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Proinflammatory polarization of adipose tissue macrophages in cows with subclinical ketosis constitutes a critical driver of adipose tissue remodeling and inflammation 认领 引用 被引量：1
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作者 Bichen Zhao Ming Li +7 位作者 Huijing Zhang Renxu Chang Jingyi Wang Wanli Zhao Yue Yang Muhammad Usman Juan J.Loor Chuang Xu 《Journal of Animal Science and Biotechnology》 SCIE CAS CSCD 2025年第6期2768-2781,共14页
Background Sustained lipolysis exacerbates subclinical ketosis(SCK)in dairy cows and is associated with inflammation and adipose tissue macrophage(ATM)infiltration.While ATM involvement in adipose homeostasis and infl... Background Sustained lipolysis exacerbates subclinical ketosis(SCK)in dairy cows and is associated with inflammation and adipose tissue macrophage(ATM)infiltration.While ATM involvement in adipose homeostasis and inflammation in early lactation is recognized,a comprehensive exploration of ATM polarization phenotypes in SCK cows is lacking.This study aimed to characterize ATM polarization and its link to lipolysis and inflammation in SCK cows.Results Subcutaneous adipose tissue samples were obtained from dairy cows to analyze protein expression and gene profiles.Compared with healthy cows,SCK cows had higher serum BHBA and NEFA,smaller adipocytes,and increased expression of lipolytic enzymes(LIPE,ATGL),indicating enhanced lipolysis.Decreased levels of FASN,PPARγ,p-SMAD3,and TGFβsuggested impaired adipogenesis.Inflammatory markers(TNF-α,IFN-γ,TLR4,Caspase1)and NFκB signaling activity were elevated.ATM infiltration was supported by increased CD9,CD68,TREM2,and CXCL1 expression.Protein abundance of M1 polarization markers(iNOS,CD86 and CCL2)in ATMs were associated with greater levels of NOS2,IL1B,CD86 and CCL2 mRNA expression in SCK cows;fluorescence intensity of NOS2 and CD86 also was elevated,alongside a higher proportion of CD68+/CD86+immunopositive cells within adipose tissue.ELISA further quantified increased concentrations of IL-1β and CCL2.Conversely,the abundance of ATM M2 polarization markers,including CD206,IL-10,KLF4,and Arg1,at both the protein and mRNA levels demonstrated a decline.Meanwhile,the proportion of CD68+/CD206+immune response cells was relatively low in SCK cows.Conclusions Overall,the present study indicated an augmented macrophage presence within adipose tissue during subclinical ketosis,with a predominance of pro-inflammatory macrophages(M1 ATM).This observation suggested a vicious cycle wherein macrophage infiltration and pro-inflammatory polarization coincide with enhanced lipolysis and an amplified inflammatory cascade. 展开更多
关键词 Adipose tissue macrophages Adipose tissue remodeling Macrophage polarization Subclinical ketosis
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Depot-dependent effects of subclinical ketosis on visceral and subcutaneous adipose tissue transcriptional cellular diversity in dairy cows 认领 引用
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作者 Hunter Ford Clarissa Strieder-Barboza 《Journal of Animal Science and Biotechnology》 SCIE CAS CSCD 2025年第6期2715-2735,共21页
Background Adipose tissue plays a central role in regulating whole-body metabolic health,facilitated by the variety of cell types and their wide-ranging functions.In addition,depot-specific differences in adipose tiss... Background Adipose tissue plays a central role in regulating whole-body metabolic health,facilitated by the variety of cell types and their wide-ranging functions.In addition,depot-specific differences in adipose tissue have been shown to play important roles in different disease states including obesity,diabetes,and metabolic dysfunction in human and animal models.For early postpartum dairy cattle,metabolic dysfunction,triggered by a negative energy balance,is often manifested as subclinical ketosis(SCK).However,the role that subcutaneous(SAT)and visceral(VAT)adipose tissue depots,and their diverse cellular compositions,play in the response to subclinical ketosis conditions is unclear.Results Flank SAT and omental VAT were collected via laparotomy from five non-ketotic(NK;BHB≤0.8 mmol/L)and five subclinical ketosis(SCK;1.4 mmol/L<BHB≤2.6 mmol/L)multiparous cows during early lactation.Following collection,nuclei were isolated from the tissue and subjected to single-nuclei RNA sequencing in order to investigate the transcriptional cellular heterogeneity.Distinct clusters of adipocytes(AD),adipose stem/progenitor cells(ASPC),immune cells(IMC),endothelial cells(EC),and pericyte/smooth muscle cells(PE/SMC)were identified in both adipose depots,with a greater abundance of ASPC in SAT compared to VAT.In addition,we identified a VAT-specific AD subtype characterized by higher expression of progenitor-like marker genes.While the abundance of none of the identified cell subtypes were different between SCK and NK,underlying transcriptional changes provided insight into potential effects of SCK.In general,SCK was associated with pro-lipogenic,anti-inflammatory,and pro-angiogenic transcriptional changes,possibly indicating a greater capacity for homeostatic responsiveness in SAT under conditions of enhanced negative energy balance.In contrast,SCK appeared to promote transcriptional changes indicative of impaired adipogenesis,impaired angiogenesis,and increased inflammation in VAT.Conclusions Uniquely,our study presents novel insight into the cellular heterogeneity of adipose tissue in dairy cattle with subclinical ketosis.Furthering our understanding of the role of adipose tissue in response to this form of metabolic challenge has the potential to enhance efforts aimed at limiting the incidence and impact of subclinical ketosis and improving the health and productivity of dairy cattle. 展开更多
