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.

Role of Oncostatin M in the prognosis of inflammatory bowel disease: A meta-analysis

BACKGROUND Oncostatin M(OSM)is a pleiotropic cytokine which is implicated in the path-ogenesis of inflammatory bowel disease(IBD).AIM To evaluate the prognostic role of OSM in IBD patients.METHODS Literature search was conducted in electronic databases(Google Scholar,Embase,PubMed,Science Direct,Springer,and Wiley).Studies were selected if they reported prognostic information about OSM in IBD patients.Outcome data were synthesized,and meta-analyses were performed to estimate standardized mean differences(SMDs)in OSM levels between treatment responders and non-res-ponders and to seek overall correlations of OSM with other inflammatory bio-markers.RESULTS Sixteen studies(818 Crohn’s disease and 686 ulcerative colitis patients treated with anti-tumor necrosis factor-based therapies)were included.OSM levels were associated with IBD severity.A meta-analysis found significantly higher OSM levels in non-responders than in responders to therapy[SMD 0.80(0.33,1.27);P=0.001],in non-remitters than in remitters[SMD 0.75(95%CI:0.35 to 1.16);P<0.0001]and in patients with no mucosal healing than in those with mucosal heal-ing[SMD 0.63(0.30,0.95);P<0.0001].Area under receiver operator curve values showed considerable variability between studies but in general higher OSM levels were associated with poor prognosis.OSM had significant correlations with Simple Endoscopic Score of Crohn’s disease[r=0.47(95%CI:0.25 to 0.64);P<0.0001],Mayo Endoscopic Score[r=0.35(95%CI:0.28 to 0.41);P<0.0001],fecal calprotectin[r=0.19(95%CI:0.08 to 0.3);P=0.001],C-reactive protein[r=0.25(95%CI:0.11 to 0.39);P<0.0001],and platelet count[r=0.28(95%CI:0.17 to 0.39);P<0.0001].CONCLUSION OSM is a potential candidate for determining the severity of disease and predicting the outcomes of anti-tumor necrosis factor-based therapies in IBD patients.

Upper gastrointestinal bleeding as an unusual manifestation of localized Ménétrier’s disease with an underlying lipoma:A case report

BACKGROUND Ménétrier’s disease is a rare condition characterized by enlarged gastric folds,usually located in the whole body and fundus of the stomach.This report presents an unusual case of localized Ménétrier’s disease elevated by a submucosal lipoma and thus looking like a polypoid mass and causing an episode of upper gastrointestinal bleeding.The mass was successfully removed with endoscopic submucosal dissection.CASE SUMMARY Esophagogastroduodenoscopy was performed on a 76-year-old male patient after an episode of upper gastrointestinal bleeding,manifesting as fatigue and melena.A large polypoid mass(4 cm×1 cm)with enlarged mucosal folds was found in the body of the stomach,between the lesser curvature and posterior wall.A small ulcer at the distal end of the mass was identified as the source of the bleeding.Biopsy was negative for neoplasia.Computed tomography showed a submucosal lesion beneath the affected mucosa,most likely a lipoma.The mass was removed en bloc with tunneling endoscopic submucosal dissection.Final pathology determined that the mass included Ménétrier’s disease and a submucosal lipoma.The patient was scheduled for follow-up esophagogastroduodenoscopy.CONCLUSION Localized Ménétrier’s disease can coexist with a submucosal lipoma creating a polypoid mass with risk of bleeding.

