A5012181670- Wound Healing and Treatments
- Diabetic Foot Ulcer Assessment and Management
- Bacterial Genetics and Biotechnology
- Bacterial biofilms and quorum sensing
- Bacteriophages and microbial interactions
- Pressure Ulcer Prevention and Management
- Toxin Mechanisms and Immunotoxins
- Surgical site infection prevention
- Laser Applications in Dentistry and Medicine
- Orthopedic Infections and Treatments
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Dermatologic Treatments and Research
- Antibiotic Resistance in Bacteria
- Cell death mechanisms and regulation
- Diabetes and associated disorders
- Cellular transport and secretion
- Immune cells in cancer
- RNA Interference and Gene Delivery
- Antimicrobial Peptides and Activities
- Vibrio bacteria research studies
- Legume Nitrogen Fixing Symbiosis
- S100 Proteins and Annexins
- Microtubule and mitosis dynamics
- Antimicrobial Resistance in Staphylococcus
- Enzyme Structure and Function
Rush University Medical Center
2014-2024
Rush University
2024
University of California, Davis
2024
University of California, San Francisco
2006-2008
University of California, Berkeley
2002-2004
Prior studies suggest that the impaired healing seen in diabetic wounds derives from a state of persistent hyper-inflammation characterized by harmful increases inflammatory leukocytes including macrophages. However, such have focused on at later time points (day 10 or older), and very little attention has been given to dynamics macrophage responses early after injury. Given importance macrophages for process healing, we studied response during late phases wounds. Here, report injury, wound...
Diabetes mellitus, commonly referred to as diabetes, is a group of metabolic disorders characterized by chronic elevation in blood glucose levels, resulting from inadequate insulin production, defective cellular response extracellular insulin, and/or impaired metabolism. The two main types that account for most diabetics are type 1 diabetes mellitus (T1DM) and 2 (T2DM), each with their own pathophysiological features. T1D an autoimmune condition where the body’s immune system attacks...
We describe a PCR-based method for the generation of plasmid multimers that can be directly transformed into Bacillus subtilis with very high efficiency. This technique is particularly useful large libraries randomly mutagenized genes, which are required optimization enzymes by directed evolution. subjected gene coding protease subtilisin to six consecutive rounds PCR at three different levels mutagenicity. The resulting 18 populations were cloned using our multimerization protocol, and...
Infection is a major co-morbidity that contributes to impaired healing in diabetic wounds. Although impairments neutrophils have been blamed for this co-morbidity, what causes these and whether they can be overcome, remain largely unclear. Diabetic neutrophils, isolated from individuals, exhibit chemotaxis impairment but peculiar functional has ignored because it appears contradict the clinical findings which blame excessive neutrophil influx as impediment chronic ulcers. Here, we report...
Type III secreted (T3SS) effectors are important virulence factors in acute infections caused by Pseudomonas aeruginosa. PA103, a well-studied human lung isolate, encodes and secretes two effectors, ExoU ExoT. is potent cytotoxin that causes necrotic cell death. In addition, PA103 can induce death macrophages an ExoU-independent but T3SS-dependent manner. We now demonstrate ExoT both necessary sufficient to cause apoptosis HeLa cells it activates the mitochondrial/cytochrome c-dependent...
Diabetic foot ulcers are responsible for more hospitalizations than any other complication of diabetes. Bacterial infection is recognized as an important factor associated with impaired healing in diabetic ulcers. Pseudomonas aeruginosa the most frequently detected Gram-negative pathogen P. has been shown to impair wounds a manner that correlates its ability form biofilm. While majority infections biofilm associated, 33% nonbiofilm nature. prevalent all wound types, which suggests...
Objective We assessed the therapeutic effects of photobiomodulation (PBM) and adipose-derived stem cell (ADS) treatments individually together on maturation step repairing a delayed healing wound model in rats with type 1 diabetes mellitus (DM1). Research design methods randomly assigned 24 DM1 to four groups (n=6 per group). Group was control (placebo) group. In group 2, allograft human ADSs were transplanted. 3 subjected PBM (wavelength: 890 nm, peak power output: 80 W, pulse frequency:...
Persistent inflammation is a major contributor to healing impairment in diabetic chronic wounds. Paradoxically, wound environment during the acute phase of completely different because it exhibits reduced macrophage response owing inadequate expression CCL2 proinflammatory cytokine. What causes reduction wounds early after injury remains unknown. In this study, we report that contrast prolonged exposure high glucose, which makes monocytes proinflammatory, short-term glucose rapid monocyte...
