Renal ischemia reperfusion (I/R) injury is a common reason of acute kidney injury. Apoptosis play an important role in the IRI. Fenofibrate, one of agonist Peroxisome proliferator-activated receptor-alpha (PPARα) has the effect of anti-apoptosis. This study was to explore the effect of Fenofibrate on renal ischemia reperfusion injury and its mechanism.
IRI was induced by bilateral renal ischemia for 45 min followed by reperfusion for 24 h. Eighteen male C57BL/6 mice were randomly divided into three groups: Sham group (Sham), IRI group (IRI), I/R-Fenofibrate group (FEN). Fenofibrate was injected at 45 min before renal ischemia. Renal histology, function, and the expression of Bax, Bcl-2, Bcl-xl p21, p53, Caspse3, CytC, p-JAK2, p-STAT3 and p-PPAR-α were assessed.
Fenofibrate precondition can significantly alleviate the renal dysfunction, the pathological change, up-regulate the expression of p-PPAR-α, Bcl-2, Bcl-xl, Caspase3 and down-regulate the expression of p-JAK2, p-STAT3, p53, p21, CytC and Bax induced by renal IR injury.
Fenofibrate precondition can protect mice against IRI by suppressing p53-mediating apoptosis which was associated with inhibiting JAK2/STAT3 signaling activation though further activating PPAR-α. Our findings suggest that Fenofibrate could be useful for preventing IR-induced renal injury.
Smoking is the most important preventable risk factor of chronic obstructive pulmonary disease and lung cancer. This study was designed to investigate oxidative damage and histopathological changes in lung tissue of rats chronically exposed to nicotine alone or supplemented with ethanol. Twenty-four male Wistar rats divided into three groups were used for the study. The nicotine group received nicotine (2.5 mg/kg/day); the nicotine-ethanol group was given simultaneously same dose of nicotine plus ethanol (0.2 g/kg/day), while the control group was administered only normal saline (1 ml/kg/day). The treatment was administered by subcutaneous injection once daily for a period of 18 weeks. Chronic nicotine administration alone or combined to ethanol caused a significant increase in malondialdehyde (MDA) level, superoxide dismutase (SOD) activity and catalase (CAT) activity in lung tissue compared to control rats suggesting an oxidative damage. However, these increases were mostly prominent in nicotine group. The histopathological examination of lung tissue of rats in both treated groups revealed many alterations in the pulmonary structures such as emphysema change (disappearance of the alveolar septa, increased irregularity and size of air sacs) and marked lymphocytic infiltration in perivascular and interstitial areas. However, the changes characterized in the nicotine group (pulmonary congestion, hemorrhage into alveoli and interstitial areas, edema) were more drastic than those observed in the nicotine-ethanol group, and they can be attributed to a significant degree of capillary endothelial permeability and microvascular leak. Conversely, the ethanol supplementation caused an appearance of fatty change and fibrosis in pulmonary tissue essentially due to a metabolism of ethanol. Finally, the lung damage illustrated in nicotine group was more severe than that observed in the nicotine-ethanol group. We conclude that the combined administration of nicotine and ethanol may moderate the effect of nicotine administered independently by counteractive interactions between these two drugs.
Thrombocytopenia is a current situation for making a blood smear in routine practice in a medical analysis laboratory. Recent automated hematology analyzers enumerate platelets and generate histograms and specific flags. Operators must be aware of the characteristics of their analyzer in order to avoid spurious results in the case where microscopy review is not possible.
We evaluated the diagnostic performance of various graphical anomalies in the detection of large platelets and platelet clumps.
Three hundred cases of thrombocytopenia were included in the study on the basis of a platelet count less than 150 × 109/L. This evaluation is expressed by the results of the sensitivity, specificity, positive predictive value and negative predictive value compared to the microscopic review of blood smear.
Graphical performances are variable according to microscopic review of blood smears. Indeed, a not fitted curve is the most sensitive change on platelet histogram to the presence of large platelet. A high specificity to the presence of platelet clumps is announced when the platelet curve fails to return to the baseline. Moreover, characteristic findings on the DIFF scattergram are very specific to the presence of platelet clumps.
A normal platelet histogram can validate with great confidence thrombocytopenia in cases where a blood smear cannot be read immediately.
The protein kinase C (PKC) family has been implicated in several physiological processes regulating platelet activation. Each isoform of PKC expressed on platelets, may have a positive and/or negative role depending on the nature and concentration of the agonist. Mice lacking PKCα show much reduced thrombus formation in vivo, while PKCθ−/− showed inhibition of aggregation in response to PAR4. On the other hand, PKCδ by associating with Fyn, inhibits platelet aggregation. In addition, PKCβ by interacting with its receptor RACK1 has been implicated in the primary phases of signaling via the αIIbβ3 and finally PKCɛ appears to be involved in platelet function downstream GPVI. The present review discusses the latest observations relevant to the role of individual PKC isoforms in platelet activation and thrombus formation.
