Interplay between long non-coding RNA MALAT1 and pyroptosis in diabetic nephropathy patients.

Diabetic nephropathy (DN) the most common micro-vascular diabetic complication is the leading cause of end-stage renal disease worldwide. Diagnosis and treatment of DN in its early stage can effectively guard against its progression. Recently, pyroptosis a special type of lytic cell death and noncoding RNA were reported to have roles in early diagnosis and progression of DN. The present study aimed to evaluate the role played by long noncoding RNA (lncRNA) MALAT1, oxidative stress and pyroptosis in early detection of DN. Sixty Type 2 DM patients were included and divided according to urinary albumin-creatinine (UACR) ratio into normoalbuminuria and microalbuminuria groups beside 20 age and sex matched healthy volunteers as controls. Serum caspase 1 and interleukin 18 (IL18) levels were immunoassayed and MALAT1 expression was assessed by real-time PCR. Additionally, glycemic, redox and inflammatory status were assessed. MALAT1 expression, serum caspase1 level, IL18 level, myeloperoxidase activity, and protein carbonyl level were significantly increased in micro-albuinuria diabetic group when compared with diabetic normo-albuminuria group. Meanwhile, catalase activity was significantly decreased. Receiver operating characteristic (ROC) curve analysis revealed that IL18 had the highest sensitivity and diagnostic accuracy for detecting early microalbuminuria and incipient DN followed by caspase1and lastly MALALT1. CONCLUSION: Pyroptosis, impaired redox and altered MALAT1 expression could be an underlying mechanism for DN development. Moreover, MALAT1 expression, caspase 1 and IL 18 levels could be regarded as a potential biomarker for early prediction of DN.

Cloning and functional characterization of Ptpcd2 as a novel cell cycle related protein tyrosine phosphatase that regulates mitotic exit.

Faithful transmission of genetic information depends on accurate chromosome segregation as cells exit from mitosis, and errors in chromosomal segregation are catastrophic and may lead to aneuploidy which is the hallmark of cancer. In eukaryotes, an elaborate molecular control system ensures proper orchestration of events at mitotic exit. Phosphorylation of specific tyrosyl residues is a major control mechanism for cellular proliferation and the activities of protein tyrosine kinases and phosphatases must be integrated. Although mitotic kinases are well characterized, phosphatases involved in mitosis remain largely elusive. Here we identify a novel variant of mouse protein tyrosine phosphatase containing domain 1 (Ptpcd1), that we named Ptpcd2. Ptpcd1 is a Cdc14 related centrosomal phosphatase. Our newly identified Ptpcd2 shared a significant homology to yeast Cdc14p (34.1%) and other Cdc14 family of phosphatases. By subcellular fractionation Ptpcd2 was found to be enriched in the cytoplasm and nuclear pellets with catalytic phosphatase activity. By means of immunofluorescence, Ptpcd2 was spatiotemporally regulated in a cell cycle dependent manner with cytoplasmic abundance during mitosis, followed by nuclear localization during interphase. Overexpression of Ptpcd2 induced mitotic exit with decreased levels of some mitotic markers. Moreover, Ptpcd2 failed to colocalize with the centrosomal marker γ-tubulin, suggesting it as a non-centrosomal protein. Taken together, Ptpcd2 phosphatase appears a non-centrosomal variant of Ptpcd1 with probable mitotic functions. The identification of this new phosphatase suggests the existence of an interacting phosphatase network that controls mammalian mitosis and provides new drug targets for anticancer modalities.

Effect of atorvastatin on inflammation and modification of vascular risk factors in rheumatoid arthritis.

OBJECTIVE: To investigate the effect of atorvastatin therapy on inflammation, disease activity, endothelial dysfunction, and arterial stiffness in patients with rheumatoid arthritis (RA). METHODS: This study included 30 patients with early RA, randomly divided into 2 groups. Group 1 (n = 15) received methotrexate (MTX; 0.2 mg/kg/week; mean (15.5 ± SD 1.3) plus prednisone (10 mg/day). Group 2 (n = 15) received MTX and prednisone with the same previous doses plus atorvastatin therapy (40 mg/day). Ten healthy individuals of similar age and sex served as controls. Disease activity, lipid profile, serum malondialdehyde (MDA), tumor necrosis factor-α (TNF-α), resistin, adiponectin, and brachial artery flow-mediated dilation (FMD) were measured before and after 6 months of treatment. RESULTS: Atorvastatin combined with MTX therapy significantly reduced serum total cholesterol, low-density lipoprotein cholesterol, and triglycerides, and increased high-density lipoprotein cholesterol (p < 0.001). Disease activity variables, serum MDA, TNF-α, resistin, adiponectin, and FMD were significantly improved by the drug combinations (p < 0.001). CONCLUSION: Atorvastatin therapy in patients with RA reduced disease activity and conventional and novel vascular risk factors that promote the atheromatous lesion. Therapy was also associated with concomitant improvement in endothelial function.

