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Attenuation of Staphylococcal enterotoxin-B (SEB)-induced lung injury (ALI) by resveratrol results from miR-193a down-regulation and alterations in metabolic profile
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Abstract<p>Resveratrol, (RES), a phytoalexin, is well-known for its anti-inflammatory and anti-oxidant properties. SEB, a superantigen, is known to trigger ALI and cause mortality. In the current study, we tested the effect of RES in a dual-dose model of SEB exposure that triggers ALI and causes 100% mortality in C3H/HeJ-mice. The data revealed RES attenuated SEB-induced ALI and prevented mortality. Forty eight hours post-SEB exposure, lung-infiltrating mononuclear cells were tested for microRNA expression profile to determine the epigenetic regulation by resveratrol. SEB-activated splenocytes were pre-treated with 50 μM of RES or vehicle for metabolic profile analysis by measuring oxygen consumption rate (OCR) and extracellular acidification rate (ECAR). We also noted significant decline in miR-193a in the lungs of RES-treated SEB group, which targeted and caused an increase in TGFβ2 and TGFβR3, potent inhibitors of T-cell proliferation, by using RT-PCR and validation by transfection studies. RES-induced downregulation of miR-193a also influenced the activity of mechanistic target of rapamycin (mTOR) as well as pyruvate kinase muscle isozyme2 (PKM2) genes, and caused RES-treated SEB-activated T cells to be quiescent metabolically in comparison to the energetic vehicle-treated SEB-activated T cells. Together, RES caused inhibition in the proliferation of SEB-activated T-cells by alterations in miR expression and metabolic profiles. (Supported by NIH grants P01AT003961, R01AT006888, R01ES019313, R01MH094755, P20GM103641 and R01AI129788).</p>
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Publication Date
Wed Mar 07 2018
Journal Name
Journal Of Cellular And Molecular Medicine
Resveratrol protects mice against SEB‐induced acute lung injury and mortality by miR‐193a modulation that targets TGF‐β signalling
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Abstract<p>Staphylococcal enterotoxin B (SEB) is a potent superantigen produced by <italic>Staphylococcus aureus</italic> that triggers a strong immune response, characterized by cytokine storm, multi‐organ failure, and often death. When inhaled, SEB can cause acute lung injury (ALI) and respiratory failure. In this study, we investigated the effect of resveratrol (RES), a phytoallexin, on SEB‐driven ALI and mortality in mice. We used a dual‐exposure model of SEB in C3H/HeJ mice, which caused 100% mortality within the first 5 days of exposure, and treatment with RES resulted in 100% survival of these mice up to 10 days post‐SEB exposure. RES reduced the inflammatory cytokines in the serum an</p> ... Show More
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Publication Date
Mon May 01 2017
Journal Name
The Journal Of Immunology
Protective effects of Δ9-Tetrahydrocannabinol (THC) results from alteration in lung dysbiosis mediated by SEB-induced acute lung injury
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Abstract<p>Inhalation of Staphylococcal Enterotoxin B (SEB) is known to induce acute lung injury (ALI) and studies from our laboratory have shown that THC, a psychoactive ingredient found in Cannabis sativa, can attenuate the ALI. In the current study, we investigated the role played by lung microbiota in ALI with or without THC treatment. A dual-dose of SEB was given to C3H/HeJ mice, which were then treated either with vehicle or THC. SEB-administration caused ALI and 100% mortality while all THC-treated mice survived and suppressed the inflammation in the lungs. Furthermore, lung microbiota was collected and 16S rRNA sequencing was performed. The data were analyzed to determine the alpha and b</p> ... Show More
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Publication Date
Fri Feb 24 2023
Journal Name
Frontiers In Pharmacology
Resveratrol attenuates staphylococcal enterotoxin B-activated immune cell metabolism via upregulation of miR-100 and suppression of mTOR signaling pathway
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Acute Respiratory Distress Syndrome (ARDS) is triggered by a variety of insults, such as bacterial and viral infections, including SARS-CoV-2, leading to high mortality. In the murine model of ARDS induced by Staphylococcal enterotoxin-B (SEB), our previous studies showed that while SEB triggered 100% mortality, treatment with Resveratrol (RES) completely prevented such mortality by attenuating inflammation in the lungs. In the current study, we investigated the metabolic profile of SEB-activated immune cells in the lungs following treatment with RES. RES-treated mice had higher expression of miR-100 in the lung mononuclear cells (MNCs), which targeted mTOR, leading to its decreased expression. Also, Single-cell RNA-seq (scRNA seq)