关键词 Adipose Dairy Depot Ketosis Single-nuclei
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Ketosis-prone diabetes mellitus:A phenotype that hospitalists need to understand 认领 引用 被引量：1
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作者 Sydney Boike Mikael Mir +7 位作者 Ibtisam Rauf Abbas B Jama Shaleen Sunesara Hisham Mushtaq Anwar Khedr Jain Nitesh Salim Surani Syed A Khan 《World Journal of Clinical Cases》 SCIE 2022年第30期10867-10872,共6页
Diabetes has been classified mainly into types 1 and 2.Some type 2 diabetes patients,when developing ketosis,have been labeled as having atypical diabetes.Lately,syndromes of ketosis-prone diabetes,primarily in patien... Diabetes has been classified mainly into types 1 and 2.Some type 2 diabetes patients,when developing ketosis,have been labeled as having atypical diabetes.Lately,syndromes of ketosis-prone diabetes,primarily in patients who we previously classified as type 2 diabetics,have emerged,and calls are being made to even reclassify diabetes.This mini-review will extensively deal with the historical,molecular,phenotypical,and clinical basis of why ketosis-prone diabetes is different than the traditional principles of type 1 and 2 diabetes and should be classified as such.Clinicians,especially those who are not diabetologists or endocrinologists,as well as hospitalists,intensivists,and primary care providers,will greatly benefit from this review. 展开更多
关键词 Diabetic ketoacidosis Diabetes Diabetes prone ketosis Ketosis Acidosis
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Hepatic metabolomics and transcriptomics to study susceptibility to ketosis in response to prepartal nutritional management 认领 引用 被引量：9
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作者 Khuram Shahzad Vincenzo Lopreiato +4 位作者 Yusheng Liang Erminio Trevisi Johan S.Osorio Chuang Xu Juan J.Loor 《Journal of Animal Science and Biotechnology》 SCIE CAS CSCD 2020年第1期194-210,共17页
Background:Ketosis in dairy cows is associated with body fat mobilization during the peripartal period.Sub-clinical and clinical ketosis arise more frequently in cows that are overfed energy during the entire dry(last... Background:Ketosis in dairy cows is associated with body fat mobilization during the peripartal period.Sub-clinical and clinical ketosis arise more frequently in cows that are overfed energy during the entire dry(last 50 to 45 days prior to parturition)or close-up period(last^28 days prepartum).Methods:A retrospective analysis was performed on 12 cows from a larger cohort that were fed a higher-energy diet[1.54 Mcal/kg of dry matter(DM);35.9%of DM corn silage and 13%of DM ground corn]during the close-up dry period,of which 6 did not develop clinical ketosis(OVE,0.83 mmol/L plasma hydroxybutyrate;BHB)and 6 were diagnosed with clinical ketosis(KET,1.4 mmol/L BHB)during the first week postpartum.A whole-transcriptome bovine microarray(Agilent Technologies)and metabolomics(GC-MS,LC-MS;Metabolon~?Inc.)were used to perform transcript and metabolite profiling of liver tissue harvested at-10 days relative to parturition which allowed to establish potential associations between prepartal transcriptome/metabolome profiles and susceptibility to clinical ketosis postpartum.Results:Cows in KET had greater(P=0.01)overall body weight between-2 and 1 week around parturition,but similar body condition score than OVE.Although dry matter intake(DMI)did not differ prepartum,KET cows had lower(P<0.01)DMI and similar milk yield as OVE cows during the first week postpartum.Transcriptome analysis revealed a total of 3065 differentially expressed genes(DEG;P≤0.05)in KET.Metabolomics identified 15 out of 313 total biochemical compounds significantly affected(P≤0.10)in KET.Among those,greater concentrations(P≤0.06,+2.3-fold)of glycochenodeoxycholate in KET cows also have been detected in humans developing non-alcoholic fatty liver disease.Bioinformatics analysis using the Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway database and the DEG revealed that,among the top 20 most-impacted metabolic pathway categories in KET,65%were overall downregulated.Those included’Metabolism of cofactors and vitamins’,’Biosynthesis of other secondary metabolites’,’Lipid’,’Carbohydrate’,and’Glycan biosynthesis and metabolism’.The lower relative concentration of glucose-6-phosphate and marked downregulation of fructose-1,6-bisphosphatase 2 and pyruvate dehydrogenase kinase 4 support a strong impairment in gluconeogenesis in prepartal liver of cows developing KET postpartum.Among the top 20 most-impacted non-metabolic pathways,85%were downregulated.Pathways such as’mTOR signalling’and’Insulin signalling’were among those.’Ribosome’,’Nucleotide excision repair’,and’Adherens junctions’were the only upregulated pathways in cows with KET.Conclusions:The combined data analyses revealed more extensive alterations of the prepartal liver transcriptome than metabolome in cows overfed energy and developing ketosis postpartum.The causative link between these tissue-level adaptations and onset of clinical ketosis needs to be studied further. 展开更多
关键词 Bioinformatics Ketosis Metabolomics Transition cow
