Expression Levels Of TNF-α Research Articles

Anti-inflammation effect of Apium graveolens Extract against lead-acetate-induced brain injury in rats

Purpose: The current study investigated the protective potential of Apium graveolens extract (APE) against lead-induced brain injury in rats by exploring anti-inflammatory and antiapoptotic mechanism. Methods: Twenty male Wistar rats were randomly allocated into four groups (n=5). The control group was orally administrated with distillate water. The second group received lead acetate 200mg/kg body weight orally for 14 days, the third group were orally administered lead acetate 200 mg lead acetate/kg body weight and vitamin E 50IU/kg body weight for 14 days. The fourth group was administrated with leas acetate like second group and APE 300mg/kg body weight for 14 days. The TNF-a levels and caspase-3 expression was analyses under ELISA and flow cytometry assay, respectively. Results: The phytochemical analysis of APE indicated the presence of alkaloids, flavonoids, tannins, saponins, and steroids. Leads acetate increased the serum levels of TNF-α and caspase-3 expression, as well as altering the brain tissue architecture. Conclusion: In conclusion, the presence of APE inhibited the lead acetate toxicity by inhibition of TNF-α proinflammation protein and caspase-3 proapoptosis protein.

Synergistic combinations of Angelica sinensis for myocardial infarction treatment: network pharmacology and quadratic optimization approach

Background and aimAngelica sinensis (Oliv.) Diels (Danggui, DG), exhibits potential in myocardial infarction (MI) treatment. However, research on its synergistic combinations for cardioprotective effects has been limited owing to inadequate approaches.Experimental procedureWe identified certain phenolic acids and phthalein compounds in DG. Network pharmacology analysis and experimental validation revealed the components that protected H9c2 cells and reduced lactate dehydrogenase levels. Subsequently, a combination of computational experimental strategies and a secondary phenotypic optimization platform was employed to identify effective component combinations with synergistic interactions. The Chou-Talalay and Zero Interaction Potency (ZIP) models were utilized to quantify the synergistic relationships. The optimal combination identified, Z-Ligustide and Chlorogenic acid (Z-LIG/CGA), was evaluated for its protective effects on cardiac function and cardiomyocytes apoptosis induced by inflammatory in a mouse model of induced by left anterior descending coronary artery ligation. Flow cytometry was further utilized to detect the polarization ratio of M1/M2 macrophages and the expression of inflammatory cytokines in serum was measured, assessing the inhibition of inflammatory responses and pro-inflammatory signaling factors by Z-LIG/CGA.Key resultsQuadratic surface analysis revealed that the Z-LIG/CGA combination displayed synergistic cardioprotective effects (combination index value <1; ZIP value >10). In vivo, Z-LIG/CGA significantly improved cardiac function and reduced the fibrotic area in mice post-MI, surpassing the results in groups treated with Z-LIG or CGA alone. Compared to the MI group, the Z-LIG/CGA group exhibited decreased ratios of the myocardial cell apoptosis-related proteins BAX/Bcl-2 and Cleaved Caspase-3/Caspase-3 in mice. Further research revealed that Z-LIG/CGA treatment significantly increased IL-1R2 levels, significantly decreased IL-17RA levels, and inhibited the activation of p-STAT1, thereby alleviating cell apoptosis after MI. Additionally, the Z-LIG/CGA combination significantly inhibited the ratio of M1/M2 macrophages and suppressed the expression levels of pro-inflammatory cytokines IL-1β, IL-6, IL-17, and TNF-α in the serum.Conclusion and implicationsWe successfully identified a synergistic drug combination, Z-LIG/CGA, which improves MI outcomes by inhibiting cardiomyocyte apoptosis and inflammatory damage through modulating macrophage polarization and regulating the IL-1R2/IL-17RA/STAT1 signaling pathway. This study provides a charming paradigm to explore effective drug combinations in traditional Chinese medicine and a promising treatment for MI.

Crocin Improves Cognitive Impairment in LPS-treated Rats through Anti-Apoptotic, Anti-Inflammatory, and Antioxidant Activities.

