Compelling evidence demonstrates that the levels of peripheral amyloid-β(Aβ)fluctuate in Alzheimer’s disease(AD)patients.Moreover,Aβdeposits have been identified in peripheral tissues.However,the relevance of peri...Compelling evidence demonstrates that the levels of peripheral amyloid-β(Aβ)fluctuate in Alzheimer’s disease(AD)patients.Moreover,Aβdeposits have been identified in peripheral tissues.However,the relevance of peripheral Aβ(misfolded or not)in pathological situations,and the temporal appearance of these pathological fluctuations,are not well understood.The presence of misfolded Aβin peripheral compartments raises concerns on potential inter-individual transmissions considering the well-reported prion-like properties of this disease-associated protein.The latter is supported by multiple reports demonstrating that Aβmisfolding can be transmitted between humans and experimental animals through multiple routes of exposure.In this mini-review,we discuss the potential implications of peripheral,disease-associated Aβin disease mechanisms,as well as in diagnostic and therapeutic approaches.展开更多
The misfolding and subsequent aggregation of proteins into amyloid fibrils underlie the onset of a variety of human disorders collectively known as amyloidosis.Transthyretin(TTR)is one of the>30 amyloidogenic prote...The misfolding and subsequent aggregation of proteins into amyloid fibrils underlie the onset of a variety of human disorders collectively known as amyloidosis.Transthyretin(TTR)is one of the>30 amyloidogenic proteins identified to date and is associated with a group of highly debilitating and life-threatening disorders called TTR amyloidosis(ATTR).ATTR comprises senile systemic amyloidosis,which is linked to wild-type(WT)TTR aggregation,and hereditary ATTR,a dominantly inherited disorder caused by the deposition of one of over 130 TTR genetic variants.Senile systemic amyloidosis is a prevalent age-related amyloidosis,affecting up to 25%of the population over 80 years of age,and is characterized by the build-up of TTR fibrils in the myocardium.Regarding hereditary ATTR,the clinical presentation is highly heterogeneous,primarily affecting the peripheral nervous system(familial amyloid polyneuropathy-FAP)or the heart(familial amyloid cardiomyopathy).In rare cases,aggregation develops in the central nervous system,giving rise to a phenotype known as familial leptomeningeal amyloidosis(Carroll et al.,2022).展开更多
In the article titled“Activation of autophagy by Citri Reticulatae Semen extract ameliorates amyloid-beta-induced cell death and cognition deficits in Alzheimer’s disease”published on pages 2467-2479,Issue 11,Volum...In the article titled“Activation of autophagy by Citri Reticulatae Semen extract ameliorates amyloid-beta-induced cell death and cognition deficits in Alzheimer’s disease”published on pages 2467-2479,Issue 11,Volume 19 of Neural Regeneration Research(Tang et al.,2024),there are some errors in selecting the appropriate images in Figure 7 by authors during assembling the images.展开更多
Although many causes of Alzheimer’s disease(AD)may exist,both the original amyloid cascade and tau hypotheses posit that abnormal misfolding and accumulation of amyloid-β(Aβ)and tau protein is the central event cau...Although many causes of Alzheimer’s disease(AD)may exist,both the original amyloid cascade and tau hypotheses posit that abnormal misfolding and accumulation of amyloid-β(Aβ)and tau protein is the central event causing the pathology.However,that conclusion could be only partly true,and there is conflicting evidence about the role of both proteins in AD,being able to precede and influence one another.Some researchers argue that these proteins are mere executors rather than primary causes of pathology.Therefore,there have been continuing refinements of both hypotheses,with alternative explanations proposed.Aβand tau proteins may be independently involved in specific neurotoxic pathways;yet there may be other crucial processes going on in early AD.Moreover,accumulating evidence suggests that Aβand tau act synergistically,rather than additively in disease onset(Jeremic et al.,2021,2023a).展开更多
Amyloid fibrils are highly organized protein or peptide aggregates,often characterized by a distinctive supramolecular cross-β-sheet structure.The formation and accumulation of these structures have been traditionall...Amyloid fibrils are highly organized protein or peptide aggregates,often characterized by a distinctive supramolecular cross-β-sheet structure.The formation and accumulation of these structures have been traditionally associated with neural or systemic human diseases,such as Alzheimer’s disease,Parkinson’s disease,type-2 diabetes,or amyotrophic lateral sclerosis(Wei et al.,2017;Wittung-Stafshede,2023).展开更多
