Design and semisynthesis of oleanolic acid derivatives as VEGF inhibitors: Inhibition of VEGF-induced proliferation, angiogenesis, and VEGFR2 activation in HUVECs / 中国天然药物

Angiogenesis inhibitors targeting the VEGF signaling pathway are developed into drugs for the treatment of vaious diseases, such as cancer, rheumatoid arthritis, and age-related macular degeneration. Recent studies have revealed that oleanolic acid (OA), a natural pentacyclic triterpenoid, inhibited the VEGF/VEGFR2 signaling pathway and angiogenesis in HUVECs, which may represent an attractive VEGF inhibitor. In this paper, rational structural modification towards OA was performed in order to improve its inhibitory effects aganist VEGF and anti-angiogenesis potential. As a result, a series of novel OA derivatives, possessing α,β-unsaturated ketone system in ring A and amide functional group at C-28, were prepared and evaluated for cytotoxicity and their ability to inhibit VEGF-induced abnormal proliferation of HUVECs. The results showed that two promising derivatives, OA-1 and OA-16, exhibited no in vitro cytotoxicity against HUVECs but showed more potent inhibitory activity against VEGF-induced proliferation and angiogenesis in HUVECs, compared with OA. The results of Western blot indicated that OA-1 and OA-16 inhibited VEGF-induced VEGFR2 activation. Furthermore, small interfering RNA experiments were performed to confirm that both compounds inhibited VEGF-induced angiogenesis via VEGFR2. Thus, the present study resulted in the discovery of new promising OA-inspired VEGF inhibitors, which can serve as potential lead compounds for the treatment of angiogenesis-related diseases.

Investigating Clinical Efficacy and Mechanism of Qingfei Paidu Decoction for Treatment of COVID-19 Based on Integrative Pharmacology / 中国实验方剂学杂志

Objective:Potential targets and pathways of Qingfei Paidu decoction（QFPD）for treating coronavirus disease-2019（COVID-19） were analyzed based on the integrative pharmacology，the efficacy and material basis was predicted.This study provide a reference for the development and clinical application of QFPD. Method:Based on the integrative pharmacology of traditional Chinese medicine（TCMIP V2.0），the key targets and pathways of the intervention of QFPD on COVID-19 were enriched，the interaction network of "formula-herb-disease-targets-pathways" was constructed to explored the molecular mechanism of QFPD for the treatment of COVID-19. Result:The research results show that key-targets such as cell tumor antigen p53（tp53），protein kinase B1（Akt1），Nuclear factor nuclear transcription factor-κB（NF-κB）p105 subunit（NFKB1），nuclear factor p65 subunit（RELA），human NF-κB inhibited protein α（NFKBIA），ect.Closely associated with lung damage.The pathways such as interleukin signaling，adrenoceptors，7 members of the family of c-type lectin domains A（CLEC7A）/inflammasome pathway，phosphoinositide-3-kinase（PI3K）/protein kinase B（Akt）inflammatory signaling pathway，tp53 regulates transcription of DNA repair ect. may be the key pathways related with QFPD's effect on the treatment of COVID-19 accompany with lung injury， fever， cough and other symptoms.The results show that QFPD has many clinical effects， such as anti-inflammatory， anti-virus， strengthening immunity， inhibit the development of pulmonary fibrosis， protecting heart and lungs， treating asthma， regulating gastrointestinal tract， etc.In addition， there is a good synergism between the original prescription and the combined prescription， and each original prescription has its own emphasiscan prevention and treatment of COVID-19. Conclusion:QFPD plays a role in balancing immunity and eliminating inflammation，and it can treat COVID-19 by multi-pathway，multi-channel，multi-target and multi-link.This study also provides a new idea for the research of prevention and treatment of modern infectious diseases by use the traditional Chinese medicine.

