Exploring the effect of C-X-C motif chemokine ligand-13 on the proliferation and migration of mesenchymal stem cells based on network pharmacology / 解剖学报

Objective To explore the effect of C-X-C motif chemokine ligand-13 (CXCL-13) on the proliferation and migration of human bone marrow mesenchymal stem cells (BMSCs) by network pharmacology. Methods To predict that the targets of CXCL-13 on BMSCs by online database. Metascape was used to perform gene ontology (GO) of the targets and Kyoto encyclopedia of genes and genomes (KEGG) pathway was used to perform enrichment analysis. The protein interaction analysis was performed by STRING 11.0 database, and the protein module of core gene was screened by using the cytoHubba 0. 1 of Cytoscape 3. 8. We divided BMSCs into control group, CXCL-13 group and PI3K inhibitor group. MTT assay, flow cytometric analysis and Transwell cell migration assay were respectively used to detect the absorbance (A) value of BMSCs in each group, the apoptosis rate and the number of cell migration. The protein contents of epidermal growth factor (EGF) and vascular endothelial growth factor (VEGF) in BMSCs supernatant were determined by ELISA. Western blotting was used to detect the protein expression of Akt and phosphorylated Akt (p-Akt) of BMSCs in each group. Results It was predicted that 21 targets of CXCL-13 effect on BMSCs. There were 32 biological processes related to cell proliferation include stem cell proliferation, regulation of endothelial cell proliferation and positive regulation of smooth muscle cell proliferation. There were 22 biological processes related to cell migration include regulating cell migration, amebic cell migration and endothelial cell migration. There were 40 KEGG pathways including cancer pathway, PI3K-Akt signaling pathway and MAPK signaling pathway. The core proteins included tumor protein P53 (TP53), epidermal growth factor receptor (EGFR), heat shock protein 90 kD alpha class B member 1 (HSP90AB1), protein kinase Ca (PRKCA), estrogen receptor 2 (ESR2) and prostaglandin E receptor 4 (PTGER4). Compared with other groups, the absorbance (A) value and cell migration number of BMSCs in CXCL-13 group increased significantly (P< 0. 01, 71=15), and the apoptosis rate decreased significantly (P<0. 01, n= 15). However, absorbance value, apoptosis rate and migration number of BMSCs in PI3K inhibitor group were contrary to those in CXCL-13 group (P<0. 01, n= 15). Compared with the control group, the protein contents of EGF and VEGF in BMSCs of CXCL-13 group increased significantly (P<0. 01, n= 15), and the relative expression of Akt and p-Akt increased significantly (P<0. 01, n = 9). However, the protein content of EGF and VEGF, and the relative expression of Akt and p-Akt in PI3K inhibitor group were opposite. Conclusion Through activating PI3K-Akt pathway, CXCL-13 may promote BMSCs paracrine EGF and VEGF proteins, and improve proliferation and migration of BMSCs, as well as inhibit BMSCs apoptosis.

Safety of protease inhibitors and Arbidol for SARS-CoV-2 pneumonia in Zhejiang Province, China / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

The aim of this study was to evaluate the safety of an antiviral regimen of protease inhibitors combined with Arbidol (umifenovir) for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pneumonia patients. The genomic sequence of SARS-CoV-2 is highly homologous to that of SARS-CoV (Zhou et al., 2020). Previously published basic and clinical research on anti-SARS-CoV treatment found that lopinavir/ritonavir (LPV/r) could improve the prognosis of SARS patients (Chan et al., 2003; Chu et al., 2004). Darunavir (DRV) is another protease inhibitor that blocks the binding of SARS-CoV-2 to human angiotensin-converting enzyme 2 (Omotuyi et al., 2020). The broad-spectrum antiviral drug Arbidol (umifenovir) also shows in vitro anti-SARS-CoV activity (Khamitov et al., 2008).

