Tumor Necrosis Factor Gene Research Articles

Genetic and histopathological alterations induced by cypermethrin in rat kidney and liver: Protection by sesame oil.

Pesticides are widespread synthesized substances used for public health protection and agricultural programs. However, they cause environmental pollution and health hazards. This study aimed to examine the protective effects of sesame oil (SO) on the genetic alterations induced by cypermethrin (CYP) in the liver and kidney of Wistar rats. Male rats were divided into four groups, each containing 10 rats: the control group received vehicle, SO group (5 mL/kg b.w), CYP group (12 mg/kg b.w), and protective group received SO (5 mL/kg b.w) plus CYP (12 mg/kg b.w). Biochemical analysis showed an increase in albumin, urea, creatinine, GPT, GOT, and lipid profiles in the CYP group. Co-administration of SO with CYP normalized such biochemical changes. CYP administration decreased both the activity and mRNA expression of the examined antioxidants. SO co-administration recovered CYP, downregulating the expression of glutathione-S-transferase (GST), catalase, and superoxide dismutase. Additionally, SO co-administration with CYP counteracted the CYP- altering the expression of renal interleukins (IL-1 and IL-6), tumor necrosis factor alpha (TNF-α), heme oxygenase-1 (HO-1), anigotensinogen (AGT), AGT receptors (AT1), and genes of hepatic glucose and fatty acids metabolism. CYP induced degenerative changes in the kidney and liver histology which are ameliorated by SO. In conclusion, SO has a protective effect against alterations and pathological changes induced by CYP in the liver and kidney at genetic and histological levels.

Associations of non-Hodgkin Lymphoma (NHL) risk with autoimmune conditions according to putative NHL loci.

Autoimmune conditions and immune system-related genetic variations are associated with risk of non-Hodgkin lymphoma (NHL). In a pooled analysis of 8,692 NHL cases and 9,260 controls from 14 studies (1988-2007) within the International Lymphoma Epidemiology Consortium, we evaluated the interaction between immune system genetic variants and autoimmune conditions in NHL risk. We evaluated the immunity-related single nucleotide polymorphisms rs1800629 (tumor necrosis factor gene (TNF) G308A), rs1800890 (interleukin-10 gene (IL10) T3575A), rs6457327 (human leukocyte antigen gene (HLA) class I), rs10484561 (HLA class II), and rs2647012 (HLA class II)) and categorized autoimmune conditions as primarily mediated by B-cell or T-cell responses. We constructed unconditional logistic regression models to measure associations between autoimmune conditions and NHL with stratification by genotype. Autoimmune conditions mediated by B-cell responses were associated with increased NHL risk, specifically diffuse large B-cell lymphoma (odds ratio (OR) = 3.11, 95% confidence interval (CI): 2.25, 4.30) and marginal zone lymphoma (OR = 5.80, 95% CI: 3.82, 8.80); those mediated by T-cell responses were associated with peripheral T-cell lymphoma (OR = 2.14, 95% CI: 1.35, 3.38). In the presence of the rs1800629 AG/AA genotype, B-cell-mediated autoimmune conditions increased NHL risk (OR = 3.27, 95% CI: 2.07, 5.16; P-interaction = 0.03) in comparison with the GG genotype (OR = 1.82, 95% CI: 1.31, 2.53). This interaction was consistent across major B-cell NHL subtypes, including marginal zone lymphoma (P-interaction = 0.02) and follicular lymphoma (P-interaction = 0.04).

Expression of innate immunity genes in kuruma shrimp Marsupenaeus japonicus after in vivo stimulation with garlic extract (allicin)

In recent times, attention has focused on immunostimulants and plant products which could have beneficial effects in disease control. At present, the application of immunostimulants has been considered a more effective approach to health management in aquaculture through the enhancement of immune capability and disease resistance in shrimp. Garlic possesses bactericidal property against bacteria and can inhibit the growth of protozoa as well as gregarine infection in cultured shrimp. However, its effect on viral disease infection has not been well studied and requires further investigation. Garlic can also stimulate shrimp haemocytes as determined by cellular immune responses (phagocytic activity, superoxide anion production and phenoloxidase activity) suggesting that the immune-stimulatory properties of garlic will be useful for improvement of shrimp health. Here, we determined the expression of the immune-related genes Penaeidin, Crustin, Lysozyme, Toll-like, and tumour necrosis factor in kuruma shrimp, upon stimulation with allicin extract. The expression of these factors was measured for the first time and was found to be elevated in intestine and lymphoid organ after stimulation for 3, 12, 24 and 48 h. We conclude that garlic can be used in shrimp culture as an alternative to antibiotics or chemotherapeutic agents; however, further research is needed under field conditions.

