TIGAR Protects Against Adenine-Induced Ferroptosis in Human Proximal Tubular Epithelial Cells by Activating the mTOR/S6KP70 Axis.

TP53-induced glycolysis and apoptosis regulator (TIGAR) acts as a switch for nephropathy, but its underlying mechanism is still unclear. The purpose of this study was to explore the potential biological significance and underlying mechanism of TIGAR in modulating adenine-induced ferroptosis in human proximal tubular epithelial (HK-2) cells. HK-2 cells under- or overexpressing TIGAR were challenged with adenine to induce ferroptosis. The levels of reactive oxygen species (ROS), iron, malondialdehyde (MDA), and glutathione (GSH) were assayed. Expression of ferroptosis-associated solute carrier family seven-member 11 (SLC7A11) and glutathione peroxidase 4 (GPX4) at the level of mRNA and protein were measured by quantitative real-time-PCR and western blotting. The phosphorylation levels of proteins in the mTOR/S6KP70 pathway were determined by western blotting. Adenine overload triggered ferroptosis in HK-2 cells, as evidenced by reduced levels of GSH, SLC7A11, and GPX4, and increased levels of iron, MDA, and ROS. TIGAR overexpression repressed adenine-induced ferroptosis and induced mTOR/S6KP70 signaling. Inhibitors of mTOR and S6KP70 weakened the ability of TIGAR to inhibit adenine-induced ferroptosis. TIGAR inhibits adenine-induced ferroptosis in human proximal tubular epithelial cells by activating the mTOR/S6KP70 signaling pathway. Therefore, activating the TIGAR/mTOR/S6KP70 axis may be a treatment for crystal nephropathies.

Bactericidal and Hemocompatible Coating via the Mixed-Charged Copolymer.

Cationic antibacterial coating based on quaternary ammonium compounds, with an efficient and broad spectrum bactericidal property, has been widely used in various fields. However, the high density of positive charges tends to induce weak hemocompatibility, which hinders the application of the cationic antibacterial coating in blood-contacting devices and implants. It has been reported that a negatively charged surface can reduce blood coagulation, showing improved hemocompatibility. Here, we describe a strategy to combine the cationic and anionic groups by using mixed-charged copolymers. The copolymers of poly (quaternized vinyl pyridine- co- n-butyl methacrylate- co-methacrylate acid) [P(QVP- co- nBMA- co-MAA)] were synthesized through free radical copolymerization. The cationic group of QVP, the anionic group of MAA, and the hydrophobic group of nBMA were designed to provide bactericidal capability, hemocompatibility, and coating stability, respectively. Our findings show that the hydrophilicity of the copolymer coating increased, and its zeta potential decreased from positive charge to negative charge with the increase of the anionic/cationic ratio. Meanwhile, the bactericidal property of the copolymer coating was kept around a similar level compared with the pure quaternary ammonium copolymer coating. Furthermore, the coagulation time, platelet adhesion, and hemolysis tests revealed that the hemocompatibility of the copolymer coating improved with the addition of the anionic group. The mixed-charged copolymer combined both bactericidal property and hemocompatibility and has a promising potential in blood-contacting antibacterial devices and implants.

[Microbial anaerobic dechlorination of polychlorinated biphenyls in paddy soil slurry].

We studied the dechlorination process of Aroclor1260, a high-chlorinated polychlorinated biphenyls (PCBs) mixture in an anaerobic paddy soil slurry, and further analyzed the related microbial community structures. The Aroclor1260 was reduced up to 55.5% in the natural paddy soil slurry in 128 days, and the reduction percentage dropped to 46.9% after incoculating the paddy soil slurry with a PCBs-dechlorination enrichment culture. The dechlorination mainly occurred in congeners of pentachlorobiphenyl, hexachlorobiphenyl, and specially, the heptachlorobiphenyl, with pentachlorobiphenyl accumulated as dechlorination intermediate. Hydrogen gas produced from fermentation of organic matters was maintained at a lower partial pressure due to its consumption during the dechlorination process, so that the methanogens was suppressed as well. The microbial community structure was significantly different between natural and inoculated paddy soils. Introducing the PCBs-dechlorination enrichment culture changed the local microbial community by the competition between the exogenetic dchlorinators and the indigenous bacteria, overall decreasing the dechlorination activity.

[Biodegradation of organic pollutants by thermophiles and their applications: a review].