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The effects of nutritional ketosis induced by Bigu-herbs regimen and ketogenic diet on diseases and aging 认领 引用
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作者 Yi-Dan Lu Xiao-Gu Liu Song Zheng 《Traditional Medicine Research》 2020年第5期322-336,共15页
The Bigu-herbs regimen,a Taoism(Taoism is an ancient Chinese Taoist philosophy system)special health-preserving technique to achieve longevity through strict abstinence from food,limits the intake of grains and uses h... The Bigu-herbs regimen,a Taoism(Taoism is an ancient Chinese Taoist philosophy system)special health-preserving technique to achieve longevity through strict abstinence from food,limits the intake of grains and uses herbs to replace normal diet to gain energy.Practicing Bigu-herbs regimen for several weeks to several years can make one lose weight,prevent diseases,and prolong life.The modern ketogenic diet(KD)mainly limits carbohydrate intake and increase fat intake.The low-carbohydrate,high-fat,and adequate protein diet is well known for its antiepileptic and neurotrophic effects.Limiting the intake of carbohydrate results in energy metabolism reprogramming to mobilize the steatolysis,energize and promote ketone bodies(KBs)production,achieving a state of nutritional ketosis(NK).The researchers summarized how ketone bodies or NK affects diseases and the aging process,as well as the side effects of KD.NK has a favorable effect on caloric intake,lipid parameters,glycemic index,and insulin sensitivity;moreover,it can be used as a treatment option for diabetes,obesity,and other metabolic disorders.NK is recognized as being neuroprotective and is good for epilepsy,Alzheimer’s disease,and emotional disturbance.Targeting the metabolic differences between tumor and normal cells,NK limits the use of glucose and impairs energy metabolism in cancer cells,inhibiting their growth and rendering them susceptible to clinical treatments.NK also affects inflammation and the release of cytokines,regulate gut flora,extend longevity and health span,and preserve physiologic functions.The side effects of KDs are controllable under the guidance of a specially trained dietitian and medical team. 展开更多
关键词 Grain avoidance Bigu-herbs regimen Ketogenic diet Nutritional ketosis Ketone body
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Trends of Kalemia at Diagnosis of Acidosis versus Non-Acidosis Diabetic Ketosis Décompensations in Ouagadougou (Burkina Faso) 认领 引用 被引量：1
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作者 Oumar Guira Hervé Tiéno +4 位作者 Abraham Bagbila Yempabou Sagna Gérard Coulibaly Lassané Zoungrana Joseph Y. Drabo 《Open Journal of Internal Medicine》 2016年第1期1-5,共5页
Introduction: Electrolyte’s profile in non-acidosis diabetic ketosis is poorly specified. We aimed to determine the nature of diabetic ketosis decompensations as well as the profile of kalemia and factors associated ... Introduction: Electrolyte’s profile in non-acidosis diabetic ketosis is poorly specified. We aimed to determine the nature of diabetic ketosis decompensations as well as the profile of kalemia and factors associated with its disorders at diagnosis of acidosis compared to non-acidosis diabetic ketosis. Methods: The study was retrospective from 1 January 2010 to 31 December 2011 in Yalgado Ouédraogo teaching hospital. Diabetic in-patients suffering from simple ketosis, keto-acidosis or mixed decompensation, who achieved blood electrolytes assessment before intensive insulin therapy were included. Results: Sixty two patients were studied. The sex ratio was 0.7 and the mean age was 41.7 years. Keto-acidosis, simple ketosis and mixed decompensation were diagnosed respectively in 18 (29%), 32 (51.6%) and 12 (19.4%) patients. Kalemia was normal in 42 (67.7%), while hypokalemia and hyperkalemia were reported respectively in 11 (17.8%) and 9 (14.5%) patients. Kalemia was often normal in all types of ketosis decompensation and disorders of kalemia occurred more in patients with keto-acidosis (50%) than those with simple ketosis (21.9%);p = 0.04. Renal failure was diagnosed in 10 patients (50%) with and 2 (4.8%) without kalemia’s disorders;p = 0.0001. Seven patients (35%) with and 4 (9.5%) without kalemia’s disorders suffered from unconsciousness;p = 0.02. It happens more in hyperkalemia (44.4%) than in normal kalemia condition (9.5%);p = 0.02. Conclusion: If kalemia is often normal in all types of diabetic ketosis emergencies, hypokalemia is the most initial frequent potassium disorder. 展开更多
关键词 Diabetic Ketosis Kalemia Disorders Burkina Faso
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Combination of nutritional ketosis and hyperoxygenation therapy-promising ground for integrative cancer treatment: a systematic review 认领 引用
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作者 Santhosh John 《TMR Integrative Medicine》 2021年第24期1-8,共8页
