Interplay between microglia and environmental risk factors in Alzheimer's disease

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.

Environmental enrichment in combination with Bifidobacterium breve HNXY26M4 intervention amplifies neuroprotective benefits in a mouse model of Alzheimer's disease by modulating glutamine metabolism of the gut microbiome

The gut microbiota-brain axis has emerged as a novel target for Alzheimer's disease(AD),a neurodegenerative disease characterised by behavioural and cognitive impairment.However,most previous microbiome-based intervention studies have focused on single factors and yielded only modest cognitive improvements.Here,we proposed a multidomain intervention strategy that combined Bifidobacterium breve treatment with environmental enrichment(EE)training.In this study,we found that compared with EE or B.breve treatment alone,B.breve intervention combined with EE amplified its neuroprotective effects on AD mice,as reflected by improved cognition,inhibited neuroinflammation and enhanced synaptic function.Moreover,using microbiome and metabolome profiling,we found that the combination of B.breve and EE treatment restored AD-related gut microbiota dysbiosis and reversed microbial metabolite changes.Finally,by integrating behavioural and neurological data with metabolomic profiles,we revealed that the underlying mechanism may involve the modulation of microbiota-derived glutamine metabolism via gut-brain interactions.Collectively,combined B.breve intervention with EE treatment can alleviate AD-related cognitive impairment and improve brain function by regulating glutamine metabolism of the gut microbiome.Our findings provide a promising multidomain intervention strategy,with a combination of dietary microbiome-based and lifestyle-targeted interventions,to promote brain function and delay the progression of AD.

Pathogenesis of Parkinson＇s disease： oxidative stress, environmental impact factors and inflammatory processes

Current hypothesis of neuronal degeneration in Parkinson＇s disease （PD） have been proposed, including formation of free radicals and oxidative stress, mitochondrial dysfunction, excitotoxicity, trophic factor deficiency, inflammatory processes, genetic factors, environmental impact factors, toxic action of nitric oxide, apoptosis, and so on. This review mainly discussed oxidative stress, environmental impact factors, and inflammatory processes in PD.

Pathogenesis of Parkinson’s disease: oxidative stress, environmental impact factors and inflammatory processes

Current hypothesis of neuronal degeneration in Parkinson’s disease (PD) have been proposed, including formation of free radicals and oxidative stress, mitochondrial dysfunction, excitotoxicity, trophic factor deficiency, inflam- matory processes, genetic factors, environmental impact factors, toxic action of nitric oxide, apoptosis, and so on. This review mainly discussed oxidative stress, environmental impact factors, and inflammatory processes in PD.

Environmental risk factors for inflammatory bowel diseases: Evidence based literature review

AIM: To advances in genetics and immunology have contributed to the current understanding of the pathogenesis of inflammatory bowel diseases(IBD). METHODS: The current opinion on the pathogenesis of IBD suggests that genetically susceptible individuals develop intolerance to dysregulated gut microflora(dysbiosis) and chronic inflammation develops as a result of environmental insults. Environmental exposures are innumerable with varying effects during the life course of individuals with IBD. Studying the relationship between environmental factors and IBD may provide the missing link to increasing our understanding of the etiology and increased incidence of IBD in recent years with implications for prevention, diagnosis, and treatment. Environmental factors are heterogeneous and genetic predisposition, immune dysregulation, or dysbiosis do not lead to the development of IBD in isolation. RESULTS: Current challenges in the study of environmental factors and IBD are how to effectively translate promising results from experimental studies to humans in order to develop models that incorporate the complex interactions between the environment, genetics, immunology, and gut microbiota, and limited high quality interventional studies assessing the effect of modifying environmental factors on the natural history and patient outcomes in IBD.CONCLUSION: This article critically reviews the current evidence on environmental risk factors for IBD and proposes directions for future research.

Influence of environmental factors on the onset and courseof inflammatory bowel disease

Numerous environmental factors have been linked with inflammatory bowel disease. These include smoking, diet, hygiene, drugs, geographical and psychosocial factors. These factors may either increase the risk of or protect against developing this condition and can also affect the course of illness in a positive or negative manner. A number of studies have examined the influence of environmental factors on inflammatory bowel diseases as a whole as well as on ulcerative colitis and Crohn's disease separately. As there are differences in the pathogenesis of ulcerative colitis and Crohn's disease, the effect of environmental factors on their onset and course is not always similar. Some factors have shown a consistent association, while reports on others have been conflicting. In this article we discuss the current evidence on the roles of these factors on inflammatory bowel disease, both as causative/protective agents and as modifiers of disease course.

