AMPK agonist alleviate renal tubulointerstitial fibrosis via activating mitophagy in high fat and streptozotocin induced diabetic mice.

Renal tubulointerstitial fibrosis was a crucial pathological feature of diabetic nephropathy (DN), and renal tubular injury might associate with abnormal mitophagy. In this study, we investigated the effects and molecular mechanisms of AMPK agonist metformin on mitophagy and cellular injury in renal tubular cell under diabetic condition. The high fat diet (HFD) and streptozotocin (STZ)-induced type 2 diabetic mice model and HK-2 cells were used in this study. Metformin was administered in the drinking water (200 mg/kg/d) for 24 weeks. Renal tubulointerstitial lesions, oxidative stress and some indicators of mitophagy (e.g., LC3II, Pink1, and Parkin) were examined both in renal tissue and HK-2 cells. Additionally, compound C (an AMPK inhibitor) and Pink1 siRNA were applied to explore the molecular regulation mechanism of metformin on mitophagy. We found that the expression of p-AMPK, Pink1, Parkin, LC3II, and Atg5 in renal tissue of diabetic mice was decreased obviously. Metformin reduced the levels of serum creatinine, urine protein, and attenuated renal oxidative injury and fibrosis in HFD/STZ induced diabetic mice. In addition, Metformin reversed mitophagy dysfunction and the over-expression of NLRP3. In vitro pretreatment of HK-2 cells with AMPK inhibitor compound C or Pink1 siRNA negated the beneficial effects of metformin. Furthermore, we noted that metformin activated p-AMPK and promoted the translocation of Pink1 from the cytoplasm to mitochondria, then promoted the occurrence of mitophagy in HK-2 cells under HG/HFA ambience. Our results suggested for the first time that AMPK agonist metformin ameliorated renal oxidative stress and tubulointerstitial fibrosis in HFD/STZ-induced diabetic mice via activating mitophagy through a p-AMPK-Pink1-Parkin pathway.

[Selenium Geochemical Characteristics and Influencing Factors of Paddy Fields in Du'an County, Guangxi].

This study used 21 rock samples and 193 sets of paddy soil and rice grain samples collected form Baiwang Town, an area of clastic sedimentary rocks in Guangxi, China, to evaluate the potential for selenium-rich agriculture. We analyzed the concentrations of selenium and heavy metals in the soil and rice samples, and discuss the influencing factors by means of statistics and correlation analysis. The results showed that the selenium-rich rate of paddy soil and rice grain in Baiwang Town were 67.4% and 64.8%, respectively, but the content of cadmium in the selenium-rich soil samples was generally higher than the baseline value for China and the background value for Guangxi. In comparison to the screening value of soil pollution risk for agricultural land(GB 15618-2018), the over-standard rate of cadmium was 46.1%, while the over-standard rates of other heavy metals were negligible. The comparison shows that the selenium-rich rate of rice was 61.1% in the southern area of Baiwang Town with a negligible heavy metal content, and the advantages of green selenium-rich rice planting were clear. The correlation analysis showed that secondary enrichment was the main form of selenium enrichment in the study area. The soil pH and texture of the root-zone soil also affected the selenium content of the soil. The selenium content of rice seeds was mainly affected by the selenium content, active selenium content, pH, and aluminum oxide content of the root-zone soil. The risk assessment showed that the level of dietary exposure to cadmium is generally within safe limits, but it is still necessary to strengthen the monitoring of cadmium in rice and control cadmium pollution to reduce the levels of dietary exposure, especially in the central region of Baiwang Town.

[Migration, Transformation Characteristics, and Ecological Risk Evaluation of Heavy Metal Fractions in Cultivated Soil Profiles in a Typical Carbonate-Covered Area].

