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Stem cell therapy has emerged as a promising approach for treatment of a number of diseases, including delayed and non-healing wounds. However, targeted systemic delivery of therapeutic cells to the dysfunctional tissues remains one formidable challenge. Herein, we present a targeted nanocarrier-mediated cell delivery method by coating the surface of the cell to be delivered with dendrimer nanocarriers modified with adhesion molecules. Infused nanocarrier-coated cells reach to destination via recognition and association with the counterpart adhesion molecules highly or selectively expressed on the activated endothelium in diseased tissues. Once anchored on the activated endothelium, nanocarriers-coated transporting cells undergo transendothelial migration, extravasation and homing to the targeted tissues to execute their therapeutic role. We now demonstrate feasibility, efficacy and safety of our targeted nanocarrier for delivery of bone marrow cells (BMC) to cutaneous wound tissues and grafted corneas and its advantages over conventional BMC transplantation in mouse models for wound healing and neovascularization. This versatile platform is suited for targeted systemic delivery of virtually any type of therapeutic cell.
Infections caused by non-tuberculous mycobacteria (NTM) is increasing wordwide. Due to the difference in treatment of NTM infections and tuberculosis, rapid species identification of mycobacterial clinical isolates is necessary for the effective management of mycobacterial diseases treatment and their control strategy. In this study, a cost-effective technique, real-time PCR coupled with high-resolution melting (HRM) analysis, was developed for the differentiation of Mycobacterial species using a novel rpoBC sequence. A total of 107 mycobacterial isolates (nine references and 98 clinical isolates) were subjected to differentiation using rpoBC locus sequence in a real-time PCR-HRM assay scheme. From 98 Mycobacterium clinical isolates, 88 species (89.7%), were identified at the species level by rpoBC locus sequence analysis as a gold standard method. M. simiae was the most frequently encountered species (41 isolates), followed by M. fortuitum (20 isolates), M. tuberculosis (15 isolates), M. kansassi (10 isolates), M. abscessus group (5 isolates), M. avium (5 isolates), and M. chelonae and M. intracellulare one isolate each. The HRM analysis generated six unique specific groups representing M. tuberculosis complex, M. kansasii, M. simiae, M. fortuitum, M. abscessus-M. chelonae group, and M. avium complex. In conclusion, this study showed that the rpoBC-based real-time PCR followed by HRM analysis could differentiate the majority of mycobacterial species that are commonly encountered in clinical specimens.
The infections due to Non-Tuberculosis Mycobacteria (NTM) are becoming an important health problem in many countries in the world. Globally, an increase in NTM infections has been reported from many countries around the world. However, limited information is available about the prevalence of NTM infections in Iran.
Homing of endothelial progenitor cells (EPC) to the ischemic tissues is a key event in neovascularization and tissue regeneration. In response to ischemic insult, injured tissues secrete several chemo-cytokines, including stromal cell-derived factor-1α (SDF-1α), which triggers mobilization and homing of bone marrow-derived EPC (BMD-EPC). We previously reported that SDF-1α-induced EPC homing is mediated by a panel of adhesion molecules highly or selectively expressed on the activated endothelium in ischemic tissues, including E-selectin. Elevated E-selectin on wound vasculature serve as docking sites for circulating EPC, which express counterpart E-selectin ligands. Here, we show that SDF-1α presented in wound tissue and released into circulation can act both locally and remotely to induce ischemic tissue endothelium and BMD-EPC to express both E-selectin and its ligands. By performing BM transplantation using E-selectin-/- and E-selectin+/+ mice as the donors and recipients respectively, we demonstrate that upregulated dual E-selectin/ligand pairs reciprocally expressed on ischemic tissue endothelium and BMD-EPC act as double-locks to secure targeted EPC- endothelium interactions by which to facilitate EPC homing and promote neovascularization and tissue repair. These findings describe a novel mechanism for BMD-EPC homing and indicate that dual E-selectin/ligand pairs may be effective targets/tools for therapeutic neovascularization and targeted cell delivery.
