Physiological research最新文献_第2页

Novel predictors of preeclampsia and pregnancy complications: the impact of type 1 diabetes mellitus on maternal and fetal circulatory levels. 子痫前期和妊娠并发症的新预测因素：1型糖尿病对母体和胎儿循环水平的影响

IF 1.9 4区医学

Physiological research Pub Date : 2025-07-23

A Cinkajzlová, K Anderlová, M Hornová, A Pařízek, M Mráz, M Kršek, M Haluzík, P Šimják

{"title":"Novel predictors of preeclampsia and pregnancy complications: the impact of type 1 diabetes mellitus on maternal and fetal circulatory levels.","authors":"A Cinkajzlová, K Anderlová, M Hornová, A Pařízek, M Mráz, M Kršek, M Haluzík, P Šimják","doi":"","DOIUrl":"","url":null,"abstract":"Pregnant women with type 1 diabetes mellitus (T1DM) are at higher risk of complication development in both mothers and their children. The present study aims to describe changes in circulating and umbilical cord concentrations of recently described predictors of pregnancy complications in a group of women with T1DM. Sixty-seven cases and 34 healthy pregnant controls were included in the study and circulatory levels of TGF-alpha, HB-EGF, BDNF, sFlt-4, PDGF, SCF, galectin-1, Fas ligand, CCL-20, P-selectin, IFNgammaR1, IL-10, IL-8, leptin, and insulin were assessed in 10 to 13, (V1), 18 to 21 (V2), 28 to 31 (V3) and 34 to 36 weeks of gestation (V4), and immediately after delivery (V5). BDNF, sFlt-4, HB-EGF, SCF, Fas ligand, galectin-1, IL-8, leptin, and insulin were higher in women with T1DM compared to controls during pregnancy (all p<0.05). While HB-EGF, CCL-20, and P-selectin correlate with maternal glucose control, circulatory SCF, P-selectin, galectin-1, PDGF, IFNgammaR1, sFlt-4, and TGF-alpha levels positively correlated with IL-10 levels suggesting that their expression is altered in the presence of inflammation. Leptin and insulin cord blood levels were higher in newborns of the mothers with T1DM relative to those without T1DM. Pregnancy of women with type 1 diabetes mellitus is associated with numerous changes in circulatory factors, but these changes are not reflected in the cord blood. The observed variations in trophic and inflammatory mediators may be linked to adverse pregnancy outcomes and could potentially be incorporated into predictive models for pregnancy complications in women with type 1 diabetes. Key words Type 1 diabetes mellitus \" Serum \" Plasma \" Cord blood \" Pregnancy complications.","PeriodicalId":20235,"journal":{"name":"Physiological research","volume":"74 3","pages":"403-417"},"PeriodicalIF":1.9,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144691285","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Myocardial fibrosis, the silent instigator of diastolic dysfunction in patients with rheumatoid arthritis. 类风湿关节炎患者舒张功能障碍的无声促动者——心肌纤维化。

IF 1.9 4区医学

Physiological research Pub Date : 2025-07-23

M Jalali, J Števlík, Y Jalali, A Gažová, J Kyselovič, Z Killinger, J Payer

引用次数: 0

Protective mechanisms of exosomes derived from human umbilical cord mesenchymal stem cells in bronchopulmonary dysplasia. 人脐带间充质干细胞外泌体在支气管肺发育不良中的保护机制。

