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Investigation of HCAR2 antagonists as a potential strategy to modulate bovine leukocytes

Journal of Animal Science and Biotechnology 2024年第4期15卷 1567-1577页

作者： Laman K.Mamedova Kirby C.Krogstad Paiton O.McDonald Laxman Pokhrel Duy H.Hua Evan C.Titgemeyer Barry J.Bradford Department of Animal Science Michigan State UniversityEast LansingMichigan 48824USA Department of Animal Sciences and Industry Kansas State UniversityManhattanKS 66506USA comparative medicine and integrative biology East LansingMI 48824USA Department of Chemistry Kansas State UniversityManhattanKS 66506USA

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 *** 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 *** 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.

关键词： Flow cytometry GPR109A HM74A Ketosis

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Progress,implications,and challenges in using humanized immune system mice in CAR-T therapy-Application evaluation and improvement

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Animal Models and Experimental medicine 2024年第1期7卷 3-11页

作者： Hanwei Yue Lin Bai NHC Key Laboratory of Human Disease comparative medicine Institute of Laboratory Animal SciencesCAMS and PUMCChao-yang DistrictBeijingChina

In recent years,humanized immune system(HIS)mice have been gradually used as models for preclinical research in pharmacotherapies and cell therapies with major breakthroughs in tumor and other fields,better mimicking the human immune system and the tumor immune microenvironment,compared to traditional immunodeficient *** better promote the application of HIS mice in preclinical research,we se-lectively summarize the current prevalent and breakthrough research and evaluation of chimeric antigen receptor(CAR)-T cells in various antiviral and antitumor *** exploring its application in preclinical research,we find that it can better reflect the actual clinical patient condition,with the advantages of providing high-efficiency detection indicators,even for progressive research and *** believe that it has better clinical patient simulation and promotion for the updated design of CAR-T cell therapy than directly transplanted immunodeficient *** characteristics of the main models are proposed to improve the use defects of the existing models by reducing the limitation of antihost reaction,combining multiple models,and unifying sources and organoid *** study of relapse and toxicity after CAR-T treatment also provides more possibilities for application and development.

关键词： antitumor antiviral CAR-T humanized immune system model humanized mice preclinical research

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Ultrasound-driven self-decomposition porphyrins as metal-free CO precursors for gas and sonodynamic synergistic therapy

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Science China Chemistry 2024年第5期67卷 1624-1635页

作者： Shuxin Liu Jinjuan Ma Xiang Xu Aiguo Wang Nan Zheng School of Chemical Engineering Dalian University of TechnologyDalian 116024China Department of comparative medicine Laboratory Animal Center Dalian Medical UniversityDalian 116000China Cancer Hospital of Dalian University of Technology Shenyang 116000China

Carbon monoxide(CO) is an endogenous therapeutic gas with an anti-tumor effect. The precise delivery and controlled release of CO in tumor tissues play crucial roles in anti-cancer treatment. However, efficient in situ generation of CO from metal-free COreleasing molecules(CORMs) remains a formidable challenge. Herein, we develop ultrasound(US)-driven self-decomposition porphyrin as organic and metal-free US-CORMs, which can spatiotemporally control the CO release(347 mmol CO/mol porphyrin) efficiently under physiologically harmless US conditions(1.0 MHz, 1.5 W/cm^(2), 50% duty cycle, 50 min). Moreover,porphyrin as a sonosensitizer can also generate reactive oxygen species(ROS) under US treatment to achieve sonodynamic therapy(SDT). Advanced functions of such porphyrin-based CORMs in CO gas-sonodynamic synergistic treatment have been demonstrated by evaluating the in vitro and in vivo anti-tumor effects.

关键词： porphyrin sonodynamic therapy metal-free CO precursors ultrasound-driven gas therapy

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Prenatal cadmium exposure impairs neural tube closure via inducing excessive apoptosis in neuroepithelium

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Journal of Environmental Sciences 2024年第4期138卷 572-584页

作者： Shiyong Zhu Xuenan Li Xueyan Dai Jinlong Li College of Veterinary medicine Northeast Agricultural UniversityHarbin 150030China Key Laboratory of the Provincial Education Department of Heilongjiang for Common Animal Disease Prevention and Treatment Northeast Agricultural UniversityHarbin 150030China Heilongjiang Key Laboratory for Laboratory Animals and comparative medicine Northeast Agricultural UniversityHarbin 150030China

