Agkistrodon halys venom antitumor component-I inhibits vasculogenic mimicry in triple-negative breast cancer cells in vitro by down-regulating MMP2 / 南方医科大学学报

OBJECTIVE@#To investigate the inhibitory effect of agkistrodon halys venom antitumor component-I (AHVAC-I) on vasculogenic mimicry (VM) formation in triple-negative breast cancer MDA-MB-231 cells and explore its possible mechanism.@*METHODS@#CCK8 assay was used to determine the optimal concentration of AHVAC-I for cell treatment based on its halfinhibitory concentration (IC50). MDA-MB-231 cells were treated with different concentrations of AHVAC-I or 5-Fu, and the changes in vasomimetic capacity of the cells were examined using Matrigel assay. The expression levels of matrix metalloproteinase-2 (MMP2) and MMP9 in the treated cells were detected using quantitative PCR and Western blotting.@*RESULTS@#Compared with the control treatment with culture medium, treatment with 5, 10 and 20 μg/mL AHVAC-I significantly reduced vasomimetic ability of MDA-MB-231 cells in a dose-dependent manner (P < 0.01). MMP2 supplementation obviously restored the vasomimetic ability of the cells inhibited by AHVAC-I.@*CONCLUSION@#AHVAC-I inhibits VM formation in triplenegative breast cancer cells in vitro by down-regulating MMP2 production.

Chrysin inhibited epithelial-mesenchymal transition of type Ⅱ alveolar epithelial cell by regulating NF-κB/Twist 1 signaling pathway / 中国中药杂志

This study aimed to assess whether chrysin(ChR) can inhibit epithelial-mesenchymal transition(EMT) of type Ⅱ alveolar epithelial cell and produce anti-pulmonary fibrosis effect by regulating the NF-κB/Twist 1 signaling pathway. Sixty rats were randomly divided into the control group, the bleomycin(BLC) group, BLC+ChR(50 mg·kg~(-1)) group and BLC+ChR(100 mg·kg~(-1)) group, with 15 rats in each group. The pulmonary fibrosis model was induced by intratracheal injection of BLC(7 500 U·kg~(-1)). Rats were orally administered with different doses of ChR after BLC injection for 28 days. The cells were divided into control group, TGF-β1 group(5 ng·mL~(-1)), and TGF-β1+ChR(1, 10, 100 μmol·L~(-1)) groups. The type Ⅱ alveolar epithelial cells were treated with TGF-β1 for 24 h, and then treated with TGF-β1 for 48 h in the presence or absence of different doses of ChR(1, 10 and 100 μmol·L~(-1)). The morphological changes and collagen deposition in lung tissues were analyzed by HE staining, Masson staining and immunohistochemistry. The mRNA and protein expression levels of collagen Ⅰ, E-cadherin, zonula occludens-1(ZO-1), vimentin, alpha smooth muscle actin(α-SMA), inhibitor of nuclear factor kappa B alpha(IκBα), nuclear factor-kappa B p65(NF-κB p65), phospho-NF-κB p65(p-p65) and Twist 1 in lung tissues and cells were detected by qPCR and Western blot, respectively. The animal experiment results showed that as compared with the BLC group, after administration of ChR for 28 days, bleomycin-induced pulmonary fibrosis in rats was significantly relieved, collagen Ⅰ expression in lung tissues was significantly reduced(P<0.05 or P<0.01), and EMT of alveolar epithelial cells was obviously inhibited [the expression levels of E-cadherin and ZO-1 were increased and the expression levels of vimentin and α-SMA were decreased(P<0.05 or P<0.01)], concomitantly with significantly reduced IκBα and p65 phosphorylation level in cytoplasm and decreased NF-κB p65 and Twist 1 expression in nucleus(P<0.05 or P<0.01). The cell experiment results showed that different doses of ChR(1, 10 and 100 μmol·L~(-1)) significantly reduced TGF-β1-induced collagen Ⅰ expression(P<0.05 or P<0.01), significantly inhibited EMT of type Ⅱ alveolar epithelial cells[the expression levels of E-cadherin and ZO-1 were increased and the expression levels of vimentin and α-SMA were decreased(P<0.05 or P<0.01)], and inhibited IκBα and p65 phosphorylation in cytoplasm and down-regulated NF-κB p65 and Twist 1 expression in nucleus induced by TGF-β1(P<0.05 or P<0.01). The results suggest that ChR can reverse EMT of type Ⅱ alveolar epithelial cell and alleviate pulmonary fibrosis in rats, and its mechanism may be associated with reducing IκBα phosphorylation and inhibiting NF-κB p65 phosphorylation and nuclear transfer, thus down-regulating Twist 1 expression.