IF 1.9 4区医学

Physiological research Pub Date : 2025-07-23

S-H Cai, L Yang, X-J He, Q-Y Zhang

{"title":"Protective mechanisms of exosomes derived from human umbilical cord mesenchymal stem cells in bronchopulmonary dysplasia.","authors":"S-H Cai, L Yang, X-J He, Q-Y Zhang","doi":"","DOIUrl":"","url":null,"abstract":"Bronchopulmonary dysplasia (BPD) is characterized by reduced alveolar formation and disordered matrix remodeling. Currently, there are no effective therapeutic approaches for it. This study aims to explore the protective effect of exosomes derived from human umbilical cord mesenchymal stem cells on BPD by regulating the immune response and inflammatory pathways of macrophages. PKH26-labeled human umbilical cord mesenchymal stem cell line exosomes (hUCMSC-Exos) were co-cultured with RAW264.7 cells, which were assigned to the following groups: normoxia, normoxia + NLRP3 activator (Nigericin), normoxia + hUCMSC-Exos + Nigericin, hyperoxia, hyperoxia + hUCMSC-Exos, and hyperoxia + hUCMSC-Exos + Nigericin. Cell viability and cytokine expression in cell supernatant were measured for each group. PKH26 exosome staining confirmed successful uptake of hUCMSC-Exos by RAW264.7 cells. hUCMSC-Exos demonstrated protective effects against reductions in cell viability induced by both Nigericin and hyperoxia. Cells in the Hyperoxia group showed significantly increased expression of inflammatory cytokines IL-33, IL-6, IL-1beta, TNF-alpha, and IL-18 compared to those in the Normoxia group, along with elevated mRNA and protein levels of NLRP3, ASC, caspase-1, IL-18, IL-1beta, and ATF4. The Hyperoxia + hUCMSC-Exos group exhibited reduced expression of IL-33, IL-6, IL-1beta, TNF-alpha, IL-18 and IL-33, IL-6, IL-1beta, TNF-alpha, and IL-18 compared to the Hyperoxia group. In contrast, the Hyperoxia + hUCMSC-Exos + Nigericin group showed elevated levels of IL-33, IL-6, IL-1beta, TNF-alpha, and IL-18, as well as increased expression of NLRP3, ASC, caspase-1, IL-18, IL-1beta, and ATF4 compared to the Hyperoxia + hUCMSC-Exos group. hUCMSC-Exos mitigate hyperoxia-induced damage to lung macrophages by reducing endoplasmic reticulum stress, inhibiting NLRP3 inflammasome expression, and regulating inflammatory cytokine release, that may be potentially useful in BPD. Key words Bronchopulmonary dysplasia \" Exosomes \" Human umbilical cord mesenchymal stem cells \" Macrophages \" NLRP3.","PeriodicalId":20235,"journal":{"name":"Physiological research","volume":"74 3","pages":"419-429"},"PeriodicalIF":1.9,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144691286","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Trigonelline attenuated sepsis-induced acute kidney injury by activating NAD+/SIRT1 Pathway. 葫芦巴碱通过激活NAD+/SIRT1通路减轻脓毒症诱导的急性肾损伤。

IF 1.9 4区医学

Physiological research Pub Date : 2025-07-23

W Lv, D Cao, F Yang

{"title":"Trigonelline attenuated sepsis-induced acute kidney injury by activating NAD+/SIRT1 Pathway.","authors":"W Lv, D Cao, F Yang","doi":"","DOIUrl":"","url":null,"abstract":"Sepsis-induced acute kidney injury (SAKI) is one of the most frequent complications in patients with sepsis and is strongly associated with poor clinical outcomes. Trigonelline (TRL), a bioactive pyridine alkaloid isolated from fenugreek, has exhibited therapeutic effects on various diseases. This study aimed to investigate the effects of TRL on SAKI and whether TRL exerted its function via NAD+/SIRT1 pathway activation. A single dose (10 mg/kg body weight) of lipopolysaccharide (LPS) was intraperitoneally administered to establish a mouse SAKI model. After 24 h, compared with the control group, the plasma levels of kidney function indicators creatinine and blood urea nitrogen, oxidative stress indicators hydrogen peroxide and malondialdehyde, and inflammatory factors tumor necrosis factor-alpha and interleukin-1beta were significantly increased. Meanwhile, hematoxylin and eosin staining results revealed that LPS treatment caused glomerular structure disruption, renal tubular luminal narrowing, and renal tubular structure deterioration. TRL treatment significantly reduced the plasma kidney function indicators, oxidative stress, and inflammatory factors levels in the SAKI mice, accompanied by improvements in the renal pathological changes. Furthermore, TRL treatment increased the NAD+ levels, upregulated the SIRT1 expression, and downregulated the NOX4 expression in the kidney of the SAKI mice. Subsequently, EX-527, a selective SIRT1 inhibitor, was used for inhibiting SIRT1, and it reversed the protective effect of TRL in SAKI. Our results revealed that TRL improved renal function and alleviated inflammation and oxidative stress in SAKI mice by NAD+/SIRT1 pathway activation. Therefore, TRL may be a potential therapeutic approach for SAKI treatment. Key words Trigonelline \" Sepsis-induced acute kidney injury \" NAD+ \" SIRT1.","PeriodicalId":20235,"journal":{"name":"Physiological research","volume":"74 3","pages":"439-447"},"PeriodicalIF":1.9,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144691322","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Altered Plasma Butyrylcholinesterase Activity in Streptozotocin-Induced Diabetic Hypertensive Rats Does Not Reflect Impaired Liver Function. 链脲霉素诱导的糖尿病高血压大鼠血浆丁基胆碱酯酶活性的改变并不反映肝功能受损。