Type 3 Secretion System (T3SS) is a highly conserved virulence structure that plays an essential role in the pathogenesis of many Gram-negative pathogenic bacteria, including Pseudomonas aeruginosa. Exotoxin T (ExoT) only T3SS effector protein expressed all T3SS-expressing P. aeruginosa strains. Here we show recognition leads to rapid phosphorylation cascade involving Abl / PKCδ NLRC4, which results NLRC4 inflammasome activation, culminating inflammatory responses limit infection wounds. We...
ABSTRACT The expression of many gene products required during the early stages Bacillus subtilis sporulation is regulated by sinIR operon proteins. Transcription from P1 promoter induced at end exponential growth. In vivo transcription studies suggest that induction repressed transition-state regulatory protein Hpr and phosphorylated form Spo0A. vitro DNase I footprinting confirmed Hpr, AbrB, Spo0A are trans -acting transcriptional factors bind to region . We have also determined transcribed...
ExoT is a type III secreted effector protein found in almost all strains of Pseudomonas aeruginosa and required for full virulence an animal model acute pneumonia. It comprised N-terminal domain with GTPase activating (GAP) activity towards Rho family GTPases C-terminal ADP ribosyltransferase (ADPRT) minimal synthetic substrate vitro. Consistent its as GTPase, has been shown to inhibit P. internalization into epithelial cells macrophages, disrupt the actin cytoskeleton through Rho-dependent...
Despite two centuries of reports linking alcohol consumption with enhanced susceptibility to bacterial infections and in particular gut-derived bacteria, there have been no studies or model systems assess the impact long-term exposure on ability epithelial barrier withstand infection. It is well established that acute leads reduction tight adherens junctions, which turn increases cellular permeability products, leading endotoxemia a variety deleterious effects both rodents human. We...
Abstract This study aims to investigate the combined effects of Pulsed wave low‐level laser therapy (PW LLLT) and human bone marrow mesenchymal stem cell‐conditioned medium (hBM‐MSC‐CM) on microbial flora tensiometrical properties an infected wound model with methicillin‐resistant staphylococcal aureus (MRSA) in experimental for Type 1 diabetes mellitus (TIDM). TIDM was induced rats by streptozotocin (STZ). One full‐thickness excision made backs rats. Next, were divided into following...
Pseudomonas aeruginosa is an opportunistic pathogen that requires preexisiting epithelial injury to cause acute infections. We report P. inhibits mammalian cytokinesis in a type III secretion system and exotoxin T (ExoT)-dependent manner. ExoT bifunctional effector protein contains N-terminal GTPase-activating domain C-terminal ADP-ribosyl transferase domain. Each of its domains kinetically, morphologically, mechanistically distinct The protein-mediated inhibition occurs early, likely as...
In patients with malignancy, the major barrier to achieving complete response is emergence of resistance current chemotherapeutic agents. One mechanisms by which tumour cells become resistant therapies altering cellular drug targets through mutations and/or deletions. Resistance this mechanism achieved more easily if has limited processes. We hypothesized that as Pseudomonas aeruginosa exotoxin T (ExoT) six proteins are required for cancer cell survival and proliferation, it highly unlikely...
Previously, we demonstrated that Pseudomonas aeruginosa ExoT induces potent apoptosis in host epithelial cells a manner primarily depends on its ADP-ribosyltransferase domain (ADPRT) activity. However, the mechanism underlying ExoT/ADPRT-induced remains undetermined. We now report ExoT/ADPRT disrupts focal adhesion sites, activates p38β and JNK, interferes with integrin-mediated survival signaling; causing atypical anoikis. show anoikis is mediated by Crk adaptor protein. found Crk-/-...
Pseudomonas aeruginosa is a Gram-negative opportunistic pathogen that causes serious infections in immunocompromised individuals and cystic fibrosis patients. ExoS ExoT are two homologous bifunctional Type III Secretion System (T3SS) virulence factors induce apoptosis target host cells. They possess GTPase Activating Protein (GAP) domain at their N-termini, which share ~76% homology, an ADP-ribosyltransferase (ADPRT) C-termini, non-overlapping substrates. Both the GAP ADPRT domains...
In patients with malignancy, the major barrier to achieving complete response is emergence of resistance current chemotherapeutic agents. One mechanisms by which tumour cells become resistant therapies altering cellular drug targets through mutations and/or deletions. Resistance this mechanism achieved more easily if has limited processes. We hypothesized that as Pseudomonas aeruginosa exotoxin T (ExoT) six proteins are required for cancer cell survival and proliferation, it highly unlikely...