Downregulation of TCF1 in HIV Infection Impairs T-cell Proliferative Capacity by Disrupting Mitochondrial Function.

Background: Despite the benefits of antiretroviral therapy (ART) for people with HIV, T-cell dysfunction cannot be fully restored. Metabolic dysregulation is associated with dysfunction of HIV-1-specific T-cells. Exploration of the factors regulating metabolic fitness can help reverse T-cell dysfunction and provide new insights into the underlying mechanism. Methods: In this study, HIV-infected individuals and HIV-negative control individuals (NCs) were enrolled. T-cell factor (TCF)1 expression in cells was determined by quantitative reverse-transcriptase polymerase chain reaction and flow cytometry. Relevant microarray data from the GEO database were analyzed to explore the underlying mechanism. The effects of TCF1 on T-cell function and metabolic function were assessed in vitro. Results: TCF7 mRNA expression in peripheral blood mononuclear cells was downregulated in rapid progressors compared with long-term non-progressors individuals and NCs. TCF1 expression on CD4+ and CD8+ T-cells was downregulated in treatment-naïve HIV-infected individuals compared with NCs. Interleukin (IL)2 production and proliferative capacity were impaired in TCF1 knockdown T-cells. Moreover, glycolytic capacity and mitochondrial respiratory function were decreased in TCF1 knockdown T-cells, and depolarized mitochondria were increased in TCF1 knockdown T-cells. Conclusion: Downregulation of TCF1 in HIV infection impairs T-cell proliferative capacity by disrupting mitochondrial function. These findings highlight the metabolic regulation as a pivotal mechanism of TCF1 in the regulation of T-cell dysfunction.

Temperature-Dependent Development of Oligota flavicornis (Coleoptera: Staphylinidae) Preying on Tetranychus cinnabarinus (Acarina: Tetranychidae).

The effect of nine constant temperatures on developmental time of Oligota flavicornis (Boisduval and Lacordaire) preying on Tetranychus cinnabarinus (Boisduval) (Acari: Tetranychidae) eggs was determined under laboratory conditions of 75 ± 5% RH and a 16:8 (L:D) h photoperiod. O. flavicornis survival rates were highest between 18 and 30°C, although O. flavicornis eggs developed successfully to adults at 12-32°C, and the developmental durations to adult at the seven temperatures (12, 15, 18, 20, 25, 30, and 32°C) were 114.41, 51.66, 33.45, 23.21, 13.43, 11.54, and 17.18 d, respectively. Two linear and seven nonlinear models (Logan-6 and Logan-10, Taylor, Lactin-1 and Lactin-2, and Brière-1 and Brière-2) were fit to the developmental rates of the immature predatory stages to estimate the thermal constant (K) and critical temperatures. The lower temperature threshold (T0) and K for the immature stages using the common linear model were 9.96°C and 225.73 degree-days and Ikemoto-Takai linear model were 11.01°C and 167.14 degree-days, respectively. The upper temperature threshold values estimated by the Logan-6 and Lactin-1 models were both 34.86°C. The T0 values estimated by the Brière-1 and Brière-2 models were 10.67 and 9.32°C for all immature stages, respectively, and the estimated optimal temperature according to the Brière-2 model was 29.59°C. Therefore, the two linear models and Brière-2 model estimates approximated the actual relationship between the temperature and developmental rate of immature O. flavicornis.

Upregulation of PDZK1 by Calculus Bovis Sativus May Play an Important Role in Restoring Biliary Transport Function in Intrahepatic Cholestasis.

