1.Protective effect of non-mitogenic haFGF on cerebral ischemia-reperfusion injury in mice
Yuzhi TAN ; Sa CAI ; Xiaokun LI ; Feng LIU ; Hualiang HU
Chinese Pharmacological Bulletin 1986;0(06):-
Aim To investigate the protective effect of non-mitogenic human acidic fibroblast growth factor (nm-haFGF) on cerebral ischemia-reperfusion injury in mice. Methods Cerebral ischemia-reperfusion model was made by ligating bilateral carotid for 20 minutes in mice. These mice were randomly divided into model group( iv NS), two doses of nm-haFGF (iv 25、50 ?g?kg-1) groups, rhaFGF group(iv 50 ?g?kg-1) and sham- operated group. Step down test and Y-type electric maze were used to examine the effect of nm-haFGF on learning and memory of mice, then Even′s Blue(EB) level and NO level in brain of these mice were measured. Results The nm-haFGF significantly decreased numbers of errors of mice in 5 min in step down test and in Y-type electric maze test; EB and NO levels in brain of these mice were lower than those of model group respectively. Conclusion The nm-haFGF can protect cerebral ischemia-reperfusion injury in mice.
2.Clinical study on Fuzheng Zhuyu Xiehuo Decoction combine with conventional western medicine therapy in the treatment of acute pancreatitis of intermingled blood stasis-toxin syndrome
Lin XIAO ; Yin XU ; Yangxiang ZHOU ; Hualiang TAN
International Journal of Traditional Chinese Medicine 2022;44(4):375-379
Objective:To explore the efficacy of Fuzheng Zhuyu Xiehuo Decoction for the patients with acute pancreatitis (AP) of intermingled blood stasis-toxin syndrome and its influence on peripheral blood inflammatory factors and microcirculation indicators.Methods:A total of 100 patients with AP, admitted to department of spleen and stomach diseases of the First Affiliated Hospital of Hunan University of Chinese Medicine and department of gastroenterology of the Central Hospital of Shaoyang, who met the inclusion criteria between March 2019 and March 2020, were divided into two groups according to the random number table method, with 50 in each group. The control group was given conventional western medicine, while the observation group was treated with Fuzheng Zhuyu Xiehuo Decoction on the basis of the control group. The TCM syndromes were scored before and after treatment, and Acute Physiology and Chronic Health Evaluation Ⅱ (APACHE Ⅱ) was used to evaluate the severity of the disease, and ELISA was adopted to detect the levels of IL-6, IL-8, TNF-α and thromboxane A2 (TXA2), prostaglandin I 2 (PGI 2) and platelet activating factor (PAF). The abdominal pain, abdominal distension, fever, gastrointestinal function recovery time and hospital stay were observed and the adverse events were recorded. Results:The total effective rate was 96.0% (48/50) in the observation group and that of the control group was 84.0% (42/50) ( χ2=4.00, P=0.045). The scores of abdominal pain, abdominal distension, fever and nausea and vomiting in observation group were significantly lower than those in the control group ( t=7.07, 7.06, 11.47, 10.30, all Ps<0.01), and the recovery times of abdominal pain, abdominal distension, fever and gastrointestinal function and hospital stay in the observation group were significantly shorter than those in the control group ( t=4.52, 4.90, 6.27, 6.55, 7.12, all Ps<0.01). After treatment, the levels of serum IL-6 [(30.15±7.04) μg/L vs. (42.37±8.29) μg/L, t=7.95], IL-8 [(39.36±8.11) μg/L vs. (50.36±10.47) μg/L, t=5.87], TNF-α [(106.28±21.04) μg/L vs. (153.45±30.23) μg/L, t=9.06] in the observation group were significantly lower than those in the control group ( P<0.01). The serum TXA2 [(223.68±40.15) ng/L vs. (257.11±50.32) ng/L, t=3.67] and PAF [(74.86±15.37) ng/L vs. (85.53±15.26) ng/L, t=3.48] in the observation group were significantly lower than those in the control group ( P<0.01) while the level of PGI 2 [(91.43±17.45) ng/L vs. (76.49±15.13) ng/L, t=4.57] in the observation group was significantly higher than those in the control group ( P<0.01). Conclusion:Fuzheng Zhuyu Xiehuo Decoction combined with western medicine can improve clinical symptoms and blood microcirculation status, relieve inflammatory response and enhance clinical efficacy of patients with AP of intermingled blood stasis-toxin syndrome.
3.High-throughput screening of SARS-CoV-2 main and papain-like protease inhibitors.
Yi ZANG ; Mingbo SU ; Qingxing WANG ; Xi CHENG ; Wenru ZHANG ; Yao ZHAO ; Tong CHEN ; Yingyan JIANG ; Qiang SHEN ; Juan DU ; Qiuxiang TAN ; Peipei WANG ; Lixin GAO ; Zhenming JIN ; Mengmeng ZHANG ; Cong LI ; Ya ZHU ; Bo FENG ; Bixi TANG ; Han XIE ; Ming-Wei WANG ; Mingyue ZHENG ; Xiaoyan PAN ; Haitao YANG ; Yechun XU ; Beili WU ; Leike ZHANG ; Zihe RAO ; Xiuna YANG ; Hualiang JIANG ; Gengfu XIAO ; Qiang ZHAO ; Jia LI
Protein & Cell 2023;14(1):17-27
The global COVID-19 coronavirus pandemic has infected over 109 million people, leading to over 2 million deaths up to date and still lacking of effective drugs for patient treatment. Here, we screened about 1.8 million small molecules against the main protease (Mpro) and papain like protease (PLpro), two major proteases in severe acute respiratory syndrome-coronavirus 2 genome, and identified 1851Mpro inhibitors and 205 PLpro inhibitors with low nmol/l activity of the best hits. Among these inhibitors, eight small molecules showed dual inhibition effects on both Mpro and PLpro, exhibiting potential as better candidates for COVID-19 treatment. The best inhibitors of each protease were tested in antiviral assay, with over 40% of Mpro inhibitors and over 20% of PLpro inhibitors showing high potency in viral inhibition with low cytotoxicity. The X-ray crystal structure of SARS-CoV-2 Mpro in complex with its potent inhibitor 4a was determined at 1.8 Å resolution. Together with docking assays, our results provide a comprehensive resource for future research on anti-SARS-CoV-2 drug development.
Humans
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Antiviral Agents/chemistry*
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COVID-19
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COVID-19 Drug Treatment
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High-Throughput Screening Assays
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Molecular Docking Simulation
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Protease Inhibitors/chemistry*
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SARS-CoV-2/enzymology*
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Viral Nonstructural Proteins