Cordyceps is treasured entomopathogenic fungi that have been used as antitumor,immunomodulating,antioxidant,and pro-sexual agent.Cordyceps,also called DongChongXiaCao in Chinese,Yartsa Gunbu(Tibetan),means winter worm...Cordyceps is treasured entomopathogenic fungi that have been used as antitumor,immunomodulating,antioxidant,and pro-sexual agent.Cordyceps,also called DongChongXiaCao in Chinese,Yartsa Gunbu(Tibetan),means winter worm-summer grass.Natural Cordyceps sinensis with parasitic hosts is difficult to be collected and the recent findings on its potential pharmacological functions,resulted in skyrocketing prices.Therefore,finding a mass-production method or an alternative for C.sinensis products is a top-priority task.In this review,we describe current status of Cordyceps research and its recent developments in Taiwan.The content and pharmacological activities of four major industrial species of Cordyceps(C.sinensis,Cordyceps militaris,Cordyceps cicadae and Cordyceps sobolifera)used in Taiwan,were reviewed.Moreover,we highlighted the effect of using different methods of fermentation and production on the morphology and chemical content of Cordyceps sp.Finally,we summarized the bottle-necks and challenges facing Cordyceps research as well as we proposed future road map for Cordyceps industry in Taiwan.展开更多
Long term hepatitis B virus (HBV) infection is a major risk factor in pathogenesis of chronic liver diseases,including hepatocellular carcinoma (HCC). The HBV encod-ed proteins,hepatitis B virus X protein and preS,app...Long term hepatitis B virus (HBV) infection is a major risk factor in pathogenesis of chronic liver diseases,including hepatocellular carcinoma (HCC). The HBV encod-ed proteins,hepatitis B virus X protein and preS,appear to contribute importantly to the pathogenesis of HCC. Both are associated with oxidative stress,which can damage cellular molecules like lipids,proteins,and DNA during chronic infection. Chronic alcohol use is another important factor that contributes to oxidative stress in the liver. Previous studies reported that treatment with antioxidants,such as curcumin,silymarin,green tea,and vitamins C and E,can protect DNA from damage and regulate liver pathogenesis-related cascades by reducing reactive oxygen species. This review summarizes some of the relationships between oxidative stress and liver pathogenesis,focusing upon HBV and alcohol,and suggests antioxidant therapeutic approaches.展开更多
AIM:To investigate the role of hepatitis B virus X-protein(HBx)-induced reactive oxygen species(ROS)on liver carcinogenesis in HBx transgenic mice and HepG2-HBx cells.METHODS:Cell growth rate was analyzed,and through ...AIM:To investigate the role of hepatitis B virus X-protein(HBx)-induced reactive oxygen species(ROS)on liver carcinogenesis in HBx transgenic mice and HepG2-HBx cells.METHODS:Cell growth rate was analyzed,and through western blotting,mitogenic signaling was observed.Endogenous ROS from wild and HBx transgenic mice and HepG2-Mock and HBx cells were assayed by FACS-calibur.Identification of oxidized and reduced phosphatase and tensin homolog(PTEN)was analyzed through N-ethylmaleimide alkylation,nonreducing electrophoresis.RESULTS:We observed that the cell-proliferation-related phosphoinositide 3-kinase/Akt pathway is activated by HBx in vivo and in vitro.Increased ROS were detected by HBx.Tumor suppressor PTEN,via dephosphorylation of Akt,was oxidized and inactivated by increased ROS.Increased oxidized PTEN activated the mitogenic pathway through over-activated Akt.However,treatment with ROS scavenger N-acetyl cysteine can reverse PTEN to a reduced form.Endogenously produced ROS also stimulated HBx expression.CONCLUSION:HBx induced ROS promoted Akt pathways via oxidized inactive PTEN.HBx and ROS maintained a positive regulatory loop,which aggravated carcinogenesis.展开更多
Variations in the prevalence of dementia in different ethnic groups have been reported worldwide, and a number of reviews have provided a picture of epidemiological studies in dementia research. However, little is kno...Variations in the prevalence of dementia in different ethnic groups have been reported worldwide, and a number of reviews have provided a picture of epidemiological studies in dementia research. However, little is known about epidemiological studies in Chinese populations. In this review, we searched PubMed and the Web of Science for original research articles published in English up to July 2013 on the prevalence, incidence, risk factors, and prognosis of dementia in Chinese populations worldwide. Except for the prevalence, we included only population-based follow-up studies. We identified 25 studies in elderly Chinese residents in China's Mainland, Hong Kong, Taiwan, and Singapore, and found a higher prevalence of dementia in China's Mainland than in the other locations, which may be due to that the studies from China's Mainland are more recent than those from other locations. A notable increase in incidence was observed when dementia cases were diagnosed using 10/66 diagnostic criteria compared to other criteria. Studies on risk factors for dementia were limited and mostly from China's Mainland. Age, gender, education, smoking, and alcohol consumption were related to the risk of dementia in Chinese populations. Only two prognostic studies were identified, and age, gender, and residential area were related to the prognosis of dementia. In conclusion, the prevalence, incidence, and risk factors for dementia found in Chinese populations were comparable to other ethnic groups, but no conclusive results on prognosis were found. The differences in prevalence and incidence were influenced by the diagnostic criteria and the time of study. Longitudinal population-based studies on the incidence, risk factors, and prognosis of dementia in Chinese populations are required.展开更多
