Two single mutations in carboxylesterase 001C improve fenvalerate hydrolase activity in Helicoverpa armigera.

Carboxylesterases (CarEs) usually play critical roles in the detoxification of toxic chemicals and therefore may be involved in insecticide resistance in agricultural pests. Previous work has shown that CarE 001C from Helicoverpa armigera was able to metabolize the isomers of cypermethrin and fenvalerate. In this study, seven mutants of CarE 001C with single amino acid substitution were produced and expressed in the Escherichia coli. Enzyme kinetic analysis indicated that all seven mutations dramatically reduced enzymatic activities toward the generic substrate α-naphthyl acetate, but in vitro metabolism assay showed that two of the mutations, H423I and R322L, significantly improved hydrolase activities toward fenvalerate, with their recorded specific activities being 3.5 and 5.1 nM·s-1·mg -1 proteins, respectively. Further, thermostability assay showed that the stability of one mutant enzyme was enhanced. This study will help us better understand the potential of CarEs in insecticide detoxification and resistance in H. armigera.

The potential impact of polymorphisms in METTL3 gene on knee osteoarthritis susceptibility.

Objective: This study was aimed to explore the correlation between METTL3 polymorphisms and susceptibility to knee osteoarthritis (KOA). Methods: The relationship of five single nucleotide polymorphisms (SNPs) in the METTL3 gene with the susceptibility of KOA was analyzed through multinomial logistic regression analysis in this a case-control study. Genotyping was performed on 228 KOA patients and 252 unaffected individuals from South China based on the TaqMan method. The MDR software (version 3.0.2) was utilized for the analysis of SNP interactions. Results: Out of the five SNPs examined, the T > G change in the METTL3 gene at the rs1061026 locus increased the risk of KOA, while rs1139130 A > G and rs1263802 C > T variants were found to be linked with a reduced risk of developing KOA with statistical significance. The rs1061027 A > C and rs1263801 C > G variants did not show significant association (p＞0.05). The rs1061026 TG/GG genotype showed a significant correlation with an increased risk of KOA in the following subgroups: the males, individuals with a BMI ranging from 24 to 28, smokers, those who were not engaged in physical exercise (PE), patients who had experienced KOA symptoms for eight years or longer, and those without a family history of the disease or reported swelling. On the other hand, the rs1139130 AG/GG genotype demonstrated a protective effect against KOA among the females, individuals with a BMI greater than or equal to 24, a unilateral KOA, or a KOA duration of 8 years or less, non-smokers, non-alcohol drinkers, those who were not engaged in PE, and those who had no injury or family history, or no experience of knee swelling. Additionally, it was observed that the rs1263802 CT/TT genotypes showed a protective effect among patients without a history of injury. Furthermore, individuals with the haplotypes GAT, GGC, TAT, and TGC were found to have a significantly lower susceptibility to KOA compared to the reference haplotype TAC. Conclusions: The METTL3 gene variant rs1061026 could increase the risk of KOA, whereas the variants of rs1139130 as well as rs1263802 might exert a protective effect against KOA. These variants could potentially function as susceptibility markers for KOA among the population from South China.

miR-145-5p inhibits epithelial-mesenchymal transition via the JNK signaling pathway by targeting MAP3K1 in non-small cell lung cancer cells.

Lung cancer is one of the most common types of tumors and the leading cause of cancer-associated mortality in the world. Additionally, non-small cell lung cancer (NSCLC) accounts for ~80% of all lung cancer cases. Epithelial-mesenchymal transition (EMT) is an important cell biological process, which is associated with cancer migration, metastasis, asthma and fibrosis in the lung. In the present study, it was revealed that miR-145-5p was able to suppress EMT by inactivating the c-Jun N-terminal kinase (JNK) signaling pathway in NSCLC cells. Mitogen-activated protein kinase kinase kinase 1 (MAP3K1) was predicted and confirmed to be a novel target of miR-145-5p. Overexpression of MAP3K1 was able to reverse the inhibition of EMT induced by miR-145-5p via the JNK signaling pathway. Overall, the results revealed that miR-145-5p inhibits EMT via the JNK signaling pathway by targeting MAP3K1 in NSCLC cells.

MiR-145 acts as a metastasis suppressor by targeting metadherin in lung cancer.

MiR-145 has been reported to be downregulated in multiple tumors. It acts as a tumor suppressor in lung cancer. In this study, we investigated the potential effects of miR-145 on invasion and metastasis and the molecular mechanism in non-small cell lung cancer. MiR-145 was downregulated in the NSCLC specimens and significantly correlated with advanced clinical stage and lymph node metastasis. In addition, AEG-1/MTDH was a direct target of miR-145, and the expression of AEG-1/MTDH was inversely correlated with miR-145 expression in NSCLC tissues. Ectopic expression of miR-145 suppressed cell invasion and metastasis in NSCLC cells. AEG-1/MTDH overexpression partially reversed the suppressive effect of miR-145. These findings provide novel insights with potential therapeutic applications for the treatment of NSCLC.