Effect of moderate livestock grazing on soil and vegetation characteristics in zokor mounds of different ages.

Mounds formed by plateau zokors (Eospalax baileyi) in alpine meadows are easily disturbed by livestock. We aimed to reveal the effect of moderate livestock grazing (from October 15 to March 15 of the following year) on plant and soil characteristics of zokor mounds. This study explored the effect of zokor mounds of different ages (2015-2018) on soil nutrient content, soil enzymatic activity, plant diversity, and aboveground biomass (AGB) at grazing and non-grazing sites. Compared with the non-grazing sites, soil organic carbon (SOC), total soil phosphorus, and ratio of SOC to total nitrogen were 16.6%-98.7% higher and soil urease activity was 8.4% and 9.6% higher in 1- and 3-year-old mounds, respectively, at the grazing sites. Grazing significantly increased the plant Pielou index, richness, and Shannon-Wiener diversity index of 4-year-old mounds by 20.7%-52.4%. Partial least squares path modeling showed that plant species diversity was the main factor affecting the plant AGB of mounds at the grazing sites, whereas soil enzyme activity was the primary factor at the non-grazing sites. We propose that moderate grazing increases soil nutrient content and the plant diversity in zokor mounds in alpine meadows, which should be considered in future grassland restoration.

Environmental and climatic drivers of phenotypic evolution and distribution changes in a widely distributed subfamily of subterranean mammals.

How environmental factors shape species morphology and distributions is a key issue in ecology, especially in similar environments. Species of Myospalacinae exhibit widespread distribution spanning the eastern Eurasian steppe and the extreme adaptation to the subterranean environment, providing an excellent opportunity for investigating species responses to environmental changes. At the national scale, we here use geometric morphometric and distributional data to assess the environmental and climatic drivers of morphological evolution and distribution of Myospalacinae species in China. Based on phylogenetic relationships of Myospalacinae species constructed using genomic data in China, we integrate geometric morphometrics and ecological niche models to reveal the interspecific variation of skull morphology, trace the ancestral state, and assess factors influencing interspecific variation. Our approach further allows us to project future distributions of Myospalacinae species throughout China. We found that the interspecific morphology variations were mainly concentrated in the temporal ridge, premaxillary-frontal suture, premaxillary-maxillary suture, and molars, and the skull morphology of the two current species in Myospalacinae followed the ancestral state; temperature and precipitation were important environmental variables influencing skull morphology. Elevation, temperature annual range, and precipitation of warmest quarter were identified as dominant factors affecting the distribution of Myospalacinae species in China, and their suitable habitat area will decrease in the future. Collectively, environmental and climate changes have an effect on skull phenotypes of subterranean mammals, highlighting the contribution of phenotypic differentiation in similar environments in the formation of species phenotypes. Climate change will further shrink their habitats under future climate assumptions in the short-term. Our findings provide new insights into effects of environmental and climate change on the morphological evolution and distribution of species as well as a reference for biodiversity conservation and species management.

Ginsenoside Rg1 improves Alzheimer's disease by regulating oxidative stress, apoptosis, and neuroinflammation through Wnt/GSK-3ß/ß-catenin signaling pathway.

Alzheimer's disease (AD) is a chronic neurodegenerative disorder that can cause cognitive impairment. Ginsenoside Rg1 (Rg1) has a significant neuroprotective effect on animals with memory impairment. However, the mechanism of how Rg1 mediates the Wnt signaling pathway and improves cognitive function by regulating oxidative stress, apoptosis, and neuroinflammation is still unclear. In this study, the spatial memory ability of tree shrews was tested by Morris water maze, the expression levels of amyloid protein (Aß1-42), ionized calcium-binding adapter molecule 1 (iba-1), nitrotyrosine (NT), and 8-hydroxyguanine (8-OHG) were detected by immunohistochemistry. Subsequently, the activity of catalase (CAT) and the glutathione peroxidase (GSH-Px) was, respectively, measured by the ammonium molybdate method and the 5,5'-dithiobis (2-nitrobenzoic acid). Furthermore, the malondialdehyde (MDA) concentration was determined by the thiobarbituric acid test. Finally, the expression levels of Beta-secretase (BACE1), superoxide dismutase (SOD), BCL2-Associated X (Bax), B-cell lymphoma-2 (Bcl-2), caspase-anti-apoptotic factor Cleaved-caspase-3 (Caspase-3), microtubule-associated proteins 2 (MAP2), Neuronal nuclear antigen (NeuN), as well as the phosphorylation of GSK-3ß and ß-catenin were detected by Western blot. This study implied that Rg1 reduced the phosphorylation of Tau protein, the deposition of Aß1-42, and the expression of BACE1. It also showed that Rg1 increased the antioxidant activity of SOD, CAT, GPx, and instead reduced the oxidation products of NT, 8-OHG, and MDA, as wells as the inflammatory factor interleukin-1 and iba-1. It further showed that Rg1 increased the ratio of Bcl-2 to Bax and expression of neuronal markers MAP2 and NeuN, but instead reduced the expression of Caspase-3, GSK-3ß, and ß-catenin. In conclusion, by regulating the Wnt/GSK-3ß/ß-catenin signaling pathway, Rg1 of moderate and high dose could alleviate oxidative stress damage, improve neuroinflammation, protect neurons, finally improve the cognitive impairment of the AD tree shrew. This study provides theoretical basis for the Rg1 clinical application in AD.

