In this article, the transmission dynamics of a Hand-Foot-Mouth disease model with treatment and vaccination interventions are studied. We calculated the basic reproduction number and proved the global stability of di...In this article, the transmission dynamics of a Hand-Foot-Mouth disease model with treatment and vaccination interventions are studied. We calculated the basic reproduction number and proved the global stability of disease-free equilibrium when R0 R0 > 1. Meanwhile, we obtained the optimal control strategies minimizing the cost of intervention and minimizing the infected person. We also give some numerical simulations to verify our theoretical results.展开更多
Outbreaks of hand-foot-mouth disease(HFMD) have occurred many times and caused serious health burden in China since 2008. Application of modern information technology to prediction and early response can be helpful ...Outbreaks of hand-foot-mouth disease(HFMD) have occurred many times and caused serious health burden in China since 2008. Application of modern information technology to prediction and early response can be helpful for efficient HFMD prevention and control. A seasonal auto-regressive integrated moving average(ARIMA) model for time series analysis was designed in this study. Eighty-four-month(from January 2009 to December 2015) retrospective data obtained from the Chinese Information System for Disease Prevention and Control were subjected to ARIMA modeling. The coefficient of determination(R^2), normalized Bayesian Information Criterion(BIC) and Q-test P value were used to evaluate the goodness-of-fit of constructed models. Subsequently, the best-fitted ARIMA model was applied to predict the expected incidence of HFMD from January 2016 to December 2016. The best-fitted seasonal ARIMA model was identified as(1,0,1)(0,1,1)12, with the largest coefficient of determination(R^2=0.743) and lowest normalized BIC(BIC=3.645) value. The residuals of the model also showed non-significant autocorrelations(P_(Box-Ljung(Q))=0.299). The predictions by the optimum ARIMA model adequately captured the pattern in the data and exhibited two peaks of activity over the forecast interval, including a major peak during April to June, and again a light peak for September to November. The ARIMA model proposed in this study can forecast HFMD incidence trend effectively, which could provide useful support for future HFMD prevention and control in the study area. Besides, further observations should be added continually into the modeling data set, and parameters of the models should be adjusted accordingly.展开更多
Objective:To investigate clinical and neuroimaging features of enterovirus71(EV71) related acute flaccid paralysis in patients with hand-fool-mouth disease.Methods:Nine patients with acute flaccid paralysis met the cr...Objective:To investigate clinical and neuroimaging features of enterovirus71(EV71) related acute flaccid paralysis in patients with hand-fool-mouth disease.Methods:Nine patients with acute flaccid paralysis met the criterion of EV71 induced hand-foot-mouth disease underwent spinal and brain MR imaging from May 2008 to Sep 2012.Results:One extremity flaccid was found in four cases(3 with lower limb,1 with upper limb),two limbs flaccid in three cases(2 with lower limbs,1 with upper limbs),and four limbs flaccid in two cases.Spinal MRI studies showed lesion with high signal in T2-weighted images(T2WI) and low signal T1-weighted images(T1WI) in the spinal cord of all nine cases,and the lesions were mainly in bilateral and unilateral anterior hom of cervical spinal cord and spinal cord below thoracic 9(T9) level.In addition,the midbrain,pons, and medulla,which were involved in 3 cases with brainstem encephalitis,demonstrated abnormal signal.Moreover,spinal cord contrast MRI studies showed mild enhancement in corresponding anterior hom of the involved side,and strong enhancement in its ventral root.Conclusions: EV71 related acute flaccid paralysis in patients with hand-foot-mouth disease mainly affected the anterior hom regions and ventral root of cervical spinal cord and spinal cord below T9 level. MR imaging could efficiendy show the characteristic pattern and extent of the lesions which correlated well with the clinical features.展开更多
