The development of neurodegenerative diseases is closely related to the disruption of central nervous system homeostasis.Microglia,as innate immune cells,play important roles in the maintenance of central nervous syst...The development of neurodegenerative diseases is closely related to the disruption of central nervous system homeostasis.Microglia,as innate immune cells,play important roles in the maintenance of central nervous system homeostasis,injury response,and neurodegenerative diseases.Lactate has been considered a metabolic waste product,but recent studies are revealing ever more of the physiological functions of lactate.Lactylation is an important pathway in lactate function and is involved in glycolysis-related functions,macrophage polarization,neuromodulation,and angiogenesis and has also been implicated in the development of various diseases.This review provides an overview of the lactate metabolic and homeostatic regulatory processes involved in microglia lactylation,histone versus non-histone lactylation,and therapeutic approaches targeting lactate.Finally,we summarize the current research on microglia lactylation in central nervous system diseases.A deeper understanding of the metabolic regulatory mechanisms of microglia lactylation will provide more options for the treatment of central nervous system diseases.展开更多
Lactate,as a metabolite,plays a significant role in a number of fields,including medical diagnostics,exercise physiology and food science.Traditional methods for lactate measurement often involve expensive and cumbers...Lactate,as a metabolite,plays a significant role in a number of fields,including medical diagnostics,exercise physiology and food science.Traditional methods for lactate measurement often involve expensive and cumbersome instrumentation.This study developed a portable and low-cost lactate measurement system,including independently detectable hardware circuits and user-friendly embedded software,computer,and smartphone applications.The experiment verified that the relative error of the detection current in the device circuit was less than 1%.The electrochemical performance was measured by comparing the[Fe(CN)_(6)]^(3−)/[Fe(CN)_(6)]^(4−)solution with the desktop electrochemical workstation CHI660E,and a nearly consistent chronoamperometry(CA)curve was obtained.Two modified lactate sensors were used for CA testing of lactate.Within the concentration range of 0.1 mmol·L^(−1)to 20 mmol·L^(−1),there was a good linear relationship between lactate concentration and steady-state current,with a correlation coefficient(R2)greater than 0.99 and good repeatability,demonstrating the reliability of the developed device.The lactate measurement system developed in this study not only provides excellent detection performance and reliability,but also achieves portability and low cost,providing a new solution for lactate measurement.展开更多
Research into lactylation modifications across various target organs in both health and disease has gained significant attention.Many essential life processes and the onset of diseases are not only related to protein ...Research into lactylation modifications across various target organs in both health and disease has gained significant attention.Many essential life processes and the onset of diseases are not only related to protein abundance but are also primarily regulated by various post-translational protein modifications.Lactate,once considered merely a byproduct of anaerobic metabolism,has emerged as a crucial energy substrate and signaling molecule involved in both physiological and pathological processes within the nervous system.Furthermore,recent studies have emphasized the significant role of lactate in numerous neurological diseases,including Alzheimer's disease,Parkinson's disease,acute cerebral ischemic stroke,multiple sclerosis,Huntington's disease,and myasthenia gravis.The purpose of this review is to synthesize the current research on lactate and lactylation modifications in neurological diseases,aiming to clarify their mechanisms of action and identify potential therapeutic targets.As such,this work provides an overview of the metabolic regulatory roles of lactate in various disorders,emphasizing its involvement in the regulation of brain function.Additionally,the specific mechanisms of brain lactate metabolism are discussed,suggesting the unique roles of lactate in modulating brain function.As a critical aspect of lactate function,lactylation modifications,including both histone and non-histone lactylation,are explored,with an emphasis on recent advancements in identifying the key regulatory enzymes of such modifications,such as lactylation writers and erasers.The effects and specific mechanisms of abnormal lactate metabolism in diverse neurological diseases are summarized,revealing that lactate acts as a signaling molecule in the regulation of brain functions and that abnormal lactate metabolism is implicated in the progression of various neurological disorders.Future research should focus on further elucidating the molecular mechanisms underlying lactate and lactylation modifications and exploring their potential as therapeutic targets for neurological diseases.展开更多
Lactate serves as a key energy metabolite in the central nervous system,facilitating essential brain functions,including energy supply,signaling,and epigenetic modulation.Moreover,it links epigenetic modifications wit...Lactate serves as a key energy metabolite in the central nervous system,facilitating essential brain functions,including energy supply,signaling,and epigenetic modulation.Moreover,it links epigenetic modifications with metabolic reprogramming.Nonetheless,the specific mechanisms and roles of this connection in astrocytes remain unclear.Therefore,this review aims to explore the role and specific mechanisms of lactate in the metabolic reprogramming of astrocytes in the central nervous system.The close relationship between epigenetic modifications and metabolic reprogramming was discussed.Therapeutic strategies for targeting metabolic reprogramming in astrocytes in the central nervous system were also outlined to guide future research in central nervous system diseases.In the nervous system,lactate plays an essential role.However,its mechanism of action as a bridge between metabolic reprogramming and epigenetic modifications in the nervous system requires future investigation.The involvement of lactate in epigenetic modifications is currently a hot research topic,especially in lactylation modification,a key determinant in this process.Lactate also indirectly regulates various epigenetic modifications,such as N6-methyladenosine,acetylation,ubiquitination,and phosphorylation modifications,which are closely linked to several neurological disorders.In addition,exploring the clinical applications and potential therapeutic strategies of lactic acid provides new insights for future neurological disease treatments.展开更多
Background Lactational performance depends heavily on age,health,and nutrition.L-Citrulline(Cit)is an effective precursor of L-arginine(Arg),an amino acid that has important roles in synthesis of nitric oxide(NO)and p...Background Lactational performance depends heavily on age,health,and nutrition.L-Citrulline(Cit)is an effective precursor of L-arginine(Arg),an amino acid that has important roles in synthesis of nitric oxide(NO)and polyamines.Ruminal microbes degrade extracellular Arg;however,extracellular L-citrulline(Cit)is not degraded by ruminal microbes due to lack of uptake and can be fed unencapsulated as a precursor for Arg.As NO is a vasodilator,an increase in blood flow and transport of molecules to mammary tissue may enhance lactational performance and milk composition.Increases in polyamine production may increase milk protein synthesis within mammary tissue,thus increasing milk protein content.This study determined,for the first time,effects of dietary Cit supplementation on milk production and milk composition of Alpine dairy goats.Methods Does were synchronized to estrus and bred to Alpine bucks.Parturition was induced on d 149 of gestation and does were suckled overnight allowing kid(s)to obtain colostrum before being milked 24 h later(d 1 of lactation).Does were assigned to either control(CON,n=24)or Cit(CIT,n=23)diets.The isonitrogenous control diet consisted of 97.63%basal diet and 2.37%supplement(1.37%L-alanine and 1.00%soybean hydrogenated oil).The CIT supplemented diet consisted of 97.63%basal diet and 2.37%supplement(0.5%Cit,0.5%L-glutamine,1%soybean hydrogenated oil,0.37%cornstarch).Diets were group fed ad-libitum by treatment group.Blood samples were collected on d 0 and 30 of lactation,milk volumes measured twice daily,and on d 10,20,and 40 of lactation,milk samples were collected.Results CIT-treated does had greater daily milk production(P<0.05)and there was an effect of day of lactation on daily milk production(P<0.0001).Sire had significant effect on daily milk production as well(P<0.05).Milk compositional analyses revealed Cit supplementation increased solid-non-fat(SNF;P<0.05)and protein(P<0.05)content in milk.Conclusions Our novel results indicate that dietary supplementation of Cit fed ad-libitum in Alpine does increased daily milk yield,milk SNF content,and protein content.Supplemental Cit may be a proxy for Arg in goats to enhance lactational performance.展开更多
