Influence of Particle Size on Ecotoxicity of Low-Density Polyethylene Microplastics, with and without Adsorbed Benzo-a-Pyrene, in Clam Scrobicularia plana

This study investigated the ecotoxicological effects of differently sized (4–6 µm and 20–25 µm) low-density polyethylene (LDPE) microplastics (MPs), with and without adsorbed benzo-a-pyrene (BaP), in clam Scrobicularia plana. Biomarkers of oxidative stress (superoxide dismutase—SOD; catalase—CAT), biotransformation (glutathione-S-transferases—GST), oxidative damage (lipid peroxidation—LPO) and neurotoxicity (acetylcholinesterase—AChE) were analysed in gills and digestive glands at different time intervals for a total of 14 days of exposure. In order to have a better impact perspective of these contaminants, an integrated biomarker response index (IBR) and Health Index were applied. Biomarker alterations are apparently more related to smaller sized (4–6 µm) MPs in gills and to virgin LDPE MPs in the digestive gland according to IBR results, while the digestive gland was more affected by these MPs according to the health index.

The role of polyphenols in overcoming cancer drug resistance: a comprehensive review

Chemotherapeutic drugs are used to treat advanced stages of cancer or following surgery. However, cancers often develop resistance against drugs, leading to failure of treatment and recurrence of the disease. Polyphenols are a family of organic compounds with more than 10,000 members which have a three-membered flavan ring system in common. These natural compounds are known for their beneficial properties, such as free radical scavenging, decreasing oxidative stress, and modulating inflammation. Herein, we discuss the role of polyphenols (mainly curcumin, resveratrol, and epigallocatechin gallate [EGCG]) in different aspects of cancer drug resistance. Increasing drug uptake by tumor cells, decreasing drug metabolism by enzymes (e.g. cytochromes and glutathione-S-transferases), and reducing drug efflux are some of the mechanisms by which polyphenols increase the sensitivity of cancer cells to chemotherapeutic agents. Polyphenols also affect other targets for overcoming chemoresistance in cancer cells, including cell death (i.e. autophagy and apoptosis), EMT, ROS, DNA repair processes, cancer stem cells, and epigenetics (e.g. miRNAs).

Association of Glutathione S-transferases (GSTT1, GSTM1 and GSTP1) Genes Polymorphisms with Nonalcoholic Fatty Liver Disease Susceptibility: A Meta-analysis of Case-control Studies

Background: Glutathione S-transferases (GSTs) genes single-nucleotide polymorphisms (SNPs) have been connected with the susceptibility of nonalcoholic fatty liver disease (NAFLD), but with inconsistent results across the current evidences. The present work was schemed to explore the association between GSTs genes polymorphisms and the NAFLD vulnerability via meta-analysis.Methods: PubMed, Web of Science, Cochrane Library, China National Knowledge Infrastructure (CNKI) and Wanfang were retrieved for eligible literatures previous to March 10, 2021. The odds ratio (OR) of the dichotomic variables and the standardized mean difference of quantitative variables with corresponding 95% confidence intervals (95%CIs) were computed to evaluate the strength of the associations. The quality of included studies were assessed via using Newcastle-Ottawa Scale (NOS).Results: In total, 7 case-control studies encompassing 804 NAFLD patients and 1362 disease-free controls in this meta-analysis. Ultimately, this analysis included six, five and five studies for GSTM1, GSTT1 and GSTP1 polymorphisms respectively. The pooled data revealed that the GSTs genes single-nucleotide polymorphisms had conspicuous associations with NAFLD susceptibility: for GSTM1, null vs. present, OR=1.46, 95%CI 1.20-1.79, P=0.0002; for GSTT1, null vs. present, OR=1.34, 95%CI 1.06-1.68, P=0.01; for GSTP1, Ile/Val or Val/Val vs. Ile/Ile, OR=1.60, 95%CI 1.23-2.09, P=0.0005.Conclusion: This work revealed that the GSTM1 null, GSTT1 null and GSTP1-Val genotypes might be related to increased NAFLD susceptibility.

GSTP1 and GSTM3 Variant Alleles Affect Susceptibility and Severity of COVID-19

Based on the premise that oxidative stress plays an important role in severe acute respiratory syndrome coronavirus (SARS-CoV-2) infection, we speculated that variations in the antioxidant activities of different members of the glutathione S-transferase family of enzymes might modulate individual susceptibility towards development of clinical manifestations in COVID-19. The distribution of polymorphisms in cytosolic glutathione S-transferases GSTA1, GSTM1, GSTM3, GSTP1 (rs1695 and rs1138272), and GSTT1 were assessed in 207 COVID-19 patients and 252 matched healthy individuals, emphasizing their individual and cumulative effect in disease development and severity. GST polymorphisms were determined by appropriate PCR methods. Among six GST polymorphisms analyzed in this study, GSTP1 rs1695 and GSTM3 were found to be associated with COVID-19. Indeed, the data obtained showed that individuals carrying variant GSTP1-Val allele exhibit lower odds of COVID-19 development (p = 0.002), contrary to carriers of variant GSTM3-CC genotype which have higher odds for COVID-19 (p = 0.024). Moreover, combined GSTP1 (rs1138272 and rs1695) and GSTM3 genotype exhibited cumulative risk regarding both COVID-19 occurrence and COVID-19 severity (p = 0.001 and p = 0.025, respectively). Further studies are needed to clarify the exact roles of specific glutathione S-transferases once the SARS-CoV-2 infection is initiated in the host cell.

