Abril Bernardette Martinez-Rizo

Pirfenidone restricts Th2 differentiation in vitro and limits Th2 response in experimental liver fibrosis

Polarized T helper type 2 (Th2) response is linked with fibrosis. Here, we evaluated the effect of the anti-fibrotic agent pirfenidone on Th type 1 (Th1) and Th2 responses. For in vivo testing; Wistar rats were made cirrhotic by intraperitoneal administration of thioacetamide. Once hepatic damage was established, pirfenidone was administered intragastrically on a daily basis during three weeks. Gene expression of Th marks was evaluated by RT-PCR and Western blot assays from liver homogenates. Pirfenidone therapy induced down-regulation of Th2 transcripts and proteins (GATA3 and IL-4), without affecting significantly Th1 genes expression (T-bet and IFN-γ). We found that the activated form of p38 MAPK (identified by Western blot) was reduced by pirfenidone treatment, which is consistent with the anti-Th2 activity observed. Pirfenidone reduced GATA3 nuclear localization without modifying its DNA binding activity (evaluated by electrophoretic mobility shift assay). For in vitro testing; human naive CD4+ T cells were cultured in either Th1 or Th2 polarizing conditions in the presence of pirfenidone and flow cytometric analysis of intracellular synthesis of IFN-γ and IL-4 was conducted. Pirfenidone impaired development of Th2 subpopulation. In conclusion, pirfenidone is capable of impairing Th2 differentiation and limits Th2 profibrogenic response. The mechanism involves p38 inhibition and regulation of GATA3 expression and translocation.

Biodegradation and Bioremediation of Organic Pesticides

Pesticides can be used to control or to manage pest populations at a tolerable level. The suffix “-cide” literally means “kill”, therefore, the term pesticide refers to a chemical substance that kills pests. It is incorrect to assume that the term pesticide refers only to insecticides. Pesticides include many different types of products with different functions or target (Table 1). The pesticide designation is formed by combining the name of the pest (e.g., insect or mite) with the suffix “-cide” (1).

Plasmin plays a key role in the regulation of profibrogenic molecules in hepatic stellate cells.

Background: Plasmin role in transforming growth factor‐β (TGF‐β)‐responsive gene regulation remains to be elucidated. Also, plasmin action on co‐repressor Ski‐related novel protein N (SnoN) and differential activation of matrix metalloproteinases (MMPs) are unknown. Thus, the role of plasmin on profibrogenic molecule expression, SnoN transcriptional kinetics and gelatinase activation was investigated.

Association of single-nucleotide polymorphisms in non-coding regions of the TLR4 gene with primary open angle glaucoma in a Mexican population.

ABSTRACT Background: Toll-like receptor 4 (TLR4) non-coding polymorphisms are associated to primary open angle glaucoma (POAG), normal tension glaucoma, and pseudoexfoliation glaucoma. This study was performed to determine whether non-coding single nucleotide polymorphisms (SNPs) in the TLR4 gene contribute to POAG in a Mexican population. Material and methods: A total of 187 unrelated Mexican patients with POAG and 109 control subjects were included. Allelic, genotypic, and haplotypic diversity was assessed for the non-coding polymorphisms rs11536889, rs1927911, rs12377632, and rs2149356 of the TLR4 gene. Genotyping of target SNPs was performed by 5′ exonuclease allelic discrimination assays. Results: Strong linkage disequilibrium was observed among the SNPs (D’ > 0.818), which were located in one haplotype block. The rs11536889 polymorphism was not associated to POAG in any case. The frequency of the minor allele of rs2149356 was significantly higher in the glaucoma group, conferring an increased risk of POAG (p = 0.0018, OR = 1.803, 95% CI 1.2556–2.5890) whereas minor allele of rs12377632 was significantly lower, attributing a protective effect (p = 0.0001, OR = 0.6662, 95% CI 0.4753–0.9339). Subjects with genotypes carrying the minor allele of rs1927911 and rs2149356 shown an increased risk for POAG (p = 0.03, OR = 1.78, 95% CI 1.10–2.87, and p < 0.0004, OR =2.62, 95%CI 1.61–4.27 respectively). Finally, we found significant risk haplotypes. The GTT haplotype (constituted by rs1927911, rs12377632, and rs2149356) reached the higher OR (p = 0.0026, OR = 4.70, 95% CI 1.73–12.77). Conclusions: We have identified intronic TLR4 SNPs as genetic susceptibility alleles for POAG in a Mexican population. Our findings support the association of the TLR4 gene with POAG.

Oxidative stress regulates the expression of the Pht cluster genes involved in phaseolotoxin synthesis in Pseudomonas syringae pv. phaseolicola NPS3121

This study evaluated the role of oxidative stress on the expression of Pht cluster genes involved in phaseolotoxin synthesis in Pseudomonas syringae pv. phaseolicola. Results demonstrate that the expression of Pht cluster genes is regulated by oxidative stress in a manner dependent of the ROS present in the cell. The presence of H2O2 and Paraquat, influences on the expression of the Pht cluster genes in function of the compound and of the concentration evaluated, demonstrating that expression of Pht genes is part of the oxidative stress response in P. syringae pv. phaseolicola NPS3121.

Abstract 1279: A polymorphism of VEGF -2489C/T is associated with prostate cancer susceptibility in Mexicans

Introduction: Prostate cancer (CaP) encompasses a range of malignant prostate tissue dysplasias that primarily affects men over 50 years, is the second leading cause of cancer mortality in males. VEGF expression is associated with tumor progression and metastasis in patients with CaP. The SNP -1154 G/A is associated with the severity of CaP populations in Tunisia and the United Kingdom while -634 G/C alone has been associated in Tunisian population. It is unknown whether these polymorphisms could serve as biomarkers in the Mexican population. Aim: To associate VEGF polymorphisms -1154 G/A and - 634 G/C with the severity of prostate cancer in patients of western Mexico. Materials and methods: The gDNA was analyzed a total of 525 men of whom 301 are presented HBP and 224 patients with clinical diagnosis of prostate cancer. For association with severity they were subclassified into high (≥7) and low grade (≤6) following the Gleason scale. Genotyping was performed by Real Time PCR using TaqMan probes system. Results. When we compare the allelic frequencies in the control group, they are in Hardy-Weinberg equilibrium. However, no significant association of the disease with polymorphisms or severity or progression was found. Conclusions: There is no association between prostate cancer and genetic polymorphisms at -634 and -1154 position of the promoter region of VEGF. Note: This abstract was not presented at the meeting. Citation Format: Abril Martinez-Rizo, Xavi Casillas-Rangel, Cuerpo Academico Investigacion Bioquimica (UAN-CA-266), Hilda Andrade-Madrid, Veronica Benites-Godinez, Nallhely Rodriguez-Ocampo. A polymorphism of VEGF -2489C/T is associated with prostate cancer susceptibility in Mexicans [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 1279. doi:10.1158/1538-7445.AM2017-1279