Background Dairy cows experiencing ketosis after calving suffer greater disease incidence and are at greater risk of leaving the herd. In vitro administration of beta-hydroxybutyric acid(BHBA;the primary blood ketone)...Background Dairy cows experiencing ketosis after calving suffer greater disease incidence and are at greater risk of leaving the herd. In vitro administration of beta-hydroxybutyric acid(BHBA;the primary blood ketone) has inhibitory effects on the function of bovine leukocytes. BHBA is a ligand of HCAR2 and the activation of these receptors promotes an anti-inflammatory response which may be related with immunosuppression observed in transition dairy cattle. The objective of this study was to identify and test antagonists for HCAR2 in bovine immune cells cultured with BHBA.Results We observed expression of HCAR2 at the protein level within lymphocytes, monocytes, and granulocytes. The proportion of cells expressing HCAR2 tended to be greater in mid-lactation compared to early lactation cows;the increase was a result of increased proportion of T and B cells expressing HCAR2. Stimulation of HCAR2 with niacin or BHBA promoted Ca^(2+) mobilization in neutrophils and mononuclear cells. Mononuclear cells treated with BHBA had diminished intracellular Ca^(2+) responses when HCAR2 was knocked down by si RNA silencing, indicating Ca^(2+) mobilization was mediated by HCAR2 signaling. Two candidate antagonists for HCAR2, synthesized from niacin(NA-1 and NA-5), were tested;monocytes and neutrophils pre-treated with NA-1 and NA-5 had reduced Ca^(2+) mobilization after incubation with BHBA. Furthermore, NA-5 but not NA-1 prevented BHBA-associated reductions in cyclic AMP.Conclusions We demonstrated that HCAR2 is present on bovine leukocytes and has greater expression later in lactation. We confirmed that BHBA and niacin derived HCAR2 antagonists alter bovine leukocyte activity. Our results demonstrate that both BHBA and niacin affect bovine leukocyte Ca^(2+) mobilization in a HCAR2-dependent manner.展开更多
Alzheimer’s disease(AD),a neurodegenerative disorder,has been determined as an outcome of genetic as well as behavioral conditions.The complete understanding of its generation and progress is yet to be understood.How...Alzheimer’s disease(AD),a neurodegenerative disorder,has been determined as an outcome of genetic as well as behavioral conditions.The complete understanding of its generation and progress is yet to be understood.However,there has been a significant progress in the diagnosis and identification of the associated risk factors of AD.Several of the risk factors were found connected with cholesterol.Scientists are mainly focusing on the reduction of amyloid β and stabilization of tau protein towards the development of its drugs.To modulate amyloid β,the key components of cholesterol metabolism have been attractive targets and the enzymes involved in the phosphorylation of tau have been tried to stabilize tau protein.This review article briefly highlights the symptoms,risk factors,and drug targets of AD.展开更多
Objective:To determine the antibacterial efficacy and brine shrimp toxicity of extracts(hexane,dichloromethane,ethyl acetate,methanol and water)obtained from the bark of Schleichera oleosa.Methods:The powdered bark sa...Objective:To determine the antibacterial efficacy and brine shrimp toxicity of extracts(hexane,dichloromethane,ethyl acetate,methanol and water)obtained from the bark of Schleichera oleosa.Methods:The powdered bark sample was Soxhlet extracted sequentially in hexanes,dichloromethane,ethyl acetate,methanol and water.Antibacterial evaluation was carried out by following the agar diffusion method and amoxicillin disc was used as a reference.Slightly modified Meyer’s method was used to determine the toxicity of the extracts in brine shrimps.Results:Among the nine bacterial strains tested,the methanolic and aqueous extracts showed promising antibacterial efficacy against Serratia marcescens,Escherarichia coli,Bacillus subtilis and Micrococcus luteus.None of the extracts were found significantly toxic to brine shrimps.Conclusions:Strong antibacterial activity and low brine shrimp toxicity of methanolic and aqueous extracts can provide new antibacterial compounds.展开更多
