Rare coding variants in TREM2, PLCG2, and ABI3 were recently associated with the susceptibility to Alzheimer’s disease (AD) in Caucasians. Frequencies and AD-associated effects of variants differ across ethnicities. To start filling the gap on AD genetics in South America and assess the impact of these variants across ethnicity, we studied these variants in Argentinian population in association with ancestry. TREM2 (rs143332484 and rs75932628), PLCG2 (rs72824905), and ABI3 (rs616338) were genotyped in 419 AD cases and 486 controls. Meta-analysis with European population was performed. Ancestry was estimated from genome-wide genotyping results. All variants show similar frequencies and odds ratios to those previously reported. Their association with AD reach statistical significance by meta-analysis. Although the Argentinian population is an admixture, variant carriers presented mainly Caucasian ancestry. Rare coding variants in TREM2, PLCG2, and ABI3 also modulate susceptibility to AD in populations from Argentina, and they may have a European heritage.

Nevoid basal cell carcinoma syndrome (NBCCS) is an autosomal dominant disorder characterized by multiple basal cell carcinomas (BCC), mainly caused by PTCH1 gene mutations. Our current study aimed to establish (1) PTCH1 germinal and somatic mutational status, (2) component and Hedgehog (HH) pathway targets gene expression patterns, and (3) profile variations according to the genetic background in BCC and normal surrounding skin (NSS). We collected 23 blood and 20 BCC patient samples and analyzed the PTCH1 gene using bidirectional sequencing and multiplex ligation-dependent probe amplification. Quantitative PCR was used to determine the mRNA expression levels of PTCH1, SMO, GLI3, and CCND1 in paired samples of BCC and NSS from 20 patients and four non-NBCCS skin controls (C). Our analyses identified 12 germline and five somatic sequence variants in PTCH1. mRNA levels of PTCH1, SMO, and GLI3 were higher in NSS compared to C samples, reaching maximum values in BCC samples (p < 0.05). NSS with PTCH1 germline mutations had modified SMO, PTCH1, and GLI3 mRNA levels compared to samples without mutation (p < 0.01). Two PTCH1 mutations in BCC led to an increase in PTCH1, SMO, and GLI3, and a decrease in CCND1 mRNA levels (p < 0.01 vs. BCC with germline mutation only). These results indicate that besides PTCH1, other genes are responsible for NBCCS and BCC development in a population exposed to high UV radiation. Additionally, the mutational events caused increased expression of HH-related genes, even in phenotypically normal skin.

Cancer stem cells (CSCs) are an important player in the resistance of cancers to therapy. In this work, we determined the flavonoids composition and biological action of Aloysia polystachya (AP) extracts in colorectal cancer. The chemical characterization of extracts was performed by HPLC. Assays of cytotoxicity, apoptosis, migration and invasion, metalloproteases activity, clonogenic growth, tumorspheres formation, Hoechts efflux, pluripotency marker expression and sensitization to chemotherapeutic drugs were performed in vitro in human HCT116 and murine CT26 colorectal cancer cells. The AP toxicity and effect in tumor growth administered alone or in combination with 5- Fluorouracile was analyzed in vivo, including histopathological studies. We found that AP extracts induced in vitro the apoptosis of colorectal cancer cell lines decreasing the CSC proportion. Moreover, they were capable to kill 5-Fluorouracile resistant side population cells. At not toxic doses in vivo, AP extracts inhibited tumor growth. Regarding the ability to reduce the CSC population, AP extracts deserves to be investigated as a useful therapy for colorectal cancer treatment.

We investigated the effect of ovariectomy(oVx) on renal and systemic hemodynamic, electrolyte excretion and total and dephosphorylated Na⁺,K⁺-ATPase α1 subunit (t-d-NKA) in normotensive Wistar rats under a normal sodium (NS, 0.24%) or high sodium (HS, 1%) intake versus intact female (IF). On NS intake, t-d-NKA was higher in oVx rats and overexpressed in the thick ascending limbs (P < .01 vs. IF) and renal plasma flow was increased. On HS intake, oVx rats maintained a greater dephosphorylated NKA, excreted less sodium, and developed arterial hypertension (134 ± 4 vs. IF 112 ± 5 mm Hg, P < .05). Sodium load caused salt-sensitive hypertension in oVx Wistar rats.