Reducing Virus Infection Risk in Space Environments through Nutrient Supplementation.

Space exploration has brought many challenges to human physiology. In order to evaluate and reduce possible pathological reactions triggered by space environments, we conducted bioinformatics analyses on the methylation data of the Mars 520 mission and human transcriptome data in the experiment simulating gravity changes. The results suggest that gene expression levels and DNA methylation levels were changed under the conditions of isolation and gravity changes, and multiple viral infection-related pathways were found in the enrichment analysis results of changed genes including Epstein Barr virus (EBV) infection, Hepatitis B virus (HBV) infection, Herpes simplex virus (HSV) infection and Kaposi's sarcoma-associated herpesvirus (KHSV) infection. In this study, we found that Epigallocatechin-3-gallate (EGCG) and vitamin D are helpful in reducing viral infection risk. In addition, the causal associations between nutrients and viral infections were calculated using Two sample Mendelian Randomization (2SMR) method, the results indicated that vitamin D can reduce EBV infection and HBV infection risk. In summary, our study suggests that space environments increase the risk of human viral infection, which may be reduced by supplementing EGCG and vitamin D. These results can be used to formulate medical plans for astronauts, which have practical application value for future space exploration.

Multi-Omics Interpretation of Anti-Aging Mechanisms for ω-3 Fatty Acids.

Aging is one of the hottest topics in biomedicine. Previous research suggested that ω-3 fatty acids have preventive effects on aging. However, most of previous studies on the anti-aging effects of ω-3 fatty acids are focused on clinical observations, and the anti-aging mechanisms of ω-3 fatty acids have not been fully elucidated. This stimulated our interest to use multi-omics data related to ω-3 fatty acids in order to interpret the anti-aging mechanisms of ω-3 fatty acids. First, we found that ω-3 fatty acids can affect methylation levels and expression levels of genes associated with age-related diseases or pathways in humans. Then, a Mendelian randomization analysis was conducted to determine whether there is a causal relationship between the effect of ω-3 fatty acids on blood lipid levels and variation in the gut microbiome. Our results indicate that the impact of ω-3 fatty acids on aging is partially mediated by the gut microbiome (including Actinobacteria, Bifidobacteria and Streptococcus). In conclusion, this study provides deeper insights into the anti-aging mechanisms of ω-3 fatty acids and supports the dietary supplementation of ω-3 fatty acids in aging prevention.

Insulin-resistance and depression cohort data mining to identify nutraceutical related DNA methylation biomarker for type 2 diabetes.

Insulin-resistance (IR) is one of the most important precursors of type 2 diabetes (T2D). Recent evidence suggests an association of depression with the onset of T2D. Accumulating evidence shows that depression and T2D share common biological origins, and DNA methylation examination might reveal the link between lifestyle, disease risk, and potential therapeutic targets for T2D. Here we hypothesize that integrative mining of IR and depression cohort data will facilitate predictive biomarkers identification for T2D. We utilized a newly proposed method to extract gene-level information from probe level data on genome-wide DNA methylation array. We identified a set of genes associated with IR and depression in clinical cohorts. By overlapping the IR-related nutraceutical-gene network with depression networks, we identified a common subnetwork centered with Vitamin D Receptor (VDR) gene. Preliminary clinical validation of gene methylation set in a small cohort of T2D patients and controls was established using the Sequenome matrix-assisted laser desorption ionization-time flight mass spectrometry. A set of sites in the promoter regions of VDR showed a significant difference between T2D patients and controls. Using a logistic regression model, the optimal prediction performance of these sites was AUC = 0.902，and an odds ratio = 19.76. Thus, monitoring the methylation status of specific VDR promoter region might help stratify the high-risk individuals who could potentially benefit from vitamin D dietary supplementation. Our results highlight the link between IR and depression, and the DNA methylation analysis might facilitate the search for their shared mechanisms in the etiology of T2D.

An organoid-based drug screening identified a menin-MLL inhibitor for endometrial cancer through regulating the HIF pathway.

