Association between trans fatty acids and COVID-19: A multivariate Mendelian randomization study.

Traditional observational studies have suggested a potential association between trans fatty acids (TFAs), which are considered to be health-damaging fatty acids, and coronavirus disease 2019 (COVID-19). However, whether there is a causal relationship between them is currently unclear. We aimed to investigate the causal link between genetically determined TFAs and COVID-19. We performed univariate and multivariate Mendelian randomization (MR) studies using summary statistics from the European Pedigree TFAs (n = 8013), COVID-19 susceptibility (n = 159 840), COVID-19 hospitalization (n = 44 986), and COVID-19 severity (n = 18 152) genome-wide association studies (GWAS). The inverse variance weighted (IVW) method was used as the primary MR analysis, and several other methods were used as supplements. In univariate MR analysis, higher levels of circulating trans, cis-18:2 TFAs were positively associated with a higher COVID-19 hospitalization rate (p < 0.0033; odds ratio [OR] = 1.637; 95% confidence interval [CI]: 1.116-2.401) and COVID-19 severity (p < 0.0033; OR = 2.575; 95% CI: 1.412-4.698). Furthermore, in multivariate MR analysis, trans, cis-18:2 had an independent and significant causal association with a higher COVID-19 hospitalization rate (p = 0.00044; OR = 1.862; 95% CI = 1.316-2.636) and COVID-19 severity (p = 0.0016; OR = 2.268; 95% CI = 1.361-3.779) after the five TFAs were adjusted for each other. Together, our findings provide evidence that trans, cis-18:2 TFAs have an independent and robust causal effect on COVID-19 hospitalization and severity.

Network Pharmacological Screening of Herbal Monomers that Regulate Apoptosis-Associated Genes in Acute Pancreatitis.

OBJECTIVES: In this study, we screened for differentially expressed genes in acute pancreatitis and the herbal monomers that regulate these genes. METHODS: Gene expression profile data were downloaded from the Gene Expression Omnibus database (GSE3644). We used the Human Protein Reference Database to determine the protein-protein interaction network and CFinder software (Department of Biological Physics of Eötvös University, Budapest, Hungary) to identify several functional modules. Then, we used Database for Annotation, Visualization and Integrated Discovery software (Frederick, Md) to perform a gene ontology-biological process functional enrichment analysis. Based on a database of herbal monomers and a literature search, we constructed a gene-herbal monomer regulatory network using Cytoscape software (San Diego, Calif), and we analyzed the relationships between apoptosis, genes, and herbal monomers. RESULTS: A total of 1745 differentially expressed genes were identified. Nine modules were identified, and the main function of module 3 was closely related to apoptosis. Within module 3, we selected 13 genes that were closely related to apoptosis for further analysis. In the gene-herbal monomer regulatory network, 18 herbal monomers that regulate multiple target genes were selected as the focus of this study. CONCLUSIONS: These herbal monomers regulate multiple target genes to induce apoptosis and may potentially be used as new drugs for acute pancreatitis treatment in the future.

Database screening of herbal monomers regulating autophagy by constructing a "disease-gene-drug" network.

BACKGROUND: Studies suggest an important role of autophagy as a target for cancer therapy. We constructed a "disease-gene-drug" network using the modular approach of bioinformatics and screened herbal monomers demonstrating functions related to autophagy regulation. METHODS: Based on the microarray results of the gene expression omnibus (GEO) database (GSE2435 and GSE31040, starvation-induced autophagy model), we used the human protein reference database (HPRD) to obtain the protein-protein interaction (PPI) network. In addition, we used the CFinder software to identify several functional modules, performed gene ontology-biological process (GO-BP) functional enrichment analysis using the DAVID software, constructed a herbal monomer-module gene regulatory network using literature search and the Cytoscape software, and then analyzed the relationships between autophagy, genes, and herbal monomers. RESULTS: We screened 544 differentially expressed genes related to autophagy, 375 pairs of differentially expressed genes, and 7 gene modules, wherein the functions of module 3 (composed of 7 genes) were enriched in "cell death". Using the constructed herbal monomer-module gene regulatory network, we found that 30 herbal monomers can simultaneously regulate these 7 genes, indicating a potential regulatory role in autophagy. CONCLUSIONS: Database screening using the disease-gene-drug network can provide new strategies and ideas for the application of herbal medicines in cancer therapy.

