Deficiencies in vitamins or other factors(B6,B12,folic acid, betaine)and genetic disorders for the metabolism of the non-protein amino acid-homocysteine(Hcy)lead to hyperhomocysteinemia(HHcy).HHcy is an integral compo...Deficiencies in vitamins or other factors(B6,B12,folic acid, betaine)and genetic disorders for the metabolism of the non-protein amino acid-homocysteine(Hcy)lead to hyperhomocysteinemia(HHcy).HHcy is an integral component of several disorders including cardiovascular disease,neurodegeneration,diabetes and alcoholic liver disease.HHcy unleashes mediators of inflammation such as NFκB,IL-1β,IL-6,and IL-8,increases production of intracellular superoxide anion causing oxidative stress and reducing intracellular level of nitric oxide(NO),and induces endoplasrnic reticulum(ER)stress which can explain many processes of Hcy-promoted cell injury such as apoptosis, fat accumulation,and inflammation.Animal models have played an important role in determining the biological effects of HHcy.ER stress may also be involved in other liver diseases such as α_1-antitrypsin(α_1-AT)deficiency and hepatitis C and/or B virus infection.Future research should evaluate the possible potentiative effects of alcohol and hepatic virus infection on ER stress-induced liver injury,study potentially beneficial effects of lowering Hcy and preventing ER stress in alcoholic humans,and examine polymorphisrn of Hcy metabolizing enzymes as potential risk-factors for the development of HHcy and liver disease.展开更多
A number of feed additives are marketed to assist in boosting the pigs' immune system, regulate gut microbiota, and reduce negative impacts of weaning and other environmental challenges.The most commonly used feed...A number of feed additives are marketed to assist in boosting the pigs' immune system, regulate gut microbiota, and reduce negative impacts of weaning and other environmental challenges.The most commonly used feed additives include acidifiers, zinc and copper, prebiotics, direct-fed microbials, yeast products, nucleotides, and plant extracts.Inclusion of pharmacological levels of zinc and copper, certain acidifiers, and several plant extracts have been reported to result in improved pig performance or improved immune function of pigs.It is also possible that use of prebiotics, direct-fed microbials, yeast,and nucleotides may have positive impacts on pig performance, but results have been less consistent and there is a need for more research in this area.展开更多
AIM: To characterise expression of known E-cadherin repressors; Snail, Slug and Twist in the development of esophageal adenocarcinoma. METHODS: E-cadherin, Slug, Snail and Twist mRNA expression in Barrett's metapl...AIM: To characterise expression of known E-cadherin repressors; Snail, Slug and Twist in the development of esophageal adenocarcinoma. METHODS: E-cadherin, Slug, Snail and Twist mRNA expression in Barrett's metaplasia and esophageal adenocarcinoma specimens was examined by real-time reverse transcription-polymerase chain reaction (RT-PCR). Semi-quantitative immunohistochemistry was used to examine cellular localisation and protein levels. The effect of Slug on epithelial mesenchymal transition (EMT) markers was examined by transfection of Slug into an adenocarcinoma line OE33.RESULTS: Cellular localisation of Slug in Barrett's metaplasia was largely cytoplasmic whilst in adenocarcinoma it was nuclear. Semi-quantitative analysis indicated that Slug was more abundant in adenocarcinoma compared to matched Barrett's metaplastic specimens. Snail and Twist were expressed in adenocarcinoma but were cytoplasmic in location and not induced compared to Barrett's mucosa. These observations were supported by mRNA studies where only Slug mRNA was shown to be over-expressed in adenocarcinoma and inversely correlated to E-cadherin expression. Overexpression of Slug in OE33 mediated E-cadherin repression and induced the mesenchymal markers vimentin and fibronectin.CONCLUSION: Progression to adenocarcinoma is associated with increased Slug expression and this may represent a mechanism of E-cadherin silencing.展开更多