Objective:To explore the Clinical observation on the treatment of severe hand-foot-mouth disease with antelope horn powder combined with auricular point application.Methods:From July 2016 to June 2018,90 children were...Objective:To explore the Clinical observation on the treatment of severe hand-foot-mouth disease with antelope horn powder combined with auricular point application.Methods:From July 2016 to June 2018,90 children were randomly divided into control group(n=30),treatment group(n=30)and control group(n=30).The control group was treated with routine western medicine,the treatment group 1 was treated with oral antelope horn powder on the basis of control group,the second group was treated with auricular point application on the basis of treatment group 1,and the time of symptom relief and clinical cure were observed in each group.Related immune function and related inflammatory factors,serum neuron-specific enolase(NSE),safety index.Results:In treatment group 1,the time of herpes regression,antipyretic,antispasmodic time and clinical cure time were shorter than those of control group,and the time of treatment 2 group was shorter than that of group 1(P<0.05).The levels of CD3,CD4 and CD8 were increased after treatment in the three groups,especially in the treatment group(P<0.05),and the levels of TNF-毩αand IL-2,IL-6,IL-10 were decreased after treatment in the three groups,especially in the treatment group(P<0.05).NSE decreased after treatment in three groups,especially in treatment group 2(P<0.05).Conclusion:The application of antelope horn powder combined with auricular point application can obviously improve the severe hand,foot and mouth disease,and the clinical curative effect is definite.It is worth popularizing and applying in clinical practice.展开更多
Objective: To investigate the effect of interferon + Potassium Sodium Dehydroandrograpolide Succinate therapy on inflammatory response and immune response in children with hand-foot-mouth disease. Methods: A total of ...Objective: To investigate the effect of interferon + Potassium Sodium Dehydroandrograpolide Succinate therapy on inflammatory response and immune response in children with hand-foot-mouth disease. Methods: A total of 116 children with hand-foot-mouth disease who were treated in this hospital between September 2016 and February 2018 were selected as the study subjects and divided into the control group (n=58) and the Potassium Sodium Dehydroandrograpolide Succinate group (n=58) by random number table method. Control group received symptomatic + interferon therapy, and Potassium Sodium Dehydroandrograpolide Succinate group received symptomatic + interferon + Potassium Sodium Dehydroandrograpolide Succinate therapy, and they were treated for 1 week. The differences in the serum contents of inflammatory factors, adhesion molecules and humoral immunity indexes were compared between the two groups before and after treatment. Results:Before treatment, serum levels of inflammatory factors, adhesion molecules and humoral immunity indexes were not significantly different between the two groups. After 1 week of treatment, serum inflammatory factors IL-1β, IL-10, PCT and hs-CRP levels of Potassium Sodium Dehydroandrograpolide Succinate group were lower than those of control group;serum adhesion molecules CD44, ICAM-1 and VCAM-1 levels were lower than those of control group;serum humoral immunity indexes IgA, IgG, C3 and C4 levels were lower than those of control group. Conclusion: Interferon + Potassium Sodium Dehydroandrograpolide Succinate therapy can effectively reduce the systemic inflammatory response and improve the humoral immune function in children with hand-foot-mouth disease.展开更多
Objective:To study the correlation of serum NSE and S100β levels with inflammatory response and immune response in children with hand-foot-mouth disease (HFMD) complicated by encephalitis.Methods:Children who were di...Objective:To study the correlation of serum NSE and S100β levels with inflammatory response and immune response in children with hand-foot-mouth disease (HFMD) complicated by encephalitis.Methods:Children who were diagnosed with hand-foot-mouth disease in Yulin Third Hospital between May 2015 and February 2017 were selected, children who were combined with central nervous system were selected as severe group, and children who were not combined with central nervous system were selected as mild group;children who received physical examination during the same period were selected as the control group. Serum was collected to determine the contents of NSE, S100β and inflammatory response mediators, and peripheral blood was collected to determine the contents of T cell subsets and NK cells.Results: Serum NSE and S100β levels of severe group and mild group were significantly higher than those of control group, and serum NSE and S100β levels of severe group were significantly higher than those of mild group;serum TNF-α, IL-6, IL-10, IL-17 and PCT levels as well as peripheral blood HLA-DR+CD4+, HLA-DR+CD8+, CD38+CD4+ and CD38+CD8+ levels of severe group and mild group were significantly higher than those of control group while peripheral blood CD3+T cell, CD4+T cell, CD8+T cell and NK cell levels were significantly lower than those of control group;serum TNF-α, IL-6, IL-10, IL-17 and PCT levels as well as peripheral blood HLA-DR+CD4+, HLA-DR+CD8+, CD38+CD4+ and CD38+CD8+ levels of severe group were significantly higher than those of mild group and positively correlated with NSE and S100β levels while peripheral blood CD3+T cell, CD4+T cell, CD8+T cell and NK cell levels were significantly lower than those of mild group and negatively correlated with NSE and S100β levels.Conclusion: The increase of serum NSE and S100β levels in children with HFMD complicated by encephalitis is closely related to inflammatory response activation and immune response disorder.展开更多
