Neuroprotective effects of a novel peptide through the Rho-integrin-Tie2 and PI3K/Akt pathways in experimental autoimmune encephalomyelitis model.

Purpose: The interaction between inflammatory cells and integrin in the endothelium plays a key role during infiltration. Previous evidence has shown that synthetic C16 peptide selectively binds to integrins αvß3 and α5ß1 and exhibits a neuroprotective effect. It has also been reported to inhibit the differentiation of microglia into the M1 (pro-inflammatory) phenotype while promoting its differentiation to the M2 (anti-inflammatory) phenotype. This study aimed to investigate the mechanisms of action of the C16 peptide in multiple sclerosis using a rodent model. Methods: Molecular, morphological, and neurophysiological assays were used to investigate the neuroprotective effects of C16 peptide and related signaling pathways in a model of EAE. Results: The results showed that C16 significantly improved the clinical score and cortical somatosensory/motor evoked potential. It also alleviated inflammatory responses, including microglial activation and leukocyte infiltration, relieved the impairment of the brain blood barrier and edema, and reduced neuronal apoptosis, axonal loss, and demyelination induced by EAE. The C16 peptide increased the expressions of pTie-2 and Tie-2, integrin αvß3, and α5ß1 and activated the PI3K/Akt signal pathway but decreased the expression of Rho. Co-treatment of C16 with Tie-2 inhibitor and PI3K inhibitor LY294002 attenuated these effects of C16. Conclusion: The C16 peptide demonstrated neuroprotection in the EAE model through the integrin, Tie-2, and PI3K/Akt signaling pathways, and it could be a potential strategy for treating inflammation-related diseases in the central nervous system.

Expression of aldose reductase in mouse endometrial epithelial cells and its role in sperm capacitation.

The survival, motility and capacitation of sperm in the female reproductive tract are important prerequisites for fertilization. The uterus is the main location for sperm capacitation. One of the most important physiological functions of the endometrial epithelium is to create a suitable uterine environment under the regulation of ovarian hormones, to ensure sperm capacitation. The composition of uterine fluid directly affects sperm capacitation. Fructose is an important component of semen that supports sperm viability and motility. Aldose reductase, a rate-limiting enzyme in the polyol pathway, metabolizes sorbitol and fructose, thereby supplying cells with necessary energy for functional activities. Existing studies have reported the presence aldose reductase in the endometrium, leading us to hypothesize that its expression in endometrial epithelium might promote sperm capacitation by maintaining the uterine environment. Yet, the mechanism of regulation has not been clarified. In this study, we investigated the expression of aldose reductase in mouse endometrial epithelium and its potential role in sperm capacitation. We initially investigated the periodic characteristics of glucose, fructose and sorbitol in uterine fluid. We then studied the temporal and spatial characteristics of aldose reductase in the endometrial epithelium. Next, we examined the effect of aldose reductase on glucose, fructose and sorbitol in uterine fluid. Finally, we explored the effect of aldose reductase on sperm capacitation and fertilization. The results showed that glucose and fructose content in uterine fluid and the expression of aldose reductase fluctuated periodically during physiological periods. Inhibition of aldose reductase in the endometrial epithelium interfered with sperm capacitation and fertilization by reducing the fructose levels in the uterine fluid. To conclude, the aldose reductase-mediated polyol pathway in endometrial epithelial cells is essential to maintain an appropriate fructose environment in the uterine fluid for sperm capacitation and fertilization.

Effect of systolic blood pressure fluctuations during resuscitation on postoperative complications following meningioma surgery: A retrospective observation study.

