Evaluating the potential of off-the-shelf engineered mesenchymal stem cells for targeted Hepatocellular Carcinoma treatment: A multisite proof-of-concept study.

Although combining 5-fluorouracil (5-FU) and Interferon-beta (IFNb) improves response rates in Hepatocellular Carcinoma (HCC), the outcomes remain suboptimal. This study investigates the feasibility of using highly transfected Mesenchymal Stem Cells (MSCs) to deliver a chemotherapeutic (5-FU) and an immunomodulator (IFNb) for localized HCC treatment. Considering the crucial role of cold-chain transportation in off-the-shelf allogeneic therapy, the study also assesses the quality and efficacy of frozen-thawed engineered MSCs, simulating a multisite study process.

Extracellular Vesicle-Enriched miRNA-Biomarkers Show Improved Utility for Detecting Alzheimer's Disease Dementia and Medial Temporal Atrophy.

Background: Emerging diagnostic modalities suggest that miRNA profiles within extracellular vesicles (EVs) isolated from peripheral blood specimens may provide a non-invasive diagnostic alternative for dementia and neurodegenerative disorders. Given that EVs confer a protective environment against miRNA enzymatic degradation, the miRNAs enriched in the EV fraction of blood samples could serve as more stable and clinically relevant biomarkers compared to those obtained from serum.

Objective: To compare miRNAs isolated from EVs versus serum in blood taken from Alzheimer's disease (AD) dementia patients and control cohorts.

Cryopreservation does not change the performance and characteristics of allogenic mesenchymal stem cells highly over-expressing a cytoplasmic therapeutic transgene for cancer treatment.

Background: Mesenchymal stem cells (MSCs) driven gene directed enzyme prodrug therapy is a promising approach to deliver therapeutic agents to target heterogenous solid tumours. To democratize such a therapy, cryopreservation along with cold chain transportation is an essential part of the logistical process and supply chain. Previously, we have successfully engineered MSCs by a non-viral DNA transfection approach for prolonged and exceptionally high expression of the fused transgene cytosine deaminase, uracil phosphoribosyl transferase and green fluorescent protein (CD::UPRT::GFP).

Development and validation of a circulating microRNA panel for the early detection of breast cancer.

Background: Mammography is widely used for breast cancer screening but suffers from a high false-positive rate. Here, we perform the largest comprehensive, multi-center study to date involving diverse ethnic groups, for the identification of circulating miRNAs for breast cancer screening.

Methods: This study had a discovery phase (n = 289) and two validation phases (n = 374 and n = 379).

Advances in quantifying circulatory microRNA for early disease detection.

Precision preventive healthcare aims to improve patient health by integrating preventive measures with early disease detection for timely intervention with precision medicine. Key to the delivery of preventive healthcare is the clinical adoption of novel assays that enable early disease detection. Such assays, typically based on biomarkers such as microRNAs (miRNAs) from liquid biopsy or excreta, are entering clinical practice after years of clinical development and validation.

Development of a microRNA Panel for Classification of Abnormal Mammograms for Breast Cancer.

Mammography is extensively used for breast cancer screening but has high false-positive rates. Here, prospectively collected blood samples were used to identify circulating microRNA (miRNA) biomarkers to discriminate between malignant and benign breast lesions among women with abnormal mammograms. The Discovery cohort comprised 72 patients with breast cancer and 197 patients with benign breast lesions, while the Validation cohort had 73 and 196 cancer and benign cases, respectively.

Development and validation of a serum microRNA biomarker panel for detecting gastric cancer in a high-risk population.

Objective: An unmet need exists for a non-invasive biomarker assay to aid gastric cancer diagnosis. We aimed to develop a serum microRNA (miRNA) panel for identifying patients with all stages of gastric cancer from a high-risk population.

Design: We conducted a three-phase, multicentre study comprising 5248 subjects from Singapore and Korea.

Development of a serum miRNA panel for detection of early stage non-small cell lung cancer.

Minimally invasive testing for early detection of lung cancer to improve patient survival is a major unmet clinical need. This study aimed to develop and validate a serum multi-microRNA (multimiR) panel as a minimally invasive test for early detection of nonsmall cell lung cancer (NSCLC) regardless of smoking status, gender, and ethnicity. Our study included 744 NSCLC cases and 944 matched controls, including smokers and nonsmokers, male and female, with Asian and Caucasian subjects.

Evaluating the Use of microRNA Blood Tests for Gastric Cancer Screening in a Stratified Population-Level Screening Program: An Early Model-Based Cost-Effectiveness Analysis.

Objectives: To evaluate cost-effectiveness of a novel screening strategy using a microRNA (miRNA) blood test as a screen, followed by endoscopy for diagnosis confirmation in a 3-yearly population screening program for gastric cancer.

Methods: A Markov cohort model has been developed in Microsoft Excel 2016 for the population identified to be at intermediate risk (Singaporean men, aged 50-75 years with Chinese ethnicity). The interventions compared were (1) initial screening using miRNA test followed by endoscopy for test-positive individuals and a 3-yearly follow-up screening for test-negative individuals (proposed strategy), and (2) no screening with gastric cancer being diagnosed clinically (current practice).

A facile and scalable in production non-viral gene engineered mesenchymal stem cells for effective suppression of temozolomide-resistant (TMZR) glioblastoma growth.

Background: Mesenchymal stem cells (MSCs) serve as an attractive vehicle for cell-directed enzyme prodrug therapy (CDEPT) due to their unique tumour-nesting ability. Such approach holds high therapeutic potential for treating solid tumours including glioblastoma multiforme (GBM), a devastating disease with limited effective treatment options. Currently, it is a common practice in research and clinical manufacturing to use viruses to deliver therapeutic genes into MSCs.

