A pilot study: Gut microbiota, metabolism and inflammation in hypertensive intracerebral haemorrhage.

AIMS: In recent years, the incidence rate of hypertensive intracerebral haemorrhage (HICH) has been increasing, accompanied by high mortality and morbidity, which has brought a heavy burden to the social economy. However, the pathogenesis of HICH is still unclear. This study intends to explore the mechanism of gut microbiota metabolism and inflammation in the process of HICH to provide a theoretical basis for the diagnosis and treatment of HICH. METHODS AND RESULTS: HE staining showed that the brain tissues of model group had obvious oedema injury, which indicated that the HICH model was successfully constructed. ELISA analysis showed that IL-1ß and TNF-α levels in blood and brain tissues were significantly increased, and IL-10 level was significantly decreased in blood. IHC analysis showed that microglia and macrophages were activated in the model group. 16S rRNA sequence showed that the diversity of gut microbiota in HICH patients decreased. Also, the microbiota belonging to Firmicutes, Proteobacteria and Verrucomicrobia changed significantly. LC-MS/MS analysis showed that the metabolic phenotype of HICH patients changed. Also, the 3,7-dimethyluric acid- and 7-methylxanthine-related metabolic pathways of caffeine metabolism pathways were downregulated in patients with HICH. Bacteroides was negatively correlated with the IL-1ß and TNF-α levels. Blautia was negatively correlated with the IL-1ß and TNF-α levels, and positively correlated with the IL-10 level. Akkermansia was negatively correlated with the 3,7-dimethyluric acid and 7-methylxanthine. CONCLUSION: Our study suggested that HICH was accompanied by the increased inflammation marker levels in peripheral blood and brain, decreased gut microbiota diversity, altered gut metabolic phenotype and downregulation of caffeine metabolism pathway. SIGNIFICANCE AND IMPACT OF THE STUDY: Our study reported that HICH accompanied by the increased inflammation, decreased gut microbiota diversity and altered gut metabolic phenotype. Due to the number of patients, this work was a pilot study.

TUBA1C expression promotes proliferation by regulating the cell cycle and indicates poor prognosis in glioma.

Gliomas are the major type of primary brain tumors. Accumulating research has demonstrated that tubulin is connected with the development and malignant progression of tumors. TUBA1C is a subtype of α-tubulin and is linked to prognosis in multiple cancers. In this study, the prognosis-related gene TUBA1C in glioma was identified and analyzed by bioinformatic approaches such as Kaplan-Meier (KM) survival time analysis, univariate and multivariate Cox analysis, receiver operating characteristic (ROC) analysis and functional enrichment analysis. Based on the above analyses, we found that glioma tissues had significantly higher expression of TUBA1C than normal brain tissues, and high expression of TUBA1C has worse prognosis in glioma. Gene set enrichment analysis (GSEA) revealed the signaling pathways related to the cell cycle. Furthermore, knockdown of TUBA1C also inhibited proliferation and migration and caused apoptosis and G2/M phase arrest in glioma cells. This study demonstrated that high TUBA1C expression correlated with poor outcomes in glioma patients and that knocking down TUBA1C suppressed glioma cell proliferation via cell cycle arrest. In addition, TUBA1C might be a therapeutic biomarker for gliomas.

Quantitative Analysis of Natural Gas Diffusion Characteristics in Tight Oil Reservoirs Based on Experimental and Numerical Simulation Methods.

As an important mechanism in gas injection development, the diffusion characteristics of natural gas in tight reservoirs are important in the dynamic prediction of the development effect and optimization of injection-production parameters. In this paper, a high-pressure and high-temperature oil-gas diffusion experimental device was built, which was used to study the effects of the porous medium, pressure, permeability, and fracture on oil-gas diffusion under tight reservoir conditions. Two mathematical models were used to calculate the diffusion coefficients of natural gas in bulk oil and cores. Besides, the numerical simulation model was established to study the diffusion characteristics of natural gas in gas flooding and huff-n-puff, and five diffusion coefficients were selected based on experimental results for simulation study. The remaining oil saturation of grids, the recovery of single layers, and the distribution of CH4 mole fraction in oil were analyzed based on the simulation results. The experimental results show that the diffusion process can be divided into three stages: the initial stage of instability, the diffusion stage, and the stable stage. The absence of medium, high pressure, high permeability, and the existence of fracture are beneficial to natural gas diffusion, which can also reduce the equilibrium time and increase the gas pressure drop. Furthermore, the existence of fracture is beneficial to the early diffusion of gas. The simulation results show that the diffusion coefficient has a greater influence on the oil recovery of huff-n-puff. For gas flooding and huff-n-puff, the diffusion features both perform such that a high diffusion coefficient results in a close diffusion distance, small sweep range, and low oil recovery. However, a high diffusion coefficient can achieve high oil washing efficiency near the injecting well. The study is helpful to provide theoretical guidance for natural gas injection in tight oil reservoirs.

