NF-κB pathway consists of canonical and non-canonical pathways.The canonical NF-κB is activated by various stimuli,transducing a quick but transient transcriptional activity,to regulate the expression of various pro...NF-κB pathway consists of canonical and non-canonical pathways.The canonical NF-κB is activated by various stimuli,transducing a quick but transient transcriptional activity,to regulate the expression of various proinflammatory genes and also serve as the critical mediator for inflammatory response.Meanwhile,the activation of the non-canonical NF-κB pathway occurs through a handful of TNF receptor superfamily members.Since the activation of this pathway involves protein synthesis,the kinetics of non-canonical NF-κB activation is slow but persistent,in concordance with its biological functions in the development of immune cell and lymphoid organ,immune homeostasis and immune response.The activation of the canonical and non-canonical NF-κB pathway is tightly controlled,highlighting the vital roles of ubiquitination in these pathways.Emerging studies indicate that dysregulated NF-κB activity causes inflammation-related diseases as well as cancers,and NF-κB has been long proposed as the potential target for therapy of diseases.This review attempts to summarize our current knowledge and updates on the mechanisms of NF-κB pathway regulation and the potential therapeutic application of inhibition of NF-κB signaling in cancer and inflammatory diseases.展开更多
Objective To study the relationship between carotid atherosclerosis and cerebral infarction (CI). Methods Between November 2008 and March 2009,147 CI patients (CI group) and 48 patients with non-cerebrovascular diseas...Objective To study the relationship between carotid atherosclerosis and cerebral infarction (CI). Methods Between November 2008 and March 2009,147 CI patients (CI group) and 48 patients with non-cerebrovascular diseases (control group) were enrolled from inpatients of Neurology Department of our hospital. The diagnostic criterion of thickened carotid intima was set as 1.0 mm≤intima-media thickness (IMT) <1.5 mm and that of carotid plaque was as IMT≥1.5 mm. Carotid atherosclerosis was divided into three levels: normal intima,thickened intima,and plaque formation. The color Doppler ultrasonography data of carotid arteries in all patients were analyzed and the severity of carotid atherosclerosis was compared between the two groups. Results In the CI group,36 (24.5%) patients had normal carotid intima,22 (15.0%) had thickened carotid intima,and 89 (60.5%) had carotid plaque. In the control group,22 (45.8%) patients had normal carotid intima,4 (8.3%) had thickened carotid intima,and 22 (45.8%) had carotid plaque. The severity of carotid atherosclerosis in the CI group was higher than that in the control group (P=0.022). There was significant difference in the constitution of carotid plaque between the two groups (P=0.001); the CI group mainly had the soft plaque (55/89,61.8%),whereas the control group mainly had the hard plaque (17/22,77.3%). The first three common locations of carotid plaque in both groups were carotid bifurcation (CI group: 73.7%; control group: 64.1%),common carotid artery (CI group: 20.4%; control group: 25.6%),and internal carotid artery (CI group: 5.9%; control group: 10.3%). The location of carotid plaque between the two groups was not significantly different (P=0.438). There was no difference in the carotid inner diameter or resistance index between the two groups (P>0.05). Conclusions Carotid atherosclerosis is to some extent able to reveal the atherosclerotic condition of cerebral arteries and act as an important predictor for the risk of CI. The color Doppler ultrasonography of carotid 展开更多
Gastric cancer(GC) is one of the most prevalent malignant types in the world and an aggressive disease with a poor 5-year survival. This cancer is biologically and genetically heterogeneous with a poorly understood ca...Gastric cancer(GC) is one of the most prevalent malignant types in the world and an aggressive disease with a poor 5-year survival. This cancer is biologically and genetically heterogeneous with a poorly understood carcinogenesis at the molecular level. Although the incidence is declining, the outcome of patients with GC remains dismal. Thus, the detection at an early stage utilizing useful screening approaches, selection of an appropriate treatment plan, and effective monitoring is pivotal to reduce GC mortalities. Identification of biomarkers in a basis of clinical information and comprehensive genome analysis could improve diagnosis, prognosis, prediction of recurrence and treatment response. This review summarized the current status and approaches in GC biomarker, which could be potentially used for early diagnosis, accurate prediction of therapeutic approaches and discussed the future perspective based on the molecular classification and profiling.展开更多
China’s population has rapidly aged over the recent decades of social and economic development as neurodegenerative disorders have proliferated,especially Alzheimer’s disease(AD)and related dementias(ADRD).AD’s inc...China’s population has rapidly aged over the recent decades of social and economic development as neurodegenerative disorders have proliferated,especially Alzheimer’s disease(AD)and related dementias(ADRD).AD’s incidence rate,morbidity,and mortality have steadily increased to make it presently the fifth leading cause of death among urban and rural residents in China and magnify the resulting financial burdens on individuals,families and society.The‘Healthy China Action’plan of 2019-2030 promotes the transition from disease treatment to health maintenance for this expanding population with ADRD.This report describes related epidemiological trends,evaluates the economic burden of the disease,outlines current clinical diagnosis and treatment status and delineates existing available public health resources.More specifically,it examines the public health impact of ADRD,including prevalence,mortality,costs,usage of care,and the overall effect on caregivers and society.In addition,this special report presents technical guidance and supports for the prevention and treatment of AD,provides expertise to guide relevant governmental healthcare policy development and suggests an information platform for international exchange and cooperation.展开更多
Non-alcoholic fatty liver disease(NAFLD) is now the most frequent chronic liver disease that occurs across all age groups and is recognized to occur in 14%-30% of the general population, representing a serious and gro...Non-alcoholic fatty liver disease(NAFLD) is now the most frequent chronic liver disease that occurs across all age groups and is recognized to occur in 14%-30% of the general population, representing a serious and growing clinical problem due to the growing prevalence of obesity and overweight. Histologically, it resembles alcoholic liver injury but occurs in patients who deny significant alcohol consumption. NAFLD encompasses a spectrum of conditions, ranging from benign hepatocellular steatosisto inflammatory nonalcoholic steatohepatitis, fibrosis, and cirrhosis. The majority of hepatocellular lipids are stored as triglycerides, but other lipid metabolites, such as free fatty acids, cholesterol, and phospholipids, may also be present and play a role in disease progression. NAFLD is associated with obesity and insulin resistance and is considered the hepatic manifestation of the metabolic syndrome, a combination of medical conditions including type 2 diabetes mellitus, hypertension, hyperlipidemia, and visceral adiposity. Confirmation of the diagnosis of NAFLD can usually be achieved by imaging studies; however, staging the disease requires a liver biopsy. Current treatment relies on weight loss and exercise, although various insulin-sensitizing agents, antioxidants and medications appear promising. The aim of this review is to highlight the current information regarding epidemiology, diagnosis, and management of NAFLD as well as new information about pathogenesis, diagnosis and management of this disease.展开更多