Persistent organic pollutants have increasingly become a critical environmental concern, while thermophiles have the high potential of degrading various kinds of environmental organic pollutants. At high temperatures, thermophiles have higher metabolic activity, and the competition by mesophiles is reduced, meanwhile, the solubility and bioavailability of some persistent organic pollutants are greatly increased, and thus, the degradation of the pollutants by thermophiles is more rapid and complete. Therefore, thermophils are of great significance for the bio-treatment of organic wastewater and the bioremediation of organic pollutants-contaminated sites. This paper introduced the research progress on the degradation of organic pollutants by thermophiles in terms of the characteristics of thermophiles in degrading organic pollutants, the effects of temperature on the degradation, the degradation pathways, the degradation enzymes, their coding genes, and practical engineering applications. The future research directions including the degradation mechanisms of thermophiles, their resources reserve, related technology strategies and their applications were also prospected.

[Research advances in microbial dechlorination of polychlorinated biphenyls].

Polychlorinated biphenyls (PCBs) are the typical persistent organic pollutants (POPs) in the environment. As a ubiquitous attenuation course of chlorinated organic compounds in anoxic environment, the microorganism-mediated reductive dechlorination process plays an important role in PCBs transformation, especially the transformation of higher chlorinated PCBs. The higher chlorinated PCBs can be dechlorinated in anaerobic condition, and thus, their persistence and toxicity can be decreased. The resultant lower chlorinated PCBs from the dechlorination can be further degraded and completely mineralized in aerobic condition. This paper summarized the research advances of PCBs microbial reductive dechlorination, introduced the mechanisms and characteristics of the dechlorination and the related specific microorganisms, and approached the affecting factors of PCBs bio-dechlorination, as well as the significances of anaerobic dechlorination coupling with aerobic degradation. The future research directions, including the complex metabolic networks of dechlorinating microbial populations, the screening of novel specific dechlorinators and their practical applications in the remediation of PCBs contaminated sites were also prospected.

Estrogenic activity of the equine estrogen metabolite, 4-methoxyequilenin.

Oxidative metabolism of estrogens has been associated with genotoxicity. O-methylation of catechol estrogens is considered as a protective mechanism. 4-Methoxyequilenin (4-MeOEN) is the O-methylated product of 4-hydroxyequilenin (4-OHEN). 4-OHEN, the major catechol metabolite of the equine estrogens present in the most widely prescribed hormone replacement therapeutics, causes DNA damage via quinone formation. In this study, estrogen receptor (ERa) binding of 4-MeOEN was compared with estradiol (E2) and equilenin derivatives including 4-BrEN using computer modeling, estrogen response element (ERE)-luciferase induction in MCF-7 cells, and alkaline phosphatase (AP) induction in Ishikawa cells. 4-MeOEN induced AP and luciferase with nanomolar potency and displayed a similar profile of activity to E2. Molecular modeling indicated that MeOEN could be a ligand for ERa despite no binding being observed in the ERa competitive binding assay. Methylation of 4-OHEN may not represent a detoxification pathway, since 4-MeOEN is a full estrogen agonist with nanomolar potency.

Activation of estrogen receptor-mediated gene transcription by the equine estrogen metabolite, 4-methoxyequilenin, in human breast cancer cells.

4-Methoxyequilenin (4-MeOEN) is an O-methylated metabolite in equine estrogen metabolism. O-methylation of catechol estrogens is considered as a protective mechanism; however, comparison of the properties of 4-MeOEN with estradiol (E(2)) in human breast cancer cells showed that 4-MeOEN is a proliferative, estrogenic agent that may contribute to carcinogenesis. 4-MeOEN results from O-methylation of 4-hydroxyequilenin, a major catechol metabolite of the equine estrogens present in hormone replacement therapeutics, which causes DNA damage via quinone formation, raising the possibility of synergistic hormonal and chemical carcinogenesis. 4-MeOEN induced cell proliferation with nanomolar potency and induced estrogen response element (ERE)-mediated gene transcription of an ERE-luciferase reporter and the endogenous estrogen-responsive genes pS2 and TGF-alpha. These estrogenic actions were blocked by the antiestrogen ICI 182,780. In the standard radioligand estrogen receptor (ER) binding assay, 4-MeOEN showed very weak binding. To test for alternate ligand-ER-independent mechanisms, the possibility of aryl hydrocarbon receptor (AhR) binding and ER-AhR cross talk was examined using a xenobiotic response element-luciferase reporter and using AhR small interfering RNA silencing in the ERE-luciferase reporter assay. The results negated the possibility of AhR-mediated estrogenic activity. Comparison of gene transcription time course, ER degradation, and rapid activation of MAPK/ERK in MCF-7 cells demonstrated that the actions of 4-MeOEN mirrored those of E(2) with potency for classical and nonclassical estrogenic pathways bracketing that of E(2). Methylation of 4-OHEN may not represent a detoxification pathway because 4-MeOEN is a full, potent estrogen agonist.

