Physiological research最新文献

Stroke-prone spontaneously hypertensive rats (SHRSP) are widely used as a model to study cerebral small vessel disease (CSVD) and its association with chronic hypertension. This study investigated the relationship between metabolic, cardiovascular, and neuronal comorbidities in 32-week-old SHRSP rats versus Wistar-Kyoto (WKY) controls, with a focus on oxidative stress, inflammation, and metabolic alterations. Despite hypertension and cardiac and renal hypertrophy, no significant cerebral vascular changes or microbleeds and no cerebral edema were detected in SHRSP. NMR-based urinary metabolomics revealed reduced gut microbiome-derived metabolites, such as p-cresylglucuronide, hippurate, and phenylacetylglycine, alongside increases in methylamine and dimethylamine. These findings reflect gut dysbiosis and altered microbial composition in hypertensive conditions. Elevated markers of oxidative stress, including thiobarbituric acid-reactive substances, and increased expression of NADPH oxidase (NOX) 2 and NOX4 in peripheral tissues suggested oxidative damage in SHRSP rats. Astrocytic hyperreactivity, indicated by increased expression of glial fibrillary acidic protein in brain cortex and hippocampus, was suggestive of neuroinflammatory responses. Our findings highlight complex interplay between hypertension, metabolism, and neuroinflammation while underscoring the variability in SHRSP models. Key words SHRSP " Neuroinflammation " Oxidative stress " Metabolomics.

We studied the effect of Methylpredisolone (MP) on ischemic brain edema after temporary occlusion of the middle cerebral artery for 90 min (MCAo90). We verified the presence of ischemic edema by determining the brain water content (BWC) by measuring dry/wet weight and by examining MRI - T2-weighted imaging, T2 relaxation times and apparent diffusion coefficient (ADC). In another group, animals were administered MP intraperitoneally 30 min after MCAo90, followed by 24 h reperfusion (MCAoMP). Edema changes were documented by the same MRI examinations. A statistically significant increase in BWC was found between the post-MCAo90 group of animals and the intact animals, demonstrating the presence of edema in the former group. A statistically significant increase in ADC was observed in the MCAo group, indicating the presence of vasogenic edema. A statistically significant difference was demonstrated between the MCAo and MCAoMP groups, with no statistically significant difference between the CG and MCAoMP groups, demonstrating a reduction in ischemic brain swelling after MP administration. The main effect of MP on ischemic brain edema is attributed to its antioxidant capacity. It can be assumed that this capacity of MP, with its complex impact on cellular metabolism, affects the movement of water in the brain and reduces ischemic brain edema. Key words Temporary occlusion of the middle cerebral artery " Brain water content " T2 relaxation " Apparent Diffusion Coefficient " Methylprednisolone.

Promoting angiogenesis to enhance the success rate of parathyroid autotransplantation represents an effective strategy for improving patient outcomes following thyroid surgery. Eyes absent homolog 1 (EYA1) may be modulated by stromal vascular fraction (SVF) and adipose-derived stem cells (ADSCs) to facilitate angiogenesis. Phototherapy, which involves the use of artificial light source irradiation for disease prevention and treatment, has emerged as a promising approach. However, it remains unclear whether ADSCs pretreated with phototherapy can promote angiogenesis in the parathyroid gland through the regulation of EYA1. Primary human ADSCs (hADSCs) were isolated and identified. The impact of various wavelengths of light on the proliferation and secretion of angiogenic factors by hADSCs was assessed using a CCK-8 assay and an ELISA. Subsequently, the influence of light-pretreated hADSCs on HUVEC proliferation, migration, and angiogenesis was evaluated through CCK-8, Transwell, tube formation assays, and ELISA. Finally, qRT-PCR and Western blot analysis were employed to examine the effects of different wavelengths of light on the expression levels of differentiation-related transcription factors in hADSCs, including EYA1. To further elucidate the role of EYA1, an EYA1 interference plasmid (si-EYA1) and its negative control plasmid (si-NC) were transfected into hADSCs to determine whether silencing EYA1 would inhibit the promotion of HUVECs migration and angiogenesis by light-pretreated hADSCs. The results demonstrated that compared with green light (516 nm) and blue light (475 nm), red light (635 nm) irradiation significantly enhanced hADSCs proliferation and the secretion of angiogenic factors. Moreover, light-pretreated (red light) hADSCs markedly promoted HUVECs proliferation, migration, and angiogenesis. Additionally, red light irradiation significantly upregulated the mRNA and protein expression of EYA1, SIX1, TGF-beta1, and Wnt1 while downregulating the mRNA and protein expression of DACH1 in hADSCs. However, silencing EYA1 attenuated the promotive effect of light-pretreated hADSCs on HUVECs migration and angiogenesis. These findings suggest that phototherapy-pretreated hADSCs may enhance HUVECs migration and angiogenesis via the activation of EYA1 and increased secretion of angiogenic factors. Key words Phototherapy " Adipose-derived stem cells " Human umbilical vein endothelial cells " Angiogenesis " Migration " Eyes absent homolog 1.

