p38-MAPK and CDK5,signaling pathways in neuroinflammation:a potential therapeutic intervention in Alzheimer's disease?

Alzheimer’s disease(AD),the most common type of dementia,affects millions of people worldwide,putting a significant strain on healthcare infrastructure and societal resources.AD is characte rized by the build-up of amyloid-beta(Aβ)plaques and neurofibrillary to ngles containing hyperphosphorylated tau protein.

Monomeric C-reactive protein:a link between chronic inflammation and neurodegeneration?

Pre-diabetic insulin resistance is associated with sub-clinical inflammation and concomitant increase in systemic C-reactive protein(CRP)levels.Type 2 diabetes mellitus(T2DM)patients register even higher chronic levels of inflammation,with excess circulating CRP originating from both typical hepatic synthesis,and also visceral white adipose tissue.

Helicobacter pylori and cytokine gene variants as predictors of premalignant gastric lesions

Gastric cancer remains the third leading cause of mortality from cancer worldwide and carries a poor prognosis,due largely to late diagnosis.The importance of the interaction between Helicobacter pylori(H.pylori)infection,the main risk factor,and host-related genetic factors has been studied intensively in recent years.The genetic predisposition for non-hereditary gastric cancer is difficult to assess,as neither the real prevalence of premalignant gastric lesions in various populations nor the environmental risk factors for cancer progression are clearly defined.For non-cardiac intestinal-type cancer,identifying the factors that modulate the progression from inflammation toward cancer is crucial in order to develop preventive strategies.The role of cytokines and their gene variants has been questioned in regard to non-self-limiting H.pylori gastritis and its evolution to gastric atrophy and intestinal metaplasia;the literature now includes various and non-conclusive results on this topic.The influence of the majority of cytokine single nucleotide polymorphisms has been investigated for gastric cancer but not for preneoplastic gastric lesions.Among the investigated gene variants onlyIL10T-819C,IL-8-251,IL-18RAP917997,IL-22 rs1179251,IL1-B-511,IL1-B-3954,IL4R-398 and IL1RN were identified as predictors for premalignant gastric lesions risk.One of the most important limiting factors is the inhomogeneity of the studies(e.g.,the lack of data on concomitant H.pylori infection,methods used to assess preneoplastic lesions,and source population).Testing the modifying effect of H.pylori infection upon the relationship between cytokine gene variants and premalignant gastric lesions,or even testing the interaction between H.pylori and cytokine gene variants in multivariable models adjusted for potential covariates,could increase generalizability of results.

Innate immunity–the hallmark of Helicobacter pylori infection in pediatric chronic gastritis

BACKGROUND Innate immunity was found to be associated with both persistence of Helicobacter pylori(H.pylori)infection and increased risk of gastric cancer.AIM To identify the risk factors associated with H.pylori infection and to establish the role of TLR9 rs352140 in suppressing or promoting inflammation related to this infection in children.METHODS We performed a study of 155 children with digestive symptoms,who were divided into two groups according to the histopathological exam:Group 1–48 children with H.pylori-induced chronic gastritis,and Group 2–control group.RESULTS Rural area and poor living conditions were significantly associated with H.pylori chronic gastritis(P=0.0042/P<0.0001).Both positive immunoglobulin A anti H.pylori and the rapid urease test were significantly associated with H.pylori infection(P<0.0001).Significantly higher values of leukocytes and neutrophils within the peripheral blood were found in children with H.pylori chronic gastritis(P=0.111/P=0.284).We found a significant positive correlation between the variant TT genotype of TLR9 rs352140 polymorphism and both leucocytes and neutrophils(P=0.0225/P=0.0292).CONCLUSION Variant TT genotype carriers of the TLR9 rs352140 gene polymorphism might have a more severe degree of inflammation.

Diabetic kidney disease in pediatric patients: A current review

In the last decades,a significant increase in the incidence of diabetic kidney disease(DKD)was observed concomitant with rising diabetes mellitus(DM)incidence.Kidney disease associated with DM in children and adolescents is represented by persistent albuminuria,arterial hypertension,progressive decline in estimated glomerular filtration rate to end-stage renal disease and increased cardiovascular and all-cause morbidity and mortality of these conditions.In medical practice,the common and still the“gold standard”marker for prediction and detection of diabetic kidney involvement in pediatric diabetes is represented by microalbuminuria screening even if it has low specificity to detect early stages of DKD.There are some known limitations in albuminuria value as a predictor biomarker for DKD,as not all diabetic children with microalbuminuria or macroalbuminuria will develop end-stage renal disease.As tubular damage occurs before the glomerular injury,tubular biomarkers are superior to the glomerular ones.Therefore,they may serve for early detection of DKD in both type 1 DM and type 2 DM.Conventional and new biomarkers to identify diabetic children and adolescents at risk of renal complications at an early stage as well as renoprotective strategies are necessary to delay the progression of kidney disease to end-stage kidney disease.New biomarkers and therapeutic strategies are discussed as timely diagnosis and therapy are critical in the pediatric diabetic population.