In orthopedics, tissue engineering approach using stem cells is a valid line of treatment for patients with bone defects. In this context, mesenchymal stromal cells of various origins have been extensively studied and...In orthopedics, tissue engineering approach using stem cells is a valid line of treatment for patients with bone defects. In this context, mesenchymal stromal cells of various origins have been extensively studied and continue to be a matter of debate. Although mesenchymal stromal cells from bone marrow are already clinically applied, recent evidence suggests that one may use mesenchymal stromal cells from extra-embryonic tissues, such as amniotic fluid, as an innovative andadvantageous resource for bone regeneration. The use of cells from amniotic fluid does not raise ethical problems and provides a sufficient number of cells without invasive procedures. Furthermore, they do not develop into teratomas when transplanted, a consequence observed with pluripotent stem cells. In addition, their multipotent differentiation ability, low immunogenicity, and anti-inflammatory properties make them ideal candidates for bone regenerative medicine. We here present an overview of the features of amniotic fluid mesenchymal stromal cells and their potential in the osteogenic differentiation process. We have examined the papers actually available on this regard, with particular interest in the strategies applied to improve in vitro osteogenesis. Importantly, a detailed understanding of the behavior of amniotic fluid mesenchymal stromal cells and their osteogenic ability is desirable considering a feasible application in bone regenerative medicine.展开更多
Colorectal cancer(CRC)is one of the leading causes of cancer and cancer-related mortality worldwide.The disease has been traditionally a major health problem in industrial countries,however the CRC rates are increasin...Colorectal cancer(CRC)is one of the leading causes of cancer and cancer-related mortality worldwide.The disease has been traditionally a major health problem in industrial countries,however the CRC rates are increasing in the developing countries that are undergoing economic growth.Several environmental risk factors,mainly changes in diet and life style,have been suggested to underlie the rise of CRC in these populations.Diet and lifestyle impinge on nuclear receptors,on the intestinal microbiota and on crucial molecular pathways that are implicated in intestinal carcinogenesis.In this respect,the epidemiological transition in several regions of the world offers a unique opportunity to better understand CRC carcinogenesis by studying the disease phenotypes and their environmental and molecular associations in different populations.The data from these studies may have important implications for the global prevention and treatment of CRC.展开更多
Mutations in the X-linked androgen receptor （AR） gene cause androgen insensitivity syndrome （AIS）, resulting in an impaired embryonic sex differentiation in 46,XY genetic men. Complete androgen insensitivity （CAI...Mutations in the X-linked androgen receptor （AR） gene cause androgen insensitivity syndrome （AIS）, resulting in an impaired embryonic sex differentiation in 46,XY genetic men. Complete androgen insensitivity （CAIS） produces a female external phenotype, whereas cases with partial androgen insensitivity （PALS） have various ambiguities of the genitalia. Mild androgen insensitivity （MAIS） is characterized by undermasculinization and gynecomastia. Here we describe a 2-month-old 46,XY female patient, with all of the characteristics of CAIS. Defects in testosterone （T） and dihydrotestosterone （DHT） synthesis were excluded. Sequencing of the AR gene showed the presence in exon 6 of a T to C transition in the second base of codon 790, nucleotide position 2369, causing a novel missense Leu790Pro mutation in the ligand-binding domain of the AR protein. The identification of a novel AR mutation in a girl with CAIS provides significant information due to the importance of missense mutations in the ligand-binding domain of the AR, which are able to induce functional abnormalities in the androgen binding capability, stabilization of active conformation, or interaction with coactivators.展开更多
AIM:To investigate the effect of methylsulfonylmethane(MSM), recently reported to have anti-cancer effects, in liver cancer cells and transgenic mice. METHODS: Three liver cancer cell lines, HepG2, Huh7-Mock and Huh7-...AIM:To investigate the effect of methylsulfonylmethane(MSM), recently reported to have anti-cancer effects, in liver cancer cells and transgenic mice. METHODS: Three liver cancer cell lines, HepG2, Huh7-Mock and Huh7-H-rasG12V, were used. Cell growth was measured by Cell Counting Kit-8 and soft agar assay. Western blot analysis was used to detect caspases, poly(ADP-ribose) polymerase(PARP), and B-cell lymphoma2(Bcl-2) expressions. For in vivo study, we administered MSM to H-ras12V transgenic mice for 3 mo. RESULTS: MSM decreased the growth of HepG2, Huh7-Mock and Huh7-H-rasG12V cells in a dose-dependent manner. That was correlated with significantly increased apoptosis and reduced cell numbers in MSM treated cells. Cleaved caspase-8, cleaved caspase-3 and cleaved PARP were remarkably increased in the liver cancer cells treated with 500 mmol/L of MSM; however, Bcl-2 was slightly decreased in 500 mmol/L. Liver tumor development was greatly inhibited in the H-ras12V transgenic mice treated with MSM, compared to control, by showing reduced tumor size and number. Cleaved PARP was significantly increased in non-tumor treated with MSM compared to control. CONCLUSION: Liver injury was also significantly attenuated in the mice treated with MSM. Taken together, all the results suggest that MSM has anti-cancer effects through inducing apoptosis in liver cancer.展开更多
