Physiological research最新文献

Pulse wave velocity is a key indicator of vascular health. This study compared pulse wave arrival time (PWAT) measurements obtained by non-invasive bioimpedance with Doppler ultrasound, the gold standard, at multiple arterial sites. Simultaneous PWAT measurements were performed using bioimpedance (-dZMAX) and Doppler ultrasound (t1 - the beginning of the blood flow, t2 - the peak of the blood flow, t3 - the end of blood flow, t1-2 - the midpoint of the blood flow/center between t1 and t2) in healthy volunteers. The agreement between R-dZMAX and the Doppler-derived time points was assessed at various locations. The lowest average error (2.46 %) was observed between R-dZMAX and t1-2, the increase at the midpoint of the systolic flow. However, significant discrepancies were found when comparing R-dZMAX with t1, t2, and t3. The level of agreement also varied according to the arterial site. Bioimpedance shows promise for PWAT estimation, particularly when R-dZMAX is used to estimate t1-2 derived from Doppler ultrasound, representing the phase of maximal systolic flow acceleration. This suggests that the maximum rate of impedance change during rapid arterial filling provides a more accurate PWAT measurement. More research is warranted to refine bioimpedance techniques for a reliable vascular assessment under various conditions. Key words Pulse wave arrival time " Pulse wave velocity " Pulse wave Doppler " Blood flow " Bioimpedance.

Myocardial infarction (MI) remains a major cause of morbidity and mortality. The ischemic myocardium undergoes necrosis and apoptosis, triggering inflammation and oxidative stress that drive fibrosis and heart failure. High-mobility group box 1 (HMGB1) protein acts as a key damage-associated molecular pattern, activating TLR4 and NFkappaB signaling to promote cytokine release and exacerbate injury. The present study investigated the role of HMGB1 in MI and its impact on inflammatory and redox-related pathways, focusing on the effects of HMGB1 blockade. Male WKY rats were divided into the following groups: sham, MI, and MI with anti-HMGB1 treatment (MI+aHMGB1). MI was induced in rats by coronary ligation followed by reperfusion, and the animals were evaluated seven days later. Plasma cytokines, total NOS activity and gene expression in the left ventricle were analyzed. MI significantly increased plasma TNF? and IL-6, while anti-HMGB1 treatment reduced both cytokines. Hmgb1 mRNA was markedly upregulated after MI and normalized by aHMGB1. MI suppressed Nos3 gene expression and total NOS activity, both of which were restored by aHMGB1. Tlr4 and NFkappaB mRNA levels were elevated after MI and remained high after HMGB1 inhibition, whereas Nos2 and IL-1beta gene expression declined. Antioxidant responses showed differential regulation: Sod1 and Sod2 were further upregulated by aHMGB1, Gpx4 expression normalized, and lipid peroxidation was found to be partially attenuated. These findings indicate that HMGB1 is a key driver of post-infarction inflammation and oxidative injury. Its inhibition modulates cytokine production, restores redox balance, and enhances endothelial protection, suggesting a promising therapeutic target for limiting myocardial damage.

The human endometrium undergoes dynamic hormonal and structural changes throughout the menstrual cycle. Their aim is to create an environment essential for embryo implantation. Successful implantation depends on the proper composition of the endometrial microenvironment, including cytokine synthesis and local immune responses. During the first trimester, uterine natural killer (uNK) cells play a key role in regulating trophoblast invasion, vascular remodelling, and establishing embryo tolerance, with nitric oxide (NO) also contributing to these processes. The study aimed to evaluate the expression patterns of NOS2 and NOS3 and their relationship to the infiltration of endometrium by uterine natural killer (uNK) cells during different menstrual phases. The endometrial tissue samples representing proliferative, early secretory, late secretory, menstrual, and hypersecretory phases were analysed by immunohistochemistry and fluorescence microscopy. NOS2 and NOS3 showed distinct cyclic patterns. NOS3 expression peaked in the early secretory phase, supporting tissue remodelling, while NOS2 expression increased progressively, reaching its maximum in the late secretory and menstrual phases. The number of uNK cells paralleled NOS2 expression, with a positive correlation suggesting a possible NO-related immunomodulatory mechanism. Elevated NOS2 expression and increased clustering of CD56+ uNK cells were observed in some cases of proliferative endometrium, possibly reflecting phase-inappropriate immune activation. These findings indicate that NOS activity and uNK cell dynamics may jointly contribute to the cyclic regulation of the endometrial microenvironment. Understanding NOS regulation and its hormonal and immune interactions may offer new insights into implantation mechanisms.