The -308G>a polymorphism of the TNF gene is associated with proliferative diabetic retinopathy in Caucasian Brazilians with type 2 diabetes.

We tested the hypothesis that tumor necrosis factor (TNF) gene polymorphisms are associated with diabetic retinopathy (DR) in Caucasians with type 2 diabetes mellitus. In a case-control study, the -238G>A (rs361525), -308G>A (rs1800629), and -857C>T (rs1799724) polymorphisms of the TNF gene were genotyped in 745 outpatients with type 2 diabetes, including 331 subjects without DR, 246 with nonproliferative DR (NPDR), and 168 with proliferative DR (PDR). Genotype and allele frequencies of the -238G>A, -308G>A, and -857C>T polymorphisms in subjects with NPDR were not significantly different from those of subjects without DR (P > 0.05 for all comparisons). However, the A allele of the -308G>A polymorphism was more frequent in subjects with PDR than in those with no DR (18.1% vs. 11.5%, corrected P = 0.035). Multivariate logistic regression analysis showed that the -308A allele was independently associated with an increased risk of PDR, under a dominant model (adjusted odds ratio [aOR], 1.82; 95% confidence interval [CI], 1.11-2.98). The combined analysis of the three polymorphisms also showed that haplotypes containing the -308A allele were associated with an increased risk of PDR (aOR, 2.36; 95% CI, 1.29-4.32). This study detected, for the first time to our knowledge, an independent association of the -308G>A polymorphism in the TNF gene with PDR in Caucasian Brazilians with type 2 diabetes. This finding suggests that TNF is a potential susceptibility gene for PDR.

Association of Tumor Necrosis Factor (TNF) promoter polymorphisms with plasma TNF-α levels and susceptibility to diabetic nephropathy in North Indian population

AimThe concept of diabetic nephropathy (DN) as a metabolic disease is now being replaced by chronic low-grade inflammatory disease. Tumor necrosis factor-alpha (TNF-α) is a proinflammatory cytokine which plays an important role in the pathogenesis and clinical outcome of DN. Therefore, this work was planned to evaluate the association of −863C/A (rs1800630) and −1031T/C (rs1799964) polymorphisms in TNF gene with plasma TNF-α levels and DN among subjects with type 2 diabetes (T2DM) in a population from North India. MethodsAge and sex matched 100 healthy controls (HC), 100 T2DM subjects without nephropathy (DM) and 100 subjects with DN were screened for above polymorphisms using the PCR-RFLP methods. Plasma TNF-α levels were measured by ELISA. Analysis of variance and logistic regression were used to associate individual polymorphisms with plasma TNF-α levels and DN. ResultsThe allelic frequencies of −863C/A were 0.86/0.14 in HC, 0.72/0.23 in DM and 0.84/0.16 in DN, and that of −1031T/C were 0.89/0.11 in HC, 0.95/0.05 in DM and 0.80/0.20 in DN. The carriers of −863A allele had significantly lower plasma TNF-α levels (p<0.05). The −863C/A (OR=0.439, 95% CI=0.244–0.789, p=0.006) and −1031T/C (OR=3.0, 95% CI=1.355–6.642, p=0.007) were strongly associated with risk of development of DN. Conclusions−863C/A was associated with low whereas −1031T/C with high TNF-α levels. The, results suggest that −863C/A polymorphism might be protective whereas −1031T/C may be associated with increased risk for DN in subjects with T2DM from North India.