The over-activated microglial cells induce neuroinflammation which has the main role in neurological disorders.The over-activated microglia can disturb neuronal function by releasing inflammatory mediators leading to ...The over-activated microglial cells induce neuroinflammation which has the main role in neurological disorders.The over-activated microglia can disturb neuronal function by releasing inflammatory mediators leading to neuronal dysfunctions and death.Thus,inhibition of over-activated microglia may be an effective therapeutic approach for modulating neuroinflammation.Experimental studies have indicated anti-neuroinflammatory effects of flavonoids such as green tea catechins.The current research was aimed to review the effect of green tea catechins in inhibiting microglial cells,inflammatory cascades,and subsequent neurological diseases.展开更多
Extracellular vesicles have been identified as pivotal mediators of intercellular communication with critical roles in physiological and pathological conditions.Via this route,several molecules(e.g.,nucleic acids,prot...Extracellular vesicles have been identified as pivotal mediators of intercellular communication with critical roles in physiological and pathological conditions.Via this route,several molecules(e.g.,nucleic acids,proteins,metabolites) can be transferred to proximal and distant targets to convey specific information.Extracellular vesicle-associated cargo molecules have been proposed as markers of several disease conditions for their potential of tracking down the generating cell.Indeed,circulating extracellular vesicles may represent biomarkers of dysfunctional cellular quality control systems especially in conditions characterized by the accrual of intracellular misfolded proteins.Furthermore,the identification of extracellular vesicles as tools for the delivery of nucleic acids or other cargo molecules to diseased tissues makes these circulating shuttles possible targets for therapeutic development.The increasing interest in the study of extracellular vesicles as biomarkers resides mainly in the fact that the identification of peripheral levels of extracellular vesicle-associated proteins might reflect molecular events occurring in hardly accessible tissues,such as the brain,thereby serving as a "brain liquid biopsy".The exploitation of extracellular vesicles for diagnostic and therapeutic purposed might offer unprecedented opportunities to develop personalized approaches.Here,we discuss the bright and dark sides of extracellular vesicles in the setting of two main neurodegenerative diseases(i.e.,Parkinson's and Alzheimer's diseases).A special focus will be placed on the possibility of using extracellular vesicles as biomarkers for the two conditions to enable disease tracking and treatment monitoring.展开更多
Background As a consequence of the demographic development with increasing proportion of older people,the prevalence of heart failure(HF)is expected to rise with considerable economic and societal costs.However,knowle...Background As a consequence of the demographic development with increasing proportion of older people,the prevalence of heart failure(HF)is expected to rise with considerable economic and societal costs.However,knowledge on cardiac structure and function among population-based samples of the exceptional old is lacking.Methods Population-based study of all persons(no exclusion criteria)living in the western part of Denmark and turning 100 years in the year 2015.In-home face-to-face interviews were conducted,and echocardiography and blood sampling for plasma Brain Natriuretic Peptide(BNP)were offered to those who were able to give consent.Results Out of 303 eligible,238(79%)participated,of which 125(53%)accepted echocardiography.Left ventricular(LV)dysfunction was present in 68(54%)of the participants of whom less than half had HF symptoms.Pulmonary hypertension was present in 31(42%)with no correlation to LV function.The well-known association between increased level of BNP and the prevalence of LV dysfunction could not be confirmed.Conclusions This in-home echocardiographic study shows that more than half of the participants had LV dysfunction,although mostly asymptomatic.There was no association between heart failure symptoms and LV dysfunction.Furthermore,BNP seems to have lost its biomarker potential to rule out heart failure in centenarians.Due to the latter,and the questionable symptom validity among centenarians,the current criteria to diagnose HF might be less valid in a centenarian population than in younger olds.展开更多
