[Significance of high expression of C5orf46 in gastric cancer and potential intervention of tarditional Chinese medicine based on bioinformatics, molecular docking, and cell experiments].

This study aims to investigate the expression, prognosis, and clinical significance of C5orf46 in gastric cancer and to study the interaction between the active components of C5orf46 and tarditional Chinese medicine. The ggplot2 package was utilized for differential expression analysis of C5orf46 in gastric cancer tissues and normal tissues. The survival package was used for survival analysis, univariate regression analysis, and multivariate regression analysis. Nomogram analysis was used to assess the connection between C5orf46 expression in gastric cancer and overall survival. The abundance of tumor-infiltrating lymphocytes was calculated by GSVA package. Coremine database, Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP) database, and PubChem database were used to search the potential components corresponding to C5orf46 gene and tarditional Chinese medicine. Molecular docking was performed to explore the binding affinity of potential components to C5orf46. Cell experiments were performed to explore the expression of C5orf46 gene in cells of the blank group, model group, and drug administration groups. As compared with normal tissues, C5orf46 expression was higher in gastric cancer tissues, which had more significant predictive effects in the early stages(T2, N0, and M0). The more advanced the tumor node metastasis(TNM) stage, the higher the C5orf46 expression and the lower the probability of survival of patients with gastric cancer. The expression of C5orf46 positively correlated with the helper T cells1 in gastric cancer and the macrophage infiltration level in gastric cancer, and negatively correlated with B cells, central memory T cells, helper T cells 17, and follicular helper T cells. Seven potential components of C5orf46 were obtained, and three active components were obtained after the screening, which matched five tarditional Chinese medicines, namely, Sojae Semen Nigrum, Jujubae Fructus, Trichosanthis Fructus, Silybi Fructus, and Bambusae Concretio Silicea. Molecular docking revealed that sialic acid and adeno-sine monophosphate(AMP) had a good binding ability to C5orf46. The results of real-time quantitative polymerase chain reaction(RT-qPCR) and Western blot showed that, as compared with the model group, the mRNA and protein expression levels of C5orf46 were significantly lower in the drug administration groups. The lowest expression level was found at the concentration of 40 µmol·L~(-1). The results of this study provide ideas for the clinical development of traditional Chinese medicine compounds for the treatment of gastric cancer as well as other cancers.

Study on the mechanism of Fufang E'jiao Jiang on precancerous lesions of gastric cancer based on network pharmacology and metabolomics.

ETHNOPHARMACOLOGICAL RELEVANCE: Fufang E'jiao Jiang (FEJ) is a prominent traditional Chinese medicine prescription, which consists of Asini Corii Colla (Donkey-hide gelatin prepared by stewing and concentrating from the hide of Equus asinus Linnaeus., ACC), Codonopsis Radix (the dried roots of Codonopsis pilosula (Franch.) Nannf., CR), Ginseng Radix et Rhizoma Rubra (the steamed and dried root of Panax ginseng C.A. Mey., GRR), Crataegi Fructus (the mature fruits of Crataegus pinnatifida Bunge., CF), and Rehmanniae Radix Praeparata (the steamed and sun dried tuber of Rehmannia glutinosa (Gaertn.) Libosch. ex Fisch. & C.A. Mey., RRP). It is a popularly used prescription for "nourishing Qi and nourishing blood". AIM OF THE STUDY: To explore the potential mechanism of FEJ on precancerous lesion of gastric cancer in rats by combining network pharmacology and metabolomics. METHODS: Traditional Chinese Medicine Systems Pharmacology and Bioinformatics Analysis Tool for Molecular mechanism of Traditional Chinese Medicine were used to identify the ingredients and potential targets of FEJ. GeneCards database was used to define PLGC-associated targets. We built a herb-component-disease-target network and analyzed the protein-protein interaction network. Underlying mechanisms were identified using Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis. In addition, 40% ethanol, N-methyl-N'-nitro-N-nitroguanidine and irregular eating were used to establish PLGC rats model. We also evaluated the efficacy of FEJ on MNNG-induced PLGC rats by body weight, histopathology, blood routine and cytokine levels, while the predicted pathway was determined by the Western blot. Ultra-performance liquid chromatography-tandem mass spectrometry-based serum non-targeted metabolomics was used to select potential biomarkers and relevant pathways for FEJ in the treatment of PLGC. RESULTS: Network pharmacology showed that FEJ exhibited anti-PLGC effects through regulating ALB, TNF, VEGFA, TP53, AKT1 and other targets, and the potential pathways mainly involved cancer-related, TNF, PI3K-AKT, HIF-1, and other signaling pathways. Animal experiments illustrated that FEJ could suppress inflammation, regulate gastrointestinal hormones, and inhibit the expression of PI3K/AKT/HIF-1α pathway-related proteins. Based on serum non-targeted metabolomics analysis, 12 differential metabolites responding to FEJ treatment were identified, and metabolic pathway analysis showed that the role of FEJ was concentrated in 6 metabolic pathways. CONCLUSION: Based on network pharmacology, animal experiments and metabolomics, we found that FEJ might ameliorate gastric mucosal injury in PLGC rats by regulating gastrointestinal hormones and inhibiting inflammation, and its mechanism of action is related to the inhibition of excessive activation of PI3K/AKT/HIF-1α signaling pathway and regulation of disorders of body energy metabolism. This comprehensive strategy also provided a reasonable way for unveiling the pharmacodynamic mechanisms of multi-components, multi-targets, and multi-pathways in Traditional Chinese Medicine.