A case-control study on prognosis between EGFR gene mutant-and wild-type non-small cell lung cancer with brain metastasis / 中国肿瘤生物治疗杂志

@#[摘 要] 目的：探讨表皮生长因子受体（epidermal growth factor receptor，EGFR）基因突变与非小细胞肺癌（non-small cell lung cancer，NSCLC）伴脑转移患者预后的相关性，为改善NSCLC合并脑转移患者预后、指导个体化治疗提供临床依据。方法：回顾性分析福建省立医院2013年1月1日至2018年9月30日期间收治的88例NSCLC合并脑转移患者的临床资料，随访取得患者的死亡时间，随访截止日期为2019年10月31日。收集和分析的临床资料包括性别、年龄、吸烟史、病理类型、基因检测、治疗情况、无进展生存期（progression free survival，PFS）、总生存期（overall survival，OS）等。运用生存分析（Kaplan-Meier生存时间曲线）评价EGFR突变型患者的预后，以单因素分析（log-rank检验）预测影响EGFR-TKI治疗效果的因素。结果：88例NSCLC脑转移患者有57例为EGFR突变型，其中位PFS（MPFS）为13.0个月（95%CI：11.951~14.049），明显高于EGFR野生型患者（P=0.003），患者中位生存期（median survival time，MST）为29.0个月（95%CI：20.531~37.468），明显高于EGFR野生型（P=0.001）。EGFR突变型中，Exon19-del突变组患者较Exon21 L858R突变组患者OS有延长趋势（P=0.05），Exon19-del+Exon20T790M突变组患者OS较Exon21 L858R突变组有延长趋势（P=0.077）。结论：EGFR突变组较野生型组NSCLC脑转移患者预后相对好些，且携带19外显子单一缺失突变的患者预后最好。

Effect of small dose capsaicin for treatment of pulmonary fibrosis in mice and its mechanism / 中国应用生理学杂志

To observe whether the mechanism of small dose capsaicin (Cap) against pulmonary fibrosis in mouse is mediated by agitating transient receptor potential vanilloid 1 (TRPV1). Methods: A total of 60 BALB/c mice were randomly divided into control (CON) group, bleomycin (BLM)group, Cap (0.5, 1,2 mg/kg) groups and Cap (2 mg/kg) plus SB-452533 (2.5 mg/kg) group. C57BL/6 mice were intratracheally injected with 3.5 mg/kg BLM to induce pulmonary fibrosis model. Animals for drugs treatment received daily drug via subcutaneous injection for 21 days. The morphological changes and collagen deposition in lung tissues were analysed by HE staining, Masson staining and immunohistochemistry. The concentration of calcitonin gene-related peptide (CGRP) in plasma was determined by ELISA. The mRNA and (or) proteins levels of α-CGRP, β-CGRP, collagen I, collagen III, E-Cadherin, zonula occludens-1 (ZO-1), vimentin, alpha smooth muscle actin (α-SMA), TRPV1, p-ERK1/2 and eukaryotic initiation factor 3a (eIF3a) were detected by qPCR and (or) Western blot. Compared with the BLM group, small dose Cap significantly reduced bleomycin-induced pulmonary fibrosis in mice and obviously reversed alveolar epithelial cells epithelial-mesenchymal transition (EMT) (the expression of E-cadherin and ZO-1 were increased(P＜0.05 or P＜0.01)and the expression of α-SMA and Vimentin were decreased (P＜0.05 or P＜0.01) after drugs treatment for 21 day, concomitantly with the increase the expressions of TRPV1 and CGRP (P＜0.05 or P＜0.01), and inhibiting ERK1/2 phosphorylation and eIF3a expression (P＜0.05 or P＜0.01). These effects of small dose Cap were abolished in the presence of TRPV1 receptor antagonist SB-452533. The results suggest that small dose Cap can reverse alveolar epithelial cells EMT and alleviate bleomycin-induced pulmonary fibrosis in mice by inhibiting ERK1/2/eIF3asignaling pathway, which is related to agitating TRPV1 receptor and releasing of CGRP.

