Objective To investigate the therapeutic action and molecular mechanisms of Oxalis comiculata L. extracts on rats with alcoholic liver disease. Methods Forty-two male Sprague Dawley(SD)rats were randomly divided into normal control group(n=10),model group(n=8),moderate dose oxalis group(n=8),high dose oxalis group(n=8)and prednisone group(n=8). The model of rat with alcoholic liver disease was established by liquor gavage;after 12 weeks,moderate dose oxalis group,high dose oxalis group and prednisone group were given the total extract of oxalis 3.5 g?kg-1?d-1,7 g?kg-1?d-1 or prednisolone acetate 0.9 mg?kg-1?d-1,respectively,the remaining two groups were given the same amount of normal saline by gavage daily for 6 weeks. Levels of indexes of liver function,superoxide dismutase(SOD),malondialdehyde(MDA),antidiuretic hormone(ADH)and aldehyde dehydrogenase(ALDH)in rats were detected. The pathological changes of liver tissues in rats were observed under light microscope;tumor necrosis factor-α(TNF-α) expression level was detected by immunohistochemical staining. Results Compared with the normal control group, the levels of aspartate aminotransferase (AST), alanine aminotransferase(ALT),alkaline phosphatase(AKP),γ-glutamyl transferase(GGT),MDA were increased significantly,while the levels of SOD,ADH and ALDH were obviously reduced in model group. Compared with the model group,AST,ALT,AKP,GGT and MDA contents were decreased significantly,while the levels of SOD, ADH and ALDH were markedly increased in the drug groups,and the changes of levels of AST,ALT,AKP,GGT, SOD,ADH in high dose oxalis group were the most obvious〔AST(U/L):117.38±22.75 vs. 201.62±17.95,ALT (U/L):33.51±11.64 vs. 59.14±9.52,AKP(U/L):95.19±24.85 vs. 169.39±37.21,GGT(U/L):46.54±14.55 vs. 89.37±12.49,SOD(U/mg):137.03±12.03 vs. 80.64±13.45,ADH(U/L):3.48±0.71 vs. 2.05±0.91,P<0.05 or P<0.01〕,and the most significant changes of MDA and ALDH were in oxalis moderate dose group〔MDA (mmol/mg):2.05±0.64 vs. 3.17±0.61,ALDH(U/L):7.59±1.95 vs. 5.71±1.33,both P<0.05〕. In normal control group,no obvious lesion was seen in the rat liver tissues. In the model group,fatty degeneration of liver cells with formation of bullae was found,while in the moderate and high dose oxalis groups,cells with macrovesicular steatosis were significantly decreased. Immunohistochemical staining showed that the expression of TNF-α in the cytoplasm and part of cell membrane of macrophage was significantly decreased in liver tissues in oxalis moderate and high dose groups. Conclusion These results show that the Oxalis comiculata L. extracts possess certain therapeutic effect on alcoholic liver disease.

OBJECTIVETo detect the embryo toxicity and the teratogenicity of DNAN in rats and provide basic data to occupational protection.

METHODS120 adult female SD rats and 60 male rats are mating for 1: 1, and the pregnant rats were randomly divided into five groups by the pregnant time. The negative control group are gavaged with 4% starch, and the three experiment groups are gavaged with DNAN suspension with the dose of 5 mg/kg, 15 mg/kg and 45 mg/kg respectively, while the positive control give aspirin of 280 mg/kg. All rats of the five groups are administrated gavage from gestation day 5 (GD5) to GD19 continuously. The rats are dislocated in GD20, and the toxicity of embryo and toetus are detected.

RESULTSThe net weight growth in all three dose group are less than that of negative group, while the dead foetus in high dose group is more than negative group. Moreover, the body weight, body lenghth, tail lenghth and the anal genital distance of foetus rats in high dose group are all less than that of negative group. The foetus external malformations of three dose groups appear no significant compared with negative group.However, the prevalences of skeleton malformation in high dose group and the internal organs malformation in the median and high dose group appear significant higher than that of negative group. There are significantly maternal reproductive toxicity, embryo toxicity and toetus toxicity in positive group.