Background Lactate is a classical byproduct of glucose metabolism,and the main lactate production pathway depends on glycolysis.Lactate stabilized HIF1αby inhibiting PHD activity,leading to hypoxic stress response an...Background Lactate is a classical byproduct of glucose metabolism,and the main lactate production pathway depends on glycolysis.Lactate stabilized HIF1αby inhibiting PHD activity,leading to hypoxic stress response and exacerbating glycolysis in multiple tissues.However,the redox induction mechanism of lactate in mammary gland has not been understood yet.Herein,we describe a lactate-responsive HIF1α/circadian control mechanism in oxidative stress in the mammary glands of dairy cows.Results The in vivo study showed that dairy cows with high lactate concentrations are associated with reduced milk yield and more ROS accumulation in mammary gland.Western blot results in MAC-T cells showed positive correlation between lactate concentrations,expression of HIF1αand oxidative stress indicators,but not circadian core components.To test how lactate-mediated HIF1αdysfunction leads to cell protection process,we investigated altered expression of circadian core related genes following HIF1αstabilization.We found that stabilized HIF1αby lactate inhibited stimulated expression of circadian core components due to the similarity of HRE and E-box transcription elements.Furthermore,we found that lactate treatment strengthened the binding of HIF1αwith BMAL1,HMOX1 and FOXO3 in MAC-T cells.Moreover,HIF1αknockdown altered expression of circadian rhythm related genes and reduced oxidative stress state.Conclusion In summary,our study highlights the central role of competitive transcriptional element occupancy in lactate-mediated oxidative stress of mammary gland,which is caused by HIF1αstabilization and circadian rhythm dysfunction.Our findings introduce a novel nutritional strategy with potential applications in dairy farming for optimizing milk production and maintaining mammary gland health.展开更多
Background Feeding spray dried plasma(SDP)to weanling pigs improves growth,but there is a lack of research on how SDP impacts oxidative stress and inflammatory response in lactating sows,and performance of their pigle...Background Feeding spray dried plasma(SDP)to weanling pigs improves growth,but there is a lack of research on how SDP impacts oxidative stress and inflammatory response in lactating sows,and performance of their piglets after weaning.Therefore,an experiment was conducted to test the hypothesis that sows fed a diet with SDP in late gestation and lactation have improved reproductive performance and reduced inflammation compared with sows fed no SDP.The second hypothesis was that pigs weaned from sows fed 0.5%SDP in lactation have reduced diarrhea incidence and improved growth performance during the initial 14 d of the nursery period regardless of dietary SDP.Results The percent of low vitality or starved pigs during lactation was less(P<0.05)from sows fed 0.5%dietary SDP compared with sows fed the diet without SDP.Dietary SDP did not influence oxidative stress markers in the plasma of sows,but serum cytokines increased(P<0.05)in sows fed the diet with 0.5%SDP compared with sows fed the diet without SDP.Pigs weaned from young sows fed no SDP or from mature sows fed 0 or 0.5%SDP had a greater gain to feed ratio when fed a phase 1 diet containing 6%SDP compared with pigs fed a diet without SDP,but the gain to feed ratio of pigs weaned from young sows fed 0.5%dietary SDP was not affected by dietary SDP in phase 1(interaction,P<0.05).Regardless of sow treatment,pigs fed a phase 1 diet with 6%SDP had greater(P<0.05)growth performance than pigs fed a phase 1 diet without SDP,and pigs fed the phase 1 diet with 6%SDP had reduced(P<0.05)diarrhea incidence in phase 1.Conclusions Feeding 0.5%dietary SDP to sows may reduce the number of mummified pigs and increase pig vitality during lactation,but adding 0.5%SDP to sow diets during lactation did not improve post-weaning performance of pigs fed a starter diet with 6%SDP.展开更多
Background Organic acids(OA)and maternal nutritional strategies have been demonstrated to promote piglet health and development.The objective of this study was to investigate the effects of incorporating OA-preserved ...Background Organic acids(OA)and maternal nutritional strategies have been demonstrated to promote piglet health and development.The objective of this study was to investigate the effects of incorporating OA-preserved cereal grains into sow diets during late gestation and lactation,aiming to reduce the metabolic demands of lactation while optimising offspring development and growth until slaughter.The experiment compared OA-preserved wheat and barley to conventionally dried grains,focusing on sow and offspring performance,as well as their faecal microbiota during lactation.Forty sows were blocked based on parity,body weight and back fat thickness on d 100 of gestation and assigned to one of two diets:a dried grain lactation diet and a preserved grain lactation diet.Sow faecal samples were collected at farrowing for the coefficient of apparent total tract digestibility(CATTD)of nutrients and microbial analysis.Offspring faecal samples were collected on d 10 postpartum and at weaning(d 26 postpartum)for microbial analysis.Results Sow body weight,back fat changes,gestation and lactation length,total piglets born,wean-to-oestrus interval,and lactation efficiency were unaffected by sow diet(P>0.05).However,sows offered the preserved grain diet exhibited improved CATTD of dry matter,nitrogen,gross energy,and neutral detergent fibre(P<0.05).While no maternal effect was observed on offspring growth during lactation(P>0.05),pigs from sows offered the preserved grain diet showed improved growth and feed efficiency from weaning until slaughter(d 168)compared to those from sows offered the dried grain diet(P<0.05).The preserved grain diet also reduced the abundance of Proteobacteria in sow faeces at farrowing and in their offspring on d 10 postpartum,and improved piglet faecal scores throughout lactation(P=0.05).At weaning,piglets from sows offered the preserved grain diet exhibited an increased abundance of Lactobacillus and reduced abundance of Alistipes in their faeces(P<0.05).Conclusion OA-preserved grains enhanced the CATTD of nutrients in sows,promoted healthier piglet faecal scores during lactation,and improved offspring growth performance post-weaning,potentially linked to beneficial changes observed in the faecal microbiota of sows and their offspring during lactation.展开更多
The interaction between the lactate receptor GPR81(also known as hydroxycarboxylic acid receptor 1,or HCAR1)and Splicing Factor Proline-and Glutamine-Rich protein promotes the tumor cell malignancy.GPR81 nuclear trans...The interaction between the lactate receptor GPR81(also known as hydroxycarboxylic acid receptor 1,or HCAR1)and Splicing Factor Proline-and Glutamine-Rich protein promotes the tumor cell malignancy.GPR81 nuclear translocation plays an important role in driving cancer progression and could serve as a potential therapeutic target.Yang et al concluded in their study that lactate and its receptor,GPR81,play crucial roles in cancer progression,and are key players in linking the lactate-rich tumor microenvironment to cancer cell behavior.The ability of nuclear GPR81 to directly regulate gene expression,combined with extracellular matrix-mediated mechanical signaling,creates a potentially robust system for the coordinated adaptation and survival of cancer cells.Understanding these interactions could lead to the discovery of new therapeutic targets and improved treatment strategies for cancer.展开更多
Background This study investigated the potential impacts of increasing linoleic andα-linolenic acid intake during lactation and wean-to-breeding on subsequent reproduction of sows.A total of 309 sows(PIC Camborough L...Background This study investigated the potential impacts of increasing linoleic andα-linolenic acid intake during lactation and wean-to-breeding on subsequent reproduction of sows.A total of 309 sows(PIC Camborough L42)were balanced by parity(140 and 169 sows representing parity 1 to 2[P1-2]and 3 to 9[P3+],respectively)and assigned within parity to a 2×2 factorial arrangement.Factors included essential fatty acid(EFA)supplementation(control diets containing 1.2%linoleic and 0.15%α-linolenic acid or diets with 3.0%linoleic and 0.38%α-linolenic acid)and supplementation period(lactation or wean-to-breeding).Tallow(low EFA diets)or soybean oil(high EFA diets)were included at 4%in sorghum-soybean meal-wheat middlings-based diets to attain targeted EFA levels.Results High levels of EFA fed during lactation had no effect on feed intake or litter performance,but increased subsequent farrowing rate(P=0.027;82.1%vs.70.4%),tended to reduce the proportion of sows removed(P=0.070;12.4%vs.20.8%),decreased the number of total pigs born in the following litter(P=0.072;15.3 vs.16.2),and increased total pigs born alive per 100 sows weaned(P=0.062;1,122 vs.974),regardless of sow parity.Young sows(P1-2)consuming the high EFA diet during lactation displayed a shorter wean-to-estrus interval(P=0.035;4.2 vs.4.6),but P3+sows were unaffected.Increasing EFA intake for P3+sows,but not P1-2 sows,resulted in more sows bred by d 5(P=0.028;91.1%vs.81.7%)and more mummies in the subsequent litter(P=0.040;0.32 vs.0.16).Feeding increased EFA to P1-2 sows during the wean-to-breeding period decreased subsequent farrowing rate(P=0.042;72.0%vs.87.7%),and increased removal rate(P=0.003;28.8%vs.9.4%).Total pigs born alive per 100 sows weaned was reduced(P=0.007)in P1-2 sows when supplemented with EFA during wean-breeding(939 vs.1,149)but was not impacted in P3+sows(1,131 vs.982).Conclusions Supplemental EFA in lactation diets benefited subsequent reproduction of sows,regardless of parity.Increasing dietary levels of EFA during the wean-to-breeding period to younger sows negatively impacted subsequent reproduction.展开更多
