Mechanism of Sophorae tonkinensis radix et rhizome-induced nephrotoxicity in rats based on network toxicology and experimental validation / 中国药理学通报

Aim To investigate the mechanism of Sophorae tonkinensis radix et rhizome (ST) induced nephrotoxicity based on network toxicology and experimental verification. Methods Through network toxicology the target of toxic components of ST was predicted, nephrotoxicity-related target genes were located, the intersection of targets was taken, the STRING platform was imported to map the target protein interactions, MetaScape database was used for GO and KEGG analysis, BioGPS database for screening the key expressed genes in rat nephrotoxicity and the component-target-pathway network was constructed. The mechanism of ST induced nephrotoxicity was verified through animal experiments, and qRT-PCR was applied to detect mRNA expression level of key genes in kidney tissue. Results Twenty toxic components of ST were screened from network toxicology, mainly including matrine, sophoridine, maackiain. A total of 135 targets were involved, and HSP90AA1, SRC, MAPK1, MAPK3, AKT1 were the main targets. A total of 169 related signaling pathways were yielded by KEGG analysis, and the mechanism of nephrotoxicity might be related to cancer pathway, PI3K-Akt signaling pathway, HIF-1 signaling pathway, MAPK signaling pathway. PPARA, RAF1, MAP2K1, SRC, AKT1 and MAPK3 were screened from BioGPS database. The results of animal experiments showed that BUN and SCr level increased (P <0. 01) in rats with high-dose group, and the kidney tissue was significantly damaged. qRT-PCR results indicated that the expression of PPARA, RAF1, MAP2K1, MAPK3 mRNA increased, the expression of AKT1 mRNA decreased in the high-dose group of ST (P <0. 05). Conclusions The mechanism of Sophorae tonkinensis radix et rhizome induced nephrotoxicity is found to be related to the combined action of multiple components, multiple targets and multiple pathways, which also provides a theoretical basis for the in-depth exploration of the toxicology.

Mechanism of Sophora tonkinensis Gagnep regulating leukocyte transendothelial migration pathway in improving acute pharyngitis based on network pharmacology / 中国药理学通报

Aim To elucidate the molecular mechanism of Sophora tonkinensis Gagnep in improving acute pharyngitis based on network pharmacology, animal experiments and quantitative real-time PCR.Methods The active components and targets of Sophora tonkinensis Gagnep were collected from the database of traditional Chinese medicinal systems databases and analysis platform(TCMSP). Targets related to acute pharyngitis were acquired through GeneCards, OMIM, DrugBank and Disgenet databases. After the common targets of the two were screened, the STRING database was used to construct the protein interaction network, and the Metascape platform was used for pathway analysis. At the same time, Cytoscape software was used to construct a network of "herbal-disease-component-target" and "herbal-disease-component-target-pathway" network. The acute pharyngitis models in rats were established to study the effect of water extract of Sophora tonkinensis Gagnep on acute pharyngitis in rats. Quantitative real-time PCR technology was used to study the effect of Sophora tonkinensis Gagnep on key gene targets in key pathways of pharyngeal tissues in rats with acute pharyngitis. Results In this experiment, 509 related targets of 21 active components of Sophora tonkinensis Gagnep were obtained, 2 167 related targets of acute pharyngitis were obtained, and 194 common targets of Sophora tonkinensis Gagnep and acute pharyngitis were obtained. KEGG pathway analysis screened 344 related signaling pathways, indicating that IL-17 signaling pathway, NF-kappa B signaling pathway and leukocyte transendothelial migration pathway might play a key role in the improvement of acute pharyngitis by Sophorae tonkinensis Gagnep. Animal experiments showed that the low dose group of Sophora tonkinensis Gagnep water extract had better therapeutic effect on acute pharyngitis. The results of quantitative real-time PCR showed that the low-dose group of Sophora tonkinensis Gagnep significantly down-regulated the expression levels of ITGB2, PIK3CA, PIK3CD and PTPN11 genes in leukocyte transendothelial migration pathway(P<0.05). Conclusions The above results show that Sophora tonkinensis Gagnep has the characteristics of multi-component, multi-target and multi-pathway synergy in improving acute pharyngitis, which provides a theoretical basis for further study on the complex mechanism of Sophora tonkinensis Gagnep in improving acute pharyngitis.