Though the cancer is a multifactorial disease,where various types of cancers exhibit varying mechanisms,pathways,genetic and cellular defects,the study of tumor micro-environment confirms that upregulated glycolysis a... Though the cancer is a multifactorial disease,where various types of cancers exhibit varying mechanisms,pathways,genetic and cellular defects,the study of tumor micro-environment confirms that upregulated glycolysis and hypoxia are the part and parcel of almost every cancer subtypes.Therefore,targeting them with nutritional ketosis and hyper-oxygenation therapies could create an unfavourable environment for cancers to thrive.The aim of this review is to study the significance of these interventions in the integrative cancer treatment.Extensive search has been carried out through the online scientific database like PubMed and other medical journals with the search words,‘cancer metabolism’,‘tumor micro environment’,‘hypoxia and tumor’,‘ketosis and cancer treatment’,‘hyperbaric oxygen therapy and cancer’and‘ozone therapy and cancer’.All biomolecule studies,preclinical and clinical studies,received as search results are reviewed.In addition,a nutritional book,named‘Healing with Whole Foods:Asian Traditions and Modern Nutrition’by Paul Pitchford is also referred.These studies recommend the use of various therapeutic approaches like ketogenic diet,ketone supplementation,hyperbaric oxygen therapy and intravenous ozone therapy,individually or in combination with standard therapies,based on its antitumor effects,safety,tolerability,its ability to potentiate the radio and chemo therapy,while decreasing its side effects and its efficiency to improve the quality of life.Rewardingly,when combined,the synergistic action of nutritional ketosis and hyperoxygenation therapies elicited profound,supra additive anti-cancer effects.As per present studies,these therapies are safe to include in an Integrative cancer treatment,though large clinical trials are needed to systematize its clinical usage. 展开更多
关键词 Cancer treatment Naturopathy Nutritional ketosis Hyperoxygenation therapies
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The Role of Vitamin D in Diabetes Ketosis and Ketoacidosis 认领 引用
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作者 Cui Zhang Jia Liu +2 位作者 Sumita Cholekho Qin Pei Huiwen Tan 《Chronic Diseases and Translational Medicine》 CAS CSCD 2025年第3期237-238,共2页
Diabetes mellitus(DM)is a common endocrine and metabolic disorder,and diabetes ketosis(DK)is a significant acute complication.Individuals with type 1 DM(T1DM)are inherently at risk for diabetic ketoacidosis(DKA).Indiv... Diabetes mellitus(DM)is a common endocrine and metabolic disorder,and diabetes ketosis(DK)is a significant acute complication.Individuals with type 1 DM(T1DM)are inherently at risk for diabetic ketoacidosis(DKA).Individuals with T2DM may develop DK under certain conditions,including infection,interruption of insulin therapy,stress,or excessive alcohol consumption.Recent studies have indicated that vitamin D supplementation reduces the risk of progression from prediabetes to T2DM and that it may also be involved in the prevention of diabetes complications.Yet most previous research has been observational correlations rather than interventional trials. 展开更多
关键词 diabetes ketosis dk prediabetes vitamin D diabetes mellitus dm vitamin d supplementation diabetic ketoacidosis dka individuals diabetes ketosis diabetic ketoacidosis
ACSL4 is a target forβ-hydroxybutyrate-induced increase in fatty acid content and lipid droplet accumulation in bovine mammary epithelial cells 认领 引用
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作者 Ming Li Jingjing Wang +8 位作者 Jia’nan Wen Juan JLoor Qianming Jiang Jingyi Wang Huijing Zhang Yue Yang Wei Yang Bingbing Zhang Chuang Xu 《Journal of Integrative Agriculture》 SCIE CAS CSCD 2026年第3期1137-1149,共13页
Ketosis,a common metabolic disease during early lactation,is associated with high circulating levels ofβ-hydroxybutyrate(BHB).A portion of BHB that reaches the mammary gland is utilized as precursor for synthesis of ... Ketosis,a common metabolic disease during early lactation,is associated with high circulating levels ofβ-hydroxybutyrate(BHB).A portion of BHB that reaches the mammary gland is utilized as precursor for synthesis of fatty acids.Recent findings from nonruminant studies revealed that long chain fatty acyl-CoA ligase 4(ACSL4)could play a role in the regulation of cellular fatty acid metabolism,but the mechanisms by which ACSL4 mediates cellular lipid metabolism in response to BHB remains unclear.To achieve the aims,we conducted in vivo or in vitro analyses using bovine mammary gland biopsies and the immortalized mammary epithelial cell line(MAC-T).The in vivo study(n=6 cows per group)involved healthy cows(plasma BHB2.0 mmol L–1)from which mammary gland tissue was biopsied.In vitro,MAC-T cells were challenged with 0,0.3,0.6,1.2,or 2.4 mmol L–1BHB for 24 h to determine an optimal dose.Subsequently,MAC-T were incubated with 1.2 mmol L–1BHB for 0,3,6,12,24,or 48 h.Furthermore,MAC-T cells were treated with small interfering ACSL4(siACSL4)for 24 h or ACSL4 overexpression plasmid(pcACSL4)for 36 h followed by a challenge with 1.2 mmol L–1BHB for 24 h.Results showed that increased mRNA and protein abundance of lipogenic genes were linked to both mammary gland and in vitro challenge with BHB.BHB increased fatty acid content by activating ACSL4 expression,whereas inhibition of ACSL4 reduced BHB-induced reactive oxygen species(ROS)overproduction,enhancement of mitochondrial membrane potential,increase in fatty acid content,and lipid droplet accumulation.Furthermore,we also elevated ACSL4 expression with an overexpression plasmid to clarify its molecular role in response to BHB challenge.ACSL4 overexpression enhances BHB-induced lipid droplet accumulation by increased fatty acid content.Overall,the information showed that ACSL4 is crucial for the process of producing fatty acids from exogenous BHB.Reduced ACSL4 decreased fatty acid content and lipid droplet accumulation,improved mitochondrial function,directed more fatty acids towards oxidation.Thus,ACSL4 plays an important role in determining the fate of intracellular fatty acids and BHB in BMECs. 展开更多