Bioinformatics screening regarding herbal components that targetedly regulate the function of tumour-associated macrophages.

As an important component of tumour stroma, tumour-associated macrophages (TAMs) promote tumour development and progression. Herbs have been increasingly used in anticancer therapies due to their wide-ranging anticancer effects and minor side-effects. However, no herb-based treatments targeting TAMs have yet been proposed. To address this issue, screening using modular analysis bioinformatics techniques found 6 core functional modules for TAMs that contain 46 total genes. Moreover, 15 potential new anticancer drugs that regulate the genes in the 6 core modules were identified through bioinformatics techniques and Fisher's exact test. Our results provide a new research avenue for targeting TAMs in anticancer therapies.

Protective effects of emodin combined with danshensu on experimental severe acute pancreatitis.

OBJECTIVE AND DESIGN: In the present experiment, we aimed to determine the feasibility and curative effects of emodin combined with danshensu on experimental severe acute pancreatitis (SAP) and the mutual benefit of this synergistic strategy by a prospective animal study. MATERIAL: Eighty Wistar rats were randomly divided into four groups (n = 20). TREATMENT: SAP was elicited by a retrograde infusion of 5.0% sodium taurocholate into the pancreatic main duct. SAP rats in each group received no further intervention, emodin alone, danshensu (DSS) alone, and emodin combined with DSS (EDSS), respectively. METHODS: 48 h after SAP induction, all surviving animals were sacrificed to collect blood and tissue samples for the following measurements: serum levels of amylase, tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta), endotoxin and D-lactate. Pancreatic levels of TNF-alpha, IL-1beta, maleic dialdehyde (MDA), myeloperoxidase (MPO) activity, nuclear factor-kappaappaB (NF-kappaB) activation as well as wet-dry weight ratio were also evaluated. Ascitic fluid was quantified and the severity of pancreatic damage was analyzed by pathological grading and scoring. RESULTS: Compared with the SAP group, the emodin, DSS and EDSS groups had significant differences in every index. Furthermore, EDSS obviously improved all the parameters mentioned above so as to counteract inflammatory response and oxidative stress, as well as most effectively abating pancreatic and intestinal barrier injury. CONCLUSIONS: EDSS exerted protective effects on SAP rats and remarkably alleviated the severity of experimental SAP. Mechanisms that might account for the beneficial effects include protecting the intestinal barrier, inhibiting over-inflammatory reaction and abating oxidative stress. The combined strategy proved to be more effective than either emodin or DSS alone and may cause synergistic effects in combination in the early stage of SAP. Broad potential for future clinical practice is foreseeable.

[The effect of hyperbaric oxygen on acute pancreatitis through downregulating hypoxia-inducible factor.].