Exploration of “principle-recipe-composition-target-activity” association of Bupleuri Radix and Scutellariae Radix drug pair for diabetes treatment based on network pharmacology / 药学学报

By using the integrated pharmacology platform and the big data of traditional Chinese medicine combined with the pharmacology thinking of "principle-recipe-composition-target-pathway-activity" in this study, we predicted the material basis and mechanisms of Bupleuri Radix and Scutellariae Radix drug pair for the treatment of diabetes. Fifty-nine active components were predicted, which included saponins, flavones, essential oil, fatty acids and so on. They acted on twenty-two direct targets and twenty-six main pathways respectively.The known disease targets of diabetes include arginine vasopressin receptor gene (AVP), retinoblastoma (RB1), receptor active modified protein (RAMP), platelet growth factor receptor (PDGFR), insulin receptor (INSR), α-glucosidase (GAA), etc. The pathways with diabetes effect involves endocrine system, circulatory system, digestive system, thyroid hormone signaling pathway, ErbB signaling pathway, PI3K-Akt signaling pathway, lipid metabolism and other related biological processes and metabolic pathways. The results of virtual screening in molecular docking technology indicate that flavonoids from Bupleuri Radix and Scutellariae Radix drug pair can easily form good docking mode and high affinity with peroxisome proliferators activated receptor γ (PPAR-γ) and glycogen synthase kinase-3β (GSK-3β), showing antidiabetic activity. The study provides information for the treatment of diabetes by Bupleuri Radix and Scutellariae Radix drug pair, and a new thought for the study of drug pair and complex prescription.

In vitro antibacteriaI effect of benzalkonium chIoride on five common oral pathogens / 中国组织工程研究

BACKGROUND: Benzalkonium chloride has been used in dental restorative materials to enhance the long-lasting antibacterial properties of materials. OBJECTIVE: To evaluate the antibacterial activity of benzalkonium chloride on oral common pathogenic bacteria in vitro. METHODS: The agar diffusion method was used to determine the inhibitory effects of antibacterial agents, 0.1% benzalkonium chloride, 3% H2O2and 5.25% sodium hypochlorite, on five kind of oral pathogens, Porphyromonas gingivalis (P.g), Prevotella intermedia (P.i), Actinobacillus actionmycemcomitans (A.a), Streptococcus mutans (S.m) and Enterococcus faecalis (E.f). The tube dilution method was used to detect the minimal inhibitory concentration of benzalkonium chloride against the five bacteria mentioned above. RESULTS AND CONCLUSION: The antibacterial effect of 0.1% benzalkonium chloride on P.g was not significantly different from that of 3% hydrogen peroxide (P＞0.05), while 0.1% benzalkonium chloride showed better effect on P.i than 3% hydrogen peroxide (P＜0.05). On P.g and P.i, the antibacterial effect of 0.1% benzalkonium chloride was worse than that of 5.25% sodium hypochloritethe ( P＜0.05). The antibacterial effect of 0.1% benzalkonium chloride on A.a and S.m was better than that of 3% hydrogen peroxide (P＜0.05), and similar to that of 5.25% sodium hypochlorite (P＞0.05). The antibacterial effect of 0.1% benzalkonium chloride on E.f was better than that of 3% hydrogen peroxide (P ＜ 0.05), but worse than that of 5.25% sodium hypochlorite (P ＜ 0.05). The minimal inhibitory concentration of benzalkonium chloride to P.g, P.i, A.a, S.m, E.f was 16, 2, 4, 2, 4 mg/L, respectively. To conclude, 0.1% benzalkonium chloride has strong antibacterial effects on P.g, P.i, A.a, S.m and E.f.

