Haptoglobin,a protein primarily recognized for its role in sequestering free hemoglobin,has been identified as a molecule with diverse and underexplored functions in the pathophysiology of various diseases.This editor...Haptoglobin,a protein primarily recognized for its role in sequestering free hemoglobin,has been identified as a molecule with diverse and underexplored functions in the pathophysiology of various diseases.This editorial explores the multifaceted roles of haptoglobin,highlighting its involvement in inflammatory responses and immune regulation and its potential implications in chronic diseases such as diabetes,cardiovascular disorders,and cancer.Through a synthesis of recent research findings,this editorial reveals the importance of haptoglobin in disease mechanisms and underscores the need for further investigation to fully elucidate its therapeutic potential.A comprehensive understanding of haptoglobin’s novel functions may catalyze the development of innovative diagnostic and therapeutic modalities in clinical practice.展开更多
INTRODUCTIONThe transforming growth factor-β （TGF-β） superfamily com- prises TGF-βs, Activin, bone morphogenetic proteins （BMPs） and other related proteins. TGF-β superfamily members act through a heteromeric ...INTRODUCTIONThe transforming growth factor-β （TGF-β） superfamily com- prises TGF-βs, Activin, bone morphogenetic proteins （BMPs） and other related proteins. TGF-β superfamily members act through a heteromeric receptor complex,, comprised of type I and type II receptors at the cell surface that transduce intracellular signals via Smad complex or mitogen-activated protein kinase （MAPK） cascade.展开更多
The G-quadruplex(G4)sequences are short fragments of 4-i nterval triple guanine(G)with frequent and ubiquitous distribution in the genome and RNA transcripts.The G4sequences are usually folded into secondary“knot”st...The G-quadruplex(G4)sequences are short fragments of 4-i nterval triple guanine(G)with frequent and ubiquitous distribution in the genome and RNA transcripts.The G4sequences are usually folded into secondary“knot”structure via Hoogsteen hydrogen bond to exert negative regulation on a variety of biological processes,including DNA replication and transcription,mRNA translation,and telomere maintenance.Recent structural biological and mouse genetics studies have demonstrated that RHAU(DHX36)can bind and unwind the G4“knots”to modulate embryonic development and postnatal organ function.Deficiency of RHAU gives rise to embryonic lethality,impaired organogenesis,and organ dysfunction.These studies uncovered the pivotal G4 resolvase function of RHAU to release the G4 barrier,which plays fundamental roles in development and physiological homeostasis.This review discusses the latest advancements and findings in deciphering RHAU functions using animal models.展开更多
Alzheimer＇s disease （AD） is the most frequent cause of dementia in the western world. In clinical terms, AD is characterized by progres- sive cognitive decline that usually begins with memory impairment. As the dis...Alzheimer＇s disease （AD） is the most frequent cause of dementia in the western world. In clinical terms, AD is characterized by progres- sive cognitive decline that usually begins with memory impairment. As the disease progresses, AD inevitably affects all intellectual functions including executive functions, leading to complete dependence for basic activities of daily life and premature death.展开更多
Alzheimer’s disease （AD） is an age-related eurodegenerative disease that represents the most common cause of dementia among the elderly people. With the increasingly aging population, AD has presented an overwhelmi...Alzheimer’s disease （AD） is an age-related eurodegenerative disease that represents the most common cause of dementia among the elderly people. With the increasingly aging population, AD has presented an overwhelming healthcare challenge to modern society; the World Alzheimer Report 2015 has estimated that 46.8 million people worldwide lived with dementia in 2015 and this number will rise to 74.7 million in 2030 and that the total cost of dementia was 818 billion in US$ in 2015 and will reach two trillion in 2030. Post-mortem studies have identified two histopathological hallmarks in the brains of AD patients; extracellular senile plaque with elevated deposition of amyloid β （Aβ） peptides, and intracellular neurofibrillary tangle composed of hyper-phosphorylated microtubule-associated protein tau.Etiologically, progressive neuronal loss within the cerebral cortex and hippocampus regions of the brain leads to irreversible decline in, and eventually complete loss of, memory and other cognitive functions that afflict AD patients. The widely-accepted amyloid cascade hypothesis for AD pathogenesis holds that accumulation and aggregation of neurotoxic Aβ peptides, due to imbalance of their generation and clearance as a result of changes in genetic makeup, aging and/or exposure to environmental risk factors, is a major and early trigger of AD. This hypothesis has continuously gained support by preclinical and clinical studies （Selkoe and Hardy, 2016）. However, the intensive and costly drug discovery efforts over the past decades based on such a hypothesis have proved extremely frustrating in developing effective therapeutics to treat or slow down the progress of AD, highlighting the need for more research to improve our understanding towards the cellular and molecular mechanisms by which Aβ peptides bring about neurotoxicity and cognitive dysfunction.展开更多
BACKGROUND： Some scholars think that hypertension is the major risk factor to cause Binswanger disease （BD）, however, BD is also found in some persons with normal blood pressure, so we presume that some other facto...BACKGROUND： Some scholars think that hypertension is the major risk factor to cause Binswanger disease （BD）, however, BD is also found in some persons with normal blood pressure, so we presume that some other factors, such as diabetes mellitus, hyperlipemia, coronary heart disease and transient ischemic attacks and so on, might participant in the onset of BD. OBJECTIVE： To comparatively observe the difference in accompanying diseases, transcranial doppler （TCD） performance, blood glucose and blood lipid level between BD patients and healthy subjects who received health examination, and between BD patients with different disease condition. DESIGN ： Case-control analysis SETTING ： Department of Emergency, Qingdao Municipal Hospita PARTICIPANTS： Totally 126 patients with BD, 65 male and 61 female, aged from 67 to 85 years old, who hospitalized in the Medical School Hospital of Qingdao University and Qingdao Municipal People＇s Hospital, were chosen, serving as BD patients group. All the patients met the clinical diagnostic criteria of BD introduced by Bennett et al. Another 126 persons, 65 male and 61 female, aged ranging from 67 to 80 years, who