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  1. Article ; Online: Yin and yang of cannabinoid CB1 receptor

    Kathryn Miranda / William Becker / Philip B. Busbee / Nicholas Dopkins / Osama A. Abdulla / Yin Zhong / Jiajia Zhang / Mitzi Nagarkatti / Prakash S. Nagarkatti

    iScience, Vol 25, Iss 9, Pp 104994- (2022)

    CB1 deletion in immune cells causes exacerbation while deletion in non-immune cells attenuates obesity

    2022  

    Abstract: Summary: While blockade of cannabinoid receptor 1 (CB1) has been shown to attenuate diet-induced obesity (DIO), its relative role in different cell types has not been tested. The current study investigated the role of CB1 in immune vs non-immune cells ... ...

    Abstract Summary: While blockade of cannabinoid receptor 1 (CB1) has been shown to attenuate diet-induced obesity (DIO), its relative role in different cell types has not been tested. The current study investigated the role of CB1 in immune vs non-immune cells during DIO by generating radiation-induced bone marrow chimeric mice that expressed functional CB1 in all cells except the immune cells or expressed CB1 only in immune cells. CB1−/− recipient hosts were resistant to DIO, indicating that CB1 in non-immune cells is necessary for induction of DIO. Interestingly, chimeras with CB1−/− in immune cells showed exacerbation in DIO combined with infiltration of bone-marrow-derived macrophages to the brain and visceral adipose tissue, elevated food intake, and increased glucose intolerance. These results demonstrate the opposing role of CB1 in hematopoietic versus non-hematopoietic cells during DIO and suggests that targeting immune CB1 receptors provides a new pathway to ameliorate obesity and related metabolic disorders.
    Keywords Immunology ; Hematology ; Human metabolism ; Science ; Q
    Language English
    Publishing date 2022-09-01T00:00:00Z
    Publisher Elsevier
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  2. Article ; Online: AhR Activation Leads to Alterations in the Gut Microbiome with Consequent Effect on Induction of Myeloid Derived Suppressor Cells in a CXCR2-Dependent Manner

    Wurood Hantoosh Neamah / Philip Brandon Busbee / Hasan Alghetaa / Osama A. Abdulla / Mitzi Nagarkatti / Prakash Nagarkatti

    International Journal of Molecular Sciences, Vol 21, Iss 9613, p

    2020  Volume 9613

    Abstract: Aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is a potent ligand for AhR and a known carcinogen. While AhR activation by TCDD leads to significant immunosuppression, how this ... ...

    Abstract Aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is a potent ligand for AhR and a known carcinogen. While AhR activation by TCDD leads to significant immunosuppression, how this translates into carcinogenic signal is unclear. Recently, we demonstrated that activation of AhR by TCDD in naïve C57BL6 mice leads to massive induction of myeloid derived-suppressor cells (MDSCs). In the current study, we investigated the role of the gut microbiota in TCDD-mediated MDSC induction. TCDD caused significant alterations in the gut microbiome, such as increases in Prevotella and Lactobacillus , while decreasing Sutterella and Bacteroides . Fecal transplants from TCDD-treated donor mice into antibiotic-treated mice induced MDSCs and increased regulatory T-cells (Tregs). Injecting TCDD directly into antibiotic-treated mice also induced MDSCs, although to a lesser extent. These data suggested that TCDD-induced dysbiosis plays a critical role in MDSC induction. Interestingly, treatment with TCDD led to induction of MDSCs in the colon and undetectable levels of cysteine. MDSCs suppressed T cell proliferation while reconstitution with cysteine restored this response. Lastly, blocking CXC chemokine receptor 2 (CXCR2) impeded TCDD-mediated MDSC induction. Our data demonstrate that AhR activation by TCDD triggers dysbiosis which, in turn, regulates, at least in part, induction of MDSCs.
    Keywords 2,3,7,8-tetrachlorodibenzo-p-dioxin ; aryl hydrocarbon receptor ; microbiome ; myeloid-derived suppressor cell ; CXCR2 ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
    Subject code 610
    Language English
    Publishing date 2020-12-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  3. Article ; Online: Endocannabinoid Anandamide Attenuates Acute Respiratory Distress Syndrome through Modulation of Microbiome in the Gut-Lung Axis

    Muthanna Sultan / Kiesha Wilson / Osama A. Abdulla / Philip Brandon Busbee / Alina Hall / Taylor Carter / Narendra Singh / Saurabh Chatterjee / Prakash Nagarkatti / Mitzi Nagarkatti

    Cells, Vol 10, Iss 3305, p

    2021  Volume 3305

    Abstract: Acute respiratory distress syndrome (ARDS) is a serious lung condition characterized by severe hypoxemia leading to limitations of oxygen needed for lung function. In this study, we investigated the effect of anandamide (AEA), an endogenous cannabinoid, ... ...