The association between ulcerative colitis(UC) and colorectal cancer(CRC) has been acknowledged. One of the most serious and life threatening consequences of UC is the development of CRC(UC-CRC). UC-CRC patients are y...The association between ulcerative colitis(UC) and colorectal cancer(CRC) has been acknowledged. One of the most serious and life threatening consequences of UC is the development of CRC(UC-CRC). UC-CRC patients are younger, more frequently have multiple cancerous lesions, and histologically show mucinous or signet ring cell carcinomas. The risk of CRC begins to increase 8 or 10 years after the diagnosis of UC. Risk factors for CRC with UC patients include young age at diagnosis, longer duration, greater anatomical extent of colonic involvement, the degree of inflammation, family history of CRC, and presence of primary sclerosing cholangitis. CRC on the ground of UC develop from non-dysplastic mucosa to indefinite dysplasia, lowgrade dysplasia, high-grade dysplasia and finally to invasive adenocarcinoma. Colonoscopy surveillance programs are recommended to reduce the risk of CRC and mortality in UC. Genetic alterations might play a role in the development of UC-CRC. 5-aminosalicylates might represent a favorable therapeutic option for chemoprevention of CRC.展开更多
Objective Evidence suggests that type 2 diabetes （T2DM） is associated with an increased risk of dementia and that glucose variability is an independent risk factor for diabetic complications. This study investigated...Objective Evidence suggests that type 2 diabetes （T2DM） is associated with an increased risk of dementia and that glucose variability is an independent risk factor for diabetic complications. This study investigated the relationship between glucose excursion and cognitive function in aged T2DM patients. Methods A total of 248 aged T2DM patients wore a continuous glucose monitoring system （CGMS） for 3 days in order to evaluate glucose excursion, including mean amplitude of glycemic excursions （MAGE） and mean of daily difference （MODD）. All subjects were evaluated with a number of accepted cognitive function tests, including the mini-mental status examination （MMSE）. The relationship between MAGE and MODD and performance on these cognitive tests was assessed. Results The MAGE and MMSE score were negatively correlated, likewise with the correlation between MODD and MMSE. Liner multivariate regression analysis showed that MAGE and MODD were also negatively related to MMSE independent of age, sex, glycemic control, hypertension, smoking, or coronary heart disease history. Conclusion Glucose excursion is related to cognitive function in aged T2DM patients. Elevated glucose excursion decreased the MMSE score, which reflects general cognitive function. Thus, therapy aimed at controlling glucose excursion may be beneficial for maintaining cognitive function in aged T2DM patients.展开更多
Although the treatment of myocardial infarction(MI)has improved considerably,it is still a worldwide disease with high morbidity and high mortality.Whilst there is still a long way to go for discovering ideal treatmen...Although the treatment of myocardial infarction(MI)has improved considerably,it is still a worldwide disease with high morbidity and high mortality.Whilst there is still a long way to go for discovering ideal treatments,therapeutic strategies committed to cardioprotection and cardiac repair following cardiac ischemia are emerging.Evidence of pathological characteristics in MI illustrates cell signaling pathways that participate in the survival,proliferation,apoptosis,autophagy of cardiomyocytes,endothelial cells,fibroblasts,monocytes,and stem cells.These signaling pathways include the key players in inflammation response,e.g.,NLRP3/caspase-1 and TLR4/MyD88/NF-κB;the crucial mediators in oxidative stress and apoptosis,for instance,Notch,Hippo/YAP,RhoA/ROCK,Nrf2/HO-1,and Sonic hedgehog;the controller of myocardial fibrosis such as TGF-β/SMADs and Wnt/β-catenin;and the main regulator of angiogenesis,PI3K/Akt,MAPK,JAK/STAT,Sonic hedgehog,etc.Since signaling pathways play an important role in administering the process of MI,aiming at targeting these aberrant signaling pathways and improving the pathological manifestations in MI is indispensable and promising.Hence,drug therapy,gene therapy,protein therapy,cell therapy,and exosome therapy have been emerging and are known as novel therapies.In this review,we summarize the therapeutic strategies for MI by regulating these associated pathways,which contribute to inhibiting cardiomyocytes death,attenuating inflammation,enhancing angiogenesis,etc.so as to repair and re-functionalize damaged hearts.展开更多
Programmed cell death-1(PD-1)/programmed cell death ligand-1(PD-L1)blocking therapy has become a major pillar of cancer immunotherapy.Compared with antibodies targeting,small-molecule checkpoint inhibitors which have ...Programmed cell death-1(PD-1)/programmed cell death ligand-1(PD-L1)blocking therapy has become a major pillar of cancer immunotherapy.Compared with antibodies targeting,small-molecule checkpoint inhibitors which have favorable pharmacokinetics are urgently needed.Here we identified berberine(BBR),a proven anti-inflammation drug,as a negative regulator of PDL1 from a set of traditional Chinese medicine(TCM)chemical monomers.BBR enhanced the sensitivity of tumour cells to co-cultured T-cells by decreasing the level of PD-L1 in cancer cells.In addition,BBR exerted its antitumor effect in Lewis tumor xenograft mice through enhancing tumorinfiltrating T-cell immunity and attenuating the activation of immunosuppressive myeloid-derived suppressor cells(MDSCs)and regulatory T-cells(Tregs).BBR triggered PD-L1 degradation through ubiquitin(Ub)/proteasome-dependent pathway.Remarkably,BBR selectively bound to the glutamic acid76 of constitutive photomorphogenic-9 signalosome 5(CSN5)and inhibited PD-1/PD-L1 axis through its deubiquitination activity,resulting in ubiquitination and degradation of PD-L1.Our data reveals a previously unrecognized antitumor mechanism of BBR,suggesting BBR is small-molecule immune checkpoint inhibitor for cancer treatment.展开更多
Non-enzymatic chitinase-3 like-protein-1(CHI3L1)belongs to glycoside hydrolase family 18.It binds to chitin,heparin,and hyaluronic acid,and is regulated by extracellular matrix changes,cytokines,growth factors,drugs,a...Non-enzymatic chitinase-3 like-protein-1(CHI3L1)belongs to glycoside hydrolase family 18.It binds to chitin,heparin,and hyaluronic acid,and is regulated by extracellular matrix changes,cytokines,growth factors,drugs,and stress.CHI3L1 is synthesized and secreted by a multitude of cells including macrophages,neutrophils,synoviocytes,chondrocytes,fibroblast-like cells,smooth muscle cells,and tumor cells.It plays a major role in tissue injury,inflammation,tissue repair,and remodeling responses.CHI3L1 has been strongly associated with diseases including asthma,arthritis,sepsis,diabetes,liver fibrosis,and coronary artery disease.Moreover,following its initial identification in the culture supernatant of the MG63 osteosarcoma cell line,CHI3L1 has been shown to be overexpressed in a wealth of both human cancers and animal tumor models.To date,interleukin-13 receptor subunit alpha-2,transmembrane protein 219,galectin-3,chemo-attractant receptor-homologous 2,and CD44 have been identified as CHI3L1 receptors.CHI3L1 signaling plays a critical role in cancer cell growth,proliferation,invasion,metastasis,angiogenesis,activation of tumor-associated macrophages,and Th2 polarization of CD4+T cells.Interestingly,CHI3L1-based targeted therapy has been increasingly applied to the treatment of tumors including glioma and colon cancer as well as rheumatoid arthritis.This review summarizes the potential roles and mechanisms of CHI3L1 in oncogenesis and disease pathogenesis,then posits investigational strategies for targeted therapies.展开更多
