ObjectiveTo investigate Fas,soluble Fas(sFas)and Fas ligand(Fas L)gene expression in thyroid tissues and thyrocytes from patients with Graves disease(GD)and to find the interrelationship between apoptosis and pathog...ObjectiveTo investigate Fas,soluble Fas(sFas)and Fas ligand(Fas L)gene expression in thyroid tissues and thyrocytes from patients with Graves disease(GD)and to find the interrelationship between apoptosis and pathogenesis of GD. MethodsThyroid tissues were obtained from 7 GD patients and 3 healthy subjects who died accidentally. Thyrocytes were cultured in Eagle′s medium. Total RNA was isolated from thyroid tissues and cultured thyrocytes. The cDNA was prepared by reverse transcription and amplified for Fas,sFas and Fas L by polymerase chain reaction(PCR). ResultsFas and sFas mRNA were detected in all samples from both GD and normal thyroid tissues and thyrocytes,but Fas L mRNA was only found in GD thyroid tissues and thyrocytes. Semi quantitative analysis showed that when compared with those of normal controls,the Fas and sFas mRNA levels were markedly increased in GD thyroid tissues(P<0.01),whereas in GD thyrocytes only the sFas mRNA levels was significantly elevated(P<0.01). ConclusionGene expression of Fas,sFas and Fas L showed abnormality in both thyroid tissues and thyrocytes from GD. The increased production of sFas might be involved in the hyperplasia of thyroid gland.展开更多
Introduction: Graves’ disease is the most common cause of hyperthyroidism. Its treatment uses synthetic antithyroid drugs but the use of aggressive radical therapy such as surgery or non-aggressive therapy such as io...Introduction: Graves’ disease is the most common cause of hyperthyroidism. Its treatment uses synthetic antithyroid drugs but the use of aggressive radical therapy such as surgery or non-aggressive therapy such as iodine-131 is not uncommon. Treatment of Graves’ disease with radioactive iodine or iratherapy is a simple, inexpensive, well-tolerated treatment. It was introduced in Senegal in 2016. We report through this work the preliminary assessment of the only nuclear medicine service in Senegal in the management of Graves’ disease by iodine-131. Patients and Methods: Retrospective study of the first cases of Graves’ disease treated with iratherapy in Senegal. Socio-demographic, clinical, paraclinical, therapeutic and evolutionary aspects were studied. Radiation protection rules have been implemented and contraception has been effective for six months in women of childbearing age. Results: 25 patients were collected with a mean age of 45 years, twenty women (80%), a family goiter in 24% and a psycho-affective context in 64% of cases. Thyrotoxicosis syndrome was associated with goiter in 68% of patients and exophthalmos in 64%. Thyroid ultrasound performed in 20 patients showed vascular goiter in 80% and thyroid scintigraphy in 3 patients, homogeneous and diffuse hyperfixation. TRAK dosed in 8 patients was still positive. All patients had received first-line medical treatment. The average duration of this treatment was more than 18 months in 92%. The empirically used iodine-131 activity averaged 15.35 mCi. Oral corticosteroid therapy was prescribed in 7 patients for the prevention of malignant orbitopathy. No early side effects were noted. The remission rate at 3 months was 52% and at 6 months was 88% to 92%. Conclusion: The effectiveness of radioactive iodine, in particular ablative doses in the treatment of hyperthyroidism, is no longer to be demonstrated. Taking into account our socioeconomic context, iratherapy should be a treatment of choice for hyperthyroidism with a good quality/price ratio and excellent tolerance.展开更多
BACKGROUND Vaccines against severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)which were approved for emergency use have been administered on a large scale globally to contain the pandemic coronavirus disease...BACKGROUND Vaccines against severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)which were approved for emergency use have been administered on a large scale globally to contain the pandemic coronavirus disease 2019(COVID-19)and to save lives.Vaccine safety is one of the issues under surveillance and a possible correlation between vaccines and thyroid function has been reported.However,reports of the impact of coronavirus vaccines on those with Graves’disease(GD)are rare.CASE SUMMARY This paper presents two patients with underlying GD in remission,both developed thyrotoxicosis and one developed thyroid storm following the adenovirus-vectored vaccine(Oxford-AstraZeneca,United Kingdom).The objective of this article is to raise awareness regarding a possible association between COVID-19 vaccination and the onset of thyroid dysfunction in patients with underlying GD in remission.CONCLUSION Receiving either the mRNA or an adenovirus-vectored vaccine for SARS-CoV-2could be safe under effective treatment.Vaccine induced thyroid dysfunction has been reported,but the pathophysiology still not well understood.Further investigation is required to evaluate the possible predisposing factors for developing thyrotoxicosis especially in patients with underlying GD.However,early awareness of thyroid dysfunction following vaccination could avoid a lifethreatening event.展开更多