TMEM16F may be a new therapeutic target for Alzheimer's disease

TMEM16F is involved in many physiological processes such as blood coagulation,cell membrane fusion and bone mineralization.Activation of TMEM16F has been studied in various central nervous system diseases.High TMEM16F level has been also found to participate in microglial phagocytosis and transformation.Microglia-mediated neuroinflammation is a key factor in promoting the progression of Alzheimer’s disease.However,few studies have examined the effects of TMEM16F on neuroinflammation in Alzheimer’s disease.In this study,we established TMEM16F-knockdown AD model in vitro and in vivo to investigate the underlying regulatory mechanism about TMEM16F-mediated neuroinflammation in AD.We performed a Morris water maze test to evaluate the spatial memory ability of animals and detected markers for the microglia M1/M2 phenotype and NLRP3 inflammasome.Our results showed that TMEM16F was elevated in 9-month-old APP/PS1 mice.After TMEM16F knockdown in mice,spatial memory ability was improved,microglia polarization to the M2 phenotype was promoted,NLRP3 inflammasome activation was inhibited,cell apoptosis and Aβplaque deposition in brain tissue were reduced,and brain injury was alleviated.We used amyloid-beta(Aβ_(25-35))to stimulate human microglia to construct microglia models of Alzheimer’s disease.The levels of TMEM16F,inducible nitric oxide synthase(iNOS),proinflammatory cytokines and NLRP3 inflammasome-associated biomarkers were higher in Aβ_(25-35) treated group compared with that in the control group.TMEM16F knockdown enhanced the expression of the M2 phenotype biomarkers Arg1 and Socs3,reduced the release of proinflammatory factors interleukin-1,interleukin-6 and tumor necrosis factor-α,and inhibited NLRP3 inflammasome activation through reducing downstream proinflammatory factors interleukin-1βand interleukin-18.This inhibitory effect of TMEM16F knockdown on M1 microglia was partially reversed by the NLRP3 agonist Nigericin.Our findings suggest that TMEM16F participates in neuroinflammation in Alzheimer’s disease through participating in polarization of microglia and activation of the NLRP3 inflammasome.These results indicate that TMEM16F inhibition may be a potential therapeutic approach for Alzheimer’s disease treatment.

Clinical utility of a new endoscopic scoring system for Crohn's disease

AIM:To evaluate the clinical value of the newly modified Simple Endoscopic Score for Crohn's disease(m SES-CD).METHODS:Seventy-six Crohn's disease(CD) patients who underwent transanal double balloon endoscopy(DBE) in our hospital between 2003 and 2012 were retrospectively reviewed. DBE is defined as small intestinal endoscopy using two attached balloons. We included patients with stenosis which hampered passage of the scope and those who underwent DBE with observation for at least 80 cm from the ileocecal valve. Our new m SES-CD assesses the endoscopic activity of two consecutive small intestinal segments located 0-40 cm and 40-80 cm from the ileocecal valve by DBE,in addition to the activity of four colorectal segments. To compare the usefulness of m SES-CD with SES-CD,we similarly divided the patients into two groups according to total m SES-CD score(low disease activity group,< 4; high disease activity group,≥ 4). The clinical value of m SES-CD in predicting clinical outcome in patients with CD was evaluated using the occurrence of surgery after DBE as an endpoint.RESULTS:Median age of the 76 CD patients was 36 years(range,16-71). Thirty-nine patients had stenosis which hampered passage of the DBE to 80 cm on the proximal side from the ileocecal valve. Median evaluable length of small intestine by DBE was 80 cm(range,3-200). A total of 74 patients had one or more small intestinal lesions detected by DBE,of which 62(83.8%) were within 80 cm of the ileocecal valve on the proximal side. Only two patients(2.7%) with proximal-side lesions more than 80 cm from the ileocecal valve did not have lesions within 80 cm. Patients with high m SES-CD scores showed significantly shorter surgeryfree survival than those with low scores(P < 0.05). In contrast,surgery-free survival did not significantly differ between the low and high SES-CD groups(P > 0.05). Multivariate analysis by a Cox proportional hazards model identified m SES-CD as an independent factor for surgery-free survival.CONCLUSION:m SES-CD is useful in evaluating the risk of surgery-free survival in patients with CD.