BACKGROUND Acute pancreatitis(AP)is a severe condition,and abdominal effusion is a significant predictor of its severity and prognosis.However,the relationship between ascites characteristics and AP outcomes remains u...BACKGROUND Acute pancreatitis(AP)is a severe condition,and abdominal effusion is a significant predictor of its severity and prognosis.However,the relationship between ascites characteristics and AP outcomes remains undefined.AIM To assess the correlation between ascites characteristics and clinical prognosis in AP patients by comparing color depth and turbidity of early ascites.METHODS This study included 667 AP patients with ascites,categorized by color and turbidity into yellow clear(n=54),yellow turbid(n=293),red brown(n=320).The trendχ2 test was employed to analyze the incidence of organ failure(OF),infected pancreatic necrosis(IPN),and mortality across groups.Receiver operating charac teristic(ROC)curves were used to evaluate the predictive value of ascites cell count,amylase,protein,and lactate dehydrogenase(LDH)for abdominal compartment syndrome(ACS)and intra-abdominal hemorrhage.RESULTS AP patients with ascites exhibited higher scores of scoring systems(such as Bedside index for severity in AP,Acute Physiology and Chronic Health Examination II,etc.)and increased complications and mortality rates(all P<0.05)compared to those without ascites.A linear association was observed between ascites color depth and turbidity and the incidence of OF,pancreatic necrosis,IPN,and mortality(P<0.05).LDH in ascites demonstrated high accuracy in predicting ACS and intra-abdominal hemorrhage,with areas under the ROC curve of 0.77 and 0.79,respectively.CONCLUSION Early in AP,ascites correlates with OF,IPN,and mortality,showing linear associations with color depth and turbidity.Ascitic LDH reliably predicts ACS and intra-abdominal hemorrhage in AP patients.展开更多
Acute pancreatitis(AP)is a complex and potentially life-threatening inflammatory condition with a highly variable clinical course,ranging from mild,selflimiting episodes to severe necrotizing forms.Among its common co...Acute pancreatitis(AP)is a complex and potentially life-threatening inflammatory condition with a highly variable clinical course,ranging from mild,selflimiting episodes to severe necrotizing forms.Among its common complications ascites has traditionally been viewed as a passive byproduct of peritoneal inflammation and enzymatic leakage with limited diagnostic or prognostic utility.However,growing evidence challenges this perspective,suggesting that ascitic fluid in AP represents a dynamic and clinically meaningful component of disease progression.In this editorial we reflected on the findings presented by Rao et al,who highlighted the diagnostic,prognostic,and therapeutic significance of ascitic fluid in AP.Easily accessible markers such as lactate dehydrogenase may provide early prognostic insight while emerging molecular biomarkers and cytokine pro-files offer promise for more precise risk stratification and individualized therapy.We argue that the systematic evaluation of ascitic fluid should be integrated into the clinical management of moderate to severe AP.Incorporating ascites analysis into standard diagnostic protocols may enhance early risk assessment,inform therapeutic decisions,and ultimately improve patient outcomes.Ascitic fluid should be recognized as a clinically valuable marker and an important source of information in the evolving landscape of AP care.展开更多
BACKGROUND Liver transplantation(LT)is the preferred treatment for end-stage liver diseases.Early allograft failure(EAF)can result in death or retransplantation.One of the key factors predicting EAF is the degree of g...BACKGROUND Liver transplantation(LT)is the preferred treatment for end-stage liver diseases.Early allograft failure(EAF)can result in death or retransplantation.One of the key factors predicting EAF is the degree of graft injury,which is typically assessed by elevated alanine aminotransferase(ALT)and aspartate aminotransferase(AST)levels.Aminotransferase levels exceeding 5000 U/L within 48 hours of LT are indicative of poor short-term graft survival.AIM To investigate outcomes in liver transplant recipients with peak aminotransferase levels exceeding 5000 U/L and to identify predictors of EAF.METHODS Adult patients who underwent LT from a deceased(brain-dead)donor between 2011 and 2024 at Hospital de Clínicas de Porto Alegre were screened.Patients with peak AST or ALT levels>5000 U/L post-LT were included,excluding those with vascular thrombosis.EAF was defined as death or retransplantation within 90 days.A receiver operating characteristic curve were generated for each EAF predictor to determine the area under the curve(AUC).Sensitivity,specificity,negative predictive value,and positive predictive value were calculated for each predictor’s best cutoff,as defined by the Youden Index.Survival curves were plotted using the Kaplan-Meier method.RESULTS Between 2011 and 2024,341 patients underwent LT.Of these,29(8.5%)patients had AST and/or ALT levels exceeding 5000 U/L within the first 48 hours post-LT.Four patients were excluded due to vascular thrombosis,resulting in a study cohort of 25 patients.EAF were also observed in 11 patients.One-year and five-year graft survival rates were 51.7%and 42.6%,respectively.For patients without EAF,one-year and five-year graft survivals were 92.3%and 76.2%,respectively.The key predictors of EAF included serum factor V and arterial lactate levels on postoperative day(POD)1,with AUCs of 0.936 and 0.919,respectively.The optimal cutoff for EAF prediction were 26.2%for serum factor V and 9 mmol/L for arterial lactate.CONCLUSION Aminotransferase levels>5000 U/L were associated with high EAF risk.However,favorable graft function indicators on POD 1 were associated with long-term survival comparable to that of general LT recipients.Serum factor V and arterial lactate levels emerged as valuable prognostic markers.展开更多
Breast cancer(BC)has the highest prevalence among cancers specific to women,and its incidence rates are increasing in many countries.Subtypes of BC,including HER2-positive or triple-negative BC,exhibit differing treat...Breast cancer(BC)has the highest prevalence among cancers specific to women,and its incidence rates are increasing in many countries.Subtypes of BC,including HER2-positive or triple-negative BC,exhibit differing treatment responses;consequently,demand for personalized therapy is increasing,and relevant precision medicine strategies are under development.Aerobic glycolysis in cancer cells can lead to excessive lactate production,which in turn promotes lactylation and influences tumor cell behavior.Epigenetic alterations and metabolic reprogramming are prominent characteristics of tumors.Because lactate and lactylation are important in cancer,further investigation of the mechanisms underlying lactate metabolism and lactylation,and the development of therapeutic strategies targeting these processes,are topics of increasing interest.This review describes current research on lactate metabolism and lactylation in BC,thus offering new perspectives for advancing treatment and management toward more precise and personalized approaches that will ultimately increase BC survival rates and patient quality of life.展开更多
Background Although several cell culture systems have been developed to investigate the function of the mam-mary gland in dairy livestock,they have potential limitations,such as the loss of alveolar structure or genet...Background Although several cell culture systems have been developed to investigate the function of the mam-mary gland in dairy livestock,they have potential limitations,such as the loss of alveolar structure or genetic and phe-notypic differences from their native counterparts.Overcoming these challenges is crucial for lactation research.Development of protocols to establish lactating organoid of livestock represents a promising goal for the future.In this study,we developed a protocol to establish a culture system for mammary organoids in dairy goats to model the mammary gland development and lactation process.Results The organoids cultured within an extracellular matrix gel maintained a bilayer structure that closely resem-bled the native architecture of mammary tissue.The expansion of mammary organoids was significantly promoted by growth factors containing epidermal growth factor and fibroblast growth factor 2 whereas the proliferative index of the organoids was significantly inhibited by the treatment with WNT inhibitors.Upon stimulation with a lactogenic medium containing prolactin,the mammary organoids exhibited efficient lactation,characterized by the accumu-lation of lipid droplets in the lumen space.The lactation could be sustained for more than 3 weeks.Importantly,the expression patterns of genes related to fatty acid synthesis and milk proteins in lactating organoids closely mirrored those observed in mammary tissues.These observations were confirmed by data from proteomic analysis that the bulk of milk proteins was produced in the lactating organoids.Conclusion This study is the first to establish a mammary organoid culture system modeling the mammary gland development and lactation process in ruminants.The efficient induction of lactation in ruminant mammary organoids holds promises for advancing the field of cell-based milk bio-manufacture in the food industry.展开更多
