In this editorial,we review the work of Razali et al published in World J Gas-troenterology,with a particular focus on the effect of rs10889677 variation in the phosphatidylinositol 3-kinase(PI3K)pathway and buparlisi...In this editorial,we review the work of Razali et al published in World J Gas-troenterology,with a particular focus on the effect of rs10889677 variation in the phosphatidylinositol 3-kinase(PI3K)pathway and buparlisib on colitis-associated cancer.The role of PI3K in promoting cancer progression has been widely recognized,as it is involved in regulating the survival,differentiation,and prolif-eration of cancer cells.The complement Clq/TNF-related protein 6(CTRP6)is a newer tumor-associated factor.Recent studies have revealed the pro-tumor effect of CTRP6 in gastric cancer,hepatocellular carcinoma,colorectal cancer,and other gastrointestinal tumors through the PI3K pathway.This article attempts to reveal the mechanism through which the CTRP6 affects the development of digestive system tumors through the PI3K pathway by summarizing recent research.展开更多
Sortilin-related receptor 1(SORL1)is a critical gene associated with late-onset Alzheimer’s disease.SORL1 contributes to the development and progression of this neurodegenerative condition by affecting the transport ...Sortilin-related receptor 1(SORL1)is a critical gene associated with late-onset Alzheimer’s disease.SORL1 contributes to the development and progression of this neurodegenerative condition by affecting the transport and metabolism of intracellularβ-amyloid precursor protein.To better understand the underlying mechanisms of SORL1 in the pathogenesis of late-onset Alzheimer s disease,in this study,we established a mouse model of SorI1 gene knockout using cluste red regularly inters paced short palindro mic repeats-associated protein 9 technology.We found that Sorl1-knocko ut mice displayed deficits in learning and memory.Furthermore,the expression of brain-derived neurotrophic factor was significantly downregulated in the hippocampus and co rtex,and amyloidβ-protein deposits were observed in the brains of 5orl1-knockout mice.In vitro,hippocampal neuronal cell synapses from homozygous Sorl1-knockout mice were impaired.The expression of synaptic proteins,including Drebrin and NR2B,was significantly reduced,and also their colocalization.Additionally,by knocking out the Sorl1 gene in N2a cells,we found that expression of the N-methyl-D-aspartate receptor,NR2B,and cyclic adenosine monophosphate-response element binding protein was also inhibited.These findings suggest that SORL1 participates in the pathogenesis of late-onset Alzheimer s disease by regulating the N-methyl-D-aspartate receptor NR2B/cyclic adenosine monophosphate-response element binding protein signaling axis.展开更多
Alzheimer s disease,among the most common neurodegenerative disorders,is chara cterized by progressive cognitive impairment.At present,the Alzheimer’s disease main risk remains genetic ris ks,but major environmental ...Alzheimer s disease,among the most common neurodegenerative disorders,is chara cterized by progressive cognitive impairment.At present,the Alzheimer’s disease main risk remains genetic ris ks,but major environmental fa ctors are increasingly shown to impact Alzheimer’s disease development and progression.Microglia,the most important brain immune cells,play a central role in Alzheimer’s disease pathogenesis and are considered environmental and lifestyle"sensors."Factors like environmental pollution and modern lifestyles(e.g.,chronic stress,poor dietary habits,sleep,and circadian rhythm disorde rs)can cause neuroinflammato ry responses that lead to cognitive impairment via microglial functioning and phenotypic regulation.However,the specific mechanisms underlying interactions among these facto rs and microglia in Alzheimer’s disease are unclear.Herein,we:discuss the biological effects of air pollution,chronic stress,gut micro biota,sleep patterns,physical exercise,cigarette smoking,and caffeine consumption on microglia;consider how unhealthy lifestyle factors influence individual susceptibility to Alzheimer’s disease;and present the neuroprotective effects of a healthy lifestyle.Toward intervening and controlling these environmental risk fa ctors at an early Alzheimer’s disease stage,understanding the role of microglia in Alzheimer’s disease development,and to rgeting strategies to to rget microglia,co uld be essential to future Alzheimer’s disease treatments.展开更多
Physical activity and exercise have several beneficial roles in enhancing both physiological and psychological well-being of an individual.In addition to aiding the regulation of aerobic and anaerobic metabolism,exerc...Physical activity and exercise have several beneficial roles in enhancing both physiological and psychological well-being of an individual.In addition to aiding the regulation of aerobic and anaerobic metabolism,exercise can stimulate the synthesis of exerkine hormones in the circulatory system.Among several exerkines that have been investigated for their therapeutic potential,Brain-derived neurotrophic factor(BDNF)is considered the most promising candidate,especially in the management of neurodegenerative diseases.Owing to the ability of physical activity to enhance BDNF synthesis,several experimental studies conducted so far have validated this hypothesis and produced satisfactory results at the pre-clinical level.This review highlights some of the recent animal model studies that have evaluated the efficiency of exercise in enhancing BDNF synthesis and promoting neuroprotective effects.Further,this review focuses on understanding the therapeutic benefits of exercise-induced exerkine synthesis as a non-pharmacological strategy in Parkinson’s disease(PD).Regarding physical activity and exerkine induction,the neuromuscular electrical stimulation(NMES)strategy could be considered as an alternate treatment modality for patients affected with PD.展开更多
This study aimed to investigate the pollution characteristics, source apportionment, and health risks associated with trace metal(loid)s(TMs) in the major agricultural producing areas in Chongqing, China. We analyzed ...This study aimed to investigate the pollution characteristics, source apportionment, and health risks associated with trace metal(loid)s(TMs) in the major agricultural producing areas in Chongqing, China. We analyzed the source apportionment and assessed the health risk of TMs in agricultural soils by using positive matrix factorization(PMF) model and health risk assessment(HRA) model based on Monte Carlo simulation. Meanwhile, we combined PMF and HRA models to explore the health risks of TMs in agricultural soils by different pollution sources to determine the priority control factors. Results showed that the average contents of cadmium(Cd), arsenic (As), lead(Pb), chromium(Cr), copper(Cu), nickel(Ni), and zinc(Zn) in the soil were found to be 0.26, 5.93, 27.14, 61.32, 23.81, 32.45, and 78.65 mg/kg, respectively. Spatial analysis and source apportionment analysis revealed that urban and industrial sources, agricultural sources, and natural sources accounted for 33.0%, 27.7%, and 39.3% of TM accumulation in the soil, respectively. In the HRA model based on Monte Carlo simulation, noncarcinogenic risks were deemed negligible(hazard index <1), the carcinogenic risks were at acceptable level(10^(-6)<total carcinogenic risk ≤ 10^(-4)), with higher risks observed for children compared to adults. The relationship between TMs, their sources, and health risks indicated that urban and industrial sources were primarily associated with As, contributing to 75.1% of carcinogenic risks and 55.7% of non-carcinogenic risks, making them the primary control factors. Meanwhile, agricultural sources were primarily linked to Cd and Pb, contributing to 13.1% of carcinogenic risks and 21.8% of non-carcinogenic risks, designating them as secondary control factors.展开更多
