Physiological research最新文献

Abnormal hip bone morphologies are associated with various diseases of the hip joint. Weight bearing, especially during growth, may be important to achieve normal acetabulum development. This study aimed to investigate whether hip bone morphologies were affected by hindlimb suspension (HS) in 4 week-old rats. In HS groups, tail suspension was applied for 0, 2, 4, and 8 weeks. Age-matched rats were used as controls. The complex of hip bones with lumbar and sacral vertebrae were assessed based on morphological indexes using three-dimensional reconstructed images from X-ray computed tomography. Acetabular widths (measured from cranial to caudal) unchanged and depths became larger in both groups with age. Acetabular lengths (from the ventral side to the dorsal side) became larger in control groups but unchanged in HS groups with age. In HS groups, acetabular width, length, and depths were smaller than the control groups at 4 and/or 8 weeks. Acetabular versions became enlarged (rotated inwards) with age in both groups, although this was particularly pronounced in HS groups. Histologically, triradiate cartilage layers in the acetabulum were thinner with age and almost disappeared at 8 weeks in both groups. However, HS decreased Safranin O staining and prolonged the presence of hypertrophic chondrocyte indicating alterations in the chondral ossification processes. Iliac wing angles remained unchanged and anterior superior iliac crest (ASIC) distances increased with age in controls. In contrast, HS groups showed narrowed iliac wing angles with small ASIC distances. These results suggest that reduced mechanical loading during growth can interfere with hip joint formation. Keywords Hindlimb suspension, Hip joint, Acetabular morphology, Triradiate cartilage.

Xi-Kun Yuan Pin-Shi Ni Zhen-Hao Yan Zhi Yu Zhuang-Zhi Wang Chen-Kai Zhang Fang-Hui Li Xiao-Ming Yu 1Sports Department, Nanjing University of Science and Technology ZiJin College, Nanjing, China, 2School of Sport Sciences, Nanjing Normal University, Nanjing, China, 3Shanghai Seventh People's Hospital, Shanghai, China To investigate the effects of life-long exercise (LLE) on age-related inflammatory cytokines, apoptosis, oxidative stress, ferroptosis markers, and the NRF2/KAEP 1/Klotho pathway in rats. Eight-month-old female Sprague-Dawley rats were divided into four groups: 1) LLE: 18-month LLE training starting at 8 months of age, 2) Old moderate-intensity continuous training (OMICT): 8 months of moderate-intensity continuous training starting at 18 months of age, 3) Adult sedentary (ASED): 8 month-old adult sedentary control group, and 4) Old sedentary (OSED): a 26-month-old sedentary control group. Hematoxylin eosin staining was performed to observe the pathological changes of kidney tissue injury in rats; Masson's staining to observe the deposition of collagen fibers in rat kidney tissues; and western blotting to detect the expression levels of IL-6, IL 1beta, p53, p21, TNF-alpha, GPX4, KAEP 1, NRF2, SLC7A11, and other proteins in kidney tissues. Results: Compared with the ASED group, the OSED group showed significant morphological changes in renal tubules and glomeruli, which were swollen and deformed, with a small number of inflammatory cells infiltrated in the tubules. Compared with the OSED group, the expression levels of inflammation-related proteins such as IL-1beta, IL-6, TNF alpha, and MMP3 were significantly lower in the LLE group. Quantitative immunofluorescence analysis and western blotting revealed that compared with the ASED group, KAEP 1 protein fluorescence intensity and protein expression levels were significantly enhanced, while Klotho and NRF2 protein fluorescence intensity and protein expression levels were reduced in the OSED group. Compared with the OSED group, KAEP 1 protein fluorescence intensity and protein expression levels were reduced in the LLE and OMICT groups. Klotho and KAEP 1 protein expression levels and immunofluorescence intensity were higher in the LLE group than in the OSED group. The expression levels of GPX4 and SLC7A11, two negative marker proteins associated with ferroptosis, were significantly higher in the LLE group than in the OSED group, while the expression of p53 a cellular senescence-associated protein that negatively regulates SLC7A11, and the downstream protein p21 were significantly decreased. LLE may ameliorated aging-induced oxidative stress, inflammatory response, apoptosis, and ferroptosis by regulating Klotho and synergistically activating the NRF2/KAEP 1 pathway. Keywords: Life-long exercise, Moderate intensity continuous training, Aging, Kidney tissue, Ferroptosis.

Hyperhomocysteinemia (HHcy) is considered an independent risk factor of cardiovascular diseases. Among the proposed mechanisms underlying homocysteine toxicity are altered protein expression and induction of oxidative stress. In the present study, we explored protein abundance and parameters related to oxidative stress in heart homogenates of rats exposed to chronic mild HHcy. Using two-dimensional gel electrophoresis followed by MALDI-TOF/TOF mass spectrometry 22 altered proteins (6 upregulated and 14 downregulated) were identified. For eight proteins the altered abundances were validated by Western blot analysis. Identified proteins are primarily involved in energy metabolism (mainly enzymes of glycolysis, pyruvate dehydrogenase complex, citric acid cycle, and ATP synthase), cardiac muscle contraction (alpha-actin and myosin light chains), stress response (heat-shock protein beta1 and alphaB-crystallin) and antioxidant defense (glutathione peroxidase 1). Diminished antioxidant defense was confirmed by decreases in total antioxidant capacity and GSH/GSSG ratio. Consistent with the decline in enzymatic and non-enzymatic antioxidant defense the protein oxidative modification, as determined by tyrosine nitration, was significantly increased. These findings suggest that both, altered protein expression and elevated oxidative stress contribute to cardiovascular injury caused by HHcy. Keywords: Homocysteine, Heart, Protein abundance, Antioxidant capacity, Nitrotyrosines.

