Cardiovascular toxicity of anaplastic lymphoma kinase inhibitors for patients with non-small cell lung cancer: a network meta-analysis.

Aim: We conducted network meta-analysis to assess cardiovascular toxicity of anaplastic lymphoma kinase-tyrosine kinase inhibitors (ALK-TKIs).Materials & methods: Eleven articles involving 2855 patients and six interventions including crizotinib, alectinib, ceritinib, lorlatinib, brigatinib and chemotherapy were analyzed.Results: No significant difference was observed in overall cardiovascular risk among ALK-TKIs. Subgroup analysis showed that for cardiac toxicity, crizotinib and alectinib were more likely to cause myocardial rhythm abnormalities. Crizotinib and ceritinib had a higher risk of Q-T prolongation than chemotherapy. For vascular toxicity, crizotinib and ceritinib had a higher risk of thrombotic events than brigatinib. Crizotinib and lorlatinib were more likely to cause blood pressure abnormalities.Conclusion: Clinicians should carefully monitoring cardiovascular events when ALK-TKIs used in NSCLCs patients with baseline cardiovascular diseases.

A network meta-analysis revealed the cardiovascular toxicity caused by ALK-TKIs in non-small cell lung cancer patients.

NAT1 is a critical prognostic biomarker and inhibits proliferation of colorectal cancer through modulation of PI3K/Akt/mTOR.

The aim of this study was to analyze the correlations between NAT1 and clinicopathological features of and prognosis in colorectal cancer (CRC). RNA sequencing data and clinical information were retrieved from The Cancer Genome Atlas database. Wilcoxon test, logistic regression and Kaplan-Meier method were used to estimate the association between NAT1 and prognosis in CRC. In vitro experiments were conducted to confirm the role of NAT1. NAT1 is significantly less expressed in CRC and independently associated with poor prognosis in CRC patients. The authors further confirmed that expression of NAT1 was significantly lower in SW116 colon cancer cells than in NCM460 cells. Overexpressed NAT1 obviously inhibited the growth of CRC cells by downregulating phosphorylation of the PI3K/Akt/mTOR signaling pathway. NAT1 may be a potential therapeutic target for CRC.

Lay abstract Colorectal cancer (CRC) is a common malignancy worldwide. Because of the limited understanding of the pathogenesis and prognostic factors associated with CRC, the treatment effect in CRC remains poor. In the present study, the authors demonstrate that NAT1 is significantly less expressed in CRC and independently associated with poor prognosis in CRC patients. NAT1 may exert antitumor activity by inhibiting phosphorylation of the PI3K/Akt/mTOR signaling pathway. These results suggest that NAT1 may be a prognostic factor in and therapeutic target for CRC.

Binding Performance of Human Intravenous Immunoglobulin and 20(S)-7-Ethylcamptothecin.

A previous study showed that intravenous immunoglobulin (IVIG) could preserve higher levels of biologically active lactone moieties of topotecan, 7-ethyl-10-hydroxycamptothecin (SN-38) and 10-hydroxycamptothecin at physiological pH 7.40. As one of camptothecin analogues (CPTs), the interaction of 7-ethylcamptothecin and IVIG was studied in vitro in this study. It was shown that the main binding mode of IVIG to 7-ethylcamptothecin was hydrophobic interaction and hydrogen bonding, which is a non-specific and spontaneous interaction. The hydrophobic antigen-binding cavity of IgG would enwrap the drug into a host-guest inclusion complex and prevent hydrolysis of the encapsulated drug, while the drug is adjacent to the chromophores of IgG and may exchange energy with chromophores and quench the fluorescence of the protein. Also, the typical ß-sheet structure of IVIG unfolded partially after binding to 7-ethylcamptothecin. Additionally, the binding properties of IVIG and six CPTs with different substituents at A-ring and/or B-ring including camptothecin, topotecan, irinotecan, 10-hydroxycamptothecin, 7-ethylcamptothecin and SN-38 were collected together and compared each other. Synergizing with anti-cancer drugs, IVIG could be used as a transporter protein for 7-ethylcamptothecin and other CPTs, allowing clinicians to devise new treatment protocols for patients.