BACKGROUND Thyroid cancer is not commonly observed in patients with Graves’disease(GD).The presence of thyroid nodules in GD is not uncommon.However,a link bet-ween these two entities has been reported.Herein,we repo...BACKGROUND Thyroid cancer is not commonly observed in patients with Graves’disease(GD).The presence of thyroid nodules in GD is not uncommon.However,a link bet-ween these two entities has been reported.Herein,we report the case of a patient with GD and thyroid cancer in Saudi Arabia,which has not been reported previously in our region.CASE SUMMARY A 26-year-old male patient with GD,receiving carbimazole for 2 years,presented to our hospital.His hyperthyroidism was controlled clinically and biochemically.On clinical examination,he was found to have a left-sided thyroid nodule.Ultra-sound revealed a 2.6 cm hypoechoic nodule with high vascularity.He was then referred for fine needle aspiration which showed that the nodule was highly suspicious for malignancy.The patient underwent total thyroidectomy and was diagnosed with multifocal classical micropapillary thyroid cancer.Post thyroid-ectomy he received radioactive iodine ablation along with levothyroxine replace-ment therapy.CONCLUSION Careful preoperative assessment and thyroid gland ultrasound might assist in screening and diagnosing thyroid cancer in patients with GD.展开更多
Exosomes are cup-shaped extracellular vesicles with a lipid bilayer that is approximately 30 to 200 nm in thickness.Exosomes are widely distributed in a range of body fluids,including urine,blood,milk,and saliva.Exoso...Exosomes are cup-shaped extracellular vesicles with a lipid bilayer that is approximately 30 to 200 nm in thickness.Exosomes are widely distributed in a range of body fluids,including urine,blood,milk,and saliva.Exosomes exert biological function by transporting factors between different cells and by regulating biological pathways in recipient cells.As an important form of intercellular communication,exosomes are increasingly being investigated due to their ability to transfer bioactive molecules such as lipids,proteins,mRNAs,and microRNAs between cells,and because they can regulate physiological and pathological processes in the central nervous system.Adult neurogenesis is a multistage process by which new neurons are generated and migrate to be integrated into existing neuronal circuits.In the adult brain,neurogenesis is mainly localized in two specialized niches:the subventricular zone adjacent to the lateral ventricles and the subgranular zone of the dentate gyrus.An increasing body of evidence indicates that adult neurogenesis is tightly controlled by environmental conditions with the niches.In recent studies,exosomes released from different sources of cells were shown to play an active role in regulating neurogenesis both in vitro and in vivo,thereby participating in the progression of neurodegenerative disorders in patients and in various disease models.Here,we provide a state-of-the-art synopsis of existing research that aimed to identify the diverse components of exosome cargoes and elucidate the therapeutic potential of exosomal contents in the regulation of neurogenesis in several neurodegenerative diseases.We emphasize that exosomal cargoes could serve as a potential biomarker to monitor functional neurogenesis in adults.In addition,exosomes can also be considered as a novel therapeutic approach to treat various neurodegenerative disorders by improving endogenous neurogenesis to mitigate neuronal loss in the central nervous system.展开更多
Neurodegenerative diseases are a group of disorders characterized by the progressive degeneration of neurons in the central or peripheral nervous system.Currently,there is no cure for neurodegenerative diseases and th...Neurodegenerative diseases are a group of disorders characterized by the progressive degeneration of neurons in the central or peripheral nervous system.Currently,there is no cure for neurodegenerative diseases and this means a heavy burden for patients and the health system worldwide.Therefore,it is necessary to find new therapeutic approaches,and antisense therapies offer this possibility,having the great advantage of not modifying cellular genome and potentially being safer.Many preclinical and clinical studies aim to test the safety and effectiveness of antisense therapies in the treatment of neurodegenerative diseases.The objective of this review is to summarize the recent advances in the development of these new technologies to treat the most common neurodegenerative diseases,with a focus on those antisense therapies that have already received the approval of the U.S.Food and Drug Administration.展开更多
