ABSTRACT
Enzymes are closely associated with the onset and progression of numerous diseases, making enzymes a primary target in innovative drug development. However, the challenge remains in identifying compounds that exhibit potent inhibitory effects on the target enzymes. With the continuous expansion of the total number of natural products and increasing difficulty in isolating and enriching new compounds, traditional high-throughput screening methods are finding it increasingly challenging to meet the demands of new drug development. Virtual screening, characterized by its high efficiency and low cost, has gradually become an indispensable technology in drug development. It represents a prominent example of the integration of artificial intelligence with biopharmaceuticals and is an inevitable trend in the rapid development of innovative drug screening in the future. Therefore, this article primarily focused on systematically reviewing the recent applications of virtual screening technology in the development of enzyme inhibitors and explored the prospects and advantages of using this technology in developing new drugs, aiming to provide essential theoretical insights and references for the application of related technologies in the field of new drug development.
Subject(s)
Artificial Intelligence , Enzyme Inhibitors , Enzyme Inhibitors/pharmacology , High-Throughput Screening Assays , Molecular Docking SimulationABSTRACT
An unusual rearrangement of saccharin-derived cyclic ketimines (SDCIs) and 3-chlorooxindoles has been developed to provide a series of spiro-1,3-benzothiazine oxindoles. The reaction features simple manipulations, short reaction times, mild reaction conditions and inexpensive reagents. It is the first example where SDCIs serve as a ring-opening reagent in organic synthesis.
ABSTRACT
Glioblastoma is the most frequent primary malignant brain tumor in adults. Oxysterols are oxidation products of cholesterol generated by enzymatic reactions. 27-hydroxycholesterol (27-HC), an oxysterol, is an abundant metabolite of cholesterol. 27-HC significantly accelerates mammary cancer growth, proliferation and progression in experimental models. However, to the best of our knowledge, the effect of 27-HC on glioblastoma has not been studied. Therefore, the present study aimed to determine the exact role of 27-HC in glioblastoma. The present study demonstrated that 27-HC promoted proliferation, epithelial to mesenchymal transition, colony formation, migration and invasion of U251 and U118 MG glioblastoma cells. Treatment with 27-HC was also associated with an increase in the formation of glioblastoma-initiating cells in U251 and U118 MG cell lines. Additionally, it was observed that high levels of 27-HC in glioblastoma tissues were associated with poor outcome in patients. In conclusion, 27-HC, a primary metabolite of cholesterol, may serve an important role in the progression of glioblastoma.
ABSTRACT
Objective: To observe the clinical efficacy of addition and subtraction therapy of Taohong Siwutang combined with Chaihu Shugansan to unstable angina pectoris with type A behavior pattern (Qi stagnation and blood stasis syndrome), and investigate its effects on proinflammatory factors and serotonin (5-HT). Method: One hundred twenty-four patients were randomly divided into control group (60 cases) and observation group(64 cases) by random number table. Patients in control group got Aspirin enteric-coated tablets, 100 mg/time, 1 time/day. Tigrillo tablets, 90 mg/time, 2 times/days. Metoprolol tartrate tablets, 50 mg/time, 2 times/days. Simvastatin tablets, 10 mg/time, 1 time/day. Nitroglycerin tablets, 0.5 mg/time. Based on the treatment in control group, patients in observation group also received addition and subtraction therapy of Taohong Siwutang combined with Chaihu Shugansan, 1 dose/day. The treatment course was 8 weeks in both groups. Number of attacks, duration, degree of pain and usage of nitroglycerin were recorded for every week. Before and after treatment, electrocardiogram was also recorded. And levels of triglyceride (TG), total cholesterol (TC), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), interleukin-6 (IL-6), tumor necrosis factor-α(TNF-α), hypersensitive C-reactive protein and 5-HT were detected. In addition, scores of Seattle Angina Scale (SAQ) and Qi stagnation and blood stasis syndrome were graded. Result: In the rank sum test, the curative effect in electrocardiogram of observation group was better than that of control group (Z=1.965, PPPPα and 5-HT in observation group were lower than those in control group (PPConclusion: On the basis of conventional western medicine, addition and subtraction therapy of Taohong Siwutang combined with Chaihu Shugansan can further control angina attack, relieve clinical symptoms, improve quality of life, regulate lipid metabolism, and can inhibit expression of proinflammatory factors and 5-HT, so it can play a role in stabilizing the disease.
ABSTRACT
OBJECTIVE: To investigate the prevalence and predictors of acute stress disorder (ASD) in the victims affected by Wenchuan earthquake in China. METHODS: A random clustered sampling method was used. Of 891 victims enrolled in the study, 874 were completely assessed with the ASD constructive questionnaire and diagnosed with DSM-IV criteria. Sociodemographic variables were obtained. Also, the major symptoms of ASD (i.e., general symptoms to a traumatic event; dissociative symptoms; re-experiencing symptoms; hyper-arousal symptoms; avoidance symptoms) were recorded. RESULTS: The incidence rate of ASD was 12.59% (110/874). The incidence rates of ASD for female and male were 15.16% (72/475) and 9.52% (38/399) respectively. There was a significant difference between female and male on the incidence rate of ASD (chi(2) = 6.26, P = 0.01). Logistic regression indicated that the ASD diagnosis was predicted by gender (beta = 0.58, P = 0.01, OR = 1.79), the condition of casualties of family members (beta = 0.60, P = 0.01, OR = 1.82), and the condition of sharp properties loss (beta = 1.02, P = 0.01, OR = 2.76). CONCLUSION: The major earthquake should have great influence on mental health of victims. The efforts to reduce casualties and property loss might help to prevent ASD. Further research is needed on gender difference among traumatic events.
