Physiological research最新文献

Bone nonunion delays fracture end repair and is associated with inflammation. Although bone nonunion can be effectively repaired in clinical practice, many cases of failure. Studies have confirmed that BMP-2 and nHA/PA66 repaired bone defects successfully. There are few studies on the effects of the combined application of BMP-2 and NHA/PA66 on bone nonunion osteogenesis and inflammation. We aimed to investigate the expression level of inflammation-related genes in patients with bone nonunion and the effect of BMP-2-infected mesenchymal stem cells combined with nHA/PA66 on the level of inflammation in femur nonunion rats. We searched for a gene expression profile related to bone nonunion inflammation (GSE93138) in the GEO public database. Bone marrow mesenchymal stem cells (MSCs) of SD rats were cultured and passed through. We infected the third generation of MSCs with lentivirus carrying BMP-2 and induced the infected MSCs to bone orientation. We detected the expression level of BMP-2 by RT-PCR and the cell viability and alkaline phosphatase (ALP) activity by CCK8 and then analyzed the cell adhesion ability. Finally, the levels of related inflammatory factors, including C-reactive protein (CRP), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha) and Erythrocyte Sedimentation Rate (ESR), were detected in nonunion rats. Our findings: The patients with nonunion had up-regulated expression of 26 differentially inflammatory genes. These genes are mainly enriched in innate immune response, extracellular region, calcium ion binding, Pantothenate and CoA biosynthesis pathways. The expression level of BMP-2 in the Lenti-BMP-2 group was higher (vs. empty lentivirus vector group: t=5.699; vs. uninfected group t=3.996). The cell activity of the MSCs + BMP-2 + nHA/PA66 group increased gradually. After being combined with nHA/PA66, MSCs transfected with BMP-2 spread all over the surface of nHA/PA66 and grew into the material pores. MSCs + BMP-2 + nHA/PA66 cells showed positive ALP staining, and the OD value of ALP was the highest. The levels of CRP, IL-6, TNF-alpha, and ESR in the MSCs + BMP-2 + nHA/PA66 group were lower than those in the MSCs and MSCs + nHA/PA66 group but higher than those in MSCs + BMP-2 group. The above comparisons were all P<0.05. The findings demonstrated that the expression level of inflammation-related genes increased in the patients with bone nonunion. The infection of MSCs by BMP-2 could promote the directed differentiation of MSCs into osteoblasts in the bone marrow of rats, enhance the cell adhesion ability and ALP activity, and reduce inflammation in rats with bone nonunion.

The aim of the study was to examine the potential role of mitochondrial permeability transition pore (mPTP) in the cardioprotective effect of chronic continuous hypoxia (CH) against acute myocardial ischemia/reperfusion (I/R) injury. Adult male Wistar rats were adapted to CH for 3 weeks, while their controls were kept under normoxic conditions. Subsequently, they were subjected to I/R insult while being administered with mPTP inhibitor, cyclosporin A (CsA). Infarct size and incidence of ischemic and reperfusion arrhythmias were determined. Our results showed that adaptation to CH as well as CsA administration reduced myocardial infarct size in comparison to the corresponding control groups. However, administration of CsA did not amplify the beneficial effect of CH, suggesting that inhibition of mPTP opening contributes to the protective character of CH.

Repetitive transcranial magnetic stimulation (rTMS) represents a non-invasive therapeutic modality acknowledged for augmenting neurological function recovery following stroke. Nonetheless, uncertainties remain regarding its efficacy in promoting cognitive function recovery in patients diagnosed with vascular dementia (VD). In this study, VD was experimentally induced in a rat model utilizing the bilateral common carotid artery occlusion method. Following a recuperation period of seven days, rats were subjected to high-frequency repetitive transcranial magnetic stimulation (HF-rTMS) at a frequency of 10 Hz. Cognitive function was assessed utilizing the Morris water maze test, and the levels of IL-6, TNF-alpha, SOD, GSH, MDA, and Fe2+ in cerebral tissue were quantitatively analyzed through enzyme-linked immunosorbent assay. Moreover, the gene and protein expressions of nuclear factor erythroid 2-related factor 2 (Nrf2) and glutathione peroxidase 4 (GPx4) were meticulously investigated via quantitative polymerase chain reaction (qPCR) and Western blotting techniques. The use of HF-rTMS notably augmented cognitive function in rats with VD, concomitantly reducing neuroinflammation, oxidative stress, and ferroptosis within the brain. The group subjected to HF-rTMS demonstrated an increase in the levels of both proteins and genes associated with Nrf2 and GPx4, in comparison to the VD group. These results highlight the potential of HF-rTMS treatment in enhancing cognitive function in rats diagnosed with VD through the modulation of the Nrf2/GPx4 signaling pathway. This modulation, in turn, mitigates processes linked with neuroinflammation, oxidative stress, and ferroptosis. Nevertheless, additional studies are essential to comprehensively elucidate the underlying mechanisms and clinical implications of HF-rTMS treatment in the treatment of VD.