BACKGROUND Clinical studies have reported that patients with gastroesophageal reflux disease(GERD)have a higher prevalence of hypertension.AIM To performed a bidirectional Mendelian randomization(MR)analysis to invest...BACKGROUND Clinical studies have reported that patients with gastroesophageal reflux disease(GERD)have a higher prevalence of hypertension.AIM To performed a bidirectional Mendelian randomization(MR)analysis to investi-gate the causal link between GERD and essential hypertension.METHODS Eligible single nucleotide polymorphisms(SNPs)were selected,and weighted median,inverse variance weighted(IVW)as well as MR egger(MR-Egger)re-gression were used to examine the potential causal association between GERD and hypertension.The MR-Pleiotropy RESidual Sum and Outlier analysis was used to detect and attempt to reduce horizontal pleiotropy by removing outliers SNPs.The MR-Egger intercept test,Cochran’s Q test and“leave-one-out”sen-sitivity analysis were performed to evaluate the horizontal pleiotropy,heterogen-eities,and stability of single instrumental variable.RESULTS IVW analysis exhibited an increased risk of hypertension(OR=1.46,95%CI:1.33-1.59,P=2.14E-16)in GERD patients.And the same result was obtained in replication practice(OR=1.002,95%CI:1.0008-1.003,P=0.000498).Meanwhile,the IVW analysis showed an increased risk of systolic blood pressure(β=0.78,95%CI:0.11-1.44,P=0.021)and hypertensive heart disease(OR=1.68,95%CI:1.36-2.08,P=0.0000016)in GERD patients.Moreover,we found an decreased risk of Barrett's esophagus(OR=0.91,95%CI:0.83-0.99,P=0.043)in essential hypertension patients.CONCLUSION We found that GERD would increase the risk of essential hypertension,which provided a novel prevent and therapeutic perspectives of essential hypertension.展开更多
Infectious diseases are the common enemies of mankind.In the course of historical development,they persistently threaten human health and safety.Even today,despite the developments in medical science,we cannot escape ...Infectious diseases are the common enemies of mankind.In the course of historical development,they persistently threaten human health and safety.Even today,despite the developments in medical science,we cannot escape the fear and suffering caused by infectious diseases.Whether in ancient or modern times,the source of infection,route of transmission,and a susceptible population are the three key conditions for the prevalence and spread of infectious diseases.All factors closely related to these three conditions can affect the prevalence of infectious diseases.China is one of the cradles of world civilization.The ancient people accumulated a great deal of experience and lessons in the long struggle against infectious diseases.In the face of the current threat posed by widespread infectious disease,it is imperative to review and summarize ancient Chinese ideas and health policies on epidemic prevention and control to inspire contemporary efforts in the prevention and control of infectious disease.The combination of prevention-oriented epidemic prevention ideology and traditional medicine provides valuable insights,especially for impoverished and medically underserved regions.展开更多
A growing body of evidence suggests that the gut microbiota contributes to the development of neurodegenerative diseases via the microbiota-gut-brain axis.As a contributing factor,microbiota dysbiosis always occurs in...A growing body of evidence suggests that the gut microbiota contributes to the development of neurodegenerative diseases via the microbiota-gut-brain axis.As a contributing factor,microbiota dysbiosis always occurs in pathological changes of neurodegenerative diseases,such as Alzheimer’s disease,Parkinson’s disease,and amyotrophic lateral sclerosis.High-throughput sequencing technology has helped to reveal that the bidirectional communication between the central nervous system and the enteric nervous system is facilitated by the microbiota’s diverse microorganisms,and for both neuroimmune and neuroendocrine systems.Here,we summarize the bioinformatics analysis and wet-biology validation for the gut metagenomics in neurodegenerative diseases,with an emphasis on multi-omics studies and the gut virome.The pathogen-associated signaling biomarkers for identifying brain disorders and potential therapeutic targets are also elucidated.Finally,we discuss the role of diet,prebiotics,probiotics,postbiotics and exercise interventions in remodeling the microbiome and reducing the symptoms of neurodegenerative diseases.展开更多
