Physiology international最新文献

The global temperature rise will have extensive consequences on our organ systems, but hypohydration caused by reduced water intake or increased water loss through sweating plays the most relevant role. Many studies have already demonstrated the association between hypohydration and impaired exercise performance, but data related to the cardiac burden of hypohydration are scarce. This study is a sub-investigation of our large, prospective, self-controlled trial on the effects of hypohydration on cardiopulmonary exercise capacity with previously published results. In the current sub-study, we analyzed the impact of hypohydration on cardiac burden in this cohort of fifty healthy, recreational athletes during cardiopulmonary exercise test.Therefore, each participant underwent cardiopulmonary exercise test with a standardized ramp protocol twice, once in hypohydrated state and once in euhydrated state as control, and the cardiac markers Troponin T, NT-pro-BNP and Chromogranin A were measured before and after the exercise test at each state. Mean age was 29.7 years and 34% of probands were female. Hypohydration led to a reduced body water, a significant decrease in oxygen uptake and lower levels of power output. Yet, Troponin T, NT-proBNP, Chromogranin A and lactate levels did not significantly differ between the two conditions.In this study cohort, decreased exercise capacity during hypohydration was more likely due to impaired cardiac output with diminished plasma volume rather than measurable cardiac stress from fluid deprivation. However, whether these data are generalizable to a diseased cohort is left unanswered and should be addressed in future randomized controlled trials.

Previous observational studies have investigated the association between urinary albumin excretion and the risk of colorectal cancer (CRC), but the results have been inconsistent. This study aimed to explore the causal association between urine albumin-to-creatinine ratio (ACR) and CRC risk through a two-sample Mendelian randomization (MR) analysis. The genome-wide association study (GWAS) data of ACR (n = 382,500) and CRC (CRC: 6,509 cases and 287,137 controls) were obtained from the IEU OpenGWAS project website and the FinnGen database, respectively. The TwoSampleMR and MR-PRESSO R packages were used to search for and analyze genetic variations that served as instrumental variables for ACR. The odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated using the inverse-variance weighted method, MR-Egger, and weighted median. Genetically predicted ACR was not associated with CRC risk (all P > 0.05). Further analysis based on the site of onset (colon or rectum) also did not show a significant association (all P > 0.05). MR-PRESSO, MR-Egger regression and leave-one-out sensitivity analysis all indicated that the current results were robust and reliable. These findings suggest that ACR does not affect CRC risk and may not be used as a marker of CRC risk in clinical practice. However, relevant studies especially in ethnically diverse populations are still needed to confirm the current findings.

The aim of this study is to show the relationship between the change in the strengthening of synaptic plasticity and tau phosphorylation and tau-kinases and phosphatase. The averages of the field excitatory-postsynaptic potential (fEPSP) and population spike (PS) in the last 5 min were used as a measure of LTP, LTD and MP. Total and phosphorylated levels of tau, kinases and phosphatases were evaluated by western blot and mRNA levels were evaluated by RT-qPCR. The stimulation of synapses by HFS and LFS+HFS increased the phosphorylation of total-tau and phospho-tau at the Thr181, Ser202/Thr205, Ser396 and Ser416 residues, and these were accompanied by increased enzymatic activity of Akt, ERK1/2. The increased phosphorylation of tau may mediate maintenance of LTP. If the increase in phosphorylation of tau cannot be prevented, together with inhibition of the subsequent LTP, this may indicate that the physiological role of hyperphosphorylated tau in synaptic plasticity may extend to pathological processes.