Objective:To observe the effects of pidotimod combined with ribavirin on inflammatory factors, T lymphocyte subsets, immunoglobulin, lactate, D-dimer and procalcitonin in children with hand-foot-mouth disease.Methods:...Objective:To observe the effects of pidotimod combined with ribavirin on inflammatory factors, T lymphocyte subsets, immunoglobulin, lactate, D-dimer and procalcitonin in children with hand-foot-mouth disease.Methods: A total of 108 children with foot-hand-and-mouth epidemic in our hospital from Jan. 2013-Dec. 2016 were divide into the observation group and the control group, each groups has 54 cases. Two groups of children were treated with isolation, the observation group was given pidotimod combined with ribavirin, and the control group was treated with ribavirin. 5 mL venous blood of two group patients were collected at admission and after 6 d treatment, respectively, to compare inflammatory factor, T lymphocyte subsets, immunoglobulin, lactate, D-dimer and procalcitonin in two groups.Results: Before treatment, the levels of inflammatory factor, T lymphocyte subsets, immunoglobulin, lactate, D-dimer and procalcitonin of two groups were not statistically significant. Compared with groups after treatment, the levels of CRP, IL-6, TNF-α were lower than that before treatment, CRP (2.23±0.37) mg/L, IL-6 (21.24±9.81) pg/mL and TNF-α (56.97±50.36) pg/mL levels in observation group after treatment were significantly lower than those in control group, the difference was statistically significant. After treatment, the levels of CD3, CD4, CD4/CD8, IgG, IgA and IgM in control group were significantly higher than that before treatment, the difference was statistically significant;After treatment, the levels of CD3 (51.26±10.27)%, CD4 (36.36±4.09)% and CD4/CD8 (1.60±0.47), IgG (10.24±1.82) mg/L, IgA (1.30±0.31) mg/L and IgM (1.48±0.30) mg/L in observation group were significantly higher than in control group, the difference was statistically significant. After treatment, the levels of lactate, D-dimer and procalcitonin in two groups were significantly lower than that before treatment, the difference was statistically significant;After treatment, the levels of lactate (1.19±0.20) mmol/L, D-dimer (150.23±27.21) ng/mL, and procalcitonin (0.08±0.02) ng/mL in observation group were significantly higher than in control group, the difference was statistically significant. Conclusion: Pidotimod combined with ribavirin has a pronounced effect on children with hand-foot-mouth disease, which can effectively reduce the body's inflammatory response, enhance immune function, improve clinical biochemical indicators, and should be widely recommended for clinical use.展开更多
In this paper,we formulate the transmission phenomena of Hand-Foot-Mouth Disease(HFMD)through non-integer derivative.We interrogate the biological meaningful results of the recommended system of HFMD.The basic reprodu...In this paper,we formulate the transmission phenomena of Hand-Foot-Mouth Disease(HFMD)through non-integer derivative.We interrogate the biological meaningful results of the recommended system of HFMD.The basic reproduction number is determined through next generation method and the impact of different parameters on the reproduction number is examined with the help of partial rank correlation coeficient(PRCC)technique.In addition,we concentrated on qualitative analysis and dynamical behavior of HFMD dynamics.Banach's and Schaefer's fixed-point theorems are used to analyze the uniqueness and existence of the solution of the proposed HFMD model.The HFMD system's Ulam-Hyers stability has been confirmed to be sufficient.To highlight the impact of the parameters on the dynamics of HFMD,we performed several simulations through numerical scheme to conceptualize the transmission route of the infection.To be more specific,numerical simulations are used to visualize the effect of input parameters on the systems dynamics.We have shown the key input parameters of the system for the control of infection in the society.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
ATP-binding cassette(ABC)transporters are ubiquitous membrane-bound proteins that are responsible for the translocation of a broad spectrum of substrates across cellular membranes,including lipids,amino acids,nucleosi...ATP-binding cassette(ABC)transporters are ubiquitous membrane-bound proteins that are responsible for the translocation of a broad spectrum of substrates across cellular membranes,including lipids,amino acids,nucleosides,sugars,and xenobiotics.Interestingly,ABC transporters are highly expressed in the brain.While their functions in the brain still need to be elucidated,several members are implicated in the pathogenesis of neurodegenerative diseases,including Alzheimer’s disease(AD),Parkinson’s disease(PD),and frontotemporal dementia.In this perspective,we will review current knowledge of ABC transporters in the central nervous system in terms of physiological functions and pathology in neurodegeneration.Furthermore,we will explore the possibilities of ABC transporters as potential targets in the development of therapeutics for neurodegenerative diseases.展开更多