Primary graft failure occurs 15 to 30 % of the time after transplantation. Although there have been improvements in preserving the lungs in good condition, there have not been studies on the regulation of transcription factors.

Methods: We carried out an experimental study involving lung transplantation to indirectly evaluate reactive oxygen species (ROS) production and VEGF expression by competitive blockade of HIF-1alpha with chetomin. There were 5 groups: Group-1: Lung blocks were perfused with 0.9 % SSF, immediately harvested, and preserved. Group-2 (I-T): Immediate transplantation and then reperfusion for 1 h. Group-3 (I-R): Lung blocks were harvested and preserved in LPD solution for 6 h and reperfused for 1 h. Group-4 (DMSO): Lung blocks were treated for 4 h with DMSO, preserved for 6 h and transplanted to a receptor treated with DMSO. Group-5 (chetomin): Lung blocks were treated for 4 h with chetomin, preserved for 6 h and transplanted to a receptor treated with chetomin. ROS, mRNA, and protein levels of HIF-1alpha and EG-VEGF were determined.

Results: The DMSO and chetomin groups had significantly lower ROS levels. Compared with those in the I-R group, the chetomin group exhibited the lowest level of HIF-1alpha.

Conclusions: Addition of chetomin to the donor and the receptor results in a significant reduction in HIF-1A, VEGF and ROS.

Effort-based decision-making is particularly relevant to psychiatric conditions where motivation deficits are prominent features. Despite its clinical significance, the neurochemical mechanisms of this cognitive process remain unclarified. This study explores the impact of serotonin synthesis inhibition (PCPA) and modulation of serotonin release and 5-HT1A receptor agonism (8-OH-DPAT) on effort-based decision-making in rats. Adult male rats were trained in a modified T-maze task where they could obtain a high reward for climbing a mesh barrier or a low reward for no extra effort. Following training, rats received either acute 8-OH-DPAT treatment or subchronic PCPA treatment and were tested on their choices between high- and low-effort arms. The goal-arm choices and goal-arm entrance latencies were recorded. Next, homovanillic acid and 5-hydroxyindoleacetic acid, metabolites of dopamine and serotonin, respectively, were quantified in the rats' prefrontal cortex, striatum, and hippocampus. 8-OH-DPAT significantly increased low-effort, low-reward choices and increased goal-arm latency. In contrast, PCPA treatment did not affect these measures. Both PCPA and 8-OH-DPAT significantly decreased 5-hydroxyindoleacetic acid levels in the prefrontal cortex and the hippocampus. 8-OH-DPAT treatment was also associated with decreased homovanillic acid levels in the hippocampus. Our findings suggest that the overall reduction of serotonin levels alone does not affect effort-based decision-making and highlights the possible role of the hippocampus and the 5-HT1A receptor in this cognitive process.

Infiltrated and activated M1 macrophages play a role in kidney injury and fibrosis during chronic kidney disease (CKD) progression. However, the specific ways that M1 macrophage polarization contributes to renal fibrosis are not fully understood. The study seeks to investigate how miR-92a-3p regulates M1 macrophage polarization and its connection to renal fibrosis in the development of CKD. Our results revealed that miR-92a-3p overexpression increased M1-macrophage activation, iNOS, IL-6, and TNF-alpha expression in RAW264.7 upon LPS stimulation. LIN28A overexpression reversed these effects. Moreover, miR-92a-3p overexpression in RAW264.7 exacerbated NRK-52E cell apoptosis induced by LPS, but LIN28A overexpression counteracted this effect. MiR-92a-3p knockout in unilateral ureteral obstruction (UUO) C57BL/6 mice led to reduced renal infiltration and fibrosis, accompanied by decreased iNOS, alpha-SMA, IL-6, TNF-alpha, and increased LIN28A. In summary, our findings suggest that miR-92a-3p may play a role in promoting renal injury and fibrosis both in vitro and in vivo. This effect is potentially achieved by facilitating M1 macrophage polarization through the targeting of LIN28A.