Birth defects have become a public health *** hazardous environmental factors exposure to embryos could increase the risk of birth ***,a toxic environmental factor,can cross the placental barrier during *** woman may be subjected to cadmium before taking precautionary protective ***,the link between birth defects and cadmium remains *** exposure can induce excessive apoptosis in neuroepithelium during embryonic development *** exposure activated the p53 via enhancing the adenosine 5‘-monophosphate(AMP)-activated protein kinase(AMPK)and reactive oxygen species'(ROS)*** cadmium decreases the level of Paired box 3(Pax3)and murine double minute 2(Mdm2),disrupting the process of p53 *** p53 accumulation induced excessive apoptosis in neuroepithelium during embryonic development *** apoptosis led to the failure of neural tube *** study emphasizes that environmental materials may increase the health risk for *** caused the failure of neural tube closure during early embryotic *** women may be exposed by cadmium before taking precautionary protective actions,because of cadmium concentration-containing foods and environmental tobacco *** suggests that prenatal cadmium exposure is a threatening risk factor for birth defects.

关键词： Cadmium Neural tube closure Excessive apoptosis p53 Embryogenesis

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Apolipoprotein E4 interferes with lipid metabolism to exacerbate depression-like behaviors in 5xFAD mice

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Animal Models and Experimental medicine 2024年第3期7卷 347-361页

作者： Yanju Gong Mingfeng Li Min Liu Xinghan Wu Yanhong Li Chuan Qin Ling Zhang iNHC Key Laboratory of Human Disease comparative medicine Beijing Engineering Research Center for Experimental Animal Models of Human Critical DiseasesInternational Center for Technology and lnnovation of Animal ModelComparative Medicine CenterInstitute of Laboratory Animal SciencesChinese Academy of Medical Sciences(CAMS)and Peking Union Medical College(PuMC)BeijingChina Changping National Laboratory(CPNL) BeijingChina

Background:Apolipoprotein E4(ApoE4)allele is the strongest genetic risk factor for late-onset Alzheimer's disease,and it can aggravate depressive symptoms in non-AD ***,the impact of ApoE4 on AD-associated depression-l ike behaviors and its underlying pathogenic mechanisms remain ***:This study developed a 5xFAD mouse model overexpressing human ApoE4(E4FAD).Behavioral assessments and synaptic function tests were conducted to explore the effects of ApoE4 on cognition and depression in 5xFAD *** in peripheral and central lipid metabolism,as well as the levels of serotonin(5-HT)andγ-aminobutyric acid(GABA)neurotransmitters in the prefrontal cortex,were *** addition,the protein levels of 24-dehydrocholesterol reductase/glycogen synthase kinase-3 beta/mammalian target of rapamycin(DHCR24/GSK3β/m TOR)and postsynaptic density protein 95/calmodulin-dependent protein kinase II/brain-derived neurotrophic factor(PSD95/CaMK-II/BDNF)were measured to investigate the molecular mechanism underlying the effects of ApoE4 on AD ***:Compared with 5xFAD mice,E4FAD mice exhibited more severe depressionlike behaviors and cognitive *** mice also exhibited increased amyloid-beta deposition in the hippocampus,increased astrocyte numbers,and decreased expression of depression-related neurotransmitters 5-HT and GABA in the prefrontal ***,lipid metabolism disorders were observed in E4FAD,manifesting as elevated low-density lipoprotein cholesterol and reduced high-density lipoprotein cholesterol in peripheral blood,decreased cholesterol level in the prefrontal cortex,and reduced expression of key enzymes and proteins related to cholesterol synthesis and *** expression of proteins related to the DHCR24/GSK3β/m TOR and PSD95/CaMK-II/BDNF pathways was also ***:This study found that ApoE4 overexpression exacerbates depressionlike behaviors in 5xFAD mice and confirmed that ApoE4 reduces co

关键词： 5xFAD mice Alzheimer's disease ApoE4 allele depression like

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Essential oils improve nursery pigs'performance and appetite via modulation of intestinal health and microbiota

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Animal Nutrition 2024年第1期16卷 174-188页

作者： Bi-Chen Zhao Tian-Hao Wang Jian Chen Bai-Hao Qiu Ya-Ru Xu Jin-Long Li College of Veterinary medicine Northeast Agricultural UniversityHarbin150030China Heilongjiang Key Laboratory for Laboratory Animals and comparative medicine Northeast Agricultural UniversityHarbin150030China Key Laboratory of the Provincial Education Department of Heilongjiang for Common Animal Disease Prevention and Treatment Northeast Agricultural UniversityHarbin150030China