关键词 bovine mammary epithelial cells fatty acid content ketosis BHB ACSL4
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Free fatty acids induce apoptosis in mammary epithelial cells from ketotic dairy cows via endoplasmic reticulum stress 认领 引用
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作者 Renxu Chang Yuanyuan Chen +7 位作者 Xinyi Xu Hongdou Jia John Mauck Juan J.Loor Yehoshav A.Ben Meir Qiushi Xu Xudong Sun Chuang Xu 《Journal of Integrative Agriculture》 SCIE CAS CSCD 2026年第5期2014-2027,共14页
The mammary glands of dairy cows with ketosis face unique challenges,including the supraphysiological circulating concentrations of free fatty acids(FFA) and apoptosis of epithelial cells.The fact that endoplasmic ret... The mammary glands of dairy cows with ketosis face unique challenges,including the supraphysiological circulating concentrations of free fatty acids(FFA) and apoptosis of epithelial cells.The fact that endoplasmic reticulum(ER) stress and apoptosis are closely related processes(at least in nonruminants) suggests that mechanisms of metabolic stressinduced apoptosis in bovine mammary epithelial cells may involve the ER stress pathway.The objective of this study was to investigate(1) the status of the ER stress pathway in mammary gland of dairy cows with ketosis,and(2) the role of ER stress in the apoptosis of bovine mammary epithelial cells challenged with high concentrations of FFA.Ketosis or exogenous FFA activated the ER stress pathway in the mammary gland of dairy cows or MAC-T cells.Pretreatment with the ER stress activator Tunicamycin(Tun) aggravated ER stress and apoptosis in MAC-T cells induced by FFA.However,ER stress inhibitor Tauroursodeoxycholate(TUDCA) attenuated ER stress induced by FFA and also attenuated the apoptosis in MAC-T cells.In conclusion,the data confirmed that FFA induced apoptosis of bovine mammary epithelial cells in dairy cows with ketosis via ER stress signaling.Thus,timely resolution of ER stress may help counteract the negative effects of ketosis on the mammary gland. 展开更多
关键词 ketosis bovine mammary epithelial cells ER stress apoptosis
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Restoring Homeodynamics:Autophagy,Ageing and the Metabolic Correction of Disease 认领 引用
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作者 Andrew Scarborough Yvoni Kyriakidou +3 位作者 Derek C.Lee Tomás Duraj Thomas N.Seyfried Isabella D.Cooper 《BIOCELL》 SCIE 2026年第6期1-39,共39页
The global rise in chronic,non-communicable diseases(NCDs)is inextricably linked to metabolic dysfunction,with hyperinsulinaemia acting as a potent upstream driver of ageing and age-related disease.Some of the most bu... The global rise in chronic,non-communicable diseases(NCDs)is inextricably linked to metabolic dysfunction,with hyperinsulinaemia acting as a potent upstream driver of ageing and age-related disease.Some of the most burdensome diseases of our time,including type 2 diabetes,cardiovascular disease,cancer,and neurodegenerative conditions,such as Alzheimer’s disease(AD),are largely underpinned by insulin resistance as part of a broader system of metabolic and mitochondrial dysfunction.These pathologies are particularly pronounced in the developed world,where obesity and other lifestyle-related conditions are major contributors to disease burden and premature mortality.As an upstream event,persistent insulin signalling biases glucose metabolism,which in turn depletes nicotinamide adenine dinucleotide(NAD+),suppresses autophagy,mitophagy and mitochondrial biogenesis,indispensable processes that maintain cellular homeodynamics.When compensatory mechanisms ultimately begin to fail,mitochondrial dysfunction and oxidative stress fuel cycles of inflammation,senescence and genomic instability.In this context,therapeutic ketosis offers an attractive strategy for metabolic restoration,with effects across insulin-dependent and downstream signalling pathways.This narrative review considers various approaches for inducing ketosis and autophagy therapeutically,including fasting,varied dietary strategies and exogenous ketogenic agents.Among these agents,ketone monoesters represent an effective and well-characterised option to rapidly elevate circulating levels of bioidentical(R)-β-hydroxybutyrate(BHB).The utilisation of BHB is fundamental to the therapeutic benefits of ketosis,functioning not only as a highly efficient mitochondrial fuel in comparison to glucose,but also a potent signalling molecule that preserves redox balance,inhibits NOD-,LRR-and pyrin domain-containing protein 3(NLRP3)inflammasome activation,facilitates NAD+availability,and epigenetically regulates antioxidant and repair genes.By promoting mitophagy and mitochondrial renewal,BHB may confer protection against the metabolic hallmarks of ageing,with therapeutic potential across a spectrum of diseases linked to hyperinsulinaemia.This model,articulated conceptually through the Concentric Zone Model of Adaptive Balance,proposes that restoring homeodynamics via ketosis represents a powerful strategy for metabolic correction,challenging the traditional paradigm of disease management.Under this conceptual framework,the review aims to examine the potential of therapeutic ketosis to restore metabolic flexibility,facilitate autophagy and regulate key nutrient-sensing pathways associated with ageing and disease. 展开更多
