Journal of Physiology and Pharmacology最新文献

{"title":"Effect of L‑arginine supplementation on homocysteine and asymmetric dimethylarginine in atherosclerotic lower limb ischemia.","authors":"M Micker, N Balcer-Dymel, E Pruszynska-Oszmalek, B Madej-Czerwonka, N Leciejewska, P Kolodziejski, M Sassek, E Grzeda, Z Checinska-Maciejewska, M Jaskula, H Krauss, A Rekas-Dudziak","doi":"10.26402/jpp.2026.3.01","DOIUrl":"10.26402/jpp.2026.3.01","url":null,"abstract":"<p><p>Chronic lower limb ischemia is a manifestation of systemic atherosclerosis frequently accompanied by lipid metabolism disorders, endothelial dysfunction, and disturbances in the L-arginine-nitric oxide (NO) pathway. Asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthase, and homocysteine (Hcy) are recognized markers of vascular risk. This study aimed to evaluate the effect of 2 months of oral L-arginine supplementation (6g/day) on serum ADMA and Hcy concentrations in patients with atherosclerotic lower limb ischemia, depending on lipid metabolism disorder type. In a randomized, double-masked, placebo-controlled trial, 87 patients (50 men, 37 women) were assigned to L-arginine or placebo. Subgroups were defined according to lipid abnormalities: hypertriglyceridemia, hypercholesterolemia, and mixed hyperlipidemia. ADMA was measured by HPLC, and Hcy by fluorescence polarization immunoassay at baseline, 30, and 60 days. L-arginine supplementation significantly reduced ADMA levels in patients with hypercholesterolemia after 30 and 60 days (P<0.05) and in those with mixed hyperlipidemia after 60 days (P<0.05), but not in those with isolated hypertriglyceridemia. Changes in Hcy were not statistically significant. A significant positive correlation between ADMA and Hcy was present in all subgroups, most consistently in hypercholesterolemia. Two-month L-arginine supplementation decreases ADMA concentrations in patients with atherosclerotic lower limb ischemia, with efficacy dependent on the underlying lipid disorder phenotype, suggesting a metabolism-specific modulation of the ADMA-NO axis.</p>","PeriodicalId":50089,"journal":{"name":"Journal of Physiology and Pharmacology","volume":"77 3","pages":"299-305"},"PeriodicalIF":2.5,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148632669","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}

{"title":"Breathing pattern and its variability in the early Parkinson's disease.","authors":"Z Turianikova, J Cernanova Krohova, B Czippelova, J Oleksakova, M Grofik, E Kurca, N Mazgutova, M Javorka","doi":"10.26402/jpp.2026.3.05","DOIUrl":"https://doi.org/10.26402/jpp.2026.3.05","url":null,"abstract":"<p><p>Parkinson's disease (PD) is a progressive neurodegenerative disorder in which respiratory disturbances may occur even in the early stages of the disease. Current pathogenetic models suggest that neurodegeneration also affects neural structures involved in the control of ventilation, potentially leading to alterations in breathing pattern. In addition to these central mechanisms, peripheral factors such as respiratory muscle weakness and chest wall rigidity may also contribute to these changes. However, evidence on breathing pattern alterations in patients with early-stage PD remains limited, and breathing pattern variability has not yet been investigated in this population. This study therefore aimed to characterize the spontaneous breathing pattern and its variability in patients with early-stage PD. We examined 17 patients with PD and 17 sex and age matched controls. We assessed a breath-to-breath respiratory measures - tidal volume, inspiratory and expiratory times - recorded using respiratory inductive plethysmography for each phase of the examination protocol (supine rest, head-up tilt, supine recovery). Further we calculated following parameters: respiratory cycle duration (Ttot), respiratory rate (fR), minute ventilation (MV), the duty cycle (Ti/Ttot), mean