Characteristics and pollution risks of potentially toxic elements and nematode community structure on farm soil near coal mines.

As one of the most important coal-producing provinces of China, Shanxi Province has been concerned about soil potentially toxic elements (PTEs) contamination in recent years. The study aimed to determine the status and sources of PTEs contamination and evaluate the quality of the soil ecology. This study investigated the degree of 13 PTEs contamination. The sources and contributions of PTEs were traced by the absolute principal component score followed by a multiple linear regression model (APCS-MLR). And the status of the soil ecosystem was verified by evaluating the soil nematode community around the coal mining areas in Jinzhong. The results showed that the mean PTEs concentration of 5 trace elements were higher than the background values of Shanxi, and safe to considerable was indicated by the pollution and ecological risk values. Soil Hg was the most contaminated element, followed by Cd. The distribution of PTEs was determined by coal mining activities (44.72%) followed by agricultural practice (32.37%) and coal transportation (21.37%). The nematode genera Acrobeloides (4.01%), Aphelenchus (20.30%), Meloidogyne (11.95%) and Aporcelaimus (2.74%) could be regarded as bioindicators of soil PTEs contamination by their tolerance. Concentrations of soil Cr, Mn, Ti and Cd showed remarkable influences on the total nematode abundance, maturity index, enrichment index, structural index, Shannon-Wiener diversity index and Pielou index of soil nematode. It is an appropriate method to evaluate the status of soil PTEs contamination combining the response of a single nematode genus and the nematode community evaluation index.

Study on the multitarget mechanism of alliin activating autophagy based on network pharmacology and molecular docking.

Due to the rapid development of bioinformatics, network pharmacology and molecular docking approaches have been successfully applied in the investigation of mechanisms of action. Here, we combined network pharmacology and molecular docking to predict the targets and reveal the molecular mechanism responsible for regulating autophagy by alliin. Based on the influence of alliin on autophagy, the targets of alliin were screened on the basis of different rules such as structural similarity by Pharmmapper, and genes associated with autophagy were collected from the GeneCards database. We focused on clarifying the biological processes and signalling pathways related to autophagy. Through the cytoHubba plug-in and a series of integrated bioinformatics analyses, the top nine hub nodes with higher degrees were obtained. And finally, through the LibDock included in Discovery Studio 2019, molecular docking method was adopted to declare the reliability of the interaction between alliin and hub targets. The results suggest that alliin-activated autophagy was possibly associated with pathways in cancer and the PI3K-AKT signalling pathway. Furthermore, the potential targets (AKT1, MAPK14, MAPK, HSPA8, EGFR, HSP90AA1, SRC HSPA1A and HSP90AB1) were swimmingly screened on the basis of this practical strategy. Molecular docking analysis indicates that alliin can bind with AKT1 and EGFR with good binding scores. This network pharmacology could be an invaluable strategy for the investigation of action mechanisms of alliin-activated autophagy. This study not only provides new and systematic insights into the underlying mechanism of alliin on autophagy, but also provides novel ideas for network approaches for autophagy-related research.

Heavy metal contamination assessment and probabilistic health risks in soil and maize near coal mines.

Objective: Coal mining activities have continuously introduced heavy metals into the soil-crop system, causing increasing damage to crops. This study integrated the analysis of the heavy metal contamination status and human health risk in soil and maize near coal mines to help formulate control strategies for soil quality, maize production, and safe consumption. Method: This study was carried out on maize agricultural land near a coal mining plant. Heavy metal contamination was assessed by the geo-accumulation index (Igeo), enrichment factor (EF), and bioaccumulation factor (BCF). The Monte Carlo simulation was used to estimate the probabilistic health risk of heavy metals exposure in soil and maize. The relationship between the concentration of heavy metal in the soil and that in maize was further visualized by correlation analysis and random forest analysis. Results: The results revealed that the mean concentrations of soil Ni, Cu, As, Cd, Sn, Zn, Pb, and Hg were all above the local background level. Ni was the most severely polluted heavy metal in maize and had a concentration higher than the risk control standard for corn in China (NY 861-2004). The Igeo values of all heavy metals were low, and EF values showed enrichment in V, Cr, Ti, Ni, and As. The assessment of probabilistic health risk exposed by heavy metals in soil and maize indicated that 1.16 and 1.46% of residents exceeded the carcinogenic risk level due to heavy metal exposure from soil and maize, respectively. Children were the most sensitive to maize and soil heavy metal exposure in the contaminated area. Ingestion of heavy metals was associated with the highest health risk to residents, followed by dermal contact and inhalation. As and Cr in soil and Cr and Ni in maize had the greatest impact on human health risk. Furthermore, maize heavy metals were affected the most by soil Cr, Cd, and V. Conclusion: These results may provide useful information for human carcinogenic risk associated with soil and maize heavy metal exposure due to coal mining activities.