关键词 Ageing autophagy homeodynamics hyperinsulinaemia ketosis ketogenic diet ketogenic metabolic therapy(KMT) β-hydroxybutyrate(BHB) metabolic flexibility mitochondrial dysfunction
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Prevalence of diabetic retinopathy across different diabetes phenotypes 认领 引用
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作者 Ashu Rastogi Anshu Khamesra 《World Journal of Diabetes》 SCIE 2026年第6期72-81,共10页
Diabetic retinopathy(DR)is a glucose-defining complication with varying prevalence reported depending upon the duration of diabetes,degree of glycemic control,and associated other microvascular complications,particula... Diabetic retinopathy(DR)is a glucose-defining complication with varying prevalence reported depending upon the duration of diabetes,degree of glycemic control,and associated other microvascular complications,particularly nephropathy,defined by albuminuria and reduced glomerular filtration rate.The prevalence of DR also varies with the diabetes phenotype,with ketosis-prone diabetes having DR as prevalent as type 2 diabetes,but less than type 1 diabetes,matched for age and gender.An increasing prevalence in ketosis-prone diabetes plausibly could be due to ketonemia increasing permeability of blood-retinal layer contributing to inflammation.The guidelines for initial screening and evaluation of DR suggest similar strategies across diabetes phenotypes.Recent advances in DR diagnosis with advanced imaging technologies with artificial intelligence shall enable earlier detection with improved accuracy across varied diabetes phenotypes to reduce preventable blindness due to DR. 展开更多
关键词 Diabetic retinopathy Ketosis prone diabetes Type 2 diabetes Type 1 diabetes Maturity-onset diabetes of the young Ketonemia Vascular permeability
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Application of an electronic nose for the diagnosis of ketosis in dairy cows 认领 引用 被引量：4
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作者 Enqiu Zhang Fang Wang +6 位作者 Chun Yin Haizhong Wang Yujun Zhu Hongwei Duan Shuai Yang Yong Zhang Junjie Hu 《Food Bioscience》 SCIE 2024年第4期2000-2008,共9页
Ketosis in dairy cows is a nutritional and metabolic disease that severely affects the milk industry and dairy cow health.An electronic nose can identify volatile organic compounds(VOCs).This study applied the electro... Ketosis in dairy cows is a nutritional and metabolic disease that severely affects the milk industry and dairy cow health.An electronic nose can identify volatile organic compounds(VOCs).This study applied the electronic nose to detect VOCs in dairy cow milk,feces,and blood.Blood ketone bodies(BHBA)were measured,and 10 ketosis cows,71 subclinical ketosis cows,and 75 healthy cows were considered the research subjects.Cow milk,feces,and blood samples were collected for electronic nose testing.The measured VOC data were processed through multivariate analysis and machine learning algorithms.The electronic nose analysis results were validated through the GC-MS analysis of the milk samples.The results unveiled spatial differences in the electronic nose VOC values of milk,feces,and blood,and the cumulative contribution rates of both principal component variables(PC)1 and PC2 reached more than 95%.The machine learning algorithm results revealed that the accuracy of the milk probabilistic neural network(PNN)was 87.5%,the stool support vector machine was 100%,and the blood PNN was 66.7%.This result revealed that electronic nose detection can effectively differentiate healthy,subclinical ketosis,and clinical ketosis cows.According to the milk GC-MS results,significant differences were noted in the VOC content of milk samples between the different groups.The aforementioned studies revealed that electronic nose can aid in the effective prediction and diagnosis of ketosis in dairy cows.This lays the foundation for establishing a new method for diagnosing ketosis in dairy cows. 展开更多
关键词 Dairy cows Ketosis Electronic nose VOCs Diagnosis
Euglycemic diabetic ketoacidosis:A missed diagnosis 认领 引用 被引量：20
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作者 Prashant Nasa Sandeep Chaudhary +1 位作者 Pavan Kumar Shrivastava Aanchal Singh 《World Journal of Diabetes》 SCIE 2021年第5期514-523,共10页
Euglycemic diabetic ketoacidosis(DKA)is an acute life-threatening metabolic emergency characterized by ketoacidosis and relatively lower blood glucose(less than 11 mmol/L).The absence of hyperglycemia is a conundrum f... Euglycemic diabetic ketoacidosis(DKA)is an acute life-threatening metabolic emergency characterized by ketoacidosis and relatively lower blood glucose(less than 11 mmol/L).The absence of hyperglycemia is a conundrum for physicians in the emergency department and intensive care units;it may delay diagnosis and treatment causing worse outcomes.Euglycemic DKA is an uncommon diagnosis but can occur in patients with type 1 or type 2 diabetes mellitus.With the addition of sodium/glucose cotransporter-2 inhibitors in diabetes mellitus management,euglycemic DKA incidence has increased.The other causes of euglycemic DKA include pregnancy,fasting,bariatric surgery,gastroparesis,insulin pump failure,cocaine intoxication,chronic liver disease and glycogen storage disease.The pathophysiology of euglycemic DKA involves a relative or absolute carbohydrate deficit,milder degree of insulin deficiency or resistance and increased glucagon/insulin ratio.Euglycemic DKA is a diagnosis of exclusion and should be considered in the differential diagnosis of a sick patient with a history of diabetes mellitus despite lower blood glucose or absent urine ketones.The diagnostic workup includes arterial blood gas for metabolic acidosis,serum ketones and exclusion of other causes of high anion gap metabolic acidosis.Euglycemic DKA treatment is on the same principles as for DKA with correction of dehydration,electrolytes deficit and insulin replacement.The dextrosecontaining fluids should accompany intravenous insulin to correct metabolic acidosis,ketonemia and to avoid hypoglycemia. 展开更多