Optimal intestinal health and functionality are essential for animal health and performance,and simultaneously intestinal nutrient transporters and intestinal peptides are also involved in appetite and feed intake control *** the potential of essential oil(EO)in improving animal performance and improving feed palatability,we hypothesized that dietary supplementation of cinnamaldehyde and carvacrol could improve performance and appetite of nursery pigs by modulating intestinal health and ***(100 mg/kg),carvacrol(100 mg/kg),and their mixtures(including 50 mg/kg cinnamaldehyde and 50 mg/kg carvacrol)were supplemented into the diets of 240 nursery pigs for 42 d,and data related to performance were ***,the influence of EO on intestinal health,appetite and gut microbiota and their correlations were *** supplementation increased(P<0.05)the body weight,average daily gain(ADG)and average daily feed intake(ADFI)of piglets,and reduced(P<0.05)diarrhea rates in nursery ***,EO increased(P<0.05)the intestinal absorption area and the abundance of tight junction proteins,and decreased(P<0.05)intestinal permeability and local *** terms of intestinal development and the mucus barrier,EO promoted intestinal development and increased(P<0.05)the number of goblet ***,we found that piglets in the EO-supplemented group had upregulated(P<0.05)levels of transporters and digestive enzymes in the intestine,which were significantly associated with daily gain and feed *** addition,EO supplementation somewhat improved appetite in nursery pigs,increased the diversity of the gut microbiome and the abundance of beneficial bacteria,and there was a correlation between altered bacterial structure and appetite-related *** findings indicate that EO is effective in promoting growth performance and nutrient absorption as well as in regulating appetite by improving intestinal health and ba

关键词： Nursery pig Essential oil Intestinal health Appetite Microbiota

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A Dietary Source of High Level of Fluoroquinolone Tolerance in mcr-Carrying Gram-Negative Bacteria

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Research 2024年第3期2023卷 105-121页

作者： Tianqi Xu Dan Fang Fulei Li Zhiqiang Wang Yuan Liu Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses College of Veterinary MedicineYangzhou UniversityYangzhou 225009China. Joint International Research Laboratory of Agriculture and Agri-Product Safety the Ministry of Education of ChinaYangzhou UniversityYangzhou 225009China. Institute of comparative medicine Yangzhou UniversityYangzhou 225009China.

The emergence of antibiotic tolerance,characterized by the prolonged survival of bacteria following antibiotic exposure,in natural bacterial populations,especially in pathogens carrying antibiotic resistance genes,has been an increasing threat to public ***,the major causes contributing to the formation of antibiotic tolerance and underlying molecular mechanisms are yet poorly ***,we show that potassium sorbate(PS),a widely used food additive,triggers a high level of fluoroquinolone tolerance in bacteria carrying mobile colistin resistance gene *** studies demonstrate that PS treatment results in the accumulation of intracellular fumarate,which activates bacterial two-component system and decreases the expression level of outer membrane protein OmpF,thereby reducing the uptake of *** addition,the supplementation of PS inhibits aerobic respiration,reduces reactive oxygen species production and alleviates DNA damage caused by bactericidal ***,we demonstrate that succinate,an intermediate product of the tricarboxylic acid cycle,overcomes PS-mediated ciprofloxacin *** multiple animal models,ciprofloxacin treatment displays failure outcomes in PS preadministrated animals,including comparable survival and bacterial loads with the vehicle *** together,our works offer novel mechanistic insights into the development of antibiotic tolerance and uncover potential risks associated with PS use.

关键词： overcome thereby additive

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Generation of double knockout cattle via CRISPR-Cas9 ribonucleoprotein(RNP)electroporation

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Journal of Animal Science and Biotechnology 2024年第1期15卷 456-462页

作者： Gyeong-Min Gim Kyeong-Hyeon Eom Dong-Hyeok Kwon Dae-Jin Jung Dae-Hyun Kim Jun-Koo Yi Jae-Jung Ha Ji-Hyun Lee Seong-Beom Lee Woo-Jae Son Soo-Young Yum Won-Wu Lee Goo Jang Laboratory of Theriogenology and Biotechnology Department of Veterinary Clinical ScienceCollege of Veterinary Medicine and the Research Institute of Veterinary ScienceSeoul National UniversitySeoulRepublic of Korea LARTBio Co. Ltd.SeoulRepublic of Korea Gyeongsangbukdo Livestock Research Institute YeongjuRepublic of Korea comparative medicine Disease Research Center Seoul National UniversitySeoulRepublic of Korea

Background Genome editing has been considered as powerful tool in agricultural ***,genome editing progress in cattle has not been fast as in other mammal species,for some disadvantages including long gestational periods,single pregnancy,and high raising ***,technically demanding methods such as microinjection and somatic cell nuclear transfer(SCNT)are needed for gene editing in *** this point of view,electroporation in embryos has been risen as an *** First,editing efficiency of our electroporation methods were tested for *** of mutation on embryo was confirmed by T7E1 *** first combination,mutation rates for MSTN and PRNP were 57.6%±13.7%and 54.6%±13.5%,*** case of MSTN/BLG,mutation rates were 83.9%±23.6%for MSTN,84.5%±18.0%for ***,the double-KO embryos were transferred to surrogates and mutation rate was identified in resultant calves by targeted deep *** recipients were transferred for MSTN/PRNP,4 calves were delivered,and one calf underwent an induction for double *** surrogates were given double-KO embryos for MSTN/BLG,and four of the six calves that were born had mutations in both *** These data demonstrated that production of genome edited cattle via electroporation of RNP could be effectively ***,MSTN and PRNP from beef cattle and MSTN and BLG from dairy cattle have been born and they will be valuable resources for future precision breeding.

