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Chitin Microparticles (CMPs) Induce M1 Macrophage Activation via Intracellular TLR2 Signaling Mechanism
Title
Chitin Microparticles (CMPs) Induce M1 Macrophage Activation via Intracellular TLR2 Signaling Mechanism.
Creator
Davis, Spring, Shibata, Yoshimi, Florida Atlantic University, Charles E. Schmidt College of Medicine, Department of Biological Sciences
Abstract/Description
Chitin Microparticles (CMPs, 1-10um), a special form of the ubiquitous and nontoxic polysaccharide Chitin (GlcNAc), is capable of inducing a switch in macrophages from the wound-healing M2 phenotype to the classically activated pro-inflammatory M1 phenotype; which has therapeutic implications in allergy and cancer. We hypothesized that TLR2 forms a complex with CMPs and Chitin-Binding Proteins (CBPs) at the surface of peritoneal macrophages and remains with that complex after internalization...
Show moreChitin Microparticles (CMPs, 1-10um), a special form of the ubiquitous and nontoxic polysaccharide Chitin (GlcNAc), is capable of inducing a switch in macrophages from the wound-healing M2 phenotype to the classically activated pro-inflammatory M1 phenotype; which has therapeutic implications in allergy and cancer. We hypothesized that TLR2 forms a complex with CMPs and Chitin-Binding Proteins (CBPs) at the surface of peritoneal macrophages and remains with that complex after internalization to initiate downstream signaling events, leading to the production of the M1 cytokine, TNFalpha. Our results from experiments performed in RAW 264.7 cells show that TLR2 and TLR1, but not TLR6, are associated with the CMP binding fraction, and that both TLR1 and TLR2 might be important for M1 activation as a result of CMP phagocytosis. This project sheds light on CMP as a potential therapeutic agent and provides more evidence for a phagocytosis-dependent TLR2 signaling pathway.
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Date Issued
2016
PURL
http://purl.flvc.org/fau/fd/FA00004762, http://purl.flvc.org/fau/fd/FA00004762
Subject Headings
Biopharmaceutics., Macrophages., Cell receptors., Ligands (Biochemistry), High performance processors.
Format
Document (PDF)
DEVELOPING PLASMA-BASED DIAGNOSTICS: FROM PANCREATIC DUCTAL ADENOCARCINOMA TO HIV
Title
DEVELOPING PLASMA-BASED DIAGNOSTICS: FROM PANCREATIC DUCTAL ADENOCARCINOMA TO HIV.
Creator
Makler, Amy, Asghar, Waseem, Florida Atlantic University, Department of Biological Sciences
Abstract/Description
Plasma-based diagnostics are ideal for detecting a variety of diseases because they offer a method of detection that is minimally invasive, readily available, and easy to use for monitoring patients as they progress through a disease or respond to treatment. The only serum marker for PDAC is CA19-9 which lacks specificity, has limited sensitivity, and is unreliable for early detection. It is therefore of great importance to develop a diagnostic that is viable for screening and early detection...
Show morePlasma-based diagnostics are ideal for detecting a variety of diseases because they offer a method of detection that is minimally invasive, readily available, and easy to use for monitoring patients as they progress through a disease or respond to treatment. The only serum marker for PDAC is CA19-9 which lacks specificity, has limited sensitivity, and is unreliable for early detection. It is therefore of great importance to develop a diagnostic that is viable for screening and early detection. Exosomal miRNA were determined via bioinformatics analyses and then examined in PDAC cell lines to identify markers with greatest potential. These markers were then examined in plasma from PDAC patients and control groups. Four markers, miR-93-5p, miR-339-3p, miR-425-5p, and miR-425-3p, emerged as the most viable biomarker panel with the ability to detect PDAC in 100% of the early stages (N=5) compared to CA19-9 which showed increased levels in only one patient with early stage PDAC. Additionally, the diagnostic has a specificity of 80% and a sensitivity of 94.7%, making it comparable to CA19-9, and may even be beneficial for use in conjunction with CA19-9. A plasma-based diagnostic was also developed for multi-strain HIV-1 detection utilizing the loop-mediated isothermal amplification (LAMP) method. LAMP primers were developed against the integrase and vpr regions of the HIV-1 genome. They were tested first in cultured HIV samples and then examined for their ability to amplify HIV-1 subtypes A-G. The integrase primer set provided a reliable means of diagnosing all 55 strains and isolates in under 30 minutes, whereas vpr was inconsistent and exhibited high variability in detecting the HIV subtypes. Our limit of detection for B-subtype with integrase was 30 viral copies/reaction. This could provide the basis for a novel, point-of-care diagnostic for use in underdeveloped regions.