It is unclear whether blood pressure variability in the post-anesthesia care unit is associated with postoperative complications. This study aims to characterize the impact of blood pressure fluctuations on postoperative complications and postoperative length of stay after meningioma surgery. Adult meningioma patients undergoing general anesthesia were retrospectively recruited. The principal exposure was blood pressure variability in the post-anesthesia care unit, calculated by noninvasive blood pressure measurements. The primary outcome was major postoperative complications, defined as II or higher in the Clavien-Dindo classification grades. Secondary outcomes included healthcare resource utilization parameters among patients. Multivariable logistic regression was used and adjusted for potential confounding variables. Data sensitivity analyses were performed via different variable transformations and propensity score matching analyses. A total of 578 patients qualified for the study, and 161 (27.9%) cases experienced postoperative complications. The multivariable analysis found that increased systolic blood pressure variability in the post-anesthesia care unit was associated with postoperative complications (adjusted odds ratio [aOR] = 1.15; 95% confidence interval [CI], 1.09-1.22, P < .001) and prolonged postoperative length of stay (adjusted regression coefficients [ß] = 1.86; 95% CI, 0.58-3.13, P = .004). Patients with postoperative complications had a higher frequency of intensive care admission (44.1% vs 15.3%), major postoperative interventions (6.6% vs 0%), and 30-day readmission (5.0% vs 0.7%). Systolic blood pressure fluctuations during resuscitation have an independent impact on postoperative complications and postoperative length of stay following meningioma surgery.

MicroRNA-27a regulates angiotensin II-induced vascular smooth muscle cell proliferation and migration by targeting α-smooth muscle-actin in vitro.

Angiotensin II (Ang II) modulates VSMCs phenotypic switch that play a critical role in the cardiovascular diseases. MicroRNA-27a (miR-27a) has been proven to be involved in regulating vascular remodeling; however, the functional role of miR-27a in VSMCs in response to Ang II stimulation need to be elucidated. Cell proliferation and migration were measured by Cell counting kit-8 (CCK-8), BrdU incorporation and scratch wound assay in VSMCs transfected with miR-27a or its inhibitor. The target of miR-27a was confirmed using bioinformatics analysis and luciferase reporter assay. Ang II treatment time-dependently increased proliferation and migration of VSMCs accompanied with downregulation of α-smooth muscle-actin (α-SMA) and upregulation of miR-27a expression. Moreover, knockdown of miR-27a in VSMCs significantly attenuated Ang II-induced cell proliferation and migration, whereas this effect was aggravated by overexpression of miR-27a. A potential mechanistic analysis revealed that miR-27a directly targeted α-SMA, which mediated miR-27a-induced cell proliferation and migration. In conclusion, these results indicate that miR-27a acts as a novel regulator of Ang II-induced proliferation and migration by directly targeting α-SMA expression in VSMCs in vitro, and may be a potential therapeutic target for treating vascular diseases.

Therapeutic Hypothermia Enhances Cold-Inducible RNA-Binding Protein Expression and Inhibits Mitochondrial Apoptosis in a Rat Model of Cardiac Arrest.

Therapeutic hypothermia is well known for its protective effect against brain injury after cardiac arrest, but the exact mechanism remains unclear. Cold-inducible RNA-binding protein (CIRP), a member of cold shock protein, enables mammalian cells to withstand decreased temperature by regulating gene translation. However, the role of CIRP in global cerebral ischemia after therapeutic hypothermia has not been clearly elucidated. In the present study, rats resuscitated from 4 min of cardiac arrest were separately treated with therapeutic hypothermia (immediately after return of spontaneous circulation (ROSC); targeted temperature at 33 °C) and therapeutic normothermia (targeted temperature at 36.8 °C) for 6 h. The hippocampus was harvested at 0 h (baseline), 6 h, 12 h, 1 day, 3 days, and 7 days after ROSC. The expression of CIRP messenger RNA (mRNA) was assessed by real-time PCR. CIRP and mitochondrial apoptosis-associated proteins were tested by Western blot. The histological changes and neurological function were respectively evaluated by hematoxylin-eosin staining and neurological deficit score (NDS). Compared with baseline, rats resuscitated from cardiac arrest showed increased expression of CIRP, Bax, Caspase 9, and Caspase 3 and decreased expression of Bcl-2 in hippocampus (P < 0.05). However, therapeutic hypothermia after ROSC alleviated the alterations of Bax, Caspase 9, Caspase 3, and Bcl-2, while further increased the hippocampal expression of CIRP mRNA and protein, when compared with the normothermia rats (P < 0.05). In addition, compared with the therapeutic normothermia rats, histopathological damage in CA1 zone and NDS were respectively decreased and increased in the hypothermia rats (P < 0.05). Our findings suggest that 32 °C therapeutic hypothermia exerts an important neuroprotective effects by up-regulating CIRP expression and inhibiting mitochondrial apoptosis factor production in the cardiac arrest rat model.