Role of Glutathione S-transferase Mu 1 and Glutathione S-transferases Theta 1 Polymorphism in the Risk of Developing Type 2 Diabetes Mellitus at Universitas Sumatera Utara Hospital, Medan

BACKGROUND: Diabetes mellitus is associated with an increased production of reactive oxygen species (ROS) and a reduction in antioxidant defense. Glutathione S-transferases (GSTs) is group of multifunction antioxidant enzyme can be used as important biomarkers for DM.. GSTM1, T1 genes variant polymorphism result in decreased or loss of enzyme activity. AIM: The study aimed to evaluate the role of GSTM1 and GSTT1 gene polymorphism in the risk of developing T2DM. METHODS: GSTM1 and GSTT1 polymorphisms were genotyped in 87 T2DM patients and 87 healthy control group to analyze their association with T2DM susceptibility by using multiplex Polymerase Chain Reaction (PCR). PCR products were electrophoresed using agarose 2%. Odds ratio (OR) with 95% confidence interval (CI) and P value were calculated using SPSS software (version 21.0). RESULTS: The genotype distribution of GSTM1 and GSTT1 were not different between T2DM patients and healthy control group (p = 0.542, OR= 0.780, CI 95%=0.350-1.737 and p=0.879, OR=1.047, CI 95%=0.577-1.903). The genotype distribution of combination of GSTM1 and GSTT1 were also not not different between T2DM patients and healthy control group (p = 0.640, OR= 0.640, CI 95%=0.224-1.83 and p=0.551, OR=0.721, CI 95%=0.245-2.120. CONCLUSION: In summary, this study showed that GSTT1 null, GSTM1 null, the combination of GSTM1 null and GSTT1 null genotype or combination of GSTM1 null and GSTT1 positive (or contrary) did not have any risk of developing T2DM at Universitas Sumatera Utara Hospital, Medan.

The Key Glutathione S-Transferase Family Genes Involved in the Detoxification of Rice Gramine in Brown Planthopper Nilaparvata lugens

Phytochemical toxins are considered a defense measure for herbivore invasion. To adapt this defensive strategy, herbivores use glutathione S-transferases (GSTs) as an important detoxification enzyme to cope with toxic compounds, but the underlying molecular basis for GST genes in this process remains unclear. Here, we investigated the basis of how GST genes in brown planthopper (BPH, Nilaparvata lugens (Stål)) participated in the detoxification of gramine by RNA interference. For BPH, the LC25 and LC50 concentrations of gramine were 7.11 and 14.99 μg/mL at 72 h after feeding, respectively. The transcriptions of seven of eight GST genes in BPH were induced by a low concentration of gramine, and GST activity was activated. Although interferences of seven genes reduced BPH tolerance to gramine, only the expression of NlGST1-1, NlGSTD2, and NlGSTE1 was positively correlated with GST activities, and silencing of these three genes inhibited GST activities in BPH. Our findings reveal that two new key genes, NlGSTD2 and NlGSTE1, play an essential role in the detoxification of gramine such as NlGST1-1 does in BPH, which not only provides the molecular evidence for the coevolution theory, but also provides new insight into the development of an environmentally friendly strategy for herbivore population management.

The catalytic activity of GSTM1 in vitro is independent of MAPK8

Background: Glutathione S-transferases (GSTs) are phase II metabolic enzymes crucial for the metabolism of electrophilic drugs. Additionally, several GST isoforms are involved in protein-protein interaction with mitogen-activated protein kinases (MAPKs), modulating apoptosis pathways. Methods: To assess the potential change of enzymatic activity, we performed a GST enzyme assay with human recombinant GSTM1 in the presence and absence of MAPK8. Recently, GSTM1 has been demonstrated to interact with MAPK8 both in silico and in vitro. The binding interface predicted in silico comprised amino acid residues present on the surface of the protein and a few were deep in the active site of the protein. Results: The experiment demonstrated that the GSTM1 activity was conserved even in the presence of MAPK8 in the assay. Conclusion: Thus, this interaction with MAPK8 may potentially cause an alteration of the catalytic activity of GSTM1.

Design, Synthesis and Characterization of Thiophene Substituted Chalcones for Possible Biological Evaluation

Development of new antimicrobial agents is a better solution to rectify drug resistance problems in society. In this circumstances new functionalized sulphur bearing heterocyclic moiety were designed, synthesized and evaluated for their in vitro antibacterial activity. The present work encompasses the designing novel series of thiophene substituted analogous linked to para amino acetophenone and different aldehydes were successfully synthesized and biological activity was predicted using various computational software’s such as Chemsketch, Molinspiration, and admetSAR. Among the synthesized thiophene substituted chalcones T-IV-I and thiophene T-IV-B displayed significant activity against Streptococcus auresis. Compounds T-IV-J, T-IV-H and T-IV-C bearing sulphur moiety possess better activity against Staphylococcus aureus. Moreover T-IV-C and T-IV-J exhibits good antibacterial activity against E. coli and Pseudomonas aeruginosa. In general, most of the synthesized compounds exhibited remarkable antibacterial activity due to the presence of sulphur atom in the heterocyclic moieties as well as its lipophilic characters. Molecular docking studies indicated that the synthesized compounds are potent inhibitor of microsomal enzyme Glutathione-S-transferases (PDB ID: 1GNW) also find the different interacting residues, bond distanceand nature of bondingbetween the target and the ligand molecules. The results provide important information for the future design of more effective antibacterial agents.