Microglia,the primary immune cells within the brain,have gained recognition as a promising therapeutic target for managing neurodegenerative diseases within the central nervous system,including Parkinson’s disease.Na...Microglia,the primary immune cells within the brain,have gained recognition as a promising therapeutic target for managing neurodegenerative diseases within the central nervous system,including Parkinson’s disease.Nanoscale perfluorocarbon droplets have been reported to not only possess a high oxygen-carrying capacity,but also exhibit remarkable anti-inflammatory properties.However,the role of perfluoropentane in microglia-mediated central inflammatory reactions remains poorly understood.In this study,we developed perfluoropentane-based oxygen-loaded nanodroplets(PFP-OLNDs)and found that pretreatment with these droplets suppressed the lipopolysaccharide-induced activation of M1-type microglia in vitro and in vivo,and suppressed microglial activation in a mouse model of Parkinson’s disease.Microglial suppression led to a reduction in the inflammatory response,oxidative stress,and cell migration capacity in vitro.Consequently,the neurotoxic effects were mitigated,which alleviated neuronal degeneration.Additionally,ultrahigh-performance liquid chromatography–tandem mass spectrometry showed that the anti-inflammatory effects of PFP-OLNDs mainly resulted from the modulation of microglial metabolic reprogramming.We further showed that PFP-OLNDs regulated microglial metabolic reprogramming through the AKT-mTOR-HIF-1αpathway.Collectively,our findings suggest that the novel PFP-OLNDs constructed in this study alleviate microglia-mediated central inflammatory reactions through metabolic reprogramming.展开更多
Background:Over the last decade,the nutritional requirements of lactating modern genotype sows have increased.The current nutritional recommendations might be unable to meet the needs of increased litter size and milk...Background:Over the last decade,the nutritional requirements of lactating modern genotype sows have increased.The current nutritional recommendations might be unable to meet the needs of increased litter size and milk production,and thus the nutritional requirements need to be re-evaluated.The current study was conducted to investigate the effects of dietary methionine to lysine(Met:Lys)ratios on the performance of and methionine metabolism in lactating sows.Results:During the 1st week of lactation,piglets reared on sows in the 0.37 to 0.57 Met:Lys ratio groups grew faster than those reared on sows in the control group(0.27)(P<0.01).The 0.37-ratio group showed increased levels of GSHPx in plasma during lactation(P<0.01)and decreased concentrations of urea nitrogen in the plasma of sows(P<0.05).Compared with the 0.27-ratio group,the levels of T-AOC and GSH-Px in the plasma and homocysteine in the milk of lactating sows were significantly increased in sows in the 0.47-ratio group(P<0.01).In sows fed a 0.57-ratio diet,the levels of glutathione and taurine in the plasma and milk were improved significantly during lactation.However,the content of TBARS in the blood(P<0.05 at day 7 and P=0.06 at weaning day)was increased(P<0.01).Moreover,there were linear increases in the levels of homocysteine in the blood and milk of sows during the lactation period(P<0.01)with increased dietary Met:Lys ratios in the lactation diet.Conclusions:The current study indicated that increasing the dietary Met:Lys ratio(0.37~0.57)in the lactation diet had no significant effect on the overall performance of sows or the colostrum and milk composition,but it increased piglet mean BW and piglet ADG during the first week of lactation.Increasing dietary methionine levels had no significant effect on antioxidant function in lactation sows,even though it increased levels of GSH and GSH-Px in the plasma of sows during lactation.However,the content of homocysteine in the plasma and milk increased during lactation due to a high level of dietary methionine.展开更多
Cutaneous manifestations are variable in patients with eosinophilic granulomatosis with polyangiitis(EGPA).We report a case where bullous eruption was a presenting manifestation of EGPA.A 55-year-old Chinese man with ...Cutaneous manifestations are variable in patients with eosinophilic granulomatosis with polyangiitis(EGPA).We report a case where bullous eruption was a presenting manifestation of EGPA.A 55-year-old Chinese man with a background of adult-onset asthma and chronic sinusitis was admitted for a 3-week history of lower limb weakness and a large bulla on his right calf with surrounding erythema.Skin biopsy showed a subepidermal blister with significant dermal eosinophilia,without vasculitis.The patient was diagnosed with EGPA with systemic involvement on the basis of a thorough medical history,eosinophilia,cardiac magnetic resonance imaging showing acute myocarditis,and nerve biopsy with eosinophilic vasculitic neuropathy.He responded well to corticosteroids and rituximab.Nonvasculitic bullous eruptions are rarely described as manifestations of EGPA.Prompt recognition of this entity is crucial for its early diagnosis.展开更多
A 52-year-old Chinese woman was diagnosed with transcription intermediary factor 1(TIF1)gamma dermatomyositis in November 2022,with manifestations of myositis,polyarthralgia,and low-grade fever.She had cutaneous manif...A 52-year-old Chinese woman was diagnosed with transcription intermediary factor 1(TIF1)gamma dermatomyositis in November 2022,with manifestations of myositis,polyarthralgia,and low-grade fever.She had cutaneous manifestations of Gottron's sign,V-neck sign,shawl sign,and flagellate erythema(Figure 1A).No interstitial lung disease was detected by high-resolution computed tomography.Comprehensive malignancy screenings,encompassing pap smear and mammogram,endoscopic examination,and computed tomography scans of the thorax,abdomen,and pelvis,were performed.They returned negative,apart from a lobulated nodule with biopsy confirmed as sclerosing pneumocytoma at the left lower lobe(Figure 1C).The therapeutic regimen,consisting of high-dose steroids and mycophenolate mofetil,effectively ameliorated the patient's myositis and rash(Figure 1B).展开更多
基金supported by the National Natural Science Foundation of China,No.82101327(to YY)President Foundation of Nanfang Hospital,Southern Medical University,No.2020A001(to WL)+1 种基金Guangdong Basic and Applied Basic Research Foundation,Nos.2019A1515110150,2022A1515012362(both to YY)Guangzhou Science and Technology Project,No.202201020111(to YY).