received health examination in the same hospital, were homeochronously chosen, serving as control group. Informed consents were obtained from all the subjects. METHODS ： After being admitted, all the subjects including BD patients and persons who homeochrenously received health examination in the same hospital were given examinations of blood pressure, blood lipid, blood glucose, electrocardiogram （ECG） and TCD. Fifty-seven patients with BD were in the stable period and 69 in the progressive period （Stable period： no local or subcortical function disorder found, and no changes in the range of white matter lesion showed by CT and/or MRI in recent 3 months; Progressive period： with local or subcortical function disorder and increase in the range of white matter lesion showed by CT and/or MRI in recent 3 months）. According to intimal thickening of carotid artery and vertebral artery preformed by TCD, BD was graded as mild intimal thickening （〈 1.1 mm）, moderate intimal thickening （1.1 to 1.2 mm） and severe intimal thickening （〉 1.2 mm）. MAIN OUTCOME MEASURES ： Comparison of the ratio of BD patients with accompanied diabetes mellitus, hypedipemia, coronary heart disease and transient ischemic attacks, TCD performance, blood glucose and blood lipid level between BD patients group and control group, and among BD patients with vadous disease conditions. RESULTS： Totally 126 BD patients and 126 subjects who received health examination all participated in the result analysis. Intergroup comparison： ①The ratio of BD patients with accompanied hypertension, diabetes mellitus, hypedipemia, transient ischemic attacks and coronary heart disease was 91.3%, 46.8%, 42.9%, 81.7% and 46.0% respectively in the BD patients group, and that was 36.5%, 17.5%, 15.9%, 34.1% and 34.1%, respectively in the control group. Significant difference existed between two groups （x^2=86.201, 24.907,25.660,58.620,9.900, P 〈 0.01 ）.②Compared with control group, anterior, middle cerebral and vertebrobasilar arteriosclerosis and insufficient cerebral blood supply existed significantly in BD patients with different disease condition （x^2=40.34,7.585,15.429, P 〈 0.01 ）.③Compared with control group, the level of blood glucose, total cholesterol and triglyceride of BD patients increased significantly （t=6.939,3.891,3.711 ,P 〈 0.01 ）. Comparison among BD patients with different disease condition： ① Compared with stable period, transient ischemic attacks and coronary heart disease were found much in the BD patients at progressive period, with significant difference （x^2=7.196,13.517,P 〈 0.01 ）.② Mild arteriosclerosis at stable period was found in 17 cases, and significant difference existed compared with progressive period （x^2=6.523,P 〈 0.05）.③ There was no significant difference in the blood glucose and blood lipid level （t=-1.755 6,0.583 1,0.824 6, P 〉 0.05）. CONCLUSION： Hypertension, cerebral arteriosclerosis, diabetes mellitus, hypedipemia, coronary heart disease and transient ischemic attacks have important effects on the onset of BD; Transient ischemic attacks and coronary heart disease can worsen the symptoms of BD patients.展开更多
Myelin is an evolutionarUy novel and important structure for the proper functioning of the vertebrate nervous system. In the central nervous system （CNS）, the myelin sheath is elaborated by oligodendrocytes, and is ...Myelin is an evolutionarUy novel and important structure for the proper functioning of the vertebrate nervous system. In the central nervous system （CNS）, the myelin sheath is elaborated by oligodendrocytes, and is composed of multiple layers of specialized cell membrane wrapping around axons with periodic interruptions at the nodes of Ranvier. The major function of the myelin sheath is to provide ionic insulation to ensure rapid and saltatory conduction of electrical pulses along axons. In addition, myelin provides neurotrophic support for axons, as they become increasingly dependent on myelin-derived signals for survival. Despite the importance of myelin in the functioning of the CNS, oligodendrocytes are particularly susceptible to genetic and environmental perturbations, and demyelination can be triggered by many pathological conditions including traumatic injury, autoimmune disease （multiple sclerosis, MS）, heavy metal toxicity, and hypoxia. Loss of myelin sheaths in the CNS not only results in the compromised conduction of electrical signals, but also causes progressive degeneration of axons and ultimately neuronal loss. Spontaneous myelin repair from immature oligodendrocyte progenitor cells （OPCs） is not effective in demyelinating lesions, due either to the absence of stimulatory developmental signals that are no longer produced in the adult environment, or to the presence of inhibitory factors peculiar to this environment.展开更多
Gastroesophageal reflux disease(GERD)is a common gastrointestinal disorder with an increasing prevalence.GERD develops when the reflux of stomach contents causes troublesome typical and atypical symptoms and/or compli...Gastroesophageal reflux disease(GERD)is a common gastrointestinal disorder with an increasing prevalence.GERD develops when the reflux of stomach contents causes troublesome typical and atypical symptoms and/or complications.Several risk factors of GERD have been identified and evaluated over the years,including a considerable amount of genetic factors.Multiple mechanisms are involved in the pathogenesis of GERD including:(1)motor abnormalities,such as impaired lower esophageal sphincter(LES)resting tone,transient LES relaxations,impaired esophageal acid clearance and delayed gastric emptying;and(2)anatomical factors,such as hiatal hernia and obesity.Genetic contribution seems to play a major role in GERD and GERD-related disorders development such Barrett's esophagus and esophageal adenocarcinoma.Twin and family studies have revealed an about 31%heritability of the disease.Numerous single-nucleotide polymorphisms in various genes like FOXF1,MHC,CCND1,anti-inflammatory cytokine and DNA repair genes have been strongly associated with increased GERD risk.GERD,Barrett'sesophagus and esophageal adenocarcinoma share several genetic loci.Despite GERD polygenic basis,specific genetic loci such as rs10419226 on chromosome 19,rs2687201 on chromosome 3,rs10852151 on chromosome 15 and rs520525 on the paired related homeobox 1 gene have been mentioned as potential risk factors.Further investigation on the risk genes may elucidate their exact function and role and demonstrate new therapeutic approaches to this increasingly common disease.展开更多