Dexmedetomidine at a dose of 1 µM attenuates H9c2 cardiomyocyte injury under 3 h of hypoxia exposure and 3 h of reoxygenation through the inhibition of endoplasmic reticulum stress.

Myocardial ischemia-reperfusion injury (MIRI) has been confirmed to induce endoplasmic reticulum stress (ERS) during downstream cascade reactions after the sufficient deterioration of cardiomyocyte function. However, clinically outcomes have been inconsistent with experimental findings because the mechanism has not been entirely elucidated. Dexmedetomidine (DEX), an α2 adrenergic receptor agonist with anti-inflammatory and organ-protective activity, has been shown to attenuate IRI in the heart. The present study aimed to determine whether DEX is able to protect injured cardiomyocytes under in vitro hypoxia/reoxygenation (H/R) conditions and evaluate the conditions under which ERS is efficiently ameliorated. The cytotoxicity of DEX in H9c2 cells was evaluated 24 h after treatment with several different concentrations of DEX. The most appropriate H/R model parameters were determined by the assessment of cell viability and injury with Cell Counting Kit-8 and lactate dehydrogenase (LDH) release assays after incubation under hypoxic conditions for 3 h and reoxygenation conditions for 3, 6, 12 and 24 h. Additionally, the aforementioned methods were used to assess cardiomyocytes cultured with various concentrations of DEX under H/R conditions. Furthermore, the degree of apoptosis and the mRNA and protein expression levels of glucose-regulated protein 78 (GRP78), C/EBP homologous protein (CHOP) and caspase-12 were evaluated in all groups. The addition of 1, 5 and 10 µM DEX to the cell culture significantly increased the proliferation of H9c2 cells by >80% under normal culture conditions. In the H/R model assessment, following 3 h of anoxia exposure, H9c2 cell viability decreased to 62.67% with 3 h of reoxygenation and to 36% with 6 h of reoxygenation compared with the control. The viability of H9c2 cells subjected to hypoxia for 3 h and reoxygenation for 3 h increased by 61.3% when pretreated with 1 µM DEX, and the LDH concentration in the supernatant was effectively decreased by 13.7%. H/R significantly increased the percentage of apoptotic cells, as detected by flow cytometry, and increased the expression levels of GRP78, CHOP and caspase-12, while treatment with either DEX or 4-phenylbutyric acid (4-PBA) significantly attenuated these effects. Additionally, despite the protective effect of DEX against H/R injury, 4-PBA attenuated the changes induced by DEX and H/R. In conclusion, treatment with 1 µM DEX alleviated cell injury, apoptosis and the increases in GRP78, CHOP and caspase-12 expression levels in H9c2 cells induced by 3 h of hypoxia and 3 h of reoxygenation.

Dexmedetomidine Attenuates Cellular Injury and Apoptosis in H9c2 Cardiomyocytes by Regulating p-38MAPK and Endoplasmic Reticulum Stress.

