Autoantibodies related to ataxia and other central nervous system manifestations of gluten enteropathy

Gluten ataxia and other central nervous system disorders could be linked to gluten enteropathy and related autoantibodies.In this narrative review,we focus on the various neuro-logical manifestations in patients with gluten sensitivity/celiac disease,immunological and autoimmune mechanisms of ataxia in connection to gluten sensitivity and the autoantibodies that could be used as a biomarker for diagnosing and following.We focused on the anti-gliadin antibodies,antibodies to different isoforms of tissue transglutaminase(TG)(anti-TG2,3,and 6 antibodies),anti-glycine receptor antibodies,anti-glutamine acid decarboxylase antibodies,anti-deamidated gliadin peptides antibodies,etc.Most studies found a higher prevalence of these antibodies in patients with gluten sensitivity and neurological dysfunction,presented as different neurological disorders.We also discuss the role of a gluten-free diet on the clinical improvement of patients and also on imaging of these disorders.

A candidate targeting molecule of insulin-like growth factor-Ⅰ receptor for gastrointestinal cancers

Advances in molecular research in cancer have brought new therapeutic strategies into clinical usage.One new group of targets is tyrosine kinase receptors,which can be treated by several strategies,including small molecule tyrosine kinase inhibitors(TKIs) and monoclonal antibodies(mAbs).Aberrant activation of growth factors/receptors and their signal pathways are required for malignant transformation and progression in gastrointestinal(GI) carcinomas.The concept of targeting specif ic carcinogenic receptors has been validated by successful clinical application of many new drugs.Type I insulin-like growth factor(IGF) receptor(IGF-IR) signaling potently stimulates tumor progression and cellular differentiation,and is a promising new molecular target in human malignancies.In this review,we focus on this promising therapeutic target,IGF-IR.The IGF/IGF-IR axis is an important modifier of tumor cell proliferation,survival,growth,and treatment sensitivity in many malignant diseases,including human GI cancers.Preclinical studies demonstrated that downregulation of IGF-IR signals reversed the neoplastic phenotype and sensitized cells to anticancer treatments.These results were mainly obtained through our strategy of adenoviruses expressing dominant negative IGF-IR(IGF-IR/dn) against gastrointestinal cancers,including esophagus,stomach,colon,and pancreas.We also summarize a variety of strategies to interrupt the IGFs/IGF-IR axis and their preclinical experiences.Several mAbs and TKIs targeting IGF-IR have entered clinical trials,and early results have suggested that these agents have generally acceptable safety profiles as single agents.We summarize the advantages and disadvantages of each strategy and discuss the merits/demerits of dual targeting of IGF-IR and other growth factor receptors,including Her2 and the insulin receptor,as well as other alternatives and possible drug combinations.Thus,IGF-IR might be a candidate for a molecular therapeutic target in human GI carcinomas.

Global analysis of a reaction-diffusion blood-stage malaria model with immune response

Malaria is one of the most dangerous diseases that threatens people's lives around the world.In this paper,we study a reaction-difusion model for the within-host dynamics of malaria infection with an antibody immune response.The model is given by a system of partial differential equations(PDEs)to describe the blood-stage of malaria life cycle.It addresses the interactions between uninfected red blood cells,antibodies,and three types of infected red blood cells,namely ringinfected red blood cells,trophozoite-infected red blood cells and schizont-infected red blood cells.Moreover,the model contains a parameter to measure the efficacy of isoleucinc starvation and its effect on the growth of malaria parasites.We show the basic properties of the model.We compute all equilibria and derive the thresholds from the conditions of existence of malaria equilibrium points.We prove the global stability of all equilibrium points based on choosing suitable Lyapunov functionals.We use the characteristic equations to verify the local instability of equilibrium points.We finally execute numerical simulations to validate the theoretical results and highlight some important observations.The results indicate that isoleucine starvation can have a critical impact on the stability of equilibrium points.When the efficacy of isoleucine starvation is high,it switchcs the system from the infection state to the malaria-free state.The presence of an antibody immune response does not lead to the elimination of malaria infection,but it suppresses the growth of malaria parasites and increases the amount of healthy red blood cells.