Tumor organoids recapitulate pathological properties and would serve as an excellent ex vivo model for drug discovery. Here, we performed an unbiased drug screening on drivers-defined tumor organoids from mouse endometrial cancer, the most prevalent gynecological malignancy in human, with a small molecule library targeting epigenetic factors. Among them, menin-MLL inhibitors MI-136 and MI-463 scored. The therapeutic capacity of MI-136 was further validated in tumor organoids in vitro and an orthotopic model in vivo. CRISPR/cas9-mediated mutations of major components of the menin-MLL complex, Men1, Kmt2a and Ash2l, inhibited the growth of tumor organoids, suggesting that the complex was the target of MI-136. Transcriptome analysis showed that the hypoxia-inducible factor (HIF) pathway was the most significantly downregulated pathway by MI-136 treatment. Consistently, Men1, Kmt2a, and Ash2l knockout also repressed the expressions of the HIF target genes. Loss of Hif1a or Hif1b partially phenocopied the inhibition of the menin-MLL complex by MI-136 or mutations in term of tumor organoid growth. Further, we found that MEN1 was upregulated in human endometrial cancers, which were tightly correlated with the expression levels of HIF1A, and associated with poor prognosis. Importantly, MI-136 also significantly inhibited the growth of endometrial cancer organoids derived from patients. Thus, our study identified MI-136 as a potential inhibitor for endometrial cancer through regulating the HIF pathway, a novel molecular mechanism distinguished from those in AML and prostate cancer.

Avicularin ameliorates human hepatocellular carcinoma via the regulation of NF­κB/COX­2/PPAR­Î³ activities.

Hepatocellular carcinoma (HCC) has become a global public health problem. Therefore, the development of novel and effective therapeutic agents for the treatment of HCC is considered an emergency. Avicularin, a bio­active flavonoid from plants, has been reported to exhibit diverse pharmacological properties. The aim of the present study was to investigate the role of avicularin in HCC and the underlying mechanism of action. Huh7 cells were treated with avicularin in a concentration­dependent manner, and the cell proliferation was examined using a 3­(4, 5­dimethylthiazol­2­yl)­2, 5­diphenyltetrazolium bromide assay kit. The cell migration and invasion abilities were detected using wounding­healing assays and Transwell assays. Flow cytometric analysis was performed to investigate the cell cycle distribution and cell apoptosis. The activity of nuclear factor (NF)­κB (p65), cyclooxygenase­2 (COX­2) and peroxisome proliferator­activated receptor γ (PPAR­Î³) were measured by reverse transcription­quantitative polymerase chain reaction and western blot analyses, respectively. The results indicated that avicularin treatment markedly decreased cell proliferation concentration­dependently in HCC, and inhibited cell migration and invasion in Huh7 cells. It was also found that the treatment of avicularin markedly inhibited the G0/G1­phase cells and decreased the accumulation of S­phase cells in the cell cycle and induced cell apoptosis. In addition, it was confirmed that the anticancer efficacy of avicularin in HCC was dependent on the regulation of NF­κB (p65), COX­2 and PPAR­Î³ activities. In conclusion, the findings suggested that avicularin serves an antineoplastic role in HCC and may provide a potential therapeutic strategy for the treatment of HCC.

Source apportionment of nitrogen and phosphorus from non-point source pollution in Nansi Lake Basin, China.

Nitrogen (N) and phosphorus (P) from non-point source (NPS) pollution in Nansi Lake Basin greatly influenced the water quality of Nansi Lake, which is the determinant factor for the success of East Route of South-North Water Transfer Project in China. This research improved Johnes export coefficient model (ECM) by developing a method to determine the export coefficients of different land use types based on the hydrological and water quality data. Taking NPS total nitrogen (TN) and total phosphorus (TP) as the study objects, this study estimated the contributions of different pollution sources and analyzed their spatial distributions based on the improved ECM. The results underlined that the method for obtaining output coefficients of land use types using hydrology and water quality data is feasible and accurate, and is suitable for the study of NPS pollution at large-scale basins. The average output structure of NPS TN from land use, rural breeding and rural life is 33.6, 25.9, and 40.5%, and the NPS TP is 31.6, 43.7, and 24.7%, respectively. Especially, dry land was the main land use source for both NPS TN and TP pollution, with the contributed proportions of 81.3 and 81.8% respectively. The counties of Zaozhuang, Tengzhou, Caoxian, Yuncheng, and Shanxian had higher contribution rates and the counties of Dingtao, Juancheng, and Caoxian had the higher load intensities for both NPS TN and TP pollution. The results of this study allowed for an improvement in the understanding of the pollution source contribution and enabled researchers and planners to focus on the most important sources and regions of NPS pollution.

