Physiological research最新文献

RThe mycotoxin fumonisin B1 (FB1) poses a significant global problem due to its presence in the food chain. This study aimed to investigate the intergenerational effects of FB1 on epigenetic changes and the corresponding signaling pathways in rat ovaries. Specifically, we examined the expression levels of DNA methyl-transferase (Dnmt3b) and the Pi3kK/Akt/mTOR/Ampk pathway. Virgin Wistar albino female rats were divided into control and FB1 treatment (doses of 20 and 50 mg/kg body weight/day) groups and monitored from day 6 of pregnancy until delivery. Female rats from the first (F1) and second (F2) generations were euthanized at 4 weeks of age, and their ovaries were collected. In addition to histopathological damage, there was a significant dose-dependent increase in Dnmt3b protein in the ovaries of F1 females (p=0.0022 and p<0.0001, respectively), but not in those of F2 females. Furthermore, overexpression of the PI3K gene was observed only in the high-dose FB1 group in both the F1 and F2 generations. In F2, significant gene overexpression of Akt was observed in the high-dose FB1 group, while no effect was observed in F1. Both treated groups of F1 females showed significant repression of the mTOR gene, whereas no effect was observed in F2 females. In addition, FB1 did not have a significant effect on the expression of the Ampk gene in either treatment group in either generation. We conclude that early-life exposure to FB1 may directly impact the ovarian function of female rats by altering methylation patterns and Pi3k/Akt/mTOR pathway in first- generation females. However, this effect appears to be recoverable in the second-generation females. Key words Mycotoxin " Fumonisin B1 " Epigenetic " Signaling pathway " Methylation " Ovary.

The cough reflex is a primary defensive mechanism for airway protection. Cough disorders are characterized by a change in the threshold for initiating the cough reflex. Various afferent inputs influence the onset and sensitivity of the cough reflex. The study aimed to determine and compare the cough reflex sensitivity between adults with asthma and healthy adults with no history of allergic, respiratory, cardiovascular, gastrointestinal, or endocrine diseases, using European Respiratory Society guidelines on the assessment of cough. We created a group of 52 healthy volunteers (mean age 33.8 years) to serve as a control group for future research into the cough reflex in defined patient groups in upcoming clinical-physiological studies. We found that in the group of healthy volunteers, the threshold concentration of capsaicin required to elicit at least two coughs (C2) was 8.46 micromol/l, while the threshold concentration for inducing at least five coughs (C5) was 26.62 micromol/l. We then compared the reactivity of afferent nerve endings in the airways of healthy adults and adults with asthma by evaluating the differences in the concentrations of capsaicin that elicited C2 and C5 in these two groups. In a group of 19 asthmatic adults (mean age 33 years), the threshold concentration of capsaicin required to induce C2 was 2.03 micromol/l, while the threshold concentration for C5 was 3.02 micromol/l. We demonstrated a significant increase in cough reflex sensitivity in adults with asthma, expressed as the C2 capsaicin concentration (P<0.01) and the C5 concentration (P<0.001). Key words Cough " Cough reflex sensitivity " Capsaicin " Asthma.

Diabetes mellitus (DM) is a chronic and widespread disease that negatively affects the male reproductive system. Carvacrol (CAR), a naturally occurring flavonoid in plants, exhibits various biological and pharmacological activities, including anti-inflammatory, antioxidant, and anticancer properties. This study aimed to investigate the potential effects of CAR on testicular tissue damage induced by diabetes, which was modeled by Streptozotocin (STZ) administration. Thirty-two male Wistar albino rats were divided into four groups: Group 1: Control (n=8), Group 2: DM (n=8), Group 3: DM+DMSO (0.1 % dimethyl sulfoxide) (n=8), and Group 4: DM+CAR (20 mg/kg) (n=8). Diabetes was induced by a single intraperitoneal STZ injection (50 mg/kg). Histological changes were assessed using Hematoxylin-Eosin (H&E) staining and the Johnsen scoring system. Apoptosis was evaluated through immunohistochemical staining for the mitochondrial apoptosis markers Bax and Bcl-2, as well as RT-qPCR analysis of their gene expression levels. Fibrosis assessment involved Masson-Trichrome staining and RT-qPCR analysis of mRNA levels for the COL1A1 and COL3A1 genes. Additionally, Total Oxidant Status (TOS), Total Antioxidant Status (TAS), Oxidative Stress Index (OSI), and C-Reactive Protein (CRP) levels were measured in testicular tissue. CAR treatment significantly improved histological alterations associated with diabetes-induced testicular damage. DM was found to increase Bax levels while reducing Bcl-2 levels, whereas CAR reduced Bax levels and increased Bcl-2 gene and protein expression. TOS and OSI levels were elevated in the DM group, whereas TAS levels increased in the DM+CAR group. No significant differences in CRP levels were observed between the groups. These findings suggest that CAR may be effective in mitigating diabetes-induced testicular damage. Key words Diabetes Mellitus " Experimental " Testis " Carvacrol " Apoptosis " Fibrosis.

