Triterpenoids from the rhizomes and roots of Gentiana scabra Bge. And their cytotoxic activities.

Phytochemical investigation on the rhizomes and roots of Gentiana scabra (Gentianaceae) led to the isolation of five new triterpenoids (1-5), together with seven known ones (6-12). The structures and absolute configurations of the new compounds were elucidated by spectroscopic data interpretation, ECD calculation and X-ray crystallographic analysis. Noticeably, compound 4 was an uncommon 3,4-seco-pentacyclic triterpenoid in natural products. The in vitro cytotoxic activities of all isolates against human cancer cell lines (HepG2, Hep3B, HCT116, and U87) were measured using MTT assay. Among them, compounds 2-9, 11, and 12 exhibited anti-proliferative effects against these tumor cell lines.

Schisandra chinensis lignans improve insulin resistance by targeting TLR4 and activating IRS-1/PI3K/AKT and NF-κB signaling pathways.

Schisandra chinensis, a traditional Chinese medicine, has been widely applied in China to treat diabetes and its complications. The aim of this study was to discover the active compounds and explain related molecular mechanism contributing to the anti-diabetic effect of Schisandra chinensis. Herein, the therapeutic effects of Schisandra chinensis extracts on type 2 diabetes mellitus (T2DM) were firstly confirmed in vivo. Subsequently, various lignans were isolated from Schisandra chinensis and tested for hypoglycemic activity in palmitic acid-induced insulin-resistant HepG2 (IR-HepG2) cells. Among these lignans, R-biar-(7S,8R)-6,7,8,9-tetrahydro-1,2,3,12,13,14-hexamethoxy-7,8-dimethyl-7-dibenzo [a, c] cyclooctenol (compound 2) and Gomisin A (compound 4) were identified significantly increased the glucose consumption in IR-HepG2 cells. Meanwhile, compounds 2 and 4 activated the insulin receptor substrate-1 (IRS-1)/phosphoinositide 3-kinase (PI3K)/Ak strain transforming (AKT) pathway, which regulates glucose transporter 2 (GLUT2) and glucose-6-phosphatase (G6Pase), essential for gluconeogenesis and glucose uptake. These compounds also inhibited the nuclear factor-κB (NF-κB) signaling pathway, reducing interleukin-6 (IL-6) levels. Importantly, the hypoglycemic effects of compounds 2 and 4 were diminished after Toll-like receptor 4 (TLR4) knockdown. Cellular thermal shift assays confirmed increased TLR4 protein stability upon treatment with these compounds, indicating direct binding to TLR4. Furthermore, TLR4 knockdown reversed the effects of compounds 2 and 4 on the NF-κB and IRS-1/PI3K/AKT pathways. Taken together, compounds 2 and 4 alleviate IR by targeting TLR4, thereby modulating the NF-κB and IRS-1/PI3K/AKT pathways. These findings suggest that compounds 2 and 4 could be developed as therapeutic agents for T2DM.

Characterization of Sesquiterpene Dimers from the Flowers of Inula japonica and the Structural Revisions of Related Compounds.

Sesquiterpene dimers are mainly found in the Asteraceae family. However, conflicting reports on the structures of these compounds can be found in the literature. Herein, we describe ten sesquiterpene dimers isolated from the flowers of Inula japonica, including configurational revisions of japonicone H (1-1), japonicone D (2-1), inulanolide A (4-1), japonicone X (5-1), and inulanolide F (5-2) to compounds 1, 2, 4, and 5, respectively. Five new related metabolites (3 and 6-9) are also described. Application of GIAO NMR/DP4+ analyses and ECD/OR calculations enabled us to revise the absolute configurations of an additional 13 sesquiterpene dimers isolated from plants of the genus Inula. Compounds 1, 2, 4, and 6 exhibited inhibition of nitric oxide production in lipopolysaccharide activated RAW264.7 macrophages with IC50 values of 4.07-10.00 µM.

Benzoate glycosides from Gentiana scabra Bge. and their lipid-lowering activity.