OBJECTIVE: To observe the therapeutic effect of hyperbaric oxygen (HBO) on acute pancreatitis (AP) by downregulating hypoxia-inducible factor (HIF). METHODS: Forty Wistar rats were randomly divided into 4 groups (n = 10): sham group, AP group, normo-oxygen group (NP) and HBO group. At 4 hours after taurocholate-induced AP, the rats of NP group and HBO group were respectively treated with oxygen or HBO for 90 min. Several parameters were measured to evaluate oxygen stress after treatment including oxygen saturation (SaO2), partial pressure of oxygen (PO2), pH, and serum LDH. Pancreatic tissues were subjected to histopathological analysis, immunostained, and homogenized for Western blotted analysis of HIF-1alpha and VEGF, and measuring myeloperoxidase activity. The serum TNF-alpha and pancreatic histopathological scores were evaluated the severity of AP. RESULTS: It was proved by immunohistochemisty that HIF in acinar cell and polymorphonuclear leukocytes (PMNs) was activated and transferred from cytoplasm into nucleus in AP group, NP group, and HBO group, following upregulation of VEGF. HBO therapy elevated blood SaO2 (99.6% +/- 0.7% vs. 87.7% +/- 1.8% or 91.2% +/- 2.5%, P < 0.05) and PaO2 [(369.1 +/- 67.6) mm Hg (1 mm Hg = 0.133 kPa) vs. (86.6 +/- 5.6) mm Hg or (99.9 +/- 4.0) mm Hg, P < 0.05]. HBO therapy attenuated the severity of AP through inhibiting AP-induced upregulation of HIF-1alpha and VEGF, as evidenced by reducing histopathological scores (12.40 +/- 1.21 vs. 16.45 +/- 1.10 or 16.38 +/- 1.10, P < 0.05), dry/wet weight ratio of pancreatic tissues, and myeloperoxidase activity. CONCLUSIONS: HIF-1alpha plays a key role in the pathogenesis of AP. HBO therapy attenuates the severity of AP through downregulating the expression of HIF-1alpha.

[Experimental study on electroacupuncture for strengthening gastrointestinal motility in the rat with acute pancreatitis].

OBJECTIVE: To explore the mechanism of EA in treatment of acute pancreatitis. METHODS: Twenty-four healthy male Wistar rats were randomly divided into 3 groups, a control group, a model group and an EA group. In the model group, rat acute pancreatitis model was prearpared by intraperitoneal injection of Caerulein, and in the EA group, EA was given at "Zusanli" (ST 36) and "Tianshu" (ST 25) of the model rat. The gastric emptying rate, small intestinal impelling ratio, myeloperoxidase activity in the pancreas tissue, pathological score of the pancreas and serum amylase were detected. RESULTS: Compared with the control group, both the gastric emptying rate and the intestinal impelling ratio significantly decreased in the model group (P<0.05), and they significantly increased in the EA group compared with the model group (P<0.05). Myeloperoxidase activity in the pancreas tissue, pathological score of the pancreas and serum amylase activity significantly decreased in the EA group as compared with the model group (P<0.05). CONCLUSION: EA can significantly improve the disturbance of gastrointestinal motility induced by acute pancreatitis and relieve pathological damage of pancreas.

[Effect of electroacupuncture on myoelectric activity of Jejunal limb After Roux-en-Y esophagojejunostomy].

OBJECTIVE: To explore the effect of electroacupuncture on myoelectric activity of Jejunal limb after Roux-en-Y esophagojejunostomy. METHODS: Fourteen health young pigs were randomly divided into 2 groups, an experimental group (total gastrectomy and Roux-en-Y esophagojejunostomy was carried out) and a control group (the abdominal cavity was closed after the electrode was placed), 7 pigs in each group. Electroacupunture was given at "Zusanli" (ST 36) in the experimental group. The changes of myoelectrogram of the jejunal limb was investigated. RESULTS: Compared with the control group, the amplitude and the frequency of the slow wave, and the amplitude and incidence rate of the spike potential in the experimental group were changed significantly; the duration of migrating motor complex (MMC) phase III was (2.6 +/- 0.7) minutes in the experimental group, which was significantly shorter than (7.1 +/- 1.1) minutes in the control group. Electroacupuncture did not significantly influence the amplitude and the frequency of the slow wave, but could increased significantly the incidence rate and the amplitude of the spike potential; after electroacupuncture, the duration of MMC phase III was (5.7 +/- 0.9) minutes, which was significantly longer than (2.6 +/- 0.7) minutes before electroacupuncture. CONCLUSION: Electroacupuncture at "Zusanli" (ST 36) can relieve the Roux-en-Y stasis syndrome through influencing myoelectric activity of the jejunum.