Ginseng-derived nanoparticles alleviate inflammatory bowel disease via the TLR4/MAPK and p62/Nrf2/Keap1 pathways.

Inflammatory bowel disease (IBD) is closely linked to the homeostasis of the intestinal environment, and exosomes can be used to treat IBD due to their high biocompatibility and ability to be effectively absorbed by the intestinal tract. However, Ginseng-derived nanoparticles (GDNPs) have not been studied in this context and their mechanism of action remains unclear. Here, we investigated GDNPs ability to mediate intercellular communication in a complex inflammatory microenvironment in order to treat IBD. We found that GDNPs scavenge reactive oxygen species from immune cells and intestinal epithelial cells, inhibit the expression of pro-inflammatory factors, promote the proliferation and differentiation of intestinal stem cells, as well as enhancing the diversity of the intestinal flora. GDNPs significantly stabilise the intestinal barrier thereby promoting tissue repair. Overall, we proved that GDNPs can ameliorate inflammation and oxidative stress in vivo and in vitro, acting on the TLR4/MAPK and p62/Keap1/Nrf2 pathways, and exerting an anti-inflammatory and antioxidant effect. GDNPs mitigated IBD in mice by reducing inflammatory factors and improving the intestinal environment. This study offers new evidence of the potential therapeutic effects of GDNPs in the context of IBD, providing the conceptual ground for an alternative therapeutic strategy.

The PI3K-Akt-mTOR pathway mediates renal pericyte-myofibroblast transition by enhancing glycolysis through HKII.

BACKGROUND: Pericyte-myofibroblast transition (PMT) has been confirmed to contribute to renal fibrosis in several kidney diseases, and transforming growth factor-ß1 (TGF-ß1) is a well-known cytokine that drives PMT. However, the underlying mechanism has not been fully established, and little is known about the associated metabolic changes. METHODS: Bioinformatics analysis was used to identify transcriptomic changes during PMT. PDGFRß + pericytes were isolated using MACS, and an in vitro model of PMT was induced by 5 ng/ml TGF-ß1. Metabolites were analyzed by ultraperformance liquid chromatography (UPLC) and tandem mass spectrometry (MS). 2-Deoxyglucose (2-DG) was used to inhibit glycolysis via its actions on hexokinase (HK). The hexokinase II (HKII) plasmid was transfected into pericytes for HKII overexpression. LY294002 or rapamycin was used to inhibit the PI3K-Akt-mTOR pathway for mechanistic exploration. RESULTS: An increase in carbon metabolism during PMT was detected through bioinformatics and metabolomics analysis. We first detected increased levels of glycolysis and HKII expression in pericytes after stimulation with TGF-ß1 for 48 h, accompanied by increased expression of α-SMA, vimentin and desmin. Transdifferentiation was blunted when pericytes were pretreated with 2-DG, an inhibitor of glycolysis. The phosphorylation levels of PI3K, Akt and mTOR were elevated during PMT, and after inhibition of the PI3K-Akt-mTOR pathway with LY294002 or rapamycin, glycolysis in the TGF-ß1-treated pericytes was decreased. Moreover, PMT and HKII transcription and activity were blunted, but the plasmid-mediated overexpression of HKII rescued PMT inhibition. CONCLUSIONS: The expression and activity of HKII as well as the level of glycolysis were increased during PMT. Moreover, the PI3K-Akt-mTOR pathway regulates PMT by increasing glycolysis through HKII regulation.

14-3-3ζ inhibits maladaptive repair in renal tubules by regulating YAP and reduces renal interstitial fibrosis.

Acute kidney injury (AKI) refers to a group of common clinical syndromes characterized by acute renal dysfunction, which may lead to chronic kidney disease (CKD), and this process is called the AKI-CKD transition. The transcriptional coactivator YAP can promote the AKI-CKD transition by regulating the expression of profibrotic factors, and 14-3-3 protein zeta (14-3-3ζ), an important regulatory protein of YAP, may prevent the AKI-CKD transition. We established an AKI-CKD model in mice by unilateral renal ischemia-reperfusion injury and overexpressed 14-3-3ζ in mice using a fluid dynamics-based gene transfection technique. We also overexpressed and knocked down 14-3-3ζ in vitro. In AKI-CKD model mice, 14-3-3ζ expression was significantly increased at the AKI stage. During the development of chronic disease, the expression of 14-3-3ζ tended to decrease, whereas active YAP was consistently overexpressed. In vitro, we found that 14-3-3ζ can combine with YAP, promote the phosphorylation of YAP, inhibit YAP nuclear translocation, and reduce the expression of fibrosis-related proteins. In an in vivo intervention experiment, we found that the overexpression of 14-3-3ζ slowed the process of renal fibrosis in a mouse model of AKI-CKD. These findings suggest that 14-3-3ζ can affect the expression of fibrosis-related proteins by regulating YAP, inhibit the maladaptive repair of renal tubular epithelial cells, and prevent the AKI-CKD transition.