Oxaliplatin(OXA)can be used as a palliative treatment for advanced hepatocellular carcinoma(HCC).While most patients still have rapid disease progression after OXA due to the drug resistance.The lactate dehydrogenase ...Oxaliplatin(OXA)can be used as a palliative treatment for advanced hepatocellular carcinoma(HCC).While most patients still have rapid disease progression after OXA due to the drug resistance.The lactate dehydrogenase A(LDHA)inhibitors can reduce the inflammation-induced effects,metastasis,and proliferation potential of cancer cells.Here,we adopt the water-in-oil attractive Pickering emulsion gel(APEG)to deliver OXA and LDHA inhibitor,GSK2837808A(GSK).OXA is dissolved in water and GSK is dissolved in iodized oil.This drugs-loaded APEG has good biocompatibility and can release OXA and GSK slowly.OXA+GSK@gel has significant anti-tumor effect on HCC model,which can effectively inhibit tumor cell proliferation and promote tumor cell apoptosis.Meanwhile,flow analysis confirm that it could activate the tumor immune microenvironment in HCC.The infiltration of CD8^(+)T cells is increased,thereby providing better anti-tumor effect.The results suggest that the APEGs loaded with OXA and GSK can effectively improve the delivery efficiency and enhance the anti-tumor therapy.展开更多
BACKGROUND Colorectal cancer(CRC)is a prevalent gastrointestinal malignancy,with its pathogenesis involving dysregulation of multiple genes,including adenomatous polyposis coli and p53.Emerging evidence suggests that ...BACKGROUND Colorectal cancer(CRC)is a prevalent gastrointestinal malignancy,with its pathogenesis involving dysregulation of multiple genes,including adenomatous polyposis coli and p53.Emerging evidence suggests that microRNA 195(miR195)plays a critical role in carcinogenesis by modulating the phosphatidylinositol 3 kinase(PI3K)/protein kinase B(AKT)signaling pathway through phosphatase and tensin homologue(PTEN),thereby influencing cellular metabolism.Loss of PTEN function leads to hyperactivation of PI3K/AKT signaling pathway,resulting in upregulated expression of lactate dehydrogenase-5(LDH-5)and promoting the tumor progression.AIM To explore the clinical relevance of miR195,LDH-5,and PTEN expression patterns in CRC patient tissues and their association with clinicopathological features and prognosis.METHODS We enrolled 53 CRC patients who received surgical resection at our hospital from January 2020 to February 2022.Fresh tumor tissues and paired adjacent normal tissues(>5 cm from the tumor margin)were collected.The mRNA expression of miR195 was quantified by real-time quantitative polymerase chain reaction,while the protein expression of LDH-5 and PTEN were assessed via immunohistochemistry.Differences in molecular expression between tumor and adjacent normal tissues were compared,along with their correlations with clinicopathological parameters and prognosis.RESULTS The positive rate of miR195 in CRC tissues(35.85%)was significantly lower than that in adjacent normal tissues(90.57%).LDH-5 displayed a higher positive rate(79.25%)in the tissues compared to normal tissues(11.32%),while PTEN expression was markedly reduced in tumors(28.30%vs 94.34%,P<0.05).Elevated expression of miR195 was observed in CRC tissues from patients with earlier tumor,node,metastasis(TNM)stages and without lymph node metastasis.Conversely,higher expression of LDH-5 was associated with advanced TNM stages,lower differentiation grades,and the presence of lymph node metastasis.Additionally,PTEN expression was higher in patients with smaller tumor diameters and no lymph node metastasis(P<0.05).In CRC tissues,miR195 showed a negative correlation with LDH-5(r=-0.883,P=0.015)but a positive correlation with PTEN(r=0.429,P=0.006).LDH-5 was negatively associated with PTEN(r=-0.396,P<0.001).Patients with miR195 positivity,LDH-5 negativity,and PTEN positivity demonstrated significantly better prognosis(P<0.05).CONCLUSION Low miR195 and PTEN expression,coupled high LDH-5 expression could constitutes a hallmark molecular signature of CRC progression.These signature may act as potential markers for diagnosis and disease assessment,and prognostic evaluation in CRC patients,eventually improving CRC management.展开更多
A recent single-center retrospective study by Rao et al has offered valuable insights into the prognostic utility of ascitic fluid characteristics in acute pancreatitis.Their findings,which demonstrate associations be...A recent single-center retrospective study by Rao et al has offered valuable insights into the prognostic utility of ascitic fluid characteristics in acute pancreatitis.Their findings,which demonstrate associations between ascitic color,turbidity,and elevated lactate dehydrogenase levels with organ failure,infected pancreatic necrosis,and in-hospital mortality provide a valuable contribution to a relatively underexplored area in pancreatology.However,the reliance on subjective visual assessment and a single time-point evaluation raises concerns regarding reproducibility and dynamic disease monitoring.Furthermore,the lack of integration with objective indicators such as polymorphonuclear cell counts,microbiological cultures,and exudative vs transudative analysis limits the interpretability of the results.Despite these limitations,the study provides a clinically relevant framework that supports further investigation and refinement through prospective,multicenter validation.展开更多
Pigeons and certain other avian species produce a milklike secretion in their crop sacs to nourish offspring,yet the detailed processes involved are not fully elucidated.This study investigated the crop sacs of 225-da...Pigeons and certain other avian species produce a milklike secretion in their crop sacs to nourish offspring,yet the detailed processes involved are not fully elucidated.This study investigated the crop sacs of 225-day-old unpaired non-lactating male pigeons(MN)and males initiating lactation on the first day after incubation(ML).Using RNA sequencing,ribosomeprofiling,andsingle-cell transcriptome sequencing(scRNA-seq),we identified a significant up-regulation of genes associated with ribosome assembly and protein synthesis in ML compared to MN.Results from scRNA-seq analysis identified 12distinct cell types and 22 clusters,with secretory epithelial cells(SECs)exhibiting marked expression of plasma cell markers,including IGLL1 and MZB1.RNA fluorescence in situ hybridization(RNA FISH)and IgY quantification confirmed the critical role of SECs in producing endogenous IgY during lactation.We propose that fibroblast-derived BAFF signals activate SECs,mimicking B cell transformation and enhancing protein production through the unfolded protein response(UPR).These findings shed light on the cellular dynamics of pigeon milk production and contribute to a broader understanding of avian biology.展开更多
Background:Whether lactated Ringer's solution is clinically superior to normal saline for routine intravenous administration of fluids is uncertain.Methods:In an open-label,two-period,two-sequence,cross-sectional,...Background:Whether lactated Ringer's solution is clinically superior to normal saline for routine intravenous administration of fluids is uncertain.Methods:In an open-label,two-period,two-sequence,cross-sectional,cluster-randomized,crossover trial,we assigned hospitals in Ontario,Canada,to use either lactated Ringer's solution or normal saline hospital-wide for a period of 12 weeks.展开更多
文摘The development of neurodegenerative diseases is closely related to the disruption of central nervous system homeostasis.Microglia,as innate immune cells,play important roles in the maintenance of central nervous system homeostasis,injury response,and neurodegenerative diseases.Lactate has been considered a metabolic waste product,but recent studies are revealing ever more of the physiological functions of lactate.Lactylation is an important pathway in lactate function and is involved in glycolysis-related functions,macrophage polarization,neuromodulation,and angiogenesis and has also been implicated in the development of various diseases.This review provides an overview of the lactate metabolic and homeostatic regulatory processes involved in microglia lactylation,histone versus non-histone lactylation,and therapeutic approaches targeting lactate.Finally,we summarize the current research on microglia lactylation in central nervous system diseases.A deeper understanding of the metabolic regulatory mechanisms of microglia lactylation will provide more options for the treatment of central nervous system diseases.
