Mechanistic Insights into the Antidepressant Effects of the Angelica sinensis and Ligusticum chuanxiong Herb Pair: Involvement of the PI3K/AKT Signaling Pathway.

Baicalin ameliorates ulcerative colitis by regulating macrophage polarization through the JAK1/STAT1/SOCS1 pathway.

Parkinson's disease (PD) is a common neurodegenerative disorder with a complex pathogenesis. 2,3,5,4'-Tetrahydroxy stilbene-2-O-β-D-glucoside (TSG) is one of the main active components of Polygonum multiflorum Thunb., which has therapeutic effects in various neurodegenerative diseases. The aim of this study was to explore the influence of TSG on the PD process. The PD mouse model was constructed via the use of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). The PD process was evaluated via behavioral tests, HE staining, immunohistochemistry, and immunofluorescence. The levels of related proteins and inflammatory factors were detected via western blotting and ELISA. The effect of TSG on the intestinal flora of MPTP-induced PD mice was evaluated through 16S rDNA sequencing. TSG intervention can significantly alleviate motor dysfunction in PD mice, increase the number of TH-positive neurons in the substantia nigra, inhibit the accumulation of α-syn and glial cell activation, reduce the expression of the tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, IL-6, iNOS, and COX2 proteins in the substantia nigra and colon, inhibit neuroinflammation and intestinal inflammation, decrease the levels of LPS, LBP, TNF-α, IL-1β, and IL-6 in the serum, suppress systemic inflammation, reduce damage to the blood-brain barrier (BBB) and intestinal barrier in PD mice, and restore species diversity and abundance of the intestinal flora in PD mice to a certain extent. TSG can improve motor coordination ability, systemic and neuroinflammatory levels, BBB injury, intestinal barrier injury, and the intestinal flora composition of PD mice, suggesting that TSG has a protective effect on MPTP-induced PD mice.

Polysaccharides from Scutellaria barbata D. Don: Anti-ulcerative colitis activity evaluation and structure feature analysis.

A novel DYRK1A inhibitor alleviates lipopolysaccharide-induced acute lung injury via suppressing inflammatory pathway.

Water extract of Ampelopsis grossedentata improves reproductive performance in laying hens by regulating gut microbiota and PI3K/AKT signaling pathway.

Background Management of wound infection and inflammation in diabetic foot is crucial for its treatment. Jiangjunsan has demonstrated potential anti-inflammatory properties and the ability to promote wound healing. This work aimed to investigate the effects of Jiangjunsan wrapping therapy (JJWT) on microbial colonies, levels of inflammatory factors, and regulation of phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) signaling pathway (SPW) in diabetic foot wounds. Methods Sixty diabetic foot patients were enrolled into a control group (CG) and a treatment group (TG), with 30 patients in each group. CG received topical magnesium sulfate in addition to standard treatment, while TG received JJWT for two weeks. The quantity of wound microbial colonies and levels of tumor necrosis factor (TNF)-α and interleukin (IL)-6 were measured before and after treatment, and Western blot analysis was utilized to assess expression levels of PI3K and AKT in wound tissues. Results After treatment, TG exhibited a significantly lower microbial colony count than CG (P < 0.05). Both groups showed a great decrease in TNF-α and IL-6 levels post-treatment (P < 0.05), with TG demonstrating lower levels of TNF-α, IL-6, PI3K, and AKT proteins relative to CG (P < 0.05). Conclusion JJWT effectively reduced microbial colony counts in diabetic foot patients, markedly suppressed the expression of TNF-α and IL-6, and enhanced wound healing by modulating PI3K/Akt SPW, indicating strong antibacterial and anti-inflammatory properties of Jiangjunsan.