Fatal systemic emphysematous infection caused by Klebsiella pneumoniae: A case report.

BACKGROUND: Systemic emphysematous infection caused by Klebsiella pneumoniae (K. pneumo niae) is a rare but severe infection which can be lethal if the diagnosis is delayed. CASE SUMMARY: We report a rare case of systemic emphysematous infection via hematogenous dissemination from a liver abscess caused by K. pneumoniae, complicated by multiple organ dysfunction syndrome, septic shock, bacteremia, emphysematous cystitis, prostate and left seminal vesicle abscesses in a diabetic patient. The patient simultaneously presented with spontaneous pneumoperitoneum secondary to rupture of the emphysematous liver abscess. His condition after admission deteriorated rapidly and he died within a short period. This disease is a great challenge for the clinician as K. pneumoniae can cause multifocal emphysematous infections and fulminant septic shock. Pneumoperitoneum following spontaneous rupture of the liver abscess can result in intra-abdominal sepsis that further increases mortality rate. Moreover, appropriate site-specific intervention and adequate drainage of numerous emphysematous liver lesions are difficult. CONCLUSION: Early diagnosis followed by efficient antibiotic therapy and surgical management are essential for systemic emphysematous infection.

Characterization of chemical composition variations in raw and processed Codonopsis Radix by integrating metabolomics and glycomics based on multiple chromatography-mass spectrometry technology.

Codonopsis Radix, a popular food homology medicine, is widely used in clinical traditional Chinese medicine and food supplement, raw products and three types of processed products are the main forms of decoction pieces in China. However, there is no scientific basis for comprehensive chemical characterization of raw and three types of processed products. Herein, we investigated qualitatively and quantificationally secondary and primary metabolites in raw Codonopsis Radix and three types of processed products by metabolomics and glycomics employing multiple chromatography-mass spectrometry technology combined with chemometric analysis further to look for differential compounds and propose the processing-induced chemical mechanisms. The results indicated that Codonopsis Radix became dark-colored and the smell of burnt incense odor was observed after processing. The principal component analysis demonstrated that secondary metabolome and glycome were significantly altered between raw and processed products, and 36 differential secondary metabolites and 11 differential primary metabolites were finally screened through orthogonal partial least-squares-discriminant analysis. The main types of compounds are alkaloids, terpenoids, glycosides, amino acids, monosaccharides, oligosaccharides, and furfural derivatives. Meanwhile, Chemical mechanisms could be involved, including oxidation, glycosidic hydrolysis, esterification, dehydration, and Maillard reaction. This work supplies a chemical basis for the application of various types of Codonopsis Radix decoction pieces.

Yishen Huoxue decoction attenuates unilateral ureteric obstruction-induced renal fibrosis and hypoxia-induced reactive oxygen species generation via adenosine monophosphate-activated protein kinase / peroxisome proliferator-activated receptor coactivator-1α / silent mating-type information regulation 2 homolog 3 pathway.

OBJECTIVE: To investigate the effeicacy of Yishen Huoxue decoction (YSHX) on renal fibrosis induced by unilateral ureteric obstruction (UUO), and on reactive oxygen species (ROS) homeostasis in human umbilical vein endothelial cells (HUVECs). METHODS: Forty male mice were randomly divided into six groups, sham group, UUO group, UUO+ resveratrol (RSV) (15 mg/kg) group, UUO + YSHX 20 mg/kg group (UUO + YSHX-L), UUO + YSHX 40 mg/kg group (UUO + YSHX-M), UUO + YSHX 80 mg/kg group (UUO + YSHX-H). Western blotting was used to measure protein expression levels. Reverse transcription-quantitative polymerase chain reaction was used to measure the mRNA expression. Immunohistochemistry was used to examine the histopathological changes of kidney tissue sample. Cell apoptosis was measured by Annexin V/PI staining. Cell viability was measured using CCK-8/WST-8 assay. RESULTS: YSHX treatment reduced α-SMA and Col-4 expressions, and increased CD31 and VE-cadherin expressions in UUO model mice. In vitro, YSHX increased cell viability and decreased apoptosis of HUVECs under hypoxic conditions. YSHX inhibited ROS generation by activating adenosine monophosphate-activated protein kinase (AMPK)/peroxisome proliferator-activated receptor coactivator-1α (PGC-1α)/silent mating-type information regulation 2 homolog 3 (Sirt3) signaling. CONCLUSION: YSHX treatment reduced 109KJ UUO-induced renal injury and fibrosis. Furthermore, YSHX treatment attenuated hypoxia-induced oxidative stress by regulating AMPK/PGC-1α/Sirt3 signaling.