Brain vascular dysfunction in Alzheimer s disease(AD) pathogenesis has become increasingly clea r.Accumulating evidence shows that damaged vascular,including large or small vessels and even neurovascular unit,may acce...Brain vascular dysfunction in Alzheimer s disease(AD) pathogenesis has become increasingly clea r.Accumulating evidence shows that damaged vascular,including large or small vessels and even neurovascular unit,may accelerate the neuropathological process of AD via disrupting brain hypoperfusion,aberrant angiogenesis,and neuroinflammatory response,etc.Thus,vascular dysfunction makes a substantially contribution to the cognitive decline of AD patients.展开更多
Introduction: Amyloidosis are systemic conditions and carpal tunnel syndrome (CTS) precedes the principal systemic complications and can be used as an early marker. Our objective was to determine the frequency of amyl...Introduction: Amyloidosis are systemic conditions and carpal tunnel syndrome (CTS) precedes the principal systemic complications and can be used as an early marker. Our objective was to determine the frequency of amyloid deposition in idiopathic CTS and its systemic impact. Methods: We retrospectively evaluated patients with CTS between September 2019 to January 2020. Samples from the anterior carpal ligament were pathologically evaluated and amyloid deposition was confirmed by apple-green birefringence on polarized light using Congo red stain. When amyloid was detected we performed genetic testing for transthyretin variants (ATTRv), immunofixation electrophoresis in serum and urine for light chains and multidisciplinary evaluation. Results: Thirty consecutive patients were included, 19 women, 11 men, mean age 70 years old (range 42 - 89 years). We identified 3 patients (10%) with amyloid deposits (mean age: 78.6 years, 2 men, 1 woman). Genetic testing for ATTRv and light chains studies were negative. During follow-up: The first patient required aortic valve replacement. The second patient developed progressive cardiac failure with syncopal episodes, atrioventricular block and atrial fibrillation and required a pacemaker and anticoagulation. The third patient had unexplained chronic edemas. The cardiac evaluation in all 3 patients revealed left ventricular hypertrophy and myocardial uptake (Perugini Score > 2) in their nuclear bone scintigraphies with technetium pyrophosphate. Two patients were treated with tafamidis and one patient died due to refractory cardiac insufficiency. Discussion: Our findings underline the importance of investigating amyloidosis in idiopathic CTS. The identification of deposits allows early diagnosis of cardiac amyloidosis leading to timely intervention and treatment.展开更多
The amyloid—what peptide can resist its entropic bliss?Without kinetic barricades and chaperones,most peptides would simply tumble down that precipice.The amyloid-β(Aβ) peptides are understood to underlie the hallm...The amyloid—what peptide can resist its entropic bliss?Without kinetic barricades and chaperones,most peptides would simply tumble down that precipice.The amyloid-β(Aβ) peptides are understood to underlie the hallmark pathology of Alzheimer's disease(AD) and are considered one of the causative factors for neurodegeneration and cognitive impairment.AD affects critical connected structures within the brain that are responsible for memory,language,and social behavior.展开更多
Transmission of misfolded amyloid-β(Aβ)aggregates between human subjects:Protein misfolding disorders are a family of diseases characterized by the accumulation of misfolded protein aggregates.These proteinaceous st...Transmission of misfolded amyloid-β(Aβ)aggregates between human subjects:Protein misfolding disorders are a family of diseases characterized by the accumulation of misfolded protein aggregates.These proteinaceous structures,also known as amyloids,are key drivers of fatal neurodegenerative disorders such as prion diseases,Alzheimer’s disease(AD),Parkinson’s disease,and others.展开更多
Need for Alzheimer's disease progression monitoring:Alzheimer's disease(AD)is an irreversible progressive brain disorder that causes severe and incurable neuro-impairment.The World Health Organization estimate...Need for Alzheimer's disease progression monitoring:Alzheimer's disease(AD)is an irreversible progressive brain disorder that causes severe and incurable neuro-impairment.The World Health Organization estimates that 55 million people are affected by AD dementia by 2020 which may exceed 78 million by 2030 and 139 in 2050.The estimated cost to manage AD is above US$1.3 trillion,which will further increase to US$2.8 trillion by 2030.展开更多
