Physiological research最新文献

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.

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.

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.

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.

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.

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.

Stroke and cerebral ischemia/reperfusion (IR) injury are severe conditions characterized by impaired blood flow to the brain, leading to tissue infarction and neurological impairments. Panax notoginseng saponins (PNS) have displayed various beneficial effects in alleviating cerebrovascular disorders. This study aimed to investigate the neuroprotective capacity of PNS in a rat model of middle cerebral artery occlusion (MCAO)-induced cerebral IR injury, focusing specifically on understanding the involvement of the sirtuin 1 (SIRT1)/nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) pathway in mediating this protective effect. Male Sprague-Dawley rats (n=45, weighing 250-280g and aged 12 weeks) were utilized in this experiment. Cerebral IR injury was induced by subjecting the rats to 30 minutes of MCAO followed by 24 hours of reperfusion. Prior to the surgery, PNS (120mg/kg) was administered once daily via gavage for 14 days. The evaluation measures included assessing cerebral infarct volume, neurological function using the Longa method, conducting histopathological analysis, examining the expression of SIRT1, Nrf2, and HO-1 genes and proteins, as well as measuring the levels of glutathione (GSH), superoxide dismutase (SOD), and malondialdehyde (MDA). Pretreatment with PNS markedly decreased infarct volume, enhanced neurological function, and mitigated histopathological alterations. Additionally, PNS intake resulted in the upregulation of SIRT1, Nrf2, and HO-1 genes and proteins, boosted enzymatic antioxidant activity, and lowered MDA levels, pointing towards a diminution in oxidative stress. The multifaceted antioxidant and neuroprotective properties of PNS underscore its promising role in preserving neuronal function, mitigating oxidative damage, and promoting tissue survival in ischemic conditions. These benefits were associated with the modulation of the SIRT1/Nrf2/HO-1 signaling pathway, emphasizing the therapeutic significance of PNS in addressing cerebral IR injury and related neurological complications. Key words: Ischemia/reperfusion injury, Neuroprotection, Oxidative stress, Panax notoginseng saponins, Stroke.

Behavioral sensitization is a phenomenon occurring after repeated administration of various psychotropic substances and it is characterized by gradually increasing response to the particular drug. It has been described for majority of addictive substances including amphetamines. It is considered to reinstate drug-seeking behaviour and plays important role in the processes associated with drug abuse and addiction. There are published reports, particularly on preclinical level, that N-acetylcysteine (NAC) may affect addictive properties of different classes of drugs (e.g., cocaine, heroin, alcohol, cannabinoids, nicotine). Since the lack of information on possible effects of NAC on amphetamine derivatives we decided to test possible influence of this substance on behavioral sensitization to methamphetamine (MET) in the mouse open field test. Our results have shown a decreased acute stimulatory effect of MET caused by NAC and moreover, there was a non-significant trend of attenuated development of behavioral sensitization to MET after simultaneous long-term administration of MET and NAC. This suppression of MET stimulatory effects therefore suggested on the preclinical level possible promising efficacy of NAC on addictive properties associated with MET similarly as it was demonstrated by other authors in association with cocaine or heroin. Key words: N-acetylcysteine, Methamphetamine, Behavioral sensitization.

Whether the lung is a primary site of platelet (PLT) production is still disputed. To address this question, PLT parameters in blood before and after pulmonary circulation in humans, rats, and rabbits were assessed by automatic hematology analyzers; bone marrow and pulmonary megakaryocytes in humans, mice, rats, and rabbits were evaluated by immunohistochemical staining; and pulmonary megakaryocytes in humans were analyzed by single-cell RNA sequencing. We found that the mean number of PLTs in rats was nearly threefold greater than that in rabbits and humans. The PLT distribution width after pulmonary circulation in humans, rats, and rabbits was consistently less than that before pulmonary circulation. However, except for the PLT population in the left atrium of rats was significantly greater than that in the right ventricle (n=20), the PLT populations between the left and right atria of rats (n=19), rabbits (n=19), and humans (n=24), between the left atrium and right ventricle of rabbits (n=19), and between the inferior vena cava and radial artery of humans (n=93) had no differences. Moreover, megakaryocytes in the lungs of mice, rats, rabbits, and humans were mononuclear, were mainly located perivascularly, and accounted for approximately 3-5 ‰. Their numbers were significantly lower, and their sizes were smaller than those of bone marrow. Conclusively, the lung can produce PLTs, but it is not a primary site of PLT biogenesis. The capability of pulmonary PLT generation differs among species; at least in rats, it is greater than that in rabbits and humans.

Metabolic-dysfunction associated steatotic liver disease (MASLD) affects approximately 30 % of the world adult population and even contributes to the increased mortality from cardiovascular disease. Dietary intervention, along with exercise, is the most important tool for the treatment of MASLD patients. Dietary composition can have profound effects on liver fat. This review summarizes the results of studies that used MR methods to study the effect of macronutrients on liver fat content. It focuses on intervention studies manipulating the content and quantity of macronutrients in long-term dietary intervention studies and, in more detail, on studies monitoring the effect of administered nutrients on changes in liver fat over several hours.