基金supported by National Natural Science Foundation of China(No.62006092)Natural Science Research Project of Anhui Educational Committee(No.2023AH030081)+1 种基金2023 New Era Education Provincial Quality Engineering Project(Graduate Education)(No.2023cxcysj103)2024 New Era Education Provincial Quality Engineering Project(Graduate Education)。
文摘Lactate,as a metabolite,plays a significant role in a number of fields,including medical diagnostics,exercise physiology and food science.Traditional methods for lactate measurement often involve expensive and cumbersome instrumentation.This study developed a portable and low-cost lactate measurement system,including independently detectable hardware circuits and user-friendly embedded software,computer,and smartphone applications.The experiment verified that the relative error of the detection current in the device circuit was less than 1%.The electrochemical performance was measured by comparing the[Fe(CN)_(6)]^(3−)/[Fe(CN)_(6)]^(4−)solution with the desktop electrochemical workstation CHI660E,and a nearly consistent chronoamperometry(CA)curve was obtained.Two modified lactate sensors were used for CA testing of lactate.Within the concentration range of 0.1 mmol·L^(−1)to 20 mmol·L^(−1),there was a good linear relationship between lactate concentration and steady-state current,with a correlation coefficient(R2)greater than 0.99 and good repeatability,demonstrating the reliability of the developed device.The lactate measurement system developed in this study not only provides excellent detection performance and reliability,but also achieves portability and low cost,providing a new solution for lactate measurement.
基金supported by Applied Basic Research Joint Fund Project of Yunnan Province,No.202301AY070001-200Middle-aged Academic and Technical Training Project for High-Level Talents,No.202105AC160065+1 种基金Yunnan Clinical Medical Center for Neurological and Cardiovascular Diseases,No.YWLCYXZX2023300077Key Clinical Specialty of Neurology in Yunnan Province,No.300064(all to CL)。
文摘Research into lactylation modifications across various target organs in both health and disease has gained significant attention.Many essential life processes and the onset of diseases are not only related to protein abundance but are also primarily regulated by various post-translational protein modifications.Lactate,once considered merely a byproduct of anaerobic metabolism,has emerged as a crucial energy substrate and signaling molecule involved in both physiological and pathological processes within the nervous system.Furthermore,recent studies have emphasized the significant role of lactate in numerous neurological diseases,including Alzheimer's disease,Parkinson's disease,acute cerebral ischemic stroke,multiple sclerosis,Huntington's disease,and myasthenia gravis.The purpose of this review is to synthesize the current research on lactate and lactylation modifications in neurological diseases,aiming to clarify their mechanisms of action and identify potential therapeutic targets.As such,this work provides an overview of the metabolic regulatory roles of lactate in various disorders,emphasizing its involvement in the regulation of brain function.Additionally,the specific mechanisms of brain lactate metabolism are discussed,suggesting the unique roles of lactate in modulating brain function.As a critical aspect of lactate function,lactylation modifications,including both histone and non-histone lactylation,are explored,with an emphasis on recent advancements in identifying the key regulatory enzymes of such modifications,such as lactylation writers and erasers.The effects and specific mechanisms of abnormal lactate metabolism in diverse neurological diseases are summarized,revealing that lactate acts as a signaling molecule in the regulation of brain functions and that abnormal lactate metabolism is implicated in the progression of various neurological disorders.Future research should focus on further elucidating the molecular mechanisms underlying lactate and lactylation modifications and exploring their potential as therapeutic targets for neurological diseases.
基金supported by the National Natural Science Foundation of China,Nos.82071383,82371392(to BN)the Natural Science Foundation of Shandong Province of China(Key Project),No.ZR2020KH007(to BN)+1 种基金“Taishan Scholar Distinguished Expert Program”of Shandong Province,No.tstp20231257(to BN)Health Commission Science and Technology Plan Project of Jinan,No.2023-1-8(to YZ).
文摘Lactate serves as a key energy metabolite in the central nervous system,facilitating essential brain functions,including energy supply,signaling,and epigenetic modulation.Moreover,it links epigenetic modifications with metabolic reprogramming.Nonetheless,the specific mechanisms and roles of this connection in astrocytes remain unclear.Therefore,this review aims to explore the role and specific mechanisms of lactate in the metabolic reprogramming of astrocytes in the central nervous system.The close relationship between epigenetic modifications and metabolic reprogramming was discussed.Therapeutic strategies for targeting metabolic reprogramming in astrocytes in the central nervous system were also outlined to guide future research in central nervous system diseases.In the nervous system,lactate plays an essential role.However,its mechanism of action as a bridge between metabolic reprogramming and epigenetic modifications in the nervous system requires future investigation.The involvement of lactate in epigenetic modifications is currently a hot research topic,especially in lactylation modification,a key determinant in this process.Lactate also indirectly regulates various epigenetic modifications,such as N6-methyladenosine,acetylation,ubiquitination,and phosphorylation modifications,which are closely linked to several neurological disorders.In addition,exploring the clinical applications and potential therapeutic strategies of lactic acid provides new insights for future neurological disease treatments.
基金supported by funding from Texas A&M AgriLife ResearchPrairie View A&M University International Center for Goat Research。
文摘Background Lactational performance depends heavily on age,health,and nutrition.L-Citrulline(Cit)is an effective precursor of L-arginine(Arg),an amino acid that has important roles in synthesis of nitric oxide(NO)and polyamines.Ruminal microbes degrade extracellular Arg;however,extracellular L-citrulline(Cit)is not degraded by ruminal microbes due to lack of uptake and can be fed unencapsulated as a precursor for Arg.As NO is a vasodilator,an increase in blood flow and transport of molecules to mammary tissue may enhance lactational performance and milk composition.Increases in polyamine production may increase milk protein synthesis within mammary tissue,thus increasing milk protein content.This study determined,for the first time,effects of dietary Cit supplementation on milk production and milk composition of Alpine dairy goats.Methods Does were synchronized to estrus and bred to Alpine bucks.Parturition was induced on d 149 of gestation and does were suckled overnight allowing kid(s)to obtain colostrum before being milked 24 h later(d 1 of lactation).Does were assigned to either control(CON,n=24)or Cit(CIT,n=23)diets.The isonitrogenous control diet consisted of 97.63%basal diet and 2.37%supplement(1.37%L-alanine and 1.00%soybean hydrogenated oil).The CIT supplemented diet consisted of 97.63%basal diet and 2.37%supplement(0.5%Cit,0.5%L-glutamine,1%soybean hydrogenated oil,0.37%cornstarch).Diets were group fed ad-libitum by treatment group.Blood samples were collected on d 0 and 30 of lactation,milk volumes measured twice daily,and on d 10,20,and 40 of lactation,milk samples were collected.Results CIT-treated does had greater daily milk production(P<0.05)and there was an effect of day of lactation on daily milk production(P<0.0001).Sire had significant effect on daily milk production as well(P<0.05).Milk compositional analyses revealed Cit supplementation increased solid-non-fat(SNF;P<0.05)and protein(P<0.05)content in milk.Conclusions Our novel results indicate that dietary supplementation of Cit fed ad-libitum in Alpine does increased daily milk yield,milk SNF content,and protein content.Supplemental Cit may be a proxy for Arg in goats to enhance lactational performance.