Rare diseases continue to pose a formidable public health challenge with lack or absence of effective treatments,demonstrating an immense need for rare disease drugs.However,the development of rare disease drugs remai...Rare diseases continue to pose a formidable public health challenge with lack or absence of effective treatments,demonstrating an immense need for rare disease drugs.However,the development of rare disease drugs remains uneven globally due to disparities in resource allocation,policy support,and medical infrastructure[1].Compared with other regions such as the USA and the EU,China exhibits distinct needs related to its particular disease spectrum,incidence,prevalence,genetic backgrounds,aetiology,and clinical practices[2].展开更多
tRNAs are essential modulators that recognize mRNA codons and bridge amino acids for mRNA translation.The tRNAs are heavily modified,which are essential for forming a complex secondary structure that facilitates codon...tRNAs are essential modulators that recognize mRNA codons and bridge amino acids for mRNA translation.The tRNAs are heavily modified,which are essential for forming a complex secondary structure that facilitates codon recognition and mRNA translation.In recent years,studies have identified the regulatory roles of tRNA modifications in mRNA translation networks.Misregulation of tRNA modifications is closely related to the progression of developmental diseases and cancers.In this review,we summarize the tRNA biogenesis process and then discuss the effects and mechanisms of tRNA modifications on tRNA processing and mRNA translation.Finally,we provide a comprehensive overview of the physiological and pathological functions of tRNA modifications,focusing on diseases including cancers.展开更多
Mouse and non-human primate models of neurodegenerative disease：The prevalence of age-related neurodegenerative diseases continues to increase with ever increasing aging population over the age of 60.Although the dif...Mouse and non-human primate models of neurodegenerative disease：The prevalence of age-related neurodegenerative diseases continues to increase with ever increasing aging population over the age of 60.Although the difficulties associated with neurodegenerative diseases present an urgent global issue,there is no effective treatment for these conditions.展开更多
In the present paper the author reviews the viewpoint of 'preventive treatment of diseases' in the ancient literature of traditional Chinese medicine (TCN) and its clinical application from (1) prevention firs...In the present paper the author reviews the viewpoint of 'preventive treatment of diseases' in the ancient literature of traditional Chinese medicine (TCN) and its clinical application from (1) prevention first before the occurrence of diseases; and (2) preventing development after onset of diseases. In the preventive treatment of diseases, the ancient Chinese doctors usually (1) regulated qi of both Conception Vessel and Governor Vessel for health care; (2) performed regular moxibustion; and (3) applied plaster to the acupoint in summer for treating winter-diseases. In the treatment of diseases after onset, the ancient Chinese usually (1) tried best to make early diagnosis and early treatment; and (2) strengthened the related internal organ in advance to check their development; and (3) employed appropriate remedies to recuperate the patient's health.展开更多
The developmental origins of health and diseases(DOHaD)is a concept stating that adverse intrauterine environments contribute to the health risks of offspring.Since the theory emerged more than 30 years ago,many epide...The developmental origins of health and diseases(DOHaD)is a concept stating that adverse intrauterine environments contribute to the health risks of offspring.Since the theory emerged more than 30 years ago,many epidemiological and animal studies have confirmed that in utero exposure to environmental insults,including hyperglycemia and chemicals,increased the risk of developing noncommunicable diseases(NCDs).These NCDs include metabolic syndrome,type 2 diabetes,and complications such as diabetic cardiomyopathy.Studying the effects of different environmental insults on early embryo development would aid in understanding the underlying mechanisms by which these insults promote NCD development.Embryonic stem cells(ESCs)have also been utilized by researchers to study the DOHaD.ESCs have pluripotent characteristics and can be differentiated into almost every cell lineage;therefore,they are excellent in vitro models for studying early developmental events.More importantly,human ESCs(hESCs)are the best alternative to human embryos for research because of ethical concerns.In this review,we will discuss different maternal conditions associated with DOHaD,focusing on the complications of maternal diabetes.Next,we will review the differentiation protocols developed to generate different cell lineages from hESCs.Additionally,we will review how hESCs are utilized as a model for research into the DOHaD.The effects of environmental insults on hESC differentiation and the possible involvement of epigenetic regulation will be discussed.展开更多
Hyaluronan(HA),a natural high molecular weight polysaccharide,has extensive applications in cosmetology and medical treatment.Hyaluronan-degrading enzymes(Hyals)act as molecular scissors that cleave HA by breaking the...Hyaluronan(HA),a natural high molecular weight polysaccharide,has extensive applications in cosmetology and medical treatment.Hyaluronan-degrading enzymes(Hyals)act as molecular scissors that cleave HA by breaking the glucosidic linkage.Hyals are present in diverse organisms,including vertebrates,invertebrates and microorganisms,and play momentous roles in biological processes.In recent years,microbial Hyals(mHyals)have gained considerable attention for their exceptional performance in the production and processing of HA.Moreover,the applications of mHyals have been greatly extended to various biomedical fields.To explore the potential applications of mHyals,a thorough comprehension is imperative.In this context,this review systematically summarizes the sources,structures,mechanisms and enzymatic properties of mHyals and discusses their biological functions in host invasion,disease development,and regulation of intestinal flora.Furthermore,versatile applications inspired by their biological functions in medicine development,molecular biology,and industrial biotechnology are comprehensively reviewed.Finally,prospects are presented to emphasize the importance of exploration,expression and characterization of mHyals and the necessity of excavating their potential in biotechnological fields.展开更多