Painful Diabetic Neuropathy (PDN) is a severe complication of diabetes, featured by intricate aetiology and multiple side effects of current therapeutic approaches. In recent years, the glymphatic system has attracted increasing attention for its role in PDN. This study investigated the regulatory effects and underlying mechanisms of Oxymatrine (OMT) on the spinal glymphatic system in PDN rat models, aiming to provide novel therapeutic insights for PDN. The PDN rat model was established by high-fat and high-sugar diet combined with streptozotocin (STZ) induction. The 50% paw withdrawal threshold (50% PWT) was measured by Von Frey filaments to evaluate neuropathic pain. Spinal glymphatic system function was observed via Magnetic Resonance Imaging (MRI). Western blotting was used to detect the expression of Aquaporin-4 (AQP-4), Metalloproteinase-9 (MMP-9), NF-κB p65, p-p65, Nrf2 and HO-1. Immunofluorescence was performed to assess AQP4 polarization and nuclear expression of p65. In addition, the levels of oxidative stress indicators (GSH, SOD, MDA) and inflammatory factors (IL-1β, IL-6, TNF-α) were determined. OMT treatment significantly alleviated PDN-related symptoms and improved the detected indicators. It effectively reduced oxidative stress and inflammatory levels, upregulated the expression of Nrf2 and HO-1, downregulated MMP-9 expression, repaired AQP-4 polarisation, and restored the function of the spinal glymphatic system in PDN rats. This study provides a theoretical foundation for the potential application of OMT as a therapeutic agent for PDN, and its multi-target regulatory mechanism offers new directions for PDN treatment.

As an important transcription factor, activin receptor-like kinase 5 (ALK5) plays a crucial role in the development of various diseases. However, there have been no reports on whether ALK5 is involved in the pathogenesis of asthma, and further exploration is needed. An in vitro asthma model was constructed using house dust mite (HDM). Quantitative real-time polymerase chain reaction and western blot were used to detect the expression of ALK5. Enzyme-linked immunosorbent assays were used to measure the levels of inflammatory factors. Oxidative stress-related factors and glycolysis-related indicators were analysed using commercial kits. Co-immunoprecipitation was used to assess the binding activity of ALK5 and Krüppel-like factor 4 (KLF4). Finaly, an HDM-induced asthmatic mouse model was established. H&E and PAS staining were used to evaluate the pathological status of mouse lungs, immunohistochemistry (IHC) was used to detect the expression of ALK5 and KLF4 in mouse lung tissue, and Masson staining was used to detect collagen deposition. The results showed that ALK5 was up-regulated in HDM-induced BEAS-2B cells. Silencing ALK5 suppressed inflammation and apoptosis in BEAS-2B cells. Furthermore, knockdown of ALK5 inhibited oxidative stress and promoted glycolysis in BEAS-2B cells. ALK5 specifically bound to KLF4 and promoted its protein degradation. Mechanistically, KLF4-mediated glycolysis was involved in the regulation of ALK5 in BEAS-2B cells. In vivo, ALK5 knockdown attenuated airway inflammation, reduced inflammatory cell infiltration, decreased collagen deposition, and improved lung histopathological damage. In conclusion, inhibiting ALK5 suppresses inflammation, apoptosis, and oxidative stress by regulating KLF4-mediated glycolysis in BEAS-2B cells, thus inhibiting the further development of asthma. Therefore, ALK5 may be a potential target for the clinical treatment of asthma.

Heat stress (HS) severely impairs boar reproductive function by inducing oxidative stress and inflammatory responses, while lycopene (LYC), as a potent antioxidant, exerts a potential protective effect on the male reproductive system. This study aimed to clarify the mechanism underlying LYC-mediated alleviation of HS-induced decline in semen quality in Rongchang boars, identify the most affected tissues, and explore its regulatory role in the Nrf2 (Nuclear factor E2-related factor 2) pathway. A total of 18 Rongchang boars with an initial body weight of 15.81 ± 1.07 kg were randomly assigned to three groups (6 boars per group): the control group (CON, 26 ± 1 °C), the heat stress group (HS, exposed to 35 ± 1 °C for 8 h daily), and the heat stress + 100 mg/kg lycopene group (HS + LYC). After 28 days of adaptive feeding and 14 days of HS treatment, samples were collected for semen quality analysis, testicular histological analysis, antioxidant index detection, transcriptome analysis, Nrf2 pathway detection, and inflammatory index detection. The results showed that HS significantly increased the sperm abnormality rate (p < 0.05), damaged the testicular structure, and induced oxidative stress in serum, lung, liver, left ventricle, testis, and epididymis (caput epididymis, corpus epididymis, cauda epididymis), with varying degrees of oxidative stress observed in these samples. Among these tissues, the testis and cauda epididymis exhibited the most significant responses to HS and LYC, with the comprehensive impact magnitudes of 317% and 514%, respectively. Enrichment analysis of differentially expressed genes (DEGs) in these two tissues revealed that the pathways mediating oxidative stress response displayed distinct tissue specificity, and all of them were closely associated with the Nrf2 antioxidant signaling pathway. HS significantly downregulated the mRNA expressions of Nrf2, Quinone Oxidoreductase (NQO1), Heme Oxygenase 1 (HMOX1) and Glutamate-Cysteine Ligase Catalytic Subunit (GCLC) genes as well as the protein level of Nrf2 in the testis and cauda epididymis, increased the protein level of Keap1, and significantly elevated the levels of interleukin-6 (IL-6), interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) in these two tissues (p < 0.05). Compared with the HS group, dietary supplementation of LYC significantly improved sperm motility and the proportion of rapidly progressive sperm, reduced the proportion of immotile sperm and sperm abnormality rate (p < 0.05), alleviated testicular damage and oxidative stress in various tissues, upregulated the mRNA expressions of Nrf2 and HMOX1 genes in the testis as well as the mRNA expressions of Nrf2, NQO1, HMOX1 and GCLC genes in cauda epididymis (p < 0.05), significantly increased the Nrf2 protein level and decreased the Keap1 protein level in these two tissues, and simultaneously decreased the levels of the aforementioned inflammatory factors (p < 0.05). In conclusion, dietary supplementation with 100 mg/kg LYC can alleviate HS-induced decline in semen quality and testicular damage by regulating the oxidative status and inflammatory level of relevant tissues (e.g., testis and cauda epididymis) in boars, and this protective effect may be associated with the regulation of the Nrf2 signaling pathway.

