Physiological research最新文献

Vitamin D is implicated in multiple metabolic processes, however, the dose-dependent relationship between serum 25-hydro-xyvitamin D [25(OH)D] concentrations and glucose-lipid metabolism remains unclear among women with a history of gestational diabetes mellitus (GDM). This study aimed to assess both linear and non-linear relationships between serum 25(OH)D levels and indicators of insulin resistance and lipid metabolism in this high-risk group. Data from 1,876 women with prior GDM were obtained from the 2007-2018 National Health and Nutrition Examination Survey (NHANES). Weighted linear regression models were applied to assess associations between serum 25(OH)D and metabolic markers, while restricted cubic spline models were used to examine non-linear relationships. Analyses were adjusted for age, ethnicity, body mass index (BMI), education, and lifestyle factors. Following multivariate adjustment, each 10 nmol/l increase in serum 25(OH)D was associated with a decrease in HOMA-IR by 0.017 units (95 % CI: -0.026, -0.007), an increase in HDL-C by 0.127 mg/dl (95 % CI: 0.102, 0.153), and a reduction in total cholesterol of 0.007 mmol/l (95 % CI: -0.009, -0.004). Restricted cubic spline analysis demonstrated a U-shaped relationship between 25(OH)D and LDL-C (p for non-linearity<0.001), with inflection point at ~50 nmol/l. The inverse association between 25(OH)D and HOMA-IR was significant in non-Hispanic white individuals (beta=-0.020, p=0.008) but not in non-Hispanic Black individuals (beta=0.009, p=0.584). The positive association between 25(OH)D and HDL-C was strongest in women with normal BMI (beta=0.114). Among women with a history of GDM, serum 25(OH)D levels were inversely associated with insulin resistance and positively associated with HDL-C. A non-linear, U-shaped relationship was observed with LDL-C. These associations varied by race/ethnicity and BMI, the potential relevance of vitamin D status in in the long-term metabolic management of individuals following GDM. Key words 25-hydroxyvitamin D " Dose-response relationship " Gestational diabetes mellitus " Insulin resistance " Lipid metabolism.

Gluten-free diet is currently recommended for people with gluten-related diseases; however some studies document their positive effects also in other diseases. Oppositely gluten is often vilified in nutrition, but serious results about their negative effects in healthy are missing, or controversial. The objective of this study is to compare the effects of different types of diets on ovarian, testicular, and thyroid morphology in an experimental mouse model. Forty-eight (n=48) laboratory mice of the BALB/c line were included in the experiment, divided into 4 groups, and maintained on special diets for 5 weeks. The control group, (6 females, 6 males) was fed a gluten-free diet. The first (E1), second (E2) and third (E3) experimental groups, (6 females, 6 males) were fed a mixture of casein hydrolysate combined with E1: pure extracted gluten in a 30 %:70 % ratio. E2: gliadins at a ratio of 30 %:70 % and E3: avenin at a ratio of 30 %:70 %. At the end of the experiment, the mice were euthanized and ovaries, testes, and thyroid glands were sampled. The samples were fixed in a 10 % formalin solution and processed into hematoxylin-eosin-stained slides. The oocyte and follicle widths of the ovaries were measured; as well as the germinal epithelium and the width of the seminiferous tubules of the testes; as well as the follicle epithelium width and the follicle width of the thyroid gland. The results showed significant differences in the width of oocytes, follicles, testicular seminiferous tubule epithelium, testicular tubules, thyroid follicle epithelium as well as differences in the width of thyroid follicles. Concentrated gluten and gliadin-based diets showed positive results compared to concentrated avenin and gluten-free diets. On the basis of animal experiment using histological methods, it seems that gluten may not be for healthy population harmful and is not recommended to be avoided outside groups of people with gluten-related disorders. Key words Celiac disease " Gluten " Non-celiac gluten sensitivity " Cereals o Nutrition.