Lactate,a byproduct of glycolysis,was thought to be a metabolic waste until the discovery of the Warburg effect.Lactate not only functions as a metabolic substrate to provide energy but can also function as a signalin...Lactate,a byproduct of glycolysis,was thought to be a metabolic waste until the discovery of the Warburg effect.Lactate not only functions as a metabolic substrate to provide energy but can also function as a signaling molecule to modulate cellular functions under pathophysiological conditions.The Astrocyte-Neuron Lactate Shuttle has cla rified that lactate plays a pivotal role in the central nervous system.Moreover,protein lactylation highlights the novel role of lactate in regulating transcription,cellular functions,and disease development.This review summarizes the recent advances in lactate metabolism and its role in neurodegenerative diseases,thus providing optimal pers pectives for future research.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
Autophagy is a multifaceted cellular process that not only maintains the homeostatic and adaptive responses of the brain but is also dynamically involved in the regulation of neural cell generation,maturation,and surv...Autophagy is a multifaceted cellular process that not only maintains the homeostatic and adaptive responses of the brain but is also dynamically involved in the regulation of neural cell generation,maturation,and survival.Autophagy facilities the utilization of energy and the microenvironment for developing neural stem cells.Autophagy arbitrates structural and functional remodeling during the cell differentiation process.Autophagy also plays an indispensable role in the maintenance of stemness and homeostasis in neural stem cells during essential brain physiology and also in the instigation and progression of diseases.Only recently,studies have begun to shed light on autophagy regulation in glia(microglia,astrocyte,and oligodendrocyte)in the brain.Glial cells have attained relatively less consideration despite their unquestioned influence on various aspects of neural development,synaptic function,brain metabolism,cellular debris clearing,and restoration of damaged or injured tissues.Thus,this review composes pertinent information regarding the involvement of autophagy in neural stem cells and glial regulation and the role of this connexion in normal brain functions,neurodevelopmental disorders,and neurodegenerative diseases.This review will provide insight into establishing a concrete strategic approach for investigating pathological mechanisms and developing therapies for brain diseases.展开更多
Although antipsychotics that act via monoaminergic neurotransmitter modulation have considera ble therapeutic effect,they cannot completely relieve clinical symptoms in patients suffering from psychiatric disorde rs.T...Although antipsychotics that act via monoaminergic neurotransmitter modulation have considera ble therapeutic effect,they cannot completely relieve clinical symptoms in patients suffering from psychiatric disorde rs.This may be attributed to the limited range of neurotransmitters that are regulated by psychotropic drugs.Recent findings indicate the need for investigation of psychotropic medications that target less-studied neurotransmitte rs.Among these candidate neurotransmitters,lactate is developing from being a waste metabolite to a glial-neuronal signaling molecule in recent years.Previous studies have suggested that cerebral lactate levels change considerably in numerous psychiatric illnesses;animal experiments have also shown that the supply of exogenous la ctate exerts an antidepressant effect.In this review,we have described how medications targeting newer neurotransmitte rs offer promise in psychiatric diseases;we have also summarized the advances in the use of lactate(and its corresponding signaling pathways)as a signaling molecule.In addition,we have described the alterations in brain lactate levels in depression,anxiety,bipolar disorder,and schizophrenia and have indicated the challenges that need to be overcome before brain lactate can be used as a therapeutic target in psychopharmacology.展开更多
文摘In this article, the transmission dynamics of a Hand-Foot-Mouth disease model with treatment and vaccination interventions are studied. We calculated the basic reproduction number and proved the global stability of disease-free equilibrium when R0 R0 > 1. Meanwhile, we obtained the optimal control strategies minimizing the cost of intervention and minimizing the infected person. We also give some numerical simulations to verify our theoretical results.