In addition to restoration of bladder, bowel, and motor functions, alleviating the accompanying debilitating pain is equally important for improving the quality of life of patients with spinal cord injury(SCI). Curren...In addition to restoration of bladder, bowel, and motor functions, alleviating the accompanying debilitating pain is equally important for improving the quality of life of patients with spinal cord injury(SCI). Currently,however, the treatment of chronic pain after SCI remains a largely unmet need. Electrical spinal cord stimulation(SCS) has been used to manage a variety of chronic pain conditions that are refractory to pharmacotherapy. Yet, its efficacy, benefit profiles, and mechanisms of action in SCI pain remain elusive, due to limited research, methodological weaknesses in previous clinical studies, and a lack of mechanistic exploration of SCS for SCI pain control. We aim to review recent studies and outline the therapeutic potential of different SCS paradigms for traumatic SCI pain. We begin with an overview of its manifestations,classification, potential underlying etiology, and currentchallenges for its treatment. The clinical evidence for using SCS in SCI pain is then reviewed. Finally, future perspectives of pre-clinical research and clinical study of SCS for SCI pain treatment are discussed.展开更多
The 18 kDa translocator protein(TSPO),previously known as the peripheral benzodiazepine receptor,is predominately localized to the outer mitochondrial membrane in steroidogenic cells.Brain TSPO expression is relativel...The 18 kDa translocator protein(TSPO),previously known as the peripheral benzodiazepine receptor,is predominately localized to the outer mitochondrial membrane in steroidogenic cells.Brain TSPO expression is relatively low under physiological conditions,but is upregulated in response to glial cell activation.As the primary index of neuroinflammation,TSPO is implicated in the pathogenesis and progression of numerous neuropsychiatric disorders and neurodegenerative diseases,including Alzheimer’s disease(AD),amyotrophic lateral sclerosis(ALS),Parkinson’s disease(PD),multiple sclerosis(MS),major depressive disorder(MDD)and obsessive compulsive disorder(OCD).In this context,numerous TSPO-targeted positron emission tomography(PET)tracers have been developed.Among them,several radioligands have advanced to clinical research studies.In this review,we will overview the recent development of TSPO PET tracers,focusing on the radioligand design,radioisotope labeling,pharmacokinetics,and PET imaging evaluation.Additionally,we will consider current limitations,as well as translational potential for future application of TSPO radiopharmaceuticals.This review aims to not only present the challenges in current TSPO PET imaging,but to also provide a new perspective on TSPO targeted PET tracer discovery efforts.Addressing these challenges will facilitate the translation of TSPO in clinical studies of neuroinflammation associated with central nervous system diseases.展开更多
AIM:To investigate if antibiotics administered within 8 h of endoscopy reduce mortality or increase the incidence of Clostridium difficile infection(CDI).METHODS:A 2-year retrospective analysis of all patients who pre...AIM:To investigate if antibiotics administered within 8 h of endoscopy reduce mortality or increase the incidence of Clostridium difficile infection(CDI).METHODS:A 2-year retrospective analysis of all patients who presented with first variceal hemorrhage was undertaken.The primary outcome measure was 28-d mortality.Secondary outcome measures were 28-d rebleeding rates and 28-d incidence of CDI.All patients were admitted to a tertiary liver unit with a consultantled,24-h endoscopy service.Patients received standard care including terlipressin therapy.Data collection included:primary and secondary outcome measures,timing of first administration of intravenous antibiotics,eti-ology of liver disease,demographics,endoscopy details and complications.A prospective study was undertaken to determine the incidence of CDI in the study population and general medical inpatients admitted for antibiotic therapy of at least 5 d duration.Statistical analysis was undertaken using univariate,non-parametric tests and multivariate logistic regression analysis.RESULTS:There were 70 first presentations of variceal hemorrhage during the study period.Seventy percent of cases were male and 65.7% were due to chronic alcoholic liver disease.In total,64/70(91.4%) patients received antibiotics as prophylaxis during their admission.Specifically,53/70(75.7%) received antibiotics either before endoscopy or within 8 h of endoscopy [peri-endoscopy(8 h) group],whereas 17/70(24.3%) received antibiotics at > 8 h after endoscopy or not at all(non peri-endoscopy group).Overall mortality and rebleeding rates were 13/70(18.6%) and 14/70(20%),respectively.The periendoscopy(8 h) group was significantly less likely to die compared with the non peri-endoscopy group [13.2% vs 35.3%,P = 0.04,odds ratio(OR) = 0.28(0.078-0.997)] and showed a trend towards reduced rebleeding [17.0% vs 29.4%,P = 0.27,OR = 0.49(0.14-1.74)].On univariate analysis,the non peri-endoscopy group [P = 0.02,OR = 3.58(1.00-12.81)],higher model for end-stage liver disease(MELD) score(P = 0.展开更多