Administration of human umbilical cord-derived mesenchymal stem cells(hUC-MSCs)is believed to be an effective method for treating neurodevelopmental disorde rs.In this study,we investigated the possibility of hUC-MSCs...Administration of human umbilical cord-derived mesenchymal stem cells(hUC-MSCs)is believed to be an effective method for treating neurodevelopmental disorde rs.In this study,we investigated the possibility of hUC-MSCs treatment of neonatal hypoxic/ischemic brain injury associated with maternal immune activation and the underlying mechanism.We established neonatal rat models of hypoxic/ischemic brain injury by exposing pregnant rats to lipopolysaccharide on day 16 or 17 of pregnancy.Rat offspring were intranasally administe red hUC-MSCs on postnatal day 14.We found that polypyrimidine tract-binding protein-1(PTBP-1)participated in the regulation of lipopolysaccharide-induced maternal immune activation,which led to neonatal hypoxic/ischemic brain injury.Intranasal delive ry of hUC-MSCs inhibited PTBP-1 expression,alleviated neonatal brain injury-related inflammation,and regulated the number and function of glial fibrillary acidic protein-positive astrocytes,there by promoting plastic regeneration of neurons and im p roving brain function.These findings suggest that hUC-MSCs can effectively promote the repair of neonatal hypoxic/ischemic brain injury related to maternal immune activation through inhibition of PTBP-1 expression and astrocyte activation.展开更多
The breadth of the enrichment site for post-translational trimethylation of histone H3 at lysine 4 （H3K4me3） on chromatin has attracted great attention recently. H3K4me3, an extensively-studied histone modification,...The breadth of the enrichment site for post-translational trimethylation of histone H3 at lysine 4 （H3K4me3） on chromatin has attracted great attention recently. H3K4me3, an extensively-studied histone modification, is reported to promote gene transcription by directing preinitiation complex assembly through interaction with effector proteins, e.g.,展开更多
Introduction Mortality due to various kinds of noncommunicable diseases (NCDs) has become an increasing focus of attention in recent years.1 With rapidly increasing globalization, lifestyles in low-and middle-income c...Introduction Mortality due to various kinds of noncommunicable diseases (NCDs) has become an increasing focus of attention in recent years.1 With rapidly increasing globalization, lifestyles in low-and middle-income countries increasingly include high-fat diets and inadequate physical exercises are resulting in an increased worldwide burden of NCDs.2,3 A study by the International Diabetes Federation (IDF) showed that about 382 million people had diabetes in 2013, and this will rise to 592 million by 2035.The number of people with type 2 diabetes is increasing in every country, and 80％ of people with diabetes live in low-and middle-income countries.The burden of NCDs and the prevalence of related risk factors such asoverweight and diabetes have also increased in China over the past decades.In 2005, NCDs accounted for an estimated 80％ of deaths and 70％ of disability-adjusted life-years lost in China.展开更多
The Sino-UK Symposium on Developmental Biology and Human Diseases opened in Tsinghua May 6, 2006. TheSymposium, which ran through May 8, 2006, was hosted by the Department of Biological Sciences and Biotechnology, Tsi...The Sino-UK Symposium on Developmental Biology and Human Diseases opened in Tsinghua May 6, 2006. TheSymposium, which ran through May 8, 2006, was hosted by the Department of Biological Sciences and Biotechnology, Tsinghua University.展开更多
Maternal nutrition is found to be the key factor that determines fetal health in utero and metabolic health during adulthood.Metabolic diseases have been primarily attributed to impaired maternal nutrition during preg...Maternal nutrition is found to be the key factor that determines fetal health in utero and metabolic health during adulthood.Metabolic diseases have been primarily attributed to impaired maternal nutrition during pregnancy,and impaired nutrition has been an immense issue across the globe.In recent years,type 2 diabetes(T2D)has reached epidemic proportion and is a severe public health problem in many countries.Although plenty of research has already been conducted to tackle T2D which is associated with obesity,little is known regarding the etiology and pathophysiology of lean T2D,a variant of T2D.Recent studies have focused on the effects of epigenetic variation on the contribution of in utero origins of lean T2D,although other mechanisms might also contribute to the pathology.Observational studies in humans and experiments in animals strongly suggest an association between maternal low protein diet and lean T2D phenotype.In addition,clear sex-specific disease prevalence was observed in different studies.Consequently,more research is essential for the understanding of the etiology and pathophysiology of lean T2D,which might help to develop better disease prevention and treatment strategies.This review examines the role of protein insufficiency in the maternal diet as the central driver of the developmental programming of lean T2D.展开更多
Genetic variants in the non-coding regions of the genome can significantly influence gene expression and regulation through various mechanisms,including altering transcription factor(TF)binding,histone modifications,a...Genetic variants in the non-coding regions of the genome can significantly influence gene expression and regulation through various mechanisms,including altering transcription factor(TF)binding,histone modifications,and chromatin accessibility.These mechanisms are increasingly recognized as playing crucial roles in the development of complex diseases[1,2].To comprehensively understand the functional impact of non-coding variants,it is essential to integrate genomic,transcriptomic,epigenomic,and proteomic data.The advent of high-throughput sequencing technologies and the availability of large-scale genomic,transcriptomic,proteomics and epigenomic data have greatly facilitated the annotation and interpretation of non-coding variants from a trans-omics perspective,enabling a more comprehensive understanding of their functional consequences.However,most current studies examining the effects of genetic variants rely on data from a single or limited number of layers,such as GREEN-DB(primarily focuses on regulatory)[3],GWAVA(based on ENCODE/GENCODE,evolutionary conservation and GC-content)[4],RegulomeDB(seven data types including TF binding sites,chromatin states,TF motifs,Footprints,eQTLs and caQTLs)[5],etc.展开更多
文摘Haptoglobin,a protein primarily recognized for its role in sequestering free hemoglobin,has been identified as a molecule with diverse and underexplored functions in the pathophysiology of various diseases.This editorial explores the multifaceted roles of haptoglobin,highlighting its involvement in inflammatory responses and immune regulation and its potential implications in chronic diseases such as diabetes,cardiovascular disorders,and cancer.Through a synthesis of recent research findings,this editorial reveals the importance of haptoglobin in disease mechanisms and underscores the need for further investigation to fully elucidate its therapeutic potential.A comprehensive understanding of haptoglobin’s novel functions may catalyze the development of innovative diagnostic and therapeutic modalities in clinical practice.