Tumor necrosis factor gene polymorphisms in advanced non-exudative age-related macular degeneration

Purpose:To investigate tumor necrosis factor (TNF)-α gene polymorphisms in advanced dry-type age-related macular degeneration (AMD) in a population from Northeastern Iran.Methods:In this case-control study, 50 patients with geographic macular atrophy and 73 gender-matched controls were enrolled. Genomic deoxyribonucleic acid (DNA) was extracted from the peripheral blood. Polymerase chain reaction was performed to analyze 2 candidate single nucleotide polymorphisms in the TNF-α gene, namely −1031 thymine (T)/cytosine (C) and −308 guanine (G)/adenine (A).Results:The distribution of the - 1031 T/C genotype was TT, 62%; TC, 36%; CC, 2% in the patients and TT, 60%; TC, 36%; CC, 4% in the controls (P = 0.94). Genotype analysis of TNF-α −308 also revealed no significant difference in distribution between patients (G, 78%; GA, 22%; AA, 0%) and controls (GG, 74%; GA, 23%; AA, 3%) (P = 0.51). None of the haplotypes nor alleles of studied TNF-α polymorphisms were significantly associated with advanced dry-type AMD.Conclusion:The findings of this study show that polymorphisms in the TNF-α gene, do not play an important role in dry-type AMD in the studied population.

Tumor necrosis factor gene expression in regular hemodialysis patients.

This study evaluates tumor necrosis factor (TNF)-alfa gene expression in patients with end-stage renal disease (ESRD) on regular hemodialysis as an expression of cardiovascular disease (CVD) risk even on a sub-clinical level and its relation to some of the parameters incriminated in the pathogenesis and the establishment of uremic arteriopathy. A total of 51 patients with ESRD on regular hemodialysis and 20 healthy subjects matching in age and gender as a control group were recruited. All selected cases were subjected to serum lipid profile, Creactive protein (CRP), TNF-alfa gene expression and Doppler study of carotid arteries to estimate carotid intimal media thickness (cIMT). Serum triglycerides (TGS) level (P <0.001), CRP positivity (P = 0.002), relative quantification (RQ) of TNF-alfa gene expression (P = 0.007) and cIMT (P = 0.02) were significantly higher while high-density lipoprotein (HDL) level (P <0.001) was significantly lower among cases compared with controls. RQ showed a significant positive correlation with CRP titer (rho = 0.583, P = 0.011). Results also showed a significant strong negative correlation between with CRP titer and cIMT (rho = -0.590, P = 0.010). CRP titer showed only a significant strong negative correlation with age (rho = -0.589, P = 0.01) and positive correlation with HDL (rho = 0.51, P = 0.031). Patients with ESRD have increased gene expression of TNF-alfa and CRP titer together with increased atherosclerosis as expressed by increased cIMT.

Comparative genomic of the BAFF and BAFF-like genes and immune response to bacteria of miiuy croaker (Miichthys miiuy)

As a member of the tumor necrosis factor (TNF) family, B cell activating factor (BAFF), also known as TNF ligand superfamily member 13B (TNF13B), playing a critical role in enhancing immune responses. BAFF is a central cytokine for B-cell survival, proliferation, maturation and immunoglobulin secretion. In the present study, we describe the identification of the miiuy croaker BAFF (designed MmBAFF) and BAFF-like (designed MmBAFF-like) genes. The cDNA of MmBAFF contains an open reading frame (ORF) of 795 nucleotides that are translated into a predicted 264 amino acids. The ORF of MmBAFF-like consists of 705 bases encoding 234 amino acids. Amino acid sequence comparison indicated that MmBAFF and MmBAFF-like possessed the TNF signatures, a predicted transmembrane domain, three conserved cysteine residues and a putative furin protease cleavage site, which were the typical characteristics of TNF gene in mammals and birds. The predicted three-dimensional (3D) structure of the MmBAFF and MmBAFF-like monomer analyzed by comparative protein modeling revealed that they were very similar to human counterpart. Comparative genomic analysis revealed that the locations of MmBAFF and MmBAFF-like genes are conserved among the bony fish. Phylogenetic analysis shows the MmBAFF is most closely related to other teleost BAFFs with the highest similarity to Epinephelus awoara. And BAFF-like cluster get together first to BAFF cluster than three closely related TNF superfamily (TNFSF) members. Real-time quantitative PCR analysis shows the MmBAFF and MmBAFF-like transcripts are expressed in a wide range of tissues with the highest expression in skin and lymphoid tissue spleen. Upon induction by Vibrio anguillarum, their expressions are significantly upregulated in liver, spleen and kidney as compared to phosphate-buffered saline injected control fish. The association of increased BAFF expression after bacterial infection suggests that it plays a potentially important role in immune system of fish.