Outcomes following peripheral nerve injury remain frustratingly poor. The reasons for this are multifactorial, although maintaining a growth permissive environment in the distal nerve stump following repair is arguabl...Outcomes following peripheral nerve injury remain frustratingly poor. The reasons for this are multifactorial, although maintaining a growth permissive environment in the distal nerve stump following repair is arguably the most important. The optimal environment for axonal regeneration relies on the synthesis and release of many biochemical mediators that are temporally and spatially regulated with a high level of incompletely understood complexity. The Schwann cell(SC) has emerged as a key player in this process. Prolonged periods of distal nerve stump denervation, characteristic of large gaps and proximal injuries, have been associated with a reduction in SC number and ability to support regenerating axons. Cell based therapy offers a potential therapy for the improvement of outcomes following peripheral nerve reconstruction. Stem cells have the potential to increase the number of SCs and prolong their ability to support regeneration. They may also have the ability to rescue and replenish populations of chromatolytic and apoptotic neurons following axotomy. Finally, they can be used in non-physiologic ways to preserve injured tissues such as denervated muscle while neuronal ingrowth has not yet occurred. Aside from stem cell type, careful consideration must be given to differentiation status, how stem cells are supported following transplantation and how they will be delivered to the site of injury. It is the aim of this article to review current opinions on the strategies of stem cell based therapy for the augmentation of peripheral nerve regeneration.展开更多
The conservation status of all the amphibians in China is analyzed,and the country is shown to be a global priority for conservation in comparison to many other countries of the world.Three Chinese regions are particu...The conservation status of all the amphibians in China is analyzed,and the country is shown to be a global priority for conservation in comparison to many other countries of the world.Three Chinese regions are particularly rich in amphibian diversity:Hengduan,Nanling,and Wuyi mountains.Sala-manders are more threatened than frogs and toads.Several smaller families show a high propensity to become seriously threatened:Bombinatoridae,Cryptobranchidae,Hynobiidae and Salamandridae.Like other parts of the world,stream-breeding,high-elevation forest amphibians have a much higher likeli-hood of being seriously threatened.Habitat loss,pollution,and over-harvesting are the most serious threats to Chinese amphibians.Over-harvesting is a less pervasive threat than habitat loss,but it is more likely to drive a species into rapid decline.Five conservation challenges are mentioned with recommendations for the highest priority research and conservation actions.展开更多
基金Supported by the U.S.National Institute of Alcohol Abuse and Alcoholism,R01 AA014428 and by the Robert E.and May R.Wright Foundation,No.263
文摘Deficiencies in vitamins or other factors(B6,B12,folic acid, betaine)and genetic disorders for the metabolism of the non-protein amino acid-homocysteine(Hcy)lead to hyperhomocysteinemia(HHcy).HHcy is an integral component of several disorders including cardiovascular disease,neurodegeneration,diabetes and alcoholic liver disease.HHcy unleashes mediators of inflammation such as NFκB,IL-1β,IL-6,and IL-8,increases production of intracellular superoxide anion causing oxidative stress and reducing intracellular level of nitric oxide(NO),and induces endoplasrnic reticulum(ER)stress which can explain many processes of Hcy-promoted cell injury such as apoptosis, fat accumulation,and inflammation.Animal models have played an important role in determining the biological effects of HHcy.ER stress may also be involved in other liver diseases such as α_1-antitrypsin(α_1-AT)deficiency and hepatitis C and/or B virus infection.Future research should evaluate the possible potentiative effects of alcohol and hepatic virus infection on ER stress-induced liver injury,study potentially beneficial effects of lowering Hcy and preventing ER stress in alcoholic humans,and examine polymorphisrn of Hcy metabolizing enzymes as potential risk-factors for the development of HHcy and liver disease.