Seven undescribed benzoate glycosides (1-7) and five known ones (8-12) were isolated from the rhizomes of Gentiana scabra Bge. Their structures were characterized by comprehensive NMR and MS spectroscopic data analysis. The lipid-lowering effects of these compounds were evaluated by measuring the triglyceride (TG) contents and intracellular lipid droplets (LDs) in oleic acid (OA)-treated HepG2 cells. The results showed that compounds 1, 5, 7, and 11 significantly reduced the TG content at 20 µM, and the Bodipy staining displayed that OA enhanced the levels of LDs in the cell, while these compounds reversed the lipid accumulation caused by OA. These findings provide a basis for further development and utilization of G. scabra as a natural source of potential lipid-lowering agents.

Risk factors for ischemic stroke in patients with Philadelphia chromosome (Ph)-negative myeloproliferative neoplasms.

BACKGROUND: Philadelphia chromosome-negative myeloproliferative neoplasms (Ph-negative MPNs) are linked with various complications, notably ischemic stroke. The study aims to identify risk factors for ischemic stroke in Ph-negative MPNs patients. METHODS: Patients were categorized into two groups based on whether they had experienced ischemic stroke. Subsequently, an analysis of demographics, biochemical makers, and genetic mutations (JAK2V617F and CALR mutations), was conducted to identify potential associations with an elevated risk of ischemic stroke in individuals with Ph-negative MPNs. RESULTS: A total of 185 patients diagnosed with Ph-negative MPNs participated in the study, including 82 with essential thrombocythemia (ET), 78 with polycythemia vera (PV), and 25 with primary myelofibrosis (PMF). Among these, 57 patients (30.8 %) had a history of ischemic stroke. Independent risk factors associated with ischemic stroke in Ph-negative MPNs patients included hypertension (OR = 5.076) and smoking (OR = 5.426). Among ET patients, smoking (OR = 4.114) and an elevated percentage of neutrophils (OR = 1.080) were both positively correlated with ischemic stroke incidence. For PV patients, hypertension (OR = 4.647), smoking (OR = 6.065), and an increased percentage of lymphocytes (OR = 1.039) were independently associated with ischemic stroke. Regardless of the presence of the JAK2V617F mutation, hypertension was the sole positively and independently associated risk factor for ischemic stroke. The odds ratios for patients with the JAK2V617F mutation was 3.103, while for those without the mutation, it was 11.25. CONCLUSIONS: Hypertension was a more substantial factor associated with an increased incidence of ischemic stroke in Ph-negative MPNs patients.

Tissue-Specific Distribution and Maternal Transfer of Persistent Organic Halogenated Pollutants in Frogs.

Persistent organic pollutants pose a great threat to amphibian populations, but information on the bioaccumulation of contaminants in amphibians remains scarce. To examine the tissue distribution and maternal transfer of organic halogenated pollutants (OHPs) in frogs, seven types of tissues from black-spotted frog (muscle, liver, kidney, stomach, intestine, heart, and egg) were collected from an e-waste-polluted area in South China. Among the seven frog tissues, median total OHP concentrations of 2.3 to 9.7 µg/g lipid weight were found (in 31 polychlorinated biphenyl [PCB] individuals and 15 polybrominated diphenyl ether [PBDE], dechlorane plus [syn-DP and anti-DP], bexabromobenzene [HBB], polybrominated biphenyl] PBB153 and -209], and decabromodiphenyl ethane [DBDPE] individuals). Sex-specific differences in contaminant concentration and compound compositions were observed among the frog tissues, and eggs had a significantly higher contaminant burden on the whole body of female frogs. In addition, a significant sex difference in the concentration ratios of other tissues to the liver was observed in most tissues except for muscle. These results suggest that egg production may involve the mobilization of other maternal tissues besides muscle, which resulted in the sex-specific distribution. Different parental tissues had similar maternal transfer mechanisms; factors other than lipophilicity (e.g., molecular size and proteinophilic characteristics) could influence the maternal transfer of OHPs in frogs. Environ Toxicol Chem 2024;43:1557-1568. © 2024 SETAC.

A comprehensive assessment of external exposure to persistent halogenated organic pollutants for residents in an e-waste recycling site, South China.