Use of Network Pharmacology to Investigate the Mechanism by Which Allicin Ameliorates Lipid Metabolism Disorder in HepG2 Cells.

Allicin has been well documented to exhibit a wide spectrum of biological activities, especially lipid-lowering activity, as a promising candidate for the management of nonalcoholic fatty liver disease (NALFD). However, the mechanisms underlying the therapeutic effects of allicin require further investigation. It is tempting to think of combining network pharmacology and experimental validation to investigate the mechanism by which allicin ameliorates lipid metabolism disorder in HepG2 cells. We established a cell model of hepatic steatosis induced by PA to investigate the antisteatotic effects of allicin. The studies showed that allicin reduced PA-induced lipid accumulation using Nile red staining and TC and TG assays. Then, 219 potential targets of allicin were successfully predicted by PharmMapper. According to Reactome Pathway Analysis, 44 potential targets related to lipid metabolism were screened out. Molecular signaling cascades mediated by allicin included PPARA, PPARG, FABP4, and FABP6 by cytoHubba and qPCR analysis. Results revealed that allicin activated the gene expression of PPARA and FABP6 and suppressed the gene expression of FABP4 and PPARG. Thus, the present study united the methods of network pharmacology and experimental validation to investigate the protein targets of allicin on PA-induced lipid metabolism disorders to supply a reference for related application for the first time.

Discovery of alliin as a putative inhibitor of the main protease of SARS-CoV-2 by molecular docking.

The outbreak of viral pneumonia caused by the novel coronavirus SARS-CoV-2 that began in December 2019 caused high mortality. It has been suggested that the main protease (Mpro) of SARS-CoV-2 may be an important target to discover pharmaceutical compounds for the therapy of this life-threatening disease. Remdesivir, ritonavir and chloroquine have all been reported to play a role in suppressing SARS-CoV-2. Here, we applied a molecular docking method to study the binding stability of these drugs with SARS-CoV-2 Mpro. It appeared that the ligand-protein binding stability of the alliin and SARS-CoV-2 Mpro complex was better than others. The results suggested that alliin may serve as a good candidate as an inhibitor of SARS-CoV-2 Mpro. Therefore, the present research may provide some meaningful guidance for the prevention and treatment of SARS-CoV-2.

Apigenin reduces the excessive accumulation of lipids induced by palmitic acid via the AMPK signaling pathway in HepG2 cells.

In recent years, increasing attention has been paid to diseases caused by excessive accumulation of lipids in the liver with therapeutic agents derived from natural products offering an alternative treatment to conventional therapies. Among these therapeutic agents, apigenin, a natural flavonoid, has been proven to exert various beneficial biological effects. In the present study, the antiadipogenic effects of apigenin in HepG2 cells was investigated. It was demonstrated that the treatment of cells with different concentrations of apigenin for 24 h significantly decreased the palmitic acid-induced increases in total cholesterol (TC) and triglyceride (TG) levels as well as intracellular lipid accumulation. In addition, apigenin increased the phosphorylated-AMP-activated protein kinase (AMPK) levels but decreased the expression levels of 3-hydroxy-3-methylglutaryl CoA reductase, sterol regulatory element-binding protein (SREBP)-1, fatty acid synthase, and SREBP-2 in a concentration-dependent manner. The present findings suggested that apigenin might improve lipid metabolism by activating the AMPK/SREBP pathway to reduce lipid accumulation in the liver.

Cordycepin alleviates hepatic lipid accumulation by inducing protective autophagy via PKA/mTOR pathway.

As the major active ingredient of Cordyceps militaris, cordycepin (3'-deoxyadenosine) has been well documented to possess lipid-lowering and anti-oxidative activities, making it a promising candidate for treatment of NAFLD. Autophagy was recently identified as a critical protective mechanism during NAFLD development. Therefore, this study aims to elucidate the mechanism of cordycepin regulating autophagy and lipid metabolism. Here, we found that cordycepin decreased palmitate-induced lipid accumulation by Oil Red O staining, Nile Red staining assays, triglyceride and total cholesterol measurements. Based on Western blot assay and immunocytochemistry, we found that cordycepin induced autophagy in PA-induced steatotic HepG2 cells. Whereas pretreatment with CQ, an autophagy inhibitor, substantially deteriorated the mitigative effects of cordycepin on PA-induced hepatic lipid accumulation. These data taken together indicate that cordycepin protects against PA-induced hepatic lipid accumulation via autophagy induction. Further, cordycepin remarkably increased the expression of P-PKA and decreased P-mTOR, whereas pretreatment with H89, a PKA inhibitor, abolished the ability of cordycepin to activate autophagy via mTOR activation. These data suggested that cordycepin protects against PA-induced hepatic lipid accumulation through the promotion of autophagy. The underlying mechanism might be associated with the PKA/mTOR pathway.