文摘A number of feed additives are marketed to assist in boosting the pigs' immune system, regulate gut microbiota, and reduce negative impacts of weaning and other environmental challenges.The most commonly used feed additives include acidifiers, zinc and copper, prebiotics, direct-fed microbials, yeast products, nucleotides, and plant extracts.Inclusion of pharmacological levels of zinc and copper, certain acidifiers, and several plant extracts have been reported to result in improved pig performance or improved immune function of pigs.It is also possible that use of prebiotics, direct-fed microbials, yeast,and nucleotides may have positive impacts on pig performance, but results have been less consistent and there is a need for more research in this area.
基金Supported by City Hospital Trust Fundthe University of Birmingham Scientific Project Grant
文摘AIM: To characterise expression of known E-cadherin repressors; Snail, Slug and Twist in the development of esophageal adenocarcinoma. METHODS: E-cadherin, Slug, Snail and Twist mRNA expression in Barrett's metaplasia and esophageal adenocarcinoma specimens was examined by real-time reverse transcription-polymerase chain reaction (RT-PCR). Semi-quantitative immunohistochemistry was used to examine cellular localisation and protein levels. The effect of Slug on epithelial mesenchymal transition (EMT) markers was examined by transfection of Slug into an adenocarcinoma line OE33.RESULTS: Cellular localisation of Slug in Barrett's metaplasia was largely cytoplasmic whilst in adenocarcinoma it was nuclear. Semi-quantitative analysis indicated that Slug was more abundant in adenocarcinoma compared to matched Barrett's metaplastic specimens. Snail and Twist were expressed in adenocarcinoma but were cytoplasmic in location and not induced compared to Barrett's mucosa. These observations were supported by mRNA studies where only Slug mRNA was shown to be over-expressed in adenocarcinoma and inversely correlated to E-cadherin expression. Overexpression of Slug in OE33 mediated E-cadherin repression and induced the mesenchymal markers vimentin and fibronectin.CONCLUSION: Progression to adenocarcinoma is associated with increased Slug expression and this may represent a mechanism of E-cadherin silencing.
基金supported by grants from the National Institutes of Health, Bethesda, MD (R01NS70814 and R21NS99879 to YG)
文摘In addition to restoration of bladder, bowel, and motor functions, alleviating the accompanying debilitating pain is equally important for improving the quality of life of patients with spinal cord injury(SCI). Currently,however, the treatment of chronic pain after SCI remains a largely unmet need. Electrical spinal cord stimulation(SCS) has been used to manage a variety of chronic pain conditions that are refractory to pharmacotherapy. Yet, its efficacy, benefit profiles, and mechanisms of action in SCI pain remain elusive, due to limited research, methodological weaknesses in previous clinical studies, and a lack of mechanistic exploration of SCS for SCI pain control. We aim to review recent studies and outline the therapeutic potential of different SCS paradigms for traumatic SCI pain. We begin with an overview of its manifestations,classification, potential underlying etiology, and currentchallenges for its treatment. The clinical evidence for using SCS in SCI pain is then reviewed. Finally, future perspectives of pre-clinical research and clinical study of SCS for SCI pain treatment are discussed.
基金support of K.C.Wong Education Foundation(China)the Project of Innovative Team for the Guangdong Universities(2018KCXTD001,China)+1 种基金financially supported by the National Natural Science Foundation of China(Nos.81701751 and 81871383)Guangdong Basic and Applied Basic Research Foundation(2020A1515011192,China)
文摘The 18 kDa translocator protein(TSPO),previously known as the peripheral benzodiazepine receptor,is predominately localized to the outer mitochondrial membrane in steroidogenic cells.Brain TSPO expression is relatively low under physiological conditions,but is upregulated in response to glial cell activation.As the primary index of neuroinflammation,TSPO is implicated in the pathogenesis and progression of numerous neuropsychiatric disorders and neurodegenerative diseases,including Alzheimer’s disease(AD),amyotrophic lateral sclerosis(ALS),Parkinson’s disease(PD),multiple sclerosis(MS),major depressive disorder(MDD)and obsessive compulsive disorder(OCD).In this context,numerous TSPO-targeted positron emission tomography(PET)tracers have been developed.Among them,several radioligands have advanced to clinical research studies.In this review,we will overview the recent development of TSPO PET tracers,focusing on the radioligand design,radioisotope labeling,pharmacokinetics,and PET imaging evaluation.Additionally,we will consider current limitations,as well as translational potential for future application of TSPO radiopharmaceuticals.This review aims to not only present the challenges in current TSPO PET imaging,but to also provide a new perspective on TSPO targeted PET tracer discovery efforts.Addressing these challenges will facilitate the translation of TSPO in clinical studies of neuroinflammation associated with central nervous system diseases.