[Effect of terracing project on temporal-spatial variation of non-point source pollution load in Hujiashan watershed, China]. / 坡改梯工程对胡家山小流域非点源污染负荷时空变化的影响.

Taking Hujiashan small watershed as the study area, based on the classified result of Landsat TM/ETM images of 2005, 2010 and 2015, combined with long-term field observation data, and used the export coefficient model, our study explored the effect of small watershed management project on temporal and spatial variation of total nitrogen (TN) load of non-point source pollution under the support of GIS technology. The results indicated that, due to the implementation of slope modification project, the area of cultivated land was significantly increased, while forest and bareland were decreased. The load of non-point source TN increased from 63208 kg in 2005 to 72778 kg in 2010, but reduced to 46876 kg in 2015. The contribution rate from residential areas was higher, the average contribution rate of the three periods was 53.5%, but it showed a decreasing trend year by year. The contribution rate of land use types was 45%, which showed an increasing trend year by year. The contribution rate of livestock was always low. From the spatial distribution, TN loading intensity was changed obviously after the terracing project. High load intensity zone was mainly concentrated on the slope of 5°-15° before terracing project. Nevertheless, high load intensity zone was concentrated on the slope of 15°-35° after terracing project, and 5°-8° had become a low load strength area. The TN load intensity changed little with time on the slope of 0°-8°, and it increased first and then decreased on the slope above 8°. With the treatment of sewage, garbage and livestock manure in rural areas, the output of nitrogen in the living and livestock breeding were significantly reduced. Due to the implementation of the project, the cultivated land area increased by 31%.

[Temporal variation of soil net nitrogen mineralization in summer maize growing period under plastic film mulched cultivation in Danjiangkou Reservoir Area, China.] / 丹江口库区覆膜耕作土壤净氮矿化随夏玉米生长期的变化.

Soil net nitrogen mineralization in cropland has a great influence on both agricultural non-point source pollution and soil nitrogen loss. A field plot experiment was conducted to explore the temporal variation of soil net nitrogen mineralization under plastic film mulching ridge-furrow in Wulongchi small watershed during summer maize growing period. Results showed that the soil net ammonification, nitrification, and nitrogen mineralization were significantly greater than those of non-mulched treatment, and the differences were 6.63, 12.96 and 19.59 mg·kg-1, respectively. During the summer maize growth period, the rate of soil net ammonification was high at seedling stage, low at heading stage, and high at maturation stage. Both the rates of soil net nitrification and nitrogen mineralization were high at jointing stage, low at heading stage, and high at maturation stage. The rate of soil net nitrogen mineralization under plastic film mulched had significant linear relation with the contents of soil total nitrogen, nitrate nitrogen, and soil water. In conclusion, the improved condition of soil water and temperature under plastic film mulched cultivation of summer maize in the growing period promoted soil net nitrogen mineralization.

[Change of Soil Nitrogen Leaching with Summer Maize Growing Periods Under Plastic Film Mulched Cultivation in Danjiangkou Reservoir Area, China].

