Genetically Determined Plasma Lipid Levels and Risk of Diabetic Retinopathy: A Mendelian Randomization Study.

Results from observational studies examining dyslipidemia as a risk factor for diabetic retinopathy (DR) have been inconsistent. We evaluated the causal relationship between plasma lipids and DR using a Mendelian randomization approach. We pooled genome-wide association studies summary statistics from 18 studies for two DR phenotypes: any DR (N = 2,969 case and 4,096 control subjects) and severe DR (N = 1,277 case and 3,980 control subjects). Previously identified lipid-associated single nucleotide polymorphisms served as instrumental variables. Meta-analysis to combine the Mendelian randomization estimates from different cohorts was conducted. There was no statistically significant change in odds ratios of having any DR or severe DR for any of the lipid fractions in the primary analysis that used single nucleotide polymorphisms that did not have a pleiotropic effect on another lipid fraction. Similarly, there was no significant association in the Caucasian and Chinese subgroup analyses. This study did not show evidence of a causal role of the four lipid fractions on DR. However, the study had limited power to detect odds ratios less than 1.23 per SD in genetically induced increase in plasma lipid levels, thus we cannot exclude that causal relationships with more modest effect sizes exist

Non-viral transfection of bone marrow-derived mesenchymal stem cell with human interferon-gamma gene and in vitro efficiency against chronic myeloid leukaemia cells

Chronic myeloid leukemia (CML) is a hematopoietic stem cell disorder caused by the BCR/ABL gene rearrangement, known as the Philadelphia (Ph) chromosome. To date, the only curative therapy for CML is allogeneic stem cell transplantation. However, significant morbidity and mortality are associated with the procedure and the need for a matched donor makes this option not available to the majority of the patients. Currently, various studies have been carried out to develop an alternative approach for CML treatment, for example targeted gene delivery of therapeutic cytokines. In this study, the feasibility of using bone marrow-derived mesenchymal stem cell (BM-MSC) in delivering human interferon-gamma (hIFN-γ) gene for targeted CML therapy was explored. Mesenchymal stem cells (MSC) were successfully isolated from human bone marrow aspirates and their biological properties were similar to those of MSC reported. Expanded BM-MSC were transfected with plasmid containing hIFN-γ gene (pORF-hIFN-γ) via nucleofection. Gene transfer efficiency was determined based on intracellular hIFN-γ expression via flow cytometry and was found to be at 54.28±11.34%. The in vitro expression of hIFN-γ mRNA and protein in BM-MSC were also analysed at intervals of 24 h, up to 5 days post nucleofection, via real-time PCR and ELISA, respectively. Real-Time PCR data analysis showed significant up-regulation of hIFN-γ mRNA in nucleofected BM-MSC when compared to non-transfected BM-MSC (P=0.043). BM-MSC harbouring pORF-hIFN-γ could express hIFN-γ protein in vitro. This cytokine production was achieved as high as 3.47±1.03 ng/ml after 72 hours of nucleofection. The effect of hIFN-γ produced in nucleofected BM-MSC on the proliferation of CML cell line (K562) in vitro was also investigated. K562 growth was inhibited at 61.12±16.38% after seven days of co-culture with BM-MSC expressing hIFN-γ (P=0.006). In conclusion, findings in the current study indicated that hIFN-γ produced by genetically engineered BM-MSC successfully inhibited the proliferation of K562 cells in vitro. Thus, MSC as cellular vehicle in hIFN-γ gene delivery could be further explored as a promising treatment option for CML patients

Report on extraordinary and exceptional items.

This project explores the discretionary nature of extraordianry item classification under SAS 8 (revised 1997) and investigates how SAS 8 (2000) deals with the various issues involved

Candidate List of yoUr Biomarker (CLUB): A Web-based Platform to Aid Cancer Biomarker Research

CLUB (“Candidate List of yoUr Biomarkers”) is a freely available, web-based resource designed to support Cancer biomarker research. It is targeted to provide a comprehensive list of candidate biomarkers for various cancers that have been reported by the research community. CLUB provides tools for comparison of marker candidates from different experimental platforms, with the ability to filter, search, query and explore, molecular interaction networks associated with cancer biomarkers from the published literature and from data uploaded by the community. This complex and ambitious project is implemented in phases. As a first step, we have compiled from the literature an initial set of differentially expressed human candidate cancer biomarkers. Each candidate is annotated with information from publicly available databases such as Gene Ontology, Swiss-Prot database, National Center for Biotechnology Information's reference sequences, Biomolecular Interaction Network Database and IntAct interaction. The user has the option to maintain private lists of biomarker candidates or share and export these for use by the community. Furthermore, users may customize and combine commonly used sets of selection procedures and apply them as a stored workflow using selected candidate lists. To enable an assessment by the user before taking a candidate biomarker to the experimental validation stage, the platform contains the functionality to identify pathways associated with cancer risk, staging, prognosis, outcome in cancer and other clinically associated phenotypes. The system is available at http://club.bii.a-star.edu.sg

<i>Cassia alata</i> and Its Phytochemicals: A Promising Natural Strategy in Wound Recovery

Cassia alata, a traditional herb with a global presence, is renowned for its anti-inflammatory, antibacterial, and antifungal properties, making it a go-to remedy for skin ailments. While it has demonstrated wound healing capabilities in both in vitro and in vivo studies, the precise mechanisms remain elusive. This review aims to highlight its key phytochemicals, their effects, and the mechanism of action. The compounds that have been reviewed and discussed include kaempferol, apigenin, quercetin, rhein, and rutin. These polyphenols play important roles in normal and impaired wound healing processes, encompassing hemostasis, inflammation, proliferation, and tissue remodeling