Brain inflammation and oxidative stress play critical roles in neuronal apoptosis and memory dysfunction in Alzheimer's disease. Crocin, a natural carotenoid in the stigma of saffron, possesses radical scavenging, anti-inflammatory, and anti-apoptotic properties. This study investigates the protective impact of crocin on neuronal apoptosis, oxidative stress, neuroinflammation, and memory deficits induced by lipopolysaccharide (LPS) in rats. Male Wistar rats received 100mg/kg of crocin for 12 days, with LPS (1mg/kg, ip) injected on days 8-12. Spatial learning and memory were evaluated in the Morris water maze two hours after LPS injection. Gene expression of nuclear factor kappa B (NF-κB), tumor necrosis factor-α (TNF-α), caspase 3, and lipid peroxidation was assessed in hippocampal homogenates at the end of the behavioral test. Histopathological changes in the hippocampus and cerebral cortex were evaluated using H&E staining. The results indicated that LPS administration caused spatial learning and memory dysfunction (P = 0.001, P < 0.01) accompanied by upregulation of Nfkb, Tnfα, and Casp3 mRNA expression (P < 0.0001), increased TNF-α (P < 0.01) and lipid peroxidation level (P < 0.01), decreased total thiol concentration (P < 0.05), tissue damage and neuronal loss in the hippocampus (P < 0.0001). Furthermore, crocin treatment at a dosage of 100mg/kg attenuated learning and memory impairments (P = 0.001, P < 0.01), downregulated Nfkb, Tnfα, and Casp3 mRNA expression (P < 0.0001), decreased TNF-α level (P < 0.01) and lipid peroxidation (P < 0.05) and increased total thiol level (P < 0.05) in the hippocampus. Crocin also ameliorated LPS-induced pathological changes and neuronal loss in the hippocampus (P < 0.001) and cerebral cortex (P < 0.01). In conclusion, the neuroprotective effects of crocin against LPS-induced histopathological and behavioral changes could be attributed to its anti-apoptotic, anti-inflammatory, and radical-scavenging activities in the rat brain.

Involvement of necroptosıs and apoptosıs ın protectıve effects of cyclosporın a on ischemıa-reperfusıon injury in rat kıdney.

We aimed to investigate the protective effects of low dose cyclosporin A (CsA) on ischemia-reperfusion (IR) injury in rat the kidney and on the apoptotic and necroptotic mechanisms involved. 1. Control group (received a single intraperitoneal (i.p.) dose of 1ml sterile saline 15min before the surgical procedure), 2. IR group (was subjected to 30min of bilateral kidney ischemia followed by 90min of reperfusion; and received a single i.p. dose of 1ml sterile saline 15min before the IR procedure, 3. IR + CsA group (received a single i.p. dose of 3mg/kg CsA 15min before the IR procedure. Renal functions (renal perfusion pressures, and serum urea-creatinine levels), kidney histological scores, MDA levels, and TNF-α, caspase-3, RIP1, RIP3, MLKL, CaMKII and CypD protein expressions were also measured. Renal perfusion pressures (PP), serum urea and creatinine levels, renal tissue MDA levels, and the protein expression levels of TNF-α, caspase-3, RIP1, RIP3, MLKL, CAMKII and CypD were significantly increased in the IR group compared to the control group (p < 0.05), Additionally, there were significant decreases in all the parameters in the IR + CsA group compared to those in the IR group (p < 0.05). Furthermore, histopathological analyses revealed significantly higher kidney injury scores in the IR group compared to the control group, and low dose CsA treatment improved the injury. A single low dose of CsA injection 15min before IR, demonstrated a protective effect on bilateral renal IR injury and a reduction in apoptotic and necroptopic markers which is resulted in improvement of renal functions.

Design and synthesis of glycyrrhetinic acid glycosides against acute lung injury and pulmonary fibrosis.