Modified Titration Intratympanic Gentamicin Injection for Unilateral Intractable Ménière's Disease

This study looked into the efficacy of a modified titration protocol of intratympanic gentamicin injection（ITG） in the patients with unilateral intractable Ménière＇s disease（MD）. Modified titration protocol of ITG at a low dose（20 mg/m L） was administered to 10 patients with definite unilateral intractable MD. After initial first two fixed ITGs on weekly basis,the patients might or might not be given any more injections,depending on the appearance of unilateral vestibular loss（UVL）. ITG was terminated if the patients satisfied the criteria of UVL. All patients were followed-up for at least two years. The effects of ITG on the vertigo attack,functional level scores and postural balance were evaluated. Of the 10 cases,8 showed the sign of UVL after receiving initial two ITGs and were not given any more intratympanic injections,and the other 2 patients were administered three ITGs. A two-year follow-up revealed that complete and substantial vertigo control was achieved in 9 cases,and limited vertigo control in 1 patient. Hearing level was lowered in 2 patients. The posture stability and functional level scores were improved. Our study showed that the modified titration protocol of ITG at a low dose could effectively control vertigo in patients with unilateral intractable MD.

Prevalence of Tinnitus in Early Stages of Ménière’s Disease

Background: The aim of this study was to identify the prevalence of tinnitus in a sample of people with early stages of Ménière’s disease. Material and methods: A postal survey was sent to 256 patients all judged to fulfil the criteria of early unilateral Ménière’s disease established by the American Academy of Otolaryngology Committee on Hearing and Equilibrium. Of these 256 patients, 136 had probable Ménière’s disease and 120 had early possible Ménière’s disease. The same questionnaire was mailed and administered to 60 control subjects with no history of vestibular dysfunction. A total of 158 subjects completed the questionnaire. Results: Tinnitus was found in 54 (63%) of the 72 members of the final unilateral vestibular Ménière’s disease group and 61 (85 %) of the 72 members of the final unilateral probable Ménière’s disease group. Conclusion: The prevalence of tinnitus as determined by a questionnaire survey was significantly greater in patients with probable Ménière’s disease than in patients with early vestibular Ménière’s disease or in control subjects. However, the prevalence of tinnitus as determined by a questionnaire survey was significantly greater in patients with early vestibular Ménière’s disease than in control subjects.

It is 2015: What are the best diagnostic and treatment options for Ménière's disease?

Ménière's disease(MD) is a common cause of recurrent vertigo. Its pathophysiology is still unclear and controversial. The most common histological finding in postmortem temporal bone studies of patients is endolymphatic hydrops(EH). However, not all cases of hydrops are associated with MD and it may represent the end point of various etiologies. The diagnostic criteria for MD have undergone changes during the past few decades. A recent collaboration among specialty societies in United States, Europe and Japan has given rise to a new set of guidelines for the diagnosis and classification of MD. The aim is to develop international consensus criteria for MD that would help improve the quality of data collected from patients. The diagnosis of MD can be difficult in some cases as there is no gold standard for testing. Previous use of audiometric data and electrocochleography are poorly sensitive as screening tools. Recently magnetic resonance imaging as a diagnostic tool for identifying EH has gained popularity in Asia and Europe. Vestibular evoked myogenic potentials are also used but lack specificity. Finally, the treatment for MD has improved with the introduction of intratympanic treatments with steroids and gentamicin as well as less invasive treatment with the Meniett device.

Late onset fulminant Wilson's disease:A case report and review of the literature

Wilson’s disease(WD)is an autosomal recessive inherited disorder of hepatic copper metabolism.WD can be present in different clinical conditions,with the most common ones being liver disease and neuropsychiatric disturbances.Most cases present symptoms at<40years of age.However,few reports exist in the literature on patients in whom the disease presented beyond this age.In this report,we present a case of late onset fulminant WD in a 58-year-old patient in whom the diagnosis was established clinically,by genetic analysis of the ATP7B gene disclosing rare mutations(G1099S and c.1707+3ins T)as well as by high hepatic copper content.We also reviewed the relevant literature.The diagnosis of WD with late onset presentation is easily overlooked.The diagnostic features and the geneticbackground in patients with late onset WD are not different from those in patients with early onset WD,except for the age.Effective treatments for this disorder that can be fatal are available and will prevent or reverse many manifestations if the disease is discovered early.

