Hongtao Bi

In a previous study, we isolated a water-soluble heteropolysaccharide (CRWP-S) from the edible lichen Cladina rangiferina (L.) Nyl., which exhibited potent free radical-scavenging capacities. However, its protective efficacy against ultraviolet B (UVB)-induced skin photoaging and the underlying molecular mechanisms remain to be fully elucidated. In this study, we established a UVB-induced photoaging model in BALB/c mice and cell senescence model in HaCaT keratinocytes to evaluate the photoprotective effects and mechanisms of CRWP-S. Microneedle-assisted topical application of CRWP-S effectively attenuated UVB-induced macroscopic photoaging phenotypes, while mitigating dermal collagen degradation and restored NRF2 expression in vivo. CRWP-S treatment enhanced HaCaT cell viability, reduced intracellular reactive oxygen species (ROS) and malondialdehyde (MDA) levels, and restored the activities of superoxide dismutase (SOD) and catalase (CAT). Mechanistically, CRWP-S inhibited senescence-associated β-galactosidase (SA-β-Gal) activity and downregulated the expression of senescence markers p53 and p21. Furthermore, CRWP-S promoted NRF2 nuclear translocation and upregulated downstream heme oxygenase-1 (HO-1) while downregulating KEAP1 expression. Pharmacological inhibition of NRF2 using ML385 largely abolished the ROS-scavenging and cytoprotective effects of CRWP-S. Taken together, these findings demonstrate that CRWP-S protects against UVB-induced skin photoaging via activation of the KEAP1–NRF2 signaling pathway, highlighting its strong potential as a functional bioactive ingredient for anti-photoaging formulations.

Arsenic is a ubiquitous environmental toxicant closely linked to multiple adverse biological effects and health impairments. In this study, we investigated the effect of exposure to sodium arsenite on reactive oxygen species (ROS) generation, DNA damage response, and G2/M arrest in HEK-293 cells. The results showed that exposure to sodium arsenite induced a concentration-dependent increase in intracellular ROS levels. Assessment of DNA damage via γ-H2AX detection and comet assay revealed that arsenite treatment also enhanced γ-H2AX expression and tailed DNA content markedly in a dose-dependent manner. Furthermore, flow cytometric analysis confirmed that arsenite concurrently triggered pronounced G2/M arrest in HEK-293 cells. Mechanistic studies revealed that exposure to sodium arsenite led to ROS-induced DNA damage in HEK-293 cells, which further led to G2/M arrest via activating the ATM-p53-p21 pathway. Notably, arsenite-induced G2/M arrest in HEK-293 cells was predominantly mediated by p21 upregulation, independent of Cdc25C-CDK1 pathway. This work deepens our comprehensive insight into the regulation of G2/M arrest upon arsenite exposure and lays a mechanistic basis for subsequent studies in more physiologically pertinent and tissue-specific models.

Neurological disorders comprise a heterogeneous spectrum-including cerebrovascular disease, neurodegeneration, autoimmune demyelination, neuropsychiatric conditions, and trauma-whose incidence and prevalence are rising with population aging, creating sustained healthcare and socioeconomic burdens. Recent work highlights laminin, a major non-collagenous BM glycoprotein, as a key regulator of central nervous system structure and function. As a core extracellular matrix scaffold and signaling hub, laminin orchestrates matrix remodeling, barrier disruption/repair, neuroinflammation, and neuronal plasticity; it contributes to neurodevelopment and axon guidance, synaptogenesis and plasticity, myelination and nodal microarchitecture, and the homeostasis of the blood-brain barrier and neurovascular unit. Based on a comprehensive literature review, this article systematically elaborates the structure and classification of laminin, its spatiotemporal distribution and physiological roles in the central nervous system, as well as the molecular mechanisms and network effects in neurological diseases. Furthermore, it evaluates the feasibility and challenges of laminin-targeted therapies, aiming to provide insights for the development of innovative precision interventions. This review systematically demonstrates that the laminin family functions not merely as a "structural hub of the basement membrane," but also holds substantial promise as an "actionable target" for neurological disorders. Through a parallel receptor network comprising integrins, α-dystroglycan, and heparan sulfate proteoglycans/syndecans, laminin couples mechanical support with signal transduction, occupying a central position in the development, homeostatic maintenance, and repair of the blood-brain barrier/neurovascular unit, synaptic architecture, and the myelin-Nodes of Ranvier microstructure. Future investigations should elucidate the profound mechanistic roles of laminin family members in neurological diseases and advance targeted therapeutic development, thereby facilitating novel strategies for the prevention and treatment of neurological disorders.

