Heat Shock Protein Family A Member 1A Attenuates Apoptosis and Oxidative Stress via ERK/JNK Pathway in Hyperplastic Prostate

MedComm, Год журнала: 2025, Номер 6(3)

Опубликована: Март 1, 2025

Benign prostatic hyperplasia (BPH) is a prevalent disorder in aging males. It investigated whether heat shock protein family A member 1A (HSPA1A), cytoprotective chaperone induced under stress, has been implicated the development of BPH. RNA-sequencing and single-cell sequencing analyses revealed significant upregulation HSPA1A BPH compared to controls. In vitro experiments elucidated that was localized epithelium stroma, with upregulated expression tissues. Moreover, silencing augmented apoptosis reactive oxygen species (ROS) accumulation, inhibiting proliferation via ERK/JNK activation, while overexpression reversed these effects BPH-1 WPMY-1 cells. Additionally, ERK1/2 suppression U0126 rescued silencing. vivo, testosterone-induced (T-BPH) rat models treated antagonist KNK437 exhibited atrophy molecular changes consistent reduced activity. Finally, we conducted tissue microarray (TMA) analysis 139 specimens from Zhongnan Hospital Wuhan University, which positive correlation between clinical parameters, including prostate volume (PV), tPSA, fPSA, IPSS. conclusion, our findings suggested attenuated oxidative stress through signaling pathway, contributing pathogenesis.

Язык: Английский

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Naoxintong Is Involved in the Coagulation Regulation of Warfarin Through the MAPK Pathway

Pharmacogenomics and Personalized Medicine, Год журнала: 2025, Номер Volume 18, С. 35 - 46

Опубликована: Янв. 1, 2025

To explore the effect of Naoxintong (NXT) on warfarin anticoagulation therapy and its potential mechanism. TCSMP, SwissTargetprediction, SuperPred, SEA, Batmanic-TCM were used to search for active ingredients targets NXT warfarin; DisGENT database was find disease coagulation disorders. Cytoscape software applied construct "drug-target"network; protein interaction network (PPI) study protein-protein interaction. GO KEGG functional analysis. The then tested in rats by analyzing factors blood before after drug administration. expression MAPK liver tissue determined Western blot. top five components affecting degree value MOL000098, MOL000422, MOL000006, MOL000358, MOL000449. TP53, AKT1, SRC, TNF, HSP90AA1, STAT3, JUN, IL6, EGFR, ESR1 core NXT, while MAPK9, MAP3K5, MAPK8, MAPK1 family important process. In vivo testing indicated that may be able participate regulation process through multiple pathways, which related MAPK. Our data suggests is involved pathway.

Язык: Английский

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Anti-inflammatory effect and mechanism of stytontriterpene D on RAW264.7 cells and zebrafish

Frontiers in Pharmacology, Год журнала: 2025, Номер 16

Опубликована: Апрель 28, 2025

Stytontriterpene D ( STD ) is a compound isolated from dried resin of Styrax tonkinensis (Pierre) Craib ex Hartw. In this study, we explored the anti-inflammatory effect in vitro and vivo examined its potential mechanism for first time. vitro, evaluated toxicity to RAW 264.7 cells using CCK8 method detected reactive oxygen species (ROS) nitric oxide (NO) contents diacetyldichlorofluorescein (DCFH-DA) Griess method. We levels interleukin-6 (IL-6), interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-κ), inducible synthase (iNOS), interleukin-10 (IL-10), arginase-1 (ARG1) via enzyme-linked immunosorbent assay measured expression related proteins NF-αB pathway western blotting. The AB zebrafish was vivo, recruitment neutrophils macrophages tail cut -induced copper sulfate inflammation models. used quantitative real-time polymerase chain reaction study inflammation-related genes with induced by sulfate. lipopolysaccharide (LPS)-induced cells, decreased IL-6, IL-1β, NO, ROS, TNF-α production, increased IL-10 ARG1 while also blocking inhibitory κBα (IκBα) phosphorylation suppressing P65 nuclear translocation. reduced inflammatory cutting not only sulfate-induced gene factors, but it inhibited mRNA NF-κB p65 IκBα. These results demonstrated that has an obvious effect, intrinsic molecular possibly caused inhibiting signaling regulating phenotypic changes M1 M2 macrophages. Thus, may play role treatment diseases.