Background Insulin treatment plays a key role in management of diabetes mellitus. Clinical researches showed that extra improvements in restoration of insulin secretion of pancreatic β cells were found in patients w...Background Insulin treatment plays a key role in management of diabetes mellitus. Clinical researches showed that extra improvements in restoration of insulin secretion of pancreatic β cells were found in patients with newly diagnosed type 2 diabetes. The purpose of this study was to investigate the effects of early insulin treatment on insulin mRNA expression and morphological alterations of β cells in a Sprague Dawley (SD) rat model of type 2 diabetes. Methods A rat model of type 2 diabetes mellitus (T2DM) was induced by a high fat diet (high energy, HE) and low doses of streptozotoxin (STZ, 40 mg/kg). A group of diabetic rats was then injected with protamine zinc insulin (PZI, 1-2 U·kg -1·d -1) for one week. Insulin mRNA expression, morphological features of pancreatic islets, and metabolic parameters were examined in rats using reverse transcriptase-polymerase chain reaction (RT-PCR), immunohistochemistry, and other techniques. Results In insulin-treated diabetic rats, insulin mRNA levels prominently increased by 81.3% (P<0.05), as compared with untreated diabetic rats. Moreover, timely insulin treatment noticeably improved the insulin content of β cells, with an increase of 10.2% (P<0.05), despite a slight reduction in fasting blood glucose (FBG), triglyceride (TG), and free fatty acid (FFA) levels, as compared to an untreated diabetic group. Conclusion Insulin treatment at the onset of T2DM effectively improves insulin synthesis, as confirmed by morphological changes to β cells in a rat model of type 2 diabetes.展开更多
Background Fall and serious fall injuries have become a major health concern for elders. Many factors including blood pressure and anti-hypertensive medication application were reported as hazards of fall. The purpose...Background Fall and serious fall injuries have become a major health concern for elders. Many factors including blood pressure and anti-hypertensive medication application were reported as hazards of fall. The purpose of this study was to determine if age related systemic functional decline related with increased fall risks in elderly patients with hypertension. Methods A total of 342 elderly hypertension patients （age 79.5 ＋ 6.7 years, male 63.8%） were recruited to the study. Comprehensive geriatric assessment （CGA）, including measurements about activity of daily living （ADL）, nutrition, cognition, depression, numbers of prescription medication and number of clinical diagnosis, was conducted to evaluate the physical and mental status of each participants. Fall risk was evaluated by Morse fall scale, Tinetti perform- ance oriented mobility assessment （POMA） and history of fall in the recent years. Participants were grouped into tertiles according to CGA score. Correlation between CGA and fall risk was analyzed through SPSS 18.0. Results Participants with higher CGA score were likely to be older, had a lower body mass index （BMI）, and a higher prevalence of cardiovascular disease, chronic obstructive pulmonary disease （COPD）, cerebrovascular disease and osteoarthropathia. Participants in higher tertile of CGA score got increased prevalence of fall risk than those in lower tertile （P 〈 0.01 T3 vs. T1, P 〈 0.01 T3 vs. T2）. Correlation analysis and regression analysis showed significant association between CGA and Morse fall scale （P 〈 0.001）, as well as CGA and POMA （P 〈 0.001）. Meanwhile, CGA components also showed co-relationships with increase fall risks. After adjusting age, BMI, benzodiazepine use, cardiovascular disease, cerebrovascular disease, COPD and osteoarthropathia, both history of fall in the recent year and rising Morse fall scale were significantly associated with ADL im- pairment （OR： 2.748, 95%CI： 1.598-4.725）, （OR： 3.310, 95%CI： 1.893-5.7展开更多
Dysregulation of mi R-124 has been reported to be involved in the pathophysiology of depression. Chaihu-Shugan-San, a traditional Chinese medicine, has antidepressive activity; however, the underlying mechanisms remai...Dysregulation of mi R-124 has been reported to be involved in the pathophysiology of depression. Chaihu-Shugan-San, a traditional Chinese medicine, has antidepressive activity; however, the underlying mechanisms remain unclear. In this study, to generate a rodent model of depression, rats were subjected to a combination of solitary confinement and chronic unpredictable mild stress for 28 days. Rats were intragastrically administered Chaihu-Shugan-San（2.835 m L/kg/d） for 4 weeks, once a day. Real-time reverse-transcription quantitative polymerase chain reaction, mi RNA microarray, western blot assay and transmission electron microscopy demonstrated that ChaihuShugan-San downregulated mi R-124 expression and upregulated the m RNA and protein levels of mitogen-activated protein kinase 14（MAPK14） and glutamate receptor subunit 3（Gria3）. Chaihu-Shugan-San also promoted synapse formation in the hippocampus. The open field test, sucrose consumption test and forced swimming test were used to assess depression-like behavior. After intragastric administration of Chaihu-Shugan-San, sucrose consumption increased, while the depressive behaviors were substantially reduced. Together, these findings suggest that Chaihu-Shugan-San exerts an antidepressant-like effect by downregulating mi R-124 expression and by releasing the inhibition of the MAPK14 and Gria3 signaling pathways.展开更多
In addition to its lipid-lowering effect, atorvastatin exerts anti-inflammatory and antioxidant effects as well. In this study, we hypothesized that atorvastatin could protect against cerebral isch-emia/reperfusion in...In addition to its lipid-lowering effect, atorvastatin exerts anti-inflammatory and antioxidant effects as well. In this study, we hypothesized that atorvastatin could protect against cerebral isch-emia/reperfusion injury. The middle cerebral artery ischemia/reperfusion model was established, and atorvastatin, 6.5 mg/kg, was administered by gavage. We found that, after cerebral ischemia/ reperfusion injury, levels of the inflammation-related factors E-selectin and myeloperoxidase were upregulated, the oxidative stress-related marker malondialdehyde was increased, and super- oxide dismutase activity was decreased in the ischemic cerebral cortex. Atorvastatin pretreatment significantly inhibited these changes. Our findings indicate that atorvastatin protects against ce-rebral ischemia/reperfusion injury through anti-inflammatory and antioxidant effects.展开更多
Chronic heart failure （CHF） is a highly prevalent condition among the elderly and is associated with considerable morbidity, institution-alization and mortality. In its advanced stages, CHF is often accompanied by t...Chronic heart failure （CHF） is a highly prevalent condition among the elderly and is associated with considerable morbidity, institution-alization and mortality. In its advanced stages, CHF is often accompanied by the loss of muscle mass and strength. Sarcopenia is a geriatric syndrome that has been actively studied in recent years due to its association with a wide range of adverse health outcomes. The goal of this review is to discuss the relationship between CHF and sarcopenia, with a focus on shared pathophysiological pathways and treatments. Mal- nutrition, systemic inflammation, endocrine imbalances, and oxidative stress appear to connect sarcopenia and CHF. At the muscular level, alterations of the ubiquitin proteasome system, myostatin signaling, and apoptosis have been described in both sarcopenia and CHF and could play a role in the loss of muscle mass and function. Possible therapeutic strategies to impede the progression of muscle wasting in CHF patients include protein and vitamin D supplementation, structured physical exercise, and the administration of angiotensin-converting enzyme inhibitors and β-blockers. Hormonal supplementation with growth hormone, testosterone, and ghrelin is also discussed as a potential treatment.展开更多