[Survey on natural nidus of Metorchis orientalis in Huaihe River Basin].

Parafossarulus striatulus, Pseudorasbora parva and brood ducks are involved in the lifecycle of Metorchis orientalis. Natural nidi of M. orientalis are confirmed in Huaihe River Basin.

Synthesis and bioactivities of two multiple antigen peptides as potential vaccine against schistosoma.

Based on the two antigenic peptides, 26-43 (P26) and 116-131 (P116), derived from 28 kDa glutathione S-transferase of Schistosoma mansoni (Sm28GST), two multiple antigenic peptides (MAPs), (P26)4-MAP and (P116)4-MAP with the same oligomeric lysine core, were synthesized by stepwise solid-phase peptide synthesis method. The antigenicities and protective effects of these two MAPs were examined on experimental animals. As shown in the dot-ELISA result, the synthetic MAPs could be recognized and bound by immunoglobins in both patient's and infected-rabbit's sera. After Kunming mice were immunized with (P26)4-MAP, the worm burden reduction rate and the liver egg reduction rate were 59.9% and 61.1%. In (P26)4-MAP or (P116)4-MAP immunized BALB/c mice, the worm burden reduction rates were 37.5% and 62.5%, respectively, and the liver egg reduction rates were 35.1% and 54.0%, respectively.

[Preliminary study on the ecology of Trichobilharzia cercariae in the Huaihe river system].

OBJECTIVE: To investigate the ecological habit and characteristics of Trichobilharzia cercariae in the Huaihe river system. METHODS: During June of 2002-May of 2003, Radix auricularia snails were collected monthly in Yaohe Fishery of the branch of the Huaihe River. The cercariae, released from the positive snails and collected by Shade Drop Bottle, were examined by direct press. Ducklings were infected by cercariae with different ages and examined for the infection by miracidia hatching method. RESULTS: The results showed a typical seasonal fluctuation in infection rate of the snails, i.e. the cercariae detection rate was 0.81% in July, 0.65% in June, 0.07%-0.26% in April, May, August, September and October respectively, with a significant difference (chi2 = 26.73, P < 0.01). The release of cercariae from the snails showed a diurnal pattern in the natural conditions, with a significant peak between 8:00-12:00. It was proven that the main factors affecting the emerging of cercariae were temperature and light. The cercariae showed positively phototaxis. It was also showed that 50% mortality of the newly released cercariae between 18-25 degrees C occurred at 41 h, and all cercariae died within 52 h. The infectivity of cercariae was age-dependent. Under 18-25 degrees C, the highest infectivity was found at 0.5-8 h after emergence, then declined steadily to negative by 40 h post-emergence. CONCLUSION: The ecological characteristics of Trichobilharzia cercariae have been preliminarily verified in the Huaihe river system.

Synthesis of serine/alanine conjugated 3',5'-TpT.

Serine and alanine phosphoramidates conjugates of 3',5'-TpT 4, 5 were synthesized. The corresponding serine phosphoamidate possesses some unique properties due to the presence of the side chain hydroxyl group.

Synthesis of a potential tetrasaccharide ligand for E-selectin.

A potential tetrasaccharide ligand for E-selectin, (Na(+-)O(3)SO-3)Galbeta-(1-->4)[Fucalpha-(1-->3)]Glcbeta-(1-->6)Gal, an analogue of the ovarian cystadenoma glycoprotein tetrasaccharide fragment, was synthesized in a highly practical way.

Bromonium ion-promoted glycosidic bond formation and simultaneous bromination of an activated aryl aglycon.

N-Bromosuccinimide (NBS) together with a catalytic amount of Me(3)SiOTf was found to be effective for the activation of thioglycosides. Concurrently with formation of the glycosidic bond, bromination took place on the activated aromatic ring of a 4-methoxyphenyl aglycon.