A5009499042- Cancer Immunotherapy and Biomarkers
- Clostridium difficile and Clostridium perfringens research
- RNA Interference and Gene Delivery
- Advanced biosensing and bioanalysis techniques
- Cancer Cells and Metastasis
- Advanced Polymer Synthesis and Characterization
- Gut microbiota and health
- Polymer Surface Interaction Studies
- Ferroptosis and cancer prognosis
- Liver physiology and pathology
- Immune cells in cancer
- Hepatocellular Carcinoma Treatment and Prognosis
- Viral gastroenteritis research and epidemiology
- Nanoparticle-Based Drug Delivery
- Inhalation and Respiratory Drug Delivery
- Pancreatic and Hepatic Oncology Research
- Viral Infections and Vectors
- Hydrogels: synthesis, properties, applications
- Cholangiocarcinoma and Gallbladder Cancer Studies
- Tuberculosis Research and Epidemiology
- Mosquito-borne diseases and control
- Cancer Genomics and Diagnostics
- DNA and Nucleic Acid Chemistry
- Cancer, Stress, Anesthesia, and Immune Response
- Gastrointestinal motility and disorders
Pacific Northwest National Laboratory
2023
Greenslopes Private Hospital
2017-2022
The University of Queensland
2017-2022
Gallipoli Medical Research Foundation
2018-2022
Texas A&M University
2011-2020
Patan Academy of Health Sciences
2017
Oxford University Clinical Research Unit Nepal
2017
Washington University in St. Louis
2013
Tilganga Institute of Ophthalmology
1982
Clostridium difficile spores must germinate in vivo to become actively growing bacteria order produce the toxins that are necessary for disease. C. vitro response certain bile acids and glycine. In other sporulating bacteria, proteins embedded within inner membrane of spore sense presence germinants trigger release Ca++-dipicolinic acid (Ca++-DPA) from core subsequent hydrolysis cortex, a specialized peptidoglycan. Based upon homology searches known germinant receptors spore-forming likely...
Comparative studies of bulk samples hydrolytically degradable poly(lactic acid) (PLA) vs core–shell block copolymer micelles having PLA cores revealed remarkable acceleration in the proteinase K enzymatic hydrolysis nanoparticulate forms and demonstrated that even with amidation-based shell cross-linking core domain remained accessible. Kinetic analyses by 1H NMR spectroscopy showed less than 20% lactic acid released from enzymatically catalyzed poly(l-lactic bulk, whereas ca. 70% degraded...
The global burden of hepatocellular carcinoma (HCC), one the frequent causes cancer-related deaths worldwide, is rapidly increasing partly due to limited treatment options available for this disease and recurrence therapy resistance. Immune checkpoint inhibitors that are proved be beneficial in advanced melanoma other cancer types currently clinical trials HCC. These ongoing testing efficacy safety a few select checkpoints Similar observations cancers, these immune blockade treatments as...
ABSTRACT Clostridium difficile spore germination is essential for colonization and disease. The signals that initiate C. are a combination of taurocholic acid (a bile acid) glycine. Interestingly, the chenodeoxycholic class (CDCA) acids competitively inhibit acid-mediated germination, suggesting compounds could be developed into drugs prophylactically prevent infection or reduce recurring However, recent report called question utility such strategy to by describing strains germinated in...
Clostridium difficile spore germination is critical for the transmission of disease. C. spores germinate in response to cholic acid derivatives, such as taurocholate (TA), and amino acids, glycine or alanine. Although receptor with which bile acids are recognized (germinant receptor) known, co-germinant has remained elusive. Here, we used EMS mutagenesis generate mutants altered requirements co-germinant, similar strategy previously identify germinant receptor, CspC. Surprisingly, identified...
Paclitaxel-loaded shell cross-linked polymeric nanoparticles having an enzymatically and hydrolytically degradable poly(lactic acid) core a glutathione-responsive disulfide poly(oligoethylene glycol)-containing corona were constructed in aqueous solution investigated for their stimuli-responsive release of the embedded therapeutics vitro cytotoxicity. Paclitaxel from PBS buffer was accelerated presence glutathione at both pH 5.5 7.4, reaching ca. 65% cumulative drug after 8 d, whereas only...
Development of multifunctional nanostructures that can be tuned to codeliver multiple drugs and diagnostic agents diseased tissues is great importance. Hierarchically assembled theranostic (HAT) based on anionic cylindrical shell cross-linked nanoparticles cationic knedel-like (cSCKs) have recently been developed by our group deliver siRNA intracellularly undergo radiolabeling. In the current study, paclitaxel, a hydrophobic anticancer drug, successfully loaded into spherical components...