An important harmful side effect of the prolonged support of the left ventricle (LV) with an LV assist device (LVAD) in patients with advanced heart failure (HF) is development of cardiac atrophy. Our first aim was to evaluate if implantation of the four-branch spring expander into LV of the rat will exhibit greater attenuation of unloading-induced cardiac atrophy as compared with the three-branch spring expander. The second aim was to assess if sex-related differences are present in the development of unloading-induced cardiac atrophy in the failing hearts with implanted either three-branch or four-branch spring expander into the LV. Heterotopic heart transplantation in the rat (HTx) served as the model of heart unloading after LVAD implantation. HF was induced by volume overload achieved by creation of the aorto-caval fistula. The degree of cardiac atrophy was assessed as the weight ratio of the heterotopically transplanted heart to the control native heart. We found that enhancement of isovolumic loading by implantation of either type of spring expander into the LV reduced the degree of post-HTx cardiac atrophy in the failing hearts but the four-branch variant was significantly more effective. In addition, we found that there were no sex-related differences in the development of unloading-induced cardiac atrophy or in the attenuation of this process in the failing hearts. We propose that enhancing cardiac work by increasing isovolumic loading via implantation of the spring expander might be a reasonable approach to attenuate the unloading-induced cardiac atrophy in the failing hearts in both sexes. Key words Heart failure in rats " Cardiac atrophy " Aorto-caval fistula " Heterotopic heart transplantation " Three-branch spring expander " Four-branch spring expander.

Regarding cardiovascular (CV) risk, patients with type 1 diabetes mellitus (T1D) are a heterogeneous population with CV risk ranging from low to very high. For personalized prevention strategies, screening for subclinical atherosclerosis may be of clinical significance. However, more data is needed. Our study aimed to describe the prevalence of prognostically significant findings on invasive coronary artery examination in patients with subclinical atherosclerosis determined by non-invasive examination of the carotid and coronary arteries. Patients with T1D for at least 10 years, without a prior history of atherosclerotic CV disease or target organ damage, followed at a large tertiary hospital were enrolled. Non-invasive examinations included carotid ultrasound for carotid plaque detection and a CT for coronary artery calcium (CAC) score evaluation. Patients with the presence of >/=2 carotid plaques and/or CAC score of >/=400 were classified as very high risk (VHR). These VHR patients were subsequently evaluated using invasive coronary angiography (ICA) for the presence of obstructive coronary artery disease (CAD) and intracoronary optical coherence tomography (OCT) for the presence of thin-cap fibroatheroma (TCFA) and very high-risk plaque. Moreover, hemodynamic stenosis relevance was assessed by the vessel fraction flow ratio (vFFR). Sixty-two T1D patients aged 50.1+/-12.7 years, 53 % women were enrolled. The criteria of VHR were fulfilled in 12/62 (19.4 %) patients, of which 6 (50 % of VHR) had both CAC>/=400 and at least 2 atherosclerotic plaques in the carotid arteries, one patient (8 % of the VHR) fulfilled only the CAC criteria and 5 (42 % of VHR) only the carotid criteria. The median CAC score of the VHR group was 606.3 (175.3-1515) and the mean number of carotid plaques was 2.75+/-1.06. ICA showed obstructive CAD in 5/12 (41.7 %) patients, and 3/12 (25 %) had vFFR-positive lesions. Using OCT, TCFA was present in 7/12 (58.3 %) and a very high-risk plaque in 4/12 (33.3 %) patients. Among asymptomatic patients with T1D, the combination of coronary artery calcium score and carotid ultrasound identifies a very high-risk group, in which 58.3 % of patients had a thin-cap fibroatheroma and 33.3 % of patients had a very high-risk plaque. Patients identified by these non-invasive techniques may benefit from intensive risk factors management. Key words Type 1 diabetes mellitus " Coronary artery calcium score " Carotid ultrasound " Optical coherence tomography " Cardiovascular risk.

