pathogenesis

摘要： The amyloid cascade hypothesis of Alzheimer’s pathogenesis:The amyloid cascade hypothesis of Alzheimer’s disease(AD)pathogenesis will shortly celebrate its thirtieth birthday(Hardy and Higgins,1992).Based on abundant genetic and biochemical evidence,it proposes that deposition of the amyloid-β(Aβ)peptide in brain parenchyma is an essential upstream trigger in AD pathogenesis that drives a cascade of events,specifically including the recruitment and pathological hyper-phosphorylation of the micro-tubule-associated protein tau,that culminate in derangement of synaptic function and,eventually,neuronal death.

摘要： Alzheimer’s disease(AD)is a degenerative neurological disease that primarily affects the elderly.Drug therapy is the main strategy for AD treatment,but current treatments suffer from poor efficacy and a number of side effects.Non-drug therapy is attracting more attention and may be a better strategy for treatment of AD.Hypoxia is one of the important factors that contribute to the pathogenesis of AD.Multiple cellular processes synergistically promote hypoxia,including aging,hypertension,diabetes,hypoxia/obstructive sleep apnea,obesity,and traumatic brain injury.Increasing evidence has shown that hypoxia may affect multiple pathological aspects of AD,such as amyloid-beta metabolism,tau phosphorylation,autophagy,neuroinflammation,oxidative stress,endoplasmic reticulum stress,and mitochondrial and synaptic dysfunction.Treatments targeting hypoxia may delay or mitigate the progression of AD.Numerous studies have shown that oxygen therapy could improve the risk factors and clinical symptoms of AD.Increasing evidence also suggests that oxygen therapy may improve many pathological aspects of AD including amyloid-beta metabolism,tau phosphorylation,neuroinflammation,neuronal apoptosis,oxidative stress,neurotrophic factors,mitochondrial function,cerebral blood volume,and protein synthesis.In this review,we summarized the effects of oxygen therapy on AD pathogenesis and the mechanisms underlying these alterations.We expect that this review can benefit future clinical applications and therapy strategies on oxygen therapy for AD.

摘要： Multiple sclerosis(MS)is a chronic immune-mediated disorder of the central nervous system(CNS)that causes focal demyelinating lesions,followed by axonal and neuronal degeneration.Several genetic and environmental factors are found to be associated with MS incidence.While MS etiology seems to be multifactorial and needs further elucidation,it is understood that the response of an immune system to specific myelin antigens triggers the onset of MS(Dendrou et al.,2015).However,how the autoimmune response initiates against myelin,and the cellular and molecular mechanisms underpinning the development and progression of MS are not fully understood.Thus,deconstructing MS pathogenesis is of paramount importance for identifying novel diagnostic and therapeutic targets for this complex disease.

摘要： The prevalence rate of type 2 diabetes is increasing year by year,simple surgery and Western medicine treatment has limitations,doing damage to liver and kidney function,resulting in islet function damage,insulin resistance,poor curative effect and many adverse reactions.According to the difference of patients'health conditions,traditional Chinese medicine has certain advantages in the treatment of this disease by acupuncture,auricular point treatment and prescription based on syndrome differentiation,taking replenishing qi and nourishing yin,invigorating spleen and resolving dampness as the basic principle to enhance the functions of viscera such as lung,spleen and kidney,and to strengthen the body resistance to eliminate pathogenic factors.The curative effect is remarkable and the side effect is extremely low.Therefore,this paper makes a comparative analysis of the current situation of the research on the pathogenesis and treatment of the disease between traditional Chinese medicine and Western medicine,in order to provide new ideas for clinical and scientific researchers.

摘要： The RNA component of mitochondrial RNA-processing endoribonuclease(RMRP)was first described as an entity that cleaved mitochondrial RNA at a priming site of mitochondrial DNA replication.This long noncoding RNA(lncRNA)was encoded by an evolutionarily conserved nuclear gene that has been characterized in many species,including human,mouse,cattle,zebrafish,toad,and yeast.It was soon learned that RMRP as a component of the RNase MRP complex was also located in the nucleus,and was critical for ribosomal RNA(rRNA)processing,particularly the biosynthesis of 5.8S rRNAs.In 2001,the first evidence of the role of RMRP in the pathogenesis of human disorders was reported,involving mutations in the RMRP gene,which caused cartilage-hair hypoplasia(CHH)1,a recessively inherited developmental disorder characterized by short stature,hypoplastic anemia,defective immunity,and predisposition to several cancers.

