ABSTRACT
The progression of renal damage in diabetic nephropathy(DN)is closely related to Nod-like receptor protein3(NLRP3)inflammasome activation. The characteristics of NLRP3 inflammasome activation include the changed expression and combination levels of NLRP3, apoptosis-associated speck-like protein(ASC)and pro-caspase-1, the increased expression levels of caspase-1, interleukin(IL)-1β and IL-18 and the excessive release levels of the relative inflammatory mediators. Its molecular regulative mechanisms involve the activation of multiple signaling pathways including reactive oxygen species(ROS)/thioredoxin-interacting protein(TXNIP)pathway, nuclear factor(NF)-κB pathway, nuclear factor erythroid-related factor 2(Nrf2)pathway, long non-coding RNA(lncRNA)pathway and mitogen-activated protein kinases(MAPKs)pathway. In addition, more importantly, never in mitosis aspergillus-related kinase 7(Nek7), as a kinase regulator, could target-combine with NLRP3 at upstream to activate NLRP3 inflammasome. Some extracts of Chinese herbal medicines(CHMs)such as quercetin, curcumin, cepharanthine, piperine and salidroside, as well as Chinese herbal compound prescriptions such as Wumei Pills both could treat NLRP3 inflammasome to ameliorate inflammatory renal damage in DN. Therefore, accurately clarifying the targets of anti-inflammatory CHMs and Chinese herbal compound prescriptions delaying DN progression by targeting the molecular regulative mechanisms of NLRP3 inflammasome activation will be one of the development directions in the future.
Subject(s)
Humans , Caspase 1/immunology , Diabetes Mellitus/drug therapy , Diabetic Nephropathies/immunology , Drugs, Chinese Herbal/therapeutic use , Inflammasomes/immunology , Interleukin-18/immunology , Interleukin-1beta/immunology , NIMA-Related Kinases , NLR Family, Pyrin Domain-Containing 3 Protein/immunologyABSTRACT
In this study, 80 diabetic patients were classified into 2 groups: group I [40 patients] without evidence of diabetic nephropathy in spite of long duration of diabetes [more than 15 years], and group II [40 patients] with overt diabetic nephropathy. The 2 groups were compared with 260 normal control group for HLA-A2 antigen. HLA-A2 antigen was more prevalent in patients with diabetic nephropathy as 77.5% of them were HLA-A2 positive compared to 30% of patients without diabetic nephropathy and 36.2% normal controls. Other factors such as family history of diabetic nephropathy, and poor glycemic control and age of onset of diabetes were more observed in patients with diabetic nephropathy. This points that, HLA typing may be useful in defining risk of renal disease in diabetic patients, also poor glycemic control may be a risk factor for initiation of diabetic nephropathy in a patient genetically susceptible for it
Subject(s)
Humans , Male , Female , Diabetic Nephropathies/diagnosis , Diabetic Nephropathies/immunology , Risk FactorsABSTRACT
Twenty diabetic uraemics and twenty two healthy matched controls comprised the material for this study. Cell mediated immunity was assessed by estimation of T-cell rosette percentage and cutaneous response to recall antigens--purified protein derivative, candida antigen and 2:4 dinitrochlorobenzene. Results analysis revealed depressed cell mediated immunity in diabetic uraemics in the form of impaired cutaneous response to recall antigens and reduction in T cell rosette percentage, in comparison to controls.