IF 1.9 4区医学

Physiological research Pub Date : 2025-07-23

T Hodbod, K Szmicsekova, A Cinakova, K Stefikova, Z Krivosikova, E Kralova, A Hrabovska

{"title":"Altered Plasma Butyrylcholinesterase Activity in Streptozotocin-Induced Diabetic Hypertensive Rats Does Not Reflect Impaired Liver Function.","authors":"T Hodbod, K Szmicsekova, A Cinakova, K Stefikova, Z Krivosikova, E Kralova, A Hrabovska","doi":"","DOIUrl":"","url":null,"abstract":"Butyrylcholinesterase (BChE) has recently been associated with metabolic imbalance. A correlation between plasma activity and lipid and glucose metabolism has been reported in animal models and human patients. Here, we investigated plasma BChE activity in a rat model of comorbid hypertension and type 1 diabetes mellitus (DM) induced by a single injection of streptozotocin (STZ, 55 mg/kg) in male spontaneously hypertensive rats (SHR) (SHR+DM). The SHR+DM animals exhibit the main characteristics of the human comorbid pathology, including hypertension and hyperglycemia. Although STZ lowered blood pressure in SHR, the animals remained hypertensive as compared to the Wistar controls. Plasma levels of triacylglycerols, cholesterol and HDL were increased, while markers of liver damage such as ALT, AST, were increased and albumin was decreased. Plasma BChE activities were similar in Wistar and SHR. In SHR+DM, plasma BChE activity was increased by 43 %. Interestingly, liver BChE activity and relative mRNA expression were decreased by 60 % in SHR and SHR+DM. While plasma BChE activity is often used as a clinical marker of liver injury, our results suggest that it may not be a reliable indicator. Key words Butyrylcholinesterase \" Streptozotocin \" Spontaneously hypertensive rats \" Diabetes mellitus \" Liver damage.","PeriodicalId":20235,"journal":{"name":"Physiological research","volume":"74 3","pages":"471-480"},"PeriodicalIF":1.9,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144691279","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Silver Needle Thermal Therapy Improves Mitochondrial Injury in the Skeletal Muscle of MPS Rats by Inhibiting the TRPV1/CaMKII Pathway. 银针热疗通过抑制TRPV1/CaMKII通路改善MPS大鼠骨骼肌线粒体损伤

