- Tuberculosis Research and Epidemiology
- Mycobacterium research and diagnosis
- Immune Cell Function and Interaction
- Biochemical and Molecular Research
- Pneumocystis jirovecii pneumonia detection and treatment
- T-cell and B-cell Immunology
- Autophagy in Disease and Therapy
- Sirtuins and Resveratrol in Medicine
- Immune cells in cancer
- Calcium signaling and nucleotide metabolism
- Antibiotic Resistance in Bacteria
- Thermal and Kinetic Analysis
- Biosensors and Analytical Detection
- BIM and Construction Integration
- RNA modifications and cancer
- Cytokine Signaling Pathways and Interactions
- HIV Research and Treatment
- nanoparticles nucleation surface interactions
- Advanced Battery Technologies Research
- Cancer therapeutics and mechanisms
- Advancements in Battery Materials
- Electron and X-Ray Spectroscopy Techniques
- SARS-CoV-2 and COVID-19 Research
- Cell Image Analysis Techniques
- Magnesium Oxide Properties and Applications
Agency for Science, Technology and Research
2015-2024
Singapore Immunology Network
2015-2024
Monad University
2024
Graphic Era University
2024
Radiology Associates
2024
Nanyang Technological University
2017-2023
Institute of Management Technology
2023
Dean College
2023
University of Massachusetts Chan Medical School
2023
University of Ulster
2020-2023
The global burden of tuberculosis (TB) morbidity and mortality remains immense. A potential new approach to TB therapy is augment protective host immune responses. We report that the antidiabetic drug metformin (MET) reduces intracellular growth Mycobacterium (Mtb) in an AMPK (adenosine monophosphate-activated protein kinase)-dependent manner. MET controls drug-resistant Mtb strains, increases production mitochondrial reactive oxygen species, facilitates phagosome-lysosome fusion. In...
In this study, we detail a novel approach that combines bacterial fitness fluorescent reporter strains with scRNA-seq to simultaneously acquire the host transcriptome, surface marker expression, and phenotype for each infected cell. This facilitates dissection of functional heterogeneity M. tuberculosis–infected alveolar (AMs) interstitial macrophages (IMs) in vivo. We identify clusters pro-inflammatory AMs associated stressed bacteria, addition three different populations IMs heterogeneous...
The electrochemical reactivity of cations such as and into crystalline materials was investigated. ionic diffusion constant microcrystalline nanocrystalline measured by the galvanostatic intermittent titration technique. ion a 500 nm found to be approximately two orders magnitude lower than for ion. In order enable practical intercalation fabricated through combustion flame synthesis For first time, reversible host structure shown feasible. An asymmetric hybrid cell configuration utilized in...
In this paper, we report on the development of a new and broadly applicable strategy to produce thermally mendable polymeric materials, demonstrated with an epoxy/poly(ϵ-caprolactone) (PCL) phase-separated blend. The initially miscible blend composed 15.5 wt % PCL undergoes polymerization-induced phase separation during cross-linking epoxy, yielding "bricks mortar" morphology wherein epoxy exists as interconnected spheres (bricks) interpenetrated percolating matrix (mortar). fully cured...
Small-angle X-ray scattering measurements were performed on zirconium acidic aqueous solutions to investigate the structure and size of polynuclear species larger than previously identified tetrameric species. Solutions with [H+]added [OH-]added ranging from 0.0 1.0 M 0.02 M, respectively, analyzed. This study demonstrates that an octameric species, Zr8(OH)20(H2O)24Cl12, exists in equilibrium Zr4(OH)8(H2O)16Cl62+, such that, for 0.05 Zr(IV) highly ([H+]added ≥ 0.6 M), tetramer is dominant...
Alleviating the burden of tuberculosis (TB) requires an understanding genetic basis that determines emergence drug-resistant mutants. PA-824 (pretomanid) is a bicyclic nitroimidazole class compound presently undergoing phase III STAND clinical trial, despite lacking identifiable markers for drug-specific resistant Mycobacterium tuberculosis. In present study, we aimed to characterize polymorphisms spontaneously generated PA-824-resistant mutant strains by surveying drug metabolism genes...