NKX2-3 and IRGM variants are associated with diseasesu sceptibility to IBD in Eastern European patients

AIM: To investigate variants of immunity-related GT-Pase family M (IRGM) and NKX2-3 genes and genotype-phenotype in Eastern European patients with inflammatory bowel disease (IBD).METHODS: We analyzed 1707 Hungarian and Czech subjects with Crohn’s disease (CD) (n = 810, age: 37.1 ± 12.6 years, duration: 10.7 ± 8.4 years) and ulcerative colitis (UC) (n = 428, age: 43.7 ± 15.0 years, duration: 12.6 ± 9.9 years), as well as 469 healthy controls. IRGM rs13361189, NKX2-3 rs10883365 and ECM1 rs13294 polymorphisms were tested by LightCy-cler allele discrimination. Detailed clinical phenotypes were determined by reviewing the medical charts. RESULTS: NKX2-3 rs10883365 variant allele was as-sociated with increased risk for CD (P = 0.009, OR = 1.24, 95% CI = 1.06-1.48) and UC (P = 0.001, OR = 1.36, 95% CI = 1.13-1.63), whereas variant IRGM allele increased risk for CD (P = 0.029, OR = 1.36, 95% CI = 1.03-1.79). In contrast, ECM1 rs13294 was not associat-ed with either CD or UC. In CD, the variant IRGM allele was associated with a colon-only location (P = 0.02, OR = 1.62, 95% CI = 1.07-2.44), whereas in UC, the ECM1 variant was associated with cutaneous manifestations (P = 0.002, OR = 3.36, 95% CI = 1.48-7.63). Variant alleles did not predict resistance to steroids or azathio-prine, efficacy of infliximab, or need for surgery. CONCLUSION: NKX2-3 and IRGM are susceptibility locifor IBD in Eastern European patients. Further studies are needed to confirm the reported phenotype-genotype associations.

Curative resection with endoscopic submucosal dissection of early gastric cancer in Helicobacter pylori-negative Ménétrier’s disease:A case report

BACKGROUND Adult-onset Ménétrier’s disease is strongly associated with Helicobacter pylori(H.pylori)infection and an elevated risk of carcinogenesis.Cases of early-stage gastric cancer developed in H.pylori-negative Ménétrier’s disease are extremely rare.We report a case of early gastric cancer in H.pylori-negative Ménétrier’s disease that was curatively resected with endoscopic submucosal dissection(ESD).CASE SUMMARY A 60-year-old woman was referred to our hospital after her medical examination detected anemia.Contrast-enhanced upper gastrointestinal(UGI)radiography revealed translucency of the nodule-aggregating surface with giant rugae.Blood tests showed hypoproteinemia and were negative for serum H.pylori immunoglobulin G antibodies.The 99mTc-DTPA-human serum albumin scintigraphy showed protein loss from the stomach.UGI endoscopy showed a 40-mm protruding erythematous lesion on giant rugae of the greater curvature of lower gastric body,suggesting early-stage gastric cancer due to Ménétrier’s disease.En bloc resection with ESD was performed for diagnosis and treatment.Histology of ESD showed well-differentiated tubular adenocarcinoma.The cancer was confined to the mucosa,and complete curative resection was achieved.Foveolar hyperplasia and atrophy of the gastric glands were observed in non-tumor areas,histologically corresponding to Ménétrier’s disease.Three years after ESD,gastric cancer had not recurred,and Ménétrier’s disease remained in remission with spontaneous regression of giant gastric rugae.CONCLUSION Complete curative resection was achieved through ESD in a patient with earlystage gastric cancer and H.pylori-negative Ménétrier’s disease.