The potential of microRNAs to protect the female reproductive system from the toxic influence of oil-related environmental contaminants has not yet been examined. The aim of the present study was to examine the ability of the microRNA miR-152 to prevent the toxic effects of toluene on ovarian cells. Porcine ovarian granulosa cells transfected or not transfected with miR-152 mimics were cultured with or without toluene (0, 10 and 100 ng/ml). The expression of miR-152; cell viability; proliferation (accumulation of PCNA, cyclin B1 and BrdU); cytoplasmic/mitochondrial apoptosis (accumulation of bax and caspase 3); and release of progesterone, testosterone and estradiol were quantified via RT-qPCR, the Trypan blue exclusion test, quantitative immunocytochemistry, the BrdU assay and ELISA. The addition of toluene reduced cell viability, decreased the levels of all the measured markers of proliferation and the release of all the measured steroid hormones, and promoted the expression of apoptosis markers. Transfection of cells with miR-152 mimics increased the expression of miR-152, cell proliferation, and progesterone release but reduced apoptosis and the release of testosterone and estradiol. Moreover, miR-152 prevented or inhibited all the toluene effects in addition to its inhibitory effect on testosterone and estradiol release. The present results demonstrate that miR-152 can protect ovarian cells from the harmful influence of toluene.

Trimethylamine N-oxide (TMAO), a bioactive metabolite of gut microbes, plays a pivotal role in the pathogenesis of kidney diseases by activating programmed cell death (PCD) pathways. However, whether trimethylamine (TMA) contributes to chronic kidney injury and which kind of PCD is involved in TMA-induced chronic kidney injury has not been previously evaluated. To observe the effect of TMA, male C57BL/6J mice were randomly divided into two groups: the Control group and the TMA group. The mice in the TMA group were intraperitoneally injected with 100 micromol/kg/day TMA for three months, whereas the mice in the Control group were injected with normal saline for the same period. After three months, plasma creatinine and blood urea nitrogen levels, indicators of kidney function, increased significantly in the TMA group as compared with those in the Control group. Furthermore, Masson staining assay showed that TMA treatment led to a larger area of fibrosis than the Control group. TMA treatment did not change the Bax/Bcl-2 ratio, RIP1, RIP3 and MLKL phosphorylation, or iron and malondialdehyde levels in kidney tissues, indicating that apoptosis, ferroptosis and necroptosis were not involved in TMA-induced chronic kidney injury. However, compared with the Control group, TMA treatment significantly upregulated NLRP3, Caspase-1, IL-1beta, cleaved-Caspase 8, Caspase-8, and ZBP1 protein expression in kidney tissues. These results indicated that the ZBP1-NLRP3 inflammasome pathway was involved in TMA-induced chronic kidney injury. In conclusion, our studies revealed that the ZBP1-NLRP3 inflammasome may take part in the progression of TMA induced chronic kidney injury.

The mechanism of rotator cuff injury remains to be elucidated. And COX-2 plays a dual role in skeletal muscle injury and regeneration, would be associated with the development of rotator cuff injury. Therefore, we chose human skeletal muscle cells (HSKMC) as an in vitro muscle tissue model and transfected lentivirus with overexpressed COX-2 to simulate the in vitro environment of rotator cuff injury. To investigate the specific molecular biological mechanism of COX-2, transcriptome sequencing (RNA-Seq) was used to analyze the differentially expressed mRNAs in HSKMC overexpressing COX-2. Enrichment analysis was performed to analyze these differentially expressed genes and real-time quantitative PCR (RT-qPCR) was used to examine the mRNA levels of genes induced by overexpression. Subsequently, the role of COX-2 in cell proliferation was confirmed by cell counting kit-8 (CCK-8), and focal adhesion kinase (FAK) and signal transducer and activator of transcription 3 (STAT3) phosphorylation induced by COX-2 was utilized by western blotting (WB). The results showed that total of 30,759 differentially expressed genes were obtained, and the expression of CYP4F3 and GPR87 was significantly increased. COX-2 could bind CYP4F3 and GPR87 and co-localize with them in the cytoplasm. Finally, COX-2 promoted the proliferation of human skeletal muscle cells by activating the FAK and STAT3 pathways.