关键词 Diabetic Ketoacidosis Sodium/glucose co-transporter-2 inhibitors Pregnancy with diabetic ketoacidosis Diabetes complications Pregnancy in diabetes Ketosis Metabolic acidosis
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Sirtuin 3 regulation:a target to alleviateβ-hydroxybutyric acid-induced mitochondrial dysfunction in bovine granulosa cells 认领 引用 被引量：3
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作者 Shanjiang Zhao Jianfei Gong +6 位作者 Yi Wang Nuo Heng Huan Wang Zhihui Hu Haoyu Wang Haobo Zhang Huabin Zhu 《Journal of Animal Science and Biotechnology》 SCIE CAS CSCD 2023年第4期1377-1394,共18页
Background During the transition period,the insufficient dry matter intake and a sharply increased in energy consumption to produce large quantities of milk,high yielding cows would enter a negative energy balance(NEB... Background During the transition period,the insufficient dry matter intake and a sharply increased in energy consumption to produce large quantities of milk,high yielding cows would enter a negative energy balance(NEB)that causes an increase in ketone bodies(KBs)and decrease in reproduction efficiency.The excess concentrations of circulating KBs,represented byβ-hydroxybutyric acid(BHBA),could lead to oxidative damage,which potentially cause injury to follicular granulosa cells(fGCs)and delayed follicular development.Sirtuin 3(Sirt3)regulates mitochondria reactive oxygen species(mitoROS)homeostasis in a beneficial manner;however,the molecular mechanisms underlying its involvement in the BHBA-induced injury of fGCs is poorly understood.The aim of this study was to explore the protection effects and underlying mechanisms of Sirt3 against BHBA overload-induced damage of fGCs.Results Our findings demonstrated that 2.4 mmol/L of BHBA stress increased the levels of mitoROS in bovine fGCs.Further investigations identified the subsequent mitochondrial dysfunction,including an increased abnormal rate of mitochondrial architecture,mitochondrial permeability transition pore(MPTP)opening,reductions in mitochondrial membrane potential(MMP)and Ca2+release;these dysfunctions then triggered the caspase cascade reaction of apoptosis in fGCs.Notably,the overexpression of Sirt3 prior to treatment enhanced mitochondrial autophagy by increasing the expression levels of Beclin-1,thus preventing BHBA-induced mitochondrial oxidative stress and mitochondrial dysfunction in fGCs.Furthermore,our data suggested that the AMPK-mTOR-Beclin-1 pathway may be involved in the protective mechanism of Sirt3 against cellular injury triggered by BHBA stimulation.Conclusions These findings indicate that Sirt3 protects fGCs from BHBA-triggered injury by enhancing autophagy,attenuating oxidative stress and mitochondrial damage.This study provides new strategies to mitigate the fGCs injury caused by excessive BHBA stress in dairy cows with ketosis. 展开更多
关键词 BHBA Dairy cows Granulosa cells Ketosis Mitochondrial function Sirt3
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Investigation of HCAR2 antagonists as a potential strategy to modulate bovine leukocytes 认领 引用 被引量：1
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作者 Laman K.Mamedova Kirby C.Krogstad +4 位作者 Paiton O.McDonald Laxman Pokhrel Duy H.Hua Evan C.Titgemeyer Barry J.Bradford 《Journal of Animal Science and Biotechnology》 SCIE CAS CSCD 2024年第4期1567-1577,共11页
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 Ca2+ mobilization in neutrophils and mononuclear cells. Mononuclear cells treated with BHBA had diminished intracellular Ca2+ responses when HCAR2 was knocked down by si RNA silencing, indicating Ca2+ 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 Ca2+ 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 Ca2+ mobilization in a HCAR2-dependent manner. 展开更多
关键词 Flow cytometry GPR109A HM74A Ketosis
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Use of sodium bicarbonate and blood gas monitoring in diabetic ketoacidosis: A review 认领 引用 被引量：3
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作者 Mit P Patel Ali Ahmed +1 位作者 Tharini Gunapalan Sean E Hesselbacher 《World Journal of Diabetes》 SCIE 2018年第11期199-205,共7页
Diabetic ketoacidosis(DKA) is a severe and toocommon complication of uncontrolled diabetes mellitus. Acidosis is one of the fundamental disruptions stemming from the disease process, the complications of which are pot... Diabetic ketoacidosis(DKA) is a severe and toocommon complication of uncontrolled diabetes mellitus. Acidosis is one of the fundamental disruptions stemming from the disease process, the complications of which are potentially lethal. Hydration and insulin administration have been the cornerstones of DKA therapy; however, adjunctive treatments such as the use of sodium bicarbonate and protocols that include serial monitoring with blood gas analysis have been much more controversial. There is substantial literature available regarding the use of exogenous sodium bicarbonate in mild to moderately severe acidosis; the bulk of the data