Sortilin-related receptor 1(SORL1)is a critical gene associated with late-onset Alzheimer’s disease.SORL1 contributes to the development and progression of this neurodegenerative condition by affecting the transport ...Sortilin-related receptor 1(SORL1)is a critical gene associated with late-onset Alzheimer’s disease.SORL1 contributes to the development and progression of this neurodegenerative condition by affecting the transport and metabolism of intracellularβ-amyloid precursor protein.To better understand the underlying mechanisms of SORL1 in the pathogenesis of late-onset Alzheimer s disease,in this study,we established a mouse model of SorI1 gene knockout using cluste red regularly inters paced short palindro mic repeats-associated protein 9 technology.We found that Sorl1-knocko ut mice displayed deficits in learning and memory.Furthermore,the expression of brain-derived neurotrophic factor was significantly downregulated in the hippocampus and co rtex,and amyloidβ-protein deposits were observed in the brains of 5orl1-knockout mice.In vitro,hippocampal neuronal cell synapses from homozygous Sorl1-knockout mice were impaired.The expression of synaptic proteins,including Drebrin and NR2B,was significantly reduced,and also their colocalization.Additionally,by knocking out the Sorl1 gene in N2a cells,we found that expression of the N-methyl-D-aspartate receptor,NR2B,and cyclic adenosine monophosphate-response element binding protein was also inhibited.These findings suggest that SORL1 participates in the pathogenesis of late-onset Alzheimer s disease by regulating the N-methyl-D-aspartate receptor NR2B/cyclic adenosine monophosphate-response element binding protein signaling axis.展开更多
Huntington'sdisease(HD)isahereditary neurodegenerative disorder for which there is currently no effectivetreatmentavailable.Consequently,the development of appropriate disease models is critical to thoroughly inve...Huntington'sdisease(HD)isahereditary neurodegenerative disorder for which there is currently no effectivetreatmentavailable.Consequently,the development of appropriate disease models is critical to thoroughly investigate disease progression.The genetic basis of HD involves the abnormal expansion of CAG repeats in the huntingtin(HTT)gene,leading to the expansion of a polyglutamine repeat in the HTT protein.Mutant HTT carrying the expanded polyglutamine repeat undergoes misfolding and forms aggregates in the brain,which precipitate selective neuronal loss in specific brain regions.Animal models play an important role in elucidating the pathogenesis of neurodegenerative disorders such as HD and in identifying potential therapeutic targets.Due to the marked species differences between rodents and larger animals,substantial efforts have been directed toward establishing large animal models for HD research.These models are pivotal for advancing the discovery of novel therapeutic targets,enhancing effective drug delivery methods,and improving treatment outcomes.We have explored the advantages of utilizing large animal models,particularly pigs,in previous reviews.Since then,however,significant progress has been made in developing more sophisticated animal models that faithfully replicate the typical pathology of HD.In the current review,we provide a comprehensive overview of large animal models of HD,incorporating recent findings regarding the establishment of HD knock-in(KI)pigs and their genetic therapy.We also explore the utilization of large animal models in HD research,with a focus on sheep,non-human primates(NHPs),and pigs.Our objective is to provide valuable insights into the application of these large animal models for the investigation and treatment of neurodegenerative disorders.展开更多
The current therapeutic drugs for Alzheimer's disease only improve symptoms,they do not delay disease progression.Therefo re,there is an urgent need for new effective drugs.The underlying pathogenic factors of Alz...The current therapeutic drugs for Alzheimer's disease only improve symptoms,they do not delay disease progression.Therefo re,there is an urgent need for new effective drugs.The underlying pathogenic factors of Alzheimer's disease are not clear,but neuroinflammation can link various hypotheses of Alzheimer's disease;hence,targeting neuroinflammation may be a new hope for Alzheimer's disease treatment.Inhibiting inflammation can restore neuronal function,promote neuro regeneration,reduce the pathological burden of Alzheimer's disease,and improve or even reverse symptoms of Alzheimer's disease.This review focuses on the relationship between inflammation and various pathological hypotheses of Alzheimer's disease;reports the mechanisms and characteristics of small-molecule drugs(e.g.,nonsteroidal anti-inflammatory drugs,neurosteroids,and plant extracts);macromolecule drugs(e.g.,peptides,proteins,and gene therapeutics);and nanocarriers(e.g.,lipid-based nanoparticles,polymeric nanoparticles,nanoemulsions,and inorganic nanoparticles)in the treatment of Alzheimer's disease.The review also makes recommendations for the prospective development of anti-inflammatory strategies based on nanocarriers for the treatment of Alzheimer's disease.展开更多