Study on effects of total saponins from Lilii Bulbus on proliferation, apoptosis, invasion and metastasis of lung cancer cells and its preliminary mechanism / 中国中药杂志

The potential role of total saponins extracted from Lilium lancifolium bulbs (TSLL) on the proliferation, apoptosis, migration and invasion of human lung cancer A549 cells and its possible mechanism were discussed. Effect of TSLL on proliferation of A549 cells were detected by CCK-8, clone formation assay and EdU staining. Effect of TSLL on apoptosis morphology of A549 cells was observed by fluorescence microscope using Annexin V/PI double staining and Hoechst 33342 staining. Effect of TSLL on cell migration and invasion was detected by Transwell migration test and Transwell invasion test, respectively. Western blot was used to detect TSLL on the expression change of intracellular associated proteins. Results showed that TSLL intervention in A549 cells within 24, 48 or 72 h significantly inhibited cell growth, and its IC₅₀values were about 229, 173 and 71 mg·L⁻¹, respectively. TSLL significantly reduced the clone formation rate of A549 cells and decreased the DNA synthesis rate of A549 cells in a concentration dependent manner. TSLL induced A549 cells apoptosis and reduced the migratory behavior of A549 cells. TSLL decreased invasion of A549 cells to the artificial basement membrane. The expression level of intracellular PCNA and the ratio of Bcl-2/Bax protein were down-regulated and procaspase 3 was activated. In addition, TSLL had no obvious effect on epithelial mesenchymal transition (EMT) related marker proteins E-cadherin and vimentin expression. The above results indicated that TSLL possess inhibitory effects against proliferation, migration and invasion of lung cancer A549 cells and apoptosis-induced effect. The anti-proliferation effect of TSLL is very likely by inhibiting intracellular DNA synthesis through reducing the expression of PCNA in lung cancer cells. And the apoptosis induction of TSLL on lung cancer cells is associated with the regulation of Bcl-2 and Bax proteins expression. Nevertheless, there is no incontestable correlation between anti-invasion and metastasis effects of TSLL and EMT in lung cancer cells.

Advances in study of pharmacological effects of ginsenoside Rg1 in hepatic diseases / 药学学报

Ginsenoside Rg1 is one of the main active components of ginseng with various pharmacological activities including anti-inflammatory, anti-oxidation, anti-aging, anti-tumor and anti-apoptosis. Ginsenoside Rg1 plays a protective role in multiple tissues and organs, which shows the multiple targeting properties of the pharmacological effects. Recently, a number of studies have demonstrated that ginsenoside Rg1 has a protective role in the liver due to its multiple pharmacological effects. In chemical liver injury models, or in other liver injury models, ginsenoside Rg1 can alleviate liver necrosis induced by oxidative stress and inflam-mation. This article provides a review of the recent studies on the efficacy of ginsenoside Rg1 in the treatment of various liver damage and the molecular mechanism.

Mechanism of ferroptosis and its role in neurological diseases / 中国药理学通报

Ferroptosis is distinct from apoptosis,autophagy,necrosis,cornification and other cell deaths from morphological,biochemical as well as genetic aspects.Ferroptosis plays a critical role in neurological diseases and cancers.Neurological diseases,such as Alzheimer's disease,Parkinson's disease,Huntington's disease,stroke,periventricular leukomalacia and so on,are characterized by multiple etiologies and mechanisms,and are potentially correlated with ferroptosis.Based on the recent researches on ferroptosis and neurological diseases,this review investigates ferroptosis and its role in neurological diseases.