文摘Microglia,the primary immune cells within the brain,have gained recognition as a promising therapeutic target for managing neurodegenerative diseases within the central nervous system,including Parkinson’s disease.Nanoscale perfluorocarbon droplets have been reported to not only possess a high oxygen-carrying capacity,but also exhibit remarkable anti-inflammatory properties.However,the role of perfluoropentane in microglia-mediated central inflammatory reactions remains poorly understood.In this study,we developed perfluoropentane-based oxygen-loaded nanodroplets(PFP-OLNDs)and found that pretreatment with these droplets suppressed the lipopolysaccharide-induced activation of M1-type microglia in vitro and in vivo,and suppressed microglial activation in a mouse model of Parkinson’s disease.Microglial suppression led to a reduction in the inflammatory response,oxidative stress,and cell migration capacity in vitro.Consequently,the neurotoxic effects were mitigated,which alleviated neuronal degeneration.Additionally,ultrahigh-performance liquid chromatography–tandem mass spectrometry showed that the anti-inflammatory effects of PFP-OLNDs mainly resulted from the modulation of microglial metabolic reprogramming.We further showed that PFP-OLNDs regulated microglial metabolic reprogramming through the AKT-mTOR-HIF-1αpathway.Collectively,our findings suggest that the novel PFP-OLNDs constructed in this study alleviate microglia-mediated central inflammatory reactions through metabolic reprogramming.
基金financially supported by the National Key Research and Development Project of China(NO.2018YFD0501003)China Agriculture Research System(NO.CARS-36)+1 种基金Hubei Provincial Creative Team Project of Agricultural Science and Technology(No.2007–620)Fundamental Research Funds for the Central Universities of China(NO.2662017PY017).
文摘Background:Over the last decade,the nutritional requirements of lactating modern genotype sows have increased.The current nutritional recommendations might be unable to meet the needs of increased litter size and milk production,and thus the nutritional requirements need to be re-evaluated.The current study was conducted to investigate the effects of dietary methionine to lysine(Met:Lys)ratios on the performance of and methionine metabolism in lactating sows.Results:During the 1st week of lactation,piglets reared on sows in the 0.37 to 0.57 Met:Lys ratio groups grew faster than those reared on sows in the control group(0.27)(P<0.01).The 0.37-ratio group showed increased levels of GSHPx in plasma during lactation(P<0.01)and decreased concentrations of urea nitrogen in the plasma of sows(P<0.05).Compared with the 0.27-ratio group,the levels of T-AOC and GSH-Px in the plasma and homocysteine in the milk of lactating sows were significantly increased in sows in the 0.47-ratio group(P<0.01).In sows fed a 0.57-ratio diet,the levels of glutathione and taurine in the plasma and milk were improved significantly during lactation.However,the content of TBARS in the blood(P<0.05 at day 7 and P=0.06 at weaning day)was increased(P<0.01).Moreover,there were linear increases in the levels of homocysteine in the blood and milk of sows during the lactation period(P<0.01)with increased dietary Met:Lys ratios in the lactation diet.Conclusions:The current study indicated that increasing the dietary Met:Lys ratio(0.37~0.57)in the lactation diet had no significant effect on the overall performance of sows or the colostrum and milk composition,but it increased piglet mean BW and piglet ADG during the first week of lactation.Increasing dietary methionine levels had no significant effect on antioxidant function in lactation sows,even though it increased levels of GSH and GSH-Px in the plasma of sows during lactation.However,the content of homocysteine in the plasma and milk increased during lactation due to a high level of dietary methionine.
文摘Cutaneous manifestations are variable in patients with eosinophilic granulomatosis with polyangiitis(EGPA).We report a case where bullous eruption was a presenting manifestation of EGPA.A 55-year-old Chinese man with a background of adult-onset asthma and chronic sinusitis was admitted for a 3-week history of lower limb weakness and a large bulla on his right calf with surrounding erythema.Skin biopsy showed a subepidermal blister with significant dermal eosinophilia,without vasculitis.The patient was diagnosed with EGPA with systemic involvement on the basis of a thorough medical history,eosinophilia,cardiac magnetic resonance imaging showing acute myocarditis,and nerve biopsy with eosinophilic vasculitic neuropathy.He responded well to corticosteroids and rituximab.Nonvasculitic bullous eruptions are rarely described as manifestations of EGPA.Prompt recognition of this entity is crucial for its early diagnosis.
文摘A 52-year-old Chinese woman was diagnosed with transcription intermediary factor 1(TIF1)gamma dermatomyositis in November 2022,with manifestations of myositis,polyarthralgia,and low-grade fever.She had cutaneous manifestations of Gottron's sign,V-neck sign,shawl sign,and flagellate erythema(Figure 1A).No interstitial lung disease was detected by high-resolution computed tomography.Comprehensive malignancy screenings,encompassing pap smear and mammogram,endoscopic examination,and computed tomography scans of the thorax,abdomen,and pelvis,were performed.They returned negative,apart from a lobulated nodule with biopsy confirmed as sclerosing pneumocytoma at the left lower lobe(Figure 1C).The therapeutic regimen,consisting of high-dose steroids and mycophenolate mofetil,effectively ameliorated the patient's myositis and rash(Figure 1B).