Pyroptosis is a form of programmed cell death mediated by gasdermin and is a product of continuous cell expansion until the cytomembrane ruptures,resulting in the release of cellular contents that can activate strong ...Pyroptosis is a form of programmed cell death mediated by gasdermin and is a product of continuous cell expansion until the cytomembrane ruptures,resulting in the release of cellular contents that can activate strong inflammatory and immune responses.Pyroptosis,an innate immune response,can be triggered by the activation of inflammasomes by various influencing factors.Activation of these inflammasomes can induce the maturation of caspase-1 or caspase-4/5/11,both of which cleave gasdermin D to release its N-terminal domain,which can bind membrane lipids and perforate the cell membrane.Here,we review the latest advancements in research on the mechanisms of pyroptosis,newly discovered influencing factors,antitumoral properties,and applications in various diseases.Moreover,this review also provides updates on potential targeted therapies for inflammation and cancers,methods for clinical prevention,and finally challenges and future directions in the field.展开更多
A total of 64 patients with acute lacunar infarction were enrolled within 24 hours of onset. The patients received conventional therapy （antiplatelet drugs and hypolipidemic drugs） alone or conventional therapy plus...A total of 64 patients with acute lacunar infarction were enrolled within 24 hours of onset. The patients received conventional therapy （antiplatelet drugs and hypolipidemic drugs） alone or conventional therapy plus 450 mg Xueshuantong once a day. The main ingredient of the Xueshuantong lyophilized powder used for injection was Panax notoginseng saponins. Assessments were made at admission and at discharge using the National Institutes of Health Stroke Scale, the Activity of Daily Living and the Mini-Mental State Examination. Additionally, the relative cerebral blood flow, relative cerebral blood volume and relative mean transit time in the region of interest were calculated within 24 hours after the onset of lacunar infarction, using dynamic susceptibility contrast magnetic resonance perfusion imaging technology. Patients underwent a follow-up MRI scan after 4 weeks of treatment. There was an improvement in the Activity of Daily Living scores and a greater reduction in the scores on the National Institutes of Health Stroke Scale in the treatment group than in the control group. However, the Mini-Mental State Examination scores showed no significant differences after 4 weeks of treatment. Compared with the control group, the relative cerebral blood flow at discharge had increased and showed a greater improvement in the treatment group. Furthermore, there was a reduction in the relative mean transit time at discharge and the value was lower in the treatment group than in the control group. The experimental findings indicate that Xueshuantong treatment improves neurological deficits in elderly patients with lacunar infarction, and the mechanism may be related to increased cerebral perfusion.展开更多
Background The existence of neurogenesis in the hippocampus of adult nonhuman primates has been confirmed in recent years, however, the biological properties of adult neural stem cells or neural progenitor cells （NPC...Background The existence of neurogenesis in the hippocampus of adult nonhuman primates has been confirmed in recent years, however, the biological properties of adult neural stem cells or neural progenitor cells （NPCs） from this region remain to be extensively explored. The present work was to investigate on the expansion of NSCs/NPCs from the hippocampus of adult cynomolgus monkeys and the examination of their characteristics in vitro. Methods NPCs isolated from the hippocampus of adult cynomolgus monkeys were expanded in vitro in serum-free media containing growth factors, and were then allowed to differentiate by removing mitotic factors. The expansion capacity of NPCs and their differentiation potential were assayed by immunohistochemical and immunocytochemical analysis. Results During primary culture, NPCs underwent cell division, proliferation and aggregation to form neurospheres that were growing in suspension. Without mitotic stimulation, most neurospheres adhered to the culture dish and started to differentiate. Eventually, nearly 12% of the differentiated cells expressed neuron specific marker-β Ⅲ-tubulin （Tuj1） and 84% expressed astrocyte specific marker-fibrillary acidic protein （GFAP）. In addition, the expression of a neural stem cell marker, nestin, was found both in NPCs and in the subgranular zone of adult monkey hippocampus, where NPCs were originally derived. Conclusions NPCs from the hippocampus of adult cynomolgus monkeys can be expanded to some extent in vitro and are capable of differentiating into neurons and astrocytes. Further experiments to promote the in vitro proliferation capacity of NPCs will be required before adult NPCs can be used as a useful cell model for studying adult neurogenesis and cell replacement therapy using adult stem cells.展开更多
Objective：To review recent research advances on tau,a major player in Alzheimer＇s disease （AD） pathogenesis,a biomarker for AD onset,and potential target for AD therapy.Data Sources：This review was based on a com...Objective：To review recent research advances on tau,a major player in Alzheimer＇s disease （AD） pathogenesis,a biomarker for AD onset,and potential target for AD therapy.Data Sources：This review was based on a comprehensive search using online literature databases,including PubMed,Web of Science,and Google Scholar.Study Selection：Literature search was based on the following keywords：Alzheimer＇s disease,tau protein,biomarker,cerebrospinal fluid （CSF）,therapeutics,plasma,imaging,propagation,spreading,seeding,prion,conformational templating,and posttranslational modification.Relevant articles were carefully reviewed,with no exclusions applied to study design and publication type.Results：Amyloid plaques enriched with extracellular amyloid beta （Aβ） and intracellular neurofibrillary tangles comprised of hyperphosphorylated tau proteins are the two main pathological hallmarks ofAD.Although the Aβ hypothesis has dominated AD research for many years,clinical Aβ-targeting strategies have consistently failed to effectively treat AD or prevent AD onset.The research focus in AD has recently shifted to the role oftau in AD.In addition to phosphorylation,tau is acetylated and proteolytically cleaved,which also contribute to its physiological and pathological functions.Emerging evidence characterizing pathological tau propagation and spreading provides new avenues for research into the molecular and cellular mechanisms underlying AD pathogenesis.Techniques to detect tau at minute levels in CSF and blood have been developed,and improved tracers have facilitated tau imaging in the brain.These advances have potential to accurately determine tau levels at early diagnostic stages in AD.Given that tau is a potential therapeutic target,anti-tau immunotherapy may potentially be a viable treatment strategy in AD intervention.Conclusion：Detecting changes in tau and targeting tau pathology represent a promising lead in the diagnosis and treatment of AD.展开更多
基金supported by the Ministry of Science and Technology of China(the National Key Research and Development Program 2016YFA0502203,2019YFA0110201,and 2019YFA0110203)the National Natural Science Foundation of China(91740111,81871232,and 31870881),1.3.5 Project of disciplines of excellence and National Clinical Research Center for Geriatrics(Z2020001),West China Hospital,Sichuan University.