BACKGROUND: Myocardial ischaemia-reperfusion injury (IRI) has been confirmed to induce endoplasmic reticulum stress (ERS) when myocardial cell function continues to deteriorate to a certain degree. The clinical applications of effective tested strategies are sometimes inconsistent with the applications evaluated in experiments, although reasonable mechanisms and diverse signalling pathways have been broadly explored. Dexmedetomidine (DEX) has been shown to attenuate IRI of the heart in animal studies. This study aimed to determine whether DEX can protect injured cardiomyocytes under hypoxia/reoxygenation (H/R) at the cellular level and whether the mechanism is related to ERS and the p38 MAPK pathway. METHODS: H9c2 cells were subjected to H/R or thapsigargin (TG) to build a model. DEX or 4-PBA was added to the medium either 1 h or 24 h before modelling, respectively. Model parameters were determined by assessing cell viability and injury, which were measured by assessing cell counting kit-8 (CCK8), lactate dehydrogenase (LDH) release and flow cytometry results, and the expression of GRP78, CHOP and caspase-12. In addition, the protein expression of p38MAPK and p-p38MAPK was examined, and SB202190, a negative regulator, was also preincubated in medium. RESULTS: Compared to that of cells in the control group, the activity of cells in the H/R and TG groups was decreased dramatically, and the LDH concentration and proportion of apoptotic cells were increased. DEX could correspondingly reverse the changes induced by H/R or TG. Additionally, DEX effectively attenuated ERS defined as increased expression of GRP78, CHOP and caspase-12. Additionally, DEX could obviously depress the P38 MAPK phosphorylation and high p-p38 MAPK expression in the TG group, indicating DEX has a function similar to that of SB202190. CONCLUSION: H/R injury in H9c2 cells can lead to abnormal ERS and apoptosis, as well as activation of the p38MAPK signalling pathway. DEX can protect cardiomyocytes by intervening in ERS, regulating p38MAPK and the downstream apoptotic signalling pathway.

Does dexmedetomidine have an antiarrhythmic effect on cardiac patients? A meta-analysis of randomized controlled trials.

BACKGROUND: Cardiac surgery patients often experience several types of tachyarrhythmias after admission to the intensive care unit (ICU), which increases mortality and morbidity. Dexmedetomidine (DEX) is a popular medicine used for sedation in the ICU, and its other pharmacological characteristics are gradually being uncovered. PURPOSE: To determine whether DEX has an antiarrhythmic effect after cardiac surgery. METHODS: The three primary databases MEDLINE, Embase (OVID SP) and the Cochrane Central Register of Controlled Trials (CENTRAL) were searched, and all English-language and randomized control-designed clinical publications comparing DEX to control medicines for sedation after elective cardiac surgery were included. Two colleagues independently extracted the data and performed other quality assessments. A subgroup analysis was performed according to the different medicines used and whether cardiopulmonary bypass (CPB) was applied. All tachyarrhythmias that occurred in the atria and ventricles were analyzed. RESULTS: A total of 1295 patients in 9 studies met the selection criteria among 2587 studies that were screened. After quantitative synthesis, our results revealed that the DEX group was associated with a lower incidence of ventricular arrhythmia (VA, OR 0.24, 95% CI 0.09-0.64, I2 = 0%, P = 0.005) than the control group. Subgroup analysis did not reveal a significant difference between the DEX and propofol subgroups (OR 0.13, 95% CI 0.03-0.56, I2 = 0%, P = 0.007). Additionally, no difference in the incidence of atrial fibrillation (AF) was observed regardless of the different control medicines (OR 0.82, 95% CI 0.60-1.10, I2 = 25%, P = 0.19) or whether CPB was applied. CONCLUSIONS: This meta-analysis revealed that DEX has an antiarrhythmic effect that decreases the incidence of VA compared to other drugs used for sedation following cardiac surgery. DEX may not have an effect on AF, but cautious interpretation should be exercised due to high heterogeneity.

Can dexmedetomidine reduce atrial fibrillation after cardiac surgery? A systematic review and meta-analysis.