Neonicotinoid Insecticides and Their Metabolites Can Pass through the Human Placenta Unimpeded.

Studies on neonicotinoid (NEO) exposure in pregnant women and fetuses are scarce, and transplacental transfer of these insecticides is unknown. In this study, parent NEOs (p-NEOs) and their metabolites (m-NEOs) were determined in 95 paired maternal (MS) and cord serum (CS) samples collected in southern China. Imidacloprid was the predominant p-NEO in both CS and MS samples, found at median concentrations of 1.84 and 0.79 ng/mL, respectively, whereas N-desmethyl-acetamiprid was the most abundant m-NEO in CS (median: 0.083 ng/mL) and MS (0.13 ng/mL). The median transplacental transfer efficiencies (TTEs) of p-NEOs and m-NEOs were high, ranging from 0.81 (thiamethoxam, THM) to 1.61 (olefin-imidacloprid, of-IMI), indicating efficient placental transfer of these insecticides. Moreover, transplacental transport of NEOs appears to be passive and structure-dependent: cyanoamidine NEOs such as acetamiprid and thiacloprid had higher TTE values than the nitroguanidine NEOs, namely, clothianidin and THM. Multilinear regression analysis revealed that the concentrations of several NEOs in MS were associated significantly with hematological parameters related to hepatotoxicity and renal toxicity. To our knowledge, this is the first analysis of the occurrence and distribution of NEOs in paired maternal-fetal serum samples.

Role of NOD-Like Receptors in a Miniature Pig Model of Diabetic Renal Injuries.

Activation of NOD-like receptor (NLR) signaling pathway can promote downstream cytokine and proinflammatory cytokines release, and inflammation induced by excess nutrients leads to renal metabolic injury. How the NLRs influence metabolic progress and then lead to the renal injury remains poorly investigated. Compared with rodents, minipigs are more similar to humans and are more ideal animal models for human disease research. In this study, we established a diabetic minipig model through a high-sugar and high-fat diet combined with streptozotocin (STZ) injection. Blood biological markers and renal pathological markers, expression of NLRP subfamily members (NLRP1 and NLRP3) and their downstream cytokines (precursors of IL-1ß and IL-18 and mature forms of IL-1ß and IL-18), expression of NLRC subfamily members (NLRC1, NLRC2, and NLRC5) and their downstream nuclear factor-κB (NF-κB) signaling pathway molecules (IKKß, IκBα, and NF-κB p65), and inflammatory cytokines (TNF-α and interleukin-6 (IL-6)) were systematically evaluated. The expression of NLRP3 and its downstream cytokine signaling molecules, the precursors of IL-1ß and IL-18, and the mature forms of IL-1ß and IL-18 was significantly upregulated. The expression levels of NLRC1, NLRC2, and NLRC5 and activation of the downstream NF-κB pathway molecules phospho-IKKß, phospho-IκBα, NF-κB p65, and phospho-NF-κB p65 were significantly increased. The TNF-α and IL-6 levels were significantly increased in diabetic pig kidneys. The TGF-ß/Smad signaling molecules, TGF-ß and P-SMAD2/3, were also increased. These results suggested that the metabolic inflammation activated by NLRs might play an important role in diabetic renal injuries.

ROBO2-mediated RALDH2 signaling is required for common nephric duct fusion with primitive bladder.