文摘NF-κB pathway consists of canonical and non-canonical pathways.The canonical NF-κB is activated by various stimuli,transducing a quick but transient transcriptional activity,to regulate the expression of various proinflammatory genes and also serve as the critical mediator for inflammatory response.Meanwhile,the activation of the non-canonical NF-κB pathway occurs through a handful of TNF receptor superfamily members.Since the activation of this pathway involves protein synthesis,the kinetics of non-canonical NF-κB activation is slow but persistent,in concordance with its biological functions in the development of immune cell and lymphoid organ,immune homeostasis and immune response.The activation of the canonical and non-canonical NF-κB pathway is tightly controlled,highlighting the vital roles of ubiquitination in these pathways.Emerging studies indicate that dysregulated NF-κB activity causes inflammation-related diseases as well as cancers,and NF-κB has been long proposed as the potential target for therapy of diseases.This review attempts to summarize our current knowledge and updates on the mechanisms of NF-κB pathway regulation and the potential therapeutic application of inhibition of NF-κB signaling in cancer and inflammatory diseases.
文摘Objective To study the relationship between carotid atherosclerosis and cerebral infarction (CI). Methods Between November 2008 and March 2009,147 CI patients (CI group) and 48 patients with non-cerebrovascular diseases (control group) were enrolled from inpatients of Neurology Department of our hospital. The diagnostic criterion of thickened carotid intima was set as 1.0 mm≤intima-media thickness (IMT) <1.5 mm and that of carotid plaque was as IMT≥1.5 mm. Carotid atherosclerosis was divided into three levels: normal intima,thickened intima,and plaque formation. The color Doppler ultrasonography data of carotid arteries in all patients were analyzed and the severity of carotid atherosclerosis was compared between the two groups. Results In the CI group,36 (24.5%) patients had normal carotid intima,22 (15.0%) had thickened carotid intima,and 89 (60.5%) had carotid plaque. In the control group,22 (45.8%) patients had normal carotid intima,4 (8.3%) had thickened carotid intima,and 22 (45.8%) had carotid plaque. The severity of carotid atherosclerosis in the CI group was higher than that in the control group (P=0.022). There was significant difference in the constitution of carotid plaque between the two groups (P=0.001); the CI group mainly had the soft plaque (55/89,61.8%),whereas the control group mainly had the hard plaque (17/22,77.3%). The first three common locations of carotid plaque in both groups were carotid bifurcation (CI group: 73.7%; control group: 64.1%),common carotid artery (CI group: 20.4%; control group: 25.6%),and internal carotid artery (CI group: 5.9%; control group: 10.3%). The location of carotid plaque between the two groups was not significantly different (P=0.438). There was no difference in the carotid inner diameter or resistance index between the two groups (P>0.05). Conclusions Carotid atherosclerosis is to some extent able to reveal the atherosclerotic condition of cerebral arteries and act as an important predictor for the risk of CI. The color Doppler ultrasonography of carotid
文摘Gastric cancer(GC) is one of the most prevalent malignant types in the world and an aggressive disease with a poor 5-year survival. This cancer is biologically and genetically heterogeneous with a poorly understood carcinogenesis at the molecular level. Although the incidence is declining, the outcome of patients with GC remains dismal. Thus, the detection at an early stage utilizing useful screening approaches, selection of an appropriate treatment plan, and effective monitoring is pivotal to reduce GC mortalities. Identification of biomarkers in a basis of clinical information and comprehensive genome analysis could improve diagnosis, prognosis, prediction of recurrence and treatment response. This review summarized the current status and approaches in GC biomarker, which could be potentially used for early diagnosis, accurate prediction of therapeutic approaches and discussed the future perspective based on the molecular classification and profiling.
基金This report was supported by a grant from Brain Science and Brain-Like Intelligence Technology of the Ministry of Science and Technology of China(2021ZD0201804).
文摘China’s population has rapidly aged over the recent decades of social and economic development as neurodegenerative disorders have proliferated,especially Alzheimer’s disease(AD)and related dementias(ADRD).AD’s incidence rate,morbidity,and mortality have steadily increased to make it presently the fifth leading cause of death among urban and rural residents in China and magnify the resulting financial burdens on individuals,families and society.The‘Healthy China Action’plan of 2019-2030 promotes the transition from disease treatment to health maintenance for this expanding population with ADRD.This report describes related epidemiological trends,evaluates the economic burden of the disease,outlines current clinical diagnosis and treatment status and delineates existing available public health resources.More specifically,it examines the public health impact of ADRD,including prevalence,mortality,costs,usage of care,and the overall effect on caregivers and society.In addition,this special report presents technical guidance and supports for the prevention and treatment of AD,provides expertise to guide relevant governmental healthcare policy development and suggests an information platform for international exchange and cooperation.
基金美国国家卫生研究院项目基金（R21-AG-043874,R01A1108907）,厄玛和保罗米尔斯坦老年健康专项奖学金（Irma and Paul Milstein Program for Senior Health fellowship）,米尔斯坦亚美医学基金会（ Milstein Medical Asian American Partnership （MMAAP） Foundation）
文摘Non-alcoholic fatty liver disease(NAFLD) is now the most frequent chronic liver disease that occurs across all age groups and is recognized to occur in 14%-30% of the general population, representing a serious and growing clinical problem due to the growing prevalence of obesity and overweight. Histologically, it resembles alcoholic liver injury but occurs in patients who deny significant alcohol consumption. NAFLD encompasses a spectrum of conditions, ranging from benign hepatocellular steatosisto inflammatory nonalcoholic steatohepatitis, fibrosis, and cirrhosis. The majority of hepatocellular lipids are stored as triglycerides, but other lipid metabolites, such as free fatty acids, cholesterol, and phospholipids, may also be present and play a role in disease progression. NAFLD is associated with obesity and insulin resistance and is considered the hepatic manifestation of the metabolic syndrome, a combination of medical conditions including type 2 diabetes mellitus, hypertension, hyperlipidemia, and visceral adiposity. Confirmation of the diagnosis of NAFLD can usually be achieved by imaging studies; however, staging the disease requires a liver biopsy. Current treatment relies on weight loss and exercise, although various insulin-sensitizing agents, antioxidants and medications appear promising. The aim of this review is to highlight the current information regarding epidemiology, diagnosis, and management of NAFLD as well as new information about pathogenesis, diagnosis and management of this disease.