This case report investigates the manifestation of cerebral amyloid angiopathy (CAA) through recurrent Transient Ischemic Attacks (TIAs) in an 82-year-old patient. Despite initial diagnostic complexities, cerebral ang...This case report investigates the manifestation of cerebral amyloid angiopathy (CAA) through recurrent Transient Ischemic Attacks (TIAs) in an 82-year-old patient. Despite initial diagnostic complexities, cerebral angiography-MRI revealed features indicative of CAA. Symptomatic treatment resulted in improvement, but the patient later developed a fatal hematoma. The discussion navigates the intricate therapeutic landscape of repetitive TIAs in the elderly with cardiovascular risk factors, emphasizing the pivotal role of cerebral MRI and meticulous bleeding risk management. The conclusion stresses the importance of incorporating SWI sequences, specifically when suspecting a cardioembolic TIA, as a diagnostic measure to explore and exclude CAA in the differential diagnosis. This case report provides valuable insights into these challenges, highlighting the need to consider CAA in relevant cases.展开更多
BACKGROUND Necrotising enterocolitis(NEC)is a critical gastrointestinal emergency affecting premature and low-birth-weight neonates.Serum amyloid A(SAA),procalcitonin(PCT),and high-mobility group box 1(HMGB1)have emer...BACKGROUND Necrotising enterocolitis(NEC)is a critical gastrointestinal emergency affecting premature and low-birth-weight neonates.Serum amyloid A(SAA),procalcitonin(PCT),and high-mobility group box 1(HMGB1)have emerged as potential biomarkers for NEC due to their roles in inflammatory response,tissue damage,and immune regulation.AIM To evaluate the diagnostic value of SAA,PCT,and HMGB1 in the context of NEC in newborns.METHODS The study retrospectively analysed the clinical data of 48 newborns diagnosed with NEC and 50 healthy newborns admitted to the hospital.Clinical,radiological,and laboratory findings,including serum SAA,PCT,and HMGB1 Levels,were collected,and specific detection methods were used.The diagnostic value of the biomarkers was evaluated through statistical analysis,which was performed using chi-square test,t-test,correlation analysis,and receiver operating characteristic(ROC)analysis.RESULTS The study demonstrated significantly elevated levels of serum SAA,PCT,and HMGB1 Levels in newborns diagnosed with NEC compared with healthy controls.The correlation analysis indicated strong positive correlations among serum SAA,PCT,and HMGB1 Levels and the presence of NEC.ROC analysis revealed promising sensitivity and specificity for serum SAA,PCT,and HMGB1 Levels as potential diagnostic markers.The combined model of the three biomarkers demonstrating an extremely high area under the curve(0.908).CONCLUSION The diagnostic value of serum SAA,PCT,and HMGB1 Levels in NEC was highlighted.These biomarkers potentially improve the early detection,risk stratification,and clinical management of critical conditions.The findings suggest that these biomarkers may aid in timely intervention and the enhancement of outcomes for neonates affected by NEC.展开更多
The use of anticoagulation therapy could prove to be controversial when trying to balance ischemic stroke and intracranial bleeding risks in patients with concurrent cerebral amyloid angiopathy(CAA)and atrial fibrilla...The use of anticoagulation therapy could prove to be controversial when trying to balance ischemic stroke and intracranial bleeding risks in patients with concurrent cerebral amyloid angiopathy(CAA)and atrial fibrillation(AF).In fact,CAA is an age-related cerebral vasculopathy that predisposes patients to intracerebral hemorrhage.Nevertheless,many AF patients require oral systemic dose-adjusted warfarin,direct oral anticoagulants(such as factor Xa inhibitors)or direct thrombin inhibitors to control often associated with cardioembolic stroke risk.The prevalence of both CAA and AF is expected to rise,due to the aging of the population.This clinical dilemma is becoming increasingly common.In patients with coexisting AF and CAA,the risks/benefits profile of anticoagulant therapy must be assessed for each patient individually due to the lack of a clear-cut consensus with regard to its risks in scientific literature.This review aims to provide an overview of the management of patients with concomitant AF and CAA and proposes the implementation of a risk-based decision-making algorithm.展开更多