Congenital anomalies of the urinary tract are a significant cause of morbidity in infancy, and many congenital anomalies are linked to ureter development; however, the mechanism by which congenital anomalies control ureter development remains unknown. The loss of Robo2 can cause ureter defects and vesicoureteral reflux. However, how Robo2 impacts ureter development is unclear. We found that ROBO2 is expressed in the common nephric duct (CND) and primitive bladder, and impacts CND migration and fusion with the primitive bladder via its novel binding partner retinaldehyde dehydrogenase-2 (RALDH2). Delayed apoptosis that is due to the failure of CND fusion with the primitive bladder in the Robo2-/-embryo results in an abnormal ureter connection to the CND, which is required for ureter development. We define a novel pathway in which the CND is remodeled by ROBO2 and retinoic acid rescued the ureter anomalies in the Robo2-/-embryo. These findings may be relevant to diverse disease conditions that are associated with altered signaling in the primitive bladder.

STAT3 Inhibition Partly Abolishes IL-33-Induced Bone Marrow-Derived Monocyte Phenotypic Transition into Fibroblast Precursor and Alleviates Experimental Renal Interstitial Fibrosis.

Previous studies of Jak-STAT inhibitors have shown promise in treating kidney diseases. The activation of Jak-STAT components is important in cell fate determination in many cell types, including bone marrow-derived cells, which are important contributors in renal interstitial fibrosis. In this study, we tested the effect of a new STAT3 inhibitor, BP-1-102, on monocyte-to-fibrocyte transition and the progression of renal interstitial fibrosis. We tested the effect of BP-1-102 in a mouse model of unilateral ureteral obstruction in vivo and IL-33-treated bone marrow-derived monocytes in vitro. BP-1-102 treatment alleviated renal interstitial fibrosis, reduced collagen deposition and extracellular matrix protein production, inhibited inflammatory cell infiltration, suppressed the percentage of CD45+ PDGFRß+, CD45+ CD34- Col I+ and CD45+ CD11b+ Col I+ cells within the obstructed kidney and reduced the mRNA levels of the proinflammatory and profibrotic cytokines IL-1ß, TGF-ß, TNF-α, ICAM-1, and CXCL16. In vitro, BP-1-102 inhibited the IL-33-induced phenotypic transition into fibroblast precursors in bone marrow-derived monocytes, marked by reduced CD45+ CD34- Col I+ and CD45+ CD11b+ Col I+ cell percentage. Our results indicate a potential mechanism by which the STAT3 inhibitor BP-1-102 inhibits bone marrow-derived monocyte transition into fibroblast precursors in an IL-33/STAT3-dependent manner and thereby alleviates renal interstitial fibrosis.

20(S)-Ginsenoside Rh2-induced apoptosis and protective autophagy in cervical cancer cells by inhibiting AMPK/mTOR pathway.

20(S)-Ginsenoside Rh2 (GRh2) has various biological activities including anticancer effects. However, no reports have investigated the connection between autophagy and apoptosis in HeLa cells treated with 20(S)-GRh2. In this study, we found that 20(S)-GRh2 suppressed proliferation and induced apoptosis in HeLa cells by activating the intrinsic apoptotic pathway and causing mitochondrial dysfunction. 20(S)-GRh2 enhanced cell autophagy through promoting the phosphorylation of AMPK, depressed the phosphorylation of AKT, and suppressed mTOR activity. Furthermore, treatment with the autophagy inhibitor 3-methyladenine (3-MA) enhanced 20(S)-GRh2-induced apoptosis, while the autophagy inducer rapamycin promoted cell survival. Moreover, the apoptosis inhibitor Z-VAD-FMK significantly restrained the apoptosis and autophagy induced by 20(S)-GRh2 in HeLa cells. We found that 20(S)-ginsenoside Rh2-induced protective autophagy promotes apoptosis of cervical cancer cells by inhibiting AMPK/mTOR pathway.

Inversion reflectance by apple tree canopy ground and unmanned aerial vehicle integrated remote sensing data.

To obtain accurate spatially continuous reflectance from Unmanned Aerial Vehicle (UAV) remote sensing, UAV data needs to be integrated with the data on the ground. Here, we tested accuracy of two methods to inverse reflectance, Ground-UAV-Linear Spectral Mixture Model (G-UAV-LSMM) and Minimum Noise Fraction-Pixel Purity Index-Linear Spectral Mixture Model (MNF-PPI-LSMM). At wavelengths of 550, 660, 735 and 790 nm, which were obtained by UAV multispectral observations, we calculated the canopy abundance based on the two methods to acquire the inversion reflectance. The correlation of the inversion and measured reflectance values was stronger in G-UAV-LSMM than MNF-PPI-LSMM. We conclude that G-UAV-LSMM is the better model to obtain the canopy inversion reflectance.