Dementia is a disorder with high societal impact and severe consequences for its patients who suffer from a progressive cognitive decline that leads to increased morbidity,mortality,and disabilities.Since there is a c...Dementia is a disorder with high societal impact and severe consequences for its patients who suffer from a progressive cognitive decline that leads to increased morbidity,mortality,and disabilities.Since there is a consensus that dementia is a multifactorial disorder,which portrays changes in the brain of the affected individual as early as 15 years before its onset,prediction models that aim at its early detection and risk identification should consider these characteristics.This study aims at presenting a novel method for ten years prediction of dementia using on multifactorial data,which comprised 75 variables.There are two automated diagnostic systems developed that use genetic algorithms for feature selection,while artificial neural network and deep neural network are used for dementia classification.The proposed model based on genetic algorithm and deep neural network had achieved the best accuracy of 93.36%,sensitivity of 93.15%,specificity of 91.59%,MCC of 0.4788,and performed superior to other 11 machine learning techniques which were presented in the past for dementia prediction.The identified best predictors were:age,past smoking habit,history of infarct,depression,hip fracture,single leg standing test with right leg,score in the physical component summary and history of TIA/RIND.The identification of risk factors is imperative in the dementia research as an effort to prevent or delay its onset.展开更多
Background Motoric cognitive risk(MCR)syndrome as a pre-dementia syndrome often co-occurring with chronic health condi-tions.This study aims to investigate the prevalence of MCR and its association with cardiometaboli...Background Motoric cognitive risk(MCR)syndrome as a pre-dementia syndrome often co-occurring with chronic health condi-tions.This study aims to investigate the prevalence of MCR and its association with cardiometabolic and panvascular multimorb-idity among older people living in rural China.Methods This population-based study included 1450 participants who were aged≥60 years(66.2%women)and who underto-ok the second wave examination of the Confucius Hometown Aging Project in Shandong,China when information to define MCR was collected.Data were collected through in-person interviews,clinical examinations,and laboratory tests.Cardiometabolic and pa-nvascular multimorbidity were defined following the international criteria.MCR was defined as subjective cognitive complaints and slow gait speed in individuals free of dementia and functional disability.Multivariable logistic regression models were used to exa-mine the associations of MCR with multimorbidity.Results MCR was present in 6.3%of all participants,and the prevalence increased with advancing age.Cerebrovascular disea-se,ischemic heart disease,heart failure,and increased serum cystatin C were associated with increased likelihoods of MCR(mult-ivariable-adjusted odds ratio range:1.90-3.02,P<0.05 for all).Furthermore,there was a dose-response relationship between the nu-mber of cardiometabolic diseases and panvascular diseases and the likelihood of MCR.The multivariable-adjusted odds ratio(95%CI)of MCR associated with cardiometabolic and panvascular multimorbidity were 2.47(1.43-4.26)and 3.85(2.29-6.47),respectiv-ely.Conclusions Older adults with cardiometabolic and panvascular multimorbidity are at a higher likelihood of MCR.These fin-dings may have implications for identifying older adults at pre-dementia state as targets for early preventive interventions to delay dementia onset.展开更多
Purpose This study examines the impact of 26-week exercise intervention facilitated by IoT devices on cognitive function,hippocampal volume,and health indicators in a real-world setting based on the Transtheoretical M...Purpose This study examines the impact of 26-week exercise intervention facilitated by IoT devices on cognitive function,hippocampal volume,and health indicators in a real-world setting based on the Transtheoretical Model.Methods Middle-aged participants(n=121,mean age=49.8±7.62 years)were randomly assigned to BrainUp(n=61)or Sham(n=60)application groups.Both groups engaged in voluntary aerobic exercise over a period of 26 weeks using an IoT device.The BrainUp application was designed to deliver personalized exercise routines aimed at enhancing participants’cognitive function and hippocampal volume based on their individual level.Results Linear mixed models revealed that both groups exhibited improvements in cognitive function and health indicators at post-intervention compared to pre-intervention,but no significant changes in hippocampal volume in either group over time.Path analysis and structural equation modeling indicated that motivation for exercise at 26 weeks played a key role in improving cognitive function and blood glucose,and alleviating depression.Conclusions Integrating physical activity with IoT devices in real-world settings shows promise for enhancing brain health and preventing hippocampal volume loss due to aging.Motivation might play a crucial role in maximizing the health benefits of physical activity,especially during the transition from the Action to Maintenance stages of behavioral changes to an active lifestyle.展开更多
文摘Cordyceps is treasured entomopathogenic fungi that have been used as antitumor,immunomodulating,antioxidant,and pro-sexual agent.Cordyceps,also called DongChongXiaCao in Chinese,Yartsa Gunbu(Tibetan),means winter worm-summer grass.Natural Cordyceps sinensis with parasitic hosts is difficult to be collected and the recent findings on its potential pharmacological functions,resulted in skyrocketing prices.Therefore,finding a mass-production method or an alternative for C.sinensis products is a top-priority task.In this review,we describe current status of Cordyceps research and its recent developments in Taiwan.The content and pharmacological activities of four major industrial species of Cordyceps(C.sinensis,Cordyceps militaris,Cordyceps cicadae and Cordyceps sobolifera)used in Taiwan,were reviewed.Moreover,we highlighted the effect of using different methods of fermentation and production on the morphology and chemical content of Cordyceps sp.Finally,we summarized the bottle-necks and challenges facing Cordyceps research as well as we proposed future road map for Cordyceps industry in Taiwan.