Increasing evidence demonstrated that the blood-brain barrier(BBB)was involved in developing cerebral amyloid angiopathy(CAA).The BBB participates in the neurovascular coupling and regulates the transport of substance...Increasing evidence demonstrated that the blood-brain barrier(BBB)was involved in developing cerebral amyloid angiopathy(CAA).The BBB participates in the neurovascular coupling and regulates the transport of substances,which is closely related to neurodegenerative diseases.In CAA,the deposition of amyloid beta(Aβ)in arteries,capillaries,and arterioles of meninges and cerebral cortex results in the destruction of the BBB,chronic inflammatory response,chronic cerebral hypoperfusion,and dysfunction of the neurovascular unit,which eventually leads to neurodegeneration.At the same time,CAA is an age-related disease.Patients with CAA often have some risk factors for cerebrovascular diseases,such as hypertension and diabetes,which can further aggravate the damage to the BBB.Thus,it is of great significance to pay attention to the BBB in the pathogenesis and future intervention targets of CAA.Therefore,this manuscript reviewed the dysfunction of the BBB in CAA.展开更多
Cerebral amyloid angiopathy(CAA)is a small vessel disease of the brain characterized by the progressive deposition of amyloid-β(Aβ)plaques in the walls of cerebral blood vessels.It presents with a subtle course and ...Cerebral amyloid angiopathy(CAA)is a small vessel disease of the brain characterized by the progressive deposition of amyloid-β(Aβ)plaques in the walls of cerebral blood vessels.It presents with a subtle course and sudden onset,and currently,there are no specific therapeutic interventions available.Accurate diagnosis of CAA could enable targeted interventions in the early stages of the disease,potentially mitigating the disease’s effects.Herein,we review the primary imaging biomarkers used in the diagnosis of CAA,including their mechanisms,imaging characteristics,and significance.We also provide an interpretation of the latest version(v2.0)of the Boston criteria,which are commonly used in the clinical diagnosis of CAA.Additionally,this study introduces various positron emission tomography(PET)tracers for CAA and reviews their application values in the diagnosis of CAA.展开更多
The hidden world of amyloid biology has suddenly snapped into atomic-level focus,revealing over 80 amyloid protein fibrils,both pathogenic and functional.Unlike globular proteins,amyloid proteins flatten and stack int...The hidden world of amyloid biology has suddenly snapped into atomic-level focus,revealing over 80 amyloid protein fibrils,both pathogenic and functional.Unlike globular proteins,amyloid proteins flatten and stack into unbranched fibrils.Stranger still,a single protein sequence can adopt wildly different two-dimensional conformations,yielding distinct fibril polymorphs.展开更多
Objective To observe the migration and differentiation of the neural precursor cells （NPCs） that derived from murine embryonic stem cells （ESCs） when they were transplanted into amyloid β （Aβ）-treated rat hipp...Objective To observe the migration and differentiation of the neural precursor cells （NPCs） that derived from murine embryonic stem cells （ESCs） when they were transplanted into amyloid β （Aβ）-treated rat hippocampus. Methods MESPU35, a murine ESC cell line that express the enhanced green fluorescent protein （EGFP）, was induced differentiation into nestin-positive NPCs by modified serum-free methods. The Aβ plaques and the differentiation of the grafted cells were observed by immunofluorescent staining. Results Comparing 16 weeks with 4 weeks post-transplantation, the migration distance increased about 5 times; the rate of migratory NPCs differentiating into glial fibrillary acidic protein （GFAP）-positive cells kept rising from （30.41 ± 1.45）% to （49.25± 1.23）%, and the rate of NPCs differentiating into neurofilament 200 （NF200） positive cells increased from （16.68±0.95）% to （27.94± 1.21）%. Meanwhile, the GFAP-positive cells targeting to the ipsilateral side of Aβ plaques increased from 60.2% to 81.3 %, while the NF200-positive cells increased from 61.3% to 84.1%. The migration distance had significant positive linear correlations to the neuronal differentiation rate （r = 0.991） and to the astrocytic differentiation rate （r = 0.953）. Conclusion Engrafted NPCs migrate targetedly to the Aβ injection site and differentiate into neurons and astrocytes.展开更多
基金supported by grants from NIH(RF1AG072491 and R01AI132695)to RM.
