Application regularity of medicinal and dietary substances for patients during COVID-19 rehabilitation / 数字中医药（英文）

@#Objective This study focused on the application regularity of medicinal and dietary substances (MDS) of traditional Chinese medicine (TCM) diet therapy during rehabilitation, in order to help patients with Corona Virus Disease 2019 (COVID-19) reduce sequelae and improve their life quality. Methods The official websites of the national and provincial health committees, the website of the National Administration of Traditional Chinese Medicine, the China BioMedical Literature Database (CBM), China National Knowledge Infrastructure (CNKI), China Science and Technology Journal Database (VIP), and Wanfang Database were used to search the keywords, such as “coronavirus” “novel coronavirus pneumonia” “COVID-19” “protocol” “guideline” “consensus” and “rehabilitation period”. The search time was from the establishment of databases to July 31, 2022. The prevention and control protocols of various provinces and cities were manually supplemented and screened out. The information on the frequency, property, flavor, meridian tropism, and efficacy of MDS was collected for association rule analysis through the Apriori algorithm. Hierarchical cluster analysis was performed using the Euclidean distance and longest distance. Results A total of 18 protocols were screened out, including 56 lists of TCM diet therapy, and 47 kinds of MDS with a frequency of 132 times during the rehabilitation of COVID-19. Among them, six lists of diet therapy were collected from national websites, 26 from local government websites, and 24 from social and academic institution websites. The intended population can be divided into seven categories including normal recovery, lung-spleen Qi deficiency, deficiency of both Qi and Yin, spleen-stomach weakness, deficiency of Yang Qi, kidney Qi deficiency, and blood deficiency. Shanyao (Dioscoreae Rhizoma) and Lianzi (Nelumbinis Semen), followed by Dazao (Jujubae Fructus) were used most commonly in MDS, with mainly flat property, sweet flavor, and spleen and lung meridians in meridian tropism. Besides, deficiency-tonifying drugs were commonly used in MDS. Through association rule analysis, 12 groups of association MDS pairs were obtained. The pair of Yiyiren (Coicis Semen) and Chenpi (Citri Reticulatae Pericarpium) had the highest Lift value, and Yiyiren (Coicis Semen) was used most frequently in the MDS category for eliminating pathogenic factors. The results of complex network analysis showed that the core MDS were Yiyiren (Coicis Semen), Shanyao (Dioscoreae Rhizoma), Huangqi (Astragali Radix), Fuling (Poria), and Dazao (Jujubae Fructus). Three core categories were classified by cluster analysis, including the category of strengthening spleen, nourishing kidney, and grasping Qi, the category of removing phlegm, abating panting, and regulating Qi, and the category of strengthening the middle-energizer and reinforcing Qi. Conclusion Based on the TCM theory, most patients during the rehabilitation of COVID-19 are in a state of lingering pathogens due to deficient vital Qi. TCM diet therapy is based on the principle of “giving both reinforcing and reducing treatment”, and the MDS combinations focus on both reinforcing the health Qi and eliminating pathogenic factors. The diet therapy mainly uses the MDS with flat property and sweet flavor, which belongs to deficiency-tonifying drugs, adding suitable MDS of pathogen-eliminating drugs according to different situations. The ultimate goal is to promote lung inflammation absorption, improve pulmonary fibrosis, increase immunity, reduce the occurrence of sequelae, and improve life quality.

IL-6 upregulation contributes to the reduction of miR-26a expression in hepatocellular carcinoma cells

A recent study showed that miR-26a is downregulated in hepatocellular carcinoma tissues and that this downregulation is an independent predictor of survival. Interestingly, the same study also reported that miR-26a downregulation causes a concomitant elevation of IL-6 expression. Because miR-26a expression was found to be transcriptionally downregulated by oncogene c-Myc in various cancers, and the expression of c-Myc was increased by IL-6 stimulation, we hypothesized that IL-6 contributes to reduction of miR-26a in hepatocellular carcinoma. Serum IL-6 was measured by ELISA and miR-26a was detected by qRT-PCR. The data of 30 patients with hepatocellular carcinoma who had undergone surgical tumor resection revealed that serum IL-6 could be considered to be a predictor of survival up to 5 years for hepatocellular carcinoma patients (log-rank test, P < 0.05). We observed that the serum IL-6 concentration was inversely correlated with miR-26a expression in cancerous tissues (Pearson correlation test, r = -0.651, P < 0.01). Furthermore, by in vitro experiments with HepG2 cells, we showed that IL-6 stimulation can lead to miR-26a suppression via c-Myc activation, whereas in normal hepatocyte LO2 cells incubation with IL-6 had no significant effect on miR-26a expression. Taken together, these results indicate that miR-26a reduction in hepatocellular carcinoma might be due to IL-6 upregulation.

Synergistic growth inhibition by sorafenib and vitamin K2 in human hepatocellular carcinoma cells

OBJECTIVE: Sorafenib is an oral multikinase inhibitor that has been proven effective as a single-agent therapy in hepatocellular carcinoma, and there is a strong rationale for investigating its use in combination with other agents. Vitamin K2 is nearly non-toxic to humans and has been shown to inhibit the growth of hepatocellular carcinoma. In this study, we evaluated the effects of a combination of sorafenib and vitamin K2 on the growth of hepatocellular carcinoma cells. METHODS: Flow cytometry, 3-(4,5-dimethyl-2-thiazolyl-2,5-diphenyl-2H-tetrazolium bromide) and nude mouse xenograft assays were used to examine the effects of sorafenib and vitamin K2 on the growth of hepatocellular carcinoma cells. Western blotting was used to elucidate the possible mechanisms underlying these effects. RESULTS: Assays for 3-(4,5-dimethyl-2-thiazolyl-2,5-diphenyl-2H-tetrazolium bromide) revealed a strong synergistic growth-inhibitory effect between sorafenib and vitamin K2. Flow cytometry showed an increase in cell cycle arrest and apoptosis after treatment with a combination of these two drugs at low concentrations. Sorafenib-mediated inhibition of extracellular signal-regulated kinase phosphorylation was promoted by vitamin K2, and downregulation of Mcl-1, which is required for sorafenib-induced apoptosis, was observed after combined treatment. Vitamin K2 also attenuated the downregulation of p21 expression induced by sorafenib, which may represent the mechanism by which vitamin K2 promotes the inhibitory effects of sorafenib on cell proliferation. Moreover, the combination of sorafenib and vitamin K2 significantly inhibited the growth of hepatocellular carcinoma xenografts in nude mice. CONCLUSIONS: Our results determined that combined treatment with sorafenib and vitamin K2 can work synergistically to inhibit the growth of hepatocellular carcinoma cells. This finding raises the possibility that this combined treatment strategy might be promising as a new therapy against hepatocellular carcinoma, especially for patients with poor liver tolerance.