Multifunctional Natural Polymer Nanoparticles as Antifibrotic Gene Carriers for CKD Therapy.

BACKGROUND: Progressive fibrosis is the underlying pathophysiological process of CKD, and targeted prevention or reversal of the profibrotic cell phenotype is an important goal in developing therapeutics for CKD. Nanoparticles offer new ways to deliver antifibrotic therapies to damaged tissues and resident cells to limit manifestation of the profibrotic phenotype. METHODS: We focused on delivering plasmid DNA expressing bone morphogenetic protein 7 (BMP7) or hepatocyte growth factor (HGF)-NK1 (HGF/NK1) by encapsulation within chitosan nanoparticles coated with hyaluronan, to safely administer multifunctional nanoparticles containing the plasmid DNA to the kidneys for localized and sustained expression of antifibrotic factors. We characterized and evaluated nanoparticles in vitro for biocompatibility and antifibrotic function. To assess antifibrotic activity in vivo, we used noninvasive delivery to unilateral ureteral obstruction mouse models of CKD. RESULTS: Synthesis of hyaluronan-coated chitosan nanoparticles containing plasmid DNA expressing either BMP7 or NGF/NKI resulted in consistently sized nanoparticles, which-following endocytosis driven by CD44+ cells-promoted cellular growth and inhibited fibrotic gene expression in vitro. Intravenous tail injection of these nanoparticles resulted in approximately 40%-45% of gene uptake in kidneys in vivo. The nanoparticles attenuated the development of fibrosis and rescued renal function in unilateral ureteral obstruction mouse models of CKD. Gene delivery of BMP7 reversed the progression of fibrosis and regenerated tubules, whereas delivery of HGF/NK1 halted CKD progression by eliminating collagen fiber deposition. CONCLUSIONS: Nanoparticle delivery of HGF/NK1 conveyed potent antifibrotic and proregenerative effects. Overall, this research provided the proof of concept on which to base future investigations for enhanced targeting and transfection of therapeutic genes to kidney tissues, and an avenue toward treatment of CKD.

Urinary Metabolites of Neonicotinoid Insecticides: Levels and Recommendations for Future Biomonitoring Studies in China.

Neonicotinoids (NEOs) are insecticides that are widely used around the world. Following exposure, NEOs get metabolized in human bodies. The biomarkers to assess human NEO exposure are not well described because of the lack of information on the metabolites of NEOs (m-NEOs). In this study, five m-NEOs including N-desmethyl-acetamiprid (N-dm-ACE), 5-hydroxy-imidacloprid (5-OH-IMI), olefin-imidacloprid (Of-IMI), 1-methyl-3-(tetrahydro-3-furylmethyl) guanidine (DIN-G), and 1-methyl-3-(tetrahydro-3-furylmethyl) (DIN-U) were measured in 275 urine samples collected from 10 cities in China. All of the m-NEOs were frequently detected in urine samples with the median concentrations ranging from 0.42 (DIN-G) to 1.02 (5-OH-IMI) ng/mL. The urinary concentrations of N-dm-ACE and 5-OH-IMI measured in China were higher than those reported from Japan and the USA. In comparison to the parent NEO (i.e., acetamiprid, ACE; imidacloprid, IMI; and dinotefuran, DIN) concentrations reported in the same set of samples by our research group, the median ratios of m-NEO to the corresponding parent NEO (m-NEO/NEO) ranged from 4.95 (DIN-G/DIN) to 37.7 (N-dm-ACE/ACE), indicating that NEOs are mainly present as metabolites rather than the parent forms. Furthermore, the ratio of Σm-NEOs/ΣNEOs was significantly (p < 0.01) higher in females than in males, suggesting that NEOs are more readily metabolized in females or females are more highly exposed to m-NEOs. To our knowledge, this is the first study to measure Of-IMI, DIN-G, and DIN-U levels in urine samples from China. We recommend biomonitoring studies to include N-dm-ACE, 5-OH-IMI, and DIN-U (and DIN-G) for clear understanding of human exposure to ACE, IMI, and DIN, respectively.

