metabolic profiling to interrogate the HMGB1-RAGE axis. HMGB1 and RAGE expression was markedly elevated in MES GBM tissues and cell lines. Importantly, higher HMGB1 expression correlated with shortened overall survival (p < 0.009). HMGB1 silencing curtailed cell motility and downregulated core epithelial-to-mesenchymal transition markers (N-cadherin, Snail). RAGE knockdown diminished tumorsphere formation efficiency and reduced transcription of stemness genes (OCT4), underscoring its role in sustaining tumor-initiating capacity. Metabolically, HMGB1/RAGE activation boosted both mitochondrial respiration and glycolysis, conferring the bioenergetic flexibility characteristic of MES GBM. The HMGB1-RAGE signaling axis orchestrates mesenchymal identity, invasiveness, stem cell-like properties, and metabolic reprogramming in GBM. Targeting this pathway may disrupt the PN-to-MES transition, mitigate therapeutic resistance, and ultimately improve outcomes for glioblastoma patients. Full article

Background/Objectives: DNA-damaging agents can contribute to genetic instability, and such agents are often used in cancer chemotherapeutic regimens due to their cytotoxicity. Thus, understanding the mechanisms involved in DNA damage processing can not only enhance our knowledge of basic DNA repair mechanisms but may also be used to develop improved chemotherapeutic strategies to treat cancer. The high-mobility group box protein 1 (HMGB1) is a known nucleotide excision repair (NER) cofactor, and its family member HMGB3 has been implicated in chemoresistance in ovarian cancer. Here, we aim to understand the potential role(s) of HMGB3 in processing DNA damage. Methods: A potential role in NER was investigated using HMGB3 knockout human cell lines in response to UV damage. Subsequently, potential roles in DNA interstrand crosslink (ICL) and DNA double-strand break (DSB) repair were investigated using mutagenesis assays, metaphase spreads, foci formation, a variety of DNA repair assays, and TagSeq analyses in human cells. Results: Interestingly, unlike HMGB1, HMGB3 does not appear to play a role in NER. We found evidence to suggest that HMGB3 is involved in the processing of both DSBs and ICLs in human cells. Conclusions: These novel results elucidate a role for HMGB3 in DNA damage repair and, surprisingly, also indicate a distinct role of HMGB3 in DNA damage repair from that of HMGB1. These findings advance our understanding of the role of HMGB3 in chemotherapeutic drug resistance and as a target for new chemotherapeutic strategies in the treatment of cancer. Full article

Conidiation and stress tolerance are pivotal traits in entomopathogenic fungi, critically influencing their production costs and environmental tolerance. While the transcription factor high-mobility group protein (HMG), characterized by a conserved HMG-box domain, has been extensively studied for its role in sexual development, its functions in entomopathogenic fungi remain largely unexplored. This study employed gene knockout to investigate the role of MaHMG in Metarhizium acridum. The deletion of MaHMG delayed conidiation initiation and caused a highly significant 58% reduction in conidial yield versus that of the wild type (WT) after 15 days. Furthermore, the conidiation pattern on microcycle induction medium (SYA) shifted from microcycle to normal conidiation. The ΔMaHMG mutant exhibited decreased conidial germination rates and markedly reduced tolerance following UV-B irradiation and heat-shock treatments, alongside increased sensitivity to the cell wall perturbant calcofluor white (CFW). RNA-seq analysis during this conidiation shift identified 88 differentially expressed genes (DEGs), with functional annotation implicating their predominant association with hyphal development, cell wall biogenesis, cell cycle progression, and conidiation. In conclusion, MaHMG functions as a critical positive regulator governing both conidiation and stress tolerance in M. acridum, underscoring its fundamental role in fungal biology and potential as a target for enhancing biocontrol agent performance. Full article