Human skin wipes from 30 participants, air, dust, and food items were collected from a former electronic waste site in South China to provide a comprehensive understanding of residents' exposure to halogenated flame retardants (HFRs) and polychlorinated biphenyls (PCBs). The total concentration of halogenated organic pollutants (HOPs) in the dust, air, food and skin wipes ranged 240-25000 ng/g, 130-2500 pg/m3, 0.08-590 ng/g wet weight, and 69-28000 ng/m2, respectively. Wild fish, vegetables, and air were dominated by PCBs, whereas dust, livestock, and poultry were dominated by HFRs. The HOP concentrations were several orders of magnitude higher in local foodstuffs than in market foodstuffs. The chemical composition on the forehead was remarkably different from that on the hand. The importance of different exposure routes depends on the residents' food choices, except decabromodiphenyl ethane (DBDPE). For residents who consumed a 100-foot diet (mainly egg) and local wild fish, diet ingestion overwhelmed other exposure routes, and PCBs were mainly contributed by fish and HFRs by egg. For residents who consumed market food, the dermal absorption of most PCB congeners and dust ingestion of highly brominated flame retardants were relatively prominent. Inhalation was found to be a crucial route for pentabromoethylbenzene (PBEB).

Prevalence and influencing factors of abnormal carotid artery intima-media thickness in Henan Province in China.

Background: Carotid intima-media thickness (CIMT) has been shown to be a valuable predictor of cardiovascular diseases (CVDs). The aim of this study was to investigate the influencing factors of CIMT among adults in Central China. Methods: A total of 2,578 participants who underwent physical examination in Henan Provincial People's Hospital between January 2018 and July 2018 were enrolled. The respondents were divided into two subgroups according to their CIMT value (CIMT ≥1.0 mm group and CIMT <1.0 mm group). Variables considered were age, gender, total cholesterol, triglycerides, low-density lipoprotein (LDL) and high-density lipoprotein (HDL) triglycerides, fasting blood glucose, and uric acid levels, as well as hypertension, diabetes, body mass index (BMI), waist-to-hip ratio, body fat percentage, and visceral fat area (VFA). Logistic regression analysis was performed to explore the potential factors influencing CIMT. Results: The proportion of CIMT ≥1.0 mm among the physical examination population was 27.42% (707/2 578). The analysis of the two groups revealed significant differences in age, sex, hypertension, diabetes, total cholesterol, and HDL cholesterol. In the logistic regression analysis, age (OR=1.071, 95%CI=1.062-1.080), male sex (OR=2.012, 95%CI=1.251-2.238), hypertension (OR=1.337, 95%CI=1.031-1.735), diabetes (OR=1.535, 95%CI=1.045-2.255), HDL cholesterol (OR=0.540, 95%CI=0.366-0.796), and LDL cholesterol (OR=1.336, 95%CI=1.154-1.544) were significantly associated with abnormal CIMT. Conclusion: Early screening should be carried out among men, the older adults, and those with hypertension, diabetes, and dyslipidemia.

Trophic Transfer of Halogenated Organic Pollutants in a Wetland Food Web: Insights from Compound-Specific Nitrogen Isotope of Amino Acids and Food Source Analysis.

A trophic position (TP) model (TPmix model) that simultaneously considered trophic discrimination factor and ßGlu/Phe variations was developed in this study and was first applied to investigate the trophic transfer of halogenated organic pollutants (HOPs) in wetland food webs. The TPmix model characterized the structure of the wetland food web more accurately and significantly improved the reliability of TMF compared to the TPbulk, TPAAs, and TPsimmr models, which were calculated based on the methods of stable nitrogen isotope analysis of bulk, traditional AAs-N-CSIA, and weighted ßGlu/Phe, respectively. Food source analysis revealed three interlocking food webs (kingfisher, crab, and frogs) in this wetland. The highest HOP biomagnification capacities (TMFmix) were found in the kingfisher food web (0.24-82.0), followed by the frog (0.08-34.0) and crab (0.56-11.7) food webs. The parabolic trends of TMFmix across combinations of log KOW in the frog food web were distinct from those of aquatic food webs (kingfisher and crab), which may be related to differences in food web composition and HOP bioaccumulation behaviors between aquatic and terrestrial organisms. This study provides a new tool to accurately study the trophic transfer of contaminants in wetlands and terrestrial food webs with diverse species and complex feeding relationships.

Association between milk and dairy consumption and executive functioning: A cross-sectional survey based on rural Chinese adolescents.