Cardiometabolic diseases (CMDs), which include hypertension, atherosclerosis, chronic kidney disease, type 2 diabetes mellitus (T2DM), metabolic syndrome, and obesity, significantly affect the heart, liver, and kidneys. A key player in the pathogenesis of these diseases is the serine-threonine kinase enzyme mTOR (mammalian target of rapamycin), which affects cellular metabolic processes through its signaling. mTOR is composed of two separate complexes: mTORC1 and mTORC2. Both complexes are essential for cardiac development and pathological stress responses. Constant activation of mTORC1 can be harmful, contributing to cardiac hypertrophy and remodeling, which can lead to heart failure. Conversely, mTORC2 supports the survival and function of cardiomyocytes during stressful situations. In the liver, mTOR signaling plays a crucial role in lipid metabolism and insulin sensitivity, both of which are affected by diet. Activation of mTORC1 in hepatocytes can cause hepatic steatosis, dyslipidemia, and insulin resistance, which are characteristics of metabolic dysfunction and type 2 diabetes mellitus (T2DM). Conversely, mTORC2 protects against steatohepatitis. Reducing mTORC1 activity in the liver improves these metabolic disturbances. Altered mTOR signaling may result from abnormal feeding states, which affect the metabolic and physiological functions of the liver and kidneys. In diabetic nephropathy, overstimulation of mTORC1 in the kidneys leads to hypertrophy, proteinuria, and eventual loss of renal function. Meanwhile, mTORC2 participates in renal ion transport. Treatment with mTOR inhibitors has ameliorated renal dysfunction in preclinical models of diabetic kidney dysfunction and the Dahl S model of salt hypertension. This review emphasizes the critical role of mTOR in the pathophysiology of cardiometabolic diseases in major organs and models. Targeting mTOR signaling pathways is a promising approach to mitigate the adverse effects of CMD on the heart, liver, and kidneys. Key words Cardiometabolic disease " mTOR " Dyslipidemia " Salt sensitive " Hypertension.

Connexin 43 (Cx43) plays a vital role in maintaining myocardial function through gap junctions (GJs) and hemichannels (HCs), facilitating crucial intercellular communication and ion exchange. Its regulation is precisely controlled by various signaling pathways that influence its phosphorylation status, trafficking, and degradation, thereby modulating myocardial function under physiological and pathological conditions. Under pathological conditions such as ischemic injury, cardiomyopathies, or heart failure, Cx43 undergoes dephosphorylation and is mislocalized from GJs at intercalated discs to the lateral membrane. This disruption in intercellular connectivity impairs electrical conduction and increases susceptibility to arrhythmias, with the loss of functional Cx43-mediated GJs further exacerbating myocardial dysfunction and contributing to disease progression. Given the critical role of Cx43 in cardiac pathology, therapeutic strategies targeting Cx43, particularly peptidomimetics, have emerged as promising cardioprotective approaches. These small synthetic peptides selectively modulate Cx43 HC activity, preventing excessive cellular stress and preserving intercellular communication. Recent advancements, including TAT-conjugated peptides and Hdc-modified analogues, have enhanced the efficacy of peptidomimetics by improving cellular uptake and therapeutic effectiveness. This review highlights the role of Cx43 and Cx43-derived peptidomimetics in cardiovascular diseases, noting their promising potential for broader clinical applications due to Cx43 dysregulation being implicated in various pathologies. Keywords Connexin 43 " Gap Junctions " Myocardial dysfunction " Peptidomimetics.