Enteroaggregative Escherichia coli (EAEC) has been implicated as an emerging cause of traveler's diarrhea, persistent diarrhea among children, and immunocompromised patients. The present study aimed to investigate the prevalence of antibiotic resistance, extendedspectrum β-lactamase (ESBL) production, and virulence factors of EAEC isolates obtained from Iranian children suffered from diarrhea.
The drug resistance is expected to be the most important challenge in infection control in Iran, where there is no local report or standard drug resistance monitoring system. Therefore, this study aimed to investigate the aerobic and anaerobic bacterial profile of nosocomial infections and their antibiotic resistance in Ahvaz, southwest Iran.
Methicillin-resistant Staphylococcus aureus (MRSA) is one of the most pathogens associated with health care. Molecular typing methods are vital for outbreak investigations of MRSA. The aim of this study was characterization of SCCmec, spa types and multidrug resistant of methicillin-resistant Staphylococcus aureus isolates in Ahvaz, Iran.
This study was aimed to evaluate the antibiotic resistance, biofilm formation, and genetic diversity of carbapenem-resistant Pseudomonas aeruginosa (CRPA) strains isolated from four types of nosocomial infections (NIs) including urinary tract infection (UTI), ventilator-associated pneumonia (VAP), surgical site infection (SSI), and bloodstream infection (BSI).
Purpose: Dental unit's environment and relevant instruments are a major source of infectious diseases caused by a variety of microorganisms. The application of various disinfectants is one of the most effective methods for reducing or eliminating microbial contamination. The objective of this study was to evaluate the antibacterial effects of deconex and sodium hypochlorite against bacterial taxa isolated from dental unit's environment of Ahvaz Jundishapur University of Medical Sciences, southwest of Iran. Methods: In order to evaluate the quality of disinfection, sampling was performed from different parts of 100 clinical units. For bacterial recovery and isolation, samples were enriched and cultured onto different microbiological culture media. Species identification was carried out using phenotypic and molecular methods (16S rDNA sequence analysis). In vitro activity of sodium hypochlorite and deconex were determined by the broth micro-dilution method. Results: According to conventional techniques, Bacillus spp (48%) was the most frequently encountered isolates, followed by staphylococcus spp (26%). By using both techniques, Bacillus subtilis was the most frequently encountered species (n=23, 21%), followed by Bacillus licheniformis (n=8, 7.4%), Streptococcus pneumonia (n=8, 7.4%), Staphylococcus epidermidis (n=8, 7.4%), Staphylococcus saprophyticus (n=8, 7.4%) and Staphylococcus warneri. The highest levels of contamination were observed in oral medications. The deconex had lower minimum inhibitory concentration (MIC) concentration in comparasion to sodium hypochlorite, which showed that deconex was a much more potent disinfectant. Conclusion: In conclusion, the results of the present in vitro study showed that deconex had promising results for decontamination of the tested microorganism, and it is recommended for disinfecting of dental units and environment. In this study, the high percentage of dental unit's contamination showed the need to improve disinfection procedures, sterilization systems, and the use of an appropriate concentration of deconex and sodium hypochlorite for dental units decontamination .
Obesity and cigarette smoke are major cardiovascular (CV) risk factors and, when coexisting in the same individuals, have additive/synergistic effects upon CVD. We studied the mechanisms involved in nicotine enhancement of CVD in Sprague Dawley rats with diet-induced obesity. The rats were fed either a high fat (HFD) or normal rat chow diet with or without nicotine (100 mg/L in drinking water) for 20 weeks. HFD rats developed central obesity, increased systolic blood pressure (SBP), aortic superoxide (O2-) production, and impaired endothelial nitric oxide synthase (eNOS) and endothelium-dependent relaxation to acetylcholine (EDR). Nicotine further increased SBP, O2- and impaired eNOS and EDR in obese rats. In the peritoneal macrophages from obese rats, tumor necrosis factor (TNF) α, interleukin 1β and CD36 were increased, and were further increased in nicotine-treated obese rats. Using PCR array we found that 3 of 84 target proinflammatory genes were increased by 2-4 fold in the aorta of obese rats, 11 of the target genes were further increased in nicotine-treated obese rats. HUVECs, incubated with conditioned medium from the peritoneal macrophages of nicotine treated-obese rats, exhibited reduced eNOS and increased NADPH oxidase subunits gp91phox and p22phox expression. Those effects were partially prevented by adding anti-TNFα antibody to the conditioned medium. Our results suggest that nicotine aggravates the CV effects of diet-induced obesity including the oxidative stress, vascular inflammation and endothelial dysfunction. The underlying mechanisms may involve in targeting endothelium by enhancement of macrophage-derived TNFα.