基金supported by National Nature Science Foundation of China(32102552 and 32172741).
文摘Background Lactate is a classical byproduct of glucose metabolism,and the main lactate production pathway depends on glycolysis.Lactate stabilized HIF1αby inhibiting PHD activity,leading to hypoxic stress response and exacerbating glycolysis in multiple tissues.However,the redox induction mechanism of lactate in mammary gland has not been understood yet.Herein,we describe a lactate-responsive HIF1α/circadian control mechanism in oxidative stress in the mammary glands of dairy cows.Results The in vivo study showed that dairy cows with high lactate concentrations are associated with reduced milk yield and more ROS accumulation in mammary gland.Western blot results in MAC-T cells showed positive correlation between lactate concentrations,expression of HIF1αand oxidative stress indicators,but not circadian core components.To test how lactate-mediated HIF1αdysfunction leads to cell protection process,we investigated altered expression of circadian core related genes following HIF1αstabilization.We found that stabilized HIF1αby lactate inhibited stimulated expression of circadian core components due to the similarity of HRE and E-box transcription elements.Furthermore,we found that lactate treatment strengthened the binding of HIF1αwith BMAL1,HMOX1 and FOXO3 in MAC-T cells.Moreover,HIF1αknockdown altered expression of circadian rhythm related genes and reduced oxidative stress state.Conclusion In summary,our study highlights the central role of competitive transcriptional element occupancy in lactate-mediated oxidative stress of mammary gland,which is caused by HIF1αstabilization and circadian rhythm dysfunction.Our findings introduce a novel nutritional strategy with potential applications in dairy farming for optimizing milk production and maintaining mammary gland health.
基金support from APC LLC,Ankeny,IA,USA,is greatly appreciated.
文摘Background Feeding spray dried plasma(SDP)to weanling pigs improves growth,but there is a lack of research on how SDP impacts oxidative stress and inflammatory response in lactating sows,and performance of their piglets after weaning.Therefore,an experiment was conducted to test the hypothesis that sows fed a diet with SDP in late gestation and lactation have improved reproductive performance and reduced inflammation compared with sows fed no SDP.The second hypothesis was that pigs weaned from sows fed 0.5%SDP in lactation have reduced diarrhea incidence and improved growth performance during the initial 14 d of the nursery period regardless of dietary SDP.Results The percent of low vitality or starved pigs during lactation was less(P<0.05)from sows fed 0.5%dietary SDP compared with sows fed the diet without SDP.Dietary SDP did not influence oxidative stress markers in the plasma of sows,but serum cytokines increased(P<0.05)in sows fed the diet with 0.5%SDP compared with sows fed the diet without SDP.Pigs weaned from young sows fed no SDP or from mature sows fed 0 or 0.5%SDP had a greater gain to feed ratio when fed a phase 1 diet containing 6%SDP compared with pigs fed a diet without SDP,but the gain to feed ratio of pigs weaned from young sows fed 0.5%dietary SDP was not affected by dietary SDP in phase 1(interaction,P<0.05).Regardless of sow treatment,pigs fed a phase 1 diet with 6%SDP had greater(P<0.05)growth performance than pigs fed a phase 1 diet without SDP,and pigs fed the phase 1 diet with 6%SDP had reduced(P<0.05)diarrhea incidence in phase 1.Conclusions Feeding 0.5%dietary SDP to sows may reduce the number of mummified pigs and increase pig vitality during lactation,but adding 0.5%SDP to sow diets during lactation did not improve post-weaning performance of pigs fed a starter diet with 6%SDP.
基金funded by the Science Foundation Ireland(BiOrbic,Dublin,Ireland)and Adesco Nutricines(Dungarvan,Waterford,Ireland)under grant number 16/RC/3889。
文摘Background Organic acids(OA)and maternal nutritional strategies have been demonstrated to promote piglet health and development.The objective of this study was to investigate the effects of incorporating OA-preserved cereal grains into sow diets during late gestation and lactation,aiming to reduce the metabolic demands of lactation while optimising offspring development and growth until slaughter.The experiment compared OA-preserved wheat and barley to conventionally dried grains,focusing on sow and offspring performance,as well as their faecal microbiota during lactation.Forty sows were blocked based on parity,body weight and back fat thickness on d 100 of gestation and assigned to one of two diets:a dried grain lactation diet and a preserved grain lactation diet.Sow faecal samples were collected at farrowing for the coefficient of apparent total tract digestibility(CATTD)of nutrients and microbial analysis.Offspring faecal samples were collected on d 10 postpartum and at weaning(d 26 postpartum)for microbial analysis.Results Sow body weight,back fat changes,gestation and lactation length,total piglets born,wean-to-oestrus interval,and lactation efficiency were unaffected by sow diet(P>0.05).However,sows offered the preserved grain diet exhibited improved CATTD of dry matter,nitrogen,gross energy,and neutral detergent fibre(P<0.05).While no maternal effect was observed on offspring growth during lactation(P>0.05),pigs from sows offered the preserved grain diet showed improved growth and feed efficiency from weaning until slaughter(d 168)compared to those from sows offered the dried grain diet(P<0.05).The preserved grain diet also reduced the abundance of Proteobacteria in sow faeces at farrowing and in their offspring on d 10 postpartum,and improved piglet faecal scores throughout lactation(P=0.05).At weaning,piglets from sows offered the preserved grain diet exhibited an increased abundance of Lactobacillus and reduced abundance of Alistipes in their faeces(P<0.05).Conclusion OA-preserved grains enhanced the CATTD of nutrients in sows,promoted healthier piglet faecal scores during lactation,and improved offspring growth performance post-weaning,potentially linked to beneficial changes observed in the faecal microbiota of sows and their offspring during lactation.
文摘The interaction between the lactate receptor GPR81(also known as hydroxycarboxylic acid receptor 1,or HCAR1)and Splicing Factor Proline-and Glutamine-Rich protein promotes the tumor cell malignancy.GPR81 nuclear translocation plays an important role in driving cancer progression and could serve as a potential therapeutic target.Yang et al concluded in their study that lactate and its receptor,GPR81,play crucial roles in cancer progression,and are key players in linking the lactate-rich tumor microenvironment to cancer cell behavior.The ability of nuclear GPR81 to directly regulate gene expression,combined with extracellular matrix-mediated mechanical signaling,creates a potentially robust system for the coordinated adaptation and survival of cancer cells.Understanding these interactions could lead to the discovery of new therapeutic targets and improved treatment strategies for cancer.