基金This paper is supported by the key young university teacher sprogram of the ministry of education(2000655)
文摘ObjectiveTo investigate Fas,soluble Fas(sFas)and Fas ligand(Fas L)gene expression in thyroid tissues and thyrocytes from patients with Graves disease(GD)and to find the interrelationship between apoptosis and pathogenesis of GD. MethodsThyroid tissues were obtained from 7 GD patients and 3 healthy subjects who died accidentally. Thyrocytes were cultured in Eagle′s medium. Total RNA was isolated from thyroid tissues and cultured thyrocytes. The cDNA was prepared by reverse transcription and amplified for Fas,sFas and Fas L by polymerase chain reaction(PCR). ResultsFas and sFas mRNA were detected in all samples from both GD and normal thyroid tissues and thyrocytes,but Fas L mRNA was only found in GD thyroid tissues and thyrocytes. Semi quantitative analysis showed that when compared with those of normal controls,the Fas and sFas mRNA levels were markedly increased in GD thyroid tissues(P<0.01),whereas in GD thyrocytes only the sFas mRNA levels was significantly elevated(P<0.01). ConclusionGene expression of Fas,sFas and Fas L showed abnormality in both thyroid tissues and thyrocytes from GD. The increased production of sFas might be involved in the hyperplasia of thyroid gland.
文摘Introduction: Graves’ disease is the most common cause of hyperthyroidism. Its treatment uses synthetic antithyroid drugs but the use of aggressive radical therapy such as surgery or non-aggressive therapy such as iodine-131 is not uncommon. Treatment of Graves’ disease with radioactive iodine or iratherapy is a simple, inexpensive, well-tolerated treatment. It was introduced in Senegal in 2016. We report through this work the preliminary assessment of the only nuclear medicine service in Senegal in the management of Graves’ disease by iodine-131. Patients and Methods: Retrospective study of the first cases of Graves’ disease treated with iratherapy in Senegal. Socio-demographic, clinical, paraclinical, therapeutic and evolutionary aspects were studied. Radiation protection rules have been implemented and contraception has been effective for six months in women of childbearing age. Results: 25 patients were collected with a mean age of 45 years, twenty women (80%), a family goiter in 24% and a psycho-affective context in 64% of cases. Thyrotoxicosis syndrome was associated with goiter in 68% of patients and exophthalmos in 64%. Thyroid ultrasound performed in 20 patients showed vascular goiter in 80% and thyroid scintigraphy in 3 patients, homogeneous and diffuse hyperfixation. TRAK dosed in 8 patients was still positive. All patients had received first-line medical treatment. The average duration of this treatment was more than 18 months in 92%. The empirically used iodine-131 activity averaged 15.35 mCi. Oral corticosteroid therapy was prescribed in 7 patients for the prevention of malignant orbitopathy. No early side effects were noted. The remission rate at 3 months was 52% and at 6 months was 88% to 92%. Conclusion: The effectiveness of radioactive iodine, in particular ablative doses in the treatment of hyperthyroidism, is no longer to be demonstrated. Taking into account our socioeconomic context, iratherapy should be a treatment of choice for hyperthyroidism with a good quality/price ratio and excellent tolerance.
文摘BACKGROUND Vaccines against severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)which were approved for emergency use have been administered on a large scale globally to contain the pandemic coronavirus disease 2019(COVID-19)and to save lives.Vaccine safety is one of the issues under surveillance and a possible correlation between vaccines and thyroid function has been reported.However,reports of the impact of coronavirus vaccines on those with Graves’disease(GD)are rare.CASE SUMMARY This paper presents two patients with underlying GD in remission,both developed thyrotoxicosis and one developed thyroid storm following the adenovirus-vectored vaccine(Oxford-AstraZeneca,United Kingdom).The objective of this article is to raise awareness regarding a possible association between COVID-19 vaccination and the onset of thyroid dysfunction in patients with underlying GD in remission.CONCLUSION Receiving either the mRNA or an adenovirus-vectored vaccine for SARS-CoV-2could be safe under effective treatment.Vaccine induced thyroid dysfunction has been reported,but the pathophysiology still not well understood.Further investigation is required to evaluate the possible predisposing factors for developing thyrotoxicosis especially in patients with underlying GD.However,early awareness of thyroid dysfunction following vaccination could avoid a lifethreatening event.