文摘The association between ulcerative colitis(UC) and colorectal cancer(CRC) has been acknowledged. One of the most serious and life threatening consequences of UC is the development of CRC(UC-CRC). UC-CRC patients are younger, more frequently have multiple cancerous lesions, and histologically show mucinous or signet ring cell carcinomas. The risk of CRC begins to increase 8 or 10 years after the diagnosis of UC. Risk factors for CRC with UC patients include young age at diagnosis, longer duration, greater anatomical extent of colonic involvement, the degree of inflammation, family history of CRC, and presence of primary sclerosing cholangitis. CRC on the ground of UC develop from non-dysplastic mucosa to indefinite dysplasia, lowgrade dysplasia, high-grade dysplasia and finally to invasive adenocarcinoma. Colonoscopy surveillance programs are recommended to reduce the risk of CRC and mortality in UC. Genetic alterations might play a role in the development of UC-CRC. 5-aminosalicylates might represent a favorable therapeutic option for chemoprevention of CRC.
基金funded by the Medical College Natural Science Foundation of Shanghai Jiaotong University (09XJ21028)
文摘Objective Evidence suggests that type 2 diabetes （T2DM） is associated with an increased risk of dementia and that glucose variability is an independent risk factor for diabetic complications. This study investigated the relationship between glucose excursion and cognitive function in aged T2DM patients. Methods A total of 248 aged T2DM patients wore a continuous glucose monitoring system （CGMS） for 3 days in order to evaluate glucose excursion, including mean amplitude of glycemic excursions （MAGE） and mean of daily difference （MODD）. All subjects were evaluated with a number of accepted cognitive function tests, including the mini-mental status examination （MMSE）. The relationship between MAGE and MODD and performance on these cognitive tests was assessed. Results The MAGE and MMSE score were negatively correlated, likewise with the correlation between MODD and MMSE. Liner multivariate regression analysis showed that MAGE and MODD were also negatively related to MMSE independent of age, sex, glycemic control, hypertension, smoking, or coronary heart disease history. Conclusion Glucose excursion is related to cognitive function in aged T2DM patients. Elevated glucose excursion decreased the MMSE score, which reflects general cognitive function. Thus, therapy aimed at controlling glucose excursion may be beneficial for maintaining cognitive function in aged T2DM patients.
基金National Natural Science Foundation of China(Grant No.82172534)National Key R&D Program of China(Grant No.2020YFC2008502)1·3·5 Project for Disciplines of Excellence,West China Hospital,Sichuan University.
文摘Although the treatment of myocardial infarction(MI)has improved considerably,it is still a worldwide disease with high morbidity and high mortality.Whilst there is still a long way to go for discovering ideal treatments,therapeutic strategies committed to cardioprotection and cardiac repair following cardiac ischemia are emerging.Evidence of pathological characteristics in MI illustrates cell signaling pathways that participate in the survival,proliferation,apoptosis,autophagy of cardiomyocytes,endothelial cells,fibroblasts,monocytes,and stem cells.These signaling pathways include the key players in inflammation response,e.g.,NLRP3/caspase-1 and TLR4/MyD88/NF-κB;the crucial mediators in oxidative stress and apoptosis,for instance,Notch,Hippo/YAP,RhoA/ROCK,Nrf2/HO-1,and Sonic hedgehog;the controller of myocardial fibrosis such as TGF-β/SMADs and Wnt/β-catenin;and the main regulator of angiogenesis,PI3K/Akt,MAPK,JAK/STAT,Sonic hedgehog,etc.Since signaling pathways play an important role in administering the process of MI,aiming at targeting these aberrant signaling pathways and improving the pathological manifestations in MI is indispensable and promising.Hence,drug therapy,gene therapy,protein therapy,cell therapy,and exosome therapy have been emerging and are known as novel therapies.In this review,we summarize the therapeutic strategies for MI by regulating these associated pathways,which contribute to inhibiting cardiomyocytes death,attenuating inflammation,enhancing angiogenesis,etc.so as to repair and re-functionalize damaged hearts.
基金supported by grants from National Natural Science Foundation of China(81973366,81773782 and 81903695)CAMS Innovation Fund for Medical Sciences(2016-12M-1-011,China)+2 种基金Open Project of State Key Laboratory of Bioactive Substance and Function of Natural Medicines(GTZK201908,China)National Mega-project for Innovative Drugs(2019ZX09721-001,China)Chinese Pharmaceutical Association-Yiling Pharmaceutical Innovation Fund for Biomedicine(GL-1-B04-20180366,China)
文摘Programmed cell death-1(PD-1)/programmed cell death ligand-1(PD-L1)blocking therapy has become a major pillar of cancer immunotherapy.Compared with antibodies targeting,small-molecule checkpoint inhibitors which have favorable pharmacokinetics are urgently needed.Here we identified berberine(BBR),a proven anti-inflammation drug,as a negative regulator of PDL1 from a set of traditional Chinese medicine(TCM)chemical monomers.BBR enhanced the sensitivity of tumour cells to co-cultured T-cells by decreasing the level of PD-L1 in cancer cells.In addition,BBR exerted its antitumor effect in Lewis tumor xenograft mice through enhancing tumorinfiltrating T-cell immunity and attenuating the activation of immunosuppressive myeloid-derived suppressor cells(MDSCs)and regulatory T-cells(Tregs).BBR triggered PD-L1 degradation through ubiquitin(Ub)/proteasome-dependent pathway.Remarkably,BBR selectively bound to the glutamic acid76 of constitutive photomorphogenic-9 signalosome 5(CSN5)and inhibited PD-1/PD-L1 axis through its deubiquitination activity,resulting in ubiquitination and degradation of PD-L1.Our data reveals a previously unrecognized antitumor mechanism of BBR,suggesting BBR is small-molecule immune checkpoint inhibitor for cancer treatment.
基金supported by Guangzhou key medical discipline construction project and the National Natural Science Foundation of China(grant numbers 81671543,81870409 to Q.Y.).
文摘Non-enzymatic chitinase-3 like-protein-1(CHI3L1)belongs to glycoside hydrolase family 18.It binds to chitin,heparin,and hyaluronic acid,and is regulated by extracellular matrix changes,cytokines,growth factors,drugs,and stress.CHI3L1 is synthesized and secreted by a multitude of cells including macrophages,neutrophils,synoviocytes,chondrocytes,fibroblast-like cells,smooth muscle cells,and tumor cells.It plays a major role in tissue injury,inflammation,tissue repair,and remodeling responses.CHI3L1 has been strongly associated with diseases including asthma,arthritis,sepsis,diabetes,liver fibrosis,and coronary artery disease.Moreover,following its initial identification in the culture supernatant of the MG63 osteosarcoma cell line,CHI3L1 has been shown to be overexpressed in a wealth of both human cancers and animal tumor models.To date,interleukin-13 receptor subunit alpha-2,transmembrane protein 219,galectin-3,chemo-attractant receptor-homologous 2,and CD44 have been identified as CHI3L1 receptors.CHI3L1 signaling plays a critical role in cancer cell growth,proliferation,invasion,metastasis,angiogenesis,activation of tumor-associated macrophages,and Th2 polarization of CD4+T cells.Interestingly,CHI3L1-based targeted therapy has been increasingly applied to the treatment of tumors including glioma and colon cancer as well as rheumatoid arthritis.This review summarizes the potential roles and mechanisms of CHI3L1 in oncogenesis and disease pathogenesis,then posits investigational strategies for targeted therapies.