Clinical, electrophysiological, and molecular findings in early onset hereditary neuropathy with liability to pressure palsy

The first episode of hereditary neuropathy with liability to pressure palsy (HNPP) in childhood is rare. We analyzed retrospectively the data of 7 patients with a deletion in PMP22 and onset of symptoms before age 18 years. Direct sequencing of the LITAF (lipopolysaccharide-induced tumor necrosis factor) gene was performed in patients and family members. Clinical presentations varied from mononeuropathies to brachial plexopathy, with recurrent episodes in 4 patients. Electrophysiological abnormalities characteristic for HNNP were found in most subjects. Analysis of the LITAF gene revealed an Ile92Val polymorphism in 6 of 7 (86%) probands and 5 of 7 (83%) family members, over 4 times greater frequency than in the general population. Clinical suspicion of HNPP even when nerve conduction study results do not fulfill HNPP criteria should indicate genetic testing. In our patients, early-onset HNPP was associated frequently with isoleucine92valine LITAF polymorphism.

Knockout of the HCC suppressor gene Lass2 downregulates the expression level of miR-694.

Homo sapiens longevity assurance homolog 2 of yeast LAG (Lass2) catalyzes the synthesis of long-chain ceramide which is an essential element of membranous structures. Deletion of Lass2 is associated with a high risk of spontaneous or DEN-induced hepatocellular carcinoma (HCC), yet the mechanism remains unclear. In the present study, we found extensive vesicles in hepatocytes of one-month-old Lass2-knockout (KO) mice. Hepatic biochemical indices were increased and expression of albumin was attenuated in the one‑month Lass2-KO liver. The results indicate that the injuries of the hepatocytes in young Lass2-KO mice, based on the results of Gene Ontology analysis of mRNA microarray of Lass2-KO liver vs. wild-type liver showed 'wounding response' was the mostly possible altered pathway in the Lass2-KO mice. miR-mRNA integrated analysis revealed that miR-694 was downregulated while its target gene tumor necrosis factor α-induced protein 3 (Tnfaip3) was upregulated, as confirmed by qPCR. The expression of NF-κB which is negatively controlled by Tnfaip3 was detected by qPCR and was found to be downregulated. Herein, we first report that Lass2 deficiency caused the downregulation of miR-694 and the upregulation of its target gene Tnfaip3 in vivo in mice, which may be related to a high risk of occurrence of HCC.

Association of the tumor necrosis factor -308 A/G promoter polymorphism with Tourette syndrome.

Several lines of evidence suggest that certain subtypes of obsessive-compulsive and tic disorders might be paediatric manifestations of post-streptococcal autoimmunity caused by cross-reactive autoantibodies. As tumor necrosis factor (TNF) is known to play a seminal role in coordinating the humoral immune response, TNF gene polymorphisms have been proposed as genetic risk factors both in obsessive-compulsive disorder (OCD) and Tourette syndrome (TS). The aim of this study was to investigate two TNF promoter polymorphisms (-238 A/G: rs361525 and -308 A/G: rs1800629) on the genetic susceptibility to OCD and TS in a child psychiatric sample (102 patients with OCD and 117 patients with TS). In the case-control set-up, the genotype and allele frequencies were compared to a control group from the general population (n = 405). As a control child psychiatric sample, 194 children with attention-deficit hyperactivity disorder were also genotyped. Our results revealed that the TNF -308 G-allele was more frequent in children with TS compared to controls (90.2% vs 84.8%, P = 0.037). For confirmation of this genetic association, a family-based analysis, the transmission disequilibrium test was used, which showed preferential transmission of the G-allele to patients with TS (nominal P-value 0.011). Moreover, this allele was also transmitted more frequently to children with tic symptoms (nominal P-value 0.039). No association was found between OCD or obsessive-compulsive symptoms and the studied TNF polymorphisms. Based on these findings, the TNF -308 G-allele can be associated with Tourette syndrome, highlighting the potential pathophysiological role of TNF dysregulation.