This study compares the interrelationships among different methods of determining predictive factors of cardiovascular risk: the Night-to-Day ratio (ND-R), Ambulatory Arterial Stiffness Index (AASI), Cardio-Ankle Vascular Index (CAVI), and Ankle-Brachial Index (ABI). A total of 8120 blood pressure measurements were obtained from 280 24h-ABPM records (29 values per daily record) of 20 patients who each provided two 7-day/24-hour monitoring sessions. For each of the two 7-day-24h-ABPM records, the ND-R and AASI were determined. CAVI and ABI were always examined at the beginning of each 7-day-24h-ABPM session. All 20 patients (12 men; 8 women; mean age 57+/-2.1 yrs; mean BMI 29.3+/-1.69 kg/m2; mean left ventricle ejection fraction 53+/-3.8 %) had chronic ischemic coronary artery disease. The correlation coefficients did not exceed 0.318. ND-R of SBP showed the highest methodological sensitivity, identifying 65 % of patients at increased risk, compared to 57.5 % for ND-R of DBP, 23.7 % for CAVI, and 2.5 % for AASI (up to 27.5 % by evaluating individual days). The different cardiovascular risk assessment methods (ND-R, AASI, CAVI and ABI) cannot be substituted for one another. No risk was demonstrated using ABI. Repeating the 7-day-24h-ABPM approximately 1 year apart (unless there is a change in medication or in clinical symptoms) revealed a significantly different results of the ND-R and AASI, which can be expected in approximately 25 % of patients. Key words Ambulatory blood pressure monitoring " Night-to-Day blood pressure ratio " Ambulatory Arterial Stiffness Index " Cardio-Ankle Vascular Index " Ankle Brachial Index " Ischemic heart disease.

Nimbin, a bioactive triterpenoid compound isolated from the neem tree (Azadirachta indica), is known for its anti-inflammatory, antioxidant, antimicrobial, and hepatoprotective properties. The study aimed to explore the impact of nimbin on cardiac markers, mitochondrial and lysosomal enzyme activities, as well as apoptotic signaling in rats induced with isoproterenol. The subcutaneous injection of isoproterenol (ISO) at a dosage of 85 mg/kg body weight over the last two consecutive days led to notable increased in the activities/levels of the cardiac markers, lysosomal glycohydrolases and cathepsins. Conversely, reductions in the functioning of mitochondrial tricarboxylic acid cycle enzymes and respiratory chain enzymes in ISO-induced rats. In ISO-induced rats, there was an augmentation in the expressions of Bax, caspase-3, caspase-9, and cytochrome c, along with a diminished level of Bcl-2. Administration of nimbin resulted in decreased activities/levels cardiac markers, lysosomal glycohydrolases, cathepsins and increased functioning of mitochondrial tricarboxylic acid cycle enzymes and respiratory chain enzymes. Additionally, decreased expressions of Bax, executioner caspases and cytochrome c, along with heightened expression of Bcl-2, were noted in rats treated with nimbin. This indicates that nimbin possesses cardioprotective properties and mitigates mitochondrial and lysosomal dysfunction in rats induced with ISO. Key words Myocardial infarction " Tricarboxylic acid (TCA) cycle enzymes " Cathepsin-D " Cardiac markers " Triterpenoid.