文摘Background This study investigated the potential impacts of increasing linoleic andα-linolenic acid intake during lactation and wean-to-breeding on subsequent reproduction of sows.A total of 309 sows(PIC Camborough L42)were balanced by parity(140 and 169 sows representing parity 1 to 2[P1-2]and 3 to 9[P3+],respectively)and assigned within parity to a 2×2 factorial arrangement.Factors included essential fatty acid(EFA)supplementation(control diets containing 1.2%linoleic and 0.15%α-linolenic acid or diets with 3.0%linoleic and 0.38%α-linolenic acid)and supplementation period(lactation or wean-to-breeding).Tallow(low EFA diets)or soybean oil(high EFA diets)were included at 4%in sorghum-soybean meal-wheat middlings-based diets to attain targeted EFA levels.Results High levels of EFA fed during lactation had no effect on feed intake or litter performance,but increased subsequent farrowing rate(P=0.027;82.1%vs.70.4%),tended to reduce the proportion of sows removed(P=0.070;12.4%vs.20.8%),decreased the number of total pigs born in the following litter(P=0.072;15.3 vs.16.2),and increased total pigs born alive per 100 sows weaned(P=0.062;1,122 vs.974),regardless of sow parity.Young sows(P1-2)consuming the high EFA diet during lactation displayed a shorter wean-to-estrus interval(P=0.035;4.2 vs.4.6),but P3+sows were unaffected.Increasing EFA intake for P3+sows,but not P1-2 sows,resulted in more sows bred by d 5(P=0.028;91.1%vs.81.7%)and more mummies in the subsequent litter(P=0.040;0.32 vs.0.16).Feeding increased EFA to P1-2 sows during the wean-to-breeding period decreased subsequent farrowing rate(P=0.042;72.0%vs.87.7%),and increased removal rate(P=0.003;28.8%vs.9.4%).Total pigs born alive per 100 sows weaned was reduced(P=0.007)in P1-2 sows when supplemented with EFA during wean-breeding(939 vs.1,149)but was not impacted in P3+sows(1,131 vs.982).Conclusions Supplemental EFA in lactation diets benefited subsequent reproduction of sows,regardless of parity.Increasing dietary levels of EFA during the wean-to-breeding period to younger sows negatively impacted subsequent reproduction.
基金Supported by National Natural Science Foundation of China,No.82360136Jiangxi Clinical Research Center for Gastroenterology,No.20223BCG74011.
文摘BACKGROUND Acute pancreatitis(AP)is a severe condition,and abdominal effusion is a significant predictor of its severity and prognosis.However,the relationship between ascites characteristics and AP outcomes remains undefined.AIM To assess the correlation between ascites characteristics and clinical prognosis in AP patients by comparing color depth and turbidity of early ascites.METHODS This study included 667 AP patients with ascites,categorized by color and turbidity into yellow clear(n=54),yellow turbid(n=293),red brown(n=320).The trendχ2 test was employed to analyze the incidence of organ failure(OF),infected pancreatic necrosis(IPN),and mortality across groups.Receiver operating charac teristic(ROC)curves were used to evaluate the predictive value of ascites cell count,amylase,protein,and lactate dehydrogenase(LDH)for abdominal compartment syndrome(ACS)and intra-abdominal hemorrhage.RESULTS AP patients with ascites exhibited higher scores of scoring systems(such as Bedside index for severity in AP,Acute Physiology and Chronic Health Examination II,etc.)and increased complications and mortality rates(all P<0.05)compared to those without ascites.A linear association was observed between ascites color depth and turbidity and the incidence of OF,pancreatic necrosis,IPN,and mortality(P<0.05).LDH in ascites demonstrated high accuracy in predicting ACS and intra-abdominal hemorrhage,with areas under the ROC curve of 0.77 and 0.79,respectively.CONCLUSION Early in AP,ascites correlates with OF,IPN,and mortality,showing linear associations with color depth and turbidity.Ascitic LDH reliably predicts ACS and intra-abdominal hemorrhage in AP patients.
文摘Acute pancreatitis(AP)is a complex and potentially life-threatening inflammatory condition with a highly variable clinical course,ranging from mild,selflimiting episodes to severe necrotizing forms.Among its common complications ascites has traditionally been viewed as a passive byproduct of peritoneal inflammation and enzymatic leakage with limited diagnostic or prognostic utility.However,growing evidence challenges this perspective,suggesting that ascitic fluid in AP represents a dynamic and clinically meaningful component of disease progression.In this editorial we reflected on the findings presented by Rao et al,who highlighted the diagnostic,prognostic,and therapeutic significance of ascitic fluid in AP.Easily accessible markers such as lactate dehydrogenase may provide early prognostic insight while emerging molecular biomarkers and cytokine pro-files offer promise for more precise risk stratification and individualized therapy.We argue that the systematic evaluation of ascitic fluid should be integrated into the clinical management of moderate to severe AP.Incorporating ascites analysis into standard diagnostic protocols may enhance early risk assessment,inform therapeutic decisions,and ultimately improve patient outcomes.Ascitic fluid should be recognized as a clinically valuable marker and an important source of information in the evolving landscape of AP care.
基金Supported by Financiamento e IncentivoàPesquisa of Hospital de Clínicas de Porto Alegre,No.170271.
文摘BACKGROUND Liver transplantation(LT)is the preferred treatment for end-stage liver diseases.Early allograft failure(EAF)can result in death or retransplantation.One of the key factors predicting EAF is the degree of graft injury,which is typically assessed by elevated alanine aminotransferase(ALT)and aspartate aminotransferase(AST)levels.Aminotransferase levels exceeding 5000 U/L within 48 hours of LT are indicative of poor short-term graft survival.AIM To investigate outcomes in liver transplant recipients with peak aminotransferase levels exceeding 5000 U/L and to identify predictors of EAF.METHODS Adult patients who underwent LT from a deceased(brain-dead)donor between 2011 and 2024 at Hospital de Clínicas de Porto Alegre were screened.Patients with peak AST or ALT levels>5000 U/L post-LT were included,excluding those with vascular thrombosis.EAF was defined as death or retransplantation within 90 days.A receiver operating characteristic curve were generated for each EAF predictor to determine the area under the curve(AUC).Sensitivity,specificity,negative predictive value,and positive predictive value were calculated for each predictor’s best cutoff,as defined by the Youden Index.Survival curves were plotted using the Kaplan-Meier method.RESULTS Between 2011 and 2024,341 patients underwent LT.Of these,29(8.5%)patients had AST and/or ALT levels exceeding 5000 U/L within the first 48 hours post-LT.Four patients were excluded due to vascular thrombosis,resulting in a study cohort of 25 patients.EAF were also observed in 11 patients.One-year and five-year graft survival rates were 51.7%and 42.6%,respectively.For patients without EAF,one-year and five-year graft survivals were 92.3%and 76.2%,respectively.The key predictors of EAF included serum factor V and arterial lactate levels on postoperative day(POD)1,with AUCs of 0.936 and 0.919,respectively.The optimal cutoff for EAF prediction were 26.2%for serum factor V and 9 mmol/L for arterial lactate.CONCLUSION Aminotransferase levels>5000 U/L were associated with high EAF risk.However,favorable graft function indicators on POD 1 were associated with long-term survival comparable to that of general LT recipients.Serum factor V and arterial lactate levels emerged as valuable prognostic markers.
基金supported by grants from the National Natural Science Foundation of China(Grant No.82302626)Gusu Health Talent Project of Suzhou,China(Grant No.GSWS2022076)Suzhou Key Laboratory of Intelligent Critical Illness Biomarkers Translational Research Project(Grant No.SZS2024029)。
文摘Breast cancer(BC)has the highest prevalence among cancers specific to women,and its incidence rates are increasing in many countries.Subtypes of BC,including HER2-positive or triple-negative BC,exhibit differing treatment responses;consequently,demand for personalized therapy is increasing,and relevant precision medicine strategies are under development.Aerobic glycolysis in cancer cells can lead to excessive lactate production,which in turn promotes lactylation and influences tumor cell behavior.Epigenetic alterations and metabolic reprogramming are prominent characteristics of tumors.Because lactate and lactylation are important in cancer,further investigation of the mechanisms underlying lactate metabolism and lactylation,and the development of therapeutic strategies targeting these processes,are topics of increasing interest.This review describes current research on lactate metabolism and lactylation in BC,thus offering new perspectives for advancing treatment and management toward more precise and personalized approaches that will ultimately increase BC survival rates and patient quality of life.
基金Innovation 2030-Biological Breeding-Major Projects(2022ZD04014)Key R&D Program of Zhejiang Province(2022C04017).