    Abstract Acute respiratory distress syndrome (ARDS) is a serious lung condition characterized by severe hypoxemia leading to limitations of oxygen needed for lung function. In this study, we investigated the effect of anandamide (AEA), an endogenous cannabinoid, on Staphylococcal enterotoxin B (SEB)-mediated ARDS in female mice. Single-cell RNA sequencing data showed that the lung epithelial cells from AEA-treated mice showed increased levels of antimicrobial peptides (AMPs) and tight junction proteins. MiSeq sequencing data on 16S RNA and LEfSe analysis demonstrated that SEB caused significant alterations in the microbiota, with increases in pathogenic bacteria in both the lungs and the gut, while treatment with AEA reversed this effect and induced beneficial bacteria. AEA treatment suppressed inflammation both in the lungs as well as gut-associated mesenteric lymph nodes (MLNs). AEA triggered several bacterial species that produced increased levels of short-chain fatty acids (SCFAs), including butyrate. Furthermore, administration of butyrate alone could attenuate SEB-mediated ARDS. Taken together, our data indicate that AEA treatment attenuates SEB-mediated ARDS by suppressing inflammation and preventing dysbiosis, both in the lungs and the gut, through the induction of AMPs, tight junction proteins, and SCFAs that stabilize the gut-lung microbial axis driving immune homeostasis.
    Keywords acute respiratory distress syndrome (ARDS) ; Staphylococcus enterotoxin B (SEB) ; anandamide (AEA) ; COVID-19 ; microbiome ; MiSeq sequencing ; Biology (General) ; QH301-705.5
    Language English
    Publishing date 2021-11-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  4. Article ; Online: Zinc deficiency (hypozincemia) in local Iraqi cattle

    Kamal M. Alsaad, / H. I. Al-Sadi, / Osama A.Abdulla

    Research Opinions in Animal & Veterinary Sciences, Vol 1, Iss 7, Pp 418-

    2011  Volume 424

    Abstract: Clinical, hematological, pathological and some biochemical parameters have been studied in local cattle and calves affected naturally with hypozincemia in Mosul, Iraq. The study was conducted on 78 local Iraqi cattle and calves, among these animals, 30 ... ...

    Abstract Clinical, hematological, pathological and some biochemical parameters have been studied in local cattle and calves affected naturally with hypozincemia in Mosul, Iraq. The study was conducted on 78 local Iraqi cattle and calves, among these animals, 30 calves were less than six months of age and 38 animals were more than three years old. Ten clinical healthy cattle of different ages were used as control. Affected cattle showed signs of alopecia in different body regions (73.6%), abnormal skin (rough, thickened, wrinkled, cracked and with dandruff ) (73.6%), paleness of mucous membranes (47.3%), intermittent diarrhoea (39.4%), decreased milk production (31.5%) and loss of appetite (26.3%), whereas affected calves showed alopecia in various body regions (90%), abnormal skin (83.3%), decreased growth rate (53.3%), swelling of joints and stiff gait (43.3%) and pica (36.6%). No significant difference has been detected in body temperature, whereas respiratory and heart rates were significantly increased in affected animals in comparison with control. Statistical analysis showed significant decrease in the total erythrocytes (TRBCs), hemoglobin (HB) and packed cell volume (PCV) in diseased cattle and calves and macrocytic normochromic type of anemia was found. The results also indicated significant decrease in lymphocytes and platelets counts, however significant increase was encountered in platelets volume, platelets distribution width, prothrombine time and activated partial thromboplastine time in diseased animals. The biochemical results revealed significant decrease in serum zinc and fibrinogen and haptoglobin level was higher in diseased cattle and calves. Microscopic lesions of the skin of zinc deficient cattle and calves were in the form of epidermal hyperplasia, parakeratosis, hyperkeratosis, acanthosis and the formation of thickened adherent scale.
    Keywords Zinc Deficiency ; Cattle ; Hematology ; Pathology ; Biochemistry ; Animal culture ; SF1-1100 ; Agriculture ; S ; DOAJ:Animal Sciences ; DOAJ:Agriculture and Food Sciences
    Subject code 630
    Language English
    Publishing date 2011-07-01T00:00:00Z
    Publisher KPK Publishers
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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