Influence of environmental factors in the development of inflammatory bowel diseases

Idiopathic inflammatory bowel diseases (IBD), Crohn’s disease (CD) and ulcerative colitis (UC), are multifactorial diseases that are manifested after disruption of a genetic predisposed individual and its intestinal microflora through an environmental stimulus. Urbanization and industrialization are associated with IBD. Epidemiological data, clinical observations and family/immigrants studies indicate the significance of environmental influence in the development of IBD. Some environmental factors have a different effect on the subtypes of IBD. Smoking and appendectomy is negatively associated with UC, but they are aggravating factors for CD. A westernized high fat diet, full of refined carbohydrates is strongly associated with the development of IBD, contrary to a high in fruit, vegetables and polyunsaturated fatty acid-3 diet that is protective against these diseases. High intake of nonsteroidal antiinflammatory drug and oral contraceptive pills as well as the inadequacy of vitamin D leads to an increased risk for IBD and a more malignant course of disease. Moreover, other factors such as air pollution, psychological factors, sleep disturbances and exercise influence the development and the course of IBD. Epigenetic mechanism like DNA methylation, histone modification and altered expression of miRNAS could explain the connection between genes and environmental factors in triggering the development of IBD.

Independent and combined effects of environmental factors and miR-126, miR-143, and miR-145 on the risk of coronary heart disease

Objective To evaluate the effects of environmental factors and microRNAs （miRNAs） （miR-126, miR-143, and miR-145） on the risk of coronary heart disease （CHD）. Methods A frequency-matched case-control study （450 patients, 450 controls） was conducted from April 2014 to December 2016 in Fuzhou City, China. Environmental factors were investigated using a self-administered questionnaire, and the expression levels of miR-126, rniR-143, and miR-145 were determined by quantitative real-time Polymerase Chain Reaction （PCR） in pe- ripheral blood mononuclear cells. Unconditional logistic regression models were used for statistical evaluation. Results Alcohol consumption, high-salt diets, high-intensity work, and lack of physical activity were significantly associated with increased CHD risk, whereas light diet was significantly associated with decreased risk. MiR-126, miR-143, and miR-145 were highly expressed in the CHD group compared with the control group. After adjustment for other environmental factors, unconditional logistic regression results revealed that miR-126, miR-143, and depression were the independent risk factors of CHD, and light diet was the independent protective factor of CHD. Conclusions Our data suggest that a family history of CHD, anxiety, and alcohol consumption was significantly associated with increased CHD risk, whereas light diet was significantly associated with decreased risk. Furthermore, miR-126 and miR-143 in combination with several risk factors, could play a joint role in the development of CHD. Therefore, it is necessary to manage patients with CHD in all directions and multiple level.

Memantine combined with environmental enrichment improves spatial memory and alleviates Alzheimer's disease-like pathology in senescence-accelerated prone-8(SAMP8) mice

Memantine is a N-methyl-D-aspartate (NMDA) receptor antagonist approved for the treatment of moderate to severe Alzheimer's disease (AD). Environmental enrichment (EE) has shown significant beneficial effects on func- tional improvement in AD. In this study, we sought to determine whether combining these two distinct therapies would yield greater benefit than either drug used alone. We investigated the effect of memantine combined with EE on spatial learning and memory and AD-like pathology in a widely used AD model, the senescence-accelerated prone mice (SAMP8). The SAMP8 mice were randomly assigned to enriched housing (EH) or standard housing (SH), where either memantine (20 mg/kg) or saline was given by gastric lavage once daily continuously for eight weeks. Our results showed that, when provided separately, memantine and EE significantly improved spatial learning and memory by shortening escape latencies and increasing the frequency of entrance into the target quadrant. When combined, memantine and EE showed additive effect on learning and memory as evidenced by significant shorter escape latencies and higher frequency of target entrance than either drug alone. Consistent with the behavior results, pathological studies showed that both memantine and EE significantly reduced hippocampal CA1 neurofibrilliary tangles (NFTs) as well as amyloid beta precursor protein (APP) levels. Combining both therapies synergistically lessened NFTs and APP expression compared to either drug alone in SAMP8 mice, indicating that the combination of memantine with EE could offer a novel and efficient therapeutic strategy for the treatment of AD.