Poor Prognosis Significance of Pretreatment Thrombocytosis in Patients with Colorectal Cancer: a Meta-Analysis.

BACKGROUND: Recently, several studies have reported that elevated platelet counts may be associated with the poor prognosis of colorectal cancer. However, conclusions remain controversial. This meta-analysis was therefore designed to analyze and evaluate the prognostic role of preoperative or pretreatment thrombocytosis in patients with colorectal cancer. MATERIALS AND METHODS: We searched PubMed, EMBASE, the Cochrane Library and Web of Science to March 29th, 2015. The citation lists of included studies were also hand-searched to identify further relevant trials. To investigate the association between thrombocytosis and prognosis of colorectal cancer, the 1-year, 3-year and 5-year survival of each studies were obtained. The odds ratio (OR) with its 95% confidence interval (CI) was used to evaluate the relation of overall survival (OS) between thrombocytosis and normal platelet counts (PLT). Likewise, disease free survival (DFS) was obtained and evaluated. The analysis was performed and assessed using Review Manager 5.2. RESULTS: A total of 14 studies (N=5,566 participants, 11 including 4,468 for OS, 6 including 1,533 for DFS) were included in this meta-analysis, of which seven (N=3810) defined thrombocytosis as a platelet count ≥ 400?109L, and 375 (9.8%) patients exhibited pretreatment thrombocytosis. Thrombocytosis have a close relationship with the poor OS of colorectal cancer compared with normal PLT, with the pooled ORs of 1-year, 3-year and 5-year survival being 0.41 [95% CI 0.34-0.51; P<0.001], 0.28 [95% CI 0.21-0.38; P<0.001] and 0.26 [95% CI 0.20-0.34; P<0.001], respectively. For DFS, the same results were showed as the pooled ORs of 1-year, 3-year and 5-year survival respectively being 0.34 [95% CI 0.24-0.50; P<0.001], 0.31 [95% CI 0.23-0.43; P<0.001] and 0.25 [95% CI 0.18-0.34; P<0.001]. CONCLUSIONS: This meta-analysis indicated that thrombocytosis may predict poor prognosis for patients with colorectal cancer, and platelet counts may be a cost-effective and noninvasive marker.

Single-walled carbon nanotubes and graphene oxides induce autophagosome accumulation and lysosome impairment in primarily cultured murine peritoneal macrophages.

The wide application of carbon nanomaterials in various fields urges in-depth understanding of the toxic effects and underlying mechanisms of these materials on biological systems. Cell autophagy was recently recognized as an important lysosome-based pathway of cell death, and autophagosome accumulation has been found to be associated with the exposure of various nanoparticles, but the underlying mechanisms are still uncertain due to the fact that autophagosome accumulation can result from autophagy induction and/or autophagy blockade. In this study, we first evaluated the toxicity of acid-functionalized single-walled carbon nanotubes and graphene oxides, and found that both carbon nanomaterials induced adverse effects in murine peritoneal macrophages, and GOs were more potent than AF-SWCNTs. Both carbon nanomaterials induced autophagosome accumulation and the conversion of LC3-I to LC3-II. However, degradation of the autophagic substrate p62 protein was also inhibited by both nanomaterials. Further analyses on lysosomes revealed that both carbon nanomaterials accumulated in macrophage lysosomes, leading to lysosome membrane destabilization, which indicates reduced autophagic degradation. The effects of AF-SWCNTs and GOs on cell autophagy revealed by this study may shed light on the potential toxic mechanism and suggest caution on their utilization.

Exposure of single-walled carbon nanotubes impairs the functions of primarily cultured murine peritoneal macrophages.

It is increasingly important to understand the single-walled carbon nanotubes' (SWCNTs) immune response as their increasingly biomedical researches and applications. Macrophages and T cells play important roles in scavenging foreign materials and pathogens and regulating immune response. In this work, primarily cultured murine peritoneal macrophages and purified splenic T cells were utilised to determine the toxic effects of SWCNTs and acid-functionalised SWCNTs (AF-SWCNTs) on the immune system, especially on macrophage functions. Macrophages were exposed to 0-50 µg/ml of CNTs for 24 h and no significant cytotoxicity was found by live/dead and annexin-V-FITC/PI analyses. The TEM images revealed that AF-SWCNTs were engulfed mostly through phagocytosis and located in lysosomes of macrophages. Measurement of mitochondrial membrane potential and proteasome subunit gene expression demonstrated that 10 and 50 µg/ml AF-SWCNTs could damage mitochondrial function and proteasome formation in a concentration-dependent manner. Functional analyses revealed that the percentage of phagocytic cells were affected significantly by 20 µg/ml CNTs, and 5 µg/ml AF-SWCNTs inhibited the phagocytic efficiency of latex beads in macrophages. The accessory cell function was affected by both AF-SWCNTs and SWCNTs at concentrations of 10 and 50 µg/ml, respectively. Furthermore, AF-SWCNT biased naïve T-cell differentiation to Th1 type by inducing the production of IFN-γ and TNF, implying the potential risk of Th1-associated diseases (e.g. autoimmune diseases and inflammation) on AF-SWCNT exposure.