Pretreatment with Lactobacillus reuteri F-9-35 attenuates ethanol-induced gastric injury in rats.

BACKGROUND: Previous studies suggested that probiotics intervention may be one of the methods for preventing and/or treating gastric ulcer. OBJECTIVE: The aim of the study was to compare the preventive effects of a spaceflight mutant Lactobacillus reuteri F-9-35 and its wild type on ethanol-induced gastric injury in rats. DESIGN: Forty rats were randomly allocated into five groups: a normal group (NOR), ethanol group (EtOH), skim milk group (MILK), L. reuteri F-9-35 group (F935) and wild-type group (WT). The NOR and EtOH groups received 1 ml of distilled water by daily gavage for 14 days. The MILK group received 1 ml of skim milk alone, while the F935 and WT groups were administered 1 ml of skim milk containing the mutant and wild type (1 × 1010 colony-forming unit/ml) by daily gavage for 14 days, respectively. Acute gastric injury was induced by absolute alcohol 1 h after the final administration of different treatments, except for the NOR group. RESULTS: Pretreatment with L. reuteri F-9-35, but not milk alone or milk with the L. reuteri wild type, showed significant reduction of ethanol-induced gastric injury, as evidenced by lowering of ulcer index, ulcer area (%), and histological lesion. F-9-35 decreased the levels of lipid peroxidation and myeloperoxidase and increased mucus, glutathione, and nitric oxide levels in gastric tissue. Moreover, F-9-35 inhibited the expression of proinflammatory genes including gastric tumor necrosis factor-α, interleukin-1ß, and cyclooxygenase-2 and decreased the activity of nuclear factor kappa B (NF-κB). CONCLUSION: These findings indicated that L. reuteri F-9-35 pretreatment can attenuate ethanol-induced gastric injury in rats by inhibiting oxidative stress and inflammatory response. Together, L. reuteri F-9-35 has potential preventive efficacy on gastric ulcer.

1,3-Dichloro-2-Propanol inhibits autophagy via P53/AMPK/mTOR pathway in HepG2 cells.

As a common food processing pollutant, 1,3-Dichloro-2-propanol can be found in foodstuffs, especially in soup spices and instant soups. Mounting researchers have unfolded the relation between 1,3-DCP and various diseases. Autophagy is a process of self-regulation and defects in autophagy have been bound up with multifarious human pathologies and metabolic diseases. Here, we explored the effects of 1,3-DCP on autophagy and traced the molecular mechanism. Our results demonstrated that 1,3-DCP dose-dependently inhibited autophagy. Meanwhile, inhibition of autophagy was accompanied by reduced P53 and p-AMPK/AMPK expressions and stimulated p-mTOR/mTOR expression. Use of a specific mTOR inhibitor (rapamycin), a reversible AMPK activator(A-769662) and a selective P53 activator (Nutlin-3a) abolished the ability of 1,3-DCP to inhibit the induction of autophagy. These evidences suggested that P53/AMPK/mTOR signalling pathway played an important role in the regulation of 1,3-DCP-inhibited autophagy. Together, our results revealed new insights into the toxicity mechanism of 1,3-DCP, supplying theoretical and scientific basis for food safety.

Lactobacillus reuteri F-9-35 Prevents DSS-Induced Colitis by Inhibiting Proinflammatory Gene Expression and Restoring the Gut Microbiota in Mice.

Probiotics are considered to be a potential treatment for ulcerative colitis (UC). The aim of this study was to compare the preventive effect of a space flight-induced mutant L. reuteri F-9-35 and its wild type on UC in vivo. Female mice were randomly assigned to five groups: one normal and four colitic. Mice from colitis groups were daily gavaged with 0.2 mL 12% (w/v) skim milk containing the mutant or wild type (1 × 1011 CFU/mL), skim milk alone or distilled water for the whole experiment period, starting 7 days before colitis induction. UC was induced by administrating mice with 3.5% (w/v) dextran sulfate sodium (DSS) in drinking water for 7 days, after which DSS was removed and maintained for 3 days as a recovery phase. The results showed that the mice fed with L. reuteri F-9-35 had less inflammatory phenotype according to macroscopic and histological analysis, reduced myeloperoxidase activity, and lower expression of proinflammatory genes (Tumor necrosis factor-α, cyclooxygenase-2 and interleukin-6) in colonic tissue compared with control. Furthermore, L. reuteri F-9-35 protected the mice from gut microbiota dysbiosis from DDS induced colitis. Neither wild type nor the milk alone had such beneficial effects. From above we conclude that L. reuteri F-9-35 has great potential in the prevention of UC as a dietary supplement. PRACTICAL APPLICATION: Ulcerative colitis (UC) is the most common inflammatory bowel diseases and there is still a lack of safe and effective treatments. Consumption of L. reuteri F-9-35 may effective in preventing human UC.