基金financially supported by the Health and Family Planning Commission of Hubei Province(No.WJ2017F047)the Health and Family Planning Commission of Wuhan(No.WG17D05)
文摘Outbreaks of hand-foot-mouth disease(HFMD) have occurred many times and caused serious health burden in China since 2008. Application of modern information technology to prediction and early response can be helpful for efficient HFMD prevention and control. A seasonal auto-regressive integrated moving average(ARIMA) model for time series analysis was designed in this study. Eighty-four-month(from January 2009 to December 2015) retrospective data obtained from the Chinese Information System for Disease Prevention and Control were subjected to ARIMA modeling. The coefficient of determination(R^2), normalized Bayesian Information Criterion(BIC) and Q-test P value were used to evaluate the goodness-of-fit of constructed models. Subsequently, the best-fitted ARIMA model was applied to predict the expected incidence of HFMD from January 2016 to December 2016. The best-fitted seasonal ARIMA model was identified as(1,0,1)(0,1,1)12, with the largest coefficient of determination(R^2=0.743) and lowest normalized BIC(BIC=3.645) value. The residuals of the model also showed non-significant autocorrelations(P_(Box-Ljung(Q))=0.299). The predictions by the optimum ARIMA model adequately captured the pattern in the data and exhibited two peaks of activity over the forecast interval, including a major peak during April to June, and again a light peak for September to November. The ARIMA model proposed in this study can forecast HFMD incidence trend effectively, which could provide useful support for future HFMD prevention and control in the study area. Besides, further observations should be added continually into the modeling data set, and parameters of the models should be adjusted accordingly.
基金funded by the Hainan Natural Science Foundation 310119Haiman Health Institution Project(No 2011-22)
文摘Objective:To investigate clinical and neuroimaging features of enterovirus71(EV71) related acute flaccid paralysis in patients with hand-fool-mouth disease.Methods:Nine patients with acute flaccid paralysis met the criterion of EV71 induced hand-foot-mouth disease underwent spinal and brain MR imaging from May 2008 to Sep 2012.Results:One extremity flaccid was found in four cases(3 with lower limb,1 with upper limb),two limbs flaccid in three cases(2 with lower limbs,1 with upper limbs),and four limbs flaccid in two cases.Spinal MRI studies showed lesion with high signal in T2-weighted images(T2WI) and low signal T1-weighted images(T1WI) in the spinal cord of all nine cases,and the lesions were mainly in bilateral and unilateral anterior hom of cervical spinal cord and spinal cord below thoracic 9(T9) level.In addition,the midbrain,pons, and medulla,which were involved in 3 cases with brainstem encephalitis,demonstrated abnormal signal.Moreover,spinal cord contrast MRI studies showed mild enhancement in corresponding anterior hom of the involved side,and strong enhancement in its ventral root.Conclusions: EV71 related acute flaccid paralysis in patients with hand-foot-mouth disease mainly affected the anterior hom regions and ventral root of cervical spinal cord and spinal cord below T9 level. MR imaging could efficiendy show the characteristic pattern and extent of the lesions which correlated well with the clinical features.