BACKGROUND: Milk and dairy product consumption continue to increase in developing countries, with positive effects on adolescent physical and mental health. However, the effect of milk and dairy product consumption on executive function of adolescents has been less reported. This study aimed to analyze the status of milk and dairy product consumption and its association with executive function among adolescents in rural areas of China. The study aims to contribute to the healthy development of adolescents in rural areas of China. METHODS: A three-stage stratified whole-group sampling method was used to investigate the milk and dairy product consumption status and executive function of 1360 adolescents in rural areas of China. One-way analysis of variance (ANOVA) and chi-square test was used to compare the milk and dairy product consumption of different categories of adolescents. Linear regression analysis and logistic regression analysis were used to analyze the association between milk and dairy product consumption and executive function. RESULTS: The proportions of adolescents in rural China with milk and dairy product consumption ≤1 t/w, 2-4 t/w, and ≥5 t/w were 39.26%, 45.07%, and 15.66%, respectively. After adjusting for relevant confounding variables, logistic regression analysis showed that compared to adolescents with milk and dairy product consumption ≥5 t/w, milk and dairy product consumption 2-4 t/w (OR = 2.115,95% CI: 1.265, 3.533) and ≤1 t/w (OR = 5.929,95% CI: 3.552,9.895) had a higher risk of inhibit control dysfunction (p < 0.05). Compared to adolescents with milk and dairy product consumption ≥5 t/w, adolescents with milk and dairy product consumption ≤1 t/w (OR = 2.141,95% CI: 1.110,4.129) had a higher risk of conversion the risk of flexibility dysfunction was also higher in adolescents with milk and dairy product consumption ≤1 t/w (OR = 2.141,95% CI: 1.110,4.129). CONCLUSION: Milk and dairy product consumption among adolescents in rural areas of China is inadequate and has a positive association with executive function. In the future, we should increase milk and dairy product consumption and improve executive function of adolescents in rural areas of China in order to promote healthy physical and mental development.

Artificial Infestation of Sarcoptes scabiei (Acari: Sarcoptidae) in Rabbits Exhibits Progressive Pathological Changes, Apoptosis, and Keratinization in the Skin.

Sarcoptes scabiei (S. scabiei) is an ectoparasite that can infest humans and 150 mammalian host species, primarily causing pruritus, crust, and alopecia. However, neither the pathological process of host skin under S. scabiei infection nor the mechanism of S. scabiei infection in regulating apoptosis and keratinization of host skin has been studied yet. In this study, a total of 56 rabbits were artificially infested with S. scabiei, and the skin samples were collected at seven different time points, including 6 h, 12 h, day 1, day 3, 1 week, 4 weeks, and 8 weeks, whereas a group of eight rabbits served as controls. We measured epidermal thickness by H&E staining, observed the skin ultrastructure by electron microscopy, and detected the degree of skin apoptosis by TUNEL staining. The level of transcription of genes related to apoptosis and keratinization was detected by quantitative real-time PCR (qRT-PCR), and the level of Bcl-2 protein expression was further detected using immunohistochemistry. Our results showed that, with increased infestation time, the epidermal layer of the rabbit skin exhibited significant thickening and keratinization, swollen mitochondria in the epidermal cells, and increased skin apoptosis. The level of caspase-1, 3, 8, 10, 14, and Bcl-2 mRNA expression was increased, whereas the level of keratin 1 and 5 was decreased after S. scabiei infestation. In conclusion, S. scabiei infestation causes thickening of the epidermis, which may be related to apoptosis-induced proliferation and skin keratinization.

Occurrence, spatial distribution, and risk assessment of short- and medium-chain chlorinated paraffins in sediment from black-odorous rivers across China.