Trigonella foenum‐graecum L. seed polysaccharides (FSP) belong to a very important species of biological macromolecules with prebiotic activity, which are the basic substances that have broad application potential in food and pharmaceutical fields. However, systematic studies focusing on the compound enzyme‐assisted extraction of FSP and their hepatoprotective effects remain limited. This study aimed to optimize the compound enzyme‐assisted extraction of FSP, analyze the structural features of deproteinized FSP (DFSP), and evaluate its therapeutic potential against metabolism‐associated fatty liver disease (MAFLD). The results showed that the optimal extraction conditions were an enzymatic hydrolysis temperature of 50°C, an enzymatic hydrolysis pH of 5.3, an enzymatic hydrolysis time of 1.9 h, and a liquid‐to‐solid ratio of 23:1 mL g ⁻¹ , under which the polysaccharide yield reached 24.88% ± 0.15%. The molecular weight distribution of fenugreek seed polysaccharides was 7157.46, 2785.65, and 642.61 Da, and they were mainly composed of mannose and galactose. In vivo experiments indicated that DFSP exerted a liver‐protective effect on MAFLD mice, accompanied by improvements in lipid metabolic parameters, antioxidant capacity, and inflammatory responses. Therefore, this study provides a scientific basis for further investigations into the fine structure and potential hepatoprotective effects of DFSP.

Background: Depression represents a major global disease burden. High-altitude hypoxia is closely associated with an increased incidence of depressive symptoms; however, the underlying mechanisms remain unclear. Methods: In this study, mice were subjected to 7 days of hypoxic exposure simulating high-altitude environments at 3000 m (14.4% O2) and 4000 m (12.7% O2). Depressive-like behaviors were assessed using the open field test, tail suspension test, and forced swim test. Enzyme-linked immunosorbent assays were employed to measure markers related to inflammatory responses, oxidative stress, and hypothalamic–pituitary–adrenal (HPA) axis activity. Additionally, 16S ribosomal RNA sequencing was performed to analyze alterations in the gut microbiota. Untargeted metabolomics was used to examine metabolite changes in the colon and hippocampus. Validation analyses included measurements of hippocampal immunofluorescence density and cortical neurotransmitter levels. Results: Hypoxic exposure induced depressive-like behaviors, as well as colonic and hippocampal tissue damage. It also exacerbated inflammation and oxidative stress, reduced gut microbiota diversity, disrupted tryptophan metabolism, decreased cortical neurotransmitter levels and brain-derived neurotrophic factor (BDNF), and increased the immunofluorescence density of hippocampal neuron–glial antigen 2 and oligodendrocyte transcription factor 2. These effects exhibited an intensity–toxicity relationship. Conclusions: Acute hypoxia is associated with gut microbiota imbalance, disrupted tryptophan metabolism, inflammatory responses, and dysfunction of the HPA axis, alongside negative emotional states. These multidimensional alterations are strongly correlated, suggesting a potential regulatory network involving the gut microbiota–tryptophan metabolism axis in hypoxia-induced emotional changes.