Expression and clinical significance of HMGA1 and CXCR4 in invasive ductal carcinoma of breast / 临床与实验病理学杂志

Purpose To investigate the expression of high mobility group protein Al (HMGA1) and C-X-C chemokine receptor 4 (CXCR4) in breast invasive ductal carcinoma and its clinical significance. Methods Immunohistochemical method was used to detect the expression of HMGA1 and CXCR4 in 105 cases of breast invasive ductal carcinoma and 80 cases of breast adenosis. The correlation between HMGA1 and CXCR4 expression and clinicopathological features was analyzed. Results The positive rate of HMGA1 and CXCR4 in breast invasive ductal carcinoma was significantly higher than that of breast adenosis(77.14％ vs 26.25％, 73.33％ vs 23.75％ ), the difference was statistically significant (P＜ 0.001). There was no significant correlation between HMGA1 and CXCR4 expression in breast cancer tissues (r = 0.104, P =0.289), suggesting that the expression of them were independent of each other. The combined detection of HMGA1 and CXCR4 could improve the sensitivity of diagnosis of (either positive) and specificity of(both positive). The positive rate of CXCR4 in PR positive breast cancer (87.5％ ) was higher than that in PR negative(60.0％ ), the difference was statistically significant (P =0.008) Conclusion HMGA1 is highly expressed in breast invasive ductal carcinoma, and CXCR4 expression is mainly low in breast invasive ductal carcinoma. HMGA1 and CXCR4 have higher sensitivity, and the combined detection of them can significantly improve the sensitivity and specificity of breast cancer diagnosis. The high expression of HMGA1 and CXCR4 in breast cancer has a certain clinical significance for the diagnosis and prognosis of breast cancer, which is expected to provide a new theoretical basis for the diagnosis and treatment of clinical breast cancer.

Advances in studies on steroidal saponins and their pharmacological activities in genus Lilium / 中国中药杂志

Genus Lilium plants contain a variety of steroidal saponins, so far at least 82 steroidal saponins have been found in the bulbs of Lilium species, including 13 spirostanol saponins (1-13), 39 isospirostanol saponins (14-52), 7 pseudospirostanol saponins (53-59), and 23 furostanol saponins (60-82). Studies have showed that these steroidal saponins exhibit a wide range of pharmacological activities, including antitumor, antibacterial, antiinflammatory, antioxidant, antidepressant, hepatoprotective, hypoglycemic, sedative-hypnotic effect, and inhibition of cAMP phosphodiesterase and Na⁺-K⁺ ATP, et al. This paper has classified and summarized the 82 steroidal saponins isolated and identified from the bulbs of Lilium species and their correlative biological activities. Also, their structural characteristics and structure-activities relationship have been discussed, which could provide references for further research and application development of Lilium plants.

Three-dimensional structure and cytokine distribution of platelet-rich fibrin

OBJECTIVES: Previous reports have revealed that several cytokines (including platelet-derived growth factor-BB, transforming growth factors-β1 and insulin-like growth factor-1) can enhance the rate of bone formation and synthesis of extracellular matrix in orthopaedics or periodontology. This study aimed to determine the concentration of cytokines within platelet-rich fibrin microstructures and investigate whether there are differences in the different portions of platelet-rich fibrin, which has implications for proper clinical use of platelet-rich fibrin gel. METHODS: Whole blood was obtained from six New Zealand rabbits (male, 7 to 39 weeks old, weight 2.7-4 kg); it was then centrifuged for preparation of platelet-rich fibrin gels and harvest of plasma. The resultant platelet-rich fibrin gels were used for cytokine determination, histological analyses and scanning electron microscopy. All plasmas obtained were subject to the same cytokine determination assays for the purpose of comparison. RESULTS: Cytokines platelet-derived growth factor-BB and transforming growth factor-β1 formed concentration gradients from high at the red blood cell end of the platelet-rich fibrin gel (p=1.88×10-5) to low at the plasma end (p=0.19). Insulin-like growth factor-1 concentrations were similar at the red blood cell and plasma ends. The porosities of the platelet-rich fibrin samples taken in sequence from the red blood cell end to the plasma end were 6.5% ± 4.9%, 24.8% ± 7.5%, 30.3% ± 8.5%, 41.4% ± 12.3%, and 40.3% ± 11.7%, respectively, showing a gradual decrease in the compactness of the platelet-rich fibrin network. CONCLUSION: Cytokine concentrations are positively associated with platelet-rich fibrin microstructure and portion in a rabbit model. As platelet-rich fibrin is the main entity currently used in regenerative medicine, assessing cytokine concentration and the most valuable portion of PRF gels is essential and recommended to all physicians.