Immunotoxicity and hematotoxicity induced by tetrachloroethylene in egyptian dry cleaning workers.

The immune and hematological systems can be a target for environmental contaminants with potential adverse effects, so the purpose of this study is to provide documentation on immunotoxicity and hematotoxicity of tetrachloroethylene, which is widely used in dry cleaning in Egypt. This study was carried out on 80 adult males. Subjects designated as controls (n = 40) were healthy persons and others were tetrachloroethylene-exposed dry-cleaning workers (n = 40). The controls and tetrachloroethylene-exposed workers were then divided into four equal groups (20 individuals/group): group I, control group never smoking; group II, smoking control group; and groups III and IV, tetrachloroethylene-exposed nonsmoking and smoking workers, respectively. Blood level of tetrachloroethylene, complete blood count, immunoglobulins (IgA, IgM, IgG, and IgE), the total numbers of white blood cells (WBC), and leukocyte differential counts, as well as interferon gamma (IFN-gamma) and interleukin-4 (IL-4), were measured. The immunotoxicity of tetrachloroethylene appeared in the form of an increase in serum immunoglobulin E in nonsmoking and smoking tetrachloroethylene-exposed workers, while the serum immunoglobulins A, M, and G levels showed no significant change in all studied groups. In addition, our results demonstrated a significant increase in white cell count, lymphocytes, natural killer (NK; CD3+CD16CD56+) cells, and B (CD19+) lymphocytes. The increase in WBC and lymphocytes may be attributed to allergic reaction. Moreover, serum and lymphocytic interlukin-4 levels were significantly increased in nonsmoking and smoking tetrachloroethylene-exposed workers. Tetrachloroethylene exposure is associated with immunotoxicity, which may lead to the augmentation of allergic diseases or appearance of autoimmune reaction.

Cigarette smoking induced liver insult concomitant with inflammatory mediators in serum crevicular fluid and bronchio alveolar lavage of schistosomal diabetic subjects with history of bronchial asthma.

Forty five smokers were classified into schistosomal cases with type-2 diabetis mellitus (GI) and with associated history of bronchial asthma (GII) and without T-2 DM (GIII). A control group (GIV) of non-diabetic non schistosomal age matched subjects who quitted smoking for >6 months were included. Assessed parameters included indices of glycemic status (glycated hemoglobin), angiogenesis (vascular endothelial growth factor) hepatic and bronchoalveolar disposition (Liver function test, metallothionein, serum levels of cotinine, cadmium selenium, copper & zinc) and bronchoalveolar lavage) (BAL) levels of surfactant proteins A & D, zinc and copper oxidative stress and fibrogenesis (total antioxidant capacity thiobarbituric acid reactive substance) and vasculopathy (angiotensin converting enzyme, P-selectin, nitrate) and periodontitis (collagenase and elastase in GCF) impact of cigarette smoking associated with trace element disbalance and enzymatic changes in crevicular fluid on altered parameters collaborative out-come. The study reflected the collaborative outcome of immune mediated mechanisms initiated by liver affection, glycemic status and history of predisposed bronchial integrity induced by oxidative stress.

Dual impact of chronic liver disease and amaebiasis on immunopathogenesis of primary osteoarthritis in Egyptians.

Sixty cases with primary knee OA were equally categorized into six groups with EHI (Gs 1, 2, 3) or without (Gs 4, 5, 6). GI included cases with HCV, GII cases with RHS & HCV and GIII cases with a history of non-active schistosomiasis whereas Gs 4, 5 & 6 included cases without EHI. Clinical examination with inclusion criteria of pathological manifestations w\as associated with biochemical evaluation of adhesion molecules (E-selectin, P-selectin, intracellular adhesion molecule-3 "ICAM-3") in plasma and synovial fluid. Synovial fluid indices (IgG, IgA, IgM, & C3) were evaluated as well as indices of inflammation and oxidative stress (Beta 2 microglobulin, Haptaglobulin, fibronectin, total thiol, superoxide dismutase, thiobarbituric acid reactive substance & hyaluronan) in synovial fluid and indices activating fibrogenesis in serum and plasma (procollagen III, plasma prolidase, Interleukin-1 beta, Interleukin-6 & TNF alpha). The results showed a positive relationship between indices activating vascular damage, fibrogenesis and immuno-inflammatory response with higher change magnitude in EHI cases particularly with combined HCV & RHS. This implement the dual role of hepatic insult and intestinal amoebiasis on immune mediated mechanisms activating inflammatory response in OA cases reflecting common signaling pathways associated with pathogenesis of multifaceted origin.