As an important form of agricultural non-point source pollution, soil nitrogen leaching deteriorates water quality. Compared with non-mulching cultivated land, field experiment explored the change characteristics of soil nitrogen leaching under plastic film mulching ridge-furrow in Wulongchi small watershed during summer maize growing period. The results showed that the amounts of mulching tillage soil TN and NO3--N leaching were significantly lower than those with non-mulched treatment, by 25.68% and 20.25%, respectively. With the advance of the summer maize growth period, leaching amount of mulched soil TN was highest at seedling stage, lowest at heading stage and higher in maturation period; leaching amount of mulched soil NO3--N was highest at seedling stage, lowest in maturation period; leaching amount of mulched soil NH4+-N was lower at seedling stage, increased to the peak at the jointing stage, decreased to the valley value at heading stage, and obviously increased in maturation period. Linear function relationship was found between mulched soil TN leaching and TN content, while exponential relationship was found between mulched soil NO3--N leaching and NO3--N content. In addition, there was linear function relationship of mulched soil TN and NO3--N leaching amount with soil moisture and rainfall. It was concluded that the plastic film mulched on summer maize could reduce the leaching loss of soil nitrogen, and it would have a significant effect on the reduction of reservoir area of agricultural non-point source pollution.

Mild Hypothermia Combined with Hydrogen Sulfide Treatment During Resuscitation Reduces Hippocampal Neuron Apoptosis Via NR2A, NR2B, and PI3K-Akt Signaling in a Rat Model of Cerebral Ischemia-Reperfusion Injury.

We investigated whether mild hypothermia combined with sodium hydrosulfide treatment during resuscitation improves neuron survival following cerebral ischemia-reperfusion injury beyond that observed for the individual treatments. Male Sprague-Dawley rats were divided into seven groups (n = 20 for each group). All rats underwent Pulsinelli 4-vessel occlusion. Ischemia was induced for 15 min using ligatures around the common carotid arteries, except for the sham group. Immediately after initiating reperfusion, the mild hypothermia (MH), sodium hydrosulfide (NaHS), hydroxylamine (HA), MH + NaHS, MH + HA, and ischemia-reperfusion (I/R) control groups received an intraperitoneal injection of saline, sodium hydrosulfide, hydroxylamine, sodium hydrosulfide, hydroxylamine, and saline, respectively, and mild hypothermia (32 to 33 °C) was induced in the MH, MH + NaHS, and MH + HA groups for 6 h. The levels of NR2A, NR2B, p-Akt, and p-Gsk-3ß in the hippocampus of the MH, NaHS, and MH + NaHS groups were higher than those in the I/R control group, with the highest levels observed in the MH + NaHS group (P < 0.05). Treatment with hydroxylamine reduced the levels of these proteins in the HA and MH + HA groups, compared with the I/R control and MH groups, respectively. The apoptotic index of the CA1 region of the hippocampus was 45.2, 66.5, 63.5, and 84.8 % in the MH + NaHS, MH, NaHS, and I/R control groups, respectively (P < 0.05), indicating that the combination treatment shifted the NR2A/NR2B balance in favor of synaptic neuron stimulation and phosphatidylinositol 3'-kinase (PI3K)/Akt signaling. The combination of mild hypothermia and sodium hydrosulfide treatment for resuscitation following ischemia-reperfusion injury was more beneficial for reducing hippocampal apoptosis and pathology than that of mild hypothermia or hydrogen sulfide treatment alone.

[Influence of soil factors on quality of panacis majoris rhizoma].

OBJECTIVE: To research and screen the soil factors which influenced the quality of Panacis Majoris Rhizoma. METHODS: By determining the effective constituent of saponin of Panacis Majoris Rhizoma from different habitats, and the soil nutrient and heavy metal content, using correlation analysis, stepwise regression analysis and other statistical methods to analyze the soil factors on the quality of Panacis Majoris Rhizoma. RESULTS: The contents of ginsenoside Ro and chikusetsusaponin NVa of samples from different habitats were different, the corresponding soil nutrient and heavy metal content were also different. The content of ginsenoside-Ro was positively related with the soil pH value (P <0. 01) and negatively related with the soil available N(P < 0.05). The content of chikusetsusaponin IVa was positively related with the soil pH (P < 0.01) and copper content (P < 0.05), and negatively with the soil available N(P < 0.05) CONCLUSION: Soil factors are the leading factors that influence the quality of Panacis Majoris Rhizoma, soil pH and soil available N were the dominating factors.