文摘AIM:To investigate if antibiotics administered within 8 h of endoscopy reduce mortality or increase the incidence of Clostridium difficile infection(CDI).METHODS:A 2-year retrospective analysis of all patients who presented with first variceal hemorrhage was undertaken.The primary outcome measure was 28-d mortality.Secondary outcome measures were 28-d rebleeding rates and 28-d incidence of CDI.All patients were admitted to a tertiary liver unit with a consultantled,24-h endoscopy service.Patients received standard care including terlipressin therapy.Data collection included:primary and secondary outcome measures,timing of first administration of intravenous antibiotics,eti-ology of liver disease,demographics,endoscopy details and complications.A prospective study was undertaken to determine the incidence of CDI in the study population and general medical inpatients admitted for antibiotic therapy of at least 5 d duration.Statistical analysis was undertaken using univariate,non-parametric tests and multivariate logistic regression analysis.RESULTS:There were 70 first presentations of variceal hemorrhage during the study period.Seventy percent of cases were male and 65.7% were due to chronic alcoholic liver disease.In total,64/70(91.4%) patients received antibiotics as prophylaxis during their admission.Specifically,53/70(75.7%) received antibiotics either before endoscopy or within 8 h of endoscopy [peri-endoscopy(8 h) group],whereas 17/70(24.3%) received antibiotics at > 8 h after endoscopy or not at all(non peri-endoscopy group).Overall mortality and rebleeding rates were 13/70(18.6%) and 14/70(20%),respectively.The periendoscopy(8 h) group was significantly less likely to die compared with the non peri-endoscopy group [13.2% vs 35.3%,P = 0.04,odds ratio(OR) = 0.28(0.078-0.997)] and showed a trend towards reduced rebleeding [17.0% vs 29.4%,P = 0.27,OR = 0.49(0.14-1.74)].On univariate analysis,the non peri-endoscopy group [P = 0.02,OR = 3.58(1.00-12.81)],higher model for end-stage liver disease(MELD) score(P = 0.
文摘Outcomes following peripheral nerve injury remain frustratingly poor. The reasons for this are multifactorial, although maintaining a growth permissive environment in the distal nerve stump following repair is arguably the most important. The optimal environment for axonal regeneration relies on the synthesis and release of many biochemical mediators that are temporally and spatially regulated with a high level of incompletely understood complexity. The Schwann cell(SC) has emerged as a key player in this process. Prolonged periods of distal nerve stump denervation, characteristic of large gaps and proximal injuries, have been associated with a reduction in SC number and ability to support regenerating axons. Cell based therapy offers a potential therapy for the improvement of outcomes following peripheral nerve reconstruction. Stem cells have the potential to increase the number of SCs and prolong their ability to support regeneration. They may also have the ability to rescue and replenish populations of chromatolytic and apoptotic neurons following axotomy. Finally, they can be used in non-physiologic ways to preserve injured tissues such as denervated muscle while neuronal ingrowth has not yet occurred. Aside from stem cell type, careful consideration must be given to differentiation status, how stem cells are supported following transplantation and how they will be delivered to the site of injury. It is the aim of this article to review current opinions on the strategies of stem cell based therapy for the augmentation of peripheral nerve regeneration.
文摘The conservation status of all the amphibians in China is analyzed,and the country is shown to be a global priority for conservation in comparison to many other countries of the world.Three Chinese regions are particularly rich in amphibian diversity:Hengduan,Nanling,and Wuyi mountains.Sala-manders are more threatened than frogs and toads.Several smaller families show a high propensity to become seriously threatened:Bombinatoridae,Cryptobranchidae,Hynobiidae and Salamandridae.Like other parts of the world,stream-breeding,high-elevation forest amphibians have a much higher likeli-hood of being seriously threatened.Habitat loss,pollution,and over-harvesting are the most serious threats to Chinese amphibians.Over-harvesting is a less pervasive threat than habitat loss,but it is more likely to drive a species into rapid decline.Five conservation challenges are mentioned with recommendations for the highest priority research and conservation actions.
