Objective:To investigate the role of the CD38/p53/ME1 axis in regulating T cell mitochondrial function and senescence during HIV infection.Methods:The expression of CD38 on T cells was examined in HIV-infected individuals receiving antiretroviral therapy(ART), untreated HIV-infected individuals, and HIV-negative healthy controls. Flow cytometry was used to compare senescence markers and mitochondrial function between CD38 + and CD38 - T cells. Malic enzyme 1(ME1) mRNA levels were measured by qRT-PCR in T cells treated with the CD38 inhibitor 78c. Mitochondrial function and senescence were assessed in T cells treated with an ME1 inhibitor. The regulatory mechanism of CD38-mediated ME1 downregulation was further explored. Results:Compared to healthy controls, T cells from HIV-infected individuals exhibited significantly elevated CD38 expression, which persisted despite ART. CD38 + T cells showed increased senescence (CD28 -CD57 + subset) and mitochondrial dysfunction[depolarization and reactive oxygen species(ROS) accumulation]. CD38 inhibition upregulated ME1 mRNA level ( P<0.05). ME1 suppression led to mitochondrial impairment (reduced membrane potential and elevated ROS) and senescence in T cells. Mechanistically, CD38 depletion increased NAD + levels and SIRT1 activity, while SIRT1/p53 inhibition rescued ME1 expression, suggesting CD38 regulates ME1 via the NAD + /SIRT1/p53 axis. Conclusions:The CD38/p53/ME1 axis drives T cell senescence in HIV infection by disrupting mitochondrial function. Targeting this pathway may ameliorate CD38-associated T cell dysfunction and immune aging.

Objective:To investigate the role of the CD38/p53/ME1 axis in regulating T cell mitochondrial function and senescence during HIV infection.Methods:The expression of CD38 on T cells was examined in HIV-infected individuals receiving antiretroviral therapy(ART), untreated HIV-infected individuals, and HIV-negative healthy controls. Flow cytometry was used to compare senescence markers and mitochondrial function between CD38 + and CD38 - T cells. Malic enzyme 1(ME1) mRNA levels were measured by qRT-PCR in T cells treated with the CD38 inhibitor 78c. Mitochondrial function and senescence were assessed in T cells treated with an ME1 inhibitor. The regulatory mechanism of CD38-mediated ME1 downregulation was further explored. Results:Compared to healthy controls, T cells from HIV-infected individuals exhibited significantly elevated CD38 expression, which persisted despite ART. CD38 + T cells showed increased senescence (CD28 -CD57 + subset) and mitochondrial dysfunction[depolarization and reactive oxygen species(ROS) accumulation]. CD38 inhibition upregulated ME1 mRNA level ( P<0.05). ME1 suppression led to mitochondrial impairment (reduced membrane potential and elevated ROS) and senescence in T cells. Mechanistically, CD38 depletion increased NAD + levels and SIRT1 activity, while SIRT1/p53 inhibition rescued ME1 expression, suggesting CD38 regulates ME1 via the NAD + /SIRT1/p53 axis. Conclusions:The CD38/p53/ME1 axis drives T cell senescence in HIV infection by disrupting mitochondrial function. Targeting this pathway may ameliorate CD38-associated T cell dysfunction and immune aging.

Objective To investigate the expression of long non-coding RNA H19 (LncRNA H19)and its regulation of histone methyltransferase 2 (enhancer of zeste homolog 2,EZH2) in the lung tissue of neonatal rats with bronchopulmonary dysplasia (BPD),and to lay a foundation for elucidating the pathogenesis of BPD lung epithelium-interstitial transformation (EMT).Methods The BPD model of SD neonatal rats was induced by hyperoxia (inhalation oxygen concentration was 85％) (n =50),and oxygen inhalation concentration of the control group was 21％ (n =50).The two groups were collected at ld,3d,7d,14d and 21d after birth in lung tissue.Immunohistochemistry,Western blot,real-time quantitative PCR and other techniques were used to detect the intracellular localization,and the expression level of EZH2 protein and the mRNA expression level of H19 and EZH2.Results Immunohistochemistry showed that EZH2 protein was located in the nucleus and cytoplasm of alveolar epithelial cells,and the expression of EZH2 protein in the model group was significantly enhanced compared with the control group.Similarly,the results of Western blot demonstrated that the expression of EZH2 protein in the model group increased from ld (control group:0.196 ± 0.030,model group 0.650 ±0.149) to 21d (control group 0.934 ± 0.215,model group 1.785 ± 0.298) rather than the control group (P ＜ 0.05).Compared with the control group,the mRNA expression level of H19 in the model group increased from 7d (control group 2.591 ± 0.211,model group 3.558 ± 0.093,P ＜ 0.05) and the expression level of EZH2 mRNA started to increase from 3d (control group 1.246 ±0.015,model group 2.148 ± 0.215,P ＜0.05).Moreover,the differences between the two groups were obvious with the time of hyperoxia exposure.Conclusion In the development of BPD,the expression levels of H19 and EZH2 protein in lung tissue is up-regulated,and the peak of H19 expression precedes EZH2,which suggest that H19 might be involved in the pathogenesis of pulmonary dysplasia induced by EZH2-mediated EMT.