Alliin attenuates 1, 3-dichloro-2-propanol-induced lipogenesis in HepG2 cells through activation of the AMP-activated protein kinase-dependent pathway.

Accumulating evidence reveals the association of 1, 3-dichloro-2-propanol (1, 3-DCP) exposure and lipogenesis. Alliin, the most abundant sulphur compound in garlic, has been demonstrated to exhibit hypoglycemic, antioxidant and anti-inflammatory activities. Here, we showed that alliin attenuated lipogenesis induced by 1,3-DCP and that the reduction was due to activation of the AMPK pathway. HepG2 cells exposed to 1,3-DCP exhibited significant increase of triglyceride(TG) and total cholesterol(TC), and alliin reduced the accumulation. Most importantly, alliin could up-regulate the phosphorylation of AMPK and down-regulate protein and gene expressions of SREBP-1; FAS; SREBP-2;HMGCR in 1,3-DCP-induced HepG2 cells. The results demonstrated that alliin was effective on attenuating 1,3-DCP-induced lipogenesis via activation of the AMPK-SREBPs signaling pathway in HepG2 cells.

Protective effects of allicin on 1,3-DCP-induced lipid metabolism disorder in HepG2 cells.

Allicin (2-propene-1-sulfinothioic acid S-2-propenyl ester), with quite a good range of hepatoprotective and antineoplastic properties, is a functional substance from garlic (Allium sativum L.) The purpose of this study was to provide evidence that allicin could protect 1,3-DCP-induced lipid metabolism disorder in HepG2 cells. Allicin reduced the accumulation of triglycerides (TG) and total cholesterol (TC) in 1,3-DCP-induced HepG2 cells. Allicin significantly increased the phosphorylation of AMP-activated protein kinase (AMPK) and down-regulated the levels of sterol regulatory element binding protein-1 (SREBP-1) and sterol regulatory element binding protein-2 (SREBP-2) in 1,3-DCP-induced HepG2 cells. Additionally, allicin had obvious recovery influence on the phosphorylation level of PKA and CREB in 1,3-DCP-induced HepG2 cells. These observations indicated that allicin alleviated lipid metabolism disorder induced by 1,3-DCP in HepG2 cells by regulating AMPK-SREBPs and PKA-CREB signaling pathways.

The midterm effectiveness of extracorporeal shockwave therapy in the management of chronic calcific shoulder tendinitis.

BACKGROUND: This systematic review explored the midterm effectiveness of extracorporeal shockwave therapy (ESWT) in reducing pain and improving shoulder function. Calcified rotator cuff tendinitis is a common cause of chronic shoulder pain that leads to significant pain and functional limitations. ESWT is an alternative to surgery when conservative treatments such as nonsteroidal antiinflammatory drugs, steroidal injections, and physiotherapy fail to relieve symptoms. It is hypothesised that ESWT is effective in the midterm for reducing pain and improving function for patients with chronic calcific tendinitis and that a dose-response relationship exists in the treatment parameters for effectiveness. MATERIALS AND METHODS: Articles were electronically searched from the Cochrane Controlled Trials Register, MEDLINE, CINAHL, PUBMED, EMBASE, SPORTSDiscus and PEDro using a comprehensive search strategy. Studies were included if they were randomized controlled trials testing the midterm effectiveness of ESWT for chronic calcific tendonitis. Methodologic quality was assessed by PEDro (total score = 10). The strength of the evidence was reported using the National Health and Medical Research Council body of evidence framework. RESULTS: Six of the nine included studies scored 7 or more for methodologic quality. All studies had follow-up periods of at least 6 months. Common methodologic flaws were insufficient blinding of clinicians and assessors. There was consistent evidence of midterm effectiveness of ESWT in reducing pain and improving shoulder function for patients with chronic calcified tendinitis. DISCUSSION: ESWT is a potential alternative to surgery with good mid-term effectiveness and minimal side effects. This review noted several limitations with the current body of evidence. Studies were mainly from a few European countries involving medical doctors, with a lack of diverse perspectives and effectiveness evaluation from other health professionals who might use this treatment option for patients with chronic calcific tendinitis. Further, the different outcome measures used and inadequate reporting details in the included studies did not permit a quantitative synthesis of the effectiveness of this treatment. A lack of follow up period beyond one year in the studies also precluded conclusion to be made on the longer term effectiveness of ESWT. CONCLUSION: Due to variable treatment parameters (eg dosage), this review was unable to provide clear guidance of the dose-effect of the midterm effectiveness of ESWT. Studies of better methodologic design using standardized treatment protocols and studies with longer follow-up are required.