This investigation attempted to discern the causal link of gut microbiota with osteoporosis, examining potential mediating factors, involving inflammatory markers and immune cell activity. Bidirectional two-sample univariable Mendelian randomization (UVMR) was used to decipher the causal link of gut microbiota with osteoporosis, verifying three core assumptions. External datasets were utilized to validate UVMR outcomes and implemented reverse analyses to identify potential reverse causality. Additionally, mediation effects were figured out through UVMR, estimating effect sizes and proportions for every qualifying mediator. It was attempted to precisely select instrumental variables (IVs), ensuring that those influenced by linkage disequilibrium (LD) or demonstrating weak correlations were excluded. The inverse-variance weighted (IVW) analysis unveiled 12 gut microbiota species that were remarkably linked with osteoporosis risk. Specifically, five families, involving Pasteurellaceae, could elevate the risk of osteoporosis, while another five, such as Oxalobacteraceae, were protective. Additionally, two inflammatory markers exhibited a remarkable linkage with osteoporosis following heterogeneity testing, and 37 distinct immune cell types were recognized as being relevant to the disease after adjusting for heterogeneity and pleiotropy. Reverse MR analysis confirmed the absence of reverse causality among gut microbiota, inflammatory factors, immune cells, and osteoporosis. Notably, mediation analysis unveiled that Cyanobacteria influenced HLA DR++ monocytes' percentage in leukocytes, contributing to osteoporosis's pathogenesis. The outcomes highlighted specific gut microbiota, inflammatory factors, and immune cells, noticeably contributing to osteoporosis's pathogenesis. The identified mediating pathways provided innovative insights into disease mechanisms and potential therapeutic targets. Key words Gut Microbiota " Inflammatory cytokines " Immune cell dynamics " Osteoporosis " Mendelian randomization.

Ca2+-sensing receptors (CaSR) are G-protein coupled receptors activated by elevated concentrations of extracellular Ca2+. Cinacalcet, a positive allosteric CaSR modulator, is used as a calcimimetic to inhibit parathyroid hormone release and thus lower serum Ca2+ in hypercalcemic patients. There is a recent trend of repurposing cinacalcet in multiple applications such as anti-cancer actions, treatment of diarrhea and prevention of kidney cyst formation. In this study we investigated whether cinacalcet inhibited proliferation of endothelial cells (EC). Inhibition of EC proliferation offers an anti-angiogenesis mechanism in suppressing tumor growth. Cinacalcet at >/=18 µM caused mitochondrial membrane depolarization, suppressed proliferation and induced apoptosis in mouse bEND.3 EC. In 2 mM Ca2+-containing bath solution, cinacalcet (>/=18 µM) caused an initial rise in [Ca2+]i followed by fura-2 leakage. Similar results were obtained in Ca2+-free or 4 mM Ca2+-containing bath solution. Cinacalcet-elicited Ca2+ signal was unaffected by NPS 2143, a negative allosteric modulator of CaSR. Cinacalcet also increased Ni2+ leakage and trypan blue uptake into cells. Cinacalcet-induced membrane leakiness and cytotoxicity did not appear to be related to membrane fluidity changes. These data suggest cinacalcet, in a manner independent of CaSR stimulation and membrane fluidity perturbation, caused membrane leakiness, eventually leading to inhibition of EC proliferation and EC death. Key words Ca2+-sensing receptors " Endothelium " Cinacalcet " Ca2+ " Membrane permeability.

Gouty arthritis is a type of inflammatory arthritis that is mediated by the deposition of monosodium urate crystals and is an important burden on healthcare worldwide. The aim of this comprehensive review is to discuss the most recent advances regarding the mechanisms of treatment for gout, from classic pharmacological interventions to emerging therapeutic strategies. The chapter dissects the pathophysiology of gout through hyperuricemia, crystal deposition, and inflammatory responses to form a basis for the discussion of current treatment approaches; pharmacological interventions are described-side by side with lifestyle modifications-including NSAIDs, colchicine, and xanthine oxidase inhibitors. Newer approaches to management are discussed, including the use of biologics targeting IL-1beta, newer agents in development, and personalized medicine. It also outlines the future directions in gout research, focusing on the development of novel imaging techniques, biomarkers for treatment response, and targeting novel pathways. This review serves as an overall guide for clinicians and researchers and all other stakeholders interested in further advancing the specialty of gouty arthritis. Key words Gouty arthritis " Serum urate " Hyperuricemia " Crystal deposition " Colchicine.