基金Supported by The 21st Century Frontier Program in the Functional Human Genome Project, No. HGM0200934the International Collaboration Program of Science and Technology, No. FGM0600914the Ministry of Education, Science and Technology, and the KRIBB Research Initiative Program Grant, No. KGM3320911, South Korea
文摘Long term hepatitis B virus (HBV) infection is a major risk factor in pathogenesis of chronic liver diseases,including hepatocellular carcinoma (HCC). The HBV encod-ed proteins,hepatitis B virus X protein and preS,appear to contribute importantly to the pathogenesis of HCC. Both are associated with oxidative stress,which can damage cellular molecules like lipids,proteins,and DNA during chronic infection. Chronic alcohol use is another important factor that contributes to oxidative stress in the liver. Previous studies reported that treatment with antioxidants,such as curcumin,silymarin,green tea,and vitamins C and E,can protect DNA from damage and regulate liver pathogenesis-related cascades by reducing reactive oxygen species. This review summarizes some of the relationships between oxidative stress and liver pathogenesis,focusing upon HBV and alcohol,and suggests antioxidant therapeutic approaches.
基金Supported by The 21st century Frontier Program in the Functional Human Genome Project,No.HGM0200934the International Collaboration Program of Science and Technology,No. FGM0600914+1 种基金the Research Program for New Drug Target Discovery Grant from the Ministry of Education,Science & Technology,No.NBM3300711the KRIBB Research Initiative Program Grant,No.KGM3320911
文摘AIM:To investigate the role of hepatitis B virus X-protein(HBx)-induced reactive oxygen species(ROS)on liver carcinogenesis in HBx transgenic mice and HepG2-HBx cells.METHODS:Cell growth rate was analyzed,and through western blotting,mitogenic signaling was observed.Endogenous ROS from wild and HBx transgenic mice and HepG2-Mock and HBx cells were assayed by FACS-calibur.Identification of oxidized and reduced phosphatase and tensin homolog(PTEN)was analyzed through N-ethylmaleimide alkylation,nonreducing electrophoresis.RESULTS:We observed that the cell-proliferation-related phosphoinositide 3-kinase/Akt pathway is activated by HBx in vivo and in vitro.Increased ROS were detected by HBx.Tumor suppressor PTEN,via dephosphorylation of Akt,was oxidized and inactivated by increased ROS.Increased oxidized PTEN activated the mitogenic pathway through over-activated Akt.However,treatment with ROS scavenger N-acetyl cysteine can reverse PTEN to a reduced form.Endogenously produced ROS also stimulated HBx expression.CONCLUSION:HBx induced ROS promoted Akt pathways via oxidized inactive PTEN.HBx and ROS maintained a positive regulatory loop,which aggravated carcinogenesis.
基金supported by the Swedish Council for Working Life and Social Researchthe Konung Gustaf V:s och Drottning Victorias Frimurare Foundation+2 种基金the Gun and Bertil Stohnes Foundationthe Alzheimer Foundation Sweden,the GamlaTjanarinnor Foundationthe Board of Research at Karolinska Institute
文摘Variations in the prevalence of dementia in different ethnic groups have been reported worldwide, and a number of reviews have provided a picture of epidemiological studies in dementia research. However, little is known about epidemiological studies in Chinese populations. In this review, we searched PubMed and the Web of Science for original research articles published in English up to July 2013 on the prevalence, incidence, risk factors, and prognosis of dementia in Chinese populations worldwide. Except for the prevalence, we included only population-based follow-up studies. We identified 25 studies in elderly Chinese residents in China's Mainland, Hong Kong, Taiwan, and Singapore, and found a higher prevalence of dementia in China's Mainland than in the other locations, which may be due to that the studies from China's Mainland are more recent than those from other locations. A notable increase in incidence was observed when dementia cases were diagnosed using 10/66 diagnostic criteria compared to other criteria. Studies on risk factors for dementia were limited and mostly from China's Mainland. Age, gender, education, smoking, and alcohol consumption were related to the risk of dementia in Chinese populations. Only two prognostic studies were identified, and age, gender, and residential area were related to the prognosis of dementia. In conclusion, the prevalence, incidence, and risk factors for dementia found in Chinese populations were comparable to other ethnic groups, but no conclusive results on prognosis were found. The differences in prevalence and incidence were influenced by the diagnostic criteria and the time of study. Longitudinal population-based studies on the incidence, risk factors, and prognosis of dementia in Chinese populations are required.