HMGB1 mediated signalling pathway plays an important role in acute injury and fibrosis in lung tissues. Glycyrrhizic acid (GL) is a HMGB1 inhibitor, and its aglycone (glycyrrhetinic acid, GA) is the major pharmacophore and plays the main role during binding to HMGB1. To improve selectivity for these lung diseases, a series of novel glycyrrhetinic acid glycosides targeting mannose acceptors in the respiratory tract and lung tissues were synthesised, and their biological activities were evaluated in vitro and in vivo. For normal lung cell lines WI-38 and Beas-2B, all the compounds but c6 showed reduced cytotoxicity vs the positive controls (GA and GL), IC50 values were > 800µM. For three cancer cells, c1 exhibited high selectivity for lung cancer cells A549. In the inflammation assays, compound c1 displayed the strongest activity of NO inhibition, and c4 was next; both them not only down-regulated the expression levels of IL-1β and TNF-α in RAW264.7 cells, but also decreased the levels of TNF-α, IL-1β, HMGB1, RAGE and ROS in A549 cells in a dose-dependent manner. Noteworthy, compound c1 of 50μM reduced the levels of HMGB1 and RAGE to 38.4 and 37.0% of the LPS group, and it showed much higher binding affinity with HMGB1 than GL, which confirmed by molecular docking; in addition, c1 also inhibited the deposition of α-SMA and Col-1 proteins in TGF-β1-activated A549 cells. In the bleomycin-induced lung fibrosis mouse model, c1 decreased fibrous protein production and deposition in the lung tissues; at a 30mg/kg dose, it reduced the levels of α-SMA and Col-1 to 48.12 and 56.37% of the BLM group, respectively. The pharmacokinetics tests showed c1 relative distribution rate in lung tissue (at 1h, 18.86%; at 2h, 12.80%) is much higher than that of GA (at 1h, 2.8%; at 2h, 1.9%). These results show compound c1 is likely to be a candidate for acute lung injury and pulmonary fibrosis.

Reprint of: M1 macrophage-targeted curcumin nanocrystals with l-arginine-modified for acute lung injury by inhalation.

Acute Lung Injury/Acute Respiratory Distress Syndrome (ALI/ARDS) with clinical manifestations of respiratory distress and hypoxemia remains a significant cause of respiratory failure, boasting a persistently high incidence and mortality rate. Given the central role of M1 macrophages in the pathogenesis of acute lung injury (ALI), this study utilized the anti-inflammatory agent curcumin as a model drug. l-arginine (L-Arg) was employed as a targeting ligand, and chitosan was initially modified with l-arginine. Subsequently, it was utilized as a surface modifier to prepare inhalable nano-crystals loaded with curcumin (Arg-CS-Cur), aiming for specific targeting of pulmonary M1 macrophages. Compared with unmodified chitosan-curcumin nanocrystals (CS-Cur), Arg-CS-Cur exhibited higher uptake in vitro by M1 macrophages, as evidenced by flow cytometry showing the highest fluorescence intensity in the Arg-CS-Cur group (P < 0.01). In vivo accumulation was greater in inflamed lung tissues, as indicated by small animal imaging demonstrating higher lung fluorescence intensity in the DiR-Arg-CS-Cur group compared to the DiR-CS-Cur group in the rat ALI model (P < 0.05), peaking at 12 h. Moreover, Arg-CS-Cur demonstrated enhanced therapeutic effects in both LPS-induced RAW264.7 cells and ALI rat models. Specifically, treatment with Arg-CS-Cur significantly suppressed NO release and levels of TNF-α and IL-6 in RAW264.7 cells (p < 0.01), while in ALI rat models, expression levels of TNF-α and IL-6 in lung tissues were significantly lower than those in the model group (P < 0.01). Furthermore, lung tissue damage was significantly reduced, with histological scores significantly lower than those in the CS-Cur group (P < 0.01). In conclusion, these findings underscore the targeting potential of l-arginine-modified nanocrystals, which effectively enhance curcumin concentration in inflammatory environments by selectively targeting M1 macrophages. This study thus introduces novel perspectives and theoretical support for the development of targeted therapeutic interventions for acute inflammatory lung diseases, including ALI/ARDS.

IL-17A Mediates Depressive-Like Symptoms by Inducing Microglia Activation in Psoriasiform Dermatitis Mice.