Cytotoxic Responses and Apoptosis in Rat Kidney Epithelial Cells Exposed to Lead / 生物医学与环境科学（英文）

The toxic effects of lead on normal rat kidney epithelial cells (NRK cells) may occur via various pathways. However, the role of intrinsic mitochondrial pathway in Lead-induced apoptosis in NRK cells has not been investigated. The purpose of our study was to investigate cytotoxic responses and cell apoptosis mediated by lead in NRK cells. NRK cells were treated with different concentrations of Lead acetate for 12 h to determine the cytotoxicity of lead. Mitochondrial transmembrane potential was also analyzed using a fluorescence spectrophotometer. Moreover, the activities of caspase-3 and caspase-9 were detected in the presence of lead. Finally, the lead-induced cell apoptosis was evaluated by flow cytometry in the present of caspase inhibitors Z-VAD-FMK and Ac-LEHD-FMK, respectively. The results would contribute to clarify the role of Lead in proliferation and apoptosis of NRK cells, and help to understand the underlying mechanism responsible for lead-induced cell apoptosis.

Dynamic distribution of the avian infectious bronchitis virus isolate strain Jin-13 in SPF chickens / 病毒学报

This study aimed to understand the dynamic distribution of infectious bronchitis virus (IBV) Jin-13 strain in SPF chickens. Ninety-day-old SPF chickens were inoculated with Jin-13, a virulent strain, and dissected at day 1, 4, 7, 10, 14, 21, 28 or 35 post-inoculation (dpi). Samples of heart, liver, spleen, lung, trachea, kidney and duodenum were collected and the N gene was detected by Sybr Green I real-time quantitative RT-PCR assays. The established method had a good linear correlation from 7.77 x 10(8) to 10(0) copies/microL. SPF chickens developed typical clinical signs of IBV at the 4th dpi, and the IBV viral concentration of tissues and organs gradually increased with a peak of up to 7.13 x 10(4) copies/microL. The viral concentration of most organs decreased by the 10th dpi, but those of the kidney, trachea and lung remained positive for IBV at 28 dpi and the heart was still positive for IBV at > 35 dpi. The results of this study, showed that the Jin-13 strain can cause prolonged virus excertion in chickens with severe renal damage.

Pathologic study of circumferential margin involvement in middle and lower rectal cancer / 中华外科杂志

<p><b>OBJECTIVE</b>To study the rule of circumferential margin involvement (CMI) in middle and low rectal cancer and improve its detection rate.</p><p><b>METHODS</b>Pathological large slices stained by HE method was combined with immunohistochemistry to study the CMI of 41 patients with middle and low rectal cancer. There were 20 female and 21 male patients, with an average age of 59.5 years (range, 33 to 77 years).</p><p><b>RESULTS</b>The positive rate of CMI by HE staining was 21.9%. The CMI positive rates of CK20, CDX2 and MMP7 by immunohistochemistry staining was 29.3%, 31.7% and 26.8%, respectively. The positive rate of CMI was 36.6% when combined both HE and immunohistochemistry test, which was significantly higher than those in single methods (all P < 0.05). The positive rate of CMI in poorly differentiated tumor was significantly higher than that in moderately and well-differentiated tumor. The positive rate of CMI in the tumors with a distance of less than 5 cm between the anal verge and the lower tumor margin was significantly higher than that in tumors with the above-mentioned distances of greater than or equal to 5 cm (P < 0.05). According to MMP7 detection, the positive rate of CMI in the group without lymphatic metastasis was significantly lower than that in N1 and N2 group (all P < 0.05). There was no significant correlation between CMI and gender, age, tumor infiltration, lymphatic metastasis, general pathological types and operation methods (P > 0.05).</p><p><b>CONCLUSIONS</b>The positive detection rate of CMI can be improved when combined large slices HE staining and immunohistochemistry. There is significant association between CMI and poorly differentiated tumor, lower location and positive lymphatic metastasis.</p>