Rcor2 underexpression in senescent mice: a target for inflammaging?

BackgroundAging is characterized by a low-grade systemic inflammation that contributes to the pathogenesis of neurodegenerative disorders such as Alzheimer’s disease (AD). However, little knowledge is currently available on the molecular processes leading to chronic neuroinflammation. In this context, recent studies have described the role of chromatin regulators in inflammation and longevity including the REST corepressor (Rcor)-2 factor, which seems to be involved in an inflammatory suppressive program.MethodsTo assess the impact of Rcor2 in age-related inflammation, gene expression levels were quantified in different tissues and ages of the spontaneous senescence-accelerated P8 mouse (P8) using the SAMR1 mouse (R1) as a control. Specific siRNA transfection in P8 and R1 astrocyte cultures was used to determine Rcor2 involvement in the modulation of neuroinflammation. The effect of lipopolysaccharide (LPS) treatment on Rcor2 levels and neuroinflammation was analyzed both in vivo and in vitro.ResultsP8 mice presented a dramatic decrease in Rcor2 gene expression compared with R1 controls in splenocytes, an alteration also observed in the brain cortex, hippocampus and primary astrocytes of these mice. Rcor2 reduction in astrocytes was accompanied by an increased basal expression of the interleukin (Il)-6 gene. Strikingly, intraperitoneal LPS injection in R1 mice downregulated Rcor2 in the hippocampus, with a concomitant upregulation of tumor necrosis factor (Tnf-α), Il1-β and Il6 genes. A negative correlation between Rcor2 and Il6 gene expression was also verified in LPS-treated C6 glioma cells. Knock down of Rcor2 by siRNA transfection (siRcor2) in R1 astrocytes upregulated Il6 gene expression while siRcor2 further increased Il6 expression in P8 astrocytes. Moreover, LPS activation provoked a further downregulation of Rcor2 and an amplified induction of Il6 in siRcor2-tranfected astrocytes.ConclusionsData presented here show interplay between Rcor2 downregulation and increased inflammation and suggest that Rcor2 may be a key regulator of inflammaging.

Whole-exome resequencing reveals recessive mutations in TRAP1 in individuals with CAKUT and VACTERL association

Congenital abnormalities of the kidney and urinary tract (CAKUT) account for approximately half of children with chronic kidney disease and they are the most frequent cause of end-stage renal disease in children in the US. However, its genetic etiology remains mostly elusive. VACTERL association is a rare disorder that involves congenital abnormalities in multiple organs including the kidney and urinary tract in up to 60% of the cases. By homozygosity mapping and whole exome resequencing combined with high-throughput mutation analysis by array-based multiplex PCR and next-generation sequencing, we identified recessive mutations in the gene TNF receptor-associated protein 1 (TRAP1) in two families with isolated CAKUT and three families with VACTERL association. TRAP1 is a heat shock protein 90-related mitochondrial chaperone possibly involved in antiapoptotic and endoplasmic reticulum-stress signaling. Trap1 is expressed in renal epithelia of developing mouse kidney E13.5 and in the kidney of adult rats, most prominently in proximal tubules and in thick medullary ascending limbs of Henle’s loop. Thus, we identified mutations in TRAP1 as highly likely causing CAKUT or CAKUT in VACTERL association.

Tumor necrosis factor gene polymorphisms and endometriosis in Asians: a systematic review and meta-analysis