Does Early Endoscopy Affect the Clinical Outcomes of Patients with Acute Nonvariceal Upper Gastrointestinal Bleeding? A Systematic Review and Meta-Analysis

Background/Aims@#In patients with acute nonvariceal upper gastrointestinal bleeding (ANVUGIB), the optimal timing of endoscopy is still a matter of dispute. We conducted a systematic review and meta-analysis to determine the clinical benefit of early endoscopy. @*Methods@#A literature search of the MEDLINE, Embase, and Cochrane databases was conducted to identify publications from inception to March 1, 2022. Eligible studies included observational cohort studies and randomized controlled trials that reported clinical outcomes of endoscopy in patients with ANVUGIB. ANVUGIB patients who underwent endoscopy within 24 hours of admission were considered to have had an early endoscopy. The primary outcome was the mortality rate in ANVUGIB patients who had early or nonearly endoscopy. @*Results@#The final analysis included five randomized controlled studies (RCTs) and 20 observational studies from the 1,206 identified articles. The mortality rate was not significantly reduced among patients who received endoscopy performed within 24 hours, whether in cohort studies nor in RCTs. For subgroup analysis, a higher mortality rate was found only among patients who received very early endoscopy within 12 hours (odds ratio, 1.66; p<0.001, I 2 =0) in cohort studies. No significant difference in mortality rates was found among patients at high risk of bleeding who received early versus nonearly endoscopy. @*Conclusions@#Early endoscopy within 24 hours does not appear to significantly reduce the mortality rates of patients with ANVUGIB. Further well-designed studies are warranted to address if very early endoscopy within 12 hours can provide a clinical benefit for patients at high risk of bleeding.

The Expression of BTG2 and Its Regulatory Effect on Radiosensitivity of Lung Adenocarcinoma / 中国生物化学与分子生物学报

Among the types of lung cancer, lung adenocarcinoma accounts for the majority, and its overall survival rate is poor. B-cell translocation gene 2 (BTG2) is a member of the antiproliferative gene family, belonging to the BTG/TOB family. Many studies have shown that BTG2 was abnormally expressed in many types of tumors, but its regulatory role in the radiosensitivity of lung adenocarcinoma remained unclear. In this study, we explored the expression level of BTG2 in patients with lung adenocarcinoma and its correlation with clinical prognosis through online database and tissue samples of lung adenocarcinoma patient. The results indicated that the expression level of BTG2 decreased significantly in lung adenocarcinoma patient with radiation resistance. Bioinformatics analysis confirmed that BTG2 could respond to radiotherapy in lung adenocarcinoma cell lines, and its low expression in lung adenocarcinoma patients was associated with poor prognosis (P < 0.05). The lentivirus overexpressing BTG2 (OE-BTG2) was transfected into human lung adenocarcinoma cell lines to increase the expression level of BTG2 including A549 and H1299. And the effect of BTG2 overexpression on the radiosensitivity of lung adenocarcinoma cell lines was detected by clone formation assay. Clone formation experiment confirmed that overexpression of BTG2 could significantly enhance the radiosensitivity of A549 and H1299 cell lines (P < 0.05). The expression levels of BTG2 and apoptosis related protein-Bax were detected by Western blotting (WB) and immunohistochemistry (IHC). The effect of BTG2 on radiation sensitivity of lung adenocarcinoma was further detected via nude mouse in vivo. WB experiment confirmed that BTG2 upregulation could significantly increase the apoptosis level of A549 and H1299 cells after radiation. Moreover, BTG2 overexpression can markedly enhance the radiosensitivity of lung adenocarcinoma (P < 0.05) and increase the protein level of Bax after radiation in vivo. In conclusion, BTG2 had low expression in lung adenocarcinoma patients and its low expression level was closely related to the poor clinical prognosis. Overexpression of BTG2 can increase the radiosensitivity of lung adenocarcinoma cell lines and promote the process of apoptosis after radiation, indicating a new target for overcoming the radiation resistance of lung adenocarcinoma.