inspiratory flow (Vt/Ti) and a measure of rapid shallow breathing (fR/Vt). In our study, patients with PD exhibited an increased respiratory rate (fR) accompanied by a preserved ratio of inspiratory and expiratory phases duration. The increase in fR, together with non-significant changes in tidal volume (Vt), resulted in elevated minute ventilation (MV). Analysis of breathing pattern variability revealed more unstable respiratory cycle duration in PD patients, manifested as increased variability of respiratory rate. We conclude that patients with early-stage PD exhibit subtle alterations in spontaneous breathing pattern and its variability, which may be detectable before the onset of clinically manifest respiratory dysfunction.</p>","PeriodicalId":50089,"journal":{"name":"Journal of Physiology and Pharmacology","volume":"77 3","pages":"345-351"},"PeriodicalIF":2.5,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148632655","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}

{"title":"Shifting the balance: expression of transforming growth factor β receptor subunit genes in relapsing-remitting multiple sclerosis patients treated with dimethyl fumarate.","authors":"L Szewczyk, M Machcinska, M Kierasinska, P Majewski, A Karlinska, R Rola, K Donskow-Lysoniewska","doi":"10.26402/jpp.2026.3.04","DOIUrl":"https://doi.org/10.26402/jpp.2026.3.04","url":null,"abstract":"<p><p>In multiple sclerosis several alterations in transforming growth factor β (TGF-β) signaling in immune cells have been observed, however, little is known about gene expression of TGF-β receptor subunits. Dimethyl fumarate is a disease modifying drug that is still used to treat relapsing-remitting multiple sclerosis. Although its inhibitory effect on TGF-β signaling associated with SMAD proteins has been observed, its effect on the expression of TGF-β receptors is unknown. Expression of genes for TGF-β receptor subunits - TGFBR1, TGFBR2, as well as the co-receptor - TGFBR3 has been examined in blood from patients with relapsing-remitting multiple sclerosis, untreated and treated with dimethyl fumarate, as well as in healthy controls, using droplet digital PCR. TGF-β1 concentrations were determined in sera, using ELISA. Untreated patients had significantly lower TGFBR3 gene expression in blood than healthy controls (p<0.0001) and significantly lower serum concentration of TGF-β1 (p=0.0268), than healthy controls. Patients treated with dimethyl fumarate had significantly lower TGFBR2 and TGFBR1 gene expression (p=0.0054 and 0.0225 respectively) and significantly higher TGF-β1 (p=0.0113) serum concentrations than untreated patients. The percentage of T cells in blood of untreated relapsing-remitting multiple sclerosis (RRMS) patients was significantly higher than in healthy controls (p=0.0054), but in dimethyl fumarate-treated patients was not significantly different from the values in the other groups. Downregulation of the TGFBR3 gene and lower TGF-β1 serum concentration in relapsing-remitting multiple sclerosis can indicate a defective regulatory immune response. Downregulation of TGFBR1 and TGFBR2 genes could be one of the mechanisms for dimethyl fumarate-induced inhibition of TGF-β signaling.</p>","PeriodicalId":50089,"journal":{"name":"Journal of Physiology and Pharmacology","volume":"77 3","pages":"335-343"},"PeriodicalIF":2.5,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148632672","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}