文摘BACKGROUND Thyroid cancer is not commonly observed in patients with Graves’disease(GD).The presence of thyroid nodules in GD is not uncommon.However,a link bet-ween these two entities has been reported.Herein,we report the case of a patient with GD and thyroid cancer in Saudi Arabia,which has not been reported previously in our region.CASE SUMMARY A 26-year-old male patient with GD,receiving carbimazole for 2 years,presented to our hospital.His hyperthyroidism was controlled clinically and biochemically.On clinical examination,he was found to have a left-sided thyroid nodule.Ultra-sound revealed a 2.6 cm hypoechoic nodule with high vascularity.He was then referred for fine needle aspiration which showed that the nodule was highly suspicious for malignancy.The patient underwent total thyroidectomy and was diagnosed with multifocal classical micropapillary thyroid cancer.Post thyroid-ectomy he received radioactive iodine ablation along with levothyroxine replace-ment therapy.CONCLUSION Careful preoperative assessment and thyroid gland ultrasound might assist in screening and diagnosing thyroid cancer in patients with GD.
基金supported by grants from the Department of Science and Technology of Sichuan Province,Nos.2021ZYD0093(to LY),2022YFS0597(to LY),2021YJ0480(to YT),and 2022ZYD0076(to JY)。
文摘Exosomes are cup-shaped extracellular vesicles with a lipid bilayer that is approximately 30 to 200 nm in thickness.Exosomes are widely distributed in a range of body fluids,including urine,blood,milk,and saliva.Exosomes exert biological function by transporting factors between different cells and by regulating biological pathways in recipient cells.As an important form of intercellular communication,exosomes are increasingly being investigated due to their ability to transfer bioactive molecules such as lipids,proteins,mRNAs,and microRNAs between cells,and because they can regulate physiological and pathological processes in the central nervous system.Adult neurogenesis is a multistage process by which new neurons are generated and migrate to be integrated into existing neuronal circuits.In the adult brain,neurogenesis is mainly localized in two specialized niches:the subventricular zone adjacent to the lateral ventricles and the subgranular zone of the dentate gyrus.An increasing body of evidence indicates that adult neurogenesis is tightly controlled by environmental conditions with the niches.In recent studies,exosomes released from different sources of cells were shown to play an active role in regulating neurogenesis both in vitro and in vivo,thereby participating in the progression of neurodegenerative disorders in patients and in various disease models.Here,we provide a state-of-the-art synopsis of existing research that aimed to identify the diverse components of exosome cargoes and elucidate the therapeutic potential of exosomal contents in the regulation of neurogenesis in several neurodegenerative diseases.We emphasize that exosomal cargoes could serve as a potential biomarker to monitor functional neurogenesis in adults.In addition,exosomes can also be considered as a novel therapeutic approach to treat various neurodegenerative disorders by improving endogenous neurogenesis to mitigate neuronal loss in the central nervous system.
基金supported by Association 2HE(Center for Human Health and Environment)by Regione Puglia-Grant Malattie Rare DUP n.246 of 2019(to CB).
文摘Neurodegenerative diseases are a group of disorders characterized by the progressive degeneration of neurons in the central or peripheral nervous system.Currently,there is no cure for neurodegenerative diseases and this means a heavy burden for patients and the health system worldwide.Therefore,it is necessary to find new therapeutic approaches,and antisense therapies offer this possibility,having the great advantage of not modifying cellular genome and potentially being safer.Many preclinical and clinical studies aim to test the safety and effectiveness of antisense therapies in the treatment of neurodegenerative diseases.The objective of this review is to summarize the recent advances in the development of these new technologies to treat the most common neurodegenerative diseases,with a focus on those antisense therapies that have already received the approval of the U.S.Food and Drug Administration.
基金Supported by National Natural Science Foundation of China(General Program),No.82070631.