Ferruginol alleviates inflammation in dextran sulfate sodium-induced colitis in mice through inhibiting COX-2, MMP-9 and NF-κB signaling

Objective: To assess the anti-inflammatory efficacy of ferruginol on dextran sulfate sodium (DSS) stimulated ulcerative colitis mice. Methods: Ulcerative colitis was induced in C57BL/6J mice by administering 2% of DSS through drinking water for 7 d. The mice in the treatment group were treated with DAA+50 mg/kg/day ferruginol orally. In the positive control group, sulfasalazine (50 mg/kg/day) was used alongside with DSS. After induction, the bodyweight, character of stool and feces occult blood were recorded daily, the disease activity index was calculated, and the colon length, colon weight, and spleen weight were recorded. The myeloperoxidase activity was assayed by spectrophotometry. Interleukin (IL)-6, IL-1β, and tumor necrosis factor-a were determined by ELISA method, and nuclear factor-κB, cyclooxygenase-2, matrix metalloproteinases-9, and inducible nitric oxide synthase by Western blotting assays. Results: Ferruginol significantly increased the bodyweight, colon weight, colon length, and decreased disease activity index and spleen weight. It exhibited anti-inflammatory activity against DSS induced ulcerative colitis in mice by reducing the activities of myeloperoxidase, tumor necrosis factor-α, nuclear factor-κβ, IL-1β, cyclooxygenase-2, matrix metalloproteinases-9, IL-6, and inducible nitric oxide synthase. Conclusions: Ferruginol could be used to treat ulcerative colitis by attenuating the inflammation in colon cells and maintaining colonic mucosal barrier integrity.

Ferruginol alleviates inflammation in dextran sulfate sodium-induced colitis in mice through inhibiting COX-2, MMP-9 and NF-κB signaling

Objective: To assess the anti-inflammatory efficacy of ferruginol on dextran sulfate sodium (DSS) stimulated ulcerative colitis mice. Methods: Ulcerative colitis was induced in C57BL/6J mice by administering 2％ of DSS through drinking water for 7 d. The mice in the treatment group were treated with DAA+50 mg/kg/day ferruginol orally. In the positive control group, sulfasalazine (50 mg/kg/day) was used alongside with DSS. After induction, the bodyweight, character of stool and feces occult blood were recorded daily, the disease activity index was calculated, and the colon length, colon weight, and spleen weight were recorded. The myeloperoxidase activity was assayed by spectrophotometry. Interleukin (IL)-6, IL-1β, and tumor necrosis factor-α were determined by ELISA method, and nuclear factor-κB, cyclooxygenase-2, matrix metalloproteinases-9, and inducible nitric oxide synthase by Western blotting assays. Results: Ferruginol significantly increased the bodyweight, colon weight, colon length, and decreased disease activity index and spleen weight. It exhibited anti-inflammatory activity against DSS induced ulcerative colitis in mice by reducing the activities of myeloperoxidase, tumor necrosis factor-α, nuclear factor-κB, IL-1β, cyclooxygenase-2, matrix metalloproteinases-9, IL-6, and inducible nitric oxide synthase. Conclusions: Ferruginol could be used to treat ulcerative colitis by attenuating the inflammation in colon cells and maintaining colonic mucosal barrier integrity.

Research progress on the role of SIRT in intestinal barrier / 基础医学与临床

SIRT is a family of highly conserved nicotine adenine dinucleotide ( NAD+)-dependent protein deacetylase which regulates several processes including cell gene stability , metabolism , aging and apoptosis . Studies have shown that SIRT has protective effects on intestinal barrier , which influences the structure and function of intestinal barrier by controlling the release of inflammatory cytokines , regulating the expression of tight junction protein in intestinal epithelial , and changing the number of Paneth and goblet cells in the intestine .