{"title":"Chuanxiong-Chishao extract promotes mesenchymal stem cell-mediated angiogenesis in ischemic myocardial infarction.","authors":"W L Shi, S S Liu, Y Wang, X Z Wang, H X Gao, N Qin, C Q Lu, P F Lu","doi":"10.26402/jpp.2026.3.03","DOIUrl":"https://doi.org/10.26402/jpp.2026.3.03","url":null,"abstract":"<p><p>Ischemic heart disease remains a leading cause of mortality worldwide. Although mesenchymal stem cell (MSC) transplantation offers a promising strategy for myocardial infarction, its therapeutic efficacy is limited by poor cell survival and insufficient regenerative capacity. Traditional Chinese medicine has been widely used to promote blood circulation and treat ischemic diseases. Chuanxiong-Chishao (<i>Ligusticum chuanxiong</i> and <i>Paeoniae Radix Rubra</i>) is a commonly used herb pair for this purpose. This study aimed to investigate whether Chuanxiong-Chishao combined with MSCs could synergistically enhance angiogenesis after myocardial infarction. A rat model of myocardial infarction (MI) was established by permanent ligation of the left anterior descending coronary artery, and the animals were randomly assigned to the sham, model, MSCs, and Chuanxiong-Chishao combined with MSCs (CC-MSCs) groups. MSCs were injected intramyocardially immediately after ligation, and herbal treatment was administered for 28 days. Cardiac function was evaluated by echocardiography, myocardial fibrosis by Masson staining, and angiogenesis by CD31 immunofluorescence. Proteomic profiling was performed using label-free quantitative analysis, and key proteins were validated by Western blot. Compared with MSCs alone, CC-MSCs significantly improved left ventricular ejection fraction, fractional shortening, and cardiac output, reduced infarct size, and enhanced neovascularization in MI rats. Proteomic analysis identified 154 differentially expressed proteins between the model and CC-MSCs groups, and Gene Ontology enrichment analysis indicated significant activation of angiogenesis-related processes. Among these proteins, CDC42, NRP1, and AMOT were markedly altered, which was further confirmed by Western blot analysis. These findings suggest that Chuanxiong-Chishao enhances MSC-mediated angiogenesis and cardiac repair after MI, potentially through modulation of angiogenesis-related protein networks.</p>","PeriodicalId":50089,"journal":{"name":"Journal of Physiology and Pharmacology","volume":"77 3","pages":"323-333"},"PeriodicalIF":2.5,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148632681","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}

{"title":"Electrodermal activity during dental procedures: effects of procedure type, age, and audiovisual interventions.","authors":"J Bereziewicz, W Bereziewicz, B Gorski, J Kowalski","doi":"10.26402/jpp.2026.3.06","DOIUrl":"10.26402/jpp.2026.3.06","url":null,"abstract":"<p><p>Dental anxiety affects roughly 15% of the general population, yet the relative contribution of procedure type, patient age, and distraction interventions to objective autonomic arousal during dental treatment remains poorly characterised. This study investigated the effects of these three factors on electrodermal activity (EDA) in a clinical dental setting. Skin conductance was continuously recorded in 65 adult patients (age 18-29: n=23; 30-55: n=19; ≥56: n=23) undergoing dental procedures under local anaesthesia at a walk-in dental clinic. Patients were randomly assigned to audiovisual intervention (n=30) or control (n=35), and EDA was measured with a wrist-worn sensor and analyzed in STATISTICA 13.0 using nonparametric tests. Extractions produced significantly elevated mean EDA (mean (M)=10.85 μS, standard deviation (SD)=5.00) compared with non-extraction procedures (M=5.20 μS, SD=5.60; Z=4.25, P<0.001, η²=0.28). Older patients (≥56 years: median (Mdn)=2.49 µS) showed lower EDA than middle-aged patients (30-55 years: Mdn=7.81 µS; H=7.96, P=0.019, η²=0.09), consistent with physiological aging and stress resilience. Procedure duration did not correlate with EDA (r(s)=0.15, P=0.23). Anti-stress ball users showed elevated EDA during extractions (Mdn=13.12 vs. 8.60 μS, Z=-2.22, P=0.026), most plausibly attributable to bilateral hand immobilisation imposed by the study protocol. Among non-extraction procedures, augmented reality glasses (AR) were associated with the lowest median EDA (Mdn=2.35 