CircXRN2 accelerates colorectal cancer progression through regulating miR-149-5p/MACC1 axis and EMT.

In China, there has been a persistent upward trend in the incidence and mortality rates of colorectal cancer (CRC), with CRC ranking second in incidence and fifth in mortality among all malignant tumors. Although circular RNAs (circRNAs) have been implicated in the progression of various cancers, their specific role in CRC progression remains largely unexplored. The objective of this study was to elucidate the role and underlying mechanisms of circXRN2 in CRC. Differential expression of circXRN2 was identified through whole transcriptome sequencing. The expression levels of circXRN2 and miR-149-5p were quantified in CRC tissues, corresponding adjacent normal tissues, and CRC cell lines using quantitative reverse transcription-polymerase chain reaction (qRT-PCR). The stability of circXRN2 was confirmed through RNase R and actinomycin D experiments. The binding interaction between circXRN2 and miR-149-5p was validated through RNA pull-down, RNA immunoprecipitation, and dual-luciferase assays. The biological functions of circXRN2 were assessed through a battery of in vitro experiments, including the CCK-8 assay, EdU assay, scratch assay, Transwell assay, and flow cytometry assay. Additionally, in vivo experiments involving a tumor transplantation model and a liver-lung metastasis model were conducted. The influence of circXRN2 on the expression of epithelial-mesenchymal transition (EMT)-related genes was determined via Western blotting analysis. In CRC tissues and cells, there was an upregulation in the expression levels of both circXRN2 and ENC1, while miR-149-5p exhibited a downregulation in its expression. The overexpression of circXRN2 was found to enhance tumor proliferation and metastasis, as evidenced by results from both in vitro and in vivo experiments. Functionally, circXRN2 exerted its antitumor effect by suppressing cell proliferation, migration, and invasion while also promoting apoptosis. Mechanistically, the dysregulated expression of circXRN2 had an impact on the expression of proteins within the EMT signaling pathway. Our results demonstrated that circXRN2 promoted the proliferation and metastasis of CRC cells through the miR-149-5p/ENC1/EMT axis, suggesting that circXRN2 might serve as a potential therapeutic target and novel biomarker in the progression of CRC.

Meta-analysis of the effectiveness and safety of Xingnaojing and naloxone in the treatment of carbon monoxide poisoning.

BACKGROUND: To evaluate the effectiveness and safety of Xingnaojing combined with naloxone in the treatment of carbon monoxide poisoning. METHODS: By retrieving the literatures published in the databases of PubMed, Cochrane Library, Web of Science, Embase, Wanfang Database, Weipu Database, and China National Knowledge Infrastructure from January 2010 to September 2021, the data of randomized controlled trials (RCTs) of Xingnaojing combined with naloxone in the treatment of carbon monoxide poisoning were extracted. The methodological quality of the included RCTs was evaluated by using the tools of bias risk evaluation of Cochrane Collaboration, and the data were statistically analyzed by using RevMan 5.3 software. RESULTS: A total of 20 literatures were included, involving in 771 cases treated by Xingnaojing combined with naloxone and 761 cases in the control group. The effective rate of the experimental group is higher than that of the control group [risk ratio (RR) = 1.20, 95% confidence interval (CI) (1.14, 1.26)]. The average awake time (STD mean difference = -2.08, 95% CI [-2.60, -1.56]), physical recovery time (STD mean difference = -2.94, 95% CI [-3.59, -2.28]), delayed encephalopathy (RR = 0.44, 95% CI [0.31, 0.62]), and adverse reactions (RR = 0.23, 95% CI [0.10, 0.54]) was lower than that of the control group. CONCLUSION: Xingnaojing combined with naloxone in the treatment of carbon monoxide poisoning is significantly superior to naloxone, but it still needs to be further verified by high-quality large samples of RCTs.

Meta-analysis of the effectiveness and safety of Shenyankangfu tablets combined with losartan potassium in the treatment of chronic glomerulonephritis.

OBJECTIVE: To conduct a systematic review of the efficacy and safety of Shenyankangfu tablets in combination with losartan potassium in the treatment of chronic glomerulonephritis. METHOD: We searched PubMed, Embase, Cochrane Library, CNKI, WanFang Data, and WeiPu for comparative studies on Shenyankangfu tablets in combination with losartan potassium in the treatment of chronic glomerulonephritis. The search period runs from the establishment of the database until September 2021. Data extraction and quality evaluation were carried out on the documents that met the inclusion criteria, and a meta-analysis of the included literature was conducted using the RevMan5.3 software. RESULTS: A total of 17 randomized controlled trials that met the inclusion criteria were included, with a total sample size of 1680 patients (841 patients in the study group and 839 in the control group). The effective rate was significantly higher in the study group than in the control group [RR = 1.22, 95% CI (1.16, 1.27), P < 0.00001]. In addition, 24-hour urine protein levels [SMD = -1.11, 95% CI (-1.40, -0.83), P < 0.00001], urine NAG enzyme [SMD = -0.99, 95% CI (-1.27, -0.72), P < 0.00001], leukotactin-1 [SMD = -2.43, 95% CI (-3.50, -1.35), P < 0.00001], and the incidence of adverse reactions [RR = 0.43, 95% CI (0.28, 0.66), P < 0.00001] were lower in the study group when compared to the control group. CONCLUSION: It is safer to treat chronic glomerulonephritis with Shyenyankangfu tablets in combination with losartan potassium. At the same time, it alleviates disease-related symptoms, reduces the influence of cytokine levels, and has fewer adverse reactions, making it more conducive to disease recovery. However, additional multi-center, randomized, control trials with large sample sizes must be conducted to confirm the findings.

The Intracellular Mechanism of Berberine-Induced Inhibition of CYP3A4 Activity.

BACKGROUND: Berberine (BBR) is an isoquinoline alkaloid extracted from the Chinese medicine, exerting a variety of pharmacological effects. BBR is partially metabolized by cytochrome 3A4 (CYP3A4) in vivo. Some reports indicated that BBR could inhibit the activity of CYP3A4. However, the underlying mechanisms are not completely understood. CYP3A4 is reported to be transcriptionally regulated by two nuclear receptors, nuclear transcription X receptor (PXR) and constitutive androstane receptor (CAR), and degraded via the ubiquitin-proteasome system. Hence, we tried to explore the mechanisms of CYP3A4 inhibition on both transcriptive and protein levels. METHODS: Western Blot, RT-PCR and Co-immunoprecipitation were used to perform the experiments. RESULTS: Our results showed that BBR inhibited the transcription of CYP3A4 gene by downregulating PXR. In addition, BBR accelerated the degradation of CYP3A4 protein via polyubiquitination pathway. CONCLUSION: These findings may lead to the determination of novel drug-drug interactions with BBR, and contribute to future clinical application of BBR.