In China, high heavy metal concentrations in cultivated soil are mainly distributed in carbonate-covered areas. The migration and transformation of heavy metals in such soils are influenced by interactions between natural processes and human activities. This study examined the profiles of nine paddy soils, derived from carbonate rocks in Guangxi. The Cd, As, Zn, Cr, Cu, Hg, Ni, and Pb contents we determined, and soil properties such as pH, Corg content, and fractions of Cd, As, Zn, and Cr were tested. Based on the above data, we assessed the vertical distribution of heavy metal fractions, as well as the ecological risks and factors affecting the migration ability of heavy metals, under the influence of human activities and natural soil formation. The results show that compared with the carbonate rocks in Guangxi, the soil profile of the study area is significantly enriched with all eight heavy metals. Among them, Cd, As, Zn, and Cr exceeded China's agricultural land (paddy field) pollution risk screening values, and Cd and As partially exceed the risk intervention values. All fractions of Cd in the soil profiles are widely distributed. The proportion of water-soluble and ion-exchange Cd fractions with high ecological risk decreased significantly from the surface to greater depths in the soil profile. As, Zn, and Cr in the soil profile were mainly in residual states, and the proportion of water-soluble and ion-exchange fractions did not change considerably with increasing depth. The evaluation results of RAC and RSP show that Cd pollution risk in the study area is relatively high, whereas As, Zn, and Cr are generally pollution-free or risk-free. In naturally developed soil in the study area, the clay mineral content and degree of soil development have significant effects on Cd migration, whereas in the cultivated layer affected by human activities, the soil pH and organic matter content are the main controlling factors. The migration ability of soil As is mainly related to soil organic matter, Fe2O3 content, and soil development degree, but organic matter has an obviously enhanced effect in the tillage layer. The main controlling factor of Zn and Cr migration in soil is pH, and the effects are more intense under the disturbance of human activities.

[Factors Affecting the Translocation and Accumulation of Cadmium in a Soil-Crop System in a Typical Karst Area of Guangxi Province, China].

To understand the main factors influencing the translocation and accumulation of cadmium (Cd) in soil-crop systems in typical karst areas, 68 sets of paddy soil and rice grain samples were collected in Guangxi Province. These were used to analyze Cd concentrations and soil properties (pH, organic matter (OM) content, oxide content, and texture). Spearman's correlation coefficients and principal component analysis (PCA) were used to examine the effects of soil properties on Cd concentrations and identify the main influencing factors. The studied soils were highly enriched in iron oxide (TFe2O3), aluminum oxide (Al2O3), and manganese oxide (MnO) compared to background levels, with average concentrations of 20.2%, 19.0%, and 0.2%, respectively. However, the soils are relatively depleted in silica (SiO2), with an average concentration of 41.0%. The soils are strongly weathered and leached in study area, giving rise to rich occurrences of Fe-Mn nodules. The concentrations of TFe2O3 and MnO in the study soils were significantly correlated with soil Cd, rice seed Cd, and the Cd bioconcentration factor (BCF). The PCA analysis further showed that TFe2O3 and MnO in soils were the main factors affecting the migration and enrichment of Cd while soil pH, OM, and Al2O3 had less of an influence. Furthermore, SiO2 and soil texture indirectly affected the migration and enrichment of Cd. It is suggested that the Fe-Mn nodules effectively adsorb and immobilize Cd in the study area soils, acting as a heavy metal scavenger that reduced the biological accessibility of Cd.

Ultrasonic treatment on physicochemical properties of water-soluble protein from Moringa oleifera seed.

Effect of ultrasonic power on the structure and functional properties of water-soluble protein extracted from defatted Moringa oleifera seed were explored. The results showed that ultrasonic treatment could reduce ß-sheet and ß-turn content of water-soluble protein from Moringa oleifera seed (MOWP) and increase the content of random coil and α-helix. Changes in intrinsic fluorescence spectra, surface hydrophobicity (H0) and thermal behaviors indicated that ultrasonic had significant effect on the tertiary structure of MOWP. The results of SEM and SDS-PAGE showed that the MOWP was aggregated but not significantly degraded by ultrasound. The solubility, foaming properties and emulsifying properties of MOWP increased firstly and then decreased with the increase of ultrasonic power. Ultrasonic treatment altered the functional properties of MOWP, which might be attributed to the exposure of hydrophilic group and the change of and secondary and tertiary structure.