Язык: Английский

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Characterization of Mucosal Immune-Related lncRNAs and mRNAs in a Mouse Model of Allergic Conjunctivitis

Journal of Inflammation Research, Год журнала: 2025, Номер Volume 18, С. 6061 - 6076

Опубликована: Май 1, 2025

Allergic conjunctivitis (AC) is a common inflammatory condition characterized by immune dysregulation in response to environmental allergens. Despite extensive research into general allergic mechanisms, the specific immunological features of ocular mucosal microenvironment remain poorly understood. Investigating immune-related mRNAs and LncRNAs may provide insights mechanisms underlying AC potential novel targets for therapeutic intervention. An model was established using female BALB/c mice sensitized with ragweed pollen. Conjunctival tissues from control groups were pooled RNA extraction, followed Illumina sequencing. Differential gene expression identified DESeq2, functional enrichment analyzed GO, KEGG, GSEA. RT-qPCR validated results, while Human Protein Atlas used assess protein expression. A murine successfully established, confirmed progressively increasing clinical scores significantly elevated scratching frequency. Transcriptomic analysis revealed significant differences lncRNAs between groups. GO indicated that both upregulated downregulated genes enriched biological processes related stimulus, system processes, signaling, metabolic processes. KEGG showed pathways such as steroid hormone biosynthesis, histidine metabolism, glycolysis/gluconeogenesis, IL-17 involved cytokine-cytokine receptor interaction hematopoietic cell lineage. GSEA pathways, including MAPK, STAT1, STAT2. Mucosal immunity-related Bpifa1, Lcn2, Reg3g AC. Co-expression also several lncRNAs, Stoml3-202 Etohd2-205. This study first systematically analyze AC, identifying immunity molecules like Bpifa1 Reg3g. These findings underscore unique involvement new modulation allergy treatment.

Язык: Английский

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Cucurbitane Glycosides and Their Potential Anti-Inflammatory Activities from Hemsleya chinensis Tubers

Molecules, Год журнала: 2025, Номер 30(11), С. 2349 - 2349

Опубликована: Май 28, 2025

Hemsleya chinensis tubers, abundantly produced in southwestern China, are commonly used as a folk medicine that excel anti-inflammation to treat enteritis, bronchitis, and tonsillitis. In this study, three previously undescribed cucurbitane glycosides, hemchinins G-H (1-3), were characterized by the presence of four glucose substitutions, well eleven ones with one β-glucoses, isolated from tubers H. chinensis. The structures confirmed using comprehensive UV, IR, HR-ESI-MS, NMR analyses, absolute configurations determined through comparison calculated experimental ECD after acid hydrolysis. Compounds 1-3 showed NO inhibition effects on LPS-induced RAW 264.7 cells. Finally, molecular docking analyses conducted obtain affinities glycosides our reported 19 triterpenes, focusing targets involved anti-inflammatory effects. results indicated they high scores proteins NF-κB, AMPK, Nrf2 signaling pathways. Among them, triterpenes sugar moiety substitution at C-3 C-26/27 better affinity ability. findings can provide insights into mechanisms species facilitate development novel therapeutic agents.

Язык: Английский

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3-Deoxysappanchalcone attenuates LPS-induced neuroinflammation in microglia cell culture and ameliorates cognitive impairment in traumatic brain injury

PLoS ONE, Год журнала: 2025, Номер 20(5), С. e0323259 - e0323259

Опубликована: Май 30, 2025

Background As one of the major public health security problems, traumatic brain injury (TBI) is characterized by cerebral dysfunction. The following neuroinflammation considered as main secondary factor. Targeting expression inflammatory cytokines could be effective in alleviating TBI-induced neuroinflammation. anti-inflammatory role natural products increasingly receiving attention. 3-Deoxysappanchalcone (3-DSC) a bioactive compound from Caesalpinia sappan L. Methods present study was designed to investigate impact 3-DSC on primary microglia and TBI models. To assess cytotoxicity, cell viability tests were conducted with varying concentrations ranging 5 20 μM. Quantitative PCR (qPCR) Enzyme-Linked Immunosorbent Assay (ELISA) utilized measure production LPS-activated treated or without (at 10 μM). Immune blotting arrays used examine activation canonical inflammation signaling pathways. further elucidate anti-inflammation effect 3-DSC, RNA-seq carried out between LPS + group. In vitro co-culture experiments evaluate protective neurons against inflammation-mediated apoptosis. Additionally, vivo performed observe spatial memory impairment. (160 μg/kg, 320 μg/kg) administered via tail vein at day 1 after (n = 6). Behavioral 7 days detect ability rats. Results results revealed that within concentration range 5–20 μM, did not cause significant cytotoxicity. qPCR ELISA assays, it found μM led reduction cytokines. immune demonstrated inhibited NF-kB MAPK RNA sequencing altered pathways key hub genes. outcomes indicated safeguard apoptosis caused Finally, showed Discussion Collectively, these findings suggest holds promise potential for development therapeutic preventive agents aimed treating neuroinflammation-related disorders. It offers new avenue research clinical applications context related

Язык: Английский

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Hypercapnia and its relationship with respiratory infections

Expert Review of Respiratory Medicine, Год журнала: 2024, Номер 18(1-2), С. 41 - 47

Опубликована: Фев. 1, 2024

Introduction Hypercapnia is developed in patients with acute and/or chronic respiratory conditions. Clinical data concerning hypercapnia and infections interaction limited.