Psoriasis is recognized as a systemic disease for its accompanying comorbidities, among which psychological disorders present a high incidence rate and affect patients' life quality. Interleukin (IL)-17A is the central pathological factor in the pathogenesis and development of psoriasis. To clarify if psoriasis-induced systemic IL-17A increase can mediate the neuronal inflammation and result in depressive-like symptoms. Psoriasiform dermatitis model was established by imiquimod (IMQ) application on male BALB/c mice and IL-17A intervention was performed by lateral ventricular catheterization. Skin structural, histopathological characteristics, and behavioral tests were assessed. Serum IL-17A levels were detected by Enzyme-linked immunosorbent assay. mRNA expression of pro-inflammatory factors IL-1β, IL-6, and tumor necrosis factor-α (TNF-α) as well as anti-inflammatory factors IL-4 and IL-10 in the hippocampus and cortex were measured by RT-qPCR. The number of microglia and hippocampal neurons was quantified by immunofluorescent assay. IMQ treatment resulted in significant skin structural and histopathological characters of psoriasiform dermatitis with elevated serum IL-17A levels, obvious depressive-like behaviors, microglia activation with increased IL-1β, IL-6, and TNF-α expression levels in the hippocampus and cortex, and notable inhibition of hippocampal neurogenesis. While, IL-17A neutralization by intracerebroventricular injection of anti-IL-17A antibody can remarkably inhibit microglia activation and decrease the abnormally increased expression levels of IL-1β, IL-6, and TNF-α in the hippocampus and cortex of psoriasiform dermatitis mice, promote hippocampal neurogenesis, thus alleviate the depressive-like behaviors. In the pathological condition of psoriasis, systemic IL-17A elevation can trigger microglia activation, provoke pro-inflammation mediators to release, evoke neuroinflammation, subsequently inhibit hippocampal neurogenesis, and result in depression. IL-17A, as an important pathogenic factor in psoriasis, contributes to its critical role in mediating systemic inflammation and depression comorbidity.

Run-Mu-Ling Granules Mitigate Ocular Surface Inflammatory Injury Associated with Dry Eye by Suppressing the NLRP3/GSDMD-Mediated Pyroptosis Pathway.

Run-Mu-Ling granules (RMLG), a traditional Chinese medicinal formula, are used to treat dry eye (DE); however, the underlying mechanism remains poorly understood. This study aimed to elucidate the potential molecular mechanisms by which RMLG alleviates ocular surface inflammation in DE. We established an in-vivo DE rat model and in-vitro human corneal epithelial cell line (HCEC) injury models. Corneal damage severity was evaluated using various tests, including corneal fluorescein staining, tear break-up time, and phenol red tear test. Hematoxylin and eosin staining was used to examine histopathological changes in corneal tissues. Terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling detected corneal cell damage in rats. Transmission electron microscopy was used to observe the microstructures of corneal tissue. Immunofluorescence and Western blotting analyses were used to assess NLRP3, GSDMD, ASC, caspase-1, IL-18, IL-1β, and TNF-α expression levels in corneal tissues and HCEC. Cell viability was determined using CCK-8 and colony formation assays, and pyroptosis was examined using Annexin V-PI staining. RMLG significantly improved tear film stability, promoted tear secretion, attenuated corneal tissue damage, enhanced HCEC activity, and suppressed pyroptosis. It also inhibited the activation of the NLRP3/GSDMD signaling pathway in corneal tissues and HCEC, reducing the release of downstream pro-inflammatory cytokines. This study suggests that NLRP3/GSDMD-mediated pyroptosis plays a crucial role in the pathogenesis of DE and that inhibition of this pathway is a key mechanism by which RMLG alleviates ocular surface inflammation in DE. These findings suggest that RMLG could be a promising therapeutic option for DE, offering new insights into its molecular action and potential clinical application.

A094: The Impact of Aerobic Exercise Combined with Intermittent Fasting on Alleviating Chronic Inflammation in Obesity