文摘In orthopedics, tissue engineering approach using stem cells is a valid line of treatment for patients with bone defects. In this context, mesenchymal stromal cells of various origins have been extensively studied and continue to be a matter of debate. Although mesenchymal stromal cells from bone marrow are already clinically applied, recent evidence suggests that one may use mesenchymal stromal cells from extra-embryonic tissues, such as amniotic fluid, as an innovative andadvantageous resource for bone regeneration. The use of cells from amniotic fluid does not raise ethical problems and provides a sufficient number of cells without invasive procedures. Furthermore, they do not develop into teratomas when transplanted, a consequence observed with pluripotent stem cells. In addition, their multipotent differentiation ability, low immunogenicity, and anti-inflammatory properties make them ideal candidates for bone regenerative medicine. We here present an overview of the features of amniotic fluid mesenchymal stromal cells and their potential in the osteogenic differentiation process. We have examined the papers actually available on this regard, with particular interest in the strategies applied to improve in vitro osteogenesis. Importantly, a detailed understanding of the behavior of amniotic fluid mesenchymal stromal cells and their osteogenic ability is desirable considering a feasible application in bone regenerative medicine.
基金Supported by Institutional NRSA,clinical oncology research training program,No.T32 CA079447(Bishehsari F)the Associazione Italiana per la Ricerca sul Cancro(AIRC),Milan to Mariani-Costantini R+3 种基金the Office for Internationalization,G.d’Annunzio University,Chietithe Carichieti Foundation,ChietiMinistero dell’Istruzione,dell’Universitàe della Ricerca(MIUR),Rome,Italythe Fondazione Umberto Veronesi,Milan,Italy and the MRC(5PT57)to Vacca M
文摘Colorectal cancer(CRC)is one of the leading causes of cancer and cancer-related mortality worldwide.The disease has been traditionally a major health problem in industrial countries,however the CRC rates are increasing in the developing countries that are undergoing economic growth.Several environmental risk factors,mainly changes in diet and life style,have been suggested to underlie the rise of CRC in these populations.Diet and lifestyle impinge on nuclear receptors,on the intestinal microbiota and on crucial molecular pathways that are implicated in intestinal carcinogenesis.In this respect,the epidemiological transition in several regions of the world offers a unique opportunity to better understand CRC carcinogenesis by studying the disease phenotypes and their environmental and molecular associations in different populations.The data from these studies may have important implications for the global prevention and treatment of CRC.
文摘Mutations in the X-linked androgen receptor （AR） gene cause androgen insensitivity syndrome （AIS）, resulting in an impaired embryonic sex differentiation in 46,XY genetic men. Complete androgen insensitivity （CAIS） produces a female external phenotype, whereas cases with partial androgen insensitivity （PALS） have various ambiguities of the genitalia. Mild androgen insensitivity （MAIS） is characterized by undermasculinization and gynecomastia. Here we describe a 2-month-old 46,XY female patient, with all of the characteristics of CAIS. Defects in testosterone （T） and dihydrotestosterone （DHT） synthesis were excluded. Sequencing of the AR gene showed the presence in exon 6 of a T to C transition in the second base of codon 790, nucleotide position 2369, causing a novel missense Leu790Pro mutation in the ligand-binding domain of the AR protein. The identification of a novel AR mutation in a girl with CAIS provides significant information due to the importance of missense mutations in the ligand-binding domain of the AR, which are able to induce functional abnormalities in the androgen binding capability, stabilization of active conformation, or interaction with coactivators.