Intrahepatic cholestasis is a main cause of hepatic accumulation of bile acids leading to liver injury, fibrosis, and liver failure. Our previous studies proved that Calculus Bovis Sativus (CBS) can restore biliary transport function through upregulating the multidrug resistance-associated protein 2 (MRP2) and breast cancer resistance protein (BCRP) in 17α-ethynylestradiol- (EE-) induced intrahepatic cholestasis rats. The regulation mechanism of CBS on these transporters, however, remains unclear. This study was designed to evaluate the possible relationship between the effect of CBS on transport activities and the regulation of CBS on the expression of PDZK1, a mainly scaffold protein which can regulate MRP2 and BCRP. Intrahepatic cholestasis model was induced in rats with injection of EE for five consecutive days and then the biliary excretion rates and cumulative biliary excretions were measured. The mRNA and protein expression levels of PDZK1 were detected by reverse transcription-quantitative real-time polymerase chain reaction, western blot, and immunohistochemical analysis. When treated with CBS, cumulative biliary excretions and mRNA and protein expressions of PDZK1 were significantly increased in intrahepatic cholestasis rats. This study demonstrated that CBS exerted a beneficial effect on EE-induced intrahepatic cholestasis rats by restoring biliary transport function, which may result from the upregulation of PDZK1 expression.

Beneficial effect of Calculus Bovis Sativus on 17α-ethynylestradiol-induced cholestasis in the rat.

AIMS: Calculus Bovis Sativus (CBS) shares similar pharmacological effects with Calculus Bovis like relieving hepatobiliary diseases. This study aims to investigate the effect and mechanism of CBS on 17α-ethynylestradiol (EE)-induced cholestasis in the rat. MAIN METHODS: CBS (50 and 150 mg/kg per day) was intragastrically (i. g.) given to experimental rats for 5 consecutive days in coadministration with EE. The levels of serum biomarkers, hepatic malondialdehyde (MDA) content and superoxide dismutase (SOD) activity were determined by biochemical methods. The bile flow in 2h was measured. The histopathology of the liver tissue was evaluated. The expression of transporter was studied by reverse transcription-quantitative real-time polymerase chain reaction (RT-qPCR) and western blot. KEY FINDINGS: CBS treatment significantly prevented EE-induced increases in serum levels of biomarkers. Decreased bile flow by EE was restored with CBS treatment. The tissue lesions were also relieved with CBS treatment. Western blot studies indicated that EE significantly decreased the protein expression of multidrug resistance-associated protein 2 (Mrp2) and breast cancer resistance protein (Bcrp), but notably increased P-glycoprotein (P-gp) protein, compared with the control group. CBS treatment significantly increased the protein expression of P-gp, Mrp2 and Bcrp compared with the EE group. RT-qPCR studies indicated that EE down-regulated Bcrp at transcriptional level. CBS up-regulated the mRNA expression of P-gp, Mrp2 and Bcrp compared with the EE group. SIGNIFICANCE: The present study indicated that CBS exerted a beneficial effect on EE-induced cholestasis in the rat, which may result from its induction of P-gp, Mrp2 and Bcrp expression.

Effects of in vitro cultivated Calculus Bovis compound on pulmonary lesions in rabbits with schistosomiasis.

AIM: To explore the interventional effects and mechanism of in vitro cultivated Calculus Bovis compound preparation (ICCBco) on pulmonary lesions in portal hypertensive rabbits with schistosomiasis. METHODS: The experimental group included 20 portal hypertensive rabbits with schistosomiasis treated by ICCBco. The control group included 20 portal hypertensive rabbits with schistosomiasis treated by praziquantel. The morphological changes of the pulmonary tissues were observed under light and electron microscopy. The expression of fibronectin (FN) and laminin (LN) in the lung tissues was analyzed by immunohistochemistry. RESULTS: Under light microscope, the alveolar exudation in the lung tissue was more frequently observed in the control group, while the alveolar space was fairly dry in the lung tissue of ICCBco group. Under electron microscope, more alveolar exudation in the lung tissue, and more macrophages, alveolar angiotelectasis and the blurred three-tier structure of alveolar-capillary barrier could be seen in the control group. In ICCBco group, fibers within the alveolar interspace slightly increased in some lung regions, and the structure of type I epithelium, basement membrane and endodermis was complete, and no obvious exudation from the alveolar space, and novascular congestion could be observed. There was a positive or strong positive expression of FN and LN in the lung tissue of the control group, while there was a negative or weak positive expression of FN and LN in ICCBco group. CONCLUSION: ICCBco can effectively prevent pulmonary complications in portal hypertensive rabbits with schistosomiasis by means of improving lung microcirculation and lowering the content of extracellular matrix.