A Network Pharmacology Study to Uncover the Multiple Molecular Mechanism of the Chinese Patent Medicine Toujiequwen Granules in the Treatment of Corona Virus Disease 2019 (COVID-19).

Since the outbreak of the novel corona virus disease 2019 (COVID-19) at the end of 2019, specific antiviral drugs have been lacking. A Chinese patent medicine Toujiequwen granules has been promoted in the treatment of COVID-19. The present study was designed to reveal the molecular mechanism of Toujiequwen granules against COVID-19. A network pharmacological method was applied to screen the main active ingredients of Toujiequwen granules. Network analysis of 149 active ingredients and 330 drug targets showed the most active ingredient interacting with many drug targets is quercetin. Drug targets most affected by the active ingredients were PTGS2, PTGS1, and DPP4. Drug target disease enrichment analysis showed drug targets were significantly enriched in cardiovascular diseases and digestive tract diseases. An "active ingredient-target-disease" network showed that 57 active ingredients from Toujiequwen granules interacted with 15 key targets of COVID-19. There were 53 ingredients that could act on DPP4, suggesting that DPP4 may become a potential new key target for the treatment of COVID-19. GO analysis results showed that key targets were mainly enriched in the cellular response to lipopolysaccharide, cytokine activity and other functions. KEGG analysis showed they were mainly concentrated in viral protein interaction with cytokine and cytokine receptors and endocrine resistance pathway. The evidence suggests that Toujiequwen granules might play an effective role by improving the symptoms of underlying diseases in patients with COVID-19 and multi-target interventions against multiple signaling pathways related to the pathogenesis of COVID-19.

Computer-Assisted Drug Virtual Screening Based on the Natural Product Databases.

BACKGROUND: Computer-assisted drug virtual screening models the process of drug screening through computer simulation technology, by docking small molecules in some of the databases to a certain protein target. There are many kinds of small molecules databases available for drug screening, including natural product databases. METHODS: Plants have been used as a source of medication for millennia. About 80% of drugs were either natural products or related analogues by 1990, and many natural products are biologically active and have favorable absorption, distribution, metabolization, excretion, and toxicology. RESULTS: In this paper, we review the natural product databases' contributions to drug discovery based on virtual screening, focusing particularly on the introductions of plant natural products, microorganism natural product, Traditional Chinese medicine databases, as well as natural product toxicity prediction databases. CONCLUSION: We highlight the applications of these databases in many fields of virtual screening, and attempt to forecast the importance of the natural product database in next-generation drug discovery.

Retrospective study on efficacy of a paclitaxel combined with a leucovorin and fluorouracil regimen for advanced gastric cancer.

PURPOSE: To investigate the efficacy of paclitaxel combined with a leucovorin and 5-fluorouracil regimen (PLF regimen; q2w) as neoadjuvant chemotherapy (NCT) for advanced gastric cancer. METHODS: A total of 183 patients with advanced gastric cancer who underwent 3 cycles of PLF regimen chemotherapy before surgery and received surgery 2 weeks after chemotherapy were enrolled as a treatment group. A total of 184 patients with advanced gastric cancer and no NCT during the same period were enrolled as the controls and treated with surgery. Both groups underwent a D2 radical gastrectomy and the standard postoperative adjuvant chemotherapy. RESULTS: In the NCT group, there were 19 cases of complete remission, 86 cases of partial remission, 72 cases of stable disease, and 6 cases of progressive disease, with an overall response rate of 57.4%. The R0 resection rate was higher than in the control group (85.2% vs 61.4%, p < .05). In the NCT group, 12 cases of esophagogastric cancer (20.7%) showed complete remission and 32 cases (55.2%) showed partial remission, while 7 cases of distal gastric cancer (5.6%) showed complete remission and 54 cases (43.2%) showed partial remission. Pathologic complete remission was higher for esophagogastric cancer than for distal gastric cancer (20.7% vs 3.2%, p < .05). Differences were found between the NCT and control groups in terms of 1-year, 3-year, and 5-year overall and disease-free survival. CONCLUSION: The PLF regimen showed good tolerability and a high response rate, especially for esophagogastric cancer. This regimen reduced the tumor size, lowered the tumor stage, and improved the R0 resection rate and survival rate.

Enhancement of heavy metal accumulation by tissue specific co-expression of iaaM and ACC deaminase genes in plants.

1-Aminocyclopropane deaminase (ACC) and tryptophan monooxygenase are two enzymes involved in plant senescence-inhibiting and growth-promoting regulation, respectively. In this study, two binary vectors were constructed in which the Agrobacterium iaaM gene was under the transcriptional control of a xylem-specific glycine-rich protein promoter alone, or co-expressed with the bacterial ACC deaminase gene, which was driven by the constitutive CaMV 35S promoter. Transgenic petunia shoots co-expressing both genes were able to root on medium supplemented with 7.5 mg l(-1) CoCl2. When T1 transgenic tobacco plants were grown in sand supplemented with Cu2+ and Co2+, tissue specific co-expression of both iaaM and ACC deaminase genes showed faster growth with larger biomass with a more extensive root system, and accumulated a greater amount of heavy metals than the empty vector control plants. When T1 transgenic tobacco plants were grown in soil watered with different concentrations of CuSO4, xylem specific expression of the iaaM gene caused the accumulation of more Cu2+ than the empty vector control at lower CuSO4 concentrations, but showed severe toxic symptoms at concentration of 100 mg l(-1) CuSO4. T1 transgenic plants co-expressing both genes accumulated more heavy metals into the plant shoots and can tolerate CuSO4 at 150 mg l(-1). In addition, plants co-expressing these two genes can grow well in a complex contaminated soil containing both inorganic and organic pollutants, while the growth of the control plants was greatly inhibited.