Myelinosome organelles in pathological retinas: ubiquitous presence and dual role in ocular proteostasis maintenance

The timely and efficient elimination of aberrant proteins and damaged organelles, formed in response to various genetic and environmental stressors, is a vital need for all cells of the body. Recent lines of evidence point out several non-classical strategies employed by ocular tissues to cope with aberrant constituents generated in the retina and in the retinal pigmented epithelium cells exposed to various stressors. Along with conventional strategies relying upon the intracellular degradation of aberrant constituents through ubiquitin-proteasome and/or lysosome-dependent autophagy proteolysis, two non-conventional mechanisms also contribute to proteostasis maintenance in ocular tissues. An exosome-mediated clearing and a myelinosome-driven secretion mechanism do not require intracellular degradation but provide the export of aberrant constituents and “waste proteins” outside of the cells. The current review is centered on the non-degradative myelinosome-driven secretion mechanism, which operates in the retina of transgenic Huntington’s disease R6/1 model mice. Myelinosome-driven secretion is supported by rare organelles myelinosomes that are detected not only in degenerative Huntington’s disease R6/1 retina but also in various pathological states of the retina and of the retinal pigmented epithelium. The intra-retinal traffic and inter-cellular exchange of myelinosomes was discussed in the context of a dual role of the myelinosome-driven secretion mechanism for proteostasis maintenance in different ocular compartments. Special focus was made on the interplay between degradative and non-degradative strategies in ocular pathophysiology, to delineate potential therapeutic approaches to counteract several vision diseases.

MNS血型系统同种抗体的分布、性质与免疫史研究

目的探讨MNS血型系统同种抗体在我院抗体筛查试验阳性的发生率和临床意义。方法回顾性分析我院2013年6月至2015年4月抗体筛查试验阳性患者中存在MNS血型系统同种抗体患者的临床资料,对其输血史、妊娠史、疾病特点进行总结分析。结果对41 550例患者进行抗体筛查试验,阳性者509例(1.2%),其中69例(69/509,13.6%)为MNS血型系统同种抗体。在此69例中,抗-M 64例,占92.8%;抗-N 2例,占2.9%;抗-S 3例,占4.3%;平均年龄(46.2±16.9)岁,有妊娠史者22例(31.9%),有输血史者14例(20.3%)。结论由于Ig G性质的抗体可引起新生儿溶血病(HDN),故应在明确孕产妇抗体筛查实验中的抗体性质后,及时为患者选择抗原阴性的血液作为储备,以确保其输血安全。MNS血型系统同种抗体可通过输血刺激产生,对于反复输血及器官移植患者,应定期做抗体筛查实验,并保留其结果,当鉴定出有特异性的同种抗体时,应给予相应抗原阴性交叉配血相合血液,以保证输血的安全性。

^(99)Tc^m—TRODAT-1 SPECT脑显像在评价苍白球腹后部毁损术治疗帕金森病长期疗效中的价值

目的探讨99Tcm-TRODAT-1SPECT脑显像在评价苍白球腹后部毁损术(PVP)治疗帕金森病(PD)疗效中的应用价值。方法对13例单侧PVP手术治疗病人、31例内科治疗PD病人和10名健康人(健康对照组),行脑99Tcm-TRODAT-1SPECT断层显像,利用感兴趣区技术测定纹状体与小脑部位DAT比值。结果健康对照组双侧纹状体摄取差异无统计学意义,内科治疗组PD病人及单侧PVP手术治疗PD病人双侧纹状体与小脑部位DAT比值(ST/CB)分别较健康对照组明显降低(P<0.05),症状对侧较症状同侧ST/CBDAT比值明显降低(P<0.05),内科治疗组PD病人同PVP手术治疗PD病人双侧ST/CB差异无统计学意义(P>0.05),但UPDRS评分前者高于后者(P<0.05)。结论99Tcm-TRODAT-1SPECT脑显像结合UPDRS评分,有助于客观评价PVP手术治疗PD的疗效,加深对PVP手术原理的理解和认识,同时为评价其他PD术式的疗效,提供新的思路和方法。