Gypenosides attenuate cholesterol-induced DNA damage by inhibiting the production of reactive oxygen species in human umbilical vein endothelial cells.

Previous studies have demonstrated that DNA damage induces atherosclerosis and that oxidative stress has an important role in DNA damage. Gypenosides (Gps), the main ingredient of Gynostemma Pentaphylla (Thunb.) Makino, have been recognized as specific antioxidants and have previously been reported to inhibit high­fat diet­induced atherosclerosis in rats. However, whether or not Gps attenuate DNA damage through their antioxidant effects remains to be elucidated. The current study was performed to clarify whether or not Gps can inhibit cholesterol­induced DNA damage through antioxidation. The present study provided new insights into the pharmacological effects of Gps on atherosclerosis. HUVECs were treated with Gps at various concentrations (1, 10 and 100 µg/ml) for 1 h. The protective effects of Gps on cholesterol­induced DNA damage were determined using immunofluorescence, western blotting, reverse­transcription quantitative polymerase chain reaction and flow cytometry. Pretreatment with Gps (1, 10 and 100 µg/ml) effectively attenuated cholesterol­induced DNA damage in HUVECs by inhibiting phosphorylation of H2AX, a member of the histone family. Furthermore, Gps (100 µg/ml) pretreatment inhibited cholesterol­induced transcription and activity of nicotinamide adenine dinucleotide phosphate­oxidase 4 and reduced intracellular ROS levels. In conclusion, Gps attenuated cholesterol­induced DNA damage by inhibiting ROS production in HUVECs, suggesting that the inhibitory effect of Gps on atherogenesis is correlated with the alleviation of DNA damage.

A 6-week mindfulness-based training on aggression and sleep quality in long-term incarcerated males / 中国心理卫生杂志

Objective:To investigate whether the mindfulness training can reduce the aggression level and im-prove the sleeping quality among incarcerated people.Methods:Fifty-four male criminals were recruited into the study.They were divided into mindfulness training group (n =25)and control group (n =29).The training group took mindfulness exercise once a week for 6 weeks.While the participants in waiting list control group waited for 6 weeks without intervention.After 6-week mindfulness training for training group and post-assessment for all partici-pants,the waiting list control group went into 6-week mindfulness training.The Five Facet Mindfulness Question-naire (FFMQ),Aggression Questionnaire (AQ)and Pittsburgh Sleep Quality Index (PSQI)were assessed before and after the intervention.Results:There were 19 valid data in training group,and 21 in control group.After 6-week training,the score difference between pre-and post-assessment of FFMQ (P <0.01 )was higher in the training group than in the control group,and the difference of AQ (P <0.01)and PSQI (P <0.01)was lower in training group than in the control group.Conclusion:The results suggest that 6-week mindfulness training could effectively reduce the aggression level and improve the sleep quality in the long-term incarcerated males.

Cassae-type diterpenes from seeds of Caesalpinia minax / 中国中药杂志

Fifteen cassaen-type diterpenes were isolated from the 95% ethanolic extract of the seeds of C. minax through various chromatographic techniques. Their structures were identified on the basis of spectroscopic data as pulcherralpin (1), caesalpinin ML (2), chamaetexane C (3), chamaetexane D (4), 6β, 18-diacetoxycassan-13, 15-diene (5), neocaesalpin K (6), neocaesalpin MP (7), neocaesalpin M (8), neocaesalpin Q (9), neocaesalpin P (10), neocaesalpin R (11), caesaldekarin D (12), caesaldekarin A (13), caesaldekarin b (14), 3β,6α-diacetoxyvouacapane (15). Among them, compounds 14, 9-11 were isolated from this plant for the first time.

Elucidating pharmacological mechanisms of natural medicines by biclustering analysis of the gene expression profile: a case study on curcumin and Si-Wu-Tang.