Research Aim: This study utilized aerobic exercise and intermittent fasting as intervention strategies to investigate their effects on the polarization of visceral fat macrophages and the amelioration of chronic fat inflammation in rats with obesity. Research Methods: Sixty male Sprague Dawley (SD) rats, aged 3 weeks, were randomly assigned to either a normal diet group (ND) or a high-fat diet group (HFD). Following a 12-week intervention period, the groups were further subdivided into the normal diet control group (ND), high-fat diet sedentary group (HC), high-fat diet intermittent fasting group (IF), high-fat diet aerobic exercise group (HE), and aerobic exercise combined intermittent fasting group (HIE). The aerobic exercise group underwent 10 weeks of medium-intensity training at 65% of their VO2max. The fasting group adhered to a 5:2 pattern, involving a 24-hour fasting period every Wednesday and Saturday commencing at 6 pm. During post-intervention, epididymal fat samples were collected, and wet weights were recorded. HE staining facilitated the observation of fat histopathology, while immunofluorescence staining was employed to identify the expression and localization of macrophage polarization-related proteins CD86 and CD206. Protein expression levels of IL-6, IL-10, TNF-Α, iNOS, and Arg-1 in adipose tissue were determined through Western blot analysis. Research Results: 1) In comparison to the NC group, the HC group exhibited a significant increase in epididymal adipose tissue weight and adipocyte surface area. 2) Following a 10-week intervention, the epididymal adipose tissue weight and adipocyte surface area in the HE, IF, and HIF groups showed a significant decrease when compared to the HC group. Notably, the HIF group demonstrated a more pronounced reduction. 3) Furthermore, in comparison to the HC group, the HIF group displayed a notable decrease in inflammation cells with a corona-like structure infiltrating the stroma of adipocytes. The protein levels of IL-6 and TNF-Α significantly decreased, while the IL-10 protein level exhibited a significant increase. Moreover, the expression of CD86 and iNOS showed a significant decrease, whereas CD206 and Arg-1 expression exhibited a significant increase. Conclusion: High-fat diet induces an increase in M1 polarization and a decrease in M2 polarization in rat adipose tissue, triggering the onset of chronic inflammation. Following a ten-week intervention, moderate-intensity aerobic exercise combined with intermittent fasting proves was more effective in ameliorating chronic inflammation in the adipose tissue of rats with obesity.

In Vitro Antileishmanial and Immune Modulation of Trigonelline Against Leishmania major.

The mechanistic study of new pharmaceutical compounds is crucial for evaluating their efficacy, identifying potential side effects, and optimising drug formulations. This study aimed to investigate the mechanism of action of trigonelline on the promastigote and amastigote stages of Leishmania major (MRHO/IR/75/ER). An initial in silico study was conducted to examine the pharmacological effects of trigonelline using molecular docking to evaluate the potential binding affinity of trigonelline with nitrate, a crucial molecule in the macrophage immune response against Leishmania. In this experimental study, the inhibitory mechanism of trigonelline on promastigotes was evaluated by measuring metacaspase expression levels. In the amastigote stage of L. major, the expression levels of inducible nitric oxide synthase (iNOS), interleukin 12 (IL-12), interferon-gamma (IFN-γ), tumour necrosis factor alpha (TNF-α), transforming growth factor-β (TGF-β) and interleukin 10 (IL-10) genes were assessed using Real-time PCR. Trigonelline demonstrated a high-binding affinity to the iNOS molecule in computer modelling. In macrophages treated with various concentrations of trigonelline, glucantime and their combination, the expression levels of metacaspase, IL-12, TNF-α, IFN-γ and iNOS genes significantly increased compared to the control group (p < 0.05), whereas IL-10 and TGF-β gene expression levels significantly decreased (p < 0.05). Trigonelline exerts its antileishmanial effects through its high antioxidant properties, non-cytotoxicity to macrophages, and its ability to enhance apoptosis and cell cycle arrest in promastigotes of L. major.

Exploring the potential anti-COPD ingredients and mechanisms of the Qingfei decoction based on UHPLC-HRMS, network pharmacology and transcriptomic analysis.