文摘Objective:To explore the Clinical observation on the treatment of severe hand-foot-mouth disease with antelope horn powder combined with auricular point application.Methods:From July 2016 to June 2018,90 children were randomly divided into control group(n=30),treatment group(n=30)and control group(n=30).The control group was treated with routine western medicine,the treatment group 1 was treated with oral antelope horn powder on the basis of control group,the second group was treated with auricular point application on the basis of treatment group 1,and the time of symptom relief and clinical cure were observed in each group.Related immune function and related inflammatory factors,serum neuron-specific enolase(NSE),safety index.Results:In treatment group 1,the time of herpes regression,antipyretic,antispasmodic time and clinical cure time were shorter than those of control group,and the time of treatment 2 group was shorter than that of group 1(P<0.05).The levels of CD3,CD4 and CD8 were increased after treatment in the three groups,especially in the treatment group(P<0.05),and the levels of TNF-毩αand IL-2,IL-6,IL-10 were decreased after treatment in the three groups,especially in the treatment group(P<0.05).NSE decreased after treatment in three groups,especially in treatment group 2(P<0.05).Conclusion:The application of antelope horn powder combined with auricular point application can obviously improve the severe hand,foot and mouth disease,and the clinical curative effect is definite.It is worth popularizing and applying in clinical practice.
文摘Objective: To investigate the effect of interferon + Potassium Sodium Dehydroandrograpolide Succinate therapy on inflammatory response and immune response in children with hand-foot-mouth disease. Methods: A total of 116 children with hand-foot-mouth disease who were treated in this hospital between September 2016 and February 2018 were selected as the study subjects and divided into the control group (n=58) and the Potassium Sodium Dehydroandrograpolide Succinate group (n=58) by random number table method. Control group received symptomatic + interferon therapy, and Potassium Sodium Dehydroandrograpolide Succinate group received symptomatic + interferon + Potassium Sodium Dehydroandrograpolide Succinate therapy, and they were treated for 1 week. The differences in the serum contents of inflammatory factors, adhesion molecules and humoral immunity indexes were compared between the two groups before and after treatment. Results:Before treatment, serum levels of inflammatory factors, adhesion molecules and humoral immunity indexes were not significantly different between the two groups. After 1 week of treatment, serum inflammatory factors IL-1β, IL-10, PCT and hs-CRP levels of Potassium Sodium Dehydroandrograpolide Succinate group were lower than those of control group;serum adhesion molecules CD44, ICAM-1 and VCAM-1 levels were lower than those of control group;serum humoral immunity indexes IgA, IgG, C3 and C4 levels were lower than those of control group. Conclusion: Interferon + Potassium Sodium Dehydroandrograpolide Succinate therapy can effectively reduce the systemic inflammatory response and improve the humoral immune function in children with hand-foot-mouth disease.
文摘Objective:To study the correlation of serum NSE and S100β levels with inflammatory response and immune response in children with hand-foot-mouth disease (HFMD) complicated by encephalitis.Methods:Children who were diagnosed with hand-foot-mouth disease in Yulin Third Hospital between May 2015 and February 2017 were selected, children who were combined with central nervous system were selected as severe group, and children who were not combined with central nervous system were selected as mild group;children who received physical examination during the same period were selected as the control group. Serum was collected to determine the contents of NSE, S100β and inflammatory response mediators, and peripheral blood was collected to determine the contents of T cell subsets and NK cells.Results: Serum NSE and S100β levels of severe group and mild group were significantly higher than those of control group, and serum NSE and S100β levels of severe group were significantly higher than those of mild group;serum TNF-α, IL-6, IL-10, IL-17 and PCT levels as well as peripheral blood HLA-DR+CD4+, HLA-DR+CD8+, CD38+CD4+ and CD38+CD8+ levels of severe group and mild group were significantly higher than those of control group while peripheral blood CD3+T cell, CD4+T cell, CD8+T cell and NK cell levels were significantly lower than those of control group;serum TNF-α, IL-6, IL-10, IL-17 and PCT levels as well as peripheral blood HLA-DR+CD4+, HLA-DR+CD8+, CD38+CD4+ and CD38+CD8+ levels of severe group were significantly higher than those of mild group and positively correlated with NSE and S100β levels while peripheral blood CD3+T cell, CD4+T cell, CD8+T cell and NK cell levels were significantly lower than those of mild group and negatively correlated with NSE and S100β levels.Conclusion: The increase of serum NSE and S100β levels in children with HFMD complicated by encephalitis is closely related to inflammatory response activation and immune response disorder.