Although its effectiveness and underlying mechanisms are not fully understood, regular physical exercise (PE) is a potential low-cost strategy to prevent or delay neurodegeneration. Plasma neurofilament light chain (NfL), an established biomarker of axonal damage, helps monitor the progression of neurodegenerative disease. Here, we tested whether moderate-intensity endurance exercise modulates body weight trajectories in a rat model of tauopathy expressing human truncated tau protein (WKY72) and how it is associated with plasma NfL. Three months old Wistar Kyoto (WKY) and tauopathic WKY72 rats underwent 10 weeks long treadmill training regimen (30 min/day, 5 days/week). NfL was quantified in plasma of experimental animals collected before the experiment, then after 4 and 8 weeks long training. Sedentary controls were tested in parallel. Body weights were recorded at the same intervals and additionally two weeks later. We found that sedentary WKY72 rats displayed a significant 8.9-fold increase in NfL, while trained WKY72 animals showed only a 3.8-fold increase (both p < 0.0001). In WKY rats, exercise paradoxically led to a modest yet significant increase in NfL (2.9-fold, p < 0.001). Moreover, PE prevented the late-stage weight loss observed in sedentary tauopathic rats. In conclusion, moderate-intensity endurance exercise attenuates plasma level of NfL in tauopathic rats, indicating the potential of exercise as a disease-modifying intervention. Our findings establish a framework for further mechanistic exploration of links between PE and neuroprotective processes. Key words Physical activity " Weight loss " Tauopathy " Neurofilament light chain.

It has been previously demonstrated that melatonin exerts antiarrhythmic effects under conditions of ischemia and reperfusion in vivo by maintaining a relatively high conduction velocity in the myocardium. However, mechanistical details of this effect remain unclear, specifically whether melatonin affects myocardium directly or via systemic mediating signaling. The aim of the present study was to assess the impact of melatonin on the expression of genes encoding proteins potentially responsible for maintaining myocardial conduction in cultured cardiomyocytes. Ventricular cardiomyocytes isolated from neonatal rats were incubated with melatonin (100 µM) for 24 hours. Melatonin at a concentration of 100 µM enhanced the mRNA expression level of Scn5a gene and increased the amplitude of INa sodium current in cultured neonatal rat cardiomyocytes, but did not affect the parameters of steady-state activation and inactivation of INa. Thus, the present study demonstrated the direct effect of melatonin on sodium current in cardiomyocytes. Keywords Cultured neonatal rat cardiomyocyte " Melatonin " Sodium channel " Sodium current.

Septic acute kidney injury (AKI) is the most common type of acute kidney failure observed in hospitalized patients, with inflammation playing a central role in its pathogenesis. The study aimed to investigate the influence of Rehmannioside A (Re A), a natural ingredient from the traditional Chinese herb Rehmanniae radix, on renal dysfunction and inflammation in septic AKI. Peripheral venous blood specimens were obtained from septic patients with and without AKI for comparing their clinical profiles. A rat model of sepsis was established through cecal ligation and puncture (CLP) surgery, followed by intraperitoneal injections of Re A. Biochemical analysis was performed to measure concentrations of kidney function indicators including blood urea nitrogen (BUN) and serum creatinine (Scr). Structural changes in kidney samples were evaluated by hematoxylin-eosin staining. Colony forming units of bacteria were counted in blood and renal samples of rats. Enzyme-linked immunosorbent assay was performed to measure serum and renal levels of proinflammatory cytokines (TNF? and IL-1?). Protein levels of factors related to MAPK and NF-?B pathways were quantified by western blotting. AKI patients showed increases in sepsis-related organ failure assessment (SOFA) score, BUN, Scr, TNF? and IL-1? levels compared to non-AKI patients. Re A improved the survival rate of CLP model rats and reversed CLP-induced increase in BUN and Scr levels. Pathological changes including renal tubular swelling and luminal narrowing induced by CLP were effectively ameliorated by Re A. In addition, Re A reduced bacterial load and proinflammatory cytokine levels in both blood and renal samples. As to the mechanism, Re A inactivated the phosphorylated levels of p38 MAPK and p65 NF-?B rat kidney samples. Re A plays renal-protective and anti-inflammatory properties in the rat model of septic AKI by inhibiting the activation of p38 MAPK and p65 NF-?B signaling. Keywords Acute kidney injury " Inflammation " Rehmannioside A " Renal dysfunction " Sepsis.