文摘Compelling evidence demonstrates that the levels of peripheral amyloid-β(Aβ)fluctuate in Alzheimer’s disease(AD)patients.Moreover,Aβdeposits have been identified in peripheral tissues.However,the relevance of peripheral Aβ(misfolded or not)in pathological situations,and the temporal appearance of these pathological fluctuations,are not well understood.The presence of misfolded Aβin peripheral compartments raises concerns on potential inter-individual transmissions considering the well-reported prion-like properties of this disease-associated protein.The latter is supported by multiple reports demonstrating that Aβmisfolding can be transmitted between humans and experimental animals through multiple routes of exposure.In this mini-review,we discuss the potential implications of peripheral,disease-associated Aβin disease mechanisms,as well as in diagnostic and therapeutic approaches.
基金funded by the Spanish Ministry of Science and Innovation(PDC2021-120914-I00)the Universitat Autònoma de Barcelona(PROOF OF CONCEPT 2020)ICREA,ICREA-Academia 2015 and 2020(to SV).
文摘The misfolding and subsequent aggregation of proteins into amyloid fibrils underlie the onset of a variety of human disorders collectively known as amyloidosis.Transthyretin(TTR)is one of the>30 amyloidogenic proteins identified to date and is associated with a group of highly debilitating and life-threatening disorders called TTR amyloidosis(ATTR).ATTR comprises senile systemic amyloidosis,which is linked to wild-type(WT)TTR aggregation,and hereditary ATTR,a dominantly inherited disorder caused by the deposition of one of over 130 TTR genetic variants.Senile systemic amyloidosis is a prevalent age-related amyloidosis,affecting up to 25%of the population over 80 years of age,and is characterized by the build-up of TTR fibrils in the myocardium.Regarding hereditary ATTR,the clinical presentation is highly heterogeneous,primarily affecting the peripheral nervous system(familial amyloid polyneuropathy-FAP)or the heart(familial amyloid cardiomyopathy).In rare cases,aggregation develops in the central nervous system,giving rise to a phenotype known as familial leptomeningeal amyloidosis(Carroll et al.,2022).
文摘In the article titled“Activation of autophagy by Citri Reticulatae Semen extract ameliorates amyloid-beta-induced cell death and cognition deficits in Alzheimer’s disease”published on pages 2467-2479,Issue 11,Volume 19 of Neural Regeneration Research(Tang et al.,2024),there are some errors in selecting the appropriate images in Figure 7 by authors during assembling the images.
基金supported by grants PID2020-115823-GB100 funded by MCIN/AEI/10.13039/501100011033SBPLY/21/180501/000150 funded by JCCM/ERDF-A way of making Europe+1 种基金2022-GRIN-34354 grant by UCLM/ERDF intramural funding to LJDJDNL.DJ held a predoctoral fellowship granted by UCLM/ESF“Plan Propio de Investigación.”。
文摘Although many causes of Alzheimer’s disease(AD)may exist,both the original amyloid cascade and tau hypotheses posit that abnormal misfolding and accumulation of amyloid-β(Aβ)and tau protein is the central event causing the pathology.However,that conclusion could be only partly true,and there is conflicting evidence about the role of both proteins in AD,being able to precede and influence one another.Some researchers argue that these proteins are mere executors rather than primary causes of pathology.Therefore,there have been continuing refinements of both hypotheses,with alternative explanations proposed.Aβand tau proteins may be independently involved in specific neurotoxic pathways;yet there may be other crucial processes going on in early AD.Moreover,accumulating evidence suggests that Aβand tau act synergistically,rather than additively in disease onset(Jeremic et al.,2021,2023a).