BACKGROUND Psychological distress,especially depression,associated with perianal fistulizing Crohn’s disease(PFCD)is widespread and refractory.However,there is a surprising paucity of studies to date that have sought...BACKGROUND Psychological distress,especially depression,associated with perianal fistulizing Crohn’s disease(PFCD)is widespread and refractory.However,there is a surprising paucity of studies to date that have sought to identify the prevalence and risk factors of depression associated with PFCD.AIM To estimate the prevalence of depressive symptoms and investigate the depression-related risk factors in patients with PFCD.METHODS The study was conducted in the form of survey and clinical data collection via questionnaire and specialized medical staff.Depressive symptoms,life quality,and fatigue severity of patients with PFCD were assessed by Patient Health Questionnaire-9,Inflammatory Bowel Disease Patient Quality of Life Questionnaire(IBDQ),and Inflammatory Bowel Disease(IBD)Fatigue Patient Self-assessment Scale.The basic demographic information,overall disease features,perianal clinical information,and laboratory inflammation indicators were also gathered.Multivariate regression analysis was ultimately used to ascertain the risk factors of depression associated with PFCD.RESULTS A total of 123 patients with PFCD were involved,and 56.91%were suffering from depression.According to multivariate logistic regression analysis,Perianal Disease Activity Index(PDAI)score[odds ratio(OR)=0.69,95%confidence interval(CI):0.50 to 0.95],IBDQ score(OR=0.93,95%CI:0.88 to 0.97),modified Van Assche index(OR=1.24,95%CI:1.01 to 1.53),and IBD Fatigue score(OR=1.72,95%CI:1.23 to 2.42)were independent risk factors of depression-related prevalence among patients with PFCD(P<0.05).Multiple linear regression analysis revealed that the increasing perianal modified Van Assche index(βvalue=0.166,95%CI:0.02 to 0.31)and decreasing IBDQ score(βvalue=-0.116,95%CI:-0.14 to-0.09)were independently associated with the severity of depression(P<0.05).CONCLUSION Depressive symptoms in PFCD patients have significantly high prevalence.PDAI score,modified Van Assche index,quality of life,and fatigue severity were the main independent risk factors.展开更多
Introduction: Obesity and overweight are a public health problem. The general objective was to determine the epidemiological aspects of obesity, overweight and associated risk factors in a semi-urban environment. Pati...Introduction: Obesity and overweight are a public health problem. The general objective was to determine the epidemiological aspects of obesity, overweight and associated risk factors in a semi-urban environment. Patients and Methods: This was a cross-sectional, descriptive study conducted on November 28 and 29, 2023 in Sébikotane. It focused on volunteers for screening for chronic non-communicable diseases. Epidemiological and clinical data were evaluated. Results: One hundred and twenty-nine cases of obesity were recorded (28%). Two hundred and eighty-two cases were overweight or obese (61.3%). The mean age was 49.55 years, with a standard deviation of 12.41 years. The age group [40 - 49 years] was the most representative, with 85 cases (30.1%), and the majority were female, with 264 cases (93.6%). Primary education was the most common, with 75 cases (46.3%). Grade 1 obesity concerned ninety-seven cases (75.2%), and diabetes was present in thirty cases (23%). Hypertension was present in ninety-five cases (33.7%). Obesity was more marked in the age group [40 - 49 years] with 45 cases (36%). Conclusion: Obesity and overweight are a major cause of morbidity and mortality. The development and implementation of a prevention and management program is essential.展开更多
Interferon regulatory factor 7 plays a crucial role in the innate immune response.However,whether interferon regulatory factor 7-mediated signaling contributes to Parkinson's disease remains unknown.Here we report...Interferon regulatory factor 7 plays a crucial role in the innate immune response.However,whether interferon regulatory factor 7-mediated signaling contributes to Parkinson's disease remains unknown.Here we report that interferon regulatory factor 7 is markedly up-regulated in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced mouse model of Parkinson's disease and co-localizes with microglial cells.Both the selective cyclic guanosine monophosphate adenosine monophosphate synthase inhibitor RU.521 and the stimulator of interferon genes inhibitor H151 effectively suppressed interferon regulatory factor 7 activation in BV2 microglia exposed to 1-methyl-4-phenylpyridinium and inhibited transformation of mouse BV2 microglia into the neurotoxic M1 phenotype.In addition,si RNA-mediated knockdown of interferon regulatory factor 7 expression in BV2 microglia reduced the expression of inducible nitric oxide synthase,tumor necrosis factorα,CD16,CD32,and CD86 and increased the expression of the anti-inflammatory markers ARG1 and YM1.Taken together,our findings indicate that the cyclic guanosine monophosphate adenosine monophosphate synthase-stimulator of interferon genes-interferon regulatory factor 7 pathway plays a crucial role in the pathogenesis of Parkinson's disease.展开更多
Aging is a physiological event dependent on multiple pathways that are linked to lifespan and processes leading to cognitive decline.This process represents the major risk factor for aging-related diseases such as Alz...Aging is a physiological event dependent on multiple pathways that are linked to lifespan and processes leading to cognitive decline.This process represents the major risk factor for aging-related diseases such as Alzheimer’s disease,Parkinson’s disease,and ischemic stroke.The incidence of all these pathologies increases exponentially with age.Research on aging biology has currently focused on elucidating molecular mechanisms leading to the development of those pathologies.Cognitive deficit and neurodegeneration,common features of aging-related pathologies,are related to the alteration of the activity and levels of neurotrophic factors,such as brain-derived neurotrophic factor,nerve growth factor,and glial cell-derived neurotrophic factor.For this reason,treatments that modulate neurotrophin levels have acquired a great deal of interest in preventing neurodegeneration and promoting neural regeneration in several neurological diseases.Those treatments include both the direct administration of neurotrophic factors and the induced expression with viral vectors,neurotrophins’binding with biomaterials or other molecules to increase their bioavailability but also cell-based therapies.Considering neurotrophins’crucial role in aging pathologies,here we discuss the involvement of several neurotrophic factors in the most common brain aging-related diseases and the most recent therapeutic approaches that provide direct and sustained neurotrophic support.展开更多