Chlorinated paraffins (CPs) were massively produced for varied industrial purposes, of which improper handling and consequent environmental release resulted in worldwide contamination. The present study investigated the occurrence and spatial distribution of short- and medium-chain chlorinated paraffins (SCCP/MCCPs) in 171 sediment samples from black-odorous urban rivers across China. Total SCCP and MCCP concentrations ranged from 8.3 to 9.4 × 104 (median: 1.1 × 103) ng/g dw, and from not-detected-value to 1.0 × 106 (median: 1.3 × 104) ng/g dw, respectively. No clear spatial distribution of SCCPs and MCCPs was observed since black-odorous urban rivers were polluted by point-sources of the SCCP/MCCPs. Significant positive correlations were identified between SCCP/MCCPs and total organic carbon, and between SCCP/MCCPs and other persistent organic matter, including polybrominated diethyl ethers, polychlorinated biphenyls, antibiotics, and plasticizers. The average ratios of MCCPs to SCCPs in most samples were divided into 11 and 16, implying the manufacturing and use of at least two types of CP technical mixtures in China. The composition of SCCP/MCCPs were similar to that in their commercial products. Ecological risk assessments by two approaches, including the Federal Environmental Quality Guidelines and Risk Quotient, both revealed that SCCP/MCCP in surface sediments confer an ecological risk. ENVIRONMENTAL IMPLICATION: SCCPs and MCCPs can be considered "hazardous materials" because of their massive production and their potential persistence, long-distance transfer, bioaccumulation potential, and toxicity. This research conducted a comprehensive study on SCCP/MCCP in black-odorous urban river sediments across China and revealed their environmental risk, which may improve understanding of SCCP/MCCP contamination characteristics.

The effect of nutritional status on clinical outcome in lung transplantation.

BACKGROUND AND OBJECTIVES: Nutritional status greatly impacts the clinical outcome of the patients receiving lung transplantation. The objective of this study was to evaluate the effect of nutritional status on the clinical outcome in lung transplant recipients. METHODS AND STUDY DESIGN: A single-center retrospective study was conducted including 73 patients received lung transplantation from December 2015 to April 2022 in the Affiliated Henan Provincial People's Hospital of Zhengzhou University. Data were collected from the hospital information system. The records of BMI, malnutrition defined by the Global Leadership Initiative on Malnutrition (GLIM) diagnostic criteria, hemoglobin and plasma albumin before operation were accessed. The primary outcome assessed was survival or mortality represented by Kaplan-Meier survival curves; the log-rank test and multivariate Cox proportional hazards regression were used to evaluate the influence of each factor on survival. RESULTS: Kaplan-Meier survival analysis showed that malnutrition, hemoglobin and plasma albumin were predictors of survival in lung transplantation (Log Rank p<0.05). Multivariate Cox regression showed that pre-operative hemoglobin <130 g/L (HR 2.532, p=0.036) and plasma albumin <35 g/L (HR 2.723, p=0.016) were associated with the decreased survival rate. CONCLUSIONS: Preoperative anemia and hypoalbuminemia increase the mortality risk of the lung transplantation patients. Pre-operative nutrition support, therefore, is likely to be critical for improving clinical outcome in patients undergoing lung transplantation.

Bioamplification and Biomagnification of Polycyclic Aromatic Hydrocarbons and Halogenated Organic Pollutants in Moths from an Electronic Waste Recycling Site.

Samples of Asota caricae (larvae, pupae, and adults) and its host plant leaf (Ficus hispida), larvae of Aloa lactinea, and mixed adult moths were collected from an electronic waste (e-waste) recycling site in south China. Polycyclic aromatic hydrocarbons, polychlorinated biphenyls, and polybrominated diphenyl ethers were found to exhibit concentrations of 420-1300, 100-860, and 7.6-49 ng/g dry weight, respectively. The different chemical compositions among the samples of the three groups indicated that at least two exposure scenarios occurred among the moths in the study area. A complex relationship between bioamplification factors and the octanol-water partition coefficient (log KOW ) was observed during metamorphosis, in which a positive relationship was evident for 5 < log KOW < 7, whereas an inverse relationship occurred for log KOW values outside of this range. The biomagnification factors (BMFs) calculated from the larvae of Asota caricae to the host plant were negatively correlated with log KOW for all chemicals, differing completely from those obtained in previous studies. However, after metamorphosis, the correlation between BMF and log KOW was found to coincide with that in previous studies. These results indicate that the biotransformation of pollutants in organisms played a key role in determining whether or not biomagnification occurred in organisms and highlight the potential application of the metabolic rate of chemicals in screening-level risk assessments of new chemicals. Environ Toxicol Chem 2022;41:2395-2403. © 2022 SETAC.

Tissue-Specific Distribution of Legacy and Emerging Organophosphorus Flame Retardants and Plasticizers in Frogs.