Comparative transcriptome analysis of the main beam and brow tine of sika deer antler provides insights into the molecular control of rapid antler growth.

BACKGROUND: Deer antlers have become a valuable model for biomedical research due to the capacities of regeneration and rapid growth. However, the molecular mechanism of rapid antler growth remains to be elucidated. The aim of the present study was to compare and explore the molecular control exerted by the main beam and brow tine during rapid antler growth. METHODS: The main beams and brow tines of sika deer antlers were collected from Chinese sika deer (Cervus nippon) at the rapid growth stage. Comparative transcriptome analysis was conducted using RNA-Seq technology. Differential expression was assessed using the DEGseq package. Functional Gene Ontology (GO) enrichment analysis was accomplished using a rigorous algorithm according to the GO Term Finder tool, and KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway enrichment analysis was accomplished with the R function phyper, followed by the hypergeometric test and Bonferroni correction. Quantitative real-time polymerase chain reaction (qRT-PCR) was carried out to verify the RNA levels for differentially expressed mRNAs. RESULTS: The expression levels of 16 differentially expressed genes (DEGs) involved in chondrogenesis and cartilage development were identified as significantly upregulated in the main beams, including transcription factor SOX-9 (Sox9), collagen alpha-1(II) chain (Col2a1), aggrecan core protein (Acan), etc. However, the expression levels of 17 DEGs involved in endochondral ossification and bone formation were identified as significantly upregulated in the brow tines, including collagen alpha-1(X) chain (Col10a1), osteopontin (Spp1) and bone sialoprotein 2 (Ibsp), etc. CONCLUSION: These results suggest that the antler main beam has stronger growth capacity involved in chondrogenesis and cartilage development compared to the brow tine during rapid antler growth, which is mainly achieved through regulation of Sox9 and its target genes, whereas the antler brow tine has stronger capacities of endochondral bone formation and resorption compared to the main beam during rapid antler growth, which is mainly achieved through the genes involved in regulating osteoblast and osteoclast activities. Thus, the current research has deeply expanded our understanding of the intrinsic molecular regulation displayed by the main beam and brow tine during rapid antler growth.

Autophagy and Acute Kidney Injury.

Acute kidney injury (AKI) is one of the major kidney diseases associated with poor clinical outcomes both in short- and long-term, which caused by toxins, transient ischemia, and so on. Autophagy is a cellular stress response that plays important roles in the pathogenesis of various diseases, including kidney diseases. Autophagy is induced in proximal tubules during AKI. It has been demonstrated that autophagy plays a renoprotective role in AKI by pharmacological and genetic inhibitory studies. However, the role of autophagy in kidney recovery and repair from AKI remains unknown mostly. In many studies, a dynamic change of autophagy was important for tubular proliferation and repair in the recovery phase of AKI. Moreover, autophagy may not only promote renal fibrosis through inducing tubular atrophy and decomposition but also prevent it by mediating intracellular degradation of excessive collagen in terms of renal fibrosis. In further researches, we expect to clarify the regulation of autophagy in kidney injury and repair, and find out therapeutic drugs for treating AKI and preventing its progression to chronic kidney disease.

Autophagy and Glomerular Diseases.

Autophagy is an endogenous and essential process which maintains cellular homeostasis and directs cell fate. The glomerular diseases are one main part of the kidney diseases, often associated with poor clinical outcomes. The regulation of autophagy contributes to the progression of various glomerular diseases, including focal segmental glomerulosclerosis, lupus nephritis, and so on. For example, it has been demonstrated that prevention of autophagic flux in the kidney epithelium and podocytes is sufficient to trigger a degenerative disease of the kidney with many of the manifestations of human FSGS. We review the roles of autophagy in glomerular diseases. Therapies in clinical use, and in preclinical or clinical development, are also discussed in relation to their effects on autophagy in glomerular diseases.

Autophagy and Diabetic Nephropathy.

In recent years, diabetic kidney disease has been the main cause of end-stage renal disease; more and more people have faced this serious public health problem worldwide. Autophagy is a conserved multistep pathway that degrades and recycles damaged organelles and macromolecules to maintain intracellular homeostasis. Autophagy plays key roles in several diseases, including kidney diseases. It has been suggested that dysregulated autophagy plays a vital role in both glomerular and tubulointerstitial pathologies in kidneys under diabetic conditions. The advances in our understanding of autophagy in diabetic kidney disease will be helpful for us to discover a new therapeutic target for the prevention and treatment of this life-threatening diabetes complication.