Impact of environmental and dietary factors on the course of inflammatory bowel disease

Besides their possible effects on the development of inflammatory bowel disease(IBD),some environmental factors can modulate the clinical course of both ulcerative colitis(UC) and Crohn's disease(CD).This review is mainly devoted to describing the current knowledge of the impact of some of these factors on the outcome of IBD,with special emphasis on smoking and diet.Although the impact of smoking on the susceptibility to develop CD and UC is firmly established,its influence on the clinical course of both diseases is still debatable.In CD,active smoking is a risk factor for postoperative recurrence.Beyond this clinical setting,smoking cessation seems to be advantageous in those CD patients who were smokers at disease diagnosis,while smoking resumption may be of benefit in ex-smokers with resistant UC.The role of dietary habits on the development of IBD is far from being well established.Also,food intolerances are very frequent,but usually inconsistent among IBD patients,and therefore no general dietary recommendations can be made in these patients.In general,IBD patients should eat a diet as varied as possible.Regarding the possible therapeutic role of some dietary components in IBD,lessons should be drawn from the investigation of the primary therapeutic effect of enteral nutrition in CD.Low-fat diets seem to be particularly useful.Also,some lipid sources,such as olive oil,medium-chain triglycerides,and perhaps omega-3 fatty acids,might have a therapeutic effect.Fermentable fiber may have a role in preventing relapses in inactive UC.

Crohn's disease environmental factors in the developing world: A case-control study in a statewide catchment area in Brazil

To identify environmental risk factors associated with the development of Crohn’s disease (CD) in order to re-assess the hygiene hypothesis. METHODSA hospital-based, case-control study was carried out with CD patients (n = 145) and controls (n = 163) representing a socioeconomically diverse statewide catchment area in Brazil. Controls were recruited from caregivers of patients seen in different outpatient clinics at the same hospital. A multi-item survey with 94 questions regarding family history of CD, perinatal and childhood circumstances, living conditions, tobacco use and familial socioeconomic status was carried out by interviewers. RESULTSOn the univariate analysis, predictive variables for CD included being male, under age of 40, a high education level, urban dweller, smaller family size, exposure to enteric pathogens and user of treated water (P < 0.005). On the multivariate analysis, variables significantly associated with CD were male gender (OR = 2.09), under age 40 (OR = 3.10), white (OR = 2.32), from a small family in childhood (OR = 2.34) and adulthood (OR = 3.02), absence of viral infections in childhood (OR = 2.23), exposure to enteric pathogens (OR = 2.41), having had an appendectomy (OR = 2.47) and prior or current smoker (OR = 2.83/1.12). CONCLUSIONMost variables supporting the “hygiene hypothesis” are associated with the development of CD but are not independent predictors of the diagnosis.

Molecular mechanisms underlying the neuroprotection of environmental enrichment in Parkinson’s disease

Parkinson’s disease is the most common movement disorder,affecting about 1%of the population over the age of 60 years.Parkinson’s disease is characterized clinically by resting tremor,bradykinesia,rigidity and postural instability,as a result of the progressive loss of nigrostriatal dopaminergic neurons.In addition to this neuronal cell loss,Parkinson’s disease is characterized by the accumulation of intracellular protein aggregates,Lewy bodies and Lewy neurites,composed primarily of the proteinα-synuclein.Although it was first described almost 200 years ago,there are no disease-modifying drugs to treat patients with Parkinson’s disease.In addition to conventional therapies,non-pharmacological treatment strategies are under investigation in patients and animal models of neurodegenerative disorders.Among such strategies,environmental enrichment,comprising physical exercise,cognitive stimulus,and social interactions,has been assessed in preclinical models of Parkinson’s disease.Environmental enrichment can cause structural and functional changes in the brain and promote neurogenesis and dendritic growth by modifying gene expression,enhancing the expression of neurotrophic factors and modulating neurotransmission.In this review article,we focus on the current knowledge about the molecular mechanisms underlying environmental enrichment neuroprotection in Parkinson’s disease,highlighting its influence on the dopaminergic,cholinergic,glutamatergic and GABAergic systems,as well as the involvement of neurotrophic factors.We describe experimental pre-clinical data showing how environmental enrichment can act as a modulator in a neurochemical and behavioral context in different animal models of Parkinson’s disease,highlighting the potential of environmental enrichment as an additional strategy in the management and prevention of this complex disease.