μS, n=12), followed by music glasses (Mdn=2.73 µS, n=4) and headphones (Mdn=4.01 µS, n=3), though group differences were non-significant (H=1.42, P=0.49). Autonomic arousal was more strongly determined by procedure invasiveness (η2=0.28) than by patient age (η²=0.09), with the invasiveness effect driven primarily by the extraction subgroup. AR glasses were well tolerated and associated with the lowest EDA in non-extraction procedures, warranting evaluation in an adequately powered trial. Adequately powered randomised controlled trials restricted to single procedure types and incorporating validated anxiety scales are required before clinical recommendations can be made.</p>","PeriodicalId":50089,"journal":{"name":"Journal of Physiology and Pharmacology","volume":"77 3","pages":"353-361"},"PeriodicalIF":2.5,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148632635","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}

{"title":"Cardioprotective role of wedelolactone in restraint stress-triggered myocardial damage and cardiac arrhythmias in Wistar rats.","authors":"J P Dong, H G Xiao","doi":"10.26402/jpp.2026.3.02","DOIUrl":"https://doi.org/10.26402/jpp.2026.3.02","url":null,"abstract":"<p><p>Restraint stress is a well-established model for inducing psychological and physiological stress that triggers oxidative damage, inflammation, and apoptosis in cardiac tissue. Wedelolactone, a bioactive coumestan derived from Eclipta alba, possesses known antioxidant and anti-inflammatory properties, but its cardioprotective effects under restraint stress have not been well elucidated. The present study aimed to evaluate the cardioprotective potential of Wedelolactone against restraint stress-induced myocardial injury through biochemical, molecular, and histopathological assessments. Male Wistar rats were divided into four groups: Control, Restraint Stress (RS), RS + wedelolactone (10 mg/kg, orally), and wedelolactone-alone. Electrocardiographic parameters, serum cardiac biomarkers (creatine kinase MB (CK-MB), lactate dehydrogenase, aspartate aminotransferase, cardiac troponin I), oxidative stress markers (malondialdehyde, superoxide dismutase, catalase, glutathione peroxidase, reduced glutathione), inflammatory mediators (tumor necrosis factor-α, interleukin-6, C-reactive protein, nuclear factor-κB), and apoptotic gene expression (Bax, Bcl-2, caspase-3 and caspase-9) were analyzed. Nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) pathway activation was evaluated by western blot, and myocardial histology was assessed using hematoxylin and eosin staining. Restraint stress caused significant increases in oxidative stress, inflammation, and apoptotic gene expression, along with histological evidence of myocyte necrosis and vascular congestion. Wedelolactone treatment markedly normalized cardiac biomarkers, restored antioxidant enzyme levels, reduced inflammatory cytokines, and downregulated pro-apoptotic genes while enhancing Nrf2/HO-1 signaling and anti-apoptotic gene expression. We found that Wedelolactone exhibits potent cardioprotective, antioxidant, anti-inflammatory, and anti-apoptotic properties against restraint stress-induced myocardial damage, primarily through activation of the Nrf2/HO-1 pathway and suppression of nuclear factor-κB signaling.</p>","PeriodicalId":50089,"journal":{"name":"Journal of Physiology and Pharmacology","volume":"77 3","pages":"307-321"},"PeriodicalIF":2.5,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148632601","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}