Advance in components with antitumor effect of Panax ginseng and their mechanisms / 中草药

Panax ginseng C. A. Mey is one of precious traditional Chinese herbal medicine for two thousand years history, due to its various pharmacological effects and wide utilization in the clinical treatment of tumors and other diseases. Presently tumor has become an important factor threatening human health that the antitumor effect of P. ginseng is attracted great attention. In this paper, the effective components of antitumor action by P. ginseng and its molecular mechanism and structure-activity relationship are summarized. Studies have shown that the main effective components of P. ginseng for antitumor effect are ginsenosides and its metabolic products of intestinal bacteria, ginseng polysaccharides, and ginseng polyacetylenes. The functional mechanism of which are clear relatively now and their main mechanisms including induction of cycle arrest, apoptosis and differentiation of tumor cells, enhancement of immunity to tumor cells, inhibition of tumor cell proliferation, invasion and metastasis, etc. And the molecular mechanism is involved in the regulation of many related genes, proteins, proteases, immune cells, cytokines, and signaling pathways, etc. In addition, the active ingredients of P. ginseng exert antitumor effect in a dose-dependent manner, and the different chemical structures of which lead to different antitumor activity. In conclusion, P. ginseng is abundant with antitumor active ingredients, which is expected to provide safe and effective natural medicine and its preparation for clinical treatment of various tumors in the future.

Advance in the treatment of glioma by neural stem cells / 药学学报

Neural stem cells (NSCs) posse the specialty of tumor tropism and be able to migrate specifically to tumor cells. NSCs are also cross the blood brain barrier. NSCs keep in touch with tumor cells preferentially under the tumor microenvironment, and surround the target cells. Based on these characteristics, NSCs can be used as a carrier for therapeutic virus, enzymes/prodrugs, genes or suicide genes, etc. which are selectively delivered to the glioma cells. NSCs may be modified by a variety of different genes to establish a reliable, safe and effective therapy for glioma.

Protection and Mechanism of Qingyuan Shenghua Decoction on Multiple Organs of Sepsis Patients after Bone Trauma / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To observe the protection of Qingyuan Shenghua Decoction (QSD) on multiple organs of sepsis patients after bone trauma, and to preliminarily explore its mechanism.</p><p><b>METHODS</b>Totally 60 sepsis patients after bone trauma were randomly assigned to the treatment group and the control group according to random digit table, 30 in each group. All patients received routine Western medical treatment. Patients in the treatment group additionally took QSD or were nasally fed with QSD, one dose per day for 1 week. Changes of WBC, oxygenation index (PaO2/FiO2), serum creatinine (SCr), total bilirubin (TBIL), aspartate aminotransferase (AST), fibrinogen (FIB), D-dimer (DD), activated partial thromboplastin time (APTT), pro-calcitonin (PCT), C-reactive protein (CRP), heart rate (HR), mean arterial pressure (MAP), intra-abdominal pressure, scores for Acute Physiology and Chronic Health Evaluation II (APACHE II), sequential organ failure assessment (SOFA) scores were observed before treatment and on day 1, 3 and 7 after treatment.</p><p><b>RESULTS</b>Compared with the control group at the same time point, MAP increased at post-treatment day 1 and 3; CRP, APTT, HR, SCr, TBIL, AST, intra-abdominal pressure at post-treatment day 3 obviously decreased in the treatment group (P < 0.05, P < 0.01). WBC, SOFA scores, PCT, CRP, APACHE II, APTT, D-D, HR, SCr, TBIL, AST and intra-abdominal pressure significantly decreased; FIB, MAP and PaO2/FiO2 obviously increased at post-treatment day 7 (P < 0.05, P < 0.01).</p><p><b>CONCLUSION</b>QSD had good protective effect on multiple organ function in sepsis patients after bone trauma, and its mechanism might be related with effectively clearing endotoxin, alleviating inflammatory reactions, and fighting against coagulation dysfunction.</p>

Expressions of fractalkine and CD11c on common carotid artery atherosclerotic plaques from apoE(-/-) mice / 中国医学科学院学报