IF 1.9 4区医学

Physiological research Pub Date : 2025-07-23

Y Huang, S An, Y Tang, X Yang, C Shen, Y Huang, L Wang, C Wo

{"title":"Silver Needle Thermal Therapy Improves Mitochondrial Injury in the Skeletal Muscle of MPS Rats by Inhibiting the TRPV1/CaMKII Pathway.","authors":"Y Huang, S An, Y Tang, X Yang, C Shen, Y Huang, L Wang, C Wo","doi":"","DOIUrl":"","url":null,"abstract":"The objective of this study is to elucidate the therapeutic mechanisms underlying silver needle thermal therapy (SNT) in alleviating skeletal muscle mitochondrial damage in a rat model of myofascial pain syndrome (MPS), with particular emphasis on its regulatory role concerning TRPV1/CaMKII. The MPS rat model was established through blunt impact and eccentric movement. Interventions included SNT and local intramuscular injections of anti-TRPV1 miRNA. Behavioral assessments were conducted to measure the mechanical and thermal pain thresholds of the rats. Histopathological staining was performed to evaluate muscle structure, while mitochondrial damage was assessed using transmission electron microscopy. Western blotting analysis was employed to quantify expression levels of TRPV1, CaMKII, and CytC. Additionally, immunofluorescence techniques were applied to analyze both the expression levels of TRPV1 and its co-localization with CaMKII. Following administration of SNT and anti-TRPV1 miRNA injections, a downregulation in the expression levels of TRPV1, CaMKII, and CytC within the muscle tissue of MPS rats was observed; concurrently, mitochondrial damage exhibited improvement. The implementation of SNT and the inhibition of TRPV1 lead to a reduction in CaMKII, thereby alleviating mitochondrial damage, indicating that TRPV1 is a potential target for silver needle thermal therapy of MPS. Key words SNT \" MPS \" Mitochondria \" TRPV1 \" CaMKII.","PeriodicalId":20235,"journal":{"name":"Physiological research","volume":"74 3","pages":"481-492"},"PeriodicalIF":1.9,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144691287","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The non-invasive transcranial Doppler for hemodynamic monitoring. 无创经颅多普勒血流动力学监测。

IF 1.9 4区医学

Physiological research Pub Date : 2025-07-23

P Scheer, J Hložková, E Brhelová, A Aksu, S Goliášová, J Doležalová, L Tlučhořová, R Mikulík

{"title":"The non-invasive transcranial Doppler for hemodynamic monitoring.","authors":"P Scheer, J Hložková, E Brhelová, A Aksu, S Goliášová, J Doležalová, L Tlučhořová, R Mikulík","doi":"","DOIUrl":"","url":null,"abstract":"The successful development and testing of new thrombolytics in animal models requires monitoring of hemodynamic changes in cerebral circulation before and after stroke. The purpose of the present study was to document that percutaneous transcranial Doppler (TCD) monitoring is able to differentiate two hemodynamic situations induced with two anesthetic protocols. Twelve adult rats divided into two groups underwent general anesthesia (60 min) using combination: 1) ketamine-xylazine-diazepam (KXD); and 2) ketamine-xylazine-urethane-alpha-chloralose (URACH). The TCD was performed with the skin and skull intact. The heart rate, peak systolic velocity, pulsatility index, and resistance index were recorded in a branch of the posterior cerebral artery. Flow detection and measurement was possible in all rat brains bilaterally. The mean heart rate was lower in the KXD 243+/-4 (range: 238 to 249) than in the URACH group 265+/-12 (range: 250 to 279), the difference between means: 22; 95 % CI [8 to 34], p=0.005) only for the first 20 min of monitoring. Peak systolic velocity was lower in the KXD 73.4+/-3.3 mm/s (range 70.3 to 76.5) vs. URACH group 93.7+/-4.0 mm/s (range: 90.0 to 97.4) during the entire observation period (difference between means: 20; 95 % CI [16 to 25], p<0.001). Same difference was observed for pulsatility and resistance indexes. TCD was able to differentiate hemodynamic changes in the rat brains, making the TCD suitable for monitoring of hemodynamic changes and explores, e.g. how such changes contribute to hemorrhagic transformation after thrombolysis. Also, TCD holds promise as a tool for monitoring of recanalization induced by thrombolytics. Key words Non-invasive monitoring \" Brain flow velocity \" Anesthesia \" Animal model.","PeriodicalId":20235,"journal":{"name":"Physiological research","volume":"74 3","pages":"393-401"},"PeriodicalIF":1.9,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144691288","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Serum Glutathione and Malondialdehyde Levels as Predictors of Early Neurological Deficits and Short-Term Outcomes in Acute Cerebral Infarction. 血清谷胱甘肽和丙二醛水平作为急性脑梗死早期神经功能缺损和短期预后的预测因子。