文摘BACKGROUND Clinical studies have reported that patients with gastroesophageal reflux disease(GERD)have a higher prevalence of hypertension.AIM To performed a bidirectional Mendelian randomization(MR)analysis to investi-gate the causal link between GERD and essential hypertension.METHODS Eligible single nucleotide polymorphisms(SNPs)were selected,and weighted median,inverse variance weighted(IVW)as well as MR egger(MR-Egger)re-gression were used to examine the potential causal association between GERD and hypertension.The MR-Pleiotropy RESidual Sum and Outlier analysis was used to detect and attempt to reduce horizontal pleiotropy by removing outliers SNPs.The MR-Egger intercept test,Cochran’s Q test and“leave-one-out”sen-sitivity analysis were performed to evaluate the horizontal pleiotropy,heterogen-eities,and stability of single instrumental variable.RESULTS IVW analysis exhibited an increased risk of hypertension(OR=1.46,95%CI:1.33-1.59,P=2.14E-16)in GERD patients.And the same result was obtained in replication practice(OR=1.002,95%CI:1.0008-1.003,P=0.000498).Meanwhile,the IVW analysis showed an increased risk of systolic blood pressure(β=0.78,95%CI:0.11-1.44,P=0.021)and hypertensive heart disease(OR=1.68,95%CI:1.36-2.08,P=0.0000016)in GERD patients.Moreover,we found an decreased risk of Barrett's esophagus(OR=0.91,95%CI:0.83-0.99,P=0.043)in essential hypertension patients.CONCLUSION We found that GERD would increase the risk of essential hypertension,which provided a novel prevent and therapeutic perspectives of essential hypertension.
文摘Infectious diseases are the common enemies of mankind.In the course of historical development,they persistently threaten human health and safety.Even today,despite the developments in medical science,we cannot escape the fear and suffering caused by infectious diseases.Whether in ancient or modern times,the source of infection,route of transmission,and a susceptible population are the three key conditions for the prevalence and spread of infectious diseases.All factors closely related to these three conditions can affect the prevalence of infectious diseases.China is one of the cradles of world civilization.The ancient people accumulated a great deal of experience and lessons in the long struggle against infectious diseases.In the face of the current threat posed by widespread infectious disease,it is imperative to review and summarize ancient Chinese ideas and health policies on epidemic prevention and control to inspire contemporary efforts in the prevention and control of infectious disease.The combination of prevention-oriented epidemic prevention ideology and traditional medicine provides valuable insights,especially for impoverished and medically underserved regions.
基金financially supported by the National Natural Science Foundation of China,No.32002235(to MT)the Science and Technology Foundation of Taian of Shandong Province,No.2020NS216(to XL)。
文摘A growing body of evidence suggests that the gut microbiota contributes to the development of neurodegenerative diseases via the microbiota-gut-brain axis.As a contributing factor,microbiota dysbiosis always occurs in pathological changes of neurodegenerative diseases,such as Alzheimer’s disease,Parkinson’s disease,and amyotrophic lateral sclerosis.High-throughput sequencing technology has helped to reveal that the bidirectional communication between the central nervous system and the enteric nervous system is facilitated by the microbiota’s diverse microorganisms,and for both neuroimmune and neuroendocrine systems.Here,we summarize the bioinformatics analysis and wet-biology validation for the gut metagenomics in neurodegenerative diseases,with an emphasis on multi-omics studies and the gut virome.The pathogen-associated signaling biomarkers for identifying brain disorders and potential therapeutic targets are also elucidated.Finally,we discuss the role of diet,prebiotics,probiotics,postbiotics and exercise interventions in remodeling the microbiome and reducing the symptoms of neurodegenerative diseases.
基金supported by the Community Development Office of Hunan Provincial Science and Technology DepartmentChina,Nos.2020SK53613(to DH),21JJ31006(to DH)the Fundamental Research Funds of Central South University,Nos.CX20220375(to TX),2023zzts215(to MZ)。
文摘Sortilin-related receptor 1(SORL1)is a critical gene associated with late-onset Alzheimer’s disease.SORL1 contributes to the development and progression of this neurodegenerative condition by affecting the transport and metabolism of intracellularβ-amyloid precursor protein.To better understand the underlying mechanisms of SORL1 in the pathogenesis of late-onset Alzheimer s disease,in this study,we established a mouse model of SorI1 gene knockout using cluste red regularly inters paced short palindro mic repeats-associated protein 9 technology.We found that Sorl1-knocko ut mice displayed deficits in learning and memory.Furthermore,the expression of brain-derived neurotrophic factor was significantly downregulated in the hippocampus and co rtex,and amyloidβ-protein deposits were observed in the brains of 5orl1-knockout mice.In vitro,hippocampal neuronal cell synapses from homozygous Sorl1-knockout mice were impaired.The expression of synaptic proteins,including Drebrin and NR2B,was significantly reduced,and also their colocalization.Additionally,by knocking out the Sorl1 gene in N2a cells,we found that expression of the N-methyl-D-aspartate receptor,NR2B,and cyclic adenosine monophosphate-response element binding protein was also inhibited.These findings suggest that SORL1 participates in the pathogenesis of late-onset Alzheimer s disease by regulating the N-methyl-D-aspartate receptor NR2B/cyclic adenosine monophosphate-response element binding protein signaling axis.