As an emerging modality for treatment, photothermal therapy demonstrates significant potential for clinical application. However, the inflammatory reaction after photothermal therapy can lead to tumor recurrence and metastasis. As a novel photothermal agent, biliverdin (BV) also demonstrates a remarkable anti-inflammatory effect. In this study, goat milk-derived extracellular vesicles (GEVs) is used to encapsulate BV. The objective was to enhance tumor uptake of the photothermal agent while alleviating the inflammatory responses associated with photothermal therapy, thereby achieving superior therapeutic outcomes. N3-GEV@BV was successfully synthesized. Additionally, it exhibited notable efficacy in photothermal therapy and demonstrated anti-inflammatory effects in vitro. Utilizing a pretargeting strategy, N3-GEV@BV can accomplish PET/CT imaging in both subcutaneous and orthotopic tumor models. After photothermal treatment, the tumor volume in the N3-GEV@BV+laser group exhibited a significant decrease relative to the other groups, with reductions of up to 1/13 observed. Furthermore, compared to N3-GEV@ICG, mice injected with N3-GEV@BV exhibited lower expression levels of inflammatory factors in both the serum and tumor tissues. As an integrated nanoprobe for diagnosis and treatment, N3-GEV@BV can successfully mediate the photothermal therapy of tumor tissue. Notably, it contributes to enhanced tumor prognosis by mitigating the inflammatory response induced by photothermal therapy, underscoring its broad potential for application.

Diet influences plaque stability through its potential to modulate inflammation, a process that involves complex interactions among various lipid metabolites. This study aims to utilize metabolomics to identify key metabolites involved in this pathway and to elucidate the mechanisms by which dietary factors affect plaque stability. The Dietary Inflammatory Index (DII), derived from dietary data, was used to assess the inflammatory potential of individual diets. Propensity score matching categorized serum samples from coronary heart disease (CHD) patients into an anti-inflammatory group (n = 108) and a pro-inflammatory group (n = 108). A comprehensive analysis of lipid profiles was performed using an UPLC-MS/MS detection platform combined with the broad-targeted lipid metabolomics technique, and lipid metabolites with significant differences were screened out. Concurrently, we measured serum levels of inflammatory factors and plaque stability. A Bayesian network model was then applied to elucidate the causal relationships among DII, lipid metabolites, inflammatory factors, and plaque stability. A lipidomics analysis identified 22 differentially expressed lipid metabolites, which were associated with sphingolipid metabolism pathways in the KEGG (Kyoto Encyclopedia of Genes and Genomes) database, particularly involving nine ceramide species. The Bayesian network model exploring the impact of DII on plaque stability comprises 16 nodes and 23 directed arcs. It revealed multiple causal relationships among DII, ceramide species, inflammatory factors, and plaque stability. Specifically, six ceramide species [Cer(d16:0/20:1), Cer(d24:3/15:1), Cer(t14:1/21:0), Cer(t20:0/18:2), Cer(t22:1/16:1), Cer(t26:1/12:1)] and five inflammatory factors (IFN-γ, IL-1β, IL-8, IL-12, IL-13) were found to be involved in these associations. Ceramide species emerged as differential lipid metabolites that distinguish between the anti-inflammatory and pro-inflammatory groups, simultaneously serving as key lipid metabolic products through which diet exerts its influence on plaque stability.