<p><b>OBJECTIVE</b>To explore the association of fractalkine (FKN) and CD11c expressions oncommon carotid artery atherosclerotic plaques from apoE(-/-) mice with the severity of atherosclerotic lesions.</p><p><b>METHODS</b>Totally 24 apoE(-/-) mice were divided into two groups and fed on a high-fat diet or a normal diet for 12 weeks. Then the blood lipids as well as the plaque area and vascular stenosis rate of the common carotid artery were measured to evaluate the severity of atherosclerotic lesions of the animals. Moreover, immunohistochemical staining was performed to examine the levels of FKN and CD11c expression.</p><p><b>RESULTS</b>The plaque areas and vascular stenosis rates of the common carotid artery in the experimental group were remarkably larger than those in control group (about 4-fold and 2-fold, respectively). The level of FKN expression in the experimental group was 2 times of that in the control group (P<0.05), and the number of CD11c (+) cells in the plaques in the experimental group was about 4 times of than in the control group (P<0.05).</p><p><b>CONCLUSION</b>The expressions of chemokine and FKN remarkably increase in apoE (-/-) atherosclerotic plaques, suggesting that chemokine and FKN may paly important roles in the development of atherosclerosis.</p>

Differential gene expression in pepper (Capsicum annuum) exposed to UV-B.

In the present paper, complementary DNA-amplified fragment length polymorphism (cDNA-AFLP) was used to examine and identify differentially expressed genes in Capsicum annuum exposed to UV-B irradiation. Around 4000 transcript derived fragments (TDFs) were visualized and in total 183 TDFs were isolated, sequenced and analyzed by Blast 2 go. Among these TDFs, 84 of them showed homology to known genes. There were 43 TDFs showing up-regulated expression, 24 TDFs showing down-regulated expression and 27 TDFs showing both up-regulated and down-regulated expression, respectively. Some of these TDFs were found to be in response/related to UV-B stress, including carbonic anhydrase, calcium-dependent protein, thionin-like protein, bzip protein and so on. In particular, chlorophyll a/b binding protein (Capcab) responding to UV-B stress was cloned. It was concluded that Capcab could play a protective role in plant anti-UV-B and maintaining photosynthetic rate under UV-B stress.

Inhibitory effect of ginseng saponin IH901 on proliferation and metastasis of ECV304 cell line and its molecular mechanism / 药学学报

This study aims to investigate the inhibitory effect on proliferation and metastasis of 20-O-(beta-D-glucopyranosyl)-20(S)-protopanaxadiol (IH901) on ECV304 cell line. MTT assay was used to examine the effect of cell proliferation inhibition and the adhesive ability of ECV304 cells to artificial basement membrane. Morphology of cell apoptosis was observed with phase contrast microscope. Apoptosis rate and cell cycle were detected by flow cytometry (FCM). Cell migration was measured by wound healing assay. ELISA kit was used to detect VEGF and bFGF. Caspases were detected by Western blotting. Results indicated that ginseng saponin IH901 can downregulate the expression of growth promoting protein VEGF and bFGF, and upregulate pro apoptosis protein cleaved caspase-9 and cleaved caspase-3. The increase in the apoptotic sub-G1 fraction is in a dose-dependent manner, and cell cycle arrests in the G0/G1 phase was detected by FCM. Morphological examination of IH901-treated samples showed cells with chromatin condensation, cell shrinkage, and all typical characteristics of apoptotic cells. Therefore, IH901 dramatically suppresses cell proliferation and adhesion and migration of ECV304 cell line.

The pathological observation of acute intoxication by Alangium Chinese in mice / 法医学杂志

OBJECTIVE@#To investigate the pathological change of mice organ intoxicated by Alangium Chinese and its poisoning mechanism.@*METHODS@#Mice were intoxicated by gavage with extract of Alangium Chinese. Then the histopathologic examination was made for evaluating the pathological changes in the organs of the poisoned mice by HE staining.@*RESULTS@#The main pathological changes included alveolar hemorrhage, pulmonary interstitial hemorrhage, sinus hepaticus expansion and congestion, hepatocyte edema, subarachnoid hemorrhage, congestion and hemorrhage of other organs.@*CONCLUSION@#The main target organs or tissue of Alangium Chinese are the lungs, liver and vascular smooth muscle. There is correlation between the toxic effect and the dosage.