The objective of this in vitro study was to examine the impact of metformin (MET) at different concentrations (0.1, 1, 10, 50, and 100 mM) on rat primary osteoblasts, as the results obtained so far are inconsistent. Osteoblast apoptosis, viability, alkaline phosphatase (ALPL) activity, production of osteoblast-specific biomarkers, including ALPL, osteocalcin (BGLAP), type I collagen alpha 1 (COL1A1), integrin-binding sialoprotein (IBSP), bone morphogenetic protein 2 (BMP2), runt-related transcription factor 2 (RUNX2), vascular endothelial growth factor (VEGF), tumor necrosis factor ligand superfamily member 11 (TNFSF11 or RANKL), as well as calcium/collagen deposition were assessed. Our results revealed that a dose of 100 mM was cytotoxic to osteoblasts and resulted in a complete loss of their viability. Therefore, this concentration was excluded from further analyses. In general, MET exhibited a dose-dependent impact on multiple osteoblast-specific functional biomarkers, with beneficial effects noted on ALPL activity (at 0.1 and 1 mM) as well as on the levels of ALPL (0.1 and 1 mM), BGLAP (at 0.1-50 mM), IBSP (at 0.1-50 mM), BMP2 (at 0.1, 10 and 50 mM), VEGF (at 0.1 and 1 mM), and RANKL (at 0.1 mM). Calcium/collagen deposition at concentrations of 0.1 and 1 mM reached the same level as control cells, higher doses (10 and 50 mM) dramatically reduced cell viability after 21 days and the aforementioned parameters could not be evaluated. It can be concluded that MET at concentrations up to 1 mM can promote osteoblast viability, osteogenic differentiation, angiogenic signaling, and reduce osteoclastogenesis. Key words Metformin " Osteoblasts " Bone health " In vitro.

Mirogabalin is a newly developed gabapentinoid drug. Several in vivo and clinical studies have demonstrated the potent analgesic effects of mirogabalin in neuropathic pain. This study aims to investigate the impact of mirogabalin on visceral pain and inflammation. Adult male Balb/c mice (20-25 g) were used in the study (n=7). Mirogabalin was administered intraperitoneally at 10, 20, and 40 mg/kg doses. Inflammatory visceral pain was induced by intraperitoneal administration of acetic acid. The number of writhing was observed after acetic acid administration, and the effective dose of mirogabalin was determined. In the second phase of the study, the effects of mirogabalin on locomotor activity and leukocyte infiltration into peritoneal tissue were examined. IL-6, GSH levels, and SOD activity were investigated biochemically. Statistical analyses were performed in the GraphPad Prism (v8.0.1) program. Mirogabalin was significantly antinociceptive at all three doses (p<0.001). Histopathologic examination showed that the effective dose of mirogabalin decreased leukocyte infiltration into the peritoneum. Mirogabalin did not affect total distance moved and mean speed in the open field test. There was no significant difference between the groups in terms of IL-6, GSH levels, and SOD activity. Our results demonstrated a significant antinociceptive effect of mirogabalin against visceral pain. In addition, anti-inflammatory effects were revealed by decreasing leukocyte infiltration. However, the fact that mirogabalin did not alter antioxidant systems and IL-6 levels suggests that other mechanisms are responsible for its anti-inflammatory effects. Key words Mirogabalin " Pain " Inflammation " Visceral " GABA.

Mitochondria participate in regulating cytosolic Ca2+ signaling by their Ca2+ handling via mitochondrial Ca2+ uniporter (MCU) and mitochondrial Na+/Ca2+ exchanger (mitoNCX). In this study, we examined how agonist-triggered cytosolic Ca2+ oscillations in human alveolar type 2 A549 cells were affected by an MCU inhibitor (MCU-i4), MCU activator (kaempferol) and mitoNCX inhibitor (CGP-37157). Whilst inhibition of MCU did not significantly repress Ca2+ oscillations, MCU activation by kaempferol considerably dampened oscillatory activities. Inhibition of mitochondrial Ca2+ efflux by CGP-37157 also suppressed Ca2+ oscillations; the suppressive effects of kaempferol and CGP 37157 were not additive. Both kaempferol and CGP-37157 caused a rise in mitochondrial matrix Ca2+ level, but their effects were not additive. Taken together, our results suggest Ca2+ oscillations in alveolar type 2 A549 cells were regulated by stimulating Ca2+ uptake into, and preventing Ca2+ efflux from, the mitochondria, with both cases resulting in disturbed Ca2+ traffic and Ca2+ accumulation in the mitochondrial matrix. Key words Mitochondria " Ca2+ oscillations " Mitochondrial Ca2+ uniporter " Mitochondrial Na+/Ca2+ exchanger " A549 cells.