Synergistic Antibacterial Activity Between 1,4-Naphthoquinone and ß-Lactam Antibiotics Against Methicillin-Resistant Staphylococcus aureus.

Aims: Currently, limited antibiotics are available to treat methicillin-resistant Staphylococcus aureus (MRSA) infections. One approach is the use of adjuvants in antibiotic therapy. 1,4-Naphthoquinones are naturally occurring alkaloids shown to have antibacterial properties. The objective of this study is to investigate the synergy between 1,4-naphthoquinone and selected ß-lactam antibiotics and to evaluate the potential use of 1,4-naphthoquinone as an adjuvant in antibiotic treatment against MRSA infections. Methods: The antibacterial activity of 1,4-naphthoquinone and plumbagin was tested against nine pathogenic bacterial strains using the microdilution broth method. The interactions between 1,4-naphthoquinone and three antibiotics (cefuroxime, cefotaxime, and imipenem) were estimated by calculating the fractional inhibitory concentration of the combination. Results: The compounds 1,4-naphthoquinone and plumbagin exhibited a broad range of bacteriostatic and bactericidal effects against both Gram-positive and Gram-negative bacteria. The interaction between 1,4-naphthoquinone and imipenem, cefuroxime, and cefotaxime was synergistic against methicillin-sensitive Staphylococcus aureus and MRSA clinical strains. Against ATCC-cultured MRSA, a synergistic effect was observed between 1,4-naphthoquinone and cefotaxime. However, combination with imipenem only produced an additive effect, and an antagonistic action was observed between 1,4-naphthoquinone and cefuroxime. Conclusions: Although individually less potent than common antibiotics, 1,4-naphthoquinone acts synergistically with imipenem, cefuroxime, and cefotaxime against MRSA clinical strains and could potentially be used in adjuvant-antibiotic therapy against multidrug resistant bacteria.

[Trace Metals Pollution and Health Risks for Planning Area Soils of 193 Chinese Cities].

Urban soils are more easily subjected to modification, especially by contamination because of various human activities, and the environmental problems caused by urban soil pollution have become more prominent. To systematically investigate concentration characteristics, pollution levels, and exposure risks of 13 trace metals in urban soils of planning areas for 193 cities above the prefectural level, located in 31 provinces (autonomous regions and municipalities) of China, levels of pollution in urban soil were evaluated using the geoaccumulation index and integrated pollution index of trace metals, and health risks of residents exposed to urban soils were quantified using the health risk assessment method recommended by the US Environmental Protection Agency (USEPA). The results show that the median concentrations of As, Be, Cd, Co, Cr, Cu, Hg, Ni, Pb, Se, Tl, V, and Zn in topsoils of urban planning areas were 9.25, 2.14, 0.174, 12.4, 68.4, 28.2, 0.095, 27.7, 31.1, 0.29, 0.61, 82.7, and 82.2 mg·kg-1, respectively. Compared with the corresponding urban soil background values, the concentrations of Cd, Hg, and Se changed significantly. The geoaccumulation index (Igeo) values showed that Hg in urban soils of the planning area was the most severe pollutant, followed by Se and Cd, which caused pollution levels of uncontaminated to moderately contaminated levels, while other trace metals were uncontaminated. The Nemerow IPI (IPIN) revealed that the soils in 22 urban planning areas were heavily polluted and 16 urban planning areas were moderately polluted; in addition, the most polluted city in China was Zhuzhou in the Hunan province. The results of health risk assessment indicate that the soils in the five urban planning areas-Chenzhou City, Huangshi City, Zhuzhou City, Xiangtan City, and Longyan City-posed potential non-carcinogenic risks to children, and the major factor triggering risks was ingestion of Pb. To understand the soil pollution status and distribution of contaminated land parcel, it is suggested to carry out detailed investigation in cities with integrated moderate to heavy pollution to establish the list of contaminated land parcel and implement pollution control and restoration.