Mycobacterium tuberculosis (Mtb) executes a plethora of immune-evasive mechanisms, which contribute to its pathogenesis, limited efficacy current therapy, and the emergence drug-resistant strains. This has led resurgence in attempts develop new therapeutic strategies/targets against (TB). We show that Mtb down-regulates sirtuin 1 (SIRT1), nicotinamide adenine dinucleotide (NAD+)-dependent deacetylase, monocytes/macrophages, TB animal models, patients with active disease. Activation SIRT1...
Metformin, the most widely administered diabetes drug, has been proposed as a candidate adjunctive host-directed therapy for tuberculosis, but little is known about its effects on human host responses to Mycobacterium tuberculosis.We investigated in vitro and vivo of metformin humans.Metformin added peripheral blood mononuclear cells from healthy volunteers enhanced cellular metabolism while inhibiting mammalian target rapamycin targets p70S6K 4EBP1, with decreased cytokine production...
The emergence of Mycobacterium tuberculosis resistant to first-line antibiotics has renewed interest in second-line antitubercular agents. Here, we aimed extend our understanding the mechanisms underlying para-aminosalicylic acid (PAS) resistance by analysis six genes folate metabolic pathway and biosynthesis thymine nucleotides (thyA, dfrA, folC, folP1, folP2, thyX) three N-acetyltransferase [nhoA, aac(1), aac(2)] among PAS-resistant clinical isolates spontaneous mutants. Mutations thyA...
Abstract Patients with type 2 diabetes (T2D) have a lower risk of Mycobacterium tuberculosis infection, progression from infection to (TB) disease, TB morality and recurrence, when being treated metformin. However, detailed mechanistic understanding these protective effects is lacking. Here, we use mass cytometry show that metformin treatment expands population memory-like antigen-inexperienced CD8 + CXCR3 T cells in naive mice, healthy individuals patients T2D. Metformin-educated increased...
BACKGROUND. Matrix metalloproteinases (MMPs) are key regulators of tissue destruction in tuberculosis (TB) and may be targets for host-directed therapy. We conducted a phase II double-blind, randomized, controlled trial investigating doxycycline, licensed broad-spectrum MMP inhibitor, patients with pulmonary TB.
Orchestration of an effective T lymphocyte response at infection sites is critical for protection against Mycobacterium tuberculosis (Mtb) infection. However, the local cell immunity landscape in human poorly defined. Tuberculous pleural effusion (TPE), caused by Mtb, characterized influx leukocytes to space, providing a platform suitable delineating complex tissue responses Mtb Using single-cell transcriptomics and receptor sequencing, we analyzed mononuclear populations paired fluid...
Significance Biosensing technologies have significant impact on medical diagnostics but difficulties in the handling of complex biospecimens, portability, and nonlinearity dynamic detection range present considerable technical bottlenecks their translation into clinical settings. Here, we nanoplasmonic electrical field-enhanced resonating device (NE 2 RD) that detects quantifies multiple biotargets from distinct specimens (i.e., saliva, serum, whole blood) with a broad linear range. Unlike...
In this study, a series of star‐shaped polycarbonates are synthesized by metal‐free organocatalytic ring‐opening polymerization benzyl chloride (BnCl) and mannose‐functionalized cyclic carbonate monomers (MTC‐BnCl MTC‐ipman) with heptakis‐(2,3‐di‐O‐acetyl)‐β‐cyclodextrin (DA‐β‐CD) as macroinitiator. The distributions compositions pendent protected mannose group (ipman) units facilely modulated varying the sequence feed ratio monomers, allowing precise control over molecular composition,...
Tuberculosis, the disease caused by bacterium M. tuberculosis , remains one of top 10 causes death worldwide. Macrophages, first cells to encounter and critical for defense against infection, are hijacked as a protected growth niche. -infected macrophages undergo metabolic reprogramming where key mitochondrial pathways modulated, but mechanisms driving this shift is unknown.
Prior immunological exposure to dengue virus can be both protective and disease-enhancing during subsequent infections with different serotypes. We provide here a systematic, longitudinal analysis of B cell, T antibody responses in the same patients. Antibody as well cell activation differentiate primary from secondary responses. Hospitalization is associated lower frequencies activated, terminally differentiated cells higher percentages effector memory CD4 cells. Patients more severe...