Integrating experimental model, LC-MS/MS chemical analysis, and systems biology approach to investigate the possible antidiabetic effect and mechanisms of Matricaria aurea (Golden Chamomile) in type 2 diabetes mellitus.

Type 2 diabetes mellitus (T2DM) is a heterogeneous disease with numerous abnormal targets and pathways involved in insulin resistance, low-grade inflammation, oxidative stress, beta cell dysfunction, and epigenetic factors. Botanical drugs provide a large chemical space that can modify various targets simultaneously. Matricaria aurea (MA, golden chamomile) is a widely used herb in Middle Eastern communities for many ailments, including diabetes mellitus, without any scientific basis to support this tradition. For the first time, this study aimed to investigate the possible antidiabetic activity of MA in a type 2 diabetic rat model, identify chemical constituents by LC-MS/MS, and then elucidate the molecular mechanism(s) using enzyme activity assays, q-RTPCR gene expression analysis, network pharmacology analysis, and molecular docking simulation. Our results demonstrated that only the polar hydroethanolic extract of MA had remarkable antidiabetic activity. Furthermore, it improved dyslipidemia, insulin resistance status, ALT, and AST levels. LC-MS/MS analysis of MA hydroethanolic extract identified 62 compounds, including the popular chamomile flavonoids apigenin and luteolin, other flavonoids and their glycosides, coumarin derivatives, and phenolic acids. Based on pharmacokinetic screening and literature, 46 compounds were chosen for subsequent network analysis, which linked to 364 candidate T2DM targets from various databases and literature. The network analysis identified 123 hub proteins, including insulin signaling and metabolic proteins: IRS1, IRS2, PIK3R1, AKT1, AKT2, MAPK1, MAPK3, and PCK1, inflammatory proteins: TNF and IL1B, antioxidant enzymes: CAT and SOD, and others. Subsequent filtering identified 40 crucial core targets (major hubs) of MA in T2DM treatment. Functional enrichment analyses of the candidate targets revealed that MA targets were mainly involved in the inflammatory module, energy-sensing/endocrine/metabolic module, and oxidative stress module. q-RTPCR gene expression analysis showed that MA hydroethanolic extract was able to significantly upregulate PIK3R1 and downregulate IL1B, PCK1, and MIR29A. Moreover, the activity of the antioxidant hub enzymes was substantially increased. Molecular docking scores were also consistent with the networks' predictions. Based on experimental and computational analysis, this study revealed for the first time that MA exerted antidiabetic action via simultaneous modulation of multiple targets and pathways, including inflammatory pathways, energy-sensing/endocrine/metabolic pathways, and oxidative stress pathways.

Comparative in silico analysis of chemotaxis system of Campylobacter fetus.

Chemoreceptor and chemotaxis signal transduction cascade genes of C. fetus subsp. fetus 82-40 show high level of similarity to that in C. jejuni and appears to include sixteen diverse transducer-like protein (tlp) genes that appear similar to nine of the twelve tlp genes in the C. jejuni NCTC 11168 with a percent identity ranging from 15 to 50%. Sixteen putative C. fetus 82-40 tlp genes belong to three classes: A, B, and C, as well as an aerotaxis gene, based on their predicted structure. C. fetus subsp. fetus 82-40 chemoreceptor and chemotaxis signal transduction pathway genes have close phylogenetic relationship of chemotaxis genes between Campylobacteraceae and Helicobacteraceae.

Diagnostic and prognostic values of adhesion molecules VCAM-1, ICAM-1 and C-reactive protein in Egyptian patients with chronic kidney disease.

Soluble intracellular adhesion molecule-1 (ICAM-1) and soluble vascular adhesion molecule-1 (VCAM-1) are markers of endothelial dysfunction which is linked to the atherosclerotic process causing a series of complications in patients with chronic kidney disease. The aim of this study was to evaluate C-reactive protein and adhesion molecules VCAM-1, ICAM-1 in patients with predialysis, chronic renal failure (CRF), on maintenance hemodialysis (HD) and after kidney transplantation (KT). Ten patients with predialysis CRF, 20 on maintenance HD, 5 after KT and 10 subjects as a control group were included in this study. We evaluated serum levels of ICAM-1, VCAM-1 as acute phase proteins, C-reactive protein (CRP) as an inflammatory marker and body mass indices (BMI), serum albumin, cholesterol, triglyceride as nutritional indices. The mean values of serum levels of VCAM-1 and ICAM-1 were significantly higher in the three groups of patients than those of the controls (P < or = 0.05). There was statistically significant difference between the serum levels of VCAM-1 in the HD patients versus all other groups with the highest level in the HD patients. The circulating level of CRP, there was a progressive increase from controls to KT, CRF and to HD with the highest level in HD patients. There was a statistically significant difference between CRP serum levels in the HD patients versus all other groups with the highest level in the HD patients. Regression analysis showed significant positive correlation between CRP and ICAM-1 in KT patients (r = 0.9051; P = 0.0346), in CRF patients (r = 0.7621; P = 0.0170) and in HD patients (r = 0.4449, P = 0.0493). As regards the correlation between CRP and VCAM-1, there was positive correlation in KT patients (r = 0.9006; P = 0.0370), in CRF patients (r = 0.7088; p = 0.0326) and in HD patients (r = 0.4498; P = 0.0466). Age and BMI did not statistically differ in the study groups. In conclusion, serum levels of soluble adhesion molecules sVCAM-1, sICAM-1 correlate positively with the stage of renal disease. Also their serum levels were correlated positively with CRP as an inflammatory index in renal diseases. Further studies are needed to assess use of monoclonal antibodies against adhesion molecules and CRP as targets for therapeutic intervention in chronic kidney diseases.

Design and validation of a multiplex polymerase chain reaction for the identification of enterotoxigenic Escherichia coli and associated colonization factor antigens.

Development of a genetic tool for the detection of genes encoding enterotoxins and colonization factors would greatly enhance enterotoxigenic Escherichia coli (ETEC) surveillance. Oligonucleotide primers were designed to amplify genes encoding human ST, porcine ST, LT and the structural genes of colonization factor antigen (CFA)/I, CS1 to CS8, CS12 to CS15, CS17 to CS22, and PCFO71. Screening 89 ETEC isolates phenotypically expressing a known CFA showed that, without exception, the multiplex polymerase chain reaction (mPCR) detected the structural gene of the expressed CFA, in addition to CS21 in 22.5% of isolates. Silent genes such as cssB (CS6) were also detected in 9.0%. Additionally, we screened 71 CFA phenotypically negative isolates and detected a CFA in more than 50% of tested isolates. In conclusion, we have designed a simple 4-step mPCR for the rapid detection of ETEC virulence factors. The assay is rapid, reproducible, relatively inexpensive, and has the potential to be field applicable.