Objective Vitamin D(VD)deficiency was reported to contribute to the progression of Crohn’s disease(CD)and affect the prognosis of CD patients.This study investigated the role of serum VD,body mass index(BMI),and tumo...Objective Vitamin D(VD)deficiency was reported to contribute to the progression of Crohn’s disease(CD)and affect the prognosis of CD patients.This study investigated the role of serum VD,body mass index(BMI),and tumor necrosis factor alpha(TNF-α)in the diagnosis of Crohn’s disease.Methods CD patients(n=76)and healthy subjects(n=76)were enrolled between May 2019 and December 2020.The serum 25-hydroxyvitamin D[25(OH)D]levels,BMI,and TNF-αlevels,together with other biochemical parameters,were assessed before treatment.The diagnostic efficacy of the single and joint detection of serum 25(OH)D,BMI,and TNF-αwas determined using receiver operating characteristic(ROC)curves.Results The levels of 25(OH)D,BMI,and nutritional indicators,including hemoglobin,total protein,albumin,and high-density lipoprotein cholesterol,were much lower,and the TNF-αlevels were much higher in the CD patients than in the healthy subjects(P<0.05 for all).The areas under the ROC curve for the single detection of 25(OH)D,BMI,and TNF-αwere 0.887,0.896,and 0.838,respectively,with the optimal cutoff values being 20.64 ng/mL,19.77 kg/m^(2),and 6.85 fmol/mL,respectively.The diagnostic efficacy of the joint detection of 25(OH)D,BMI,and TNF-αwas the highest,with an area under the ROC curve of 0.988(95%CI:0.968–1.000).Conclusion The joint detection of 25(OH)D,TNF-α,and BMI showed high sensitivity,specificity,and accuracy in CD diagnosis;thus,it would be effective for the diagnosis of CD in clinical practice.展开更多
Previous studies have found that deficiency in nuclear receptor-related factor 1(Nurr1),which participates in the development,differentiation,survival,and degeneration of dopaminergic neurons,is associated with Parkin...Previous studies have found that deficiency in nuclear receptor-related factor 1(Nurr1),which participates in the development,differentiation,survival,and degeneration of dopaminergic neurons,is associated with Parkinson s disease,but the mechanism of action is perplexing.Here,we first asce rtained the repercussion of knocking down Nurr1 by pe rforming liquid chromatography coupled with tandem mass spectrometry.We found that 231 genes were highly expressed in dopaminergic neurons with Nurr1 deficiency,14 of which were linked to the Parkinson’s disease pathway based on Kyoto Encyclopedia of Genes and Genomes analysis.To better understand how Nurr1 deficiency autonomously invokes the decline of dopaminergic neurons and elicits Parkinson’s disease symptoms,we performed single-nuclei RNA sequencing in a Nurr1 LV-shRNA mouse model.The results revealed cellular heterogeneity in the substantia nigra and a number of activated genes,the preponderance of which encode components of the major histocompatibility Ⅱ complex.Cd74,H2-Ab1,H2-Aα,H2-Eb1,Lyz2,Mrc1,Slc6α3,Slc47α1,Ms4α4b,and Ptprc2 were the top 10 diffe rentially expressed genes.Immunofluorescence staining showed that,after Nurr1knockdown,the number of CD74-immunoreactive cells in mouse brain tissue was markedly increased.In addition,Cd74 expression was increased in a mouse model of Parkinson’s disease induced by treatment with 6-hydroxydopamine.Ta ken togethe r,our res ults suggest that Nurr1 deficiency results in an increase in Cd74 expression,thereby leading to the destruction of dopaminergic neuro ns.These findings provide a potential therapeutic target for the treatment of Parkinson’s disease.展开更多
Biologic agents with various mechanisms against Crohn’s disease(CD)have been released and are widely used in clinical practice.However,two anti-tumor necrosis factor(TNF)agents,infliximab(IFX)and adalimumab(ADL),are ...Biologic agents with various mechanisms against Crohn’s disease(CD)have been released and are widely used in clinical practice.However,two anti-tumor necrosis factor(TNF)agents,infliximab(IFX)and adalimumab(ADL),are the only biologic agents approved by the Food and Drug Administration for pediatric CD currently.Therefore,in pediatric CD,the choice of biologic agents should be made more carefully to achieve the therapeutic goal.There are currently no headto-head trials of biologic agents in pediatric or adult CD.There is a lack of accumulated data for pediatric CD,which requires the extrapolation of adult data for the positioning of biologics in pediatric CD.From a pharmacokinetic point of view,IFX is more advantageous than ADL when the inflammatory burden is high,and ADL is expected to be advantageous over IFX in sustaining remission in the maintenance phase.Additionally,we reviewed the safety profile,immunogenicity,preference,and compliance between IFX and ADL and provide practical insights into the choice of anti-TNF therapy in pediatric CD.Careful evaluation of clinical indications and disease behavior is essential when prescribing anti-TNF agents.In addition,factors such as the efficacy of induction and maintenance of remission,safety profile,immunogenicity,patient preference,and compliance play an important role in evaluating and selecting treatment options.展开更多
Objectives:This study aims to ascertain if cultural factors influence the childbirth place choice of women in Oyigbo.Materials and Methods:The study used a cross‑sectional study design using a self‑structured question...Objectives:This study aims to ascertain if cultural factors influence the childbirth place choice of women in Oyigbo.Materials and Methods:The study used a cross‑sectional study design using a self‑structured questionnaire as the instrument to collect data from 384 volunteers through simple random sampling,and these data were analyzed using frequency and percentage for descriptive statistics while Chi‑square was used for inferential statistics at 0.05 level of significance.Results:The influence of cultural factors such as family traditions(χ^(2)=12.56,P=0.006),beliefs(χ^(2)=70.66,P=0.000),lack of confidence in health facilities(χ^(2)=367.83,P=0.000),and the presence of male skilled birth attendants(χ^(2)=50.85,P=0.000)were statistically significant to the choice of childbirth place,while patriarchal system(χ^(2)=2.99,P=0.393)was not statistically significant to the choices of childbirth places of women in Oyigbo.Religion had a statistically significant influence on childbirth place(χ^(2)=125.46,P=0.000).Conclusion:This study shows that religious and cultural factors have a significant influence on the childbirth place choices of women in Oyigbo Local Government Area of Rivers State.展开更多