Epidemiological studies of migration and environmental risk factors in the inflammatory bowel diseases

Inflammatory bowel diseases(IBD)are idiopathic chronic diseases of the gastrointestinal tract well known to be associated with both genetic and environmental risk factors.Permissive genotypes may manifest into clinical phenotypes under certain environmental influences and these may be best studied from migratory studies.Exploring differences between first and second generation migrants may further highlight the contribution of environmental factors towards the development of IBD.There are few opportunities that have been offered so far.We aim to review the available migration studies on IBD,evaluate the known environmental factors associated with IBD,and explore modern migration patterns to identify new opportunities and candidate migrant groups in IBD migration research.

Non-alcoholic fatty liver disease and the impact of genetic,epigenetic and environmental factors in the offspring

Non-alcoholic fatty liver disease(NAFLD)is the most common chronic liver disease worldwide and is strongly associated with metabolic deregulation.More recently,a significant impact of parental NAFLD in the offspring was demonstrated and has been widely discussed.However,pathogenetic pathways implicated in the inheritance by the offspring and relatives are still under debate.Probably,multiple mechanisms are involved as well as in NAFLD pathogenesis itself.Among the multifactorial involved mechanisms,genetic,epigenetic and environmental backgrounds are strongly related to NAFLD development in the offspring.Thus,based on recent evidence from the available literature concerning genetic,epigenetic and environmental disease modifiers,this review aimed to discuss the relationship between parental NAFLD and its impact on the offspring.

Environmental Determinants of Disease Prevalence in Rural Western Nepal

Environmental determinants causing unexpected disease rampant are seemed major challenges to be protective from inevitable hazards and to deal the future consequences in terms of human health loss. This paper explores the major environmental determinants stimulating disease prevalence in western hilly areas of Nepal. Cross-sectional analytical research design for household level primary data was treated with the binary logit regression model to identify the determinants of disease prevalence. Extreme winter temperature, decreasing winter rainfall, sporadic rain, drying spout and decreasing the tree species are the major environmental determinants;hand washing, proper management of solid waste from kitchen and habit of drinking boiled water are as household behavioral determinants;and adequate family members, higher education, use of pesticide to control the insects and use of clean cooking fuels are socioeconomic determinants encouraging disease prevalence. Plantation of large perennial and medicinal plants, proper management of warm clothes or heaters especially for old people and children having respiratory problems for extreme winter;management of water tank for long drought in winter and community awareness campaign for the protection of spout are urgent needs for the prevention of current disease prevalence. Ergo, the recommendations are made accordingly.

Incidence, Severity and Gravity of Cassava Mosaic Disease in Savannah Agro-Ecological Region of DR-Congo: Analysis of Agro-Environmental Factors

African Cassava mosaic disease (ACMD) is the most severe and widespread disease caused by viruses limiting production of the crop in sub-Saharan Africa. The objective of the present study was to evaluate CMD incidence, severity, and gravity under different agro-environmental conditions. A total of 222 fields were surveyed in 23 different locations. All the farmers grow only local cassava varieties without applications of fertilizers. Overall, mean CMD incidences for all sites surveyed were 58.2% and 51.7%, in 2009 and 2010, respectively. Disease severity ranged from 2.4 to 3.1 on a scale of 1 to 5. Mean disease gravity varied from 29.7% to 62%, in 2010, and 2009, respectively. Detailed analysis of agronomic and environmental revealed no significant association between cassava stand locations, age, land topography and the development of CMD. Likewise intercropping practices and field topping did not affect the development of CMD in all the fields surveyed. There were significant differences in the number of white flies (Bemisia tabaci) per plant in 2009 and 2010, but no significant correlations between the number of B. tabaci per plant and CMD incidence, severity, and gravity was found. In most fields, CMD appears to originate mostly from unhealthy cassava cuttings used for planting.

The effects of the environmental factors on Laminaria disease caused by alginic acid decomposing bacteria

-The rot disease of Laminaria occurs often in nurseries of sporeling and commercial cultivation in the sea and results in economic loss greatly. Usually the disease outbreaks accompanied with massive multiplication of alginic acid decomposing bacteria. From the section of the decaying Lamuutria which resulted from the inoculation of alginic acid decomposing bacteria, it was observed that the bacteria invaded the epiderm of the Laminaria surface at first, then entered the ex-odermis, endodermis and pith. In addition, there were a great amount of bacteria in the intercellular region and a lot of free cells of the algae in the decaying areas. The wall of some free cells was decomposed, which led to soft tissue or disintegration. Alginic acid decomposing bacteria are normal epiphytic microorganisms growing on Lamuutria surface. These bacteria do not cause disease at normal environmental conditions. The experiments showed that the unfavourable conditions, e. g. , wounding, overcrowding, high temperature reduced the ability of antibacterial activity and made the algae more susceptible to the pathogens and favoured the multiplication of alginic acid decomposing bacteria and finally led to the disease outbreak. The unfavourable environmental factors which resulted from a variety of reasons were the main cause of the disease.