The Helicobacter pylori cag pathogenicity island (cagPAI) is involved in delivery of CagA effector protein and peptidoglycan into host cells and also in IL-8 induction in the human gastric tissue. Diversity of cagPAI may affect disease status and clinical outcome of the infected patients. Our study was aimed to investigate diversity of this island and its intactness in Iranian patients to investigate possible associations between cagPAI integrity and pathological changes of the infected tissue.
Out of the 75 patients, H. pylori strains were obtained from 30 patients with severe active gastritis (SAG) (n = 11), moderate chronic gastritis (CG) (n = 14) and intestinal metaplasia/dysplasia (IM) (n = 5). Intactness of the cagPAI was determined using 12 sets of primer pairs specific for functionally important loci of cagPAI by polymerase chain reaction (PCR).
The cagPAI positive strains were significantly observed in patients with SAG (52.4%) in comparison to those presenting CG (33.3%) and IM (14.3%). In addition, the presence of intact cagPAI was 87.5% in H. pylori strains isolated from patients with SAG, which was higher than those obtained from patients with CG (12.5%) or IM (0%). A significant increase in the frequency of cagα-cagY and cagW-cagT segments, as exterior proteins of the CagPAI, was illustrated in strains from SAG patients compared with those from patients with CG.
Overall, these results strongly proposed an association between the severity of histopathological changes and intactness of cagPAI in the gastric tissue of patients infected with H. pylori.
The aim of the present study is to explore the association between the APOA5 polymorphisms and haplotypes with obesity in Moroccan patients. The study was performed in 459 subjects, Obese (n = 164) and non-obese (n = 295). All subjects were genotyped for the APOA5 -1131T > C (rs662799) and c.56C > G (rs3135506) polymorphisms. The contribution of APOA5 polymorphisms and haplotypes in the increased risk of obesity were explored using logistic regression analyses. The -1131T > C and c.56C > G polymorphisms were significantly associated with obesity. Both polymorphisms were strongly associated with increased BMI. Analysis of constructed haplotypes showed a significant association between CG haplotype and susceptibility to obesity (OR [95%CI] = 3.09 [1.93–4.97]; P < 0.001). These results support a potential role for APOA5 common variants and related haplotypes as risk factors for obesity.
Longevity can mostly be determined with relative accuracy from birth and death registers when available. Aging is a multifactorial process, much more difficult to quantitate. Every measurable physiological function declines with specific speeds over a wide range. The mechanisms involved are also different, genetic factors are of importance for longevity determinations. The best-known genes involved are the Sirtuins, active at the genetic and epigenetic level. Aging is multifactorial, not “coded” in the genome. There are, however, a number of well-studied physical and biological parameters involved in aging, which can be determined and quantitated. We shall try to identify parameters affecting longevity as well as aging and suggest some reasonable predictions for the future.
The aim of this study was to investigate the role of IL-1β (−511C>T), TNFα (-308 G>A), IL-10 (-1082 G > A) and IL-1RN VNTR polymorphisms in the susceptibility to rheumatoid arthritis (RA) in Tunisians.
Using PCR-based methods, 104 RA patients and 150 healthy controls were investigated. We compared allele and genotype frequencies in RA patients versus controls and analyzed their correlations with erosive form (EF).
IL1-RN VNTR A1A3 genotype is associated with higher risk of RA (P = 0.012, OR = 4.31). Among the cases, males who carry this genotype were more exposed to RA (P = 0.044, OR = 8, 47). For IL1- β gene, a significantly higher frequency of the -511C/C genotype was observed in RA patients in comparison to controls (P = 0.013, OR = 2.45). This higher frequency was especially observed in women (P = 0,003, OR = 3.42). In contrast, IL10−1082G/G genotype was less common in patients (P = 0.046, OR = 0.46). According to EF, men carrying IL1-RN VNTR A1A3 (P = 0.005 OR = 5.28) and IL1-β−511C/C (P = 0.015 OR = 2.61) genotypes develop non EF of RA. Moreover, TNFα-308 A allele (P = 0.024, OR = 1.84) and A/A genotype (P = 0.033, OR = 3.1) were positively associated to EF of RA. However, G allele (P = 0.024, OR = 0.31) and GG genotype (P = 0.31, OR = 0.031) of the TNFα-308 were protectors.
Our results indicated that IL-1RN VNTR, IL-1β (−511C>T) and IL-10 (-1082 G>A) are associated with susceptibility to RA, and that IL-1RN VNTR, IL-1β (−511C>T) and TNFα (-308 G>A) are associated with severity of RA.
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