The endothelial-mesenchymal transition (EndMT) of endothelial progenitor cells (EPCs) plays a notable role in pathological vascular remodeling. Emerging evidence indicated that long non-coding RNA-regulator of reprogramming (linc-ROR) can promote epithelial-mesenchymal transition (EMT) in a variety of cancer cells. Nevertheless, the function of linc-ROR in EPC EndMT has not been well elucidated. The present study investigated the effect and possible mechanisms of function of linc-ROR on the EndMT of EPCs. A linc-ROR overexpression lentiviral vector (LV linc-ROR) or a linc-ROR short hairpin RNA lentiviral vector (LV-shlinc-ROR) was used to up or downregulate linc-ROR expression in EPCs isolated from human umbilical cord blood. Functional experiments demonstrated that LV-linc-ROR promoted the proliferation and migration of EPCs, but inhibited EPC angiogenesis in vitro. In the meantime, reverse transcription-quantitative PCR and western blotting results showed that the expression of the endothelial cell markers vascular endothelial-cadherin and CD31 was decreased, while the expression of the mesenchymal cell markers ?-smooth muscle actin and SM22? was increased at both mRNA and protein levels in LV-linc-ROR-treated EPCs, indicating that linc-ROR induced EPC EndMT. Mechanistically, the dual-luciferase reporter assay demonstrated that microRNA (miR/miRNA)-145 was a direct target of linc-ROR, and miR-145 binds to the 3'-untranslated region of Smad3. Moreover, LV-shlinc-ROR increased the expression of miR-145, but decreased the expression of Smad3. In conclusion, linc-ROR promotes EPC EndMT, which may be associated with the miR-145/Smad3 signaling pathway. Keywords: Endothelial progenitor cells, Endothelial to mesenchymal transition, Linc-ROR, MiR-145, Atherosclerosis.

In this study, we investigated the mechanism underlying electrocardiogram (ECG) alterations in a rabbit model of acute pulmonary thromboembolism (PTE). Twelve healthy adult New Zealand white rabbits were used, with eight in the experimental group (PTE group) and four in the control group. After developing the rabbit model of acute PTE, ECG and coronary angiography were performed. HE staining was conducted on the right and left ventricular tissues, and polymerase chain reaction (PCR) was used to determine brain natriuretic peptide (BNP), tumor necrosis factor-alpha (TNF-?), and Troponin I (TNI) mRNA expression in the myocardium. There were considerable changes in the ST segment of the ECG in the PTE group. Coronary angiography revealed the absence of spasm, stenosis, and occlusion. In the plasma of the PTE group, the levels of D-dimer, BNP, TNF-?, and TNI were significantly elevated, and these changes were statistically significant (P<0.05). PCR analysis of ventricular myocardial tissue indicated significantly higher levels of BNP, TNF-?, and TNI mRNA in the PTE group than in the control group. These differences were statistically significant (P<0.05). The ST-T variations on the ECG of rabbits with acute PTE correlate strongly with the temporary changes in right heart volume caused by acute PTE. Keywords: Animal model of pulmonary embolism, B-type natriuretic peptide, Electrocardiogram, Pulmonary thromboembolism, Troponin I, Tumor necrosis factor-alpha.

Gestational diabetes mellitus (GDM) is a common disease during pregnancy that has adverse effects on both the mother and fetus. There are currently rare researches on the effect of vitamin supplementation on GDM pregnant mother and their offspring on animal and cell levels systematically. This work supplemented the GDM pregnant mouse model with vitamin D and found that vitamin D can effectively alleviate the hyperglycemia in GDM pregnant mice, increase blood insulin and adiponectin concentrations, and improve GTT and ITT in pregnant mice. In addition, vitamin D can reduce the incidence of death and high birth weight of offspring caused by GDM. The offspring of GDM pregnant mice had higher blood glucose levels in the first 5 weeks after birth compared to the normal group, and then returned to normal levels. Vitamin D can alleviate abnormal glucose metabolism in newborn mice. The therapeutic effect exhibited by vitamin D may be due to their anti-inflammatory effects, as vitamin D supplementation significantly reduces the levels of TFN-?, MCP-1, IL-1? and IL-8 in the blood. Vitamin D also regulates liver lipid metabolism, resulting in a decrease in liver lipid accumulation and a decrease in blood triglycerides (TG) and cholesterol (CHO). The results of this study demonstrate that vitamin D supplementation can serve as an effective treatment strategy for alleviating GDM symptoms. Keywords: Gestational diabetes mellitus, Vitamin D, Glucose metabolism, Anti-inflammatory.