We performed a mechanical analysis of the commonly used needles for ultrasound-guided interventions in the musculoskeletal system. Specifically, focusing on the ability to absorb potential physical loads and the degree of deformation during the procedure, the needle gauge best suited for those procedures is evaluated. A customized tensile-compression device was used for an experimental buckling strength test on three commonly used needle types with specific gauge sizes. The loss of structural integrity, loss of needle stability, and buckling load were modeled also theoretically using finite element analysis software. Theoretical software needle buckling analysis detected the load for the first buckling mode of the needle, when the highest value was reached for the G20 needle with the load 18.8 N. The load for G21 needle was 9.7 N and for G23 8 N. Experimental data with customized tensile-compression device aligned theoretical data when the highest value was reached for the G20 needle with the load 19.7±1.9 N. The load for G21 needle was 10.6+/-2.7 N and for G23 7.9+/-0.7 N. Theoretical and practical experiments have shown that the standard G20 needle model exhibits the highest mechanical tolerance for potential interventions in the musculoskeletal system. Key words Interventional ultrasound " Needle " Buckling strength.

Osteoarthritis (OA) is a severe chronic inflammatory disorder with limited treatment options. Naringin (nar) has been shown to protect against OA; however, its mechanisms of action on OA remain poorly understood. This study aims to investigate the molecular mechanism of nar in treating OA via network pharmacology and experiments. Differentially expressed genes (DEGs) were identified using GSE283079 dataset. Protein-protein interaction (PPI) network was constructed using STRING database, and protein interactions were analyzed. Network pharmacology was employed to investigate the molecular interaction network influenced by nar in OA, and molecular docking was applied to predict the binding interactions between nar and core genes. The OA mouse models were constructed using anterior cruciate ligament transection (ACLT) to explore the action of nar in vivo. The OA damage was examined using Hematoxylin and Eosin (HE) and Safranin-O/Fast Green staining, along with Osteoarthritis Research Society International (OARSI) scoring for quantitative histopathological evaluation. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) positive rate and inflammation factor (tumor necrosis factor (TNF)-alpha and interleukin (IL)-1beta), and reactive oxygen species (ROS) levels were detected using corresponding assay kits. The protein expression was analyzed using western blot. Cell viability and cell apoptosis were examined using cell counting kit 8 (CCK8) assay kit and flow cytometry assays. In GSE283079 dataset, the up-regulation of DEGs was enriched in immune response activation, cartilage development, collagen metabolic process, and leukocyte proliferation. Additionally, matrix metalloproteinase 13 (MMP13), MMP1, and phospholipase A2 group IIA (PLA2G2A) may be the core genes for nar-protected OA. The binding energy of nar and MMP13 was strongest. In vivo OA models, nar mitigated OA progression and reduced OARSI scores. Mechanistically, nar suppressed cell apoptosis, inflammation factor productions, extracellular matrix (ECM) degradation, and ROS production via decreasing MMP13. Nar alleviates OA malignant progression via reducing MMP13. Key words Osteoarthritis " Naringin " Network pharmacology " MMP13 " Molecular mechanism.

NMDA receptor hypofunction can lead to behavioral and cognitive disturbances, including hyperlocomotion, and is considered a core pathophysiological mechanism underlying cognitive and negative symptoms in schizophrenia. This study examined whether treatment with the mGlu2/3 receptor agonist LY379268 (1 and 2 mg/kg) could counteract such disruptions induced by the NMDA antagonist MK-801 (0.1 mg/kg). Rats were tested under two conditions: an aversive learning task (active place avoidance on a rotating arena) and a non-aversive open field test. Additionally, local field potentials were recorded from the medial prefrontal cortex during the open field test and later under urethane anesthesia. Contrary to expectations, LY379268 did not consistently alleviate MK-801-induced impairments. In the aversive learning context, the combination of MK-801 with LY379268 (2 mg/kg) paradoxically led to exacerbated hyperlocomotion and impaired navigational performance. In contrast, the 1 mg/kg dose of LY379268 had a modest beneficial effect in the non-aversive setting, slightly reducing MK-801-induced hyperactivity. Electrophysiological recordings revealed that MK-801, alone or in combination with LY379268 (1 mg/kg), disrupted theta-high gamma phase-amplitude coupling in the open field test, indicating impaired neural processing. Under anesthesia, MK-801 increased low gamma power. LY379268 did not reverse this alteration. These findings highlight the task- and dose-dependent nature of LY379268's effects. While it offered limited improvement in a non-aversive environment, it failed to mitigate and sometimes exacerbated deficits in more challenging, aversive tasks. This complexity underscores the need for further research to refine the therapeutic potential of mGlu2/3 modulation in conditions associated with glutamatergic dysfunction. Key words MK-801 " LY379268 " Electrophysiology " Medial prefrontal cortex " Hyperlocomotion.