Background Numerous studies have described the association between polymorphisms in the tumor necrosis factor (TNF) gene and risk of endometriosis. However, the results remain controversial. Here we reviewed studies reporting the association between TNF gene polymorphisms and endometriosis risk in Asians. Methods PubMed and Embase were searched. Twelve case-control studies assessing the role of multiple TNF gene polymorphisms in endometriosis were included. If no less than two articles evaluated one variant, meta-analysis was conducted; otherwise, narrative analysis was chosen. A fixed- or random-effects model was employed according to the heterogeneity among studies. The strength of the association between TNF gene polymorphisms and endometriosis risk was assessed by odds ratios and 95% confidence intervals. Results For TNF-α -238G&gt;A, -308G&gt;A, -857C&gt;T, and -863C&gt;A, no significant associations were identified from all genetic models. For TNF-α -850T&gt;C, results from one study showed that patients harboring the heterozygote TC were less susceptible to endometriosis than patients harboring the homozygote TT. For TNF-α -1031T&gt;C, a mild increase in endometriosis risk was found in the Asian population. Meta-analysis from two studies found that the TNF-β +252&gt;G polymorphism had a protective effect in Chinese individuals. Due to the limitations of the included studies, it is necessitated to perform more studies to elucidate the possible roles of TNF gene polymorphisms in the pathogenesis of endometriosis. Conclusions TNF-α -1031T&gt;C and TNF-β +252A&gt;G were significantly associated with the risk of endometriosis in Asian and Chinese populations, respectively. To further evaluate these associations, more large-scale, rigorously designed studies are needed.

Study of tumor necrosis factor-α-308 promoter polymorphism in psoriasis vulgaris

Background The etiology of psoriasis is still unclear. Defining the molecular genetics of psoriasis may enhance our understanding of the disease process. An association of psoriasis vulgaris with functional polymorphisms in the tumor necrosis factor (TNF) gene has been reported in some populations. Objective To analyze the association of polymorphisms of the TNF-α gene in psoriasis vulgaris cases and its relation to TNF-α serum levels in the etiopathogenesis of this disease in a sample of Egyptian patients. Patients and methods This case–control study included 30 patients with psoriasis vulgaris and 20 controls who were examined to detect G–A transition polymorphism at position −308 of the TNF-α gene by PCR and estimation of TNF-α serum levels by enzyme linked immunosorbent assay. Results Compared with the controls, patients with psoriasis vulgaris showed a high frequency of the TNF-α-308GG genotype (P Conclusion A significant association was found between the different genotypes of the TNF-α gene polymorphism and psoriasis, suggesting that the TNF-α gene polymorphism may play a possible active role in the etiopathogenesis of psoriasis vulgaris.

Associations between TNF gene polymorphisms (−308 A/G, −238 A/G, −1031 C/T and −857 T/C) and genetic susceptibility to T1D: a meta-analysis

The aim of this study was to estimate the associations between tumor necrosis factor (TNF) gene polymorphisms and type 1 diabetes (T1D) using meta-analysis. Relevant studies were searched using PubMed and Embase up to August 2013. A total of 32 comparisons from 21 studies examining the associations between TNF polymorphisms and T1D were included in the present meta-analysis. Our meta-analysis identified a significant association between TNF -308 A/G polymorphism A allele and T1D in all subjects [odds ratio (OR) 2.001, 95 % confidence interval (CI) 1.732-2.312). Significant associations of AA and AA+AG genotype of TNF -308 A/G polymorphism with genetic susceptibility to T1D were also found (OR 3.203, 95 % CI 2.373-4.324; OR 2.232, 95 % CI 1.881-2.649). After stratification by ethnicity, significant associations of T1D with TNF -308 A/G polymorphism under all genetic models (A allele and AA, AA+AG genotype) were still detected in European (OR 1.952, 95 % CI 1.675-2.274; OR 3.108, 95 % CI 2.169-4.455; OR 2.249, 95 % CI 1.870-2.706, respectively) and non-European populations (OR 2.152, 95 % CI 1.488-3.112; OR 3.439, 95 % CI 2.000-5.914; OR 2.207, 95 % CI 1.496-3.257, respectively). Our meta-analysis also revealed an association of TNF -857 T/C polymorphism T allele with T1D risk (OR 1.647, 95 % CI 1.431-1.896). Furthermore, analysis of TT and TT+TC genotype indicated the same result patterns as shown by the TNF -857 T/C polymorphism T allele (OR 2.206, 95 % CI 1.467-3.317; OR 1.762, 95 % CI 1.490-2.083). In conclusion, our meta-analysis results indicate that TNF -308 A/G and -857 T/C polymorphisms are involved in the genetic background of T1D.