Exposure to small independent space (SIS) causes stress‐related behavioral and neural abnormalities, but the time‐dependent mechanisms and gut microbiota‐hippocampus interactions remain unclear. To investigate the time‐dependent effects of acute and chronic restraint stress (CRS) on mouse behavior, neuroendocrine function, gut microbiota, and hippocampal activity. Behavioral assessments were conducted using the open field test and tail suspension test. Meanwhile, enzyme‐linked immunosorbent assay (ELISA) was applied to measure neurotransmitters, hypothalamic–pituitary–adrenal (HPA) axis markers, and inflammatory factors; 16S rRNA sequencing was used for gut microbiota analysis; liquid chromatography–tandem mass spectrometry (LC–MS/MS) for metabolite identification; and immunofluorescence staining for hippocampal structure observation. Acute SIS induced depression‐like behaviors. Chronic SIS showed peak despair at 4 days (d), followed by persistent depression at 8 d. Norepinephrine (NE) increased while 5‐hydroxytryptamine (5‐HT) decreased; NE depletion at 4 d coincided with reduced hippocampal glucocorticoid receptor (GR) expression. Both acute (2 h) and chronic (4 d) SIS reduced gut microbiota diversity and disrupted tyrosine metabolism. Hippocampal tests showed neuronal compensation at 6 h post‐acute stress and neuronal apoptosis with glial dysfunction after 4 d of chronic stress. SIS damages via the “gut microbiota‐tyrosine metabolism‐hippocampus axis,” with 4 d of chronic exposure as a critical decompensation point, offering a time‐specific intervention target.

The typical pathology of pulmonary hypertension (PH) is characterized by pulmonary vasoconstriction and irreversible pulmonary vascular remodeling. Vascular remodeling is the process of structural changes and cellular rearrangement of blood vessels due to injury and is a significant factor in conditions such as PH. Echinacoside (ECH) is a phenylethanol glycoside from Tibetan herbs, and our previous study found that ECH modulated calcium channels on pulmonary artery smooth muscle cells (PASMCs) and improved pulmonary vasoconstriction. To investigate the role of ECH in improving pulmonary vascular remodeling in PH, we constructed hypoxia‐induced hypoxic pulmonary hypertension (HPH) and MCT‐induced pulmonary arterial hypertension (PAH) models. Transcriptomic analysis revealed significant enrichment of Cav1.2, Cav3.2, and PKC/MAPK signaling pathways in PAH rats. ECH effectively inhibited Cav1.2 and Cav3.2 protein and mRNA expression, as well as the phosphorylation levels of PKC/MAPK, in HPH and PAH. In addition, ECH effectively reduced mean pulmonary artery pressure (mPAP) and right ventricular hypertrophy index (RVHI) and improved pulmonary vascular remodeling in HPH and PAH rats. In short, we found that ECH improved pulmonary vascular remodeling by modulating Cav1.2 and Cav3.2/PKC/MAPK pathways. Furthermore, this improvement was effective in both HPH and PAH.

Syphilis has emerged as a major public health challenge in China and is characterized by increasing incidence rates and shifting epidemiological patterns.

In the post-COVID-19 era, depression incidence has risen sharply, and a healthy diet is confirmed to lower this risk. However, two critical gaps remain: it is unclear whether nutrients alleviate depressive symptoms by improving the gut microbiota, and existing evidence has notable limitations. This study aimed to address these by exploring how deficiencies in key nutrients (protein, lipids, sugars, vitamins, and minerals) affect gut microbiota diversity—potentially a driver of early depression—and systematically evaluating clinical/basic research on nutrients' role in gut microbiota-mediated depression intervention. Results showed nutrients enhance gut microbiota abundance and diversity, regulate the gut-brain axis to boost short-chain fatty acid (SCFA) and neurotransmitter synthesis, and reduce inflammation, thereby alleviating depression. Thus, a healthy anti-inflammatory diet (rich in vegetables, fruits, fish) may lower depressive symptom risk. Three key research gaps were identified: 1. Mechanistic evidence relies heavily on animal studies (e.g., mouse neurotransmitter experiments) with insufficient large-scale human randomized controlled trials (RCTs) to confirm causality; 2. Conflicting findings exist [e.g., alpha-linolenic acid (ALA) has no antidepressant effect in some human cohorts]; 3. The dose-response relationship (e.g., fiber needed to elevate SCFAs to antidepressant levels) is unquantified. Future studies should quantify dietary patterns and target gut microbiota metabolism to advance early depression prevention and deepen understanding of diet-microbiota-depression links.