Genetic Alterations of SMYD4 in Solid Tumors Using Integrative Multi-Platform Analysis.

SMYD4 is a member of the SMYD family that has lysine methyltransferase function. Little is known about the roles of SMYD4 in cancer. The aim of this study is to investigate genetic alterations in the SMYD4 gene across the most prevalent solid tumors and determine its potential as a biomarker. We performed an integrative multi-platform analysis of the most common mutations, copy number alterations (CNAs), and mRNA expression levels of the SMYD family genes using cohorts available at the Cancer Genome Atlas (TCGA), cBioPortal, and the Catalogue of Somatic Mutations in Cancer (COSMIC). SMYD genes displayed a lower frequency of mutations across the studied tumors, with none of the SMYD4 mutations detected demonstrating sufficient discriminatory power to serve as a biomarker. In terms of CNAs, SMYD4 consistently exhibited heterozygous loss and downregulation across all tumors evaluated. Moreover, SMYD4 showed low expression in tumor samples compared to normal samples, except for stomach adenocarcinoma. SMYD4 demonstrated a frequent negative correlation with other members of the SMYD family and a positive correlation between CNAs and mRNA expression. Additionally, patients with low SMYD4 expression in STAD and LUAD tumors exhibited significantly poorer overall survival. SMYD4 demonstrated its role as a tumor suppressor in the majority of tumors evaluated. The consistent downregulation of SMYD4, coupled with its association with cancer progression, underscores its potential usefulness as a biomarker.

Alpha-1-antitrypsin: A possible host protective factor against Covid-19.

Understanding Covid-19 pathophysiology is crucial for a better understanding of the disease and development of more effective treatments. Alpha-1-antitrypsin (A1AT) is a constitutive tissue protector with antiviral and anti-inflammatory properties. A1AT inhibits SARS-CoV-2 infection and two of the most important proteases in the pathophysiology of Covid-19: the transmembrane serine protease 2 (TMPRSS2) and the disintegrin and metalloproteinase 17 (ADAM17). It also inhibits the activity of inflammatory molecules, such as IL-8, TNF-α, and neutrophil elastase (NE). TMPRSS2 is essential for SARS-CoV-2-S protein priming and viral infection. ADAM17 mediates ACE2, IL-6R, and TNF-α shedding. ACE2 is the SARS-CoV-2 entry receptor and a key component for the balance of the renin-angiotensin system, inflammation, vascular permeability, and pulmonary homeostasis. In addition, clinical findings indicate that A1AT levels might be important in defining Covid-19 outcomes, potentially partially explaining associations with air pollution and with diabetes. In this review, we focused on the interplay between A1AT with TMPRSS2, ADAM17 and immune molecules, and the role of A1AT in the pathophysiology of Covid-19, opening new avenues for investigating effective treatments.

Hematopoietic stem cell transplantation (HSCT): an approach to autoimmunity.

HSCT provides the opportunity to replace a damaged tissue. It is the most important treatment for high risk hematologic malignant and non malignant disorders. An important challenge in the identification of matched donors/patients is the HLA diversity. The Mexican Bone Marrow Registry (DONORMO) has nowadays > 5000 donors. The prevalent alleles are Amerindian, Mediterranean (Semitic and Spanish genes) and African. In theory, it is possible to find 11% of 6/6 A-B-DR low resolution matches for 70% of patients with Mexican ancestry. We contributed with 39 unrelated, cord blood and autologous HSCT for patients with malignant, genetic and autoimmune disorders. Overall disease survival was 50% (2-7 years) depending on the initial diagnosis, conditioning, disease evolution or other factors. Clinical studies using autologous and unrelated HSC are performed on patients with refractory autoimmune diseases producing mixed results: mainly, T1D, RA, MS, SLE. Improvement has been observed in skin damage and quality of life in SLE and systemic sclerosis. Disease stabilization in 2/3 of MS patients. However, in RA and T1D, initial benefits have been followed by eventual relapse. With growing clinical experience and protocol improvement, treatment-related mortality is decreasing. Proof efficacy will be achieved by comparing HSCT with standard therapy in autoimmunity.