The effects of alpha-pinene (AP), a monoterpenoid, known for its antioxidant, anti-inflammatory, and anti-apoptotic properties, on methotrexate (MTX)-induced cardiac and hepatic damage were investigated in this study. Male Sprague-Dawley rats were divided into Control, Vehicle, AP, MTX, and AP+MTX groups (n=7). AP (50 mg/kg/day, 14 days) was applied subcutaneously in the AP and AP+MTX groups. MTX (20 mg/kg) was injected three days before sacrification. Serum CK-MB, troponin T, ALT, and AST levels, as well as cardiac and hepatic MDA, GSH, caspase-3, and p53 levels, were measured by ELISA. Histological changes in tissues were evaluated by scoring in terms of tissue damage and cellular degeneration parameters after hematoxylin-eosin staining. MTX caused significant increase in serum CK-MB, troponin T, ALT, and AST levels, hepatic and cardiac lipid peroxidation, GSH depletion, and caspase-3 level. However, tissue levels of p53 did not change significantly. MTX-induced histological deterioration was observed in both tissues. These MTX-induced changes were significantly reduced in the AP+MTX group. Present results show that MTX-induced cardiac and hepatic damage is prevented by AP pretreatment. This protection can be attributed to the antioxidant and anti-apoptotic properties of AP. Considering the importance of MTX in cancer treatment, AP appears to have highly promising potential as a cardioprotective and hepatoprotective agent in anti-tumoral therapy. Key words: MDA, GSH, Caspase-3, p53, Oxidative stress, Apoptosis.

Once considered a metabolic waste product, today it is considered an important signaling molecule continuously forming under aerobic conditions. Lactate, a molecule primarily known as a byproduct of glycolysis, has gained importance in recent years due to its multifaceted role in various biological processes. Misconceptions surrounding lactate have persisted for centuries, especially the belief that elevated lactate levels were solely a result of low oxygen levels shaped early understanding. However, current research challenges this view and expands our comprehension of lactate's various roles. Unfortunately, despite all of the mentioned above lactate is rooted in modern society as a deterrent word and many people do not know its value in the human body, let alone clinical implementations or physical performance. The main goal of this review is to refresh current knowledge regarding lactate research and spread the overall information among a professional society. Key words: Lactate, Lactate metabolism, Lactic acid, Disease metabolism, Lactate shuttle.

Measuring T cell response can add information about antivirus immunity provided by antibody test results. The study evaluates the impact of a third mRNA COVID-19 vaccine dose on T cell response and antibody production in kidney transplant recipients (25 KTRs) versus healthy controls (26 Hc). Results show a significant rise in S-activated CD4+CD154+IFN?+TNF?+ double producer cells in both KTRs (p=0.025) and Hc (p=0.009) as well as increased spike antibody response in KTRs (p=0.00019) and Hc (p=3.10-8) third-month post-third dose. Moreover, the study revealed a drop in seronegative KTRs (non-responders) from 9/25 (36%) pre-third dose to 2/25 (7%) at 3 months post-third dose while 5/9 (56%) of non-responders post-second dose showed specific T cell responses. Notably, the third dose significantly improved seroconversion rates in both KTRs and Hc, although Hc individuals exhibited higher antibody levels. Key words: mRNA COVID-19 vaccine, T cells, SARS-CoV-2 antibodies, Kidney transplantation, mRNA vaccination.

Idiopathic pulmonary fibrosis (IPF) is a severe and currently incurable disease that is associated with irreversible fibrotic remodeling of the lung parenchyma. Pathological remodeling of the lung leads to damage of the alveolo-capillary barrier. There is a reduction in the diffusing capacity of the lungs for respiratory gases. Later, changes in the mechanical properties of lung tissue occur - their compliance decreases and respiratory work increases. Impaired respiratory gases exchange with restrictive ventilatory failure lead to tissue hypoxia and muscle weakness. Progressive respiratory insufficiency develops. The triggers of fibrotic remodeling of the lung are currently unknown, as are the pathomechanisms that keep this process active. IPF can only be slowed pharmacologically, not reversed. It is therefore very important to start its treatment as soon as possible. Early detection of IPF patients requires a multidisciplinary approach. Diagnosis, treatment initiation, and monitoring in specialized centers offer the best chance of slowing disease progression, enhancing quality of life, and extending patient survival. In addition to antifibrotic therapy, good lifestyle management, maintenance of physical fitness and treatment of associated chronic diseases such as diabetes and cardiac comorbidities are important. Lung transplantation is an option for some patients with IPF. This is a challenging treatment modality, requiring close collaboration with transplant centers and expert selection of suitable candidates, influenced, among other things, by the availability of suitable donor lungs. Our article aims to provide current information about IPF, focusing on its functional consequences and clinical manifestation. We discuss the molecular and cellular mechanisms potentially involved in IPF development, as well as the morphological changes observed in lung biopsies and high-resolution computed tomography (HRCT) images. Finally, we summarize the existing treatment options. Key words: Idiopathic pulmonary fibrosis, Lung biopsy, HRCT, Antifibrotic therapy, Lung transplantation.