Coiled-coil domain containing 25 (CCDC25) regulates cell proliferation, migration, and invasion in clear cell renal cell carcinoma by targeting the ILK-NF-κB signaling pathway.

Increasing evidence has demonstrated that the expression of coil domains containing 25 (CCDC25) in various malignancies is abnormally high. However, the potential regulatory role and mechanism of CCDC25 in the development of clear cell renal cell carcinoma (ccRCC) are still unclear. In this experiment, we combined in vitro experiments such as wound healing, CCK8, and transwell assay with in vivo experiments on tumor formation in nude mice to evaluate the effect of CCDC25 on the proliferation, migration, and invasion of renal cancer cells. In addition, we also used Western blotting and qPCR to evaluate the role of CCDC25 in activating the integrin-linked kinase (ILK)-NF-κB signaling pathway. Here, we demonstrate that compared to normal tissues and cell lines, CCDC25 is overexpressed in both human ccRCC tissues and cell lines. After CCDC25 knockdown, it has obvious inhibitory effect on the proliferation, migration, and invasion of cancer cells in vitro and in vivo. In contrast, CCDC25 overexpression promotes these effects. Additionally, we also discovered that CCDC25 interacts with ILK and coordinates the activation of the NF-κB signaling pathway downstream. Generally, our study suggests that CCDC25 plays a vital role in the development of ccRCC, which also means that it may be a potential therapeutic target for ccRCC.

Neutrophil extracellular traps promote acetaminophen-induced acute liver injury in mice via AIM2.

Excessive acetaminophen (APAP) can induce neutrophil activation and hepatocyte death. Along with hepatocyte dysfunction and death, NETosis (a form of neutrophil-associated inflammation) plays a vital role in the progression of acute liver injury (ALI) induced by APAP overdose. It has been shown that activated neutrophils tend to migrate towards the site of injury and participate in inflammatory processes via formation of neutrophil extracellular traps (NETs). In this study we investigated whether NETs were involved in hepatocyte injury and contributed to APAP-induced ALI progression. ALI mouse model was established by injecting overdose (350 mg/kg) of APAP. After 24 h, blood and livers were harvested for analyses. We showed that excessive APAP induced multiple programmed cell deaths of hepatocytes including pyroptosis, apoptosis and necroptosis, accompanied by significantly increased NETs markers (MPO, citH3) in the liver tissue and serum. Preinjection of DNase1 (10 U, i.p.) for two consecutive days significantly inhibited NETs formation, reduced PANoptosis and consequently alleviated excessive APAP-induced ALI. In order to clarify the communication between hepatocytes and neutrophils, we induced NETs formation in isolated neutrophils, and treated HepaRG cells with NETs. We found that NETs treatment markedly increased the activation of GSDMD, caspase-3 and MLKL, while pre-treatment with DNase1 down-regulated the expression of these proteins. Knockdown of AIM2 (a cytosolic innate immune receptor) abolished NETs-induced PANoptosis in HepaRG cells. Furthermore, excessive APAP-associated ALI was significantly attenuated in AIM2KO mice, and PANoptosis occurred less frequently. Upon restoring AIM2 expression in AIM2KO mice using AAV9 virus, both hepatic injury and PANoptosis was aggravated. In addition, we demonstrated that excessive APAP stimulated mtROS production and mitochondrial DNA (mtDNA) leakage, and mtDNA activated the TLR9 pathway to promote NETs formation. Our results uncover a novel mechanism of NETs and PANoptosis in APAP-associated ALI, which might serve as a therapeutic target.

[Evidence mapping analysis of clinical research on traditional Chinese medicine in treatment of vertigo].

In this study, the evidence map system was used to sort out the clinical research evidence on traditional Chinese medicine(TCM) treatment of vertigo and understand the evidence distribution in this field. CNKI, Wanfang, VIP, SinoMed, PubMed, EMbase, and Web of Science were searched for the clinical randomized controlled trial(RCT) and systematic reviews/Meta-analysis on TCM treatment of vertigo in recent five years, and the evidence was analyzed and presented in the form of text and charts. The Cochrane handbook for systematic reviews of interventions was used to evaluate the quality of the clinical RCT, and the AMSTAR mea-surement tool was used to evaluate the quality of the systematic reviews/Meta-analysis. A total of 382 RCTs and eight systematic reviews/Meta-analysis were included. In recent five years, the number of published articles has been on the rise. There were many intervention measures and TCM therapies for vertigo. Outcome indicators mainly included clinical efficacy, TCM syndrome score, vertigo score, occurrence of adverse reactions, and effective rate. The overall quality of clinical RCT and systematic reviews/Meta-analysis was low. Most studies have proven the potential efficacy of TCM in treating vertigo, but there was still no clear clinical evidence of efficacy. The results show that TCM has advantages in the treatment of vertigo, but there are also problems. More high-quality studies are still lacking, suggesting that more large-sample and multi-center RCT should be conducted in the future, and the quality of relevant syste-matic reviews/Meta-analysis should be improved to fully explore the advantages of TCM in the treatment of vertigo, and provide strong support for the effectiveness and safety of TCM in the treatment of vertigo.