基金Supported by The World Class Institute(WCI) Program of the Na-tional Research Foundation of Korea(NRF),No.WCM0101222Ministry of Education,Science and Technology of Korea(MEST),the National R and D Program for Cancer Control,Ministry of Health and Welfare,South Korea,No.BCM0061213KRIBB Research Initiative Program Grant,No.KGM3141312
文摘AIM:To investigate the effect of methylsulfonylmethane(MSM), recently reported to have anti-cancer effects, in liver cancer cells and transgenic mice. METHODS: Three liver cancer cell lines, HepG2, Huh7-Mock and Huh7-H-rasG12V, were used. Cell growth was measured by Cell Counting Kit-8 and soft agar assay. Western blot analysis was used to detect caspases, poly(ADP-ribose) polymerase(PARP), and B-cell lymphoma2(Bcl-2) expressions. For in vivo study, we administered MSM to H-ras12V transgenic mice for 3 mo. RESULTS: MSM decreased the growth of HepG2, Huh7-Mock and Huh7-H-rasG12V cells in a dose-dependent manner. That was correlated with significantly increased apoptosis and reduced cell numbers in MSM treated cells. Cleaved caspase-8, cleaved caspase-3 and cleaved PARP were remarkably increased in the liver cancer cells treated with 500 mmol/L of MSM; however, Bcl-2 was slightly decreased in 500 mmol/L. Liver tumor development was greatly inhibited in the H-ras12V transgenic mice treated with MSM, compared to control, by showing reduced tumor size and number. Cleaved PARP was significantly increased in non-tumor treated with MSM compared to control. CONCLUSION: Liver injury was also significantly attenuated in the mice treated with MSM. Taken together, all the results suggest that MSM has anti-cancer effects through inducing apoptosis in liver cancer.
文摘The over-activated microglial cells induce neuroinflammation which has the main role in neurological disorders.The over-activated microglia can disturb neuronal function by releasing inflammatory mediators leading to neuronal dysfunctions and death.Thus,inhibition of over-activated microglia may be an effective therapeutic approach for modulating neuroinflammation.Experimental studies have indicated anti-neuroinflammatory effects of flavonoids such as green tea catechins.The current research was aimed to review the effect of green tea catechins in inhibiting microglial cells,inflammatory cascades,and subsequent neurological diseases.
基金partially funded by an Intramural Research Grant from the Università Cattolica del Sacro Cuore [D1 2020 to EM]the nonprofit research foundation “Centro Studi Achille e Linda Lorenzon”(to AP,EM,and RC)。
文摘Extracellular vesicles have been identified as pivotal mediators of intercellular communication with critical roles in physiological and pathological conditions.Via this route,several molecules(e.g.,nucleic acids,proteins,metabolites) can be transferred to proximal and distant targets to convey specific information.Extracellular vesicle-associated cargo molecules have been proposed as markers of several disease conditions for their potential of tracking down the generating cell.Indeed,circulating extracellular vesicles may represent biomarkers of dysfunctional cellular quality control systems especially in conditions characterized by the accrual of intracellular misfolded proteins.Furthermore,the identification of extracellular vesicles as tools for the delivery of nucleic acids or other cargo molecules to diseased tissues makes these circulating shuttles possible targets for therapeutic development.The increasing interest in the study of extracellular vesicles as biomarkers resides mainly in the fact that the identification of peripheral levels of extracellular vesicle-associated proteins might reflect molecular events occurring in hardly accessible tissues,such as the brain,thereby serving as a "brain liquid biopsy".The exploitation of extracellular vesicles for diagnostic and therapeutic purposed might offer unprecedented opportunities to develop personalized approaches.Here,we discuss the bright and dark sides of extracellular vesicles in the setting of two main neurodegenerative diseases(i.e.,Parkinson's and Alzheimer's diseases).A special focus will be placed on the possibility of using extracellular vesicles as biomarkers for the two conditions to enable disease tracking and treatment monitoring.
基金support from the Novo Nordisk Foundationthe Faculty of Health Sciences, University of Southern Denmark+2 种基金the Health Foundation (Helsefonden) (Grant No.16B-0271)the Lundbeck Foundation (Grant No. R260-2017722)supported by a grant from the Velux Foundation
文摘Background As a consequence of the demographic development with increasing proportion of older people,the prevalence of heart failure(HF)is expected to rise with considerable economic and societal costs.However,knowledge on cardiac structure and function among population-based samples of the exceptional old is lacking.Methods Population-based study of all persons(no exclusion criteria)living in the western part of Denmark and turning 100 years in the year 2015.In-home face-to-face interviews were conducted,and echocardiography and blood sampling for plasma Brain Natriuretic Peptide(BNP)were offered to those who were able to give consent.Results Out of 303 eligible,238(79%)participated,of which 125(53%)accepted echocardiography.Left ventricular(LV)dysfunction was present in 68(54%)of the participants of whom less than half had HF symptoms.Pulmonary hypertension was present in 31(42%)with no correlation to LV function.The well-known association between increased level of BNP and the prevalence of LV dysfunction could not be confirmed.Conclusions This in-home echocardiographic study shows that more than half of the participants had LV dysfunction,although mostly asymptomatic.There was no association between heart failure symptoms and LV dysfunction.Furthermore,BNP seems to have lost its biomarker potential to rule out heart failure in centenarians.Due to the latter,and the questionable symptom validity among centenarians,the current criteria to diagnose HF might be less valid in a centenarian population than in younger olds.
