Objective: The efficacy of antidepressants is influenced by a combination of genetic, individual, and environmental factors. This study aimed to investigate the association between the miR-182 rs76481776 polymorphism and the response to antidepressant treatment in major depressive disorder (MDD) patients, and its underlying molecular mechanisms. Methods: This study enrolled 180 MDD patients and 180 healthy controls. The rs76481776 genotype was determined using TaqMan-based qPCR. The severity of depression and treatment response were assessed using the Hamilton Depression Rating Scale (HAMD). The expression of miR-182 and BDNF was measured using RT-qPCR. The regulatory relationship between miR-182 and BDNF was confirmed through a luciferase reporter gene assay. The correlation between miR-182 and BDNF expression was evaluated using the Pearson correlation coefficient. Results: The T allele of rs76481776 was a significant risk factor for MDD (OR = 2.182, 95% CI: 1.424−3.345, p ＜ 0.001) and was significantly associated with higher baseline scores on the HAMD. Moreover, individuals carrying the T allele (CT/TT genotype) exhibited a significantly poorer response to antidepressant treatment and a lower remission rate within 12 months compared to those with the CC genotype (p ＜ 0.05). Mechanistically, miR-182 was highly expressed in patients with MDD (p ＜ 0.05), and its expression was even higher in T allele carriers (p ＜ 0.05). miR-182 could directly target and suppress BDNF, leading to decreased BDNF expression in MDD patients, and its expression was significantly and inversely correlated with BDNF expression. Conclusion The T allele of rs76481776 diminished the therapeutic efficacy of antidepressants by up-regulating miR-182 expression and subsequently suppressing BDNF expression.

Objective:To elucidate the quasispecies variation of 3′ half-length genome in HIV-1 CRF103_01B-infected patients in Beijing using single genome amplification (SGA).Methods:This study enrolled six CRF103_01B-infected patients who were diagnosed during a drug resistance monitoring for newly diagnosed cases or newly treated cases with antiviral therapy in Beijing from 2017 to 2020. RNA was extracted from their plasma samples, and 3′ end of cDNA was diluted by serial dilution method after reverse transcription. Nested PCR was used to amplify the 3′ half-length genome sequences of HIV-1 quasispecies. MEGA 11 was used to construct Neighbor-Joining (NJ) tree and calculate the intrahost genetic distance. Genetic variation in HIV-1 quasispecies was visualized by online Highlighter tool. BootScan analysis was performed using Simplot 3.5 software to analyze inter-quasispecies recombination. Virus tropism was predicted by online Geno2pheno tool.Results:Among the six CRF103_01B-infected patients, five were men who have sex with men. A total of 144 3′ half-length genome SGA sequences (19-36 sequences/case) were obtained. The NJ tree based on the 3′ half-length genome of HIV-1 quasispecies revealed different degrees of genetic diversity. The HIV-1 quasispecies in BL4748-00 case of acute infection has the least variation with the intrahost distance of 0.002±0.000, showing genetic homogeneity. The quasispecies sequences from BL4981-00, BL3150-00 and BL3558-00 cases formed at least three subclusters, respectively, with different evolutionary directions, and their intrahost distance ranked from 0.031±0.004 to 0.016±0.002 (BL3150-00>BL3558-00>BL4981-00). The quasispecies sequences from the couple BL3022-00 (female) and BL3023-00 clustered into a large monophyletic cluster (bootstrap value=100%), and the intrahost distance of the latter (0.025±0.003) was higher than that of the former (0.019±0.002). Inter-quasispecies recombination was observed in BL3558-00 case. The quasispecies from the six patients were CCR5-tropic viruses.Conclusions:The diversity of quasispecies variation in CRF103_01B-infected patients is related to disease progress. Genetic homogeneity is observed in acute HIV infection, while multiple evolutionary directions are detected in chronic infection. Co-infection or superinfection cases are not found, but there are recombination events among quasispecies in some cases.

ObjectlveTo evaluate the role of cannabinoid receptor 2 (CB2 receptor) in microglial injury induced by glutamate.MethodsMicroglia cells were randomly divided into 4 grups:control group (group C),microglial injury group ( group Ⅰ),specific CB2 receptor agonist AM 1241 group ( group AM1241 ) and specific CB2 receptor antagonist AM630 group (group AM630).In group C,the cells were cultured routinely for 26 h.In group Ⅰ,the cells were incubated in the culture medium containing glutamate 10 mmol/L for 24 h.In group AM1241,the cells were incubated in the culture medium containing AM1241 2 μmol/L for 2 h,and then in the culture medium containing glutamate 10 mmol/L for 24 h.In group AM630,the cells were incubated in the culture medium containing AM630 2 μmol/L for 2 h,and then in the culture medium containing glutamate 10 mmol/L for 24 h.The cell viability and release of LDH were measured.Microglial morphology was observed under microscope.Results Compared with group C,the cell viability was significantly decreased,and the release of LDH was significantly increased in groups Ⅰ,AM1241 and AM630 (P ＜ 0.05).Compared with group Ⅰ,the cell viability was significantly increased,and the release of LDH was significantly decreased in group AM1241 ( P ＜ 0.05).There was no significant difference in the cell viability and the release of LDH between groups 1 and AM630 ( P ＞ 0.05).Conclusion Glutamate induces microglial injury through inhibiting the function of CB2 receptor.