Liver cirrhosis is the consequence of chronicisation and of the evolution of untreated liver diseases. The complexity of the disease and the complications it can cause have been and are still intensively researched, aiming to discover new therapies or improve existing ones for the effective management of liver cirrhosis. Currently, the treatment used is directed against the cause that caused the disease, if it is known; in advanced cases, liver transplantation is the only valid therapeutic option. Hepatoprotectors that are currently on the market are numerous, having as common properties the antioxidant, anti-inflammatory, stabilizing properties of the hepatocytic membrane; A few examples: the ethanolic extract of Curcuma longa, the extract from the plant called Sophora flavescens, the extract of Glycyrrhiza glabra, silymarin (extracted from Sylibum marianum), the extract of Ganoderma lucidum, etc. Liver cirrhosis is accompanied by generalized hypovitaminosis, so supplementing the diet with hydro- and liposoluble vitamins is mandatory. Protein-caloric malnutrition can be prevented by a hyperprotein diet, especially beneficial being the supplementation with branched-chain amino acids, which are also applicable in the prophylaxis and treatment of hepatic encephalopathy. Nanoparticles are a state-of-the-art therapeutic option, proving increased bioavailability, for example polydopamine nanoparticles loaded with l-arginine have been tested as therapy in liver cirrhosis. Among the innovative treatment directions in liver cirrhosis are hybrid products (e.g. hybrid polymer nanoparticles loaded with caffeic acid), cell cultures and artificial or bioartificial liver support.

Poor sleep increases pain, at least in part, by disrupting endogenous pain modulation. However, the efficacy of endogenous analgesia in sleep-deprived subjects has never been tested. To assess this issue, we chose three different ways of triggering endogenous analgesia: (1) acupuncture, (2) acute stress, and (3) noxious stimulation, and compared their ability to decrease the pronociceptive effect induced by REM-SD (Rapid Eye Movement Sleep Deprivation) with that to decrease inflammatory hyperalgesia in the classical carrageenan model. First, we tested the ability of REM-SD to worsen carrageenan-induced hyperalgesia: A low dose of carrageenan (30 µg) in sleep-deprived Wistar rats resulted in a potentiated hyperalgesic effect that was more intense and longer-lasting than that induced by a higher standard dose of carrageenan (100 µg) or by REM-SD alone. Then, we found that (1) acupuncture, performed at ST36, completely reversed the pronociceptive effect induced by REM-SD or by carrageenan; (2) immobilization stress completely reversed the pronociceptive effect of REM-SD, while transiently inhibited carrageenan-induced hyperalgesia; (3) noxious stimulation of the forepaw by capsaicin also reversed the pronociceptive effect of REM-SD and persistently increased the nociceptive threshold above the baseline in carrageenan-treated animals. Therefore, acupuncture, stress, or noxious stimulation reversed the pronociceptive effect of REM-SD, while each intervention affected carrageenan-induced hyperalgesia differently. This study has shown that while sleep loss may disrupt endogenous pain modulation mechanisms, it does not prevent the activation of these mechanisms to induce analgesia in sleep-deprived individuals.

Lactate, a metabolite of exercise, plays a crucial role in the body. In these studies, we aimed to investigate the role of G protein-coupled receptor 81 (GPR81), a specific receptor for lactate, in regulating lipid storage in the gastrocnemius muscle of rats. To achieve this, we measured the impact of sodium 3-hydroxybutyrate (3-OBA) concentration and time on the cAMP-PKA signaling pathway in the gastrocnemius muscles of rats. Our investigation involved determining the effects of administering 3-OBA at a concentration of 3 mmol L-1 just 15 min before exercise. As expected, exercise led to a notable increase in intramuscular lactate concentration in rats. However, injecting 3-OBA prior to exercise yielded intriguing results. It not only further augmented the cAMP-PKA signaling pathway but also boosted the expression of lipolysis-related proteins such as hormone-sensitive lipase (HSL) and adipose triglyceride lipase (ATGL). Simultaneously, it decreased the expression of fat-synthesizing proteins, including acetyl CoA carboxylase (ACC) and fatty acid synthase (FAS), while increasing the protein expression of cytochrome c oxidase subunit Ⅳ(COX Ⅳ) and the activity of citrate synthetase (CS). Unfortunately, there was no significant change observed in intramuscular triglyceride (IMTG) content. In summary, our findings shed light on the role of lactate in partially regulating intramuscular triglycerides during exercise.