基金supported by grants by NIH grant AR-044741(Y-PL) and R01DE023813 (Y-PL)
文摘INTRODUCTIONThe transforming growth factor-β （TGF-β） superfamily com- prises TGF-βs, Activin, bone morphogenetic proteins （BMPs） and other related proteins. TGF-β superfamily members act through a heteromeric receptor complex,, comprised of type I and type II receptors at the cell surface that transduce intracellular signals via Smad complex or mitogen-activated protein kinase （MAPK） cascade.
基金National Key Research and Development Program of ChinaGrant/Award Number:2019YFA0801601+1 种基金National Natural Science Foundation of ChinaGrant/Award Number:31930029,91854111 and 31571490。
文摘The G-quadruplex(G4)sequences are short fragments of 4-i nterval triple guanine(G)with frequent and ubiquitous distribution in the genome and RNA transcripts.The G4sequences are usually folded into secondary“knot”structure via Hoogsteen hydrogen bond to exert negative regulation on a variety of biological processes,including DNA replication and transcription,mRNA translation,and telomere maintenance.Recent structural biological and mouse genetics studies have demonstrated that RHAU(DHX36)can bind and unwind the G4“knots”to modulate embryonic development and postnatal organ function.Deficiency of RHAU gives rise to embryonic lethality,impaired organogenesis,and organ dysfunction.These studies uncovered the pivotal G4 resolvase function of RHAU to release the G4 barrier,which plays fundamental roles in development and physiological homeostasis.This review discusses the latest advancements and findings in deciphering RHAU functions using animal models.
文摘Alzheimer＇s disease （AD） is the most frequent cause of dementia in the western world. In clinical terms, AD is characterized by progres- sive cognitive decline that usually begins with memory impairment. As the disease progresses, AD inevitably affects all intellectual functions including executive functions, leading to complete dependence for basic activities of daily life and premature death.
基金supported in parts by grants from the Disciplinary Group of Psychology and Neuroscience Xinxiang Medical University,China(2016PN-KFKT-06)Department of Education of Henan Province,China(16IRTSTHN020)+1 种基金the National Natural Science Foundation of China(31471118)UK Alzheimer’s Research Trust(ART/PPG2009A/2)
文摘Alzheimer’s disease （AD） is an age-related eurodegenerative disease that represents the most common cause of dementia among the elderly people. With the increasingly aging population, AD has presented an overwhelming healthcare challenge to modern society; the World Alzheimer Report 2015 has estimated that 46.8 million people worldwide lived with dementia in 2015 and this number will rise to 74.7 million in 2030 and that the total cost of dementia was 818 billion in US$ in 2015 and will reach two trillion in 2030. Post-mortem studies have identified two histopathological hallmarks in the brains of AD patients; extracellular senile plaque with elevated deposition of amyloid β （Aβ） peptides, and intracellular neurofibrillary tangle composed of hyper-phosphorylated microtubule-associated protein tau.Etiologically, progressive neuronal loss within the cerebral cortex and hippocampus regions of the brain leads to irreversible decline in, and eventually complete loss of, memory and other cognitive functions that afflict AD patients. The widely-accepted amyloid cascade hypothesis for AD pathogenesis holds that accumulation and aggregation of neurotoxic Aβ peptides, due to imbalance of their generation and clearance as a result of changes in genetic makeup, aging and/or exposure to environmental risk factors, is a major and early trigger of AD. This hypothesis has continuously gained support by preclinical and clinical studies （Selkoe and Hardy, 2016）. However, the intensive and costly drug discovery efforts over the past decades based on such a hypothesis have proved extremely frustrating in developing effective therapeutics to treat or slow down the progress of AD, highlighting the need for more research to improve our understanding towards the cellular and molecular mechanisms by which Aβ peptides bring about neurotoxicity and cognitive dysfunction.