基金the National Institutes of Health, National Institute of General Medical Sciences (R01 GM128659) for financial supportThe Attune Cytpix, located in the MSU Flow Cytometry Core Facility, is supported by the Equipment Grants Program, award #2022-70410-38419, from the U.S. Department of Agriculture (USDA), National Institute of Food and Agriculture (NIFA)。
文摘Background Dairy cows experiencing ketosis after calving suffer greater disease incidence and are at greater risk of leaving the herd. In vitro administration of beta-hydroxybutyric acid(BHBA;the primary blood ketone) has inhibitory effects on the function of bovine leukocytes. BHBA is a ligand of HCAR2 and the activation of these receptors promotes an anti-inflammatory response which may be related with immunosuppression observed in transition dairy cattle. The objective of this study was to identify and test antagonists for HCAR2 in bovine immune cells cultured with BHBA.Results We observed expression of HCAR2 at the protein level within lymphocytes, monocytes, and granulocytes. The proportion of cells expressing HCAR2 tended to be greater in mid-lactation compared to early lactation cows;the increase was a result of increased proportion of T and B cells expressing HCAR2. Stimulation of HCAR2 with niacin or BHBA promoted Ca^(2+) mobilization in neutrophils and mononuclear cells. Mononuclear cells treated with BHBA had diminished intracellular Ca^(2+) responses when HCAR2 was knocked down by si RNA silencing, indicating Ca^(2+) mobilization was mediated by HCAR2 signaling. Two candidate antagonists for HCAR2, synthesized from niacin(NA-1 and NA-5), were tested;monocytes and neutrophils pre-treated with NA-1 and NA-5 had reduced Ca^(2+) mobilization after incubation with BHBA. Furthermore, NA-5 but not NA-1 prevented BHBA-associated reductions in cyclic AMP.Conclusions We demonstrated that HCAR2 is present on bovine leukocytes and has greater expression later in lactation. We confirmed that BHBA and niacin derived HCAR2 antagonists alter bovine leukocyte activity. Our results demonstrate that both BHBA and niacin affect bovine leukocyte Ca^(2+) mobilization in a HCAR2-dependent manner.
文摘Alzheimer’s disease(AD),a neurodegenerative disorder,has been determined as an outcome of genetic as well as behavioral conditions.The complete understanding of its generation and progress is yet to be understood.However,there has been a significant progress in the diagnosis and identification of the associated risk factors of AD.Several of the risk factors were found connected with cholesterol.Scientists are mainly focusing on the reduction of amyloid β and stabilization of tau protein towards the development of its drugs.To modulate amyloid β,the key components of cholesterol metabolism have been attractive targets and the enzymes involved in the phosphorylation of tau have been tried to stabilize tau protein.This review article briefly highlights the symptoms,risk factors,and drug targets of AD.
基金Supported by Nepal Academy of Science and Technology.
文摘Objective:To determine the antibacterial efficacy and brine shrimp toxicity of extracts(hexane,dichloromethane,ethyl acetate,methanol and water)obtained from the bark of Schleichera oleosa.Methods:The powdered bark sample was Soxhlet extracted sequentially in hexanes,dichloromethane,ethyl acetate,methanol and water.Antibacterial evaluation was carried out by following the agar diffusion method and amoxicillin disc was used as a reference.Slightly modified Meyer’s method was used to determine the toxicity of the extracts in brine shrimps.Results:Among the nine bacterial strains tested,the methanolic and aqueous extracts showed promising antibacterial efficacy against Serratia marcescens,Escherarichia coli,Bacillus subtilis and Micrococcus luteus.None of the extracts were found significantly toxic to brine shrimps.Conclusions:Strong antibacterial activity and low brine shrimp toxicity of methanolic and aqueous extracts can provide new antibacterial compounds.