文摘Dementia is a disorder with high societal impact and severe consequences for its patients who suffer from a progressive cognitive decline that leads to increased morbidity,mortality,and disabilities.Since there is a consensus that dementia is a multifactorial disorder,which portrays changes in the brain of the affected individual as early as 15 years before its onset,prediction models that aim at its early detection and risk identification should consider these characteristics.This study aims at presenting a novel method for ten years prediction of dementia using on multifactorial data,which comprised 75 variables.There are two automated diagnostic systems developed that use genetic algorithms for feature selection,while artificial neural network and deep neural network are used for dementia classification.The proposed model based on genetic algorithm and deep neural network had achieved the best accuracy of 93.36%,sensitivity of 93.15%,specificity of 91.59%,MCC of 0.4788,and performed superior to other 11 machine learning techniques which were presented in the past for dementia prediction.The identified best predictors were:age,past smoking habit,history of infarct,depression,hip fracture,single leg standing test with right leg,score in the physical component summary and history of TIA/RIND.The identification of risk factors is imperative in the dementia research as an effort to prevent or delay its onset.
基金Supported by the Department of Science and Technology(No.2008GG30002058)the Department of Health(No.2009-067)+2 种基金the Department of Natural Science Foundation(ZR2010HL031)in Shandong,Chinathe Swedish Research Council(No.2017-00740&No.2017-05819)the Swedish Foundation for International Cooperation in Research and Higher Education(CH2019-8320),Stockholm,Sweden.
文摘Background Motoric cognitive risk(MCR)syndrome as a pre-dementia syndrome often co-occurring with chronic health condi-tions.This study aims to investigate the prevalence of MCR and its association with cardiometabolic and panvascular multimorb-idity among older people living in rural China.Methods This population-based study included 1450 participants who were aged≥60 years(66.2%women)and who underto-ok the second wave examination of the Confucius Hometown Aging Project in Shandong,China when information to define MCR was collected.Data were collected through in-person interviews,clinical examinations,and laboratory tests.Cardiometabolic and pa-nvascular multimorbidity were defined following the international criteria.MCR was defined as subjective cognitive complaints and slow gait speed in individuals free of dementia and functional disability.Multivariable logistic regression models were used to exa-mine the associations of MCR with multimorbidity.Results MCR was present in 6.3%of all participants,and the prevalence increased with advancing age.Cerebrovascular disea-se,ischemic heart disease,heart failure,and increased serum cystatin C were associated with increased likelihoods of MCR(mult-ivariable-adjusted odds ratio range:1.90-3.02,P<0.05 for all).Furthermore,there was a dose-response relationship between the nu-mber of cardiometabolic diseases and panvascular diseases and the likelihood of MCR.The multivariable-adjusted odds ratio(95%CI)of MCR associated with cardiometabolic and panvascular multimorbidity were 2.47(1.43-4.26)and 3.85(2.29-6.47),respectiv-ely.Conclusions Older adults with cardiometabolic and panvascular multimorbidity are at a higher likelihood of MCR.These fin-dings may have implications for identifying older adults at pre-dementia state as targets for early preventive interventions to delay dementia onset.
基金a grant from Technology-based Startups of New Energy and Industrial Technology Development Organization.
文摘Purpose This study examines the impact of 26-week exercise intervention facilitated by IoT devices on cognitive function,hippocampal volume,and health indicators in a real-world setting based on the Transtheoretical Model.Methods Middle-aged participants(n=121,mean age=49.8±7.62 years)were randomly assigned to BrainUp(n=61)or Sham(n=60)application groups.Both groups engaged in voluntary aerobic exercise over a period of 26 weeks using an IoT device.The BrainUp application was designed to deliver personalized exercise routines aimed at enhancing participants’cognitive function and hippocampal volume based on their individual level.Results Linear mixed models revealed that both groups exhibited improvements in cognitive function and health indicators at post-intervention compared to pre-intervention,but no significant changes in hippocampal volume in either group over time.Path analysis and structural equation modeling indicated that motivation for exercise at 26 weeks played a key role in improving cognitive function and blood glucose,and alleviating depression.Conclusions Integrating physical activity with IoT devices in real-world settings shows promise for enhancing brain health and preventing hippocampal volume loss due to aging.Motivation might play a crucial role in maximizing the health benefits of physical activity,especially during the transition from the Action to Maintenance stages of behavioral changes to an active lifestyle.