Profiles of parabens and their metabolites in paired maternal-fetal serum, urine and amniotic fluid and their implications for placental transfer.

Six parabens and their four metabolites were measured in paired maternal serum (MS) and cord serum (CS) samples collected from 95 pregnant women to elucidate placental transfer of this class of compounds. Matched maternal urine (MU) and amniotic fluid (AF) collected from 13 of 95 pregnant women were also analyzed to examine partition of these chemicals between maternal and fetal tissues. The placental transfer rates (PTRs; concentration ratio of parabens between CS and MS) of methyl- (MeP), ethyl- (EtP), propyl-parabens (PrP) were 0.81, 0.63, and 0.60, respectively. Furthermore, the PTRs of OH-MeP (0.93) and OH-EtP (1.8) were higher than those of their corresponding parent parabens, which suggested that hydroxylation increased placental transfer rates of parabens. Structure-dependent placental transfer mechanisms were observed. A significant negative correlation between molecular weights (or log Kow) of MeP, EtP, PrP, and p-hydroxy benzoic acid (4-HB) and PTRs suggested passive diffusion as a mechanism of placental transfer of these chemicals. Nevertheless, other hydroxylated metabolites (OH-EtP, OH-MeP, and 3,4-dihydroxy benzoic acid (3,4-DHB)) showed a positive correlation between molecular weight (or log Kow) and PTRs, which suggested that the placental transfer is mediated by protein binding of these metabolites. The MU to MS concentration ratios of MeP (MU/MSMeP) and PrP (MU/MSPrP) were 71 and 81, respectively, and MU/MSMeP was two orders of magnitude higher than that found for the metabolite (MU/MSOH-MeP: 0.35), suggesting that hydroxylation metabolite reduced urinary elimination of parabens. To our knowledge, this is the first time to report the occurrence and distribution of parabens and their metabolites in paired maternal-fetal serum, urine, and AF samples in China. Our results provide novel information on placental transfer of parabens and their metabolites.

One-step sample processing method for the determination of perchlorate in human urine, whole blood and breast milk using liquid chromatography tandem mass spectrometry.

A one-step sample processing was developed to determine the levels of perchlorate in human urine, whole blood and breast milk by using liquid chromatography tandem mass spectrometry (LC-MS/MS). Athena C18-WP column was used to separate and analyze perchlorate. Perchlorate and isotope-labeled perchlorate (Cl18O4-) internal standards were spiked in the sample matrix through vortex mixing, centrifugation, and filtration. The filtrate was collected and subjected to LC analysis. The developed method was validated for its reproducibility, linearity, trueness, and recovery. Satisfactory recovery of perchlorate ranged from 81% to 117% with intraday relative standard deviations (RSDs) (n = 3) and inter-day RSDs (n = 9) of 5-18% and of 5-16%, respectively. Good linearity (R2 ≥ 0.99) was observed. Limits of detection and quantification for perchlorate ranged from 0.06 µg/L to 0.3 µg/L and from 0.2 µg/L to 1 µg/L, respectively. Perchlorate concentrations were found in human urine (n = 38) and whole blood (n = 8) samples with the range of 6.5-288.6 µg/L and 0.3-2.8 µg/L, respectively. These results indicate the applicability of our developed method in determining perchlorate level in real samples. Moreover, this method is also highly reliable, sensitive and selective in detecting perchlorate in human urine, whole blood and breast milk samples and may be applicable to other matrixes i.e. saliva, serum, plasma, milk powder and dairy milk.

Heavy metals in human urine, foods and drinking water from an e-waste dismantling area: Identification of exposure sources and metal-induced health risk.