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Date Issued
2023
PURL
http://purl.flvc.org/fau/fd/FA00014141
Subject Headings
Plasma, Biomarkers, Carcinoma, Pancreatic Ductal, HIV-1, Diagnosis
Format
Document (PDF)
Protective mechanism of Sulindac against animal model of ischemic stroke
Title
Protective mechanism of Sulindac against animal model of ischemic stroke.
Creator
Modi, Jigar P., Charles E. Schmidt College of Medicine, Department of Biological Sciences
Abstract/Description
The Effect of Sulindac was studied on an animal model of ischemic stroke. Sulindac, a non steroid anti inflammatory drug (NSAID) could protect cell death due to hypoxia/reoxygenation. This drug was given 2 days before and 24 hrs after ischemia until animals were sacrificed on 3rd or 11th day. Infarct size was measured for these animals. Sulindac induced Hsp 27 in ischemic penumbra and core on Day 3 & 11 with uncoated nylon suture which shows its cell-survival and anti-apoptotic activity. Also...
Show moreThe Effect of Sulindac was studied on an animal model of ischemic stroke. Sulindac, a non steroid anti inflammatory drug (NSAID) could protect cell death due to hypoxia/reoxygenation. This drug was given 2 days before and 24 hrs after ischemia until animals were sacrificed on 3rd or 11th day. Infarct size was measured for these animals. Sulindac induced Hsp 27 in ischemic penumbra and core on Day 3 & 11 with uncoated nylon suture which shows its cell-survival and anti-apoptotic activity. Also, it increased expression of cell survival markers such as Akt, Bcl2 & Grp 78 in ischemic penumbra and core. With silicon suture it reduced expression of Hsp 27 in ischemic penumbra and core, alleviating cell stress and having pro-survival and anti-stress effects. In conclusion sulindac may have excellent potential as neuro protective agent against oxidative stress in cerebral ischemia.
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Date Issued
2011
PURL
http://purl.flvc.org/FAU/3333056
Subject Headings
Apoptosis, Biochemical markers, Diagnostic use, Oxidation reduction reaction, Cerebral ischemia, Prevention
Format
Document (PDF)
Influence of sex hormones and genetic predisposition in dry eye in Sjèogren's syndrome
Title
Influence of sex hormones and genetic predisposition in dry eye in Sjèogren's syndrome: a new clue to the immunopathogenesis of dry eye disease.
Creator
Mostafa, Safinaz, Charles E. Schmidt College of Medicine, Department of Biological Sciences
Abstract/Description
Sjèogren's syndrome (S) is a chronic autoimmune disease characterized by ocular and oral dryness and primarily affects post menopausal women. In the present study we investigated the time course of lymphocytic infiltration, apoptosis, caspase-3 activity and different cytokines levels in the lacrimal glands of both genetically predisposed and control mice to elucidate immunopathological mechanism leading to dry eye. The results of our experiments showed that ovariectomy accelerated...
Show moreSjèogren's syndrome (S) is a chronic autoimmune disease characterized by ocular and oral dryness and primarily affects post menopausal women. In the present study we investigated the time course of lymphocytic infiltration, apoptosis, caspase-3 activity and different cytokines levels in the lacrimal glands of both genetically predisposed and control mice to elucidate immunopathological mechanism leading to dry eye. The results of our experiments showed that ovariectomy accelerated pathological findings of SS by increasing lympocytic infiltration, cytokine production, lacrimal gland cell death and cleaved caspase-3 activity, and these effects were more pronounced and persistent in the genetically predisposed mouse model of SS. In addition, we observed that lymphocytic infiltration occurred earlier compared to apoptosis which may perpetuate immune mediated destruction of lacrimal epithelial cells. Furthermore, treatment with physioloigical doses of 17-B Estradiol (E2) or DIhydrotestosterone (DHT) prevented all these pathological events observed after ovariectomy.
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Date Issued
2011
PURL
http://purl.flvc.org/FAU/3353086
Subject Headings
Dry eye syndromes, Immunological aspects, Sjèogren's syndrome, Immunological aspects, Disease susceptibility, Human genome, Medical genetics
Format
Document (PDF)