[Bioavailability, Translocation, and Accumulation Characteristic of Heavy Metals in a Soil-Crop System from a Typical Carbonate Rock Area in Guangxi, China].

This study uses 68 sets of paddy soil and rice grain samples collected from an area of carbonate rocks in Guangxi Province, China, to explore the ecological risks of heavy metals (As, Cd, Cr, Cu, Hg, Pb, Ni, and Zn) in soils from a high background area. We analyzed the concentrations of these heavy metals in soil and grain samples, and their chemical speciation in soil, and use these data to assess the associated ecological risks by means of statistics, a geo-accumulation index, bioconcentration factors (BCF), and correlation analysis. The arithmetic mean values of heavy metals concentrations in soil samples from the study area were (75.8±50.1), (1.91±1.02), (467.0±253.1), (48.5±9.8), (0.21±0.08), (76.2±28.1), (84.2±25.0), and (258.0±122.6) mg·kg-1 for As, Cd, Cr, Cu, Hg, Ni, Pb, and Zn, respectively, which were remarkably higher than of those from other regions within Guangxi Province and China. In comparison to China's soil environmental quality standard risk screening values (GB 15618-2018), the over-standard rates of Cd, As, and Cr were 95.6%, 86.8%, and 69.1%, respectively. In comparison to risk intervention values, the over-standard rates of Cd, As, and Cr were 27.9%, 17.6%, and 5.9%, respectively. Speciation analysis on heavy metals indicated that As, Cr, Cu, Ni, Pb, and Zn were mainly found in a residual form, and accounted for>80% of the total concentrations, and had a low bioavailability. The bioactive components (F1+F2+F3) of Cd accounted for 21%, and the bioactivity of Cd was higher than other elements. The potential bioavailable components (F4+F5+F6) of Hg accounted for 44%, with low total concentrations, which are understood to have little potential ecological harm for crops. However, the over-standard rates of Pb, Cd, and Cr in rice grains were only 23.5%, 8.8%, and 2.9%, respectively. Correlation analysis showed that there was no significant correlation between the concentrations of heavy metals in soils and the corresponding rice grains. The mean BCFs of each heavy metal were <0.1, and the BCFs of Hg, Pb, As, Cr, and Ni were <0.05. Overall, we found relatively high concentrations, low activity, and low ecological risks for heavy metals in the study area. For high geological background materials such as carbonate rocks, factors such as metal speciation, biological activity, and crop over-standard rates should be taken into account along with the traditional use of the total amount of heavy metals in a soil as the evaluation standard when formulating pollution control policies.

The Impact of Vitamin D Receptor Gene Polymorphisms on the Susceptibility of Diabetic Vascular Complications: A Meta-Analysis.

Background: To determine whether vitamin D receptor (VDR) gene polymorphisms are correlated with susceptibility to diabetic vascular complications. Methods: We included all eligible studies, and used Stata12.0 to calculate the pooled results. Results: Eight thousand eleven diabetic patients and 1635 normal controls from 27 studies were included. Our results showed that there was no correlation between VDR gene TaqI variants and diabetic nephropathy (DN) or diabetic retinopathy (DR) susceptibility. In comparison with diabetic patients without DN, there was a link between the VDR gene ApaI variant and DN susceptibility under allelic model (p = 0.029) in all populations. In addition, the VDR gene BsmI variant correlated with DN under both dominant (p = 0.005) and allelic (p = 0.003) models in Asian populations. The VDR gene FokI variant was also correlated with DN susceptibility under the recessive model (p = 0.027) in the Asian subgroup. In comparison with diabetic patients without DR, we identified a link between the VDR gene ApaI variant and DR susceptibility under the dominant model (p = 0.034) in all populations. Also, the VDR gene FokI variant was correlated with DR under the recessive (p = 0.016), the allelic (p = 0.001), and the dominant (p < 0.001) models in all populations. When compared with healthy controls, the VDR gene BsmI variant was associated with DR under the additive (p = 0.014), the allelic (p = 0.033), and the dominant (p < 0.001) models in Indian populations. Conclusions: The VDR gene BsmI, ApaI, and FokI gene variants are associated with DN and DR susceptibility. No association was found between the VDR gene TaqI gene variants and diabetic vascular complications.