关键词： Beta-lactoglobulin Cattle CRISPR-Cas9 Electroporation Knockout MSTN PRNP

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A comparative study of the anti-fatigue activity of extracts from different parts of Cistanche tubulosa(Schenk)Wight Author links open overlay panel

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Journal of Traditional Chinese Medical Sciences 2024年第2期11卷 222-231页

作者： Jianteng Dong Junjun Li Yizhou Liu Lingwen Cui Xiangning Liu Gang Wang Qixin Wang David N.Criddle Pengfei Tu Chun Li School of Traditional Chinese medicine Beijing University of Chinese MedicineBeijing102488China Modern Research Center for Traditional Chinese medicine School of Chinese Materia MedicaBeijing University of Chinese MedicineBeijing102488China Institute of Chinese Materia Medica China Academy of Chinese Medical SciencesBeijing100700China Department of Molecular&Clinical Cancer medicine Institute of SystemsMolecular&Integrative BiologyUniversity of LiverpoolLiverpoolL693BXUK Peking University School of Pharmaceutical Sciences Beijing100191China

Objective To evaluate the anti-fatigue effects of different extracts from Cistanche tubulosa(Schenk)Wight(***,Rou Cong Rong),focusing on central and exercise-induced fatigue in *** study investigated the pharmacological effects of the total oligosaccharides,polysaccharides,and phenylethanoid glycosides(CPhGs)extracted from *** Models of sleep deprivation and forced swimming fatigue were established to simulate central and exercise-induced *** mice were treated with different extracts of ***,and their effects were assessed using behavioral tests to measure exercise capacity,learning,and memory *** analyses were performed to evaluate the changes in serum and brain neurotransmitter levels,liver and muscle glycogen storage,and various fatigue-related *** This study found that treatment with *** extract improved exercise capacity,learning,and memory in *** oligosaccharides from *** enhanced adrenocorticotropic hormone,cholinesterase,and thyroid-stimulating hormone levels,reduced cortisol levels in central fatigue models,and ameliorated biochemical markers of exercise-induced fatigue,including lowering lactic acid,blood urea nitrogen,and malondialdehyde *** the tested extracts,the total oligosaccharides showed the most comprehensive anti-fatigue *** The anti-fatigue effects of ***,particularly those of its total oligosaccharides,are pronounced in both central and exercise-induced *** effects are mediated by the regulation of neurotransmitter levels,enhancement of glycogen storage,and improvement of antioxidant enzyme activity,suggesting potential therapeutic benefits in fatigue-related conditions.

关键词： Cistanche tubulosa Anti-fatigue Central fatigue Exercise fatigue Oligosaccharides

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Meta-analysis on integrative medicine for the treatment of malignant ascites: a comparative study

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Journal of Traditional Chinese medicine 2015年第1期35卷 11-14页

作者： Li Yuan Lou Yanni Deng Bo Jia Liqun Oncology Department of integrative medicine China-Japan Friendship Hospital

OBJECTIVE: To compare the efficacy of integrated Chinese and Western medicine with that of only Western medicine for the treatment of malignant ***: All randomized controlled trials(January 2004 to March 2013) from the China National Knowledge Infrastructure Database, Chinese Biomedical Literature Database, and Wanfang Database were searched with keywords. Meta-analysis was conducted by combining the odds ratios of the individual studies. Review Manager 5.0 was used for the ***: One thousand one hundred and fifty-six patients from 19 randomized controlled trails were included. Of them, 630 patients were treated with integrated Chinese and Western medicine(the integrative group), and 526 patients were treated with Western medicine alone(the control group). The Meta-analysis showed that the total effective rate was 78.73% in the integrated group, and 59.13% in the control group. The effective percentage was sig-nificantly higher in the integrative group than that of the control group [OR = 2.85, 95% CI(2.16,3.74),P integrative group was better than that in the control group. integrative medicine may be beneficial for malignant ascites.

关键词： Ascites integrative medicine Treat-ment outcome Meta-analysis

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