Previous studies have shown that fibroblast growth factor 13 is downregulated in the brain of both Alzheimer’s disease mouse models and patients,and that it plays a vital role in the learning and memory.However,the u...Previous studies have shown that fibroblast growth factor 13 is downregulated in the brain of both Alzheimer’s disease mouse models and patients,and that it plays a vital role in the learning and memory.However,the underlying mechanisms of fibroblast growth factor 13 in Alzheimer’s disease remain unclear.In this study,we established rat models of Alzheimer’s disease by stereotaxic injection of amyloid-β(Aβ_(1-42))-induced into bilateral hippocampus.We also injected lentivirus containing fibroblast growth factor 13 into bilateral hippocampus to overexpress fibroblast growth factor 13.The expression of fibroblast growth factor 13 was downregulated in the brain of the Alzheimer’s disease model rats.After overexpression of fibroblast growth factor 13,learning and memory abilities of the Alzheimer’s disease model rats were remarkably improved.Fibroblast growth factor 13 overexpression increased brain expression levels of oxidative stress-related markers glutathione,superoxide dismutase,phosphatidylinositol-3-kinase,AKT and glycogen synthase kinase 3β,and anti-apoptotic factor BCL.Furthermore,fibroblast growth factor 13 overexpression decreased the number of apoptotic cells,expression of pro-apoptotic factor BAX,cleaved-caspase 3 and amyloid-βexpression,and levels of tau phosphorylation,malondialdehyde,reactive oxygen species and acetylcholinesterase in the brain of Alzheimer’s disease model rats.The changes were reversed by the phosphatidylinositol-3-kinase inhibitor LY294002.These findings suggest that overexpression of fibroblast growth factor 13 improved neuronal damage in a rat model of Alzheimer’s disease through activation of the phosphatidylinositol-3-kinase/AKT/glycogen synthase kinase 3βsignaling pathway.展开更多
Background: In lacustrine communities, whether in Benin or elsewhere, populations use impregnated mosquito nets (IMNs) as fishing nets. This depletes the lake of its fishery resources, which in turn are contaminated b...Background: In lacustrine communities, whether in Benin or elsewhere, populations use impregnated mosquito nets (IMNs) as fishing nets. This depletes the lake of its fishery resources, which in turn are contaminated by the pyrethroids impregnated in the nets. This study aims to determine the scale and factors associated with the use of pyrethroid-impregnated mosquito nets as fishing tools in the municipality of Sô-Ava in Benin. Methods: This is a cross-sectional and analytical study with two components. First, a quantitative component was made up of 280 volunteers who were interviewed in the seven districts of the city. Data collection was done in two phases: the first from September to October 2020, and the second in August 2022. Data were analyzed with Stata and logistic regression was used. Another qualitative component was made up of forty participants chosen by reasoned choice, of which 32 were split into four focus groups of eight members each, and the rest participated in semi-structured interviews. Triangulation of the different sources was used to analyze the data. Results: Around 67% of the population reported using impregnated mosquito nets as fishing tools and 33% exclusively for malaria. Seasonal fishermen (ORa = 2.03, CI = 1.35 - 4.97, P = 0.004) and years of professional experience (ORa = 1.53, CI = 1.00 - 2.05, P = 0.021) increase the risk of using these nets as fishing tools. The use of insecticide-treated mosquito nets against mosquitoes causes skin scratching and impairs breathing because of the impregnation products, as reported by respondents. Conclusion: A high prevalence of inappropriate use of impregnated mosquito nets in fishing practices is highlighted in this study. Interviews in the field revealed that nets are diverted for fishing purposes to increase the volume of catches. Consequently, it will be appropriate to assess the pyrethroid content in water and fishery products.展开更多
As an important indicator parameter of fluid identification,fluid factor has always been a concern for scholars.However,when predicting Russell fluid factor or effective pore-fluid bulk modulus,it is necessary to intr...As an important indicator parameter of fluid identification,fluid factor has always been a concern for scholars.However,when predicting Russell fluid factor or effective pore-fluid bulk modulus,it is necessary to introduce a new rock skeleton parameter which is the dry-rock VP/VS ratio squared(DVRS).In the process of fluid factor calculation or inversion,the existing methods take this parameter as a static constant,which has been estimated in advance,and then apply it to the fluid factor calculation and inversion.The fluid identification analysis based on a portion of the Marmousi 2 model and numerical forward modeling test show that,taking the DVRS as a static constant will limit the identification ability of fluid factor and reduce the inversion accuracy.To solve the above problems,we proposed a new method to regard the DVRS as a dynamic variable varying with depth and lithology for the first time,then apply it to fluid factor calculation and inversion.Firstly,the exact Zoeppritz equations are rewritten into a new form containing the fluid factor and DVRS of upper and lower layers.Next,the new equations are applied to the four parameters simultaneous inversion based on the generalized nonlinear inversion(GNI)method.The testing results on a portion of the Marmousi 2 model and field data show that dynamic DVRS can significantly improve the fluid factor identification ability,effectively suppress illusion.Both synthetic and filed data tests also demonstrate that the GNI method based on Bayesian deterministic inversion(BDI)theory can successfully solve the above four parameter simultaneous inversion problem,and taking the dynamic DVRS as a target inversion parameter can effectively improve the inversion accuracy of fluid factor.All these results completely verified the feasibility and effectiveness of the proposed method.展开更多
文摘In this editorial,we review the work of Razali et al published in World J Gas-troenterology,with a particular focus on the effect of rs10889677 variation in the phosphatidylinositol 3-kinase(PI3K)pathway and buparlisib on colitis-associated cancer.The role of PI3K in promoting cancer progression has been widely recognized,as it is involved in regulating the survival,differentiation,and prolif-eration of cancer cells.The complement Clq/TNF-related protein 6(CTRP6)is a newer tumor-associated factor.Recent studies have revealed the pro-tumor effect of CTRP6 in gastric cancer,hepatocellular carcinoma,colorectal cancer,and other gastrointestinal tumors through the PI3K pathway.This article attempts to reveal the mechanism through which the CTRP6 affects the development of digestive system tumors through the PI3K pathway by summarizing recent research.
