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

MedComm, Journal Year: 2025, Volume and Issue: 6(3)

Published: March 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.

Language: Английский

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

Pharmacogenomics and Personalized Medicine, Journal Year: 2025, Volume and Issue: Volume 18, P. 35 - 46

Published: Jan. 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.

Language: Английский

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

Frontiers in Pharmacology, Journal Year: 2025, Volume and Issue: 16

Published: April 28, 2025

Introduction 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. Methods , 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 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. Results 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. Conclusion 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.

Language: Английский

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Hypercapnia and its relationship with respiratory infections

Expert Review of Respiratory Medicine, Journal Year: 2024, Volume and Issue: 18(1-2), P. 41 - 47

Published: Feb. 1, 2024

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

Language: Английский

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

BioFactors, Journal Year: 2024, Volume and Issue: unknown

Published: April 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.

Language: Английский

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

Chemistry & Biodiversity, Journal Year: 2024, Volume and Issue: 21(4)

Published: Feb. 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.

Language: Английский

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Milk-derived small extracellular vesicles inhibit the MAPK signaling pathway through CD36 in chronic apical periodontitis

International Journal of Biological Macromolecules, Journal Year: 2024, Volume and Issue: 274, P. 133422 - 133422

Published: June 24, 2024

Small extracellular vesicles derived from milk (Milk-sEVs) have the advantages of easy availability, low cost, toxicity, and inhibition inflammation. CD36 mediates inflammation stress in a variety disease states. The purpose this study was to investigate role Milk-sEVs inhibiting fibroblast through provide reference data for treatment chronic apical periodontitis.

Language: Английский

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

Foods, Journal Year: 2024, Volume and Issue: 13(16), P. 2616 - 2616

Published: Aug. 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.

Language: Английский

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EXAMINING THE IMPACT OF PERMISSIBILITY HYPERCAPNIA ON POSTOPERATIVE DELIRIUM AMONG ELDERLY PATIENTS UNDERGOING THORACOSCOPIC-LAPAROSCOPIC ESOPHAGECTOMY: A SINGLE-CENTER INVESTIGATIVE STUDY

Shock, Journal Year: 2024, Volume and Issue: 62(3), P. 319 - 326

Published: May 30, 2024

ABSTRACT Objective: This study explores how permissive hypercapnia, a key aspect of lung-protective ventilation, impacts postoperative delirium in elderly patients following thoracic surgery. Methods: A single-center trial at The Second Hospital Anhui Medical University involved 136 undergoing thoracoscopic esophageal cancer resection. Randomly assigned to maintain PaCO 2 35–45 mm Hg (group N) or 46–55 H). Primary outcome: (POD) incidence 1–3 days post-surgery. Secondary endpoints included monitoring rSO , cardiovascular parameters (MAP, HR), pH, OI, and respiratory (VT, RR, Cdyn, PIP) specific time points. Perioperative tests assessed CRP/ALB ratio (CAR) systemic inflammatory index (SII). VAS scores were documented for 3 days. Results: Postoperatively, group H showed significantly lower POD than N (7.4% vs. 19.1%, P = 0.043). Group exhibited higher during surgery ( < 0.05). Patients maintained better stability with blood pressure heart rate on T2–4 Respiratory more stable TV, PIP, Cdyn OLV had pH OI CRP CAR levels rose less the first day 1 week later Conclusions: Maintaining reduces incidence, possibly by enhancing stabilizing intraoperative respiration/circulation.

Language: Английский

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Hepatoprotective effect of prenatal celecoxib in weaning preeclamptic rats: Role of HMGB1/MAPKs signaling

European Journal of Pharmacology, Journal Year: 2024, Volume and Issue: 978, P. 176769 - 176769

Published: June 24, 2024

Language: Английский

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