文摘Background Although several cell culture systems have been developed to investigate the function of the mam-mary gland in dairy livestock,they have potential limitations,such as the loss of alveolar structure or genetic and phe-notypic differences from their native counterparts.Overcoming these challenges is crucial for lactation research.Development of protocols to establish lactating organoid of livestock represents a promising goal for the future.In this study,we developed a protocol to establish a culture system for mammary organoids in dairy goats to model the mammary gland development and lactation process.Results The organoids cultured within an extracellular matrix gel maintained a bilayer structure that closely resem-bled the native architecture of mammary tissue.The expansion of mammary organoids was significantly promoted by growth factors containing epidermal growth factor and fibroblast growth factor 2 whereas the proliferative index of the organoids was significantly inhibited by the treatment with WNT inhibitors.Upon stimulation with a lactogenic medium containing prolactin,the mammary organoids exhibited efficient lactation,characterized by the accumu-lation of lipid droplets in the lumen space.The lactation could be sustained for more than 3 weeks.Importantly,the expression patterns of genes related to fatty acid synthesis and milk proteins in lactating organoids closely mirrored those observed in mammary tissues.These observations were confirmed by data from proteomic analysis that the bulk of milk proteins was produced in the lactating organoids.Conclusion This study is the first to establish a mammary organoid culture system modeling the mammary gland development and lactation process in ruminants.The efficient induction of lactation in ruminant mammary organoids holds promises for advancing the field of cell-based milk bio-manufacture in the food industry.
基金supported by Natural Science Foundation of Zhejiang Province(Nos.LY20H160033,LY22H160019)National Key Research and Development Program of China(No.YS2021YFC3000089)+1 种基金Zhejiang Province Science and Technology Plan Project(No.2024C03175)National Natural Science Foundation of China(Nos.82074208,22278352,82473004).
文摘Oxaliplatin(OXA)can be used as a palliative treatment for advanced hepatocellular carcinoma(HCC).While most patients still have rapid disease progression after OXA due to the drug resistance.The lactate dehydrogenase A(LDHA)inhibitors can reduce the inflammation-induced effects,metastasis,and proliferation potential of cancer cells.Here,we adopt the water-in-oil attractive Pickering emulsion gel(APEG)to deliver OXA and LDHA inhibitor,GSK2837808A(GSK).OXA is dissolved in water and GSK is dissolved in iodized oil.This drugs-loaded APEG has good biocompatibility and can release OXA and GSK slowly.OXA+GSK@gel has significant anti-tumor effect on HCC model,which can effectively inhibit tumor cell proliferation and promote tumor cell apoptosis.Meanwhile,flow analysis confirm that it could activate the tumor immune microenvironment in HCC.The infiltration of CD8^(+)T cells is increased,thereby providing better anti-tumor effect.The results suggest that the APEGs loaded with OXA and GSK can effectively improve the delivery efficiency and enhance the anti-tumor therapy.
文摘BACKGROUND Colorectal cancer(CRC)is a prevalent gastrointestinal malignancy,with its pathogenesis involving dysregulation of multiple genes,including adenomatous polyposis coli and p53.Emerging evidence suggests that microRNA 195(miR195)plays a critical role in carcinogenesis by modulating the phosphatidylinositol 3 kinase(PI3K)/protein kinase B(AKT)signaling pathway through phosphatase and tensin homologue(PTEN),thereby influencing cellular metabolism.Loss of PTEN function leads to hyperactivation of PI3K/AKT signaling pathway,resulting in upregulated expression of lactate dehydrogenase-5(LDH-5)and promoting the tumor progression.AIM To explore the clinical relevance of miR195,LDH-5,and PTEN expression patterns in CRC patient tissues and their association with clinicopathological features and prognosis.METHODS We enrolled 53 CRC patients who received surgical resection at our hospital from January 2020 to February 2022.Fresh tumor tissues and paired adjacent normal tissues(>5 cm from the tumor margin)were collected.The mRNA expression of miR195 was quantified by real-time quantitative polymerase chain reaction,while the protein expression of LDH-5 and PTEN were assessed via immunohistochemistry.Differences in molecular expression between tumor and adjacent normal tissues were compared,along with their correlations with clinicopathological parameters and prognosis.RESULTS The positive rate of miR195 in CRC tissues(35.85%)was significantly lower than that in adjacent normal tissues(90.57%).LDH-5 displayed a higher positive rate(79.25%)in the tissues compared to normal tissues(11.32%),while PTEN expression was markedly reduced in tumors(28.30%vs 94.34%,P<0.05).Elevated expression of miR195 was observed in CRC tissues from patients with earlier tumor,node,metastasis(TNM)stages and without lymph node metastasis.Conversely,higher expression of LDH-5 was associated with advanced TNM stages,lower differentiation grades,and the presence of lymph node metastasis.Additionally,PTEN expression was higher in patients with smaller tumor diameters and no lymph node metastasis(P<0.05).In CRC tissues,miR195 showed a negative correlation with LDH-5(r=-0.883,P=0.015)but a positive correlation with PTEN(r=0.429,P=0.006).LDH-5 was negatively associated with PTEN(r=-0.396,P<0.001).Patients with miR195 positivity,LDH-5 negativity,and PTEN positivity demonstrated significantly better prognosis(P<0.05).CONCLUSION Low miR195 and PTEN expression,coupled high LDH-5 expression could constitutes a hallmark molecular signature of CRC progression.These signature may act as potential markers for diagnosis and disease assessment,and prognostic evaluation in CRC patients,eventually improving CRC management.
文摘A recent single-center retrospective study by Rao et al has offered valuable insights into the prognostic utility of ascitic fluid characteristics in acute pancreatitis.Their findings,which demonstrate associations between ascitic color,turbidity,and elevated lactate dehydrogenase levels with organ failure,infected pancreatic necrosis,and in-hospital mortality provide a valuable contribution to a relatively underexplored area in pancreatology.However,the reliance on subjective visual assessment and a single time-point evaluation raises concerns regarding reproducibility and dynamic disease monitoring.Furthermore,the lack of integration with objective indicators such as polymorphonuclear cell counts,microbiological cultures,and exudative vs transudative analysis limits the interpretability of the results.Despite these limitations,the study provides a clinically relevant framework that supports further investigation and refinement through prospective,multicenter validation.
基金supported by the Department of Agriculture and Rural Affairs of Jiangxi Province,China (JXARS-09)Science and Technology Program of Guangdong Province,China (2020B1212060060)。
文摘Pigeons and certain other avian species produce a milklike secretion in their crop sacs to nourish offspring,yet the detailed processes involved are not fully elucidated.This study investigated the crop sacs of 225-day-old unpaired non-lactating male pigeons(MN)and males initiating lactation on the first day after incubation(ML).Using RNA sequencing,ribosomeprofiling,andsingle-cell transcriptome sequencing(scRNA-seq),we identified a significant up-regulation of genes associated with ribosome assembly and protein synthesis in ML compared to MN.Results from scRNA-seq analysis identified 12distinct cell types and 22 clusters,with secretory epithelial cells(SECs)exhibiting marked expression of plasma cell markers,including IGLL1 and MZB1.RNA fluorescence in situ hybridization(RNA FISH)and IgY quantification confirmed the critical role of SECs in producing endogenous IgY during lactation.We propose that fibroblast-derived BAFF signals activate SECs,mimicking B cell transformation and enhancing protein production through the unfolded protein response(UPR).These findings shed light on the cellular dynamics of pigeon milk production and contribute to a broader understanding of avian biology.
文摘Background:Whether lactated Ringer's solution is clinically superior to normal saline for routine intravenous administration of fluids is uncertain.Methods:In an open-label,two-period,two-sequence,cross-sectional,cluster-randomized,crossover trial,we assigned hospitals in Ontario,Canada,to use either lactated Ringer's solution or normal saline hospital-wide for a period of 12 weeks.