基金supported by the Community Development Office of Hunan Provincial Science and Technology DepartmentChina,Nos.2020SK53613(to DH),21JJ31006(to DH)the Fundamental Research Funds of Central South University,Nos.CX20220375(to TX),2023zzts215(to MZ)。
文摘Sortilin-related receptor 1(SORL1)is a critical gene associated with late-onset Alzheimer’s disease.SORL1 contributes to the development and progression of this neurodegenerative condition by affecting the transport and metabolism of intracellularβ-amyloid precursor protein.To better understand the underlying mechanisms of SORL1 in the pathogenesis of late-onset Alzheimer s disease,in this study,we established a mouse model of SorI1 gene knockout using cluste red regularly inters paced short palindro mic repeats-associated protein 9 technology.We found that Sorl1-knocko ut mice displayed deficits in learning and memory.Furthermore,the expression of brain-derived neurotrophic factor was significantly downregulated in the hippocampus and co rtex,and amyloidβ-protein deposits were observed in the brains of 5orl1-knockout mice.In vitro,hippocampal neuronal cell synapses from homozygous Sorl1-knockout mice were impaired.The expression of synaptic proteins,including Drebrin and NR2B,was significantly reduced,and also their colocalization.Additionally,by knocking out the Sorl1 gene in N2a cells,we found that expression of the N-methyl-D-aspartate receptor,NR2B,and cyclic adenosine monophosphate-response element binding protein was also inhibited.These findings suggest that SORL1 participates in the pathogenesis of late-onset Alzheimer s disease by regulating the N-methyl-D-aspartate receptor NR2B/cyclic adenosine monophosphate-response element binding protein signaling axis.
基金supported by the National Natural Science Foundation of China,Nos.82071190 and 82371438(to LC)Innovative Strong School Project of Guangdong Medical University,No.4SG21230G(to LC)Scientific Research Foundation of Guangdong Medical University,No.GDMUM2020017(to CL)。
文摘Alzheimer s disease,among the most common neurodegenerative disorders,is chara cterized by progressive cognitive impairment.At present,the Alzheimer’s disease main risk remains genetic ris ks,but major environmental fa ctors are increasingly shown to impact Alzheimer’s disease development and progression.Microglia,the most important brain immune cells,play a central role in Alzheimer’s disease pathogenesis and are considered environmental and lifestyle"sensors."Factors like environmental pollution and modern lifestyles(e.g.,chronic stress,poor dietary habits,sleep,and circadian rhythm disorde rs)can cause neuroinflammato ry responses that lead to cognitive impairment via microglial functioning and phenotypic regulation.However,the specific mechanisms underlying interactions among these facto rs and microglia in Alzheimer’s disease are unclear.Herein,we:discuss the biological effects of air pollution,chronic stress,gut micro biota,sleep patterns,physical exercise,cigarette smoking,and caffeine consumption on microglia;consider how unhealthy lifestyle factors influence individual susceptibility to Alzheimer’s disease;and present the neuroprotective effects of a healthy lifestyle.Toward intervening and controlling these environmental risk fa ctors at an early Alzheimer’s disease stage,understanding the role of microglia in Alzheimer’s disease development,and to rgeting strategies to to rget microglia,co uld be essential to future Alzheimer’s disease treatments.
文摘Physical activity and exercise have several beneficial roles in enhancing both physiological and psychological well-being of an individual.In addition to aiding the regulation of aerobic and anaerobic metabolism,exercise can stimulate the synthesis of exerkine hormones in the circulatory system.Among several exerkines that have been investigated for their therapeutic potential,Brain-derived neurotrophic factor(BDNF)is considered the most promising candidate,especially in the management of neurodegenerative diseases.Owing to the ability of physical activity to enhance BDNF synthesis,several experimental studies conducted so far have validated this hypothesis and produced satisfactory results at the pre-clinical level.This review highlights some of the recent animal model studies that have evaluated the efficiency of exercise in enhancing BDNF synthesis and promoting neuroprotective effects.Further,this review focuses on understanding the therapeutic benefits of exercise-induced exerkine synthesis as a non-pharmacological strategy in Parkinson’s disease(PD).Regarding physical activity and exerkine induction,the neuromuscular electrical stimulation(NMES)strategy could be considered as an alternate treatment modality for patients affected with PD.
