Anti-Autophagy Mechanism of Zhi Gan Prescription Based on Network Pharmacology in Nonalcoholic Steatohepatitis Rats.

Background and Aims: Zhi Gan prescription (ZGP) has been clinically proven to exert a favorable therapeutic effect on nonalcoholic steatohepatitis (NASH). This study purpose to reveal the underlying molecular mechanisms of ZGP action in NASH. Methods: Systematic network pharmacology was used to identify bioactive components, potential targets, and the underlying mechanism of ZGP action in NASH. High fat (HF)-induced NASH model rats were used to assess the effect of ZGP against NASH, and to verify the possible molecular mechanisms as predicted by network pharmacology. Results: A total of 138 active components and 366 potential targets were acquired in ZGP. In addition, 823 targets of NASH were also screened. In vivo experiments showed that ZGP significantly improved the symptoms in HF-induced NASH rats. qRT-PCR and western blot analyses showed that ZGP could regulate the hub genes, PTEN, IL-6 and TNF in NASH model rats. In addition, ZGP suppressed mitochondrial autophagy through mitochondrial fusion and fission via the PINK/Parkin pathway. Conclusion: ZGP exerts its effects on NASH through mitochondrial autophagy. These findings provide novel insights into the mechanisms of ZGP in NASH.

Increased cell apoptosis in human lung adenocarcinoma and in vivo tumor growth inhibition by RBM10, a tumor suppressor gene.

Tumor suppressor genes are frequently deleted or mutated in lung cancer. The RNA-binding motif protein 10 (RBM10) gene has the ability to suppress tumor activity, but the role of RBM10 during the development of lung cancer has yet to be elucidated. The current study investigated the expression levels of RBM10 in non-tumor and tumor tissues obtained from patients with adenocarcinoma using reverse transcription-polymerase chain reaction and western blot analysis, and identified a reduction in RBM10 expression in lung tumor tissue. To investigate the in vitro and in vivo function of RBM10, A549 human non-small cell lung cancer cells were transfected with the pcDNA-RBM10 vector. Flow cytometry was used to analyze the levels of apoptosis in the transfected cells. Western blot analysis was used to evaluate the expression of B-cell lymphoma 2 (Bcl-2), cleaved caspase-3, caspase-9 and poly (ADP-ribose) polymerase (PARP) proteins in A549 cells and tissues from the A549 xenograft Bagg Albino coat (BALB/c) nude mice model. RBM10 mRNA levels were significantly decreased in adenocarcinoma cells, but not in the non-tumor tissues. The A549 cells and tumor tissues exhibited significant growth inhibition following transfection with the pcDNA-RBM10 vector, which was determined using a cell proliferation assay. Flow cytometry analysis of cells stained with Annexin V/propidium iodide indicated that the overexpression of RBM10 induced apoptosis in A549 cells. The present study demonstrated that the expression levels of Bcl-2 protein were decreased and the expression levels of cleaved caspase-3, caspase-9 and PARP proteins were significantly increased in the A549 cells and cells from ex vivo tumor tissues that were injected with RBM10 vector-containing Salmonella enterica subspecies enterica serovar typhimurium. Notably, the current study identified that the accumulated and stable overexpression of RBM10 in the xenograft BALB/c nude mice model significantly inhibited the tumor growth rate. These results may provide novel insights into the use of RBM10 for lung cancer diagnosis and therapy.

Lower Expression of SPRY4 Predicts a Poor Prognosis and Regulates Cell Proliferation in Colorectal Cancer.

BACKGROUND/AIMS: Colorectal cancer (CRC) is the third most common type of cancer worldwide. Sprouty proteins are modulators of mitogeninduced signal transduction processes and therefore can influence the process of cancerogenesis. The encoded protein of Sprouty homolog 4 (SPRY4) is associated with various human cancers. However, its biological role and clinical significance in CRC development and progression are unknown. METHODS: The aim of this study was to evaluate the expression and biological role of SPRY4 in colorectal cancer. qRT-PCR was performed to investigate the expression of SPRY4 in tumor tissues and corresponding non tumor colorectal tissues from 70 patients. The effect of SPRY4 on proliferation was evaluated by MTT and colony formation assays. CRC cells transfected with SPRY4 were injected into nude mice to study the effect of SPRY4 on tumorigenesis in vivo. RESULTS: The lower expression of SPRY4 was remarkably correlated with deep tumor invasion and advanced TNM stage. Multivariate analyses revealed that SPRY4 expression served as an independent predictor for overall survival. Using 5-aza treatment, we also observed that SPRY4 expression can be affected by DNA methylation. Further experiments revealed that overexpressed SPRY4 significantly inhibited CRC cell proliferation both in vitro and in vivo. CONCLUSION: Our study demonstrated that SPRY4 is involved in the development and progression of colorectal cancer by regulating cell proliferation and shows that SPRY4 may be a potential diagnostic and prognostic target in patients with colorectal cancer.

A Low Input Current and Wide Conversion Ratio Buck Regulator with 75% Efficiency for High-Voltage Triboelectric Nanogenerators.

It is meaningful to research the Triboelectric Nanogenerators (TENG), which can create electricity anywhere and anytime. There are many researches on the structures and materials of TENG to explain the phenomenon that the maximum voltage is stable and the current is increasing. The output voltage of the TENG is high about 180-400 V, and the output current is small about 39 µA, which the electronic devices directly integration of TENG with Li-ion batteries will result in huge energy loss due to the ultrahigh TENG impedance. A novel interface circuit with the high-voltage buck regulator for TENG is introduced firstly in this paper. The interface circuit can transfer the output signal of the TENG into the signal fit to a lithium ion battery. Through the circuit of the buck regulator, the average output voltage is about 4.0 V and the average output current is about 1.12 mA. Further, the reliability and availability for the lithium ion battery and the circuit are discussed. The interface circuit is simulated using the Cadence software and verified through PCB experiment. The buck regulator can achieve 75% efficiency for the High-Voltage TENG. This will lead to a research hot and industrialization applications.