Five types of tissues, including the liver, kidney, intestine, lung, and heart, were collected from black-spotted frogs and bullfrogs to study the tissue-specific accumulation of organophosphorus flame retardants (PFRs) and plasticizers. Thirteen PFRs and nine plasticizers were detected, with average total concentrations of 1.4-13 ng/g ww and 858-5503 ng/g ww in black-spotted frogs, 3.6-46 ng/g ww and 355-3504 ng/g ww in bullfrogs. Significant differences in pollutant concentrations among different tissues in the two frog species were found, indicating the specific selectivity distribution of PFRs and plasticizers. Overall, liver tissues exhibited significantly higher pollutant concentrations. The pollutant concentration ratios of other tissue to the sum of liver tissue and other tissues (OLR, Cother/(Cother + Cliver)) corresponding to male frogs were significantly greater than those of females, suggesting that male frogs could have higher metabolic potentials for PFRs and plasticizers. No obvious correlations between OLR and log KOW were found, indicating that the other factors (e.g., bioaccumulation pathway and metabolism) besides lipophicity could influence the deposition of PFRs and plasticizers in frog livers. Different parental transfer patterns for PFRs and plasticizers were observed in frogs when using different tissues as parental tissues. Moreover, the liver tissues had similar parental transfer mechanism with muscle tissues.

Spatial Distribution, Bioconversion and Ecological Risk of PCBs and PBDEs in the Surface Sediment of Contaminated Urban Rivers: A Nationwide Study in China.

Surface sediments of polluted urban rivers can be a reservoir of hydrophobic persistent organic pollutants (POPs). In this study, we comprehensively assessed the contamination of two groups of POPs, that is, polychlorinated biphenyls (PCBs) and polybrominated diphenyl ethers (PBDEs), in 173 black-odorous urban rivers in China. Spatial distribution of PCBs and PBDEs showed similar patterns but very different contamination levels in surface sediments, that is, average concentrations of 10.73 and 401.16 ng/g dw for the ∑PCBs and ∑PBDEs, respectively. Tetra-/di-CBs and deca-BDE are major PCBs and PBDEs and accounted for 59.11 and 95.11 wt % of the ∑PCBs and ∑PBDEs, respectively. Compared with the persistence of PBDEs, the EF changes of chiral PCBs together with previous cultivation evidence indicated indigenous bioconversion of PCBs in black-odorous urban rivers, particularly the involvement of uncharacterized Dehalococcoidia in PCB dechlorination. Major PCB sources (and their relative contributions) included pigment/painting (25.36%), e-waste (22.92%), metallurgical industry (13.25%), and e-waste/biological degradation process (10.95%). A risk assessment indicated that exposure of resident organisms in urban river sediments to deca-/penta-BDEs could pose a high ecological risk. This study provides the first insight into the contamination, conversion and ecological risk of PCBs and PBDEs in nationwide polluted urban rivers in China.

Legacy and emerging organophosphorus flame retardants and plasticizers in frogs: Sex difference and parental transfer.

Black-spotted frogs and bullfrogs from an e-waste polluted area were collected and examined for legacy and emerging organophosphorus flame retardants (PFRs) and plasticizers. Total concentrations of PFRs and plasticizers were 0.62-15 ng/g wet weight (ww) and 316-4904 ng/g ww in muscles, 2.2-59 ng/g ww and 127-5757 ng/g ww in eggs and gonads, and 1.2-15 ng/g ww and 51-1510 ng/g ww in oviducts, respectively. For muscle tissues, concentrations of ∑PFRs, triethyl phosphate, tris-(2-chloroethyl) phosphate, and tris-(chloro-2-propyl) phosphate were significantly higher in the males than females (p < 0.05). However, for reproductive tissues, eggs exhibited higher levels of those contaminants than gonads (p < 0.05). No significant sex difference in levels of plasticizers was observed in muscles. In contrast, levels for (2-ethylhexyl) phthalate, di-n-butyl phthalate, and di-iso-butyl phthalate in gonads were significantly higher than those in eggs (p < 0.05). Significantly negative linear correlations between maternal transfer ratios and log KOW were found in female frogs. Paternal transfer potentials were first significantly and positively correlated to log KOW (<6) and then decreased afterward in the males. These results indicated that parental transfer was answer for the sex-specific accumulation of PFRs and plasticizers in frogs.

miR-128-3p contributes to mitochondrial dysfunction and induces apoptosis in glioma cells via targeting pyruvate dehydrogenase kinase 1.