文摘Objective:To observe the effects of pidotimod combined with ribavirin on inflammatory factors, T lymphocyte subsets, immunoglobulin, lactate, D-dimer and procalcitonin in children with hand-foot-mouth disease.Methods: A total of 108 children with foot-hand-and-mouth epidemic in our hospital from Jan. 2013-Dec. 2016 were divide into the observation group and the control group, each groups has 54 cases. Two groups of children were treated with isolation, the observation group was given pidotimod combined with ribavirin, and the control group was treated with ribavirin. 5 mL venous blood of two group patients were collected at admission and after 6 d treatment, respectively, to compare inflammatory factor, T lymphocyte subsets, immunoglobulin, lactate, D-dimer and procalcitonin in two groups.Results: Before treatment, the levels of inflammatory factor, T lymphocyte subsets, immunoglobulin, lactate, D-dimer and procalcitonin of two groups were not statistically significant. Compared with groups after treatment, the levels of CRP, IL-6, TNF-α were lower than that before treatment, CRP (2.23±0.37) mg/L, IL-6 (21.24±9.81) pg/mL and TNF-α (56.97±50.36) pg/mL levels in observation group after treatment were significantly lower than those in control group, the difference was statistically significant. After treatment, the levels of CD3, CD4, CD4/CD8, IgG, IgA and IgM in control group were significantly higher than that before treatment, the difference was statistically significant;After treatment, the levels of CD3 (51.26±10.27)%, CD4 (36.36±4.09)% and CD4/CD8 (1.60±0.47), IgG (10.24±1.82) mg/L, IgA (1.30±0.31) mg/L and IgM (1.48±0.30) mg/L in observation group were significantly higher than in control group, the difference was statistically significant. After treatment, the levels of lactate, D-dimer and procalcitonin in two groups were significantly lower than that before treatment, the difference was statistically significant;After treatment, the levels of lactate (1.19±0.20) mmol/L, D-dimer (150.23±27.21) ng/mL, and procalcitonin (0.08±0.02) ng/mL in observation group were significantly higher than in control group, the difference was statistically significant. Conclusion: Pidotimod combined with ribavirin has a pronounced effect on children with hand-foot-mouth disease, which can effectively reduce the body's inflammatory response, enhance immune function, improve clinical biochemical indicators, and should be widely recommended for clinical use.
文摘In this paper,we formulate the transmission phenomena of Hand-Foot-Mouth Disease(HFMD)through non-integer derivative.We interrogate the biological meaningful results of the recommended system of HFMD.The basic reproduction number is determined through next generation method and the impact of different parameters on the reproduction number is examined with the help of partial rank correlation coeficient(PRCC)technique.In addition,we concentrated on qualitative analysis and dynamical behavior of HFMD dynamics.Banach's and Schaefer's fixed-point theorems are used to analyze the uniqueness and existence of the solution of the proposed HFMD model.The HFMD system's Ulam-Hyers stability has been confirmed to be sufficient.To highlight the impact of the parameters on the dynamics of HFMD,we performed several simulations through numerical scheme to conceptualize the transmission route of the infection.To be more specific,numerical simulations are used to visualize the effect of input parameters on the systems dynamics.We have shown the key input parameters of the system for the control of infection in the society.