Biochar alleviates apple replant disease by reducing the growth of Fusarium oxysporum and regulating microbial communities

Apple replant disease(ARD)negatively affects plant growth and reduces yields in replanted orchards.In this study,biochar was applied to apple replant soil with Fusarium oxysporum.Our aim was to investigate whether biochar could promote plant growth and alleviate apple replant disease by reducing the growth of harmful soil microorganisms,changing soil microbial community structure and improving the soil environment.This experiment included five treatments:apple replant soil(CK),methyl bromide fumigation apple replant soil(FM),replant soil with biochar addition(2%),replant soil with F.oxysporum spore solution(8×10^(7)spores·mL^(-1)),and replant soil with biochar and F.oxysporum spore solution addition.Seedling biomass,the activity of antioxidant enzymes in the leaves and roots,and soil environmental variables were measured.Microbial community composition and community structure were analyzed using 16SrDNA and ITS2 gene sequencing.Biochar significantly reduced the abundance of F.oxysporum and increased soil microbial diversity and richness.Biochar also increased the soil enzyme activities(urease,invertase,neutral phosphatase,and catalase),the biomass(plant height,fresh weight,dry weight)and the activity of antioxidant enzymes(superoxide dismutase,peroxidase,and catalase).The root indexes of apple seedlings was also increased in replant soil by biochar.In sum,biochar promoted the growth of plants,improved the replant soil environment,and alleviated apple replant disease.

Einstein Hybrid Structure of q-Rung Orthopair Fuzzy Soft Set and Its Application for Diagnosis of Waterborne Infectious Disease

This research is devoted to diagnosing water-borne infectious diseases caused by floods employing a novel diagnosis approach,the Einstein hybrid structure of q-rung orthopair fuzzy soft set.This approach integrates parts of fuzzy logic and soft set theory to develop a robust alternative for disease detection in stressful situations,especially in areas affected by floods.Compared to the traditional intuitionistic fuzzy soft set and Pythagorean fuzzy soft set,the q-rung orthopair fuzzy soft set(q-ROFSS)adequately incorporates unclear and indeterminate facts.The major objective of this investigation is to formulate the q-rung orthopair fuzzy soft Einstein hybrid weighted average(q-ROFSEHWA)operator and its specific characteristics.Moreover,our stated operator is implementing intelligentmulti-criteria group decision-making(MCGDM)methodology.Floods are severe natural catastrophes that raise the risk of diseases and epidemics,particularly those caused by contaminants in the water,such as gastrointestinal diseases,respiratory infections,vector-borne diseases,skin infections,and water-borne parasites.The designed MCGDM strategy tackles the prevalence of certain conditions in flood-affected patients.A comparative investigation determined that the suggested method for detecting water-borne infectious disease due to floods is more effective and productive than conventional methods because of its logical structure.

Etiopathogenesis of inflammatory bowel diseases

Theories explaining the etiopathogenesis of inflammatory bowel disease （IBD） have been proposed ever since Crohn＇s disease （CD） and ulcerative colitis （UC） were recognized as the two major forms of the disease. Although the exact cause（s） and mechanisms of tissue damage in CD and UC have yet to be completely understood, enough progress has occurred to accept the following hypothesis as valid： IBD is an inappropriate immune response that occurs in genetically susceptible individuals as the result of a complex interaction among environmental factors, microbial factors, and the intestinal immune system. Among an almost endless list of environmental factors, smoking has been identified as a risk factor for CD and a protective factor for UC. Among microbial factors, no convincing evidence indicates that classical infectious agents cause IBD, while mounting evidence points to an abnormal immune response against the normal enteric flora as being of central importance. Gut inflammation is mediated by cells of the innate as well as adaptive immune systems, with the additional contribution of non-immune cells, such as epithelial, mesenchymal and endothelial cells, and platelets.