Ischemia/reperfusion (I/R) injury causes myocardial damage, and Ginkgolide C (GC), a component of Ginkgo biloba, shows potential for cardioprotection. However, its effects on I/R-induced cardiac dysfunction and mechanisms are unclear. This study evaluates GC preconditioning in rats, focusing on its impact on cardiac function, myocardial injury, and the PI3K/Akt pathway. GC preconditioning was assessed using an isolated rat heart model of I/R injury. Cardiac function (LVDP, LVEDP, +dp/dtmax, -dp/dtmax), infarct size, histopathological changes, injury, and oxidative stress markers were measured. Rat cardiomyocytes were treated with GC to assess viability, contraction, and apoptosis. Molecular docking and protein analysis explored GC's interaction with the Akt pathway. GC preconditioning significantly improved cardiac function, with a marked enhancement in LVDP, +dp/dtmax, and -dp/dtmax in the GC50 group compared to the I/R group (P<0.01). GC treatment also reduced myocardial infarct size (14.8 %±2.4 % vs. 25.5 %±1.9 %, P<0.01), decreased LDH release, and alleviated histopathological damage, including myocyte necrosis and inflammatory infiltration. Furthermore, GC significantly improved cardiomyocyte viability and contraction amplitude, particularly at 50 ?M. At the molecular level, GC activated the Akt pathway, as evidenced by increased p-Akt expression. Co-treatment with the PI3K inhibitor LY294002 reversed the protective effects of GC, confirming the involvement of the Akt pathway. Additionally, GC preconditioning reduced oxidative stress, as indicated by enhanced SOD activity and decreased levels of myocardial injury markers (LDH, CK-MB), and decreased apoptosis, reflected by a lower Bax/Bcl-2 ratio. GC preconditioning reduces I/R-induced myocardial injury in rats by activating the PI3K/Akt pathway, reducing oxidative stress, inhibiting apoptosis, and improving cell viability. These results support GC's potential for treating ischemic heart disease and suggest Akt-targeted interventions for myocardial protection. Keywords Ginkgolide C " Ischemia/reperfusion injury " Cardioprotection " PI3K/Akt pathway.

Breakfast, the first meal of the day, plays a critical role in energy balance and dietary regulation. Although normal weight-obesity (NW-O) is considered a body composition problem among female university students, whether breakfast skipping is associated with NW-O remains unknown. This study aimed to investigate the relationship between breakfast skipping and body composition, nutritional status, and chronotype in female university students with normal body mass index (BMI). Two hundred Japanese university students were divided into two groups: those who rarely ate breakfast (SKIP) and those who ate breakfast almost daily (TAKE). Body composition such as percentage of body fat (%BF), fat-free mass (FFM) and appendicular muscle mass (AMM), chronotype (Morningness-Eveningness Questionnaire; MEQ), dietary intake, and physical activity level (PAL) were compared between the two groups. Our results showed that PAL was not significantly different between the two groups. Although body weight and BMI were not significantly different between the two groups, %BF was significantly higher and FFM was significantly lower in the SKIP group than in the TAKE group. The SKIP group had a significantly higher proportion of body fat of >30 % (55.8 %) than the TAKE group (34.1 %). Although the total energy intake was not significantly different between the two groups, the percentage of fat intake was significantly higher in the SKIP group. The multiple regression analyses of all participants showed that %BF and AMM were negatively and positively associated with PAL and breakfast consumption frequency, respectively. The SKIP group had a significantly lower MEQ score and a significantly higher number of evening types (41.9 %) than the TAKE group (23.5 %). These results suggest that the habit of breakfast consumption and chronotype-specific lifestyle interventions are necessary to prevent NW-O. Keywords Breakfast " Normal weight obesity " Body fat " Muscle mass " Energy intake " Morningness-Eveningness Questionnaire.