Diagnostic value of thoracoscopy routine pleural biopsy combined with frozen biopsy for pleural effusion / 中国内镜杂志

Objective To investigate the diagnostic value and safety of thoracoscopy routine pleural biopsy combined with frozen biopsy for pleural effusion. Methods A retrospective analysis was made on the pathological diagnosis rate of pleural effusion. Results 120 cases in thoracoscopy, 103 cases were confirmed with routine biopsy specimens (85.8%), 16 cases found in the lesions with conventional clamp not satisfactory tissue specimens, combined with frozen cut obtained satisfactory specimens, the diagnostic accuracy rate of 16 cases of cryobiopsy was 100.0%, and the total diagnostic accuracy rate of medical thoracoscopy combined with pleural biopsy and cryobiopsy was 95.0%. There was significant difference between conventional biopsy and cryobiopsy (P < 0.05). Conclusion Medical thoracoscopy combined with pleural biopsy and cryobiopsy can achieve a higher rate of pathological diagnosis, and the complications are mild, so it is worthy of clinical promoting.

Combined detection of pleural biopsy under medical thoracoscopy and serum tumor markers in diagnosis of pleural effusion with unknown reason / 中国内镜杂志

Objective To discuss combined detection of pleural biopsy under medical thoracoscopy and pulmonary serum tumor markers in diagnosis of pleural effusion with unknown reason.Methods 76 patients with pleural effusion caused by unknown reason from January 2014 to March 2016 were retrospectively analyzed. Pleural biopsy was conducted under medical thoracoscopy and sent for pathological examination, and 10 ml venous blood was collected from these patients upon admission for testing serum tumor markers (CEA, SCC-AG, ProGRP and CYFRA21-1).Results Among the 76 patients, there were 32 cases with benign lesions (14 with pulmonary tuberculosis, 9 with inlfammatory lesions, 6 with granulomatous inlfammation, 2 with empyema and 1 with hamartoma) and 44 cases with malignant lesions (18 with adenocarcinoma, 13 with squamous carcinoma, 6 with small cell lung cancer, 3 with adeno-squamous carcinoma, 2 with mesothelioma, 1 with large cell carcinoma and 1 with thymoma). The detection of serum tumor markers showed statistically significant differences in the levels of CEA, SCC-AG, ProGRP and CYFRA21-1 in serum between the malignant pleural effusion group and benign pleural effusion group (P = 0.021,P = 0.006,P = 0.003 andP = 0.010). The levels of various serum tumor markers in the malignant pleural effusion group were obviously higher than those in the benign pleural effusion group. According to the pathological results, patients with pleural effusions not caused by lung cancer (2 with mesothelioma and 1 with thymoma) were eliminated from 44 patients with malignant pleural effusions. The rest 41 patients with pleural effusions caused by lung cancer were divided into non-small cell lung cancer and small cell lung cancer according to the pathological types. The results showed that there were statistically signiifcant differences in the levels of CEA, ProGRP and CYFRA21-1 between non-small cell lung cancer and small cell lung cancer (P = 0.036,P = 0.005 andP = 0.008), while there was no statistically signiifcant difference in the level of SCC-AG (P = 0.811).Conclusions Due to high detection rate and high accuracy in detecting pleural effusions caused by unknown reason, medical thoracoscopy is of great signiifcance, especially for the diagnosis of malignant pleural effusions of pleural metastases. However, serum indicators may provide important reference values for us before the pathological results are available. Thus, it is an important means of diagnosing malignant pleural effusions caused by lung cancer and should be promoted in clinic.