{"title":"Stable pentadecapeptide therapy counteracts gentamicin-induced nephrotoxicity <i>via</i> nitric oxide-system modulation: evidence from a triple nitric oxide-agent approach in rats.","authors":"I Vukoja, J Vlainic, M Francina, I Barisic, G Zukanovic, I Miskulin, L Kralj, M Popovic Dolic, D Dulcic, A M Tubikanec, S Sikiric, I Krezic, M Kordic, L Beketic Oreskovic, I Oreskovic, S Strbe, B Staresinic, T Pavelic Turudic, D Perovic, V Bilic, D Stancic Rokotov, A Boban Blagaic, S Seiwerth, P Sikiric, A Skrtic","doi":"10.26402/jpp.2026.3.08","DOIUrl":"https://doi.org/10.26402/jpp.2026.3.08","url":null,"abstract":"<p><p>In rats, stable gastric pentadecapeptide (BPC 157) therapy may resolve severe gentamicin nephrotoxicity (100 mg/kg ip/daily through 8 days) and the nitric oxide (NO)-system relation. We applied BPC 157 (10 µg/kg, 10 ng/kg, in drinking water or daily intraperitoneally) along with a triple NO-agent approach. Triple NO-agent approach captures NO-system, as a whole, simultaneously the inhibition (N(G)-nitro-L-arginine methylester (L-NAME) 5 mg/kg ip/daily), the overstimulation (L-arginine, 100 mg/kg ip/daily), and the immobilization (L-NAME + L-arginine/daily). BPC 157 therapy counteracted gentamicin nephrotoxicity clinical presentation (i.e., close to normal), serum urea, and creatinine (i.e., values close to normal preserved), maintained diuresis (polyuria/oliguria completely avoided), and no renal mass increase. Finally, fully preserved normal tubular epithelium cells and nephron presentation were present in the microscopy. Counteracted were in kidney gentamicin-increased malondialdehyde (MDA)-levels, and gentamicin-decreased NO-, and superoxide dismutase (SOD)-levels. NO-agents exhibited the opposite (worsening/attenuation) relations: L-arginine (a further increase of urea and creatinine serum values, polyuria, oliguria) <i>vs.</i> L-NAME relations (decrease of the increased urea and creatinine serum values, delayed polyuria, avoided oliguria, less tubular necrosis). These opposite points, combined (L-NAME + L-arginine), resulted in even stronger lesions, and more pronounced oliguria occurred, indicating the annihilation of the beneficial effect of L-NAME when it was combined with L-arginine. BPC 157 regimens (peroral or intraperitoneal) overwhelmed these NO-agents' effects. Thereby, in general, a triple NO-agent approach can reveal all essential gentamicin points of the NO-system (attenuation (L-NAME)/worsening (L-arginine)), revealing the full spectrum of the NO-system functions. Combined with the BPC 157 application, the triple NO-agent approach shows BPC 157's full efficacy in maintaining and/or reestablishing NO-system effects and functions, and kidney integrity in the gentamicin-rats.</p>","PeriodicalId":50089,"journal":{"name":"Journal of Physiology and Pharmacology","volume":"77 3","pages":"377-395"},"PeriodicalIF":2.5,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148632593","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}

{"title":"Modulation of erlotinib activity by supramolecular and nanoscale interactions in pancreatic cancer cells.","authors":"A Kozik, S Stempak, L Poreba, U Glowacka, A Wisniewska, L Szeleszczuk, M Magierowski, M Lasota","doi":"10.26402/jpp.2026.3.07","DOIUrl":"https://doi.org/10.26402/jpp.2026.3.07","url":null,"abstract":"<p><p>Pancreatic cancer remains one of the most aggressive malignancies with limited therapeutic options and poor prognosis. Erlotinib (OSI-774), a small-molecule tyrosine kinase inhibitor (TKI), is clinically used in combination with gemcitabine, yet its efficacy is limited by modest improvements in overall survival (OS) and significant side effects. The aggregation of erlotinib in aqueous solutions further restricts its bioavailability. This study investigates the potential of Congo red (CR), a supramolecular carrier, to enhance the therapeutic impact of erlotinib against pancreatic cancer cells. Biophysical analyses using UV-visible spectroscopy (UV-Vis) and dynamic light scattering (DLS) confirmed the formation of stable CR-erlotinib co-aggregates with optimal molar ratio of 5:1. The effects of erlotinib alone and in combination with CR (CR:OSI-774) were evaluated on two pancreatic cancer cell lines (PANC-1 and BxPC-3). CR:OSI-774 