摘要： Liver fibrosis is a complex pathological process controlled by a variety of cells,mediators and signaling pathways.Hepatic stellate cells play a central role in the development of liver fibrosis.In chronic liver disease,hepatic stellate cells undergo dramatic phenotypic activation and acquire fibrogenic properties.This review focuses on the pathophysiological mechanisms of hepatic stellate cells activation in liver fibrosis.They enter the cell cycle under the influence of various triggers.The“Initiation”phase of hepatic stellate cells activation overlaps and continues with the“Perpetuation”phase,which is characterized by a pronounced inflammatory and fibrogenic reaction.This is followed by a resolution phase if the injury subsides.Knowledge of these pathophysiological mechanisms paved the way for drugs aimed at preventing the development and progression of liver fibrosis.In this respect,impairments in intracellular signaling,epigenetic changes and cellular stress response can be the targets of therapy where the goal is to deactivate hepatic stellate cells.Potential antifibrotic therapy may focus on inducing hepatic stellate cells to return to an inactive state through cellular aging,apoptosis,and/or clearance by immune cells,and serve as potential antifibrotic therapy.It is especially important to prevent the formation of liver cirrhosis since the only radical approach to its treatment is liver transplantation which can be performed in only a limited number of countries.

摘要： Spinal cord injury(SCI),either from trauma or degenerative changes,can res ult in severe disability and impaired quality of life.Understanding the cellular processes and molecular mechanisms that underlie SCI is imperative to identifying molecular targets for potential therapy.Recent studies have shown that non-coding RNAs,including both long non-coding RNAs(lncRNAs)and circular RNAs(circRNAs),regulate various cellular processes in SCI.In this review,we will describe the changes in lncRNA and circRNA expression that occur after SCI and how these changes may be related to SCI progression.Current evidence for the roles of lncRNAs and circRNAs in neuronal cell death and glial cell activation will also be reviewed.Finally,the possibility that lncRNAs and circRNAs are novel modulato rs of SCI pathogenesis will be discussed.

摘要： ATXN2 one gene with multiple phenotype effects:ATXN2 gene encodes a cytosolic protein(ataxin-2)with pleiotropic functions(see below).This gene contains a number of exonic Cytosine-Adenine-Guanine(CAG)-repeats which encodes a polyglutamine tract(polyQ)in the N-terminal intrinsically disordered region(IDR)of the protein.ATXN2CAG repeats are interrupted by CAA codons which is relevant only for DNA and RNA but not for protein since CAA also encodes glutamine(Q).

摘要： BACKGROUND Kissing molars(KMs)are a scarcely reported form of molar impaction in which the occlusal surfaces contact each other within a single dental follicle and the roots point in opposite directions.The direction of KMs impaction is generally tilted.KMs with vertical direction impaction have not been reported in the literature.CASE SUMMARY A 25-year-old female visited a dentist for right maxillary wisdom teeth extraction and was diagnosed with two vertically impacted KMs in the left mandible on panoramic radiography.After cone-beam computed tomography examination confirmed no secondary complication,the patient chose to undergo observation and regular follow-up.A literature review of KMs revealed that vertical impacted KMs are rare;high-quality evidence regarding their prevalence is still lacking.At present,the causality of KMs is controversial.In this study,we have tried to provide a detailed definition of KMs to allow an accurate evaluation of their prevalence and classification based on their impaction direction which may be related to their pathogenesis.The treatment plan of KMs depends on the condition and location of the affected teeth and associated complications;they may be either directly extracted or treated using a multidisciplinary approach including maxillofacial surgeons and orthodontists.CONCLUSION KMs are a rare clinical condition of impacted teeth with unclear pathogenesis.Vertically impacted KMs were seldom reported.Reasonable definition and classification of KMs can help in the understanding of their causes and prevalence.

摘要： There is a critical need to develop animal models to alleviate vaccine and drug development difficulties against zoonotic viral infections.The coronavirus family,which includes severe acute respiratory syndrome coronavirus 1 and severe acute respiratory syndrome coronavirus 2,crossed the species barrier and infected humans,causing a global outbreak in the 21st century.Because humans do not have pre-existing immunity against these viral infections and with ethics governing clinical trials,animal models are therefore being used in clinical studies to facilitate drug discovery and testing efficacy of vaccines.The ideal animal models should reflect the viral replication,clinical signs,and pathological responses observed in humans.Different animal species should be tested to establish an appropriate animal model to study the disease pathology,transmission and evaluation of novel vaccine and drug candidates to treat coronavirus disease 2019.In this context,the present review summarizes the recent progress in developing animal models for these two pathogenic viruses and highlights the utility of these models in studying SARS-associated coronavirus diseases.