Lycium barbarum extract promotes M2 polarization and reduces oligomeric amyloid-β-induced inflammatory reactions in microglial cells

Lycium barbarum(LB)is a traditional Chinese medicine that has been demonstrated to exhibit a wide variety of biological functions,such as antioxidation,neuroprotection,and immune modulation.One of the main mechanisms of Alzheimer’s disease is that microglia activated by amyloid beta(Aβ)transform from the resting state to an M1 state and release pro-inflammatory cytokines to the surrounding environment.In the present study,immortalized microglial cells were pretreated with L.barbarum extract for 1 hour and then treated with oligomeric Aβfor 23 hours.The results showed that LB extract significantly increased the survival of oligomeric Aβ-induced microglial cells,downregulated the expression of M1 pro-inflammatory markers(inducible nitric oxide synthase,tumor necrosis factorα,interleukin-6,and interleukin-1β),and upregulated the expression of M2 anti-inflammatory markers(arginase-1,chitinase-like protein 3,and interleukin-4).LB extract also inhibited the oligomeric Aβ-induced secretion of tumor necrosis factorα,interleukin-6,and interleukin-1βin microglial cells.The results of in vitro cytological experiments suggest that,in microglial cells,LB extract can inhibit oligomeric Aβ-induced M1 polarization and concomitant inflammatory reactions,and promote M2 polarization.

Cu-3.0Ni-0.64Si合金的热变形行为

对Cu-3.0Ni-0.64Si合金进行了变形温度为750~900℃、变形速率为0.001~1s^(-1)条件下的等温压缩实验。结果表明,随着变形温度升高或变形速率降低,峰值应力明显降低,合金容易发生动态再结晶。通过线性回归分析,求得Cu-3.0Ni-0.64Si合金的变形激活能为410.4kJ/mol,建立了Cu-3.0Ni-0.64Si合金的高温热变形流变应力本构方程6)ε=e^(40.56)[sinh(0.017σ)]^(5.21)exp[-410.4×10~3/(RT)]。分别讨论了变形温度和变形速率对Cu-3.0Ni-0.64Si合金在等温压缩变形中显微组织的影响。最后基于动态材料模型理论,用Prasad失稳判据,得到不同真应变量下的热加工图。优化后的工艺参数为变形温度860~900℃和变形速率0.002~0.01s^(-1)。

Astrocytes protect dopaminergic neurons against aminochrome neurotoxicity

Astrocytes protect neurons by modulating neuronal function and survival.Astrocytes support neurons in several ways.They provide energy through the astrocyte-neuron lactate shuttle,protect neurons from excitotoxicity,and internalize neuronal lipid droplets to degrade fatty acids for neuronal metabolic and synaptic support,as well as by their high capacity for glutamate uptake and the conversion of glutamate to glutamine.A recent reported astrocyte system for protection of dopamine neurons against the neurotoxic products of dopamine,such as aminochrome and other o-quinones,were generated under neuromelanin synthesis by oxidizing dopamine catechol structure.Astrocytes secrete glutathione transferase M2-2 through exosomes that transport this enzyme into dopaminergic neurons to protect these neurons against aminochrome neurotoxicity.The role of this new astrocyte protective mechanism in Parkinson´s disease is discussed.