IF 1.9 4区医学

Physiological research Pub Date : 2025-04-30

Y-X Wang, J-Y Wang, H Yang, R Zhang, R Cao, W Hong, S Jiang

{"title":"Serum Glutathione and Malondialdehyde Levels as Predictors of Early Neurological Deficits and Short-Term Outcomes in Acute Cerebral Infarction.","authors":"Y-X Wang, J-Y Wang, H Yang, R Zhang, R Cao, W Hong, S Jiang","doi":"","DOIUrl":"","url":null,"abstract":"This study investigates the association between serum glutathione (GSH) and malondialdehyde (MDA) levels and early neurological deficits and short-term outcomes in individuals with acute cerebral infarction (ACI). The study included 114 patients with ACI within 48 hours of symptom onset, between January and August 2023, alongside 96 healthy individuals as a control group. Neurological deficits were assessed using the National Institute of Health Stroke Scale (NIHSS), classifying deficits as mild (<5) or moderate to severe (>/=5). Associations between GSH and MDA levels with early neurological deficits were analyzed. Short-term prognosis, assessed three months post-discharge using the Modified Rankin Scale (mRS), was examined in relation to GSH and MDA levels in patients with ACI. Independent predictors of neurological deficits and short-term outcomes were identified through binary logistic regression analysis. Compared to the control group, patients with ACI had higher rates of hypertension, diabetes, smoking, and alcohol consumption. Additionally, elevated levels of MDA, glycated hemoglobin, triglycerides, C-reactive protein (CRP), and D-dimer levels were observed, whereas GSH and high-density lipoprotein (HDL) levels were lower. Among those with moderate to severe ACI, levels of CRP, MDA, triglycerides, low-density lipoprotein (LDL), uric acid, and D-dimer levels were higher compared to mild ACI, while HDL and GSH levels were significantly lower. Low serum GSH levels and elevated MDA levels are associated with early neurological deficits and short-term prognosis in ACI, serving as independent risk factors for adverse prognosis. The combined assessment of MDA, infarct volume, and LDL provides enhanced predictive value for adverse prognosis in patients with ACI. Keywords: Acute cerebral infarction, Malondialdehyde, Neurological deficits, Serum glutathione, Short-term prognosis.","PeriodicalId":20235,"journal":{"name":"Physiological research","volume":"74 2","pages":"327-336"},"PeriodicalIF":1.9,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12148082/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144161769","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Agonist-Triggered Ca2+ Release From Functionally Connected Endoplasmic Reticulum and Lysosomal Ca2+ Stores in bEND.3 Endothelial Cells. 2 .受体激动剂触发的钙离子从功能连接的内质网释放和溶酶体Ca2+储存内皮细胞。

IF 1.9 4区医学

Physiological research Pub Date : 2025-04-30

Cing-Yu Chen, Yu-Jen Chen, Cheng-An Wang, Chen-Hsiu Lin, Jong-Shiuan Yeh, Paul Chan, Lian-Ru Shiao, Yuk-Man Leung