文摘Amyloid fibrils are highly organized protein or peptide aggregates,often characterized by a distinctive supramolecular cross-β-sheet structure.The formation and accumulation of these structures have been traditionally associated with neural or systemic human diseases,such as Alzheimer’s disease,Parkinson’s disease,type-2 diabetes,or amyotrophic lateral sclerosis(Wei et al.,2017;Wittung-Stafshede,2023).
基金supported by the Science and Technology Innovation 2030-Major Projects,No.2022ZD021 1 600the National Natural Science Foundation of China,Nos.82271574 and82071204 (all to CX)。
文摘Brain vascular dysfunction in Alzheimer s disease(AD) pathogenesis has become increasingly clea r.Accumulating evidence shows that damaged vascular,including large or small vessels and even neurovascular unit,may accelerate the neuropathological process of AD via disrupting brain hypoperfusion,aberrant angiogenesis,and neuroinflammatory response,etc.Thus,vascular dysfunction makes a substantially contribution to the cognitive decline of AD patients.
文摘Introduction: Amyloidosis are systemic conditions and carpal tunnel syndrome (CTS) precedes the principal systemic complications and can be used as an early marker. Our objective was to determine the frequency of amyloid deposition in idiopathic CTS and its systemic impact. Methods: We retrospectively evaluated patients with CTS between September 2019 to January 2020. Samples from the anterior carpal ligament were pathologically evaluated and amyloid deposition was confirmed by apple-green birefringence on polarized light using Congo red stain. When amyloid was detected we performed genetic testing for transthyretin variants (ATTRv), immunofixation electrophoresis in serum and urine for light chains and multidisciplinary evaluation. Results: Thirty consecutive patients were included, 19 women, 11 men, mean age 70 years old (range 42 - 89 years). We identified 3 patients (10%) with amyloid deposits (mean age: 78.6 years, 2 men, 1 woman). Genetic testing for ATTRv and light chains studies were negative. During follow-up: The first patient required aortic valve replacement. The second patient developed progressive cardiac failure with syncopal episodes, atrioventricular block and atrial fibrillation and required a pacemaker and anticoagulation. The third patient had unexplained chronic edemas. The cardiac evaluation in all 3 patients revealed left ventricular hypertrophy and myocardial uptake (Perugini Score > 2) in their nuclear bone scintigraphies with technetium pyrophosphate. Two patients were treated with tafamidis and one patient died due to refractory cardiac insufficiency. Discussion: Our findings underline the importance of investigating amyloidosis in idiopathic CTS. The identification of deposits allows early diagnosis of cardiac amyloidosis leading to timely intervention and treatment.
基金supported by the National Institutes of Health Grant (R01-AG062469)the Grantin-Aid of Research,Artistry,Scholarship program (GIA,Project 143977) at the University of Minnesotafunding from the Center for Drug Design (CDD),University of Minnesota (to SSM)。
文摘The amyloid—what peptide can resist its entropic bliss?Without kinetic barricades and chaperones,most peptides would simply tumble down that precipice.The amyloid-β(Aβ) peptides are understood to underlie the hallmark pathology of Alzheimer's disease(AD) and are considered one of the causative factors for neurodegeneration and cognitive impairment.AD affects critical connected structures within the brain that are responsible for memory,language,and social behavior.