Interleukin-4 affects microglial autophagic flux

Interleukin-4 plays an important protective role in Alzheimer’s disease by regulating microglial phenotype,phagocytosis of amyloid-β,and secretion of anti-inflammatory and neurotrophic cytokines.Recently,increasing evidence has suggested that autophagy regulates innate immunity by affecting M1/M2 polarization of microglia/macrophages.However,the role of interleukin-4 in microglial autophagy is unknown.In view of this,BV2 microglia were treated with 0,10,20 or 50 ng/mL interleukin-4 for 24,48,or 72 hours.Subsequently,light chain 3-II and p62 protein expression levels were detected by western blot assay.BV2 microglia were incubated with interleukin-4(20 ng/mL,experimental group),3-methyladenine(500μM,autophagy inhibitor,negative control group),rapamycin(100 nM,autophagy inductor,positive control group),3-methyladenine+interleukin-4(rescue group),or without treatment for 24 hours,and then exposed to amyloid-β(1μM,model group)or vehicle control(control)for 24 hours.LC3-II and p62 protein expression levels were again detected by western blot assay.In addition,expression levels of multiple markers of M1 and M2 phenotype were assessed by real-time fluorescence quantitative polymerase chain reaction,while intracellular and supernatant amyloid-βprotein levels were measured by enzyme-linked immunosorbent assay.Our results showed that interleukin-4 induced microglial autophagic flux,most significantly at 20 ng/mL for 48 hours.Interleukin-4 pretreated microglia inhibited blockade of amyloid-β-induced autophagic flux,and promoted amyloid-βuptake and degradation partly through autophagic flux,but inhibited switching of amyloid-β-induced M1 phenotype independent on autophagic flux.These results indicate that interleukin-4 pretreated microglia increases uptake and degradation of amyloid-βin a process partly mediated by autophagy,which may play a protective role against Alzheimer’s disease.

Novel nervous and multi-system regenerative therapeutic strategies for diabetes mellitus with mTOR

Throughout the globe,diabetes mellitus（DM） is increasing in incidence with limited therapies presently available to prevent or resolve the significant complications of this disorder.DM impacts multiple organs and affects all components of the central and peripheral nervous systems that can range from dementia to diabetic neuropathy.The mechanistic target of rapamycin（m TOR） is a promising agent for the development of novel regenerative strategies for the treatment of DM.m TOR and its related signaling pathways impact multiple metabolic parameters that include cellular metabolic homeostasis,insulin resistance,insulin secretion,stem cell proliferation and differentiation,pancreatic β-cell function,and programmed cell death with apoptosis and autophagy.m TOR is central element for the protein complexes m TOR Complex 1（m TORC1） and m TOR Complex 2（m TORC2） and is a critical component for a number of signaling pathways that involve phosphoinositide 3-kinase（PI 3-K）,protein kinase B（Akt）,AMP activated protein kinase（AMPK）,silent mating type information regulation 2 homolog 1（Saccharomyces cerevisiae）（SIRT1）,Wnt1 inducible signaling pathway protein 1（WISP1）,and growth factors.As a result,m TOR represents an exciting target to offer new clinical avenues for the treatment of DM and the complications of this disease.Future studies directed to elucidate the delicate balance m TOR holds over cellular metabolism and the impact of its broad signaling pathways should foster the translation of these targets into effective clinical regimens for DM.

Vibrational Studies of Different Human Body Disorders Using FTIR Spectroscopy

Some of the important features of the bands occur in the present study. The band called amide A is available in all the diseased and healthy controls and the frequency of the band ranges from 3380 cm﹣1 to 3480.74 cm﹣1. The band due to C-H band and called hydrocarbon band was found only in paralytic and Alzheimer diseased along with normal healthy controls. Carbide band (C=C) is found only in Duchenne muscular dystrophy, paralytic and Alzheimer’s disease patients. Amide I was intact in all disorders with normal persons. Peroxide band (O-O) was found in all the cases of study. Amide IV band was found in paralytic, muscular dystrophy, Alzheimer’s diseases and normal controls. The amide V band was found in Alzheimer’s diseases only. The appearance or disappearance of the bands is a good sign to understand the mechanisms at the molecular level. FTIR spectroscopy may help in the diagnosis of the disease at the early stage of the onset. This spectroscopy can be used nicely for the study of hair, vaginal fluid, nails, urine, mucus, semen, synovial fluid, blood, hemoproteins, skin, and tears for human beings. We can also use it to understand the effect of adulteration on food and paint technology. FTIR is an indicator to explore the changes occurring at molecular level.