On Tuesday, December ninth, the scientist, educator, physician, and university professor Miloš Langmeier passed away. He was a creative and active individual with whom I had the great fortune to collaborate, and I am honored to call myself his student. Along with many others, I was a small part of his laboratories of functional morphology, allowing me the wonderful opportunity to be influenced by his exemplary academic guidance and the systematic organization of scientific work. He was a knowledgeable physiologist and pathophysiologist, the author of numerous textbooks and scholarly articles. His primary interest lay in the functional morphology of synaptic structures, and he authored several works on excitotoxicity, epileptogenesis, and hypoxia. His academic interests were both broad and profound. In his laboratories, we studied the effects of nicotine on limbic structures, established models of audiogenic epilepsy, observed the influence of ethanol on the development of various brain structures, and utilized models of hypobaric and normobaric hypoxia. Discussions regarding the results we obtained were characterized by critical thinking among PhD students, which I now recognize as an invaluable learning method that Professor Langmeier provided. He was highly qualified, and his authority was firmly established. This fostered a sense of certainty and motivation for further study among all of us as students. Professor Langmeier had a unique ability to attract young people to the field of physiology, creating an environment that emphasized the importance of both pedagogical work and the continuous search for new experimental topics. Through his gentle influence, he cultivated a spirit of teamwork in the laboratories, skillfully managed conflicts, and stressed that creative work should not be restricted to weekends. He valued well-executed work, and we collectively celebrated the accomplishments of research articles, secured grants, and defended doctorates as achievements for the entire laboratory. Under his leadership, the system of functional morphology laboratories at the Institute of Physiology underwent a significant and challenging reconstruction, which required considerable effort and for which he rightfully took pride. I must acknowledge his crucial role in shaping the physiology curriculum for future dentists and his significant contributions as a member to the Council of Higher Education Institutions. Although I will not attempt to enumerate all of Professor Langmeier's merits, successes, and accolades, I believe it is unnecessary. His students and colleagues will chiefly remember his intelligent humor, extensive knowledge across many disciplines, generosity, diligence, sense of justice, pedagogical expertise, and genuine enthusiasm for scientific inquiry. He was a Professor Verus in both, his field and his university. We will all miss him greatly. Thank you for everything professor. Rest in peace. Vladimír Riljak.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a chronic progressive disorder characterized by an excess accumulation of lipids in the liver. The aim of this study was to examine the role of bilirubin (BR), the catabolic heme product and a putative peroxisome proliferator-activated receptor alpha (PPARalpha) agonist, in an in vitro model of MASLD. In our study, we used human hepatoblastoma HepG2 cells exposed to oleic (OA)/palmitic acid (PA) (2:1 ratio, 24 h) with subsequent treatment with BR or fenofibrate (FF, a clinically used PPARalpha agonist) at clinically relevant concentrations. A significant increase in total cellular lipid content after OA/PA treatment (p<0.05) was observed. When treated with BR and FF, intracellular concentrations of OA and PA decreased significantly (p<0.05). Changes in lipid content were attenuated by GW6471 (a PPARalpha antagonist) indicating the importance of PPARalpha pathway in a mechanism of action of BR and FF. Furthermore, we observed a significant increase in the gene expression of a pyruvate dehydrogenase kinase 4 after treatment with FF; FF also increased mitochondrial respiration. Collectively, our data indicate that both BR and FF reduce the accumulation of OA/PA in HepG2 cells exposed to these fatty acids, presumably by up-regulating fatty acid oxidation via PPARalpha pathway. Key words Bilirubin " Fatty acids " Fenofibrate " MASLD " PPARalpha.