Previous results show that halothane gas anaesthesia has a suppressive effect on the visually evoked single-cell activities in the feline caudate nucleus (CN). In this study, we asked whether the low-frequency neuronal signals, the local field potentials (LFP) are also suppressed in the CN of anaesthetized animals.To answer this question, we compared the LFPs recorded from the CN of two halothane-anaesthetized (1.0%), paralyzed, and two awake, behaving cats during static and dynamic visual stimulation. The behaving animals were trained to perform a visual fixation task.Our results denoted a lower proportion of significant power changes to visual stimulation in the CN of the anesthetized cats in each frequency range (from delta to beta) of the LFPs, except gamma. These differences in power changes were more obvious in static visual stimulation, but still, remarkable differences were found in dynamic stimulation, too. The largest differences were found in the alpha and beta frequency bands for static stimulation. Concerning dynamic stimulation, the differences were the biggest in the theta, alpha and beta bands.Similar to the single-cell activities, remarkable differences were found between the visually evoked LFP changes in the CN of the anaesthetized, paralyzed and awake, behaving cats. The halothane gas anaesthesia and the immobilization suppressed the significant LFP power alterations in the CN to both static and dynamic stimulation. These results suggest the priority of the application of behaving animals even in the analysis of the visually evoked low-frequency electric signals, the LFPs recorded from the CN.

Background: It has been reported that long non-coding RNA THAP9-AS1 exerts carcinogenic role by mediating miRNAs and target genes in various human cancers. However, whether THAP9-AS1 influences the progression of nasopharyngeal carcinoma (NPC) remains unknown.

Methods: The transcriptional levels of THAP9-AS1 and miR-185-5p were estimated via quantitative real time polymerase chain reaction (qRT-PCR) assay. The protein level of SOX13 was detected with western blotting assay. Additionally, methyl thiazolyl tetrazolium (MTT) assay as well as colony formation assay were utilized to measure cell growth. The apoptotic cells were observed by employing Terminal-deoxynucleoitidyl Transferase Mediated Nick End Labeling (TUNEL) staining analysis, and transwell assay was introduced to test cell migration in addition to invasion. Moreover, the relationship between miR-185-5p and THAP9-AS1 or SOX13 was estimated through dual-luciferase reporter gene assay.

Results: THAP9-AS1 was overexpressed in head and neck squamous cell carcinoma (HNSCC) tissues and NPC cells. Besides, silencing of THAP9-AS1 depressed the life processes of NPC cells including cell growth, migration as well as invasion but facilitated cell apoptosis. Further investigation proved that miR-185-5p was the direct target of THAP9-AS1. Besides, the knockdown of THAP9-AS1 notably reduced the transcriptional level of miR-185-5p. Furthermore, THAP9-AS1 served as a sponge of miR-185-5p to modulate the expression of SOX13, which regulated the development of NPC cells.

Conclusion: This work verified that THAP9-AS1 promoted NPC cell progression at least partly by mediating the miR-185-5p/SOX13 axis.

Objective: Gastric cancer is the most frequent gastrointestinal malignancy with a poor prognosis. Rac GTPase activation protein 1 (RACGAP1) is a novel tumor promotor, whose detailed effect on gastric cancer remains to be further elucidated. Hence, this study identifies the action of RACGAP1 on gastric cancer and investigates the potential mechanism.

Methods: RACGAP1 expression in gastric cancer was analyzed based on the data of The Cancer Genome Atlas (TCGA) database. Cell proliferation was measured by CCK-8 and colony formation assay. Cell migration and invasion were evaluated by transwell assay. Cell apoptosis was assessed by flow cytometry. Cell autophagy was evaluated via determining LC3.

Results: RACGAP1 presented at high level in gastric cancer cells. Overexpressed RACGAP1 potentiated gastric cancer cell proliferation, migration, and invasion. Besides, silenced RACGAP1 induced cell apoptosis and autophagy. Furthermore, RACGAP1 suppressed the expression of SIRT1 and Mfn2.

Conclusion: RACGAP1 was overexpressed in gastric cancer. RACGAP1 potentiated aggressive behaviors of gastric cancer, and suppressed cell apoptosis and autophagy via modulating SIRT1/Mfn2. RACGAP1 may be a valuable target in the treatment of gastric cancer.