Effects of serum containing Chinese medicine Sanpi Pingwei () formula on proliferation and apoptosis of human SGC-7901 cells / 中国结合医学杂志

<p><b>OBJECTIVE</b>To investigate the effects of serum containing Chinese medicine (CM) Sanpi Pingwei (, SPPW) formula on the proliferation and apoptosis of human SGC-7901 cells and the possible mechanism.</p><p><b>METHODS</b>Serum containing CM SPPW formula (SPPW serum) was prepared by a serum pharmacology method. Human SGC-7901 cells were incubated with SPPW serum at three different concentrations and with the anticancer drug 5-fluorouracil (5-FU), respectively. Cell proliferation was assessed by MTT assay, and cell apoptosis was detected by flow cytometry assay. Real-time quantitative polymerase chain reaction (RT-PCR) and Western blot assay were employed to confirm the expressions of Bcl-2, Bax and p53 in SGC-7901 cells at mRNA and protein levels, respectively.</p><p><b>RESULTS</b>SPPW serum suppressed the proliferation of SGC-7901 cells in a time- and dose-dependent manner. The colony forming rate of negative control was 48.2%, while those in the three SPPW serum groups and the 5-FU group decreased significantly (P<0.01). The number of colony forming units in the SPPW high dosage group was significantly smaller than that in the 5-FU group (P<0.01). MTT assay showed that SPPW serum restrained the proliferation of SGC-7901 cells, and the inhibition rate increased significantly in a dose-dependent manner. Annexin V/PI Assay suggested that SPPW serum induced the apoptosis of SGC-7901 cells significantly. RT-PCR and western blot assay indicated that SPPW serum upregulated the protein and mRNA expression levels of Bax and p53 in SGC-7901 cells, but downregulated the protein and mRNA expressions of Bcl-2.</p><p><b>CONCLUSIONS</b>SPPW formula inhibits the proliferation of SGC-7901 cells in vitro and induces the cell apoptosis. It plays an anticancer role by regulating the expressions of Bax, p53 and Bcl-2 in SGC-7901 cells.</p>

Effect of SPPW on the invasive and metastatic capacities of human gastric cancer cells / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To clarify the action and possible mechanisms of SPPW, a Chinese herbal preparation consisting of Herba Scutellariae Barbatae, Radix Astragalus, Radix Glycyrrhizae, etc., in suppressing the metastasis of human gastric cancer, by way of observing its effect on the invasive and metastatic capacities of gastric cancer cells.</p><p><b>METHODS</b>In vitro serial sub-cultured human gastric cancer cell line SGC-7901 at the logarithmic growth phase were randomly divided into 5 groups, i.e. the negative control group, the 4 treatment groups intervened respectively with SPPW at three different doses (high, middle, and low), and 5-FU. The adhesion capacities of gastric cancer cells to matrigel were detected by MTT assay 48 h after intervention. The invasive and migratory capacities of gastric cancer cells were determined by Transwell assay. The mRNA and protein expressions of metalloproteinase-9 (MMP-9) and vascular endothelial growth factor (VEGF) in gastric cancer cells were detected by Western blot and Real-time polymerase chain reaction (RT-PCR) respectively.</p><p><b>RESULTS</b>Compared with the negative control group, the adhesive, invasive and migratory capacities of gastric cancer cells were all significantly inhibited in the four treatment groups (P<0.05, P<0.01). In addition, the protein and mRNA expressions of MMP-9 and VEGF were down-regulated (P<0.01). Significant dose-dependent relation existed in the three SPPW treatment groups (P<0.01). Compared with the 5-FU treatment group, the high dose SPPW treatment group showed significant difference in inhibiting the adhesive and metastatic capacities of gastric cancer cells, lowering VEGF protein expression, and mRNA expressions of MMP-9 and VEGF (P<0.01).</p><p><b>CONCLUSIONS</b>SPPW could lower the adhesion of gastric cancer cells to matrigel, and lower the invasion and migration of gastric cancer cells. Meanwhile, it could down-regulate the mRNA and protein expressions of MMP-9 and VEGF, which may possibly be one of its mechanisms for influencing the invasion and metastasis of gastric cancer cells.</p>

Applying the Bacterial Diversity Investigation on the Teaching Class / 微生物学通报

The aims of microbiology experiment teaching are not only to cultivate the students’ capacity of basic operation,but also to expanse their knowledge scope.We applied the bacterial diversity on the teach-ing class to make the students understand the progress of microorganism genomics research.It is helpful to cultivate the students’ innovative spirit and ability.Easy to work,clear result and low cost facilitated the spread of this experiment in the university.