complexes demonstrated significantly lower IC₅₀ and IC₉₀ values compared to erlotinib monotherapy, indicating enhanced anti-proliferative effects. While erlotinib induced apoptosis, CR:OSI-774 primarily triggered necrotic cell death. Importantly, both compounds significantly inhibited cancer cell migration and invasion, with CR:OSI-774 showing superior inhibition of invasive capacity. CR alone did not negatively affect cell viability or apoptosis/necrosis rates. Nanomechanical measurements using atomic force microscopy revealed an increase in cellular stiffness after treatment, particularly in cells exposed to the CR-erlotinib complex, suggesting changes in cytoskeletal organization associated with reduced motility. Furthermore, quantitative protein analysis using the Jess capillary electrophoresis system revealed a decrease in AKT phosphorylation without significant changes in total AKT levels, indicating effective modulation of EGFR signaling via supramolecular aggregation. These findings suggest that supramolecular aggregation with CR represents a promising strategy to enhance erlotinib efficacy in pancreatic cancer therapy while potentially reducing systemic toxicity. The approach opens new avenues for personalized medicine and targeted anti-cancer therapy.</p>","PeriodicalId":50089,"journal":{"name":"Journal of Physiology and Pharmacology","volume":"77 3","pages":"363-376"},"PeriodicalIF":2.5,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148632596","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}

{"title":"Exosomal microRNA-143-3P and its effect on biological behavior and angiogenesis in breast cancer.","authors":"H Y Yang, S Jiang, Y Sun, S J Zhang, J Y Xiao","doi":"10.26402/jpp.2026.3.10","DOIUrl":"https://doi.org/10.26402/jpp.2026.3.10","url":null,"abstract":"<p><p>We undertook this study to investigate the effect of exosomal microRNA-143-3p (miR-143-3p) on the biological behavior and angiogenesis in breast cancer. We transfected human breast cancer cells (MDA-MB-231) with miR-143-3p Agomir or Agomir-NC, and we isolated the exosomes (ex) that were secreted and named these miR-143-3p Agomir-ex and Agomir-NC-ex, respectively. We performed real-time polymerase chain reaction (real-time PCR) to detect the level of exosomal miR-143-3p. We treated the MDA-MB-231 cells with exosomal miR-143-3p Agomir-ex and Agomir-NC-ex. We measured the cellular miR-143-3p concentration using real-time PCR, cell proliferation using the cell counting kit-8 (CCK-8), apoptosis using flow cytometry, the abilities of cell migration and invasion using FCM (flow cytometry), and the levels of vascular endothelial growth factor (VEGF) in cell supernatants using the enzyme-linked immunosorbent assay (ELISA). We constructed nude mouse MDA-MB-231 cell transplantation tumor models and injected Agomir-NC, miR-143-3p Agomir, Agomir-NC-ex, and miR-143-3p Agomir-ex intratumorally to observe the tumor growth. Next, we isolated the tumor tissues and measured the expression of miR-143-3p, pathological change, apoptosis, levels of Ki67, VEGF, and CD31, and microvessel density using real-time PCR, hematoxylin and eosin (HE) staining, terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining, and immunohistochemistry, respectively. We found that, in comparison with Agomir-NC-ex, the expression of miR-143-3p was upregulated in miR-143-3p Agomir-ex, and miR-143-3p Agomir-ex increased the levels of miR-143-3p in breast cancer cells, inhibited the proliferation, migration, and invasion of breast cancer cells, promoted apoptosis, and decreased the levels of VEGF in the cell supernatant. Our experiments with the nude mouse transplantation tumor revealed that both miR-143-3p Agomir-ex and miR-143-3p Agomir reduced tumor growth and the expression of Ki67 protein, increased the levels of miR-143-3p, promoted tumor cell apoptosis, and inhibited the expressions of CD31 protein and VEGF, and angiogenesis. In our current study, we found that the exosomal miR-143-3p inhibited malignant biological behavior and angiogenesis in breast cancer.</p>","PeriodicalId":50089,"journal":{"name":"Journal of Physiology and Pharmacology","volume":"77 3","pages":"415-426"},"PeriodicalIF":2.5,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148632630","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}