Cardiac atrophy is the most common complication of prolonged application of the left ventricle (LV) assist device (LVAD) in patients with advanced heart failure (HF), obviously, it is a consequence of LVAD-induced mechanical unloading. Previous studies employing heterotopic heart transplantation (HTx) as a model of heart unloading after LVAD implantation discovered sex-linked differences in the course of unloading-induced in the healthy hearts. It remains to be clarified if sex-related differences are present in the failing hearts after heterotopic HTx. Therefore, we first compared the course of unloading-induced cardiac atrophy in the failing hearts in intact (without gonadectomy) male and female rats, and in animals after gonadectomy, to explore the influence of sex hormones on this process. Second, we examined if the animal's sex modifies the effects of increased isovolumic loading of the LV on the course of unloading-induced cardiac atrophy. Heterotopic abdominal heart transplantation (HTx) was used as a rat model of heart unloading. HF was induced by volume overload achieved by creation of aorto-caval fistula. Increased isovolumic loading was obtained by implantation of specially designed three-branch spring expander into the LV. The degree of cardiac atrophy was assessed as the whole heart weight (HW) ratio of the heterotopically transplanted to the native control heart. We found that decreases in HW after HTx were similar in intact male and female rats, similarly in intact and gonadectomized animals. Implantation of the expander significantly and comparably reduced decreases in HW in male and in female rats. We conclude that there are no sex-linked differences in the development of unloading-induced cardiac atrophy in the failing hearts. Our results also show that enhanced isovolumic heart loading obtained using the spring expander attenuates the development of unloading-induced cardiac atrophy in the failing hearts; the degree of attenuation is similar in both sexes. Key words Heart failure " Cardiac atrophy " Sex differences " Heterotopic heart transplantation " Mechanical heart unloading.

Ulcerative colitis (UC) is a chronic inflammatory bowel disorder. Currently, the global incidence of UC has significantly increased. Traditional treatment methods are relatively limited, with generally poor efficacy and many side effects. In contrast, acupuncture holds great promise due to its significant efficacy, reduced relapse rate, and minimal side effects. In recent years, basic research on acupuncture treatment for UC has achieved substantial progress. However, the specific targets and pathways involved are still unclear. Therefore, this review aims to summarize and consolidate the mechanisms of acupuncture and acupuncture combined with drug therapy for UC. We primarily review the mechanisms of acupuncture treatment for UC from two aspects: intestinal inflammation and intestinal barrier. In terms of intestinal inflammation, acupuncture improves UC by regulating various inflammatory molecules such as TNF-alpha, IL-1beta, IL-10, NF-kappaB, and immune cells such as neutrophils, Th1, Th2, Treg, Th17. Concerning the intestinal barrier, we focus on the impact of acupuncture on the damage to intestinal epithelial cells (IECs). Moreover, acupuncture also possesses the capacity to reshape the gut microbiota, thereby repairing the biological barrier. Furthermore, the combination of acupuncture and medication for treating UC is a promising direction, which requires further exploration by researchers. This review thoroughly explains the molecular mechanisms of acupuncture in treating UC, establishing a foundation for further research on the effectiveness of acupuncture in UC treatment and offering a new perspective on the combination of acupuncture and medication. Key words Acupuncture " Electroacupuncture " Ulcerative colitis " Intestinal inflammation " Intestinal barrier.

The activation of Calcium-Sensing Receptors (CaSRs) reduces detrusor activity in bladder tissues. Also, hydrogen sulfide (H2S) produces in bladder tissue and regulates the bladder smooth muscles tone. However, there is no evidence of the interaction between CaSRs and H2S in bladder tissue. The aim of this study is to investigate the possible contribution of L-cysteine/H2S pathway in CaSRs-mediated relaxation responses in isolated mouse bladder tissue. CaCl2 (1, 2, 3, 5, 10 mM) was applied to isolated mouse bladder tissues pre-contracted with carbachol (1 microM). CaCl2-induced relaxations were performed in the presence of PAG (10 mM), AOAA (1 mM), and Calhex-231 (5 microM), cystathionine-gamma-lyase (CSE), cystathionine-beta-synthase (CBS) and CaSR inhibitor, respectively. L-cysteine (1 microM-10 mM), an H2S substrate, was used to induced a concentration-dependent relaxant response in isolated bladder tissues pre-contracted with carbachol. L-cysteine induced relaxations were performed in the presence of PAG (CSE inhibitor, 10 mM), AOAA (CBS inhibitor, 1 mM) and Calhex-231 (CaSR inhibitor, 5 microM). CaCl2-induced relaxations were decreased by PAG and AOAA. Also, Calhex-231 decreased the CaCl2-induced relaxant responses. L-cysteine-induced relaxant responses were reduced in the presence of PAG (10 mM) and AOAA (1 mM). Calhex-231 (5 microM) caused a significant decrease in L-cysteine-induced relaxations. Also, Calhex-231 reduced the increase in H2S production in the presence of L-cysteine. In addition, CaCl2 increased basal H2S generation, and PAG (10 mM), AOAA (1 mM) and Calhex-231 (5 microM) reduced the increase in H2S production stimulated with CaCl2. In conclusion, CSE and CBS-derived endogenous H2S formation may, at least in part, contribute to CaSR-mediated relaxation responses, and CaSRs involve in endogenous H2S relaxation responses in isolated mouse bladder tissue. Key words Bladder o CaSRs " Calhex-231 " Hydrogen sulfide " L-cysteine " Mouse.

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.

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.

Rheumatoid arthritis (RA) is a chronic systemic inflammatory disease associated with increased cardiovascular morbidity and mortality. Myocardial fibrosis, a key pathological consequence of prolonged inflammation, contributes to diastolic dysfunction and the development of heart failure with preserved ejection fraction (HFpEF) in RA patients. Understanding its pathophysiology, early detection, and potential therapeutic strategies is crucial for improving patient outcomes. In this study we explore the underlying mechanisms of myocardial fibrosis in RA, focusing on immune-mediated pathways, oxidative stress, and extracellular matrix dysregulation, with concise look at the impact of immunosuppressive therapy on cardiac remodeling and role of speckle-tracking echocardiography (STE) in detecting subclinical myocardial fibrosis, emphasizing global longitudinal strain (GLS) as a promising surrogate marker. Key words Rheumatoid arthritis " Myocardial fibrosis " Diastolic dysfunction " Cardiovascular disease surveillance " Strain echocardiography.

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.