文摘BACKGROUND： Some scholars think that hypertension is the major risk factor to cause Binswanger disease （BD）, however, BD is also found in some persons with normal blood pressure, so we presume that some other factors, such as diabetes mellitus, hyperlipemia, coronary heart disease and transient ischemic attacks and so on, might participant in the onset of BD. OBJECTIVE： To comparatively observe the difference in accompanying diseases, transcranial doppler （TCD） performance, blood glucose and blood lipid level between BD patients and healthy subjects who received health examination, and between BD patients with different disease condition. DESIGN ： Case-control analysis SETTING ： Department of Emergency, Qingdao Municipal Hospita PARTICIPANTS： Totally 126 patients with BD, 65 male and 61 female, aged from 67 to 85 years old, who hospitalized in the Medical School Hospital of Qingdao University and Qingdao Municipal People＇s Hospital, were chosen, serving as BD patients group. All the patients met the clinical diagnostic criteria of BD introduced by Bennett et al. Another 126 persons, 65 male and 61 female, aged ranging from 67 to 80 years, who received health examination in the same hospital, were homeochronously chosen, serving as control group. Informed consents were obtained from all the subjects. METHODS ： After being admitted, all the subjects including BD patients and persons who homeochrenously received health examination in the same hospital were given examinations of blood pressure, blood lipid, blood glucose, electrocardiogram （ECG） and TCD. Fifty-seven patients with BD were in the stable period and 69 in the progressive period （Stable period： no local or subcortical function disorder found, and no changes in the range of white matter lesion showed by CT and/or MRI in recent 3 months; Progressive period： with local or subcortical function disorder and increase in the range of white matter lesion showed by CT and/or MRI in recent 3 months）. According to intimal thickening of carotid artery and vertebral artery preformed by TCD, BD was graded as mild intimal thickening （〈 1.1 mm）, moderate intimal thickening （1.1 to 1.2 mm） and severe intimal thickening （〉 1.2 mm）. MAIN OUTCOME MEASURES ： Comparison of the ratio of BD patients with accompanied diabetes mellitus, hypedipemia, coronary heart disease and transient ischemic attacks, TCD performance, blood glucose and blood lipid level between BD patients group and control group, and among BD patients with vadous disease conditions. RESULTS： Totally 126 BD patients and 126 subjects who received health examination all participated in the result analysis. Intergroup comparison： ①The ratio of BD patients with accompanied hypertension, diabetes mellitus, hypedipemia, transient ischemic attacks and coronary heart disease was 91.3%, 46.8%, 42.9%, 81.7% and 46.0% respectively in the BD patients group, and that was 36.5%, 17.5%, 15.9%, 34.1% and 34.1%, respectively in the control group. Significant difference existed between two groups （x^2=86.201, 24.907,25.660,58.620,9.900, P 〈 0.01 ）.②Compared with control group, anterior, middle cerebral and vertebrobasilar arteriosclerosis and insufficient cerebral blood supply existed significantly in BD patients with different disease condition （x^2=40.34,7.585,15.429, P 〈 0.01 ）.③Compared with control group, the level of blood glucose, total cholesterol and triglyceride of BD patients increased significantly （t=6.939,3.891,3.711 ,P 〈 0.01 ）. Comparison among BD patients with different disease condition： ① Compared with stable period, transient ischemic attacks and coronary heart disease were found much in the BD patients at progressive period, with significant difference （x^2=7.196,13.517,P 〈 0.01 ）.② Mild arteriosclerosis at stable period was found in 17 cases, and significant difference existed compared with progressive period （x^2=6.523,P 〈 0.05）.③ There was no significant difference in the blood glucose and blood lipid level （t=-1.755 6,0.583 1,0.824 6, P 〉 0.05）. CONCLUSION： Hypertension, cerebral arteriosclerosis, diabetes mellitus, hypedipemia, coronary heart disease and transient ischemic attacks have important effects on the onset of BD; Transient ischemic attacks and coronary heart disease can worsen the symptoms of BD patients.
文摘Myelin is an evolutionarUy novel and important structure for the proper functioning of the vertebrate nervous system. In the central nervous system （CNS）, the myelin sheath is elaborated by oligodendrocytes, and is composed of multiple layers of specialized cell membrane wrapping around axons with periodic interruptions at the nodes of Ranvier. The major function of the myelin sheath is to provide ionic insulation to ensure rapid and saltatory conduction of electrical pulses along axons. In addition, myelin provides neurotrophic support for axons, as they become increasingly dependent on myelin-derived signals for survival. Despite the importance of myelin in the functioning of the CNS, oligodendrocytes are particularly susceptible to genetic and environmental perturbations, and demyelination can be triggered by many pathological conditions including traumatic injury, autoimmune disease （multiple sclerosis, MS）, heavy metal toxicity, and hypoxia. Loss of myelin sheaths in the CNS not only results in the compromised conduction of electrical signals, but also causes progressive degeneration of axons and ultimately neuronal loss. Spontaneous myelin repair from immature oligodendrocyte progenitor cells （OPCs） is not effective in demyelinating lesions, due either to the absence of stimulatory developmental signals that are no longer produced in the adult environment, or to the presence of inhibitory factors peculiar to this environment.
文摘Gastroesophageal reflux disease(GERD)is a common gastrointestinal disorder with an increasing prevalence.GERD develops when the reflux of stomach contents causes troublesome typical and atypical symptoms and/or complications.Several risk factors of GERD have been identified and evaluated over the years,including a considerable amount of genetic factors.Multiple mechanisms are involved in the pathogenesis of GERD including:(1)motor abnormalities,such as impaired lower esophageal sphincter(LES)resting tone,transient LES relaxations,impaired esophageal acid clearance and delayed gastric emptying;and(2)anatomical factors,such as hiatal hernia and obesity.Genetic contribution seems to play a major role in GERD and GERD-related disorders development such Barrett's esophagus and esophageal adenocarcinoma.Twin and family studies have revealed an about 31%heritability of the disease.Numerous single-nucleotide polymorphisms in various genes like FOXF1,MHC,CCND1,anti-inflammatory cytokine and DNA repair genes have been strongly associated with increased GERD risk.GERD,Barrett'sesophagus and esophageal adenocarcinoma share several genetic loci.Despite GERD polygenic basis,specific genetic loci such as rs10419226 on chromosome 19,rs2687201 on chromosome 3,rs10852151 on chromosome 15 and rs520525 on the paired related homeobox 1 gene have been mentioned as potential risk factors.Further investigation on the risk genes may elucidate their exact function and role and demonstrate new therapeutic approaches to this increasingly common disease.