Green tea polyphenols attenuate hepatic steatosis, and reduce insulin resistance and inflammation in high-fat diet-induced rats.

Non­alcoholic fatty liver disease (NAFLD) is characterized by hepatic steatosis, insulin resistance and inflammation; however, the exact pathogenesis of NAFLD is not fully understood. Green tea polyphenols (GTP) exhibit beneficial effects against metabolic syndrome. However, the effect of GTP on NAFLD remains largely unknown. The aim of the present study was to investigate the effects of GTP on NAFLD in high­fat diet (HFD)­induced rats. The NAFLD rat model was induced with a HFD for 8 weeks. A total of 30 adult male Sprague Dawley rats were randomly divided into three groups: i) Normal control group; ii) HFD group; and iii) HFD with GTP group. Hematoxylin and eosin and Oil Red O analyses were performed. The levels of alanine aminotransferase (ALT), aspartate amino-transferase (AST) and inflammatory cytokines in the serum, as well as oxidative stress markers and hepatic lipids in the liver were measured. In addition, parameters associated with glucose metabolism were also assessed. Western blotting and RT­qPCR were used to determine the expression levels of 5' adenosine monophosphate­activated protein kinase (AMPK). HFD­induced rats exhibited features associated with NAFLD. GTP intervention significantly reduced serum ALT and AST levels. Fasting serum glucose, insulin resistance and hepatic lipid levels were all decreased in the GTP­treated rats. GTP also significantly decreased the levels of TNF­α, IL­6 and malondialdehyde. In contrast, superoxide dismutase levels were increased in the liver. Furthermore, GTP also significantly increased phosphorylation of AMPK and attenuated histopathological changes indicative of injury in liver tissue. GTP has a protective effect on HFD­induced hepatic steatosis, insulin resistance and inflammation, and the underlying mechanism may involve the AMPK pathway.

Mitochondria-Targeted Peptide SS31 Attenuates Renal Tubulointerstitial Injury via Inhibiting Mitochondrial Fission in Diabetic Mice.

OBJECTIVE: Renal tubular injury is an early characteristic of diabetic nephropathy (DN) that is related to mitochondrial dysfunction. In this study, we explore the effects and mechanisms of mitochondria-targeted peptide SS31 on renal tubulointerstitial injury in DN. METHOD: 40 C57BL/6 mice were randomly divided into control group, STZ group, STZ+SS31 group, and STZ+normal saline group. SS31 was intraperitoneally injected to the mice every other day for 24 weeks. Renal lesions and the expression of Drp1, Mfn1, Bcl-2, Bax, Caspase1, IL-1ß, and FN were detected. In in vitro studies, HK-2 cells were incubated with different concentrations of D-glucose (5, 30 mM) or combined with SS31 and Drp1 inhibitor Midivi1. Mitochondrial ROS, membrane potential, and morphology have been detected to evaluate the mitochondrial function. RESULTS: Compared with diabetic mice, the levels of serum creatinine and microalbuminuria were significantly decreased in the SS31 group. Renal tubulointerstitial fibrosis, oxidative stress, and apoptosis were observed in diabetic mice, while the pathological changes were reduced in the SS31-treatment group. SS31 could decrease the expression of Drp1, Bax, Caspase1, IL-1ß, and FN in the renal tissue of diabetic mice, while increasing the expression of Mfn1. Additionally, mitochondria exhibit focal enlargement and crista swelling in renal tubular cells of diabetic mice, while SS31 treatment could partially block these changes. An in vitro study showed that pretreatment with SS31 or Drp1 inhibitor Mdivi1 could restore the level of mitochondrial ROS, the membrane potential levels, and the expressions of Drp1, Bax, Caspase1, IL-1ß, and FN in HK-2 cells under high-glucose conditions. CONCLUSION: SS31 protected renal tubulointerstitial injury in diabetic mice through a decrease in mitochondrial fragmentation via suppressing the expression of Drp1 and increasing the expression of Mfn1.