基金supported by grants from the Alzheimer’s Association(AARGD-18-566576)NIH/NIA(RF1AG072491)NIH/NIAID(R01AI132695)to RM。
文摘Transmission of misfolded amyloid-β(Aβ)aggregates between human subjects:Protein misfolding disorders are a family of diseases characterized by the accumulation of misfolded protein aggregates.These proteinaceous structures,also known as amyloids,are key drivers of fatal neurodegenerative disorders such as prion diseases,Alzheimer’s disease(AD),Parkinson’s disease,and others.
基金Florida Polytechnic University,Lakeland,USA for providing support。
文摘Need for Alzheimer's disease progression monitoring:Alzheimer's disease(AD)is an irreversible progressive brain disorder that causes severe and incurable neuro-impairment.The World Health Organization estimates that 55 million people are affected by AD dementia by 2020 which may exceed 78 million by 2030 and 139 in 2050.The estimated cost to manage AD is above US$1.3 trillion,which will further increase to US$2.8 trillion by 2030.
文摘This case report investigates the manifestation of cerebral amyloid angiopathy (CAA) through recurrent Transient Ischemic Attacks (TIAs) in an 82-year-old patient. Despite initial diagnostic complexities, cerebral angiography-MRI revealed features indicative of CAA. Symptomatic treatment resulted in improvement, but the patient later developed a fatal hematoma. The discussion navigates the intricate therapeutic landscape of repetitive TIAs in the elderly with cardiovascular risk factors, emphasizing the pivotal role of cerebral MRI and meticulous bleeding risk management. The conclusion stresses the importance of incorporating SWI sequences, specifically when suspecting a cardioembolic TIA, as a diagnostic measure to explore and exclude CAA in the differential diagnosis. This case report provides valuable insights into these challenges, highlighting the need to consider CAA in relevant cases.
文摘BACKGROUND Necrotising enterocolitis(NEC)is a critical gastrointestinal emergency affecting premature and low-birth-weight neonates.Serum amyloid A(SAA),procalcitonin(PCT),and high-mobility group box 1(HMGB1)have emerged as potential biomarkers for NEC due to their roles in inflammatory response,tissue damage,and immune regulation.AIM To evaluate the diagnostic value of SAA,PCT,and HMGB1 in the context of NEC in newborns.METHODS The study retrospectively analysed the clinical data of 48 newborns diagnosed with NEC and 50 healthy newborns admitted to the hospital.Clinical,radiological,and laboratory findings,including serum SAA,PCT,and HMGB1 Levels,were collected,and specific detection methods were used.The diagnostic value of the biomarkers was evaluated through statistical analysis,which was performed using chi-square test,t-test,correlation analysis,and receiver operating characteristic(ROC)analysis.RESULTS The study demonstrated significantly elevated levels of serum SAA,PCT,and HMGB1 Levels in newborns diagnosed with NEC compared with healthy controls.The correlation analysis indicated strong positive correlations among serum SAA,PCT,and HMGB1 Levels and the presence of NEC.ROC analysis revealed promising sensitivity and specificity for serum SAA,PCT,and HMGB1 Levels as potential diagnostic markers.The combined model of the three biomarkers demonstrating an extremely high area under the curve(0.908).CONCLUSION The diagnostic value of serum SAA,PCT,and HMGB1 Levels in NEC was highlighted.These biomarkers potentially improve the early detection,risk stratification,and clinical management of critical conditions.The findings suggest that these biomarkers may aid in timely intervention and the enhancement of outcomes for neonates affected by NEC.
文摘The use of anticoagulation therapy could prove to be controversial when trying to balance ischemic stroke and intracranial bleeding risks in patients with concurrent cerebral amyloid angiopathy(CAA)and atrial fibrillation(AF).In fact,CAA is an age-related cerebral vasculopathy that predisposes patients to intracerebral hemorrhage.Nevertheless,many AF patients require oral systemic dose-adjusted warfarin,direct oral anticoagulants(such as factor Xa inhibitors)or direct thrombin inhibitors to control often associated with cardioembolic stroke risk.The prevalence of both CAA and AF is expected to rise,due to the aging of the population.This clinical dilemma is becoming increasingly common.In patients with coexisting AF and CAA,the risks/benefits profile of anticoagulant therapy must be assessed for each patient individually due to the lack of a clear-cut consensus with regard to its risks in scientific literature.This review aims to provide an overview of the management of patients with concomitant AF and CAA and proposes the implementation of a risk-based decision-making algorithm.