基金supported by Project of Chongqing Science and Technology Bureau (cstc2022jxjl0005)。
文摘This study aimed to investigate the pollution characteristics, source apportionment, and health risks associated with trace metal(loid)s(TMs) in the major agricultural producing areas in Chongqing, China. We analyzed the source apportionment and assessed the health risk of TMs in agricultural soils by using positive matrix factorization(PMF) model and health risk assessment(HRA) model based on Monte Carlo simulation. Meanwhile, we combined PMF and HRA models to explore the health risks of TMs in agricultural soils by different pollution sources to determine the priority control factors. Results showed that the average contents of cadmium(Cd), arsenic (As), lead(Pb), chromium(Cr), copper(Cu), nickel(Ni), and zinc(Zn) in the soil were found to be 0.26, 5.93, 27.14, 61.32, 23.81, 32.45, and 78.65 mg/kg, respectively. Spatial analysis and source apportionment analysis revealed that urban and industrial sources, agricultural sources, and natural sources accounted for 33.0%, 27.7%, and 39.3% of TM accumulation in the soil, respectively. In the HRA model based on Monte Carlo simulation, noncarcinogenic risks were deemed negligible(hazard index <1), the carcinogenic risks were at acceptable level(10^(-6)<total carcinogenic risk ≤ 10^(-4)), with higher risks observed for children compared to adults. The relationship between TMs, their sources, and health risks indicated that urban and industrial sources were primarily associated with As, contributing to 75.1% of carcinogenic risks and 55.7% of non-carcinogenic risks, making them the primary control factors. Meanwhile, agricultural sources were primarily linked to Cd and Pb, contributing to 13.1% of carcinogenic risks and 21.8% of non-carcinogenic risks, designating them as secondary control factors.
基金Supported by Developing Program for High-level Academic Talent in Jiangsu Hospital of Chinese Medicine,No.y2021rc03Postgraduate Research and Innovation Program of Jiangsu Province,China,No.KYCX23_2172.
文摘BACKGROUND Psychological distress,especially depression,associated with perianal fistulizing Crohn’s disease(PFCD)is widespread and refractory.However,there is a surprising paucity of studies to date that have sought to identify the prevalence and risk factors of depression associated with PFCD.AIM To estimate the prevalence of depressive symptoms and investigate the depression-related risk factors in patients with PFCD.METHODS The study was conducted in the form of survey and clinical data collection via questionnaire and specialized medical staff.Depressive symptoms,life quality,and fatigue severity of patients with PFCD were assessed by Patient Health Questionnaire-9,Inflammatory Bowel Disease Patient Quality of Life Questionnaire(IBDQ),and Inflammatory Bowel Disease(IBD)Fatigue Patient Self-assessment Scale.The basic demographic information,overall disease features,perianal clinical information,and laboratory inflammation indicators were also gathered.Multivariate regression analysis was ultimately used to ascertain the risk factors of depression associated with PFCD.RESULTS A total of 123 patients with PFCD were involved,and 56.91%were suffering from depression.According to multivariate logistic regression analysis,Perianal Disease Activity Index(PDAI)score[odds ratio(OR)=0.69,95%confidence interval(CI):0.50 to 0.95],IBDQ score(OR=0.93,95%CI:0.88 to 0.97),modified Van Assche index(OR=1.24,95%CI:1.01 to 1.53),and IBD Fatigue score(OR=1.72,95%CI:1.23 to 2.42)were independent risk factors of depression-related prevalence among patients with PFCD(P<0.05).Multiple linear regression analysis revealed that the increasing perianal modified Van Assche index(βvalue=0.166,95%CI:0.02 to 0.31)and decreasing IBDQ score(βvalue=-0.116,95%CI:-0.14 to-0.09)were independently associated with the severity of depression(P<0.05).CONCLUSION Depressive symptoms in PFCD patients have significantly high prevalence.PDAI score,modified Van Assche index,quality of life,and fatigue severity were the main independent risk factors.
文摘Introduction: Obesity and overweight are a public health problem. The general objective was to determine the epidemiological aspects of obesity, overweight and associated risk factors in a semi-urban environment. Patients and Methods: This was a cross-sectional, descriptive study conducted on November 28 and 29, 2023 in Sébikotane. It focused on volunteers for screening for chronic non-communicable diseases. Epidemiological and clinical data were evaluated. Results: One hundred and twenty-nine cases of obesity were recorded (28%). Two hundred and eighty-two cases were overweight or obese (61.3%). The mean age was 49.55 years, with a standard deviation of 12.41 years. The age group [40 - 49 years] was the most representative, with 85 cases (30.1%), and the majority were female, with 264 cases (93.6%). Primary education was the most common, with 75 cases (46.3%). Grade 1 obesity concerned ninety-seven cases (75.2%), and diabetes was present in thirty cases (23%). Hypertension was present in ninety-five cases (33.7%). Obesity was more marked in the age group [40 - 49 years] with 45 cases (36%). Conclusion: Obesity and overweight are a major cause of morbidity and mortality. The development and implementation of a prevention and management program is essential.
基金supported by the National Natural Science Foundation of China,Nos.82171429,81771384a grant from Wuxi Municipal Health Commission,No.1286010241190480(all to YS)。
文摘Interferon regulatory factor 7 plays a crucial role in the innate immune response.However,whether interferon regulatory factor 7-mediated signaling contributes to Parkinson's disease remains unknown.Here we report that interferon regulatory factor 7 is markedly up-regulated in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced mouse model of Parkinson's disease and co-localizes with microglial cells.Both the selective cyclic guanosine monophosphate adenosine monophosphate synthase inhibitor RU.521 and the stimulator of interferon genes inhibitor H151 effectively suppressed interferon regulatory factor 7 activation in BV2 microglia exposed to 1-methyl-4-phenylpyridinium and inhibited transformation of mouse BV2 microglia into the neurotoxic M1 phenotype.In addition,si RNA-mediated knockdown of interferon regulatory factor 7 expression in BV2 microglia reduced the expression of inducible nitric oxide synthase,tumor necrosis factorα,CD16,CD32,and CD86 and increased the expression of the anti-inflammatory markers ARG1 and YM1.Taken together,our findings indicate that the cyclic guanosine monophosphate adenosine monophosphate synthase-stimulator of interferon genes-interferon regulatory factor 7 pathway plays a crucial role in the pathogenesis of Parkinson's disease.