[Association of Body Mass Index and Risk Stratification of Thyroid Nodules in a Multi-center Healthy Population].

Objective To investigate the relationship between body mass index(BMI)and risk levels of thyroid nodules in a multi-center healthy population. Methods A total of 6070 subjects were enrolled from five medical physical examination centers in China from January 2015 to December 2017. All the participants'general information and parameters were recorded. Thyroid nodules were detected by color Doppler ultrasonography. All ultrasound doctors received uniform training before study. Results Among all the subjects,5773(95.1%;with 4274 nodules identified in 2833 subjects)were from northern China and 297(4.9%,with 183 nodules identified in 158 subjects)from central China(χ2=1.923,P=0.092). The nodules were single in 1479 of 2991 subjects(49.4%)and multiple in 1512 subjects(50.6%). Nodules larger than 1 cm accounted for 13.3% and nodules smaller than 1 cm accounted for 86.7%. Compared with the non-thyroid nodule group,the thyroid nodule group had significantly more women(χ2=156.36,P=0.000),older age(t=-18.768,P=0.000),and higher fasting blood glucose(FBG) level(t=-3.808,P=0.000). Among all the nodules,the prevalence rates of benign,very-low-risk,low-risk,moderate risk,and high risk were 4.5%,6.6%,85.0%,0.1%,and 3.7%,respectively,according to the ATA guidelines. Notably,there were 4291 nodules at moderate or lower risks and 166 nodules at high risk. Compared with the former,patients with high-risk nodules had significantly lower BMI(χ2=25.161,P=0.000)and high FBG(t=3.357,P=0.000). Multivariate non-conditional Logistic regression showed low BMI(OR=2.900,95%CI:1.461-5.783,P=0.002)and high FBG level(OR=0.803,95%CI:0.675-0.955,P=0.013)were independent risk factors for high-risk nodules. Compared with subjects with normal weight or obese populations,subjects with low BMI had significantly higher detection rate of high-risk nodules(χ2=25.16,P=0.000). In ≥55 year-old group,significantly more high-risk nodules were detected in low BMI group(χ2=44.868,P=0.000). Conclusion Low weight is associated with high-risk thyroid nodules among people ≥55 years old.

Antioxidant and hepatoprotective effects of extract of ginkgo biloba in rats of non-alcoholic steatohepatitis.

OBJECTIVE: To evaluate the therapeutic effect and mechanism of extract of ginkgo biloba (EGB) in treatment of diet-induced non-alcoholic steatohepatitis (NASH) in rats. METHODS: The experiment was conducted in the Laboratory, Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan, China from June 2009 to December 2009. In this study, the rat model of NASH was produced by feeding high-fat diet. Sixty rats were randomly divided into 3 groups: Normal group: normal diet, drinking water; Model group: high-fat diet, single-distilled water 10 ml/kg gavage once a day for 12 weeks; and Treated group: high-fat diet, EGB 6 mg/kg gavage once a day for 12 weeks. At the end of 12 weeks, all rats were killed. The serum biochemical, fibrosis markers, superoxide dismutase (SOD), malondialdehyde (MDA), the pathological changes, and the expression levels of nuclear factor KB (NF-κB)p65 protein in the liver were observed. RESULTS: The contents of serum alanine transaminase aspartate aminotransferase, fibrosis markers, and pathological grading of liver fibrosis and the staining intensity of NF-κBp65 protein in the liver of rats in treated group were significantly lower than those in the model group. Activities of superoxide dismutase were elevated, but levels of malondialdehyde were decreased in the treated group as compared with the model group. CONCLUSION: Extract of ginkgo biloba has antioxidant and hepatoprotective effects and can inhibit liver fibrosis in rat of NAHS.