文摘Increasing evidence demonstrated that the blood-brain barrier(BBB)was involved in developing cerebral amyloid angiopathy(CAA).The BBB participates in the neurovascular coupling and regulates the transport of substances,which is closely related to neurodegenerative diseases.In CAA,the deposition of amyloid beta(Aβ)in arteries,capillaries,and arterioles of meninges and cerebral cortex results in the destruction of the BBB,chronic inflammatory response,chronic cerebral hypoperfusion,and dysfunction of the neurovascular unit,which eventually leads to neurodegeneration.At the same time,CAA is an age-related disease.Patients with CAA often have some risk factors for cerebrovascular diseases,such as hypertension and diabetes,which can further aggravate the damage to the BBB.Thus,it is of great significance to pay attention to the BBB in the pathogenesis and future intervention targets of CAA.Therefore,this manuscript reviewed the dysfunction of the BBB in CAA.
基金funded by the National Natural Science Foundation of China(82372018 and 81701753)The Beijing Natural Science Foundation(7222299)+1 种基金Beijing Medical Authority Cultivation Program(PX2022035)Medical Innovation Capability Improvement Plan of Capital Medical University(12300124).
文摘Cerebral amyloid angiopathy(CAA)is a small vessel disease of the brain characterized by the progressive deposition of amyloid-β(Aβ)plaques in the walls of cerebral blood vessels.It presents with a subtle course and sudden onset,and currently,there are no specific therapeutic interventions available.Accurate diagnosis of CAA could enable targeted interventions in the early stages of the disease,potentially mitigating the disease’s effects.Herein,we review the primary imaging biomarkers used in the diagnosis of CAA,including their mechanisms,imaging characteristics,and significance.We also provide an interpretation of the latest version(v2.0)of the Boston criteria,which are commonly used in the clinical diagnosis of CAA.Additionally,this study introduces various positron emission tomography(PET)tracers for CAA and reviews their application values in the diagnosis of CAA.
文摘The hidden world of amyloid biology has suddenly snapped into atomic-level focus,revealing over 80 amyloid protein fibrils,both pathogenic and functional.Unlike globular proteins,amyloid proteins flatten and stack into unbranched fibrils.Stranger still,a single protein sequence can adopt wildly different two-dimensional conformations,yielding distinct fibril polymorphs.
基金This work was supported by the National Natural Science Foundation of China （No. 30571770）.
文摘Objective To observe the migration and differentiation of the neural precursor cells （NPCs） that derived from murine embryonic stem cells （ESCs） when they were transplanted into amyloid β （Aβ）-treated rat hippocampus. Methods MESPU35, a murine ESC cell line that express the enhanced green fluorescent protein （EGFP）, was induced differentiation into nestin-positive NPCs by modified serum-free methods. The Aβ plaques and the differentiation of the grafted cells were observed by immunofluorescent staining. Results Comparing 16 weeks with 4 weeks post-transplantation, the migration distance increased about 5 times; the rate of migratory NPCs differentiating into glial fibrillary acidic protein （GFAP）-positive cells kept rising from （30.41 ± 1.45）% to （49.25± 1.23）%, and the rate of NPCs differentiating into neurofilament 200 （NF200） positive cells increased from （16.68±0.95）% to （27.94± 1.21）%. Meanwhile, the GFAP-positive cells targeting to the ipsilateral side of Aβ plaques increased from 60.2% to 81.3 %, while the NF200-positive cells increased from 61.3% to 84.1%. The migration distance had significant positive linear correlations to the neuronal differentiation rate （r = 0.991） and to the astrocytic differentiation rate （r = 0.953）. Conclusion Engrafted NPCs migrate targetedly to the Aβ injection site and differentiate into neurons and astrocytes.