PURPOSE: Cardiac surgery patients always present with atrial fibrillation (AF) after admission to the intensive care unit, leading to high mortality and lengthy hospitalization. Dexmedetomidine (DEX) is a popular medication used for sedation in the intensive care unit; however, whether it can reduce AF needs to be analyzed. MATERIALS AND METHODS: Three primary databases, Medline, Embase (Ovid SP) and the Cochrane Central Register of Controlled Trials (CENTRAL), were searched. All English language and randomized control designed clinical publications comparing DEX to control medicines for sedation after elective cardiac surgery were included. Two independent colleagues conducted the data extraction and quality assessments. The subgroup analysis was performed according to the medicine used, age, AF history, and whether previous beta-blocker premedication and cardiopulmonary bypass (CPB) were applied. The overall incidence of AF was analyzed. RESULTS: A total of 1,295 patients in nine studies met the selection criteria among 2,587 studies screened from the database. After quantitative synthesis, our results revealed that the DEX group was not associated with a decreased incidence of AF compared with the placebo (risk ratio [RR] 0.76, 95% CI 0.37, 1.55, P=0.44) and morphine groups (RR 0.86, 95% CI 0.56, 1.31, P=0.48). Subgroup analysis also indicated that the DEX vs propofol comparison exhibited no difference: 1) for patients of age >60 years (P=0.69) or ≤60 years (P=0.69); 2) under CPB surgery (P=0.45) or without CPB surgery (P=0.88); 3) with beta-blocker premedication (P=0.32) or without beta-blocker premedication (P=0.90); and 4) with AF history (RR 1.07, 95% CI 0.85, 1.36, P=0.57) or without AF history (P=0.30). CONCLUSION: This meta-analysis revealed that DEX could not reduce the incidence of AF compared to control medicines following cardiac surgery. DEX may have an increased influence on AF occurrence if patients had a history of AF. However, cautious interpretation should be made due to high clinical heterogeneity.

Thymus-expressed chemokine promotes survival of PC12 cells via PI3K pathway.

We reported previously that CCR9 was neuroprotective in the mouse hippocampal neurons. This study was aimed to investigate if thymus-expressed chemokine (TECK)/CCL25 could promote survival of PC12 cells though its receptor CCR9. pEGFP-N1/CCR9 recombinant was constructed and transfected into PC12 cells. Along with this, 50 nM NGF was used to induce PC12 cells to differentiate into sympathetic-like neurons. We show here that under serum-free conditions and within a concentration range (50-200 nM), TECK rescued pEGFP-N1/CCR9 transfected PC12 cells from undergoing apoptosis in serum-free medium; however, it did not exert a similar effect on the cells in the control. On the other hand, the PC12 cells succumbed to a higher concentration of TECK (≥ 300 nM). Bim expression was up-regulated in PC12 cells cultured in serum-free medium in the absence of factors or with anti-TECK+TECK; however, it was not up-regulated in TECK-treated PC12 cells. p-Akt was detected at 15 min which lasted for at least 60 min when PC12 cells were cultured in serum-free medium with TECK. Additionally, it was shown that such an effect was effectively blocked by PI3K inhibitor, Wortmannin. These data suggest that TECK promotes survival of serum-deprived PC12 cells through its receptor, CCR9, most likely via the PI3K/Akt signaling pathway.

Antibacterial lignans and triterpenoids from Rostellularia procumbens.

One new lignan, rostellulin A ( 1), four known lignans, justin B ( 2), justicidin C ( 3), cilinaphthalide A ( 4), and justicidin A ( 5), and four known triterpenoids, ursolic acid ( 6), euscaphic acid ( 7), 2 alpha-hydroxyursolic acid ( 8), and tormentic acid ( 9), have been isolated from the whole plants of Rostellularia procumbens. Their structures were established on the basis of spectral data, including extensive NMR experiments. To our knowledge, compounds 6 - 9 are known compounds but not previously isolated from R. procumbens, 4 was previously reported from other Rostellularia species. Antibacterial activities of 1 - 9 were evaluated against eight bacterial strains with the agar dilution method, and they were found to possess antimicrobial activity with MIC values in the range of 1.56 - 100 microg/mL. None of the lignans exhibited cytotoxic activity against HCT-8 and Bel-7402 cells at concentrations up to 5 microg/mL.

Antibacterial thymol derivatives isolated from Centipeda minima.

Two new monoterpenoids, 8,10-dihydroxy-9(2)-methylbutyryloxythymol (1) and 10-hydroxy-8,9-dioxyisopropylidene-thymol (2), together with five known thymol derivatives: 8,9,10-trihydroxythymol (3), thymol-beta-glucopyranoside (4), 9-hydroxythymol (5), 8,10-dihydroxy-9-isobutyryloxythymol (6), and 8-hydroxy-9,10-diisobutyryloxythymol (7), were isolated from Centipeda minima. Their structures were identified by means of spectroscopic analyses. Interestingly, compound 2 is not an extraction artifact according to a close HPLC examination of material after extraction by analytical MeOH at ambient temperature. The antibacterial activities of compounds 1-7 were evaluated against eight microbial strains by the agar dilution method.