{"title":"Triptolide ameliorates renal injury in lupus nephritis by regulating TRAF6 mRNA stability <i>via</i> the hsa_circ_0001439/ELAVL1 axis.","authors":"X W Zhou, C H Wu, P P Ma, G Cai, B M Zhang, Z Z Yang","doi":"10.26402/jpp.2026.3.09","DOIUrl":"https://doi.org/10.26402/jpp.2026.3.09","url":null,"abstract":"<p><p>Lupus nephritis (LN), a severe complication of systemic lupus erythematosus (SLE), is closely associated with aberrant immune-inflammatory responses. Currently, reliable non-invasive biomarkers are lacking, and existing treatments remain limited. Targeting autoimmune and inflammatory pathways offers new therapeutic potential. Triptolide (TP), a diterpenoid triepoxide compound extracted from the traditional Chinese medicine <i>Tripterygium wilfordii</i>, exhibits potent immunosuppressive, anti-inflammatory, and anti-proteinuric effects, demonstrating remarkable efficacy in tumors, inflammation, autoimmune diseases, and kidney-related disorders. This study investigates the mechanism by which TP ameliorates LN through the hsa_circ_0001439/ELAVL1 axis to regulate TNF receptor-associated factor 6 (TRAF6) mRNA stability. <i>In vitro</i> (human renal tubular epithelial cell line) and <i>in vivo</i> (MRL/lpr mouse model) experiments were conducted. Renal function was assessed by measuring 24-hour urinary albumin, blood urea nitrogen, and serum creatinine levels. Serum levels of inflammatory cytokines, including tumor necrosis factor-alpha, interferon-gamma, and interleukin-2, were detected by ELISA. Renal histopathological changes were observed via hematoxylin-eosin and periodic acid-Schiff staining. The cytotoxicity of TP was determined using the cell counting kit-8 (CCK-8) assay. The expression of hsa_circ_0001439, ELAVL1, and TRAF6 mRNA was measured by quantitative real-time polymerase chain reaction. Protein expression of TRAF6 and its downstream pathway components (phosphorylated p65/p65, phosphorylated p38/p38) was detected by Western blot. Apoptosis was analyzed by flow cytometry, and intracellular reactive oxygen species levels were measured to assess oxidative damage. Immunoglobulin G and complement component 3 deposition were evaluated by immunofluorescence. The interactions among hsa_circ_0001439, ELAVL1, and TRAF6 were investigated using RNA pull-down, fluorescence in situ hybridization-immunofluorescence, RNA immunoprecipitation, and dual-luciferase reporter assays. TRAF6 mRNA stability was examined following Actinomycin D treatment. Bioinformatics analysis revealed upregulation of hsa_circ_0001439 in LN (P<0.05). TP improved renal function and histopathology in LN mice (P<0.05). Silencing hsa_circ_0001439 or ELAVL1 alleviated renal injury (P<0.05), while their overexpression reversed TP's therapeutic effects (P<0.05). Hsa_circ_0001439 bound to ELAVL1 to stabilize TRAF6 mRNA (P<0.05). In rescue experiments, TP reduced inflammation (P<0.05), but hsa_circ_0001439/ELAVL1 overexpression counteracted this effect (P<0.05). TRAF6 inhibition further mitigated oxidative damage (P<0.05), confirming TRAF6 as a key target. This study elucidates that TP alleviates LN by inhibiting TRAF6-driven inflammation via the hsa_circ_0001439/ELAVL1 axis, providing a potential therapeutic target for LN treatment.</p>","PeriodicalId":50089,"journal":{"name":"Journal of Physiology and Pharmacology","volume":"77 3","pages":"397-413"},"PeriodicalIF":2.5,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148632617","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}