{"title":"Agonist-Triggered Ca2+ Release From Functionally Connected Endoplasmic Reticulum and Lysosomal Ca2+ Stores in bEND.3 Endothelial Cells.","authors":"Cing-Yu Chen, Yu-Jen Chen, Cheng-An Wang, Chen-Hsiu Lin, Jong-Shiuan Yeh, Paul Chan, Lian-Ru Shiao, Yuk-Man Leung","doi":"","DOIUrl":"","url":null,"abstract":"Endoplasmic reticulum (ER) and lysosomes are physiologically active, physically and functionally connected intracellular Ca2+ stores. In this study we investigated agonist-triggered Ca2+ release from these two stores in mouse microvascular endothelial bEND.3 cells. Addition of nigericin to discharge lysosomal Ca2+ did not affect endoplasmic reticulum Ca2+ release induced by cyclopiazonic acid (CPA) and vice versa, suggesting lysosomes and ER were separate Ca2+ stores whose Ca2+ content was not readily reduced by depletion of the counterpart. ATP triggered Ca2+ release was partially inhibited by Ned-19 (lysosomal two-pore channel inhibitor) or xestospongin C (inositol 1,4,5-trisphosphate receptor-channel inhibitor), suggesting ATP mobilized Ca2+ from both ER and lysosomes. Whilst ATP-triggered Ca2+ release did not affect subsequent CPA- or nigericin-induced Ca2+ discharge, pretreatment with either CPA or nigericin abolished subsequent ATP-triggered Ca2+ release. Thus, the empty state of ER suppressed lysosomal Ca2+ release elicited by ATP, and vice versa, the empty state of lysosome inhibited ATP triggered Ca2+ release from ER. These data suggest cross-talk of the two organelles on the Ca2+ filling state to regulate agonist-stimulated Ca2+ release of each other.","PeriodicalId":20235,"journal":{"name":"Physiological research","volume":"74 2","pages":"249-254"},"PeriodicalIF":1.9,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12148140/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144161723","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Podophyllotoxin Alleviates DSS-Induced Ulcerative Colitis via PI3K/AKT Pathway Activation. 鬼臼毒素通过激活PI3K/AKT通路缓解dss诱导的溃疡性结肠炎。

IF 1.9 4区医学

Physiological research Pub Date : 2025-04-30

T Li, X Wang, J Wang

{"title":"Podophyllotoxin Alleviates DSS-Induced Ulcerative Colitis via PI3K/AKT Pathway Activation.","authors":"T Li, X Wang, J Wang","doi":"","DOIUrl":"","url":null,"abstract":"This study systematically evaluated the therapeutic effects of podophyllotoxin in a DSS-induced mouse model of ulcerative colitis. A total of 374 podophyllotoxin-related targets were identified through database screening, and by intersecting them with 1,741 UC-related targets, 120 potential therapeutic targets were obtained. Subsequent GO and KEGG enrichment analyses revealed that these targets are primarily involved in biological processes such as the positive regulation of protein kinase B signaling, cellular response to lipopolysaccharide, and inflammatory responses, with significant enrichment in key pathways like the PI3K-Akt signaling pathway. Molecular docking results indicated that podophyllotoxin has strong binding activity with several targets related to inflammation and signal transduction. Animal experiments further validated the significant therapeutic effects of podophyllotoxin in the DSS-induced ulcerative colitis mouse model. Particularly at high doses, podophyllotoxin effectively alleviated ulcerative colitis symptoms, reduced pathological damage to colonic tissues, and enhanced intestinal barrier function. Additionally, podophyllotoxin significantly lowered the levels of inflammatory cytokines (TNF-?, IL-1?, IL-6) in the serum and colonic tissues of ulcerative colitis model mice and improved oxidative stress status. More importantly, podophyllotoxin effectively restored the impaired intestinal mucosal barrier function by enhancing the expression of tight junction proteins such as ZO-1 and occludin. Finally, the study revealed that podophyllotoxin may alleviate ulcerative colitis symptoms and promote colonic tissue repair by activating the PI3K/AKT signaling pathway. These findings provide strong experimental evidence for the potential use of podophyllotoxin as a therapeutic agent for ulcerative colitis and offer valuable insights for the future development of ulcerative colitis treatment strategies targeting the PI3K/AKT pathway. Key words: Podophyllotoxin, Ulcerative Colitis, Inflammation, PI3K/AKT.","PeriodicalId":20235,"journal":{"name":"Physiological research","volume":"74 2","pages":"287-300"},"PeriodicalIF":1.9,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12148157/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144161763","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0