We compared the therapeutic effects of dietary adjustment and fish oil in rats with experimental non-alcoholic fatty liver disease (NAFLD) induced by high-fat diet. The NAFLD rats were either maintained on high-fat diet, or transferred from high-fat diet to normal diet, or received a diet with lard replaced with fish oil. Control rats received normal diet throughout the experiment. The liver coefficient, blood lipids, activities of transaminases, and the severity of hepatic steatosis in NAFLD rats were improved by both dietary adjustment and fish oil (p < 0.05). Dietary adjustment led to a significant decrease in the levels of inflammatory factors in the liver of NAFLD rats (p < 0.05); in rats receiving fish oil, these parameters also tended to decrease. A large number of inflammatory cells were found in the colonic mucosa of rats fed with high-fat diet and the serum level of LPS in these rats was higher than in the control. Neither dietary adjustment, nor fish oil consumption reduced the serum level of LPS in NAFLD rats. Thus, dietary adjustment and fish oil administration improved the levels of blood lipids and liver inflammation in NAFLD rats. The beneficial effect of dietary adjustment on the level of liver inflammation in NAFLD was more pronounced.

This study aimed to analyze the dynamic changes in gut microbiota during high-fat diet (HFD)-induced obesity in mice, investigate the transmissibility of obesity-associated inflammation via fecal microbiota transplantation (FMT), and identify key bacterial genera linked to inflammation. In experiment 1, 8 control group mice and 12 obese group mice were fed a normal diet (ND) and a HFD, respectively, and fecal samples were collected from six mice in each group at weeks 4, 8, and 12. The results showed that long-term HFD (12weeks) significantly reduced the diversity and richness of the gut microbiota (p < 0.05). HFD significantly affected the composition of the gut microbiota during the experimental period, with an increase in the relative abundance of harmful bacteria genera such as Escherichia-Shigella and Proteus (p < 0.05). In experiment 2, the transmissibility of obesity-associated inflammation was validated through a fecal FMT experiment. The results indicated that the intestinal microbiota of obese mice increased the inflammation level of recipient mice (p < 0.05), and the composition of the intestinal microbiota in the obese recipient group was significantly affected by that in the obese donor group. Furthermore, correlation analysis revealed that the relative abundances of Proteus and Escherichia-Shigella were positively correlated with the levels of inflammatory factors in the serum and ileal tissue (p < 0.05), suggesting that these two bacterial genera may serve as potential pro-inflammatory biomarkers. This study revealed the dynamic changes in the gut microbiota during HFD-induced obesity, confirmed the critical role of the gut microbiota in the transmission of inflammation, and provided a new theoretical basis for the intervention of obesity-related diseases.

Long Noncoding RNA SATB1-AS1 Suppresses Inflammatory Response and Injury in Dental Pulp Stem Cells Through the miR-15a-5p/E2F3 Axis

Atherosclerosis (AS) is a leading cause of cardiovascular-related death worldwide. The role and regulatory mechanism of GAS6-AS2 in AS remain unclear. To investigate the diagnostic/prognostic value of GAS6-AS2 in AS and clarify its molecular mechanism. 107 AS patients and 105 healthy controls were included. The levels of GAS6-AS2, miR-138-5p, and mRNA were measured using RT-qPCR. ROC curve, K-M survival analysis, and Cox regression were performed to evaluate the diagnostic and prognostic value of GAS6-AS2. Bioinformatics prediction and dual-luciferase reporter assay were performed to verify the regulatory axis. Ox-LDL-induced VSMCs were used to construct an AS cell model. The biological functions were assessed using CCK-8, SA-β-Gal, and ELISA. GAS6-AS2 expression was significantly increased in AS patients and in VSMCs treated with ox-LDL, and it showed high diagnostic accuracy and risk prediction for patients with AS. Knockdown of GAS6-AS2 reduced SA-β-Gal-positive cells, downregulated the expression of senescence-related genes and proteins (p16, p21, p53), and decreased the levels of inflammatory factors (IL-6, IL-1β) in ox-LDL-induced VSMCs. Mechanistically, GAS6-AS2 directly bound to miR-138-5p and inhibited its expression, while miR-138-5p targeted AKT1 to suppress its expression. Rescue experiments confirmed that the GAS6-AS2/miR-138-5p/AKT1 axis mediated ox-LDL-induced VSMC senescence and inflammation. GAS6-AS2 is a potential diagnostic and prognostic biomarker for AS. It regulates ox-LDL-induced VSMC senescence and inflammatory response through the sponging of miR-138-5p to upregulate AKT1, providing a novel molecular target for AS treatment.