A highly efficient non-viral process for programming mesenchymal stem cells for gene directed enzyme prodrug cancer therapy.

Mesenchymal stem cells (MSCs) driven gene-directed enzyme prodrug therapy has emerged as a potential strategy for cancer treatment. The tumour-nesting properties of MSCs enable these vehicles to target tumours and metastases with effective therapies. A crucial step in engineering MSCs is the delivery of genetic material with low toxicity and high efficiency.

Microbial astaxanthin biosynthesis: recent achievements, challenges, and commercialization outlook.

Astaxanthin is a natural pigment, known for its strong antioxidant activity and numerous health benefits to human and animals. Its antioxidant activity is known to be substantially greater than β-carotene and about a thousand times more effective than vitamin E. The potential health benefits have generated a growing commercial interest, and the escalating demand has prompted the exploration of alternative supply chain.

Serves As a Gateway for Identifying Sesquiterpene Biosynthetic Enzymes in Higher Fungi.

Terpenoids constitute a structurally diverse group of natural products with wide applications in the pharmaceutical, nutritional, flavor and fragrance industries. Fungi are known to produce a large variety of terpenoids, yet fungal terpene synthases remain largely unexploited. Here, we report the sesquiterpene network and gene clusters of the black poplar mushroom Among 11 putative sesquiterpene synthases (STSs) identified in its genome, nine are functional, including two novel synthases producing viridiflorol and viridiflorene.

Polymer-Based Precipitation of Extracellular Vesicular miRNAs from Serum Improve Gastric Cancer miRNA Biomarker Performance.

Circulating miRNAs are promising liquid biopsy biomarkers for noninvasive cancer detection. However, detection of subtle, but meaningful differences in circulating miRNA quantities between diseased and healthy samples remains a key challenge in clinical settings because biomarker signal/noise ratios are often low. Because extracellular vesicles (EVs) are key sources of circulating miRNAs in serum, it was hypothesized that isolating EVs would enrich miRNA biomarkers, leading to enhanced diagnostic ability and improved biomarker performance.

Strategies for the Biosynthesis of Pharmaceuticals and Nutraceuticals in Microbes from Renewable Feedstock.

Backgrounds: Abundant and renewable biomaterials serve as ideal substrates for the sustainable production of various chemicals, including natural products (e.g., pharmaceuticals and nutraceuticals).

Combining Circulating MicroRNA and NT-proBNP to Detect and Categorize Heart Failure Subtypes.

Background: Clinicians need improved tools to better identify nonacute heart failure with preserved ejection fraction (HFpEF).

Objectives: The purpose of this study was to derive and validate circulating microRNA signatures for nonacute heart failure (HF).

Methods: Discovery and validation cohorts (N = 1,710), comprised 903 HF and 807 non-HF patients from Singapore and New Zealand (NZ).

Enhanced transfection of a macromolecular lignin-based DNA complex with low cellular toxicity.

Cationic polymers remain attractive tools for non-viral gene transfer. The effectiveness of these vectors rely on the ability to deliver plasmid DNA (pDNA) into the nucleus of cells. While we have previously demonstrated the potential of Lignin-PGEA-PEGMA as a non-viral gene delivery vector, alterations of cellular phenotype and cytotoxicity were observed post transfection.

Multidimensional heuristic process for high-yield production of astaxanthin and fragrance molecules in Escherichia coli.

Optimization of metabolic pathways consisting of large number of genes is challenging. Multivariate modular methods (MMMs) are currently available solutions, in which reduced regulatory complexities are achieved by grouping multiple genes into modules. However, these methods work well for balancing the inter-modules but not intra-modules.

Trehalose significantly enhances the recovery of serum and serum exosomal miRNA from a paper-based matrix.

The preservation of nucleic acids from clinical samples is critical to facilitate accurate molecular diagnosis. The use of a paper matrix, Flinders Technology Associates (FTA) Elute cards, to archive DNA and viral RNA is well-documented. However, the feasibility of FTA Elute cards for archiving serum and serum exosomal microRNAs (miRNAs) remains unclear.

A "plug-n-play" modular metabolic system for the production of apocarotenoids.

Apocarotenoids, such as α-, β-ionone, and retinol, have high commercial values in the food and cosmetic industries. The demand for natural ingredients has been increasing dramatically in recent years. However, attempts to overproduce β-ionone in microorganisms have been limited by the complexity of the biosynthetic pathway.

Establishing multiple omics baselines for three Southeast Asian populations in the Singapore Integrative Omics Study.

The Singapore Integrative Omics Study provides valuable insights on establishing population reference measurement in 364 Chinese, Malay, and Indian individuals. These measurements include > 2.5 millions genetic variants, 21,649 transcripts expression, 282 lipid species quantification, and 284 clinical, lifestyle, and dietary variables.

Revalorizing Lignocellulose for the Production of Natural Pharmaceuticals and Other High Value Bioproducts.

Lignocellulose is the most abundant renewable natural resource on earth and has been successfully used for the production of biofuels. A significant challenge is to develop cost-effective, environmentally friendly and efficient processes for the conversion of lignocellulose materials into suitable substrates for biotransformation. A number of approaches have been explored to convert lignocellulose into sugars, e.

Multienzyme Biosynthesis of Dihydroartemisinic Acid.

One-pot multienzyme biosynthesis is an attractive method for producing complex, chiral bioactive compounds. It is advantageous over step-by-step synthesis, as it simplifies the process, reduces costs and often leads to higher yield due to the synergistic effects of enzymatic reactions. In this study, dihydroartemisinic acid (DHAA) pathway enzymes were overexpressed in , and whole-cell biotransformation of amorpha-4,11-diene (AD) to DHAA was demonstrated.