文摘Aging is a physiological event dependent on multiple pathways that are linked to lifespan and processes leading to cognitive decline.This process represents the major risk factor for aging-related diseases such as Alzheimer’s disease,Parkinson’s disease,and ischemic stroke.The incidence of all these pathologies increases exponentially with age.Research on aging biology has currently focused on elucidating molecular mechanisms leading to the development of those pathologies.Cognitive deficit and neurodegeneration,common features of aging-related pathologies,are related to the alteration of the activity and levels of neurotrophic factors,such as brain-derived neurotrophic factor,nerve growth factor,and glial cell-derived neurotrophic factor.For this reason,treatments that modulate neurotrophin levels have acquired a great deal of interest in preventing neurodegeneration and promoting neural regeneration in several neurological diseases.Those treatments include both the direct administration of neurotrophic factors and the induced expression with viral vectors,neurotrophins’binding with biomaterials or other molecules to increase their bioavailability but also cell-based therapies.Considering neurotrophins’crucial role in aging pathologies,here we discuss the involvement of several neurotrophic factors in the most common brain aging-related diseases and the most recent therapeutic approaches that provide direct and sustained neurotrophic support.
基金This research was funded by Guangzhou Science and Technology Plan Projects(No.202002020066)the Young Scientists to the NSFC Application of Guangdong Provincial People’s Hospital(No.8210120306)the Open Foundation of the State Key Laboratory of Bioactive Seaweed Substance(No.SKL-BMSG2022-03)。
文摘Objective Vitamin D(VD)deficiency was reported to contribute to the progression of Crohn’s disease(CD)and affect the prognosis of CD patients.This study investigated the role of serum VD,body mass index(BMI),and tumor necrosis factor alpha(TNF-α)in the diagnosis of Crohn’s disease.Methods CD patients(n=76)and healthy subjects(n=76)were enrolled between May 2019 and December 2020.The serum 25-hydroxyvitamin D[25(OH)D]levels,BMI,and TNF-αlevels,together with other biochemical parameters,were assessed before treatment.The diagnostic efficacy of the single and joint detection of serum 25(OH)D,BMI,and TNF-αwas determined using receiver operating characteristic(ROC)curves.Results The levels of 25(OH)D,BMI,and nutritional indicators,including hemoglobin,total protein,albumin,and high-density lipoprotein cholesterol,were much lower,and the TNF-αlevels were much higher in the CD patients than in the healthy subjects(P<0.05 for all).The areas under the ROC curve for the single detection of 25(OH)D,BMI,and TNF-αwere 0.887,0.896,and 0.838,respectively,with the optimal cutoff values being 20.64 ng/mL,19.77 kg/m^(2),and 6.85 fmol/mL,respectively.The diagnostic efficacy of the joint detection of 25(OH)D,BMI,and TNF-αwas the highest,with an area under the ROC curve of 0.988(95%CI:0.968–1.000).Conclusion The joint detection of 25(OH)D,TNF-α,and BMI showed high sensitivity,specificity,and accuracy in CD diagnosis;thus,it would be effective for the diagnosis of CD in clinical practice.
基金supported by the National Natural Science Foundation of China,No. 81971006 (to DSG)。
文摘Previous studies have found that deficiency in nuclear receptor-related factor 1(Nurr1),which participates in the development,differentiation,survival,and degeneration of dopaminergic neurons,is associated with Parkinson s disease,but the mechanism of action is perplexing.Here,we first asce rtained the repercussion of knocking down Nurr1 by pe rforming liquid chromatography coupled with tandem mass spectrometry.We found that 231 genes were highly expressed in dopaminergic neurons with Nurr1 deficiency,14 of which were linked to the Parkinson’s disease pathway based on Kyoto Encyclopedia of Genes and Genomes analysis.To better understand how Nurr1 deficiency autonomously invokes the decline of dopaminergic neurons and elicits Parkinson’s disease symptoms,we performed single-nuclei RNA sequencing in a Nurr1 LV-shRNA mouse model.The results revealed cellular heterogeneity in the substantia nigra and a number of activated genes,the preponderance of which encode components of the major histocompatibility Ⅱ complex.Cd74,H2-Ab1,H2-Aα,H2-Eb1,Lyz2,Mrc1,Slc6α3,Slc47α1,Ms4α4b,and Ptprc2 were the top 10 diffe rentially expressed genes.Immunofluorescence staining showed that,after Nurr1knockdown,the number of CD74-immunoreactive cells in mouse brain tissue was markedly increased.In addition,Cd74 expression was increased in a mouse model of Parkinson’s disease induced by treatment with 6-hydroxydopamine.Ta ken togethe r,our res ults suggest that Nurr1 deficiency results in an increase in Cd74 expression,thereby leading to the destruction of dopaminergic neuro ns.These findings provide a potential therapeutic target for the treatment of Parkinson’s disease.
文摘Biologic agents with various mechanisms against Crohn’s disease(CD)have been released and are widely used in clinical practice.However,two anti-tumor necrosis factor(TNF)agents,infliximab(IFX)and adalimumab(ADL),are the only biologic agents approved by the Food and Drug Administration for pediatric CD currently.Therefore,in pediatric CD,the choice of biologic agents should be made more carefully to achieve the therapeutic goal.There are currently no headto-head trials of biologic agents in pediatric or adult CD.There is a lack of accumulated data for pediatric CD,which requires the extrapolation of adult data for the positioning of biologics in pediatric CD.From a pharmacokinetic point of view,IFX is more advantageous than ADL when the inflammatory burden is high,and ADL is expected to be advantageous over IFX in sustaining remission in the maintenance phase.Additionally,we reviewed the safety profile,immunogenicity,preference,and compliance between IFX and ADL and provide practical insights into the choice of anti-TNF therapy in pediatric CD.Careful evaluation of clinical indications and disease behavior is essential when prescribing anti-TNF agents.In addition,factors such as the efficacy of induction and maintenance of remission,safety profile,immunogenicity,patient preference,and compliance play an important role in evaluating and selecting treatment options.