Expression of PD-1/PD-L1 in peripheral blood mononuclear cells in lung cancer patients and its biological significance / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To analyze the expression of co-stimulatory molecules PD-1/PD-L1 in peripheral blood mononuclear cells in lung cancer patients, and to explore its biological significance.</p><p><b>METHODS</b>One hundred and thirty-three lung cancer patients, 25 lung infection patients and 23 healthy donors were enrolled in this study. 100 µl of whole blood from these subjects were collected. Multi-color immunofluorescence staining and flow cytometry were used to detect PD-1/PD-L1 expression. The results were statistically analyzed.</p><p><b>RESULTS</b>The expression level of CD3⁺CD8⁺ T cells in the lung cancer patients was (38.83 ± 1.74)%, significantly lower than that in the control group [(43.25 ± 3.35)%, P < 0.05]. CD8⁺CD28⁺ T cell subset in the peripheral blood of lung cancer patients was (17.73 ± 1.21)% significantly lower than that of the healthy donors [(27.96 ± 2.72)%, P < 0.01]. The CD8⁺CD28⁻ T cell subset was (21.19 ± 1.92)% in the lung cancer patients, significantly higher than that of the healthy control group [(15.18 ± 2.93)%, P < 0.05]. The expression level of PD-1 on the surface of CD8⁺CD28⁺ T cells was (10.67 ± 1.12)% in the group of lung cancer patients, significantly higher than that of the control group [(5.32 ± 1.58)%, P < 0.01]. It was also found that the expression of PD-1 on CD8⁺CD28⁻ T cells was up-regulated in the group of lung cancer patients (7.46 ± 1.25)%, significantly higher than that of the healthy control group [(2.68+1.07)%, P < 0.01]. The expression level of PD-L1 on CD68⁺ cells in the lung cancer patients was (16.03 ± 2.06)%, significantly higher than that of the healthy control group [(9.32 ± 2.00)%, P < 0.05].</p><p><b>CONCLUSION</b>Up-regulation of PD-1/PD-L1 on peripheral blood cells in lung cancer patients negatively regulates the lymphocytes, inhibits the immune response for killing tumor cells, and promotes tumor development and immune escape.</p>

SOX40L: an important inflammatory mediator in adult bronchial asthma

<p><b>INTRODUCTION</b>The role of soluble OX40 ligand (sOX40L) in adult bronchial asthma is unclear. This study aims to determine the serum concentrations of sOX40L in adult patients with bronchial asthma, and discussed its relationship with pulmonary function.</p><p><b>MATERIALS AND METHODS</b>We measured the pulmonary function using the spirometer and detected the serum concentrations of sOX40L by enzyme linked immunosorbent assay (ELISA) in 19 healthy persons in the control group, 58 acute asthmatic adult patients who were grouped according to their disease severity: 18 mild grade, 24 moderate grade, 16 severe grade, and 24 persons in a stable asthmatic group.</p><p><b>RESULTS</b>The serum concentrations of sOX40L in asthmatic adult patients (6.80 ± 4.95 ng/L) were distinctly higher than those in the control group (3.98 ± 2.83 ng/L, P <0.05), and they were negatively correlated with pulmonary function indexes (FEV1%, FVC%, FEV1/FVC) (r = -0.754, P <0.01, r = -0.557, P <0.01, r = -0.457, P <0.01, respectively). Moreover, the serum concentrations of sOX40L showed obvious differences among control, mild, moderate, and severe groups (3.98 ± 2.83, 4.87 ± 1.89, 6.97 ± 5.91, 8.71 ± 5.18 ng/L, respectively; P <0.01). The concentrations of sOX40L decreased to the same extent as the control group after therapeutic treatments were provided to the asthmatic adult patients.</p><p><b>CONCLUSION</b>The concentrations of sOX40L were found to be high in adult asthmatic patients and were associated with the severity of the disease. Therefore, sOX40L could be a potential inflammatory mediator in the pathogenesis of asthma.</p>

An unusual case of Welder's siderosis with local massive fibrosis: a case report / 中华医学杂志(英文版)

Welder's siderosis was traditionally described as "benign pneumoconiosis" because of the absence of associated symptoms, functional impairment or pulmonary fibrosis. Although several authors have reported evidence of fibrosis in the lungs of welders, siderosis with local massive fibrosis has been rarely described. In this paper, we present a case of Welder's siderosis with local massive fibrosis mimicking lung cancer.