CONCLUSIONDNAN can induced maternal reproductive toxicity, embryo toxicity and the teratogenicity to rats.

Animals ; Anisoles ; toxicity ; Female ; Male ; Pregnancy ; Rats ; Rats, Sprague-Dawley ; Teratogens ; toxicity ; Toxicity Tests

Unlike the well-established picture for the entry of enveloped viruses, the mechanism of cellular entry of non-enveloped eukaryotic viruses remains largely mysterious. Picornaviruses are representative models for such viruses, and initiate this entry process by their functional receptors. Here we present the structural and functional studies of SCARB2, a functional receptor of the important human enterovirus 71 (EV71). SCARB2 is responsible for attachment as well as uncoating of EV71. Differences in the structures of SCARB2 under neutral and acidic conditions reveal that SCARB2 undergoes a pivotal pH-dependent conformational change which opens a lipid-transfer tunnel to mediate the expulsion of a hydrophobic pocket factor from the virion, a pre-requisite for uncoating. We have also identified the key residues essential for attachment to SCARB2, identifying the canyon region of EV71 as mediating the receptor interaction. Together these results provide a clear understanding of cellular attachment and initiation of uncoating for enteroviruses.
Acids ; chemistry ; Amino Acid Sequence ; Animals ; Capsid Proteins ; chemistry ; genetics ; metabolism ; Enterovirus A, Human ; genetics ; metabolism ; physiology ; HEK293 Cells ; Host-Pathogen Interactions ; Humans ; Hydrogen-Ion Concentration ; Lysosome-Associated Membrane Glycoproteins ; chemistry ; genetics ; metabolism ; Molecular Docking Simulation ; Molecular Sequence Data ; Protein Binding ; Protein Conformation ; Protein Interaction Mapping ; Protein Structure, Tertiary ; RNA, Viral ; genetics ; metabolism ; Receptors, Scavenger ; chemistry ; genetics ; metabolism ; Sequence Homology, Amino Acid ; Sf9 Cells ; Static Electricity ; Virion ; genetics ; metabolism ; Virus Attachment

BACKGROUND: Non-transport unintentional injuries (NTUIs) are major public concerns, especially among children and adolescents in low- and middle-income countries. With environmental and cognitive changes, a recent systematic description of global trends and regional differences concerning NTUIs is urgently needed for the global agenda of relevant policy-making and intervention target findings. METHODS: We used mortality, population, and socio-demographic-index (SDI) data from Global Burden of Disease 2019 to analyze the trends of NTUIs mortality. We applied the slope index of inequality (SII) and relative index of inequality (RII) to measure the absolute and relative inequality between countries and territories. The concentration curve and concentration index (CI) were also used to measure the inequality. We conducted a sensitivity analysis to make our findings credible. RESULTS: In 2019, there were 205,000 deaths due to NTUIs among children and adolescents aged 5 to 24 years, which decreased from 375,000 in 1990. In 2019, the age-standardized mortality rate (ASMR) was 8.13 per 100,000, ranging from the lowest in the Netherlands (0.90 per 100,000) to the highest in the Solomon Islands (29.34 per 100,000). The low-middle SDI group had the highest ASMR of NTUIs, while the low SDI group had the slowest decrease. After excluding the death caused by "exposure to forces of nature" and "other unintentional injuries", drowning accounted for the most deaths in almost every SDI group, gender, and age group, but the major causes of death varied in different subgroups. For example, animal contact was a major cause in low and low-middle SDI groups but less in high SDI groups, while high and high-middle SDI groups had a higher proportion of deaths for foreign body and poisonings. The SII showed a declining trend, but the RII and CI did not, which might indicate that inequality was persistent. Similar results were found in the sensitivity analysis. CONCLUSIONS Despite the declining trend of the mortality rate and the narrowing gap between countries, there were still a large number of children and adolescents dying from NTUIs, and those experiencing social-economic disadvantages remained at high mortality. Embedding the prevention of NTUIs into sustainable development goals might contribute to the progress of reducing death and inequalities, which ensures that no one is left behind.
Global Burden of Disease