Nocardia species belong to the aerobic actinomycetes group of bacteria which are gram-positive and partially acid-fast Bacilli. These bacteria may sometimes be associated with nosocomial infections. Nocardia diseases are not required to be reported to public health authorities in Iran. Hence, the present study was designed to determine the prevalence of human Nocardia spp. in Iran by using a systematic review and meta-analysis according to the preferred reporting items for systematic reviews and meta-Analyses statement.
The global rise in drug-resistant Mycobacterium tuberculosis (M.tb), and especially the significant prevalence of isoniazid (INH)-resistance constitute a significant challenge to global health. Therefore, the present study aimed to investigate mutations in prevalent gene loci-involved in INH-resistance phenotype-among M.tb clinical isolates from southwestern Iran.
Long-term trends in freshwater bacterial community composition (BCC) and dynamics are not yet well characterized, particularly in large lake ecosystems. We addressed this gap by temporally (15 months) and spatially (6 sampling locations) characterizing BCC variation in lakes Erie and St. Clair; two connected ecosystems in the Laurentian Great Lakes.
Little is known about the impact of the ecosystem disruption and its contribution on the non-tuberculosis mycobacteria (NTM) diseases (cases) rate in Florida (FL), a state with a high prevalence of NTM in the United States. We aimed to evaluate the epidemiological distribution of NTM in FL and identify its association with extreme weather events.
Non-tuberculous mycobacterial (NTM) infections are growing concern in many countries around the globe including Iran. Among them, Mycobacterium kansasii (M. kansasii) causes both pulmonary and extra-pulmonary infections. Despite the high prevalence of M. kansasii isolates in Iran, unfortunately little is known about the epidemiological aspects of M. kansasii infection. Hence, the aim of the present study was to investigate the molecular identification, determination of subtypes variation and geographic distribution of clinical isolates of M. kansasii isolates.
Neonatal hyperoxia induces long-term systemic vascular stiffness and cardiovascular remodeling, but the mechanisms are unclear. Chemokine receptor 7 (CXCR7) represents a key regulator of vascular homeostasis and repair by modulating TGF-β1 signaling. This study investigated whether pharmacological CXCR7 agonism prevents neonatal hyperoxia-induced systemic vascular stiffness and cardiac dysfunction in juvenile rats. Newborn Sprague Dawley rat pups assigned to room air or hyperoxia (85% oxygen), received CXCR7 agonist, TC14012 or placebo for 3 weeks. These rat pups were maintained in room air until 6 weeks when aortic pulse wave velocity doppler, cardiac echocardiography, aortic and left ventricular (LV) fibrosis were assessed. Neonatal hyperoxia induced systemic vascular stiffness and cardiac dysfunction in 6-week-old rats. This was associated with decreased aortic and LV CXCR7 expression. Early treatment with TC14012, partially protected against neonatal hyperoxia-induced systemic vascular stiffness and improved LV dysfunction and fibrosis in juvenile rats by decreasing TGF-β1 expression. In vitro, hyperoxia-exposed human umbilical arterial endothelial cells and coronary artery endothelial cells had increased TGF-β1 levels. However, treatment with TC14012 significantly reduced the TGF-β1 levels. These results suggest that dysregulation of endothelial CXCR7 signaling may contribute to neonatal hyperoxia-induced systemic vascular stiffness and cardiac dysfunction.
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