Qingfei Decoction (QFD) is recognized as one of the 100 classic prescriptions by the National Administration of Traditional Chinese Medicine of China and is widely used for the treatment of pulmonary diseases. Chronic obstructive pulmonary disease (COPD) is a common respiratory condition primarily characterized by airway obstruction. It's necessary to examine the therapeutic effect of QFD in the treatment of COPD and elucidate its potential effective components, targets, and pathways. This study utilized UHPLC coupled with HRMS to identify the chemical constituents of QFD, resulting in the qualitative analysis of 68 compounds. Network pharmacology predicted 30 gene targets, including IL6, AKT1, and EGFR, and revealed 45 compounds, including ruscogenin, schisandrin A, and esculetin that may contribute to its therapeutic effects on COPD. Subsequently, an elastase-induced COPD mouse model was employed to evaluate the efficacy of QFD. The effects of QFD were assessed through hematoxylin and eosin (H&E) staining, periodic acid-Schiff (PAS) staining, and real-time quantitative polymerase chain reaction (RT-qPCR) on lung tissues. Transcriptomic analysis indicating QFD treatment of COPD primarily acted on the IL-17 signaling pathway, which was consistent with the network pharmacology results. Furthermore, RT-qPCR, immunofluorescence, and western blot demonstrated reduced mRNA and protein expression levels of TRAF3IP2, TRAF6, IL17, and TNFα. These findings confirmed that QFD effectively reduced inflammation, likely by down-regulating the IL-17 signaling pathway, thereby treating COPD.

Advanced whole transcriptome sequencing and artificial intelligence/machine learning (AI/ML) in imiquimod-induced psoriasis-like inflammation of human keratinocytes.

Although the HaCaT keratinocyte model has been used in previous research to study the effects of antipsoriatic agents, there is still a lack of comprehensive understanding of the mechanism of imiquimod (IMQ)-induced proliferation and signal transduction in psoriasis-like keratinocytes. This study aimed to investigate the molecular mechanisms and pathways associated with psoriasis-like inflammation caused by IMQ in human keratinocytes. HaCaT cells were exposed to different concentrations of IMQ to induce inflammation similar to that observed in psoriasis. Cell viability was evaluated using the MTT assay and cell morphology was examined using phase-contrast microscopy. Gene expression profiles were analyzed through whole transcriptome sequencing, followed by bio-informatics network analysis using IPA software. The GSEA was conducted with the aim of identifying enriched pathways. The expression of key cytokines IL-6 and TNF-α was confirmed by QPCR. Artificial intelligence/machine learning (AI/ML) algorithms were used to predict potential diseases and phenotypes associated with the observed gene profiles. IMQ treatment demonstrated a substantial positive impact on cell survival without any detectable alterations in the morphology of HaCaT cells. A comprehensive analysis of the entire set of transcribed genes identified 513 genes that exhibited differential expression. Bioinformatics analysis revealed key pathways associated with immune response, cellular proliferation, and cytokine signaling. GSEA identified significant enrichment in the IFN-γ response and JAK-STAT signaling pathways. QPCR analysis confirmed the increased mRNA expression levels of IL-6 and TNF-α in cells treated with IMQ. AI/ML algorithms have identified potential correlations with diseases, such as multiple sclerosis, lympho-proliferative malignancy, and autoimmune disorders. Our results highlight the importance of specific genes and pathways, particularly those associated with IFN-γ pathway and IL-6/JAK-STAT signaling. AI/ML predictions indicate potential associations with various diseases and provide valuable insights for the development of novel therapeutic approaches for psoriasis and related disorders.

Sodium Butyrate Ameliorates Postoperative Delirium by Regulating Gut Microbiota Dysbiosis to Inhibit Astrocyte Activation in Aged Mice.

Postoperative delirium (POD) is a common complication in elderly surgical patients, with limited targeted interventions due to incomplete understanding of its pathophysiological mechanisms. Central nervous system (CNS) inflammation, involving glial cell activation, particularly astrocytes, is considered crucial in POD development. Butyrate, a four-carbon fatty acid, has shown protective effects in CNS diseases, but its potential in mitigating POD remains unclear. This study aimed to investigate the impact of sodium butyrate on POD in aged mice. Behavioral tests, including open field, Y maze, and food burying tests, demonstrated that sodium butyrate preconditioning ameliorated laparotomy-induced delirium in aged mice. Pre-treatment with sodium butyrate inhibited astrocyte activation in the hippocampus, reduced interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) expression levels, and protected hippocampal neurons. Furthermore, the study revealed a connection between gut microbiota regulation and central neuroprotective effects mediated by astrocyte activation inhibition. Sodium butyrate improved the intestinal morphological barrier by rebalancing gut microbiota, inhibiting Proteobacteria and Actinobacteria, reducing Allobaculum and Bacteroides abundance, and increasing Oscillospira abundance. This regulation decreased gut permeability, limiting the entry of toxic substances into the bloodstream, thereby reducing inflammation spread and astrocyte overactivation, leading to central anti-inflammatory effects. In conclusion, sodium butyrate may ameliorate POD by inhibiting astrocyte-mediated neuroinflammation through gut microbiota rebalancing.