文摘Background Insulin treatment plays a key role in management of diabetes mellitus. Clinical researches showed that extra improvements in restoration of insulin secretion of pancreatic β cells were found in patients with newly diagnosed type 2 diabetes. The purpose of this study was to investigate the effects of early insulin treatment on insulin mRNA expression and morphological alterations of β cells in a Sprague Dawley (SD) rat model of type 2 diabetes. Methods A rat model of type 2 diabetes mellitus (T2DM) was induced by a high fat diet (high energy, HE) and low doses of streptozotoxin (STZ, 40 mg/kg). A group of diabetic rats was then injected with protamine zinc insulin (PZI, 1-2 U·kg -1·d -1) for one week. Insulin mRNA expression, morphological features of pancreatic islets, and metabolic parameters were examined in rats using reverse transcriptase-polymerase chain reaction (RT-PCR), immunohistochemistry, and other techniques. Results In insulin-treated diabetic rats, insulin mRNA levels prominently increased by 81.3% (P<0.05), as compared with untreated diabetic rats. Moreover, timely insulin treatment noticeably improved the insulin content of β cells, with an increase of 10.2% (P<0.05), despite a slight reduction in fasting blood glucose (FBG), triglyceride (TG), and free fatty acid (FFA) levels, as compared to an untreated diabetic group. Conclusion Insulin treatment at the onset of T2DM effectively improves insulin synthesis, as confirmed by morphological changes to β cells in a rat model of type 2 diabetes.
文摘Background Fall and serious fall injuries have become a major health concern for elders. Many factors including blood pressure and anti-hypertensive medication application were reported as hazards of fall. The purpose of this study was to determine if age related systemic functional decline related with increased fall risks in elderly patients with hypertension. Methods A total of 342 elderly hypertension patients （age 79.5 ＋ 6.7 years, male 63.8%） were recruited to the study. Comprehensive geriatric assessment （CGA）, including measurements about activity of daily living （ADL）, nutrition, cognition, depression, numbers of prescription medication and number of clinical diagnosis, was conducted to evaluate the physical and mental status of each participants. Fall risk was evaluated by Morse fall scale, Tinetti perform- ance oriented mobility assessment （POMA） and history of fall in the recent years. Participants were grouped into tertiles according to CGA score. Correlation between CGA and fall risk was analyzed through SPSS 18.0. Results Participants with higher CGA score were likely to be older, had a lower body mass index （BMI）, and a higher prevalence of cardiovascular disease, chronic obstructive pulmonary disease （COPD）, cerebrovascular disease and osteoarthropathia. Participants in higher tertile of CGA score got increased prevalence of fall risk than those in lower tertile （P 〈 0.01 T3 vs. T1, P 〈 0.01 T3 vs. T2）. Correlation analysis and regression analysis showed significant association between CGA and Morse fall scale （P 〈 0.001）, as well as CGA and POMA （P 〈 0.001）. Meanwhile, CGA components also showed co-relationships with increase fall risks. After adjusting age, BMI, benzodiazepine use, cardiovascular disease, cerebrovascular disease, COPD and osteoarthropathia, both history of fall in the recent year and rising Morse fall scale were significantly associated with ADL im- pairment （OR： 2.748, 95%CI： 1.598-4.725）, （OR： 3.310, 95%CI： 1.893-5.7
基金supported by the National Natural Science Foundation of China,No.81503415,81574038,81603671the China Postdoctoral Science Foundation Grant,No.2016M600709+1 种基金a grant from the Science and Technology Planning Project of Guangdong Province of China,No.2014A020221062a grant from the Science and Technology Planning Project of Shenzhen City of China,No.JCYJ20150401170235349,JCYJ20160428105749954
文摘Dysregulation of mi R-124 has been reported to be involved in the pathophysiology of depression. Chaihu-Shugan-San, a traditional Chinese medicine, has antidepressive activity; however, the underlying mechanisms remain unclear. In this study, to generate a rodent model of depression, rats were subjected to a combination of solitary confinement and chronic unpredictable mild stress for 28 days. Rats were intragastrically administered Chaihu-Shugan-San（2.835 m L/kg/d） for 4 weeks, once a day. Real-time reverse-transcription quantitative polymerase chain reaction, mi RNA microarray, western blot assay and transmission electron microscopy demonstrated that ChaihuShugan-San downregulated mi R-124 expression and upregulated the m RNA and protein levels of mitogen-activated protein kinase 14（MAPK14） and glutamate receptor subunit 3（Gria3）. Chaihu-Shugan-San also promoted synapse formation in the hippocampus. The open field test, sucrose consumption test and forced swimming test were used to assess depression-like behavior. After intragastric administration of Chaihu-Shugan-San, sucrose consumption increased, while the depressive behaviors were substantially reduced. Together, these findings suggest that Chaihu-Shugan-San exerts an antidepressant-like effect by downregulating mi R-124 expression and by releasing the inhibition of the MAPK14 and Gria3 signaling pathways.
基金the Natural Science Foundation of Hunan Province in China,No.11JJ5081grants from Hunan Provincial Science and Technology Department in China,No.2012SK3226 and 2011SK3236the National Natural Science Foudation of China,No.81271298/H0906
文摘In addition to its lipid-lowering effect, atorvastatin exerts anti-inflammatory and antioxidant effects as well. In this study, we hypothesized that atorvastatin could protect against cerebral isch-emia/reperfusion injury. The middle cerebral artery ischemia/reperfusion model was established, and atorvastatin, 6.5 mg/kg, was administered by gavage. We found that, after cerebral ischemia/ reperfusion injury, levels of the inflammation-related factors E-selectin and myeloperoxidase were upregulated, the oxidative stress-related marker malondialdehyde was increased, and super- oxide dismutase activity was decreased in the ischemic cerebral cortex. Atorvastatin pretreatment significantly inhibited these changes. Our findings indicate that atorvastatin protects against ce-rebral ischemia/reperfusion injury through anti-inflammatory and antioxidant effects.
文摘Chronic heart failure （CHF） is a highly prevalent condition among the elderly and is associated with considerable morbidity, institution-alization and mortality. In its advanced stages, CHF is often accompanied by the loss of muscle mass and strength. Sarcopenia is a geriatric syndrome that has been actively studied in recent years due to its association with a wide range of adverse health outcomes. The goal of this review is to discuss the relationship between CHF and sarcopenia, with a focus on shared pathophysiological pathways and treatments. Mal- nutrition, systemic inflammation, endocrine imbalances, and oxidative stress appear to connect sarcopenia and CHF. At the muscular level, alterations of the ubiquitin proteasome system, myostatin signaling, and apoptosis have been described in both sarcopenia and CHF and could play a role in the loss of muscle mass and function. Possible therapeutic strategies to impede the progression of muscle wasting in CHF patients include protein and vitamin D supplementation, structured physical exercise, and the administration of angiotensin-converting enzyme inhibitors and β-blockers. Hormonal supplementation with growth hormone, testosterone, and ghrelin is also discussed as a potential treatment.