Antibiotic resistance is one of the world's greatest public health challenges and adjunct probiotic therapies are strategies that could lessen this burden. Clostridioides difficile infection (CDI) a prime example where decrease disease incidence through prevention. Human-derived Lactobacillus reuteri produces antimicrobial compound reuterin known to prevent C. colonization antibiotic-treated fecal microbial communities. However, mechanism inhibition unclear. We show inhibits outgrowth from...
Dual functional hierarchically assembled nanostructures, with two unique functions of carrying therapeutic cargo electrostatically and maintaining radiolabeled imaging agents covalently within separate component building blocks, have been developed via the supramolecular assembly several spherical cationic shell cross-linked nanoparticles clustered around a central anionic cylinder. The shells hydrophobic core domain cylindrical nanostructure assemblies were utilized to complex negatively...
In this work, multifunctional biosynthetic hybrid nanostructures were prepared and studied for their potential utility in the recognition inhibition of mRNA sequences inducible nitric oxide synthase (iNOS), which are overexpressed at sites inflammation, such as cases acute lung injury. Shell cross-linked knedel-like polymer nanoparticles (SCKs) that present peptide nucleic acids, binding to complementary mRNAs, cell penetrating peptides (CPPs), gain entry, along with fluorescent labels...
Hepatocellular carcinoma (HCC) is the most common type of primary hepatic malignancy. HCC one leading causes cancer deaths worldwide. The oral multi-tyrosine kinase inhibitor Sorafenib standard first-line therapy in patients with advanced unresectable HCC. Despite significant survival benefit post treatment Sorafenib, many had progressive disease as a result acquiring drug resistance. Circumventing resistance to by exploring and targeting possible molecular mechanisms pathways an area active...
In this work, degradable cationic shell cross-linked knedel-like (deg-cSCK) nanoparticles were developed as an alternative platform to replace similar nondegradable cSCK that have been utilized for nucleic acids delivery. An amphiphilic diblock copolymer poly(acrylamidoethylamine)90-block-poly(dl-lactide)40 (PAEA90-b-PDLLA40) was synthesized, self-assembled in aqueous solution, and using a hydrolyzable cross-linker afford deg-cSCKs with average core diameter of 45 ± 7 nm. These fluorescently...
Functionally-responsive amphiphilic core-shell nanoscopic objects, capable of either complete or partial inversion processes, were produced by the supramolecular assembly pH-responsive block copolymers, without with covalent crosslinking shell layer, respectively. A new type well-defined, dual-functionalized boronic acid- and amino-based diblock copolymer poly(3-acrylamidophenylboronic acid)(30)-block-poly(acrylamidoethylamine)(25) (PAPBA(30)-b-PAEA(25)) was synthesized sequential reversible...
Hepatocellular carcinoma (HCC) is the fastest growing cause of cancer‑related deaths globally. Epithelial‑to‑mesenchymal transition (EMT) a cellular process that confers HCC tumor cells with ability to evade immune system. Immune escape in most tumors, including HCC, controlled by checkpoint molecules. The aim present study was investigate association between EMT and identify novel therapeutic targets for HCC. An vitro model reversible utilized based on cytokine necrosis factor (TNF)‑α...
Gallbladder cancer (GBC) is one of the most common and aggressive biliary tract cancers with a dismal prognosis. Ongoing clinical trials are evaluating few selected immune checkpoint inhibitors (ICIs) as monotherapy for treatment GBC patients. However, only subset patients benefits from these treatments. To improve ICI therapy response, molecular mechanisms that confer resistance to (IC) blockade needs be explored. Epithelial-to-mesenchymal transition (EMT) program stem cells (CSCs) have...
Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer with a high mortality rate. Epithelial-to-mesenchymal transition (EMT) confers cells immune evasive ability by modulating expression checkpoints in many cancers. Thus, aim our study to examine interplay between EMT and checkpoint molecules HCC. A reversible model was utilised transforming growth factor (TGF)-β1 as an inducer for HCC cell lines Hep3B PLC/PRF/5. were treated TGF-β1 72 h status examined. In addition,...
Cholangiocarcinoma (CCA) is a hepatobiliary malignancy associated with steadily increasing incidence and poor prognosis. Ongoing clinical trials are assessing the effectiveness safety of few immune checkpoint inhibitors (ICIs) in CCA patients. However, these ICI treatments as monotherapies may be effective for proportion patients CCA. The prevalence distribution other checkpoints (ICs) remain unclear. In this pilot study, we screened databases expression 19 ICs assessed prognostic...
Acute lung injury (ALI) is a complex syndrome with many aetiologies, resulting in the upregulation of inflammatory mediators host, followed by dyspnoea, hypoxemia and pulmonary oedema. A central mediator inducible nitric oxide synthase (iNOS) that drives production NO continued inflammation. Thus, it useful to have diagnostic therapeutic agents for targeting iNOS expression. One general approach target precursor mRNA antisense nucleic acids. Peptide acids (PNAs) advantages make them an ideal...