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.
文摘ATP-binding cassette(ABC)transporters are ubiquitous membrane-bound proteins that are responsible for the translocation of a broad spectrum of substrates across cellular membranes,including lipids,amino acids,nucleosides,sugars,and xenobiotics.Interestingly,ABC transporters are highly expressed in the brain.While their functions in the brain still need to be elucidated,several members are implicated in the pathogenesis of neurodegenerative diseases,including Alzheimer’s disease(AD),Parkinson’s disease(PD),and frontotemporal dementia.In this perspective,we will review current knowledge of ABC transporters in the central nervous system in terms of physiological functions and pathology in neurodegeneration.Furthermore,we will explore the possibilities of ABC transporters as potential targets in the development of therapeutics for neurodegenerative diseases.
基金supported by the National Natural Science Foundation of China,Nos.82230042 and 81930029(to ZY),U2004201(to FG and RYP)the China Postdoctoral Science Foundation,No.2020M683748(to RYP)。
文摘Lactate,a byproduct of glycolysis,was thought to be a metabolic waste until the discovery of the Warburg effect.Lactate not only functions as a metabolic substrate to provide energy but can also function as a signaling molecule to modulate cellular functions under pathophysiological conditions.The Astrocyte-Neuron Lactate Shuttle has cla rified that lactate plays a pivotal role in the central nervous system.Moreover,protein lactylation highlights the novel role of lactate in regulating transcription,cellular functions,and disease development.This review summarizes the recent advances in lactate metabolism and its role in neurodegenerative diseases,thus providing optimal pers pectives for future research.
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.
基金supported by NIH R01NS103981 and R01CA273586(to CW)。
文摘Autophagy is a multifaceted cellular process that not only maintains the homeostatic and adaptive responses of the brain but is also dynamically involved in the regulation of neural cell generation,maturation,and survival.Autophagy facilities the utilization of energy and the microenvironment for developing neural stem cells.Autophagy arbitrates structural and functional remodeling during the cell differentiation process.Autophagy also plays an indispensable role in the maintenance of stemness and homeostasis in neural stem cells during essential brain physiology and also in the instigation and progression of diseases.Only recently,studies have begun to shed light on autophagy regulation in glia(microglia,astrocyte,and oligodendrocyte)in the brain.Glial cells have attained relatively less consideration despite their unquestioned influence on various aspects of neural development,synaptic function,brain metabolism,cellular debris clearing,and restoration of damaged or injured tissues.Thus,this review composes pertinent information regarding the involvement of autophagy in neural stem cells and glial regulation and the role of this connexion in normal brain functions,neurodevelopmental disorders,and neurodegenerative diseases.This review will provide insight into establishing a concrete strategic approach for investigating pathological mechanisms and developing therapies for brain diseases.
基金financially supported by the National Nature Science Foundation of China,Nos.82271508(to YC)82001384(to YC)82271316(to HG)。
文摘Although antipsychotics that act via monoaminergic neurotransmitter modulation have considera ble therapeutic effect,they cannot completely relieve clinical symptoms in patients suffering from psychiatric disorde rs.This may be attributed to the limited range of neurotransmitters that are regulated by psychotropic drugs.Recent findings indicate the need for investigation of psychotropic medications that target less-studied neurotransmitte rs.Among these candidate neurotransmitters,lactate is developing from being a waste metabolite to a glial-neuronal signaling molecule in recent years.Previous studies have suggested that cerebral lactate levels change considerably in numerous psychiatric illnesses;animal experiments have also shown that the supply of exogenous la ctate exerts an antidepressant effect.In this review,we have described how medications targeting newer neurotransmitte rs offer promise in psychiatric diseases;we have also summarized the advances in the use of lactate(and its corresponding signaling pathways)as a signaling molecule.In addition,we have described the alterations in brain lactate levels in depression,anxiety,bipolar disorder,and schizophrenia and have indicated the challenges that need to be overcome before brain lactate can be used as a therapeutic target in psychopharmacology.