基金This work was supported by a special program from the National Key Research and Development Program of China(2021YFA1101000 to LZ)the Chinese National Natural Science Funds(U20A201376,U20A20393,and 31925013 to LZ,82041009,31871405,and 32125016 to FZ,92169122 and 31701232 to FX,32025011 to FW,31822031,31970664,31961160725 to JH and TL)+3 种基金the Science and Technology Plan Project of Suzhou(SYS2019020 to FX)the Jiangsu National Science Foundation(BK20180043 to FZ)Natural Science Foundation of Zhejiang Province(LZ19C070001 to FW)the Key Project of University Natural Science Foundation of Jiangsu Province(19KJA550003 to FZ).
文摘Pyroptosis is a form of programmed cell death mediated by gasdermin and is a product of continuous cell expansion until the cytomembrane ruptures,resulting in the release of cellular contents that can activate strong inflammatory and immune responses.Pyroptosis,an innate immune response,can be triggered by the activation of inflammasomes by various influencing factors.Activation of these inflammasomes can induce the maturation of caspase-1 or caspase-4/5/11,both of which cleave gasdermin D to release its N-terminal domain,which can bind membrane lipids and perforate the cell membrane.Here,we review the latest advancements in research on the mechanisms of pyroptosis,newly discovered influencing factors,antitumoral properties,and applications in various diseases.Moreover,this review also provides updates on potential targeted therapies for inflammation and cancers,methods for clinical prevention,and finally challenges and future directions in the field.
基金supported by the Technological Foundation Project of Traditional Chinese Medicine Science of Zhejiang Province,No.2012ZA077
文摘A total of 64 patients with acute lacunar infarction were enrolled within 24 hours of onset. The patients received conventional therapy （antiplatelet drugs and hypolipidemic drugs） alone or conventional therapy plus 450 mg Xueshuantong once a day. The main ingredient of the Xueshuantong lyophilized powder used for injection was Panax notoginseng saponins. Assessments were made at admission and at discharge using the National Institutes of Health Stroke Scale, the Activity of Daily Living and the Mini-Mental State Examination. Additionally, the relative cerebral blood flow, relative cerebral blood volume and relative mean transit time in the region of interest were calculated within 24 hours after the onset of lacunar infarction, using dynamic susceptibility contrast magnetic resonance perfusion imaging technology. Patients underwent a follow-up MRI scan after 4 weeks of treatment. There was an improvement in the Activity of Daily Living scores and a greater reduction in the scores on the National Institutes of Health Stroke Scale in the treatment group than in the control group. However, the Mini-Mental State Examination scores showed no significant differences after 4 weeks of treatment. Compared with the control group, the relative cerebral blood flow at discharge had increased and showed a greater improvement in the treatment group. Furthermore, there was a reduction in the relative mean transit time at discharge and the value was lower in the treatment group than in the control group. The experimental findings indicate that Xueshuantong treatment improves neurological deficits in elderly patients with lacunar infarction, and the mechanism may be related to increased cerebral perfusion.
基金This work was supported by grants from the National Basic Research Program of China (No.973, 2001CB510104), National Natural Science Foundation of China (No. 30460141), and Program for New Century Excellent Talents in University (2005).
文摘Background The existence of neurogenesis in the hippocampus of adult nonhuman primates has been confirmed in recent years, however, the biological properties of adult neural stem cells or neural progenitor cells （NPCs） from this region remain to be extensively explored. The present work was to investigate on the expansion of NSCs/NPCs from the hippocampus of adult cynomolgus monkeys and the examination of their characteristics in vitro. Methods NPCs isolated from the hippocampus of adult cynomolgus monkeys were expanded in vitro in serum-free media containing growth factors, and were then allowed to differentiate by removing mitotic factors. The expansion capacity of NPCs and their differentiation potential were assayed by immunohistochemical and immunocytochemical analysis. Results During primary culture, NPCs underwent cell division, proliferation and aggregation to form neurospheres that were growing in suspension. Without mitotic stimulation, most neurospheres adhered to the culture dish and started to differentiate. Eventually, nearly 12% of the differentiated cells expressed neuron specific marker-β Ⅲ-tubulin （Tuj1） and 84% expressed astrocyte specific marker-fibrillary acidic protein （GFAP）. In addition, the expression of a neural stem cell marker, nestin, was found both in NPCs and in the subgranular zone of adult monkey hippocampus, where NPCs were originally derived. Conclusions NPCs from the hippocampus of adult cynomolgus monkeys can be expanded to some extent in vitro and are capable of differentiating into neurons and astrocytes. Further experiments to promote the in vitro proliferation capacity of NPCs will be required before adult NPCs can be used as a useful cell model for studying adult neurogenesis and cell replacement therapy using adult stem cells.
基金This work was supported by grants from the National Natural Science Foundation of China （No. 81671352, 91232709）, the National Key Project of Research and Development Plan （No. 2016YFC1306404）, the National Institute of Health （No. R21 AG048519, R01 AG021173, R01 AG038710, R01 AG044420, R01 NS046673, RF1 AG056130, and RF1 AG056114）, the Tanz Family Fund as well as scholarship from China Scholarship Council （No. 201608350068）.
文摘Objective：To review recent research advances on tau,a major player in Alzheimer＇s disease （AD） pathogenesis,a biomarker for AD onset,and potential target for AD therapy.Data Sources：This review was based on a comprehensive search using online literature databases,including PubMed,Web of Science,and Google Scholar.Study Selection：Literature search was based on the following keywords：Alzheimer＇s disease,tau protein,biomarker,cerebrospinal fluid （CSF）,therapeutics,plasma,imaging,propagation,spreading,seeding,prion,conformational templating,and posttranslational modification.Relevant articles were carefully reviewed,with no exclusions applied to study design and publication type.Results：Amyloid plaques enriched with extracellular amyloid beta （Aβ） and intracellular neurofibrillary tangles comprised of hyperphosphorylated tau proteins are the two main pathological hallmarks ofAD.Although the Aβ hypothesis has dominated AD research for many years,clinical Aβ-targeting strategies have consistently failed to effectively treat AD or prevent AD onset.The research focus in AD has recently shifted to the role oftau in AD.In addition to phosphorylation,tau is acetylated and proteolytically cleaved,which also contribute to its physiological and pathological functions.Emerging evidence characterizing pathological tau propagation and spreading provides new avenues for research into the molecular and cellular mechanisms underlying AD pathogenesis.Techniques to detect tau at minute levels in CSF and blood have been developed,and improved tracers have facilitated tau imaging in the brain.These advances have potential to accurately determine tau levels at early diagnostic stages in AD.Given that tau is a potential therapeutic target,anti-tau immunotherapy may potentially be a viable treatment strategy in AD intervention.Conclusion：Detecting changes in tau and targeting tau pathology represent a promising lead in the diagnosis and treatment of AD.