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Publication Date
Wed May 01 2019
Journal Name
The Journal Of Immunology
Protective effect of resveratrol on the integrity of alveolar and intestinal epithelial barrier in SEB-induced acute lung injury
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Abstract<p>Acute lung injury (ALI) is a state of inflammation that breaks down the lung endothelial and epithelial cell barriers. In the current study, we investigated the role of resveratrol (RES) in regulating the expression and functions of tight junction proteins (TJP) in epithelial cell responses following exposure to this superantigen. To this end, C3H mice were given resveratrol orally twice prior to intranasal challenge with lethal SEB doses. 16S rRNA results showed that there were microbes transported in the blood in addition to the lung and colonic tissues. For this purpose, we used a reporter E. coli-GFP labeled bacterium to monitor and examine the viability of this bacterium in case </p> ... Show More
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Publication Date
Tue May 01 2018
Journal Name
The Journal Of Immunology
Marijuana THC treatment led to decreased metabolic functions of Staphylococcal enterotoxin B-activated lymphocytes
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Abstract<p>Studies from our laboratory have shown that Δ9-Tetrahydrocannabinol (THC), an ingredient found in marijuana plant Cannabis sativa, can attenuate acute lung injury induced by Staphylococcus enterotoxin B (SEB). In the current study, we investigated the role of THC on the metabolism of SEB-activated lymphocytes. To this end, we determined metabolic potential of SEB-activated lymphocytes treated with vehicle or THC by performing the Cell Mito Stress Test. The oxygen consumption rate (OCR) in THC-treated cells was decreased when compared to vehicle-treated group whereas the extracellular acidification rate (ECAR) was similar in both the groups. Specifically, electron transport chain inhi</p> ... Show More
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Publication Date
Tue Jun 16 2020
Journal Name
Frontiers In Pharmacology
Administration of Δ9‐Tetrahydrocannabinol (THC) Post‐Staphylococcal Enterotoxin B Exposure Protects Mice From Acute Respiratory Distress Syndrome and Toxicity
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Publication Date
Tue Apr 01 2008
Journal Name
Journal Of The Faculty Of Medicine Baghdad
Down-Regulation of Progesterone hormone in Recurrent pregnancy Loss
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Background:
Progesterone hormone is important in the preparation for and in maintaining of pregnancy through different mechanisms but mainly by shifting the balance from Th1 to Th2 mediated
immunity to avoid rejection of the fetus; in this study we tried to find out whether there is a relation between the level of the expression of progesterone and its stimulant HCG hormone and recurrent pregnancy loss (RPL).
Patients and Methods:
Immunohistochemistry technique was performed to detect and determine the expression of progesterone and HCG hormones using paraffin embedded sections of curate samples obtained from 40 women, who where divided into three groups: 24 women with RPL, 10 women with abortion

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Publication Date
Tue May 01 2018
Journal Name
The Journal Of Immunology
Resveratrol treatment alters lung microbiome in the murine ovalbumin-induced asthma model by increasing mucus-degrading <i>Akkermansia muciniphila</i>.
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Abstract<p>Asthma is a chronic inflammatory disease that involves the narrowing of the lung airways and excessive mucus production. Resveratrol (RES), a polyphenolic stilbene, is known to control asthmatic attacks via different molecular mechanisms. However, no studies have examined the effect of resveratrol on the microbiome in the ovalbumin (OVA)-induced asthma mouse model. In this study, we induced asthma in BALB/c mice by injecting OVA followed by 7 days treatment with RES. Plethysmography showed that the expiratory resistance in the lung tissue was significantly reduced in the RES treated group, while mean volume, peak expiratory flow, and frequency of respiration was increased. Histopathol</p> ... Show More
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Publication Date
Fri Jun 16 2023
Journal Name
Iraqi Journal Of Pharmaceutical Sciences ( P-issn 1683 - 3597 E-issn 2521 - 3512)
Carvone exerts lung anti-inflammatory effect through hampering NF-KB pathway in lipopolysaccharide-induced acute lung injury in mice
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                Background: Acute lung injury (ALI) is among the most serious conditions characterized by an exacerbation of inflammatory response that can result from a persistent lung infection. Carvone is chiral monoterpenoid ketone present in the essential oils of dill, caraway, and spearmint. It shows antioxidant, anti-inflammatory, and antimicrobial effects among others. In this study, the lung anti-inflammatory and protective effects and potential mechanism of action of carvone were investigated in ALI induced by Lipopolysaccharide (LPS).

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Publication Date
Mon May 01 2017
Journal Name
The Journal Of Immunology
Resveratrol improves a murine model of asthma through alterations in the gut microbiome
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Abstract<p>Asthma is a condition characterized by bronchial spasms, inflammation, and mucous hypersecretion which leads to difficulties in respiration. Asthmatic patients are usually presented with recurrent attacks of coughing, wheezing, and shortness of breath which could be life-threatening. More than three million cases of asthma in the United States are diagnosed annually. Resveratrol, a polyphenolic stilbene, is known to be useful in controlling asthmatic attacks via different molecular mechanisms within the lung epithelium and infiltrating immune cells. However, few studies mentioned the effect of resveratrol on the microbiome in ovalbumin-induced asthma mouse model. In this study, we ind</p> ... Show More
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