Glioma, like most cancers, possesses a unique bioenergetic state of aerobic glycolysis known as the Warburg effect, which is a dominant phenotype of most tumor cells. Glioma tumors exhibit high glycolytic metabolism with increased lactate production. Data derived from the gene expression profiling interactive analysis (GEPIA) database show that pyruvate dehydrogenase kinase 1 (PDK1) is significantly highly expressed in glioma tissues compared with corresponding normal tissues. PDK1 is a key enzyme in the transition of glycolysis to tricarboxylic acid cycle, via inactivating PDH and converting oxidative phosphorylation to Warburg effect, resulting in increment of lactate production. Silencing of PDK1 expression resulted in reduced lactate and ATP, accumulation of ROS, mitochondrial damage, decreased cell growth, and increased cell apoptosis. Aberrant expression of miR-128 has been observed in many human malignancies. Mechanistically, we discover that overexpressed miR-128-3p disturbs the Warburg effect in glioma cells via reducing PDK1. Our experiments confirmed that the miR-128-3p/PDK1 axis played a pivotal role in cancer cell metabolism and growth. Collectively, these findings suggest that therapeutic strategies to modulate the Warburg effect, such as targeting of PDK1, might act as a potential therapeutic target for glioma treatment.

Short- and medium-chain chlorinated paraffins in aquatic organisms from an e-waste site: Biomagnification and maternal transfer.

Chlorinated paraffins (CPs) are globally pervasive contaminants that are toxic to humans and wildlife. Inconsistent biomagnification behaviors in different food chains have been reported, and very few studies have been conducted to investigate the maternal transfer of CPs in ovoviviparous species. This study investigated the biomagnification of short- and medium-chain chlorinated paraffins (S/MCCPs) in two aquatic food chains, as well as maternal transfer of S/MCCPs in watersnakes collected from an e-waste polluted pond in southern China. The concentrations of SCCPs and MCCPs varied from 1.2 to 250 µg/g lipid weight (lw) and from 2.3 to 200 µg/g lw in the collected organisms. The SCCP homologue profiles in prey (fish and prawn) differed from those in predators (watersnake and waterbird egg), while MCCP homologue group patterns were homogeneous. All maternal transfer concentration ratios (egg to muscle) of S/MCCPs in the watersnakes were lower than 1 and negatively correlated with the octanol-water partition coefficients (log KOW), different from the maternal transfer of halogenated aromatic pollutants in the watersnake. Biomagnification factors (BMFs) of S/MCCPs for fish-watersnake muscle food chain were larger than 1, while BMFs for the fish-waterbird egg food chain were less than 1. However, when watersnake egg was used to calculate BMF, no biomagnification was found. BMFs in the two food chains showed significant positive linear correlations with chlorine atoms, but no significant correlation with carbon atom numbers, which suggested that a congener-group-specific elimination and excretion process for S/MCCPs exist.

Effects of aflatoxin B1 on the cell cycle distribution of splenocytes in chickens.

The purpose of the present study was to evaluate effects of aflatoxin B1 (AFB1) on the cell cycle and proliferation of splenic cells in chickens. A total of 144 one-day-old Cobb male chickens were randomly divided into 2 equal groups of 72 each and were fed on diets as follows: a control diet and a 0.6 mg/kg AFB1 diet for 21 days. The AFB1 diet reduced body weight, absolute weight and relative weight of the spleen in broilers. Histopathological lesions in AFB1 groups were characterized as slight congestion in red pulp and lymphocytic depletion in white pulp. Compared with the control group, the expression levels of ataxia-telangiectasia mutated (ATM), cyclin E1, cyclin-dependent kinases 6 (CDK6), CDK2, p53, p21 and cyclin B3 mRNA were significantly increased, while the mRNA expression levels of cyclin D1, cdc2 (CDK1), p16, p15 were significantly decreased in the AFB1 groups. Significantly decreased proliferating cell nuclear antigen (PCNA) expression and arrested G0G1 phases of the cell cycle were also seen in the AFB1 groups. In conclusion, dietary AFB1 could induce cell cycle blockage at G0G1 phase and impair the immune function of the spleen. Cyclin D1/CDK6 complex, which inhibits the activin/nodal signaling pathway, might play a significant role in the cell cycle arrest induced by AFB1.