Mechanism of ischemic brain injury repair by endothelial progenitor cell­derived exosomes.

Ischemic stroke is a refractory disease that seriously endangers human health and life. The main treatment aim of stroke is to alleviate brain injury. The present study aimed to investigate the effects and mechanisms of endothelial progenitor cell (EPC)­derived exosomes in repairing ischemic brain injury. Sprague­Dawley rat models of cerebral ischemia­reperfusion (IR) injury were established by middle cerebral artery occlusion. The IR model rats were then treated with PBS, EPC or exosomes; untreated and Sham rats were used as control. EPCs were obtained from tibias and femurs, and exosomes were isolated from the EPCs and characterized. To measure brain injury, 2,3,5­triphenyltetrazolium chloride staining was used to measure the infarct area, neurological deficit was scored, hematoxylin and eosin staining was used to examine pathological changes and TUNEL staining was used to quantify apoptosis. Immunofluorescence staining and reverse transcription­quantitative PCR were used to determine CD31 and VEGF protein and mRNA expressions, respectively, and western blot analysis was used out to measure the protein expression levels of Wnt3a, GSK­3ß and phosphorylated (p)­GSK­3ß. Compared with rats in the Control and Sham groups, in IR model rats the nerve fibers were slightly necrotic and swollen and the number of nerve cells was reduced. Following EPC treatment, the brain tissue exhibited mild liquefaction and degeneration in the small focus area with mild edema in the stroma. The numbers of nerve cells decreased, and the distribution of nerve cells was not very uniform; proliferation of glial cells was observed. Following treatment with exosomes, the distribution of nerve cells was more uniform with less degeneration and necrosis; the proliferation of glial cells was remarkable. Compared with the Control group, the infarct size, neurological defect score, percentage of apoptotic cells, expression of CD31, VEGF, Wnt3a, and p­GSK­3ß were significantly higher in the IR model (P<0.05). After EPC and exosome treatments, the infarct size, neurological defect score, percentage of apoptotic cells, expression of Wnt3a, and p­GSK­3ß were significantly reduced (P<0.05), whereas the mRNA and protein expression levels of CD31 and VEGF were significantly increased (P<0.05). Results from the present study demonstrated that EPC­derived exosomes may alleviate ischemic injury by inhibiting apoptosis and promoting angiogenesis. These findings suggested that exosomes may have a protective role for nerve cells and may be a potentially effective option for treating stroke. However, human clinical studies are needed to validate these findings from animals.

Kinetic Model and Numerical Simulation of Microbial Growth, Migration, and Oil Displacement in Reservoir Porous Media.

Microbial enhanced oil recovery (MEOR) is a potential tertiary oil recovery method. However, past research has failed to describe microbial growth and metabolism reasonably, especially quantification of reaction equations and operating parameters is still not clear. The present study investigated the ability of bacteria extracted from Ansai Oilfield for MEOR. Through core flooding experiments, bacteria-treated experiments produced approximately 6.28-9.81% higher oil recovery than control experiments. Then, the microbial reaction kinetic model was established based on laboratory experimental data and mass conservation. Furthermore, the proposed model was validated by matching core flooding experiment results. Lastly, the effects of different injection parameters on bacteria growth, bacteria migration, metabolite migration, residual oil distribution, and oil recovery were studied by establishing a field-scale model. The results indicate that the injected bacteria concentration and nutrient concentration have a great influence on bacteria growth in a reservoir and the low nutrient concentration seriously restricts bacteria growth. Compared with the injected bacteria concentration, nutrient concentration has a decisive effect on bacteria and metabolite migration. The injected bacteria concentration has little effect on oil recovery, while nutrient concentration and slug volume have a significant effect on oil recovery.