argue against significant benefit in important clinical outcomes and suggest possible adverse effects with the use of bicarbonate. However, there is scant data to support or refute the role of bicarbonate therapy in very severe acidosis. Arterial blood gas(ABG) assessment is an element of some treatment protocols, including society guidelines, for DKA. We review the evidence supporting these recommendations. In addition, we review the data supporting some less cumbersome tests, including venous blood gas assessment and routine chemistries. It remains unclear that measurement of blood gas pH, via arterial or venous sampling, impacts management of the patient substantially enough to warrant the testing, especially if sodium bicarbonate administration is not being considered. There are special circumstances when serial ABG monitoring and/or sodium bicarbonate infusion are necessary, which we also review. Additional studies are needed to determine the utility of these interventions in patients with severe DKA and pH less than 7.0. 展开更多
关键词 Diabetic ketoacidosis Sodium bicarbonate Blood gas analysis Acidosis Ketosis Ketone bodies Hyperglycemia
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Early vs late oral nutrition in patients with diabetic ketoacidosis admitted to a medical intensive care unit 认领 引用
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作者 Kirill Lipatov Kevin K Kurian +4 位作者 Courtney Shaver Heath D White Shekhar GhamANDe AlejANDro C Arroliga Salim Surani 《World Journal of Diabetes》 SCIE 2019年第1期57-62,共6页
BACKGROUND Diabetic ketoacidosis(DKA) has an associated mortality of 1% to 5%. Upon admission, patients require insulin infusion and close monitoring of electrolyte and blood sugar levels with subsequent transitioning... BACKGROUND Diabetic ketoacidosis(DKA) has an associated mortality of 1% to 5%. Upon admission, patients require insulin infusion and close monitoring of electrolyte and blood sugar levels with subsequent transitioning to subcutaneous insulin and oral nutrition. No recommendations exist regarding the appropriate timing for initiation of oral nutrition.AIM To assess short-term outcomes of oral nutrition initiated within 24 h of patients being admitted to a medical intensive care unit(MICU) for DKA.METHODS A retrospective observational cohort study was conducted at a single academic medical center. The patient population consisted of adults admitted to the MICU with the diagnosis of DKA. Baseline characteristics and outcomes were compared between patients receiving oral nutrition within(early nutrition group) and after(late nutrition group) the first 24 h of admission. The primary outcome was 28-d mortality. Secondary outcomes included 90-d mortality, MICU and hospital lengths of stay(LOS), and time to resolution of DKA.RESULTS There were 128 unique admissions to the MICU for DKA with 67 patientsreceiving early nutrition and 61 receiving late nutrition. The APACHE(Acute Physiology and Chronic Health Evaluation) IV mortality and LOS scores and DKA severity were similar between the groups. No difference in 28-or 90-d mortality was found. Early nutrition was associated with decreased hospital and MICU LOS but not with prolonged DKA resolution, anion gap closure, or greater rate of DKA complications.CONCLUSION In patients with DKA, early nutrition was associated with a shorter MICU and hospital LOS without increasing the rate of DKA complications. 展开更多
关键词 Diabetes mellitus Diabetic ketoacidosis Diabetic complications Acidosis Ketosis Critical care
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Preserving finger length in a patient with symmetric digital gangrene under local anesthesia:A case report 认领 引用
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作者 Keun Hyung Kim In Chang Ko +1 位作者 Hoon Kim Soo Yeon Lim 《World Journal of Clinical Cases》 SCIE 2023年第27期6640-6645,共6页
BACKGROUND Case reports of symmetric digital gangrene resulting from high-dose vasopressors use in patients with alcoholic ketoacidosis,leading to cardiac arrest,are rare.To date,no specific treatment method for autol... BACKGROUND Case reports of symmetric digital gangrene resulting from high-dose vasopressors use in patients with alcoholic ketoacidosis,leading to cardiac arrest,are rare.To date,no specific treatment method for autolysis or surgical amputation or guidelines for determining the level of amputation have been established.CASE SUMMARY In this case report,we describe a treatment method that effectively preserved the function of fingers by surgical treatment under local anesthesia with a minimum operative time,while also preserving finger length to the maximum possible extent.CONCLUSION Our approach may contribute to improved postoperative quality of life by preserving finger length. 展开更多
关键词 Acidosis Disseminated intravascular coagulation Ketosis Purpura fulminans Surgical amputation Case report
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“酮粉法”连续一年监测大群奶牛酮病试验简报 认领 引用
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作者 吴齐鸿 商常发 +2 位作者 李光辉 刘士喜 陈会良 《安徽科技学院学报》 1989年第1期48-50,共3页
为探寻监测奶牛酮病的方法,试验用“酮粉法”快速检验酮病的效果,探讨安徽省奶牛酮病的发病规律,为防治本病提供科学依据,在一年时间内,连续对安徽合肥保健奶牛场和淮南奶牛一场、二场的泌乳母牛,进行了全面的,每月一次的监测。通过对... 为探寻监测奶牛酮病的方法,试验用“酮粉法”快速检验酮病的效果,探讨安徽省奶牛酮病的发病规律,为防治本病提供科学依据,在一年时间内,连续对安徽合肥保健奶牛场和淮南奶牛一场、二场的泌乳母牛,进行了全面的,每月一次的监测。通过对近一万头次的监测发现,这几个场奶牛酮病的发病率在头年的十一月份到第二年的四月份发病率较高(平均为3.7%),其中二月份发病率最高(6.62%)。 展开更多
关键词 Tongfen" method (invented in this test) ketosis inci-dence
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