Natural medicines have attracted wide attention in recent years. It is of great significance to clarify the pharmacological mechanisms of natural medicines. In prior studies, we established a method for elucidating pharmacological mechanisms of natural products contained in connectivity map (cMap), in terms of module profiles of gene expression in chemical treatments. In this study, we explore whether this methodology is applicable to dissecting the pharmacological mechanisms of natural medicines beyond the agents contained in cMap. First, the gene expression profiles of curcumin (a typical isolated natural medicine) and Si-Wu-Tang (a classic traditional Chinese medicine formula) treatments were merged with those of cMap-derived 1309 agents, respectively. Then, a biclustering analysis was performed using FABIA method to identify gene modules. The biological functions of gene modules provide preliminary insights into pharmacological mechanisms of both natural medicines. The module profile can be characterized by a binary vector, which allowed us to compare the expression profiles of natural medicines with those of cMap-derived agents. Accordingly, we predicted a series of pharmacological effects for curcumin and Si-Wu-Tang by the indications of cMap-covered drugs. Most predictions were supported by experimental observations, suggesting the potential use of this method in natural medicine dissection.

Dissecting traditional Chinese medicines by omics and bioinformatics.

Traditional Chinese medicines (TCM) are a rich source of potential leads for drug development. However, there are fundamental differences between traditional Chinese medical concepts and modern pharmacology, which greatly hinder the modern development of TCM. To address this challenge, new techniques associated with genomics, transcriptomics, proteomics, metabolomics and bioinformatics have been used to dissect the pharmacological mechanisms of TCM. This review article provides an overview of the current research in this area, and illustrates the potential of omic and bioinformatic methods in TCM-based drug discovery.

Triterpene constituents from Rosa cymosa Tratt / 中国中药杂志

The constituents in 95% ethanol extract of the root of Rosa cymosa Tratt were purified by column chromatography techniques, leading to isolation of eleven triterpenes. Their structures were elucidated by spectroscopic data as pomolic acid (1), fupenzic acid (2), ursolic acid (3), euscaphic acid (4), arjunic acid (5), tomentic acid (6), 3β-E-feruloyl corosolic acid (7), 1β-hydroxyeuscaphic acid (8), myrianthic acid (9), cecropiacic acid (10), and ilexoside B (11). Among them, compounds 3, 6-8, 10 and 11 were obtained from this plant for the first time, and compounds 7 and 10 were obtained from this genus for the first time.

[Effect and mechanism of gypenoside on the inflammatory molecular expression in high-fat induced atherosclerosis rats].

OBJECTIVE: To evaluate the effect and possible mechanism of gypenoside (GP) on expression of inflammatory factors in aortic lesion of rats with high-fat induced atherosclerosis. METHODS: Atherosclerotic rat model was established by feeding high-fat diet and intraperitoneal injection of vitamin D3. Sixty healthy male SD rats were randomly divided into the normal group, the model group, the simvastatin treated group and the three GP groups treated respectively with different dosages of GP. Rats were sacrificed 7 weeks later, their histopathological changes in thoracic aorta were observed by light microscope; expressions of intercellular adhesion molecule 1 (ICAM-1), monocyte chemotactic protein-1 (MCP-1) and nuclear factor-kappaBp65 (NF-kappaBp65) in aortic wall were detected by immunohistochemistry; serum level of oxidized low-density lipoprotein (ox-LDL) was determined by ELISA; serum total antioxidant capacity determined by colorimetry, and serum malondialdehyde (MDA) level determined by Thiobarbituric acid method. RESULTS: In comparing with the model group, GPS showed actions in lessening the atherosclerosis lesion; reducing expressions of ICAM-1, MCP-1 and NF-kappaBp65 in aortic wall (P<0.01) and serum levels of MDA, ox-LDL (P < 0.01), as well as increasing the serum level of total antioxidant capacity (P < 0.01 ). CONCLUSION: GP can down-regulate the expressions of ICAM-1 and MCP-1, inhibit the atherosclerosis formation in experimental rats, its mechanism might be related with its anti-oxidation effect and further inhibiting on the NF-kappaB activation.