Язык: Английский

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Nerolidol rescues hippocampal injury of diabetic rats through inhibiting NLRP3 inflammasome and regulation of MAPK/AKT pathway

BioFactors, Год журнала: 2024, Номер unknown

Опубликована: Апрель 16, 2024

Abstract Despite the observation of diabetes‐induced brain tissue damage and impaired learning memory, underlying mechanism remains elusive, effective, targeted therapeutics are lacking. Notably, NLRP3 inflammasome is highly expressed in hippocampus diabetic individuals. Nerolidol, a naturally occurring compound with anti‐inflammatory antioxidant properties, has been identified as potential therapeutic option for metabolic disorders. However, ameliorative capacity nerolidol on hippocampal injury its remain unclear. Network pharmacology molecular docking was used to predict signaling pathways targets treatment diabetes. Then established rat model using streptozotocin (STZ) combined high‐fat diet administered. Morris water maze assess spatial memory capacity. Hematoxylin eosin Nissl staining detect neuronal hippocampus. Transmission electron microscopy extent mitochondria, endoplasmic reticulum (ER) synapses. Immunofluorescence GFAP, IBA1, expression Western blot apoptosis (Bcl‐2, BAX, Cleaved‐Caspase‐3); synapses (postsynaptic densifying protein 95, SYN1, Synaptophysin); mitochondria (DRP1, OPA1, MFN1, MFN2); ER (GRP78, ATF6, CHOP, caspase‐12); (NLRP3, ASC, caspase‐1); inflammatory cytokines (IL‐18, IL‐1β, TNF‐α); AKT (P‐AKT); mitogen‐activated kinase (MAPK) pathway (P‐ERK, P‐p38, P‐JNK) related expression. showed that nerolidol's possible mechanisms treating diabetes MAPK/AKT effects. Animal experiments demonstrated could improve blood glucose, lipids, rats. Furthermore, synaptic, mitochondrial, ultrastructure rats by potentially affecting ER‐related proteins. Further studies revealed decreased neuroinflammation, factor while also decreasing MAPK enhancing improves cannot be shown cognitive function. In conclusion, our study reveals first time can ameliorate damage, ER, mitochondrial we suggest may inhibit affected AKT. These findings provide new experimental basis use associated disease.

Язык: Английский

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The Galloyl Group Enhances the Inhibitory Activity of Catechins against LPS-Triggered Inflammation in RAW264.7 Cells

Foods, Год журнала: 2024, Номер 13(16), С. 2616 - 2616

Опубликована: Авг. 21, 2024

The galloyl group in catechins was confirmed to be crucial for their health benefits. However, whether the catechins’ had a contribution anti-inflammation remains unclear. This study investigated properties and mechanisms of RAW264.7 cells by using ELISA, fluorometry, flow cytometer, Western blot, molecular docking. Results showed that enhanced inhibitory abilities on inflammatory cytokines (NO, PGE2, IL-1β, TNF-α) ROS release LPS-induced cells. suppression likely mediated delaying from G0/G1 S phase, blocking COX-2 iNOS via TLR4/MAPK/NF-κB pathway with PU.1 as an upstream target. research proved existence groups indispensable anti-inflammatory capacities offered theoretical basis mechanism galloylated catechins. Future is needed verify effects various sources macrophages or Caco-2/RAW264.7 cell co-culture system.

Язык: Английский

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Osthole Activates the Cholinergic Anti‐Inflammatory Pathway via α7nAChR Upregulation to Alleviate Inflammatory Responses

Chemistry & Biodiversity, Год журнала: 2024, Номер 21(4)

Опубликована: Фев. 23, 2024

Abstract Osthole (also known as Osthol) is the main anti‐inflammatory coumarin found in Cnidium monnieri and severs exclusive quality‐controlled component according Chinese Pharmacopoeia. However, its underlying mechanism remains unknown. In this study, we demonstrated that treatment significantly inhibited generation of TNF‐α, but not IL‐6 classical LPS‐stimulated RAW264.7 macrophage model. addition, LPS induced activation both MAPK NF‐κB signalling pathways, which former was dose‐dependently restrained by via suppressing phosphorylation JNK P38 proteins, while IκB P65 proteins remained unaffected. Interestingly, up‐regulated expression key cholinergic pathway regulator α7nAChR, TNF‐α inhibition effect also alleviated α7nAChR antagonist methylbetaine. These results demonstrate may regulate promoting thereby activate vagus nerve‐dependent pathway.

Язык: Английский

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