Downregulating PDPK1 and taking phillyrin as PDPK1-targeting drug protect hepatocytes from alcoholic steatohepatitis by promoting autophagy.

The health risk stemming from drinking alcohol is serious, sometimes even life-threatening. Alcoholic steatohepatitis (ASH) is a critical stage leading to cirrhosis and end-stage liver disease. However, its pathogenesis is still far from clearly understood, and a treatment that is widely recognised as effective has not been discovered. Interestingly, PDPK1,3-phosphoinositide-dependent protein kinase 1, also known as PDK1, was observed to be obviously increased in the ASH model by our researchers. We also investigated the protective role of autophagy in ASH. Here, we studied the function of PDPK1 and found an efficient treatment to alleviate symptoms by targeting PDPK1 in ASH. In our study, PDPK1 affected hepatocyte self-healing by inhibiting autophagy. Both inhibiting PDPK1 and the phosphorylation of PDPK1 (ser241) could protect hepatocytes from suffering heavy alcoholic hepatitis.

Efficacy and safety of traditional Chinese herbal medicine combined with HAART in the treatment of HIV/AIDS: A protocol for systematic review and meta-analysis.

BACKGROUND: Acquired immunodeficiency syndrome (AIDS) is one of the infectious diseases pandemic in the word. Traditional Chinese herbal medicine, as an alternative and complementary therapy of highly active antiretroviral therapy (HAART), has been put into the treatment of human immunodeficiency virus (HIV)/AIDS over 30 years due to its good therapeutic effects and high safety, while there is a lack of evidence-based medicine support. The purpose of this study is to explore the efficacy and safety of traditional Chinese herbal medicine combined with HAART for HIV/AIDS patients. METHODS: We will search all randomized controlled trials of Chinese herbal medicine combined with HAART in the treatment of HIV/AIDS from electronic databases including PubMed, Cochrane Library, Embase, China National Knowledge Infrastructure, WanFang, China Science and Technology Journal Database and Chinese Biomedical Literature Database from inception to December 31, 2021. Literature screening will be conducted through EndNote software, and data extraction will be processed according to inclusion and exclusion criteria by two independent researchers. We will use Review Manager 5.4 and Stata 16 software for data analysis and publication bias test. RESULTS: This systematic review and meta-analysis will provide a high-quality evidence for the efficacy and safety of traditional Chinese herbal medicine combined with HAART in the treatment of HIV/AIDS. CONCLUSION: The conclusion of this review will provide an objective assessment to evaluate whether Chinese herbal medicine integrated with HAART has the effect of improving the efficiency and depressing the toxicity. REGISTRATION NUMBER: INPLASY2021110082.

Associations of anthropometric adiposity indexes with hypertension risk: A systematic review and meta-analysis including PURE-China.

BACKGROUND AND OBJECTIVE: The association between hypertension and obesity has been confirmed, while no agreement has been reached about which anthropometric adiposity index is the best. This meta-analysis aimed to perform a systematic review and meta-analysis on the associations of hypertension risk with body mass index (BMI), waist circumstance (WC), waist-to-hip ratio (WHR), and waist-to-height ratio (WHtR), and a prospective urban and rural epidemiology study from China (PURE-China) was added into this meta-analysis as an individual study. METHODS: Systematic literature searching was conducted to identify relevant articles published up to September 2018 in CNKI, WANFANG Data, Web of Science, SinoMed, PubMed, MEDLINE, EMBASE, Cochrane Library and cross-referencing. Literature reporting the association of hypertension risk with BMI, WC, WHR, and WHtR were defined as eligible. PURE-China data were analyzed and included as 1 eligible study into meta-analyses. Summary odds ratio (OR) and area under receiver operating characteristic curve (AUC) were pooled using meta-analysis methods. Heterogeneity and publication bias were evaluated. Subgroups based on gender, country and study design were conducted as well. RESULTS: Thirty-eight original articles including PURE-China were included into meta-analyses, involving 309,585 subjects. WHtR had the strongest association with hypertension risk (OR, 1.68; 95% confidence interval, [CI]:1.29-2.19) and prediction ability (AUC, 70.9%; 95% CI: 67.8%-74.2%), which were also confirmed in subgroup analyses based on gender and country. However, BMI was found to have the highest prediction ability in adjusted models of PURE-China and followed WC, both of which were superior to WHtR (73.7% and 73.4% vs 73.2%). CONCLUSIONS: Our overall meta-analysis further confirmed WHtR as a good indicator at discriminating those individuals at increased risk of hypertension, and in some cases, it is better than BMI, WC, and WHR.