Up-regulation of IL-12 expression in patients with chronic hepatitis B is mediated by the PI3K/Akt pathway.

Hepatitis B virus (HBV) replicates noncytopathically in hepatocytes, but HBV or proteins encoded by HBV genome could induce cytokines, chemokines expression by hepatocytes.IL-12 is a typical proinflammatory cytokine that plays a critical role in host defense against pathogens, including the HBV. However, the role of IL-12 in chronic hepatitis B (CHB) remains unclear. The aims of this study were to detect the expression of IL-12 in CHB patients and explore the molecular mechanism of HBV-induced IL-12 expression. The results showed that serum levels and hepatic expression of IL-12 were significantly upregulated in CHB patients. HBx protein increased IL-12 expression in a dose-dependent manner. Furthermore, inhibition of PI3K/Akt significantly decreased the HBx-induced IL-12 expression and Akt activation. Taken together, these results indicate that the molecular mechanism of HBV-induced IL-12 expression involves activation of the PI3K/Akt pathway by HBx, leading to transactivation of the IL-12 p35 and p40 promoters.

Increased miR-16 expression induced by hepatitis C virus infection promotes liver fibrosis through downregulation of hepatocyte growth factor and Smad7.

Hepatitis C virus (HCV) is involved in the initiation and progression of liver fibrosis by regulating genes encoding host proteins. However, the underlying mechanism of HCV-induced liver fibrosis is still to be determined. Reverse transcription polymerase chain reaction (RT-PCR) and western blot were performed to investigate the effect of HCV infection on the expression of the cellular microRNA miR-16 and its target genes encoding hepatocyte growth factor (HGF) and Smad7 in patients infected with HCV and in a liver cell line, QSG-7701, transfected with Ad-HCV, a recombinant adenovirus construct for expression of the HCV core protein. Regulation of HGF and Smad7 expression by miR-16 was assessed using luciferase reporter construct assays and miR-16 mimic transfection. Interferon-α (IFN-α) was used to verify the alteration of gene expression induced by HCV in QSG-7701 cells. Here, we found that miR-16 levels were increased in patients with HCV infection and were correlated with HGF and Smad7 expression levels in patients with HCV infection. Furthermore, HGF and Smad7 were predicted by bioinformatics analysis to be targets of miR-16. Upregulation of miR-16 and decreased HGF and Smad7 expression were still shown in QSG-7701 cells infected with Ad-HCV. Additionally, interferon-α (IFN-α) could reverse the changes in gene expression induced by HCV infection. These results suggest that the upregulation of miR-16 expression induced by HCV infection is a novel mechanism that contributes to downregulation of HGF and Smad7 in the development of liver fibrosis.

Machine learning predicts cancer-associated deep vein thrombosis using clinically available variables.

PURPOSE: To develop and validate machine learning (ML) models for cancer-associated deep vein thrombosis (DVT) and to compare the performance of these models with the Khorana score (KS). METHODS: We randomly extracted data of 2100 patients with cancer between Jan. 1, 2017, and Oct. 31, 2019, and 1035 patients who underwent Doppler ultrasonography were enrolled. Univariate analysis and Lasso regression were applied to select important predictors. Model training and hyperparameter tuning were implemented on 70% of the data using a ten-fold cross-validation method. The remaining 30% of the data were used to compare the performance with seven indicators (area under the receiver operating characteristic curve [AUC], sensitivity, specificity, accuracy, balanced accuracy, Brier score, and calibration curve), among all five ML models (linear discriminant analysis [LDA], logistic regression [LR], classification tree [CT], random forest [RF], and support vector machine [SVM]), and the KS. RESULTS: The incidence of cancer-associated DVT was 22.3%. The top five predictors were D-dimer level, age, Charlson Comorbidity Index (CCI), length of stay (LOS), and previous VTE (venous thromboembolism) history according to RF. Only LDA (AUC = 0.773) and LR (AUC = 0.772) outperformed KS (AUC = 0.642), and combination with D-dimer showed improved performance in all models. A nomogram and web calculator https://webcalculatorofcancerassociateddvt.shinyapps.io/dynnomapp/ were used to visualize the best recommended LR model. CONCLUSION: This study developed and validated cancer-associated DVT predictive models using five ML algorithms and visualized the best recommended model using a nomogram and web calculator. The nomogram and web calculator developed in this study may assist doctors and nurses in evaluating individualized cancer-associated DVT risk and making decisions. However, other prospective cohort studies should be conducted to externally validate the recommended model.