基金supported by the National Key Research and Development Program of China (2021YFA0805300,2021YFA0805200)National Natural Science Foundation of China (32170981,82371874,82394422,82171244,82071421,82271902)+1 种基金Guangzhou Key Research Program on Brain Science (202007030008)Department of Science and Technology of Guangdong Province (2021ZT09Y007,2020B121201006,2018B030337001)。
文摘Huntington'sdisease(HD)isahereditary neurodegenerative disorder for which there is currently no effectivetreatmentavailable.Consequently,the development of appropriate disease models is critical to thoroughly investigate disease progression.The genetic basis of HD involves the abnormal expansion of CAG repeats in the huntingtin(HTT)gene,leading to the expansion of a polyglutamine repeat in the HTT protein.Mutant HTT carrying the expanded polyglutamine repeat undergoes misfolding and forms aggregates in the brain,which precipitate selective neuronal loss in specific brain regions.Animal models play an important role in elucidating the pathogenesis of neurodegenerative disorders such as HD and in identifying potential therapeutic targets.Due to the marked species differences between rodents and larger animals,substantial efforts have been directed toward establishing large animal models for HD research.These models are pivotal for advancing the discovery of novel therapeutic targets,enhancing effective drug delivery methods,and improving treatment outcomes.We have explored the advantages of utilizing large animal models,particularly pigs,in previous reviews.Since then,however,significant progress has been made in developing more sophisticated animal models that faithfully replicate the typical pathology of HD.In the current review,we provide a comprehensive overview of large animal models of HD,incorporating recent findings regarding the establishment of HD knock-in(KI)pigs and their genetic therapy.We also explore the utilization of large animal models in HD research,with a focus on sheep,non-human primates(NHPs),and pigs.Our objective is to provide valuable insights into the application of these large animal models for the investigation and treatment of neurodegenerative disorders.
基金supported by the National Natural Science Foundation of China,Nos.82072051 and 81771964(both to JG)the Natural Science Foundation of Shanghai Municipal Science and Technology Commission,No.22ZR147750(to YY)+2 种基金Science and Technology Support Projects in Biomedicine Field of Shanghai Science and Technology Commission,No.19441907500(to YY)Innovative Clinical Research Project of Changzheng Hospital,No.2020 YLCYJ-Y02(to YY)Characteristic Medical Service Project for the Army of Changzheng Hospital,No.2020 CZWJFW12(to YY)。
文摘The current therapeutic drugs for Alzheimer's disease only improve symptoms,they do not delay disease progression.Therefo re,there is an urgent need for new effective drugs.The underlying pathogenic factors of Alzheimer's disease are not clear,but neuroinflammation can link various hypotheses of Alzheimer's disease;hence,targeting neuroinflammation may be a new hope for Alzheimer's disease treatment.Inhibiting inflammation can restore neuronal function,promote neuro regeneration,reduce the pathological burden of Alzheimer's disease,and improve or even reverse symptoms of Alzheimer's disease.This review focuses on the relationship between inflammation and various pathological hypotheses of Alzheimer's disease;reports the mechanisms and characteristics of small-molecule drugs(e.g.,nonsteroidal anti-inflammatory drugs,neurosteroids,and plant extracts);macromolecule drugs(e.g.,peptides,proteins,and gene therapeutics);and nanocarriers(e.g.,lipid-based nanoparticles,polymeric nanoparticles,nanoemulsions,and inorganic nanoparticles)in the treatment of Alzheimer's disease.The review also makes recommendations for the prospective development of anti-inflammatory strategies based on nanocarriers for the treatment of Alzheimer's disease.