基金supported by the National Key Research and Development Program of China(2023YFC2508500)Beijing Municipal Health Commission(Beijing Demonstration Research Ward BCRW20200303)+1 种基金the National Natural Science Foundation of China(82272951 and 82272953)the Chinese Academy of Medical Sciences(2022-I2M-C&T-B-070).
文摘Rare diseases continue to pose a formidable public health challenge with lack or absence of effective treatments,demonstrating an immense need for rare disease drugs.However,the development of rare disease drugs remains uneven globally due to disparities in resource allocation,policy support,and medical infrastructure[1].Compared with other regions such as the USA and the EU,China exhibits distinct needs related to its particular disease spectrum,incidence,prevalence,genetic backgrounds,aetiology,and clinical practices[2].
基金funded by the National Natural Science Foundation of China(81922052,81974435,and 81772999)a Distinguished Young Scholars grant from the Natural Science Foundation of Guangdong(2019B151502011)the Guangzhou People’s Livelihood Science and Technology Project(201903010006)。
文摘tRNAs are essential modulators that recognize mRNA codons and bridge amino acids for mRNA translation.The tRNAs are heavily modified,which are essential for forming a complex secondary structure that facilitates codon recognition and mRNA translation.In recent years,studies have identified the regulatory roles of tRNA modifications in mRNA translation networks.Misregulation of tRNA modifications is closely related to the progression of developmental diseases and cancers.In this review,we summarize the tRNA biogenesis process and then discuss the effects and mechanisms of tRNA modifications on tRNA processing and mRNA translation.Finally,we provide a comprehensive overview of the physiological and pathological functions of tRNA modifications,focusing on diseases including cancers.
文摘Mouse and non-human primate models of neurodegenerative disease：The prevalence of age-related neurodegenerative diseases continues to increase with ever increasing aging population over the age of 60.Although the difficulties associated with neurodegenerative diseases present an urgent global issue,there is no effective treatment for these conditions.
文摘In the present paper the author reviews the viewpoint of 'preventive treatment of diseases' in the ancient literature of traditional Chinese medicine (TCN) and its clinical application from (1) prevention first before the occurrence of diseases; and (2) preventing development after onset of diseases. In the preventive treatment of diseases, the ancient Chinese doctors usually (1) regulated qi of both Conception Vessel and Governor Vessel for health care; (2) performed regular moxibustion; and (3) applied plaster to the acupoint in summer for treating winter-diseases. In the treatment of diseases after onset, the ancient Chinese usually (1) tried best to make early diagnosis and early treatment; and (2) strengthened the related internal organ in advance to check their development; and (3) employed appropriate remedies to recuperate the patient's health.
文摘The developmental origins of health and diseases(DOHaD)is a concept stating that adverse intrauterine environments contribute to the health risks of offspring.Since the theory emerged more than 30 years ago,many epidemiological and animal studies have confirmed that in utero exposure to environmental insults,including hyperglycemia and chemicals,increased the risk of developing noncommunicable diseases(NCDs).These NCDs include metabolic syndrome,type 2 diabetes,and complications such as diabetic cardiomyopathy.Studying the effects of different environmental insults on early embryo development would aid in understanding the underlying mechanisms by which these insults promote NCD development.Embryonic stem cells(ESCs)have also been utilized by researchers to study the DOHaD.ESCs have pluripotent characteristics and can be differentiated into almost every cell lineage;therefore,they are excellent in vitro models for studying early developmental events.More importantly,human ESCs(hESCs)are the best alternative to human embryos for research because of ethical concerns.In this review,we will discuss different maternal conditions associated with DOHaD,focusing on the complications of maternal diabetes.Next,we will review the differentiation protocols developed to generate different cell lineages from hESCs.Additionally,we will review how hESCs are utilized as a model for research into the DOHaD.The effects of environmental insults on hESC differentiation and the possible involvement of epigenetic regulation will be discussed.
基金financially supported by the National Key Research and Development Program of China(No.2021YFC2100900)the National Natural Science Foundation of China(No.32171261)+1 种基金the Taishan Industry Leading Talent of Shandong Province(No.tscx202211017)the Postgraduate Research&Practice Innovation Program of Jiangsu Province(No.KYCX23_2575).
文摘Hyaluronan(HA),a natural high molecular weight polysaccharide,has extensive applications in cosmetology and medical treatment.Hyaluronan-degrading enzymes(Hyals)act as molecular scissors that cleave HA by breaking the glucosidic linkage.Hyals are present in diverse organisms,including vertebrates,invertebrates and microorganisms,and play momentous roles in biological processes.In recent years,microbial Hyals(mHyals)have gained considerable attention for their exceptional performance in the production and processing of HA.Moreover,the applications of mHyals have been greatly extended to various biomedical fields.To explore the potential applications of mHyals,a thorough comprehension is imperative.In this context,this review systematically summarizes the sources,structures,mechanisms and enzymatic properties of mHyals and discusses their biological functions in host invasion,disease development,and regulation of intestinal flora.Furthermore,versatile applications inspired by their biological functions in medicine development,molecular biology,and industrial biotechnology are comprehensively reviewed.Finally,prospects are presented to emphasize the importance of exploration,expression and characterization of mHyals and the necessity of excavating their potential in biotechnological fields.