文摘Objectives:This study aims to ascertain if cultural factors influence the childbirth place choice of women in Oyigbo.Materials and Methods:The study used a cross‑sectional study design using a self‑structured questionnaire as the instrument to collect data from 384 volunteers through simple random sampling,and these data were analyzed using frequency and percentage for descriptive statistics while Chi‑square was used for inferential statistics at 0.05 level of significance.Results:The influence of cultural factors such as family traditions(χ^(2)=12.56,P=0.006),beliefs(χ^(2)=70.66,P=0.000),lack of confidence in health facilities(χ^(2)=367.83,P=0.000),and the presence of male skilled birth attendants(χ^(2)=50.85,P=0.000)were statistically significant to the choice of childbirth place,while patriarchal system(χ^(2)=2.99,P=0.393)was not statistically significant to the choices of childbirth places of women in Oyigbo.Religion had a statistically significant influence on childbirth place(χ^(2)=125.46,P=0.000).Conclusion:This study shows that religious and cultural factors have a significant influence on the childbirth place choices of women in Oyigbo Local Government Area of Rivers State.
文摘Previous studies have shown that fibroblast growth factor 13 is downregulated in the brain of both Alzheimer’s disease mouse models and patients,and that it plays a vital role in the learning and memory.However,the underlying mechanisms of fibroblast growth factor 13 in Alzheimer’s disease remain unclear.In this study,we established rat models of Alzheimer’s disease by stereotaxic injection of amyloid-β(Aβ_(1-42))-induced into bilateral hippocampus.We also injected lentivirus containing fibroblast growth factor 13 into bilateral hippocampus to overexpress fibroblast growth factor 13.The expression of fibroblast growth factor 13 was downregulated in the brain of the Alzheimer’s disease model rats.After overexpression of fibroblast growth factor 13,learning and memory abilities of the Alzheimer’s disease model rats were remarkably improved.Fibroblast growth factor 13 overexpression increased brain expression levels of oxidative stress-related markers glutathione,superoxide dismutase,phosphatidylinositol-3-kinase,AKT and glycogen synthase kinase 3β,and anti-apoptotic factor BCL.Furthermore,fibroblast growth factor 13 overexpression decreased the number of apoptotic cells,expression of pro-apoptotic factor BAX,cleaved-caspase 3 and amyloid-βexpression,and levels of tau phosphorylation,malondialdehyde,reactive oxygen species and acetylcholinesterase in the brain of Alzheimer’s disease model rats.The changes were reversed by the phosphatidylinositol-3-kinase inhibitor LY294002.These findings suggest that overexpression of fibroblast growth factor 13 improved neuronal damage in a rat model of Alzheimer’s disease through activation of the phosphatidylinositol-3-kinase/AKT/glycogen synthase kinase 3βsignaling pathway.
文摘Background: In lacustrine communities, whether in Benin or elsewhere, populations use impregnated mosquito nets (IMNs) as fishing nets. This depletes the lake of its fishery resources, which in turn are contaminated by the pyrethroids impregnated in the nets. This study aims to determine the scale and factors associated with the use of pyrethroid-impregnated mosquito nets as fishing tools in the municipality of Sô-Ava in Benin. Methods: This is a cross-sectional and analytical study with two components. First, a quantitative component was made up of 280 volunteers who were interviewed in the seven districts of the city. Data collection was done in two phases: the first from September to October 2020, and the second in August 2022. Data were analyzed with Stata and logistic regression was used. Another qualitative component was made up of forty participants chosen by reasoned choice, of which 32 were split into four focus groups of eight members each, and the rest participated in semi-structured interviews. Triangulation of the different sources was used to analyze the data. Results: Around 67% of the population reported using impregnated mosquito nets as fishing tools and 33% exclusively for malaria. Seasonal fishermen (ORa = 2.03, CI = 1.35 - 4.97, P = 0.004) and years of professional experience (ORa = 1.53, CI = 1.00 - 2.05, P = 0.021) increase the risk of using these nets as fishing tools. The use of insecticide-treated mosquito nets against mosquitoes causes skin scratching and impairs breathing because of the impregnation products, as reported by respondents. Conclusion: A high prevalence of inappropriate use of impregnated mosquito nets in fishing practices is highlighted in this study. Interviews in the field revealed that nets are diverted for fishing purposes to increase the volume of catches. Consequently, it will be appropriate to assess the pyrethroid content in water and fishery products.
基金the National Natural Science Foundation of China(41904116,41874156,42074167 and 42204135)the Natural Science Foundation of Hunan Province(2020JJ5168)the China Postdoctoral Science Foundation(2021M703629)for their funding of this research.
文摘As an important indicator parameter of fluid identification,fluid factor has always been a concern for scholars.However,when predicting Russell fluid factor or effective pore-fluid bulk modulus,it is necessary to introduce a new rock skeleton parameter which is the dry-rock VP/VS ratio squared(DVRS).In the process of fluid factor calculation or inversion,the existing methods take this parameter as a static constant,which has been estimated in advance,and then apply it to the fluid factor calculation and inversion.The fluid identification analysis based on a portion of the Marmousi 2 model and numerical forward modeling test show that,taking the DVRS as a static constant will limit the identification ability of fluid factor and reduce the inversion accuracy.To solve the above problems,we proposed a new method to regard the DVRS as a dynamic variable varying with depth and lithology for the first time,then apply it to fluid factor calculation and inversion.Firstly,the exact Zoeppritz equations are rewritten into a new form containing the fluid factor and DVRS of upper and lower layers.Next,the new equations are applied to the four parameters simultaneous inversion based on the generalized nonlinear inversion(GNI)method.The testing results on a portion of the Marmousi 2 model and field data show that dynamic DVRS can significantly improve the fluid factor identification ability,effectively suppress illusion.Both synthetic and filed data tests also demonstrate that the GNI method based on Bayesian deterministic inversion(BDI)theory can successfully solve the above four parameter simultaneous inversion problem,and taking the dynamic DVRS as a target inversion parameter can effectively improve the inversion accuracy of fluid factor.All these results completely verified the feasibility and effectiveness of the proposed method.