Adhesion, proliferation and osteodifferentiation of bone mesenchymal stem cells on PLGA-ASP-PEG tri-bolck polymer scaffolds / 中国骨伤

<p><b>OBJECTIVE</b>To explore the adhesion,proliferation and osteodifferentiation of bone mesenchymal stem cells (BMSCs)on the prepared lactic acid/glycolic acid/asparagic acid-co-polyethylene glycol(PLGA-[ASP-PEG])tri-block polymer scaffolds.</p><p><b>METHODS</b>Modified PLGA with polyethylene glycol (PEG) and asparagic acid(ASP)that has many liga nds,and then the synthesis PLGA-[ASP-PEG] tri-block polymer material was prepared. BMSCs were cultured in PLGA-[ASP-PEG] polymer material and poly lactic acid-co-glycolic acid(PLGA)were used as control group. Precipitation method, MUT assay and total cellular protein detection were used to test the adhersion and proliferation of BMSCs. After the third generation of BMSCs was cultured on PLGA-[ASP-PEG] tri-block polymer scaffolds for 14 day and 28 day with osteogenic supplements,the osteodifferentiation of MSCs were observed through alkaline phosphatase(ALP) staining and calcium tubercle staining.</p><p><b>RESULTS</b>BMSCs grew adherent to the surface of PLGA-[ASP-PEG] polymer scaffolds and the number of BMSCs was much higher than that of PLGA. The precipitation method suggested that adhesion and proliferation of BMSCs on the surface of PLGA-[ASP-PEG] was much higher than the control group (P < 0.05). MTU assay showed that after BMSCs were cultured for 20 days,the absorbance A of PLGA-[ASP-PEG] polymer scaffolds and PLGA were 1.336 and 0.780 respectively. Total cellular protein could image the adhersion and proliferation of BMSCs indirectly. After BMSCs were cultured for 12 days,the total cellular protein of PLGA-[ASP-PEG] and PLGA were 66.44 microg/pore and 41.23 microg/pore respectively. PLGA-[ASP-PEG] polymer scaffolds had well biocompatibility and cell adhersion. The positive results with ALP staining and calcium tubercle staining in both groups indicated tri-block polymer scaffold and its degradations had no effect on osteodifferentiation.</p><p><b>CONCLUSION</b>PLGA-[ASP-PEG]could improve the adhesion and proliferation of seed cells on bone-matrixmaterial, maintain the morphous of seed cells and had no obvious effect on cell osteodifferentiation.</p>

Studies on chemical constituents of Sarcandra glabra / 中国中药杂志

<p><b>OBJECTIVE</b>To study antibacterial chemical constituents of Sarcandra glabra.</p><p><b>METHOD</b>The constituents of the chloroform and EtOAc-soluble portions of the EtOH extract from the whole plant of S. glabra, which posses the antibacterial activities, were isolated and purified with column chromatography. The compounds were identified by physical and spectroscopic techniques.</p><p><b>RESULT</b>Six compounds were isolated and identified as 4, 4'-biisofraxidin (1), esculetin (2), fraxetin (3), scoparone (4), isofraxidin (5), scopoletin(6), respectively.</p><p><b>CONCLUSION</b>Compound 1 is a novel natural product. Compounds 24 were isolated from the plants of Chloranthaceae for the first time. The antibacterial activities of these six compounds were tested for the first time. Some compounds may have potential for future study and development as plant-derived oral antibacterial agents.</p>

Clinical study on effect of Shenyin Oral Liquid in treating mild cognitive impairment / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To observe the therapeutic effect of Shenyin Oral Liquid (SOL) in relieving mild cognitive impairment (MCI) and decreasing the Alzheimer's disease (AD) transformation rate.</p><p><b>METHODS</b>One hundred and seventeen MCI patients were randomly assigned to the Chinese medicine group (42 cases), the vitamin E group (38 cases) and the placebo group (37 cases). The treatment course was 12 months and a 6-month follow-up was conducted after ending the treatment course.</p><p><b>RESULTS</b>After treatment, the scores of clock drawing test (CDT), nonsensical figure recognition and mini-mental state examination (MMSE) raised significantly in the Chinese medicine group (P < 0.05 or P < 0.01), the activity of acetylcholine esterase in erythrocytic membrane was lower in the Chinese medicine group than that in the placebo group and the Vitamin E group (P < 0.05 or P < 0.01). Six months after the treatment, there were 2 and 5 cases in the placebo group and the vitamin E group which were diagnosed as AD, respectively, and none in the Chinese medicine group.</p><p><b>CONCLUSION</b>SOL has an effect similar to cholinesterase inhibitor, it could improve cognitive function in MCI patients and reduce the AD transformation rate in them.</p>