Polymorphisms of the FTO, LEPR and MTHFR genes may play a role in MS in Malaysian schizophrenia patients receiving long-term treatment with APs.

Background In recent years, the high mobility group box-1 (HMGB1) protein, a damage-associated molecular pattern (DAMP) molecule, has been found to play multifunctional roles in the pathogenesis of colorectal cancer. Although much attention has been given to the diagnostic and prognostic values of HMGB1 in colorectal cancer, the exact functional roles of the protein as well as the mechanistic pathways involved have remained poorly defined. This systematic review aims to discuss what is currently known about the roles of HMGB1 in colorectal cancer development, growth and progression, and to highlight critical areas for future investigations. To achieve this, the bibliographic databases Pubmed, Scopus, Web of Science and ScienceDirect were systematically screened for articles from inception till June 2018, which address associations of HMGB1 with colorectal cancer. Conclusions HMGB1 plays multiple roles in promoting the pathogenesis of colorectal cancer, despite a few contradicting studies. HMGB1 may differentially regulate disease-related processes, depending on the redox status of the protein in colorectal cancer. Binding of HMGB1 to various protein partners may alter the impact of HMGB1 on disease progression. As HMGB1 is heavily implicated in the pathogenesis of colorectal cancer, it is crucial to further improve our understanding of the functional roles of HMGB1 not only in colorectal cancer, but ultimately in all types of cancers.

The objectives of this study were to examine the effects of ethnicity, gender and a proton pump inhibitor (PPI), omeprazole, on the human gut microbiome. PPIs are commonly used for the treatment of acid-related disorders. We hypothesised that PPI therapy might perturb microbial communities and alter the gut microbiome. METHODS Healthy subjects of Chinese (n = 12), Malay (n = 12) and Indian (n = 10) ancestry, aged 21-37 years, were enrolled. They provided a baseline stool sample (Day 1) and were then given a course of omeprazole at therapeutic dose (20 mg daily) for seven days. Stool samples were collected again on Day 7 and 14 (one week after stopping omeprazole). Microbial DNA was extracted from the stool samples, followed by polymerase chain reaction, library construction, 16S rRNA sequencing using Illumina MiSeq, and statistical and bioinformatics analyses. RESULTS The findings showed an increase in species richness (p = 0.018) after omeprazole consumption on Day 7, which reverted to baseline on Day 14. There were significant increases in the relative abundance of Streptococcus vestibularis (p = 0.0001) and Veillonella dispar (p = 0.0001) on Day 7, which diminished on Day 14. Faecalibacterium prausnitzii, Sutterella stercoricanis and Bacteroides denticanum were characteristic of Chinese, Malays and Indians, respectively. Lactobacillaceae and Bacteroides xylanisolvens were the signature taxa of male and female subjects, respectively. CONCLUSION The study demonstrated alterations in the gut microbiome following omeprazole treatment. This may explain the underlying pathology of increased risk of Clostridium difficile infections associated with omeprazole therapy.

Background:Although aberrant expression of cytokines and small molecules (analytes) is well documented in acute myeloid leukaemia (AML), their co-expression patterns are not yet identified. In addition, plasma baselines for some analytes that are biomarkers for other cancers have not been previously reported in AML.Methods:We used multiplex array technology to simultaneously detect and quantify 32 plasma analyte (22 reported analytes and 10 novel analytes) levels in 38 patients.Results:In our study, 16 analytes are found to be significantly deregulated (13 higher, 3 lower, Mann–Whitney U-test, P-value <0.005), where 5 of them have never been reported before in AML. We predicted a seven-analyte-containing multiplex panel for diagnosis of AML and, among them, MIF could be a possible therapeutic target. In addition, we observed that circulating analytes show five co-expression signatures.Conclusions:Circulating analyte expression in AML significantly differs from normal, and follow distinct expression patterns.

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Introduction: Acute myeloid leukemia (AML) is a disparate hematopoietic malignancy, with many subtypes and variable responsiveness to therapy. Identification of a targetable biomarker can be used to improve survival outcome of this disease. High mobility group box 1 (HMGB1), contributes to the progression of AML by inducing various cytokines production and angiogenic vascular endothelial growth factor (VEGF). Receptor for advanced glycation end products (RAGE) exists as both a membrane and soluble receptor (sRAGE). HMGB1 is a ligand for RAGE, with sRAGE serving as a natural antagonist of RAGE signaling. Accumulating evidence suggests that HMGB1/sRAGE axis is critically involved in many cancers.Objective: The aim of this study was to investigate whether there is a difference in the plasma levels of HMGB1/sRAGE between AML patients with good and poor prognosis and those who go into relapse.Methods: A total of 97 plasma samples from peripheral blood were analysed for the study (47 AML, 50 healthy subjects). HMGB1 and sRAGE levels were measured using ELISA and analysed using GraphPad Prism 5.0.Results: HMGB1 levels were found to be significantly higher in relapsed AML cases as compared to newly diagnosed cases (49.81 ± 25.25 (N=11) vs 9.461 ± 4.770 (N=36), pg/ml, p = 0.0161). HMGB1 was also significantly higher among new AML cases classified as having poor prognosis as compared to good prognosis (26.11 ± 13.31 (N=12) vs 1.135 ± 0.7147 (N=24), pg/ml, p = 0.0114). Although sRAGE levels were also high where HMBG1 levels were high, the differences were not significant.Conclusion: HMGB1 may be used as a prognostic biomarker, as it appears to promote AML progression with higher levels seen in more malignant forms. Unravelling the mechanisms of HMGB1 in the pathogenesis of AML could provide means to regulate its expression and activities and serve as an effective treatment for more aggressive subtypes.International Journal of Human and Health Sciences Supplementary Issue: 2019 Page: 59