Electronic waste or e-waste dismantling activities are known to release metals. However, the human exposure pathways of metals, and their association with oxidative stress in e-waste dismantling areas (EDAs) remain unclear. In this study, our results revealed elevated geometric mean concentrations in vegetables (Cd 0.096 and Pb 0.35 µg/g fw), rice (Cd 0.15, Pb 0.20, and 12.3 µg/g fw), hen eggs (Cd 0.006 and Pb 0.071 µg/g fw), and human urine (Cd 2.12, Pb 4.98, Cu 22.2, and Sb 0.20 ng/mL). Our calculations indicate that rice consumption source accounted for the overwhelming proportion of daily intakes (DIs) of Cd (61-64%), Cu (85-89%), and Zn (75-80%) in children and adults living in EDA; vegetables were the primary contributors to the DIs of Cd (30-32%); and rice (20-29%), vegetables (28-38%), and dust ingestion (26-45%) were all important exposure sources of Pb. Risk assessment predicted that DIs of Cd, Pb, Cu, and Zn via food consumption poses health risks to local residents of EDAs, and the urinary concentrations of analyzed metals were significantly (Pearson correlation coefficient: r = 0.324-0.710; p < 0.01) associated with elevated 8-OHdG, a biomarker of oxidative stress in humans.

Serum concentrations of bisphenol A and its alternatives in elderly population living around e-waste recycling facilities in China: Associations with fasting blood glucose.

In the present study, concentrations of bisphenol A (BPA) and its six alternatives were quantified in serum samples collected from elder population living around an e-waste recycling facilities as well as an reference area in China. BPA, bisphenol AF (BPAF), and bisphenol F (BPF) were frequently detected (detection rates: > 65%) in serum samples collected from residents living near e-waste dismantling facilities, with geometric mean (GM) concentrations of 3.2, 0.0074, and 0.062 ng/mL, respectively. The detection frequencies of other four bisphenols (BPs) in serum samples were lower than 25%, regardless of the sampling areas. Significant difference (Mann-Whitney U-test, p < 0.05) was observed in the serum concentration of BPA, but not BPAF and BPF, between the e-waste recycling and reference areas. This finding indicated e-waste dismantling activities are correlated with human BPA exposure. Significant higher (p < 0.05) detection rates of donors who had abnormal fasting blood glucose (FBG) levels were found in e-waste recycling areas (45%) than those found in reference area. Our results suggested BPA and BPAF exposure might associated with abnormal FBG in participants living in e-waste sites. To our knowledge, this study is first determination of BPs in serum samples and assessment of health risk of elderly people from BPs exposure in e-waste dismantling area.

20(S)-Ginsenoside Rg3 Promotes HeLa Cell Apoptosis by Regulating Autophagy.

20(S)-Ginsenoside Rg3 (GRg3) has various bioactivities including anti-cancer effects and inhibition of autophagy. However, no reports have investigated the appearance of autophagy or the connection between autophagy and apoptosis in HeLa cells treated with 20(S)-GRg3. Cell viability was measured by CCK-8 (cell counting kit-8) assays. Apoptosis and the cell cycle were analyzed by Hoechst 33342 staining and flow cytometry. Apoptotic pathways were examined by ROS (reactive oxygen species) determination and rhodamine 123 assays. Western blot analysis was used to determine changes in protein levels. Autophagy induction was monitored by acidic vesicular organelle staining and EGFP-LC3 transfection. 20(S)-GRg3 inhibited autophagy of cells in a starved state, making it impossible for cells to maintain a steady state through autophagy, and then induced apoptosis. 20(S)-GRg3 blocked the late stage of autophagy (fusion of lysosomes and degradation of autophagic lysosomes), including a decrease in acidic vesicular organelle fluorescence, increased LC3 I-II conversion, accumulation of EGFP-LC3 fluorescence, GFP-mRFP-LC3 red-green fluorescence ratio, degradation of the substrate p62, and loss of the balance between autophagy and apoptosis, which induced apoptosis. ROS increased, the mitochondrial membrane potential decreased, apoptotic inducer AIF was released from mitochondria, and nuclear transfer occurred, triggering a series of subsequent apoptotic events. Autophagy inducer rapamycin inhibited the apoptosis induced by 20(S)-GRg3, whereas autophagy inhibitor BA1 promoted apoptosis induced by 20(S)-GRg3. Therefore, 20(S)-GRg3 promoted HeLa cell apoptosis by regulating autophagy. In the autophagic state, 20(S)-GRg3 can be used as a novel autophagy inhibitor in synergy with tumor-blocking therapies such as chemotherapy, which supports its application in the medical field.