基金the National Natural Science Foundation of China,No.81471308(to JL)Stem cell Clinical Research Registry Program,No.CMR-20161129-1003(to JL)+2 种基金Liaoning Province Excellent Talent Program Project of China,No.XLYC1902031(to JL)Dalian Innovation Fund of China,No.2018J11CY025(to JL)National Defense Science and Technology New Special Zone Contract,No.19-163-00-kx-003-001-01(to JL)。
文摘Administration of human umbilical cord-derived mesenchymal stem cells(hUC-MSCs)is believed to be an effective method for treating neurodevelopmental disorde rs.In this study,we investigated the possibility of hUC-MSCs treatment of neonatal hypoxic/ischemic brain injury associated with maternal immune activation and the underlying mechanism.We established neonatal rat models of hypoxic/ischemic brain injury by exposing pregnant rats to lipopolysaccharide on day 16 or 17 of pregnancy.Rat offspring were intranasally administe red hUC-MSCs on postnatal day 14.We found that polypyrimidine tract-binding protein-1(PTBP-1)participated in the regulation of lipopolysaccharide-induced maternal immune activation,which led to neonatal hypoxic/ischemic brain injury.Intranasal delive ry of hUC-MSCs inhibited PTBP-1 expression,alleviated neonatal brain injury-related inflammation,and regulated the number and function of glial fibrillary acidic protein-positive astrocytes,there by promoting plastic regeneration of neurons and im p roving brain function.These findings suggest that hUC-MSCs can effectively promote the repair of neonatal hypoxic/ischemic brain injury related to maternal immune activation through inhibition of PTBP-1 expression and astrocyte activation.
基金supported by faculty start up funding provided by The Methodist Hospital Research Institute,Texas,United States
文摘The breadth of the enrichment site for post-translational trimethylation of histone H3 at lysine 4 （H3K4me3） on chromatin has attracted great attention recently. H3K4me3, an extensively-studied histone modification, is reported to promote gene transcription by directing preinitiation complex assembly through interaction with effector proteins, e.g.,
文摘Introduction Mortality due to various kinds of noncommunicable diseases (NCDs) has become an increasing focus of attention in recent years.1 With rapidly increasing globalization, lifestyles in low-and middle-income countries increasingly include high-fat diets and inadequate physical exercises are resulting in an increased worldwide burden of NCDs.2,3 A study by the International Diabetes Federation (IDF) showed that about 382 million people had diabetes in 2013, and this will rise to 592 million by 2035.The number of people with type 2 diabetes is increasing in every country, and 80％ of people with diabetes live in low-and middle-income countries.The burden of NCDs and the prevalence of related risk factors such asoverweight and diabetes have also increased in China over the past decades.In 2005, NCDs accounted for an estimated 80％ of deaths and 70％ of disability-adjusted life-years lost in China.
文摘The Sino-UK Symposium on Developmental Biology and Human Diseases opened in Tsinghua May 6, 2006. TheSymposium, which ran through May 8, 2006, was hosted by the Department of Biological Sciences and Biotechnology, Tsinghua University.
基金Supported by the National Institutes of Health Grants,No. HL102866, HL58144 and DK114689
文摘Maternal nutrition is found to be the key factor that determines fetal health in utero and metabolic health during adulthood.Metabolic diseases have been primarily attributed to impaired maternal nutrition during pregnancy,and impaired nutrition has been an immense issue across the globe.In recent years,type 2 diabetes(T2D)has reached epidemic proportion and is a severe public health problem in many countries.Although plenty of research has already been conducted to tackle T2D which is associated with obesity,little is known regarding the etiology and pathophysiology of lean T2D,a variant of T2D.Recent studies have focused on the effects of epigenetic variation on the contribution of in utero origins of lean T2D,although other mechanisms might also contribute to the pathology.Observational studies in humans and experiments in animals strongly suggest an association between maternal low protein diet and lean T2D phenotype.In addition,clear sex-specific disease prevalence was observed in different studies.Consequently,more research is essential for the understanding of the etiology and pathophysiology of lean T2D,which might help to develop better disease prevention and treatment strategies.This review examines the role of protein insufficiency in the maternal diet as the central driver of the developmental programming of lean T2D.
基金supported by the National Key R&D Program of China(2021YFF0703701,2021YFF0704500,and 2022YFC3400405)Strategic Priority Research Program of the Chinese Academy of Sciences(XDB38040300)+3 种基金14th Five-year Informatization Plan of Chinese Academy of Sciences(CAS-WX2021SF-0203)National Natural Science Foundation of China(32200478)China Postdoctoral Science Foundation(2022M713311 and GZC20232899)National Genomics Data Center,China。
文摘Genetic variants in the non-coding regions of the genome can significantly influence gene expression and regulation through various mechanisms,including altering transcription factor(TF)binding,histone modifications,and chromatin accessibility.These mechanisms are increasingly recognized as playing crucial roles in the development of complex diseases[1,2].To comprehensively understand the functional impact of non-coding variants,it is essential to integrate genomic,transcriptomic,epigenomic,and proteomic data.The advent of high-throughput sequencing technologies and the availability of large-scale genomic,transcriptomic,proteomics and epigenomic data have greatly facilitated the annotation and interpretation of non-coding variants from a trans-omics perspective,enabling a more comprehensive understanding of their functional consequences.However,most current studies examining the effects of genetic variants rely on data from a single or limited number of layers,such as GREEN-DB(primarily focuses on regulatory)[3],GWAVA(based on ENCODE/GENCODE,evolutionary conservation and GC-content)[4],RegulomeDB(seven data types including TF binding sites,chromatin states,TF motifs,Footprints,eQTLs and caQTLs)[5],etc.