Polydatin ameliorates DSS-induced colitis in mice through inhibition of nuclear factor-kappaB activation.

Nuclear factor- κB (NF- κB) plays a pivotal role in the regulation of immune and inflammatory responses. The real-time expression level of NF- κB reflects the development of ulcerative colitis (UC). Polydatin has vast pharmacological activities, including inhibiting the production of inflammatory mediators, inducing the production of antioxidants, regulating immune function, etc. The purpose of this study was to investigate the potential inhibitory effects of polydatin on NF- κB pathway activation in a mouse UC model. The results showed that polydatin treatment downregulated NF- κB p65 activity and expression, blocked the expression of TNF- α, IL-6 and IL-1 ß at both mRNA and protein levels, decreased myeloperoxidase (MPO) activity, and alleviated inflammatory damage of colitis in mice with UC (p < 0.05), suggesting that the anti-inflammation effects of polydatin can be attributed, at least partially, to the blocking of the NF- κB pathway.

Ovarian endometrioid carcinoma resembling sex cord-stromal tumor: A case report.

BACKGROUND: Ovarian endometrioid carcinoma resembling sex cord-stromal tumor (ECSCSs) is rare. CASE SUMMARY: We present a rare case of primary ECSCSs in the left ovary. A 39-year-old female patient had persistent dull pain in the lower abdomen for more than 1 mo, and she was initially diagnosed with pelvic inflammatory disease at a hospital. The patient received transabdominal hysterectomy, bilateral salpingo-oophorectomy, and pelvic and para-aortic lymph node dissection at our hospital and finally diagnosed with ECSCSs. After the operation, the patient received eight courses of cisplatinum + etoposide + bleomycin chemotherapy treatment and no evidence of tumor recurrence or metastasis was found in a 2-year follow-up period. CONCLUSION: Ovarian endometrioid carcinoma is similar to the ovary sex cord-stromal tumor, especially when the cord-like structure is obvious. The clinical diagnosis for this tumor is difficult before surgery and pathology examination. The necessary immunohistochemical markers are of positive significance for assisting diagnosis and differential diagnosis.

The complete chloroplast genome of 'black tiger 2' (Kadsura coccinea (lem.) A.C. Smith) in southeast of China and phylogenetic relationshipsAQ1.

A new super Kadsura coccinea, named 'black tiger 2', was selected from variant forms of seedlings. In this study, The complete chloroplast (cp) genome of 'black tiger 2' was obtained. The complete cp genome is 145,608 in length, and contained 126 genes, including 83 protein-coding genes, 8 ribosomal RNA genes, and 35 transfer RNA genes. Phylogenetic analyses established that 'black tiger 2' was closely clustered with other Schisandraceae species such as Schisandra chinensis and Illicium, which helps elucidate the phylogenetic relationship between 'black tiger 2' and other species.

Urinary metabonomics for diagnosis of depression in hepatitis B virus-infected patients.