Structural identification and anti-stomatitis activity of one arabinose-rich polysaccharide from Rehmannia glutinosa

The anti-stomatitis effects of polysaccharides from natural sources have been relatively few reported. In this study, a polysaccharide RGP-5A was isolated and purified from Rehmannia glutinosa, and its structural characteristics and anti-stomatitis activity were evaluated. The molecular weight of RGP-5A was 1.35×105Da, containing ten monosaccharides, of which arabinose was the main monosaccharide component. Methylation and NMR analysis showed that RGP-5A contained uronic acid, pyranoside and α-glycosidic bonds. The main glycosidic bond connection mode of RGP-5A polysaccharide was 4-Gal(p)-UA; the backbone of RGP-5A is mainly composed of →4)-β-d-Galp(1→and →4)-α-d-GalpA(1→residue, and the terminal signal is identified as T-α-L-Araf (1→. Furthermore, RGP-5A polysaccharide could significantly reduce the secretion levels and protein expression levels of human TNF-α, IL-6, IL-8, and IL-1β in LPS induced HGFs. The findings indicate that this natural polysaccharide from Rehmannia glutinosa has the potential to treat stomatitis.

Green synthesis of Pd nanoparticle embedded into chitosan-pectin polymeric composite as an efficient nanocatalyst in the Suzuki-Miyaura coupling reactions and accelerating the osteoarthritis articular cartilage repair

Green synthesis of Pd nanoparticle embedded into chitosan-pectin polymeric composite as an efficient nanocatalyst in the Suzuki-Miyaura coupling reactions and accelerating the osteoarthritis articular cartilage repair

Estrogen hindrance escalates inflammation and neurodegeneration in the hippocampal regions of collagen-induced arthritis female Sprague-Dawley rats.

This study aims to investigate the effect of estrogen hindrance, i.e., menopause in women for instance with rheumatoid arthritis on the brain hippocampal region by using collagen-induced arthritis (CIA) female rat model (RA). CIA was induced in female rats by injecting bovine type II collagen and incomplete Freund's adjuvant. Estrogen receptor antagonist, fulvestrant (Ful), was given to RA rats to create estrogen hindrance. Control (C) and RA rats were injected with saline and DMSO, respectively, while RA + Ful rats received a 7-day fulvestrant injection. Following experiment completion, rats were sacrificed, and brains were harvested. Brains were stained with H&E and cresyl violet staining and morphological changes in the hippocampus were identified. Additionally, oxidative stress, inflammatory, and apoptosis markers' levels in the hippocampus were analyzed by qPCR, ELISA, and immunohistochemistry techniques. RA + Ful rats showed neuronal atrophy and reduced neurogenesis in the hippocampal regions. NOX4, NF-κB, IL-1β, IL-6, TNF-α, IKK-β, and Bax protein expression levels in the hippocampus were increased, whereas hippocampal Bcl-2, caspase-3, caspase-9, and IGF-1R protein expression levels were decreased. Furthermore, RA + Ful rats had lower levels of antioxidants PON-1 and catalase in the hippocampal regions. The changes in these molecular markers were statistically significant when compared to RA rats without Ful treatment (p < 0.05). Estrogen hindrance exaggerated oxidative stress, inflammation, and apoptosis which resulted in neuronal degeneration in the hippocampal regions in rheumatoid arthritis.

Lignin Isolated by Microwave-Assisted Acid-Catalyzed Solvolysis Induced Cell Death in Mammalian Tumor Cells by Modulating Apoptotic Pathways.