TNF -308 G/A Polymorphism and Risk of Acne Vulgaris: A Meta-Analysis

BackgroundThe -308 G/A polymorphism in the tumor necrosis factor (TNF) gene has been implicated in the risk of acne vulgaris, but the results are inconclusive. The present meta-analysis aimed to investigate the overall association between the -308 G/A polymorphism and acne vulgaris risk.MethodsWe searched in Pubmed, Embase, Web of Science and CNKI for studies evaluating the association between the -308 G/A gene polymorphism and acne vulgaris risk. Data were extracted and statistical analysis was performed using STATA 12.0 software.ResultsA total of five publications involving 1553 subjects (728 acne vulgaris cases and 825 controls) were included in this meta-analysis. Combined analysis revealed a significant association between this polymorphism and acne vulgaris risk under recessive model (OR = 2.73, 95% CI: 1.37–5.44, p = 0.004 for AA vs. AG + GG). Subgroup analysis by ethnicity showed that the acne vulgaris risk associated with the -308 G/A gene polymorphism was significantly elevated among Caucasians under recessive model (OR = 2.34, 95% CI: 1.13–4.86, p = 0.023).ConclusionThis meta-analysis suggests that the -308 G/A polymorphism in the TNF gene contributes to acne vulgaris risk, especially in Caucasian populations. Further studies among different ethnicity populations are needed to validate these findings.

Long-acting beneficial effect of percutaneously intramyocardially delivered secretome of apoptotic peripheral blood cells on porcine chronic ischemic left ventricular dysfunction

The quantity of cells with paracrine effects for use in myocardial regeneration therapy is limited. This study investigated the effects of catheter-based endomyocardial delivery of secretome of 2.5 × 109 apoptotic peripheral blood mononuclear cells (APOSEC) on porcine chronic post-myocardial infarction (MI) left ventricular (LV) dysfunction and on gene expression. Closed-chest reperfused MI was induced in pigs by 90-min occlusion followed by reperfusion of the mid-LAD (day 0). At day 30, animals were randomized to receive porcine APOSEC (n = 8) or medium solution (control; n = 8) injected intramyocardially into the MI border zone using 3D NOGA guidance. At day 60, cardiac MRI with late enhancement and diagnostic NOGA (myocardial viability) were performed. Gene expression profiling of the infarct core, border zone, and normal myocardium was performed using microarray analysis and confirmed by quantitative real-time PCR. Injection of APOSEC significantly decreased infarct size (p < 0.05) and improved cardiac index and myocardial viability compared to controls. A trend towards higher LV ejection fraction was observed in APOSEC vs. controls (45.4 ± 5.9% vs. 37.4 ± 8.9%, p = 0.052). Transcriptome analysis revealed significant downregulation of caspase-1, tumor necrosis factor and other inflammatory genes in APOSEC-affected areas. rtPCR showed higher expression of myogenic factor Mefc2 (p < 0.05) and downregulated caspase genes (p < 0.05) in APOSEC-treated pigs. In conclusion, overexpression of MEF2c and repression of caspase was related to decreased infarct size and improved cardiac function in secretome-treated animals. Altered gene expression 1-month post-APOSEC treatment proved the long-acting effects of cell-free therapy with paracrine factors.

Enfermedad inflamatoria intestinal, hacia la nutrición personalizada

La incidencia de la enfermedad inflamatoria intestinal (EII) está en aumento en los países que adquieren un estilo de vida occidental. Su etiopatogenia no está bien definida pero se asocia a causas multifactoriales. En individuos genéticamente predispuestos, diferentes factores ambientales desencadenan alteraciones en la respuesta inmune. Como resultado se pierde la tolerancia hacia la microbiota intestinal comensal, produciéndose daños en los tejidos e inflamación crónica. Entre los factores de riesgo ambiental se encuentra la dieta. Dietas con alto contenido en sacarosa, hidratos de carbonos refinados, ácidos grasos poliinsaturados omega-6 y con bajo contenido en fibra se relacionan con un mayor riesgo de presentar EII, particularmente Enfermedad de Crohn (EC). Las recomendaciones nutricionales en la EII no pueden generalizarse, ya que todos los pacientes no responden de la misma manera ante éstas. La aparición de disciplinas como la nutrigenética, nutrigenómica y epigenética permiten una mayor comprensión de la patogenia de la enfermedad y, a su vez, nos abren la posibilidad hacia un abordaje individualizado desde el punto de vista nutricional. Un ejemplo de ello lo encontramos en los portadores del polimorfismo 857C/T en el gen TNF (Tumor Necrosis Factor), en los que una dieta elevada en ácidos grasos saturados y monoinsaturados resulta perjudicial, asociándose a un fenotipo más activo de enfermedad. En el presente trabajo se realiza una revisión de los artículos científicos más recientes en estas disciplinas en relación a la EII y sus posibles aplicaciones terapéuticas nutricionales, como el uso de antioxidantes o la proporción de ácidos grasos poliinsaturados v-6/v-3. Para la búsqueda de estos artículos se ha utilizado la base de datos del National Center for Biotechnology Information (NCBI), seleccionando los de mayor interés comprendidos entre 2007-2012.