BACKGROUND: Depression is concomitantly presented in Hepatitis B Virus (HBV)-infected patients and decreases these patients' quality of life. However, there are no laboratory-based methods to objectively diagnose this disorder. OBJECTIVES: The aim of this study was to investigate the alteration of urinary metabolites in depressed HBV-infected patients. PATIENTS AND METHODS: In this study, 81 depressed HBV-infected patients, 68 non-depressed HBV-infected patients and 64 Healthy Controls (HC) were recruited. A nuclear magnetic resonance (NMR)-based urinary metabonomic method was used to characterize the urinary metabolic profiling of depressed and non-depressed subjects. RESULTS: Seventeen differential urinary metabolites responsible for discriminating depressed HBV-infected patients from non-depressed HBV-infected patients and HC were identified. Among these metabolites, pyruvate, isobutyrate, N-methylnicotinamide, α-hydroxybutyrate, acetoacetate and malonate were identified as potential biomarkers for diagnosing depression in HBV-infected patients. A combined panel of these potential biomarkers could effectively discriminate depressed HBV-infected patients from non-depressed HBV-infected patients and HC, with an average accuracy of 89.6% in the training set and a predictive accuracy of 86.4% in the test set. CONCLUSIONS: These findings suggest that NMR-based urinary metabonomics approach might be a useful tool for the clinical diagnosis of depression in HBV-infected patients and the six potential biomarkers could be helpful for developing an objective diagnostic method. Limited by the number of recruited subjects, future studies are required to validate our conclusions.

Triterpenoids from Ganoderma lucidum and their cytotoxic activities.

From the ethyl acetate fraction of the fruiting body of Ganoderma lucidum, a new triterpenoid, ethyl 7ß-hydroxy-4,4,14α-trimethyl-3,11,15-trioxo-5α-chol-8-en-24-oate (4), named ethyl lucidenates A, along with three known compounds, ganodermanondiol (1), lucidumol B (2) and methyl lucidenates A (3) were isolated by silica gel column, ODS column chromatography and PHPLC. Their structures were established on the basis of spectroscopic analysis and chemical evidence. The isolated compounds were tested using in vitro MTT assay for their cytotoxic activities against the K562, HL-60, CA46, HepG2, SW480 and SMMC-7221 cancer cell lines. Among them, compound 4 showed cytotoxicity against HL-60 and CA46 cancer cell lines with IC(50) values of 25.98 and 20.42 µg mL(-1), respectively.

Anti-oxidant effects of resveratrol on mice with DSS-induced ulcerative colitis.

BACKGROUND AND AIMS: Oxidant/antioxidant balance is suggested to be an important factor for the recurrence and progression of ulcerative colitis (UC). The aim of the study is to investigate the potential protective role of resveratrol (Res) against dextran sodium sulfate (DSS)-induced oxidative damage in colon of mice with UC. METHODS: UC was induced in mice by oral administration of synthetic DSS (molecular weight 5000) for 7 days. Mice were divided into normal group, colitis control group, low-dose Res-treated group (RLD-treated group), and high-dose Res-treated group (RHD-treated group). Inhibitory effects of concomitant treatment with Res were assessed daily using a Disease Activity Index (DAI) and severity of histological changes. MDA, MPO, SOD and GSH-PX activity of colonic tissue were determined in colon samples by chemical colorimetry. TNF-alpha, IL-8, IFN-gamma, p22(phox) and gp91(phox) expression levels were detected using quantitative reverse-transcriptase polymerase chain reaction (qRT-PCR), ELISA, and Western blot analysis. RESULT: Administration of Res significantly inhibited the severity of UC compared to the colitis control group. Colonic tissue MDA and MPO activities decreased significantly in Res-treated groups compared to colitis control groups. Furthermore, colonic tissue SOD and GSH-Px activities increased significantly in Res-treated groups compared to colitis control groups. The expression levels of TNF-alpha, IL-8, IFN-gamma, p22(phox), and gp91(phox) also decreased significantly in the Res-treated group compared to the colitis control group. CONCLUSIONS: Oral administration of Res exerts marked inhibitory effects on UC in mice. Resveratrol may play an important role in preventing DSS-induced oxidative damage.