BackgroundSepsis remains a major cause of hospital mortality. Sepsis-induced intestinal injury is regarded as the driving force behind the rapid progression of critical conditions such as shock and sepsis, and serves as the initiating factor of subsequent organ dysfunction. Therefore, the development of effective therapeutic agents to restore intestinal barrier function is crucial for improving outcomes in sepsis.MethodsA caecal ligation and puncture (CLP) model was established in mice to induce sepsis, and intestinal epithelial cells (IEC-6) were treated with lipopolysaccharide (LPS) to simulate sepsis in vitro. These models were used to investigate the protective efficacy and molecular mechanisms of hydroxysafflor yellow A (HSYA) against sepsis-induced intestinal barrier dysfunction.ResultsHSYA alleviated intestinal barrier dysfunction in septic mice, markedly reduced levels of inflammatory factors, and improved survival. In vitro, HSYA enhanced barrier function of IECs, reduced mitochondrial fragmentation and reactive oxygen species (ROS) accumulation, promoted proliferation and inhibited apoptosis by upregulating the expression of Bcl-2 and SOD2.ConclusionThe study demonstrated the therapeutic potential and underlying mechanisms of HSYA in ameliorating sepsis-induced intestinal barrier injury, providing a new strategy for sepsis treatment.

The changes in serum inflammatory factor levels in children with simple febrile seizures and their clinical significance.

Detoxification metabolic pathways and hepatotoxicity mechanisms of B[a]P in reproductive clam Ruditapes philippinarum.

Excessive stress leads to injury and dysfunction, but the underlying mechanism remains unclear. As a human longevity gene, forkhead box O3a (FoxO3a) is a transcription factor that regulates various cellular processes, including the response to oxidative stress, apoptosis, and autophagy. This study aims to explore whether FoxO3a in the dentate gyrus (DG) of the hippocampus is involved in the formation of anxiety- and depressive-like behavior and cognitive impairment in stressed rats and to investigate the detailed mechanism. This study was conducted using the 6-week chronic unpredictable stress (CUS) model. Before the stress treatment, we injected an adeno-associated virus (AAV) vector to overexpress FoxO3a specifically in the DG. Following the 6-week CUS treatment, a series of behavioral tests was conducted. Depression-like behavior was assessed using the sucrose preference test (SPT) and the open field test (OFT). The state of desperation was assessed with the forced swim test (FST) and tail suspension test (TST). Anxiety-like behavior was measured in the elevated plus maze (EPM) and OFT. Cognitive function was examined using the Y-maze test (Y-maze), novel object recognition test (NORT), and Morris water maze test (MWM). The level of reactive oxygen species (ROS) and activities of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) were measured. The levels of inflammatory factors were detected by ELISA. Pathological injury in DG was observed using thionine staining. The expression levels of FoxO3a, brain-derived neurotrophic factor (BDNF), postsynaptic density protein 95 (PSD95), synaptophysin (SYN), and proliferation marker Ki67 (Ki67) were determined using western blot. CUS leads to various abnormal changes, including anxiety- and depressive-like behavior, cognitive impairment, oxidative stress, neuroinflammation, neuropathological alterations in the DG, and decreased expression of FoxO3a, BDNF, PSD95, SYN, and Ki67. All these abnormal changes were significantly alleviated by targeted AAV-FoxO3a injection in the DG. In conclusion, our study demonstrates that the downregulation of FoxO3a induced by CUS in the DG triggers oxidative stress and inflammatory response, inhibits cell proliferation, and induces abnormal synaptic plasticity, ultimately leading to anxiety- and depressive-like behaviors and cognitive impairment.