Lignin, the most abundant renewable aromatic polymer, has been shown to suppress the growth of mammalian tumor cells. Despite extensive studies on lignin structure and its engineering, there is little information on the biological activity of lignin in relation to its molecular structure or the molecular mechanisms by which lignin suppresses tumor cells in mammalian species. Here, we prepared microwave-assisted acid-catalyzed solvolysis lignin (MASL) from Japanese cedar and Eucalyptus globulus and assessed its effects on human and mouse tumor cells. SEC indicated that MASL consists of oligomeric aromatics from the woody plants. Our data showed that MASL significantly reduced the viability of tumor cells by modulating apoptotic pathways. MASL treatment upregulated TNF-α, Fas, and FasL expression levels, while suppressing anti-apoptotic NF-κB and mTOR pathways in tumor cells. In vivo experiments were also performed using tumor-bearing mice to confirm the anti-tumor effects of MASL. Repetitive administrations of a MASL (YM CL1T) significantly inhibited tumor growth in mice in association with elevation of caspase 3 expression. These findings strongly suggest the potential usefulness of low-molecular-weight lignin as an effective therapeutic against malignancies.

MiR-214-3p inhibits LPS-induced macrophage inflammation and attenuates the progression of dry eye syndrome by regulating ferroptosis in cells.

Dry eye disease (DED) is an ocular illness caused by insufficient tear secretion or poor tear quality, and inflammation is a key factor in its pathogenesis. Previous studies have shown that miRNAs are important regulatory factors in DED. The purpose of this study was to explore the potential mechanism by which miR-214-3p influenced the DED process by regulating the macrophage inflammatory response. We induced THP-1 cells to differentiate into M0 macrophages with 100 ng/mL phorbol-12-myristate-13-acetate (PMA) and then added 15 ng/mL lipopolysaccharide (LPS) to induce inflammation. The expression of related genes and proteins was detected via RT‒qPCR, Western blotting, ELISA and immunofluorescence staining; cell viability was measured using the CCK-8 assay; and flow cytometry was used to detect ROS levels. In tear and serum samples from DED patients, the levels of miR-214-3p, IL-10, and Arg1 were decreased, and the levels of IL-6, TNF-α, IL-1β, and iNOS expression were increased. Moreover, the overexpression of miR-214-3p attenuated the effect of LPS and inhibited M1 polarization and inflammation in macrophages. Mechanistically, miR-214-3p inhibited macrophage ferroptosis by downregulating TFRC expression, thereby inhibiting macrophage M1 polarization and inflammation and alleviating the progression of DED. Our study indicated that the upregulation of miR-214-3p expression might be a new target for DED therapy.

Hepcidin agonists grape seed proanthocyanidins and berberine hydrochloride improve immunity and prevention against bacterial infection in grass carp (Ctenopharyngodon idella)

Hepcidin agonists grape seed proanthocyanidins and berberine hydrochloride improve immunity and prevention against bacterial infection in grass carp (Ctenopharyngodon idella)

Hydrocortisone improves post-resuscitation myocardial dysfunction by inhibiting the NF-κB pathway.

Myocardial dysfunction is a major cause of early mortality after successful cardiopulmonary resuscitation (CPR) following cardiac arrest (CA). Following the return of spontaneous circulation, myocardial ischemia-reperfusion injury can activate the NF-κB pathway, leading to the transcription of inflammatory genes that impair myocardial function. While clinical studies show hydrocortisone (HC) improves outcomes in CA patients during CPR, its specific role in modulating the NF-κB pathway is unclear. In this study, we established an in vitro model by inducing hypoxia/reoxygenation (H/R) injury in H9C2 cardiomyocytes using Na2S2O4, followed by HC treatment. The results showed that HC treatment of H/R-injured cardiomyocytes promoted proliferation, inhibited apoptosis, and suppressed the NF-κB pathway, thereby reducing interleukin-6 (IL-6), interleukin-8 (IL-8), and tumor necrosis factor-alpha (TNF-α) levels. Moreover, inhibition of the NF-κB pathway enhanced the proliferative capacity of H/R cardiomyocytes, decreased apoptosis rates, and reduced IL-6, IL-8, and TNF-α expression levels, with these effects being further amplified by HC treatment. These findings were further supported by in vivo experiments. In conclusion, our study suggests that HC may promote H/R cardiomyocyte proliferation, inhibit apoptosis, and alleviate inflammatory responses by suppressing the NF-κB pathway, providing new evidence to support its potential clinical application in CA management.