Delayed ethanol elimination and enhanced susceptibility to ethanol-induced hepatosteatosis after liver resection.

To investigate ethanol-induced hepatic steatosis after liver resection and the mechanisms behind it. First, the preliminary examination was performed on 6 sham-operated (Sham) and 30 partial hepatectomy (PH) male Wistar rats (8-wk-old) to evaluate the recovery of the liver weight and liver function after liver resection. PH rats were sacrificed at the indicated time points (4, 8, and 12 h; 1, 3, and 7 d) after PH. Second, the time point for the beginning of the chronic ethanol exposure (1 wk after sham- or PH-operation) was determined based on the results of the preliminary examination. Finally, pair-feeding was performed with a controlled diet or with a 5-g/dL ethanol liquid diet for 28 d in another 35 age-matched male Wistar rats with a one-week recovery after undergoing a sham- (n = 15) or PH-operation (n = 20) to evaluate the ethanol-induced liver injury after liver resection. Hepatic steatosis, liver function, fatty acid synthase (Fas) gene expression level, the expression of lipid metabolism-associated enzyme regulator genes [sterol regulatory element binding protein (Srebp)-1 and peroxisome proliferator-activated receptor (Ppar)-α], the mediators that alter lipid metabolism [plasminogen activator (Pai)-1 gene expression level and tumor necrosis factor (Tnf)-α production], and hepatic class-1 alcohol dehydrogenase (Adh1)-associated ethanol elimination were investigated in the 4 groups based on histological, immunohistochemical, biochemical, Western blotting, reverse transcriptase chain reaction, and blood ethanol concentration analyses. The relevant gene expression levels, liver weight, and liver function were assessed before and 1 wk after surgery to determine the subject's recovery from the liver resection using the rats that had been subjected to the preliminary examination. In the PH rats, ethanol induced marked hepatic steatosis with impaired liver functioning, as evidenced by the accumulation of fatty droplets within the hepatocytes, the higher increases in their hepatic triglyceride and blood alanine aminotransferase and blood aspartate aminotransferase levels after the 28-d pair-feeding period. The Sham-ethanol rats, not the PH-ethanol rats, demonstrated the up-regulation of Srebp-1 and the down-regulation of Ppar-α mRNA expression levels after the 28-d pair-feeding period. The 28-d ethanol administration induced the up-regulation of Pai-1 gene expression level and an overproduction of TNF-α in the Sham and the PH rats; however, the effect was more significant in the PH rats. The PH-ethanol rats (n = 4) showed higher residual blood ethanol concentrations than did the Sham-ethanol rats (n = 6) after a 5-h fast (0.66 ± 0.4 mg/mL vs 0.2 ± 0.1 mg/mL, P < 0.05); these effects manifested without up-regulation of Adh1 gene expression, which was present in the Sham-ethanol group after the 28-d pair-feeding period. One week after the liver resection, the liver weight, function, the gene expression levels of Fas, Srebp-1, Ppar-α, Pai-1 and Tnf-α recovered; however, the Adh1 gene expression did not recover in rats. Desensitization to post-hepatectomy ethanol treatment and slow recovery from PH in Adh1 gene expression enhanced the susceptibility to ethanol-induced hepatic steatosis after PH in rats.