It’s the academia, dummy! or when quantity supersedes quality

Many of us, faculty members dedicated to the profession of university professor, began our professional careers investing the best years of our youth in academically preparing ourselves in the best way possible. We continued our careers by searching for a renowned institution to work for. Its prestige provided us with a solid foundation for quick growth, thus reaching the top of the academic hierarchy, making us feel that we made the best investment for our future. Since it is our responsibility to prepare ourselves, it is also our responsibility to make sure this preparation bears the best fruit for society and our families. But also, we aspire to heighten our prestige, even a little, so that at the dusk of our professional life we can feel the satisfaction of having accomplished our mission in society and be rewarded with the appreciation and respect of our colleagues (which results in sincere affection), who we also respect and admire, and fulfill the debt to our family who supported us and sacrificed so much for our eagerness to pursue professional success, a success that has only one noble goal: academic excellence

Origin of personalized medicine in pioneering, passionate, genomic research

Personalized medicine, one of the main promises of the Human Genome Project (HGP) that began three decades ago, is now a new therapeutic paradigm. With its arrival the era of developing drugs to suit all patients, yet often having to withdraw a promising new one because a minority of patients was at risk, even though it had proved valuable for the majority was consigned to history as were trial-and-error strategies being the predominant means of tailoring therapy. But how did it originate and the earliest examples emerge? Is it true that the first personalized diagnostic test was the companion test for Herceptin®? This account of a remarkable journey from genomic and translational research to therapeutic and diagnostic innovations, describes how sequencing the human growth hormone (hGH) locus provided proof of principle for HGP-inspired personalized medicine. Sequencing this locus and the resultant biomanufacture of HGH and the development of a test capable of detecting which patients would benefit from its administration helped silence the skeptics who questioned the validity of such an approach. The associated companion diagnostic was created four years before the invention of the HercepTest® (registered as the first companion diagnostics ever developed). By cultivating genomic research with passion and pursuing its applications, we and many others contributed to the emergence of a new diagnostics industry, the discovery of better actionable gene-targets and to a revitalized pharmaceutical industry capable of developing safer and more effective therapies. In combination, these developments are beginning to fulfill the promise of the HGP, offering each patient the opportunity to adopt the right treatment at the correct dosage in an opportune manner

La reacción en cadena de la polimerasa a dos décadas de su invención

La PCR, tÈcnica inventada por Kary B. Mullis en 1983, emplea un par de oligonucleÛtidos para de- limitar una regiÛn de interÈs y una polimerasa para extenderlos, utilizando ambas hebras del gen en cuestiÛn como plantilla. Al repetir este ciclo dece- nas de veces, se duplica cada vez el fragmento de ADN en cuestiÛn. AsÌ se logra copiar millones de veces la secuencia de interÈs, aunque se encuentre entre millones de otras secuencias de ADN. A 20 aÒos de su invenciÛn, la PCR se cataloga como la estrella de las herramientas de la biologÌa mole- cular. En la actualidad son innumerables las aplica- ciones de su utilizaciÛn en m ̇ltiples campos de las ciencias biolÛgicas, agropecuarias y de la salud

Rational design for the recombinant expression of the Receptor Binding Domain of SARS-CoV-2 Spike Glycoprotein

Background: COVID-19 represents a significant threat to global human health. SARS-CoV-2, the etiologic viral agent, needs to be under-covered at the structural biology level to facilitate the rational design of diagnostic tests and vaccine candidates. SARS-CoV-2 Receptor Binding Domain of Spike protein (RBD-S) acts as the key to open the gate, to enter the cells during infection. Thus, it is a stronger candidate for designing effective antigens for vaccines and diagnostics. Here, we relied on the viral DNA codifying to RBD-S to use synthetic biology for optimizing the recombinant expression of this (rRBD-S) as a proof of concept of rational designs of bioprocess for vaccine candidates and immunogens to improved rapid diagnostic tests. Methods: rRBD-S coding sequences inspired on RBD-S ectodomain from SARS-CoV-2 were designed, codon-optimized, tagged, synthesized, cloned in an expression vector (pD444-MR), and transformed into C41(DE3)pLysS E. coli strain. Expression of recombinant RBD-S was resulting in a protein purified using Ni-IMAC (Nickel Immobilized metal affinity chromatography). Results: rRBD-S produced result in a ~30KDa protein with yields of 4.618 gr L-1. Protein was recovered from the bacterial soluble fraction without refolding process. Conclusions: rRBD-S is an important tool for immunity diagnostics as Lateral-Flow-Devices, structural biology studies, and even as vaccine candidate for combating SARS-CoV-2. Notably considering the advantages of rational subunit vaccines for immune response against other vaccines technologies whose effectiveness in the long-term process has not been demonstrated yet. Acknowledgements: We thank HIDALGO´s Council of Science, Technology and Innovation (CITNOVA) for the GRANT 20201122 to LMRM

Disección transcripcional del Locus GH del genoma humano

El locus de la hormona del crecimiento humano (hGH) presenta variaciones en los niveles de expre- sión en algunos de sus componentes hasta en tres órdenes de magnitud. Este estudio comparó deleciones (140 a 3,100 pb) y la fuerza de transcrip- ción de todos los promotores del locus con un gen reportero (hGH-N) mediante expresión transitoria. Los promotores largos tuvieron mayor expresión, paradójicamente hGH-V fue uno de los más acti- vos. Se detectaron tres elementos promotores ne- gativos y se evaluó la activación transcripcional di- ferencial para los diferentes promotores, mediante su respuesta a la acción de hormonas y cotransfec- ción de vectores expresores de factores transcripcionales

Effect of AGTR1 and BDKRB2 gene polymorphisms on atorvastatin metabolism in a Mexican population

Abstract. Discrepancies in the response to drugs are partially due to polymorphisms in genes involved in drug metabolism and transport. The frequency, pattern and impact of these polymorphisms vary among populations. In the present study, the pharmacokinetics and pharmacogenetics of atorvastatin (ATV) in a Mexican population were investigated. The study cohort exhibited differing ATV metabolizing phenotypes, and in subsequent allelic discrimination assays, single nucleotide polymorphisms in the angiotensinogen, angiotensin II type 1 receptor (AGTR1) and bradykinin B2 receptor (BDKRB2) genes were genotyped and their effects on the pharmacokinetic parameters of ATV were assessed. Additionally, association studies were performed to test for a correlation between metabolizing phenotypes and genetic variants. It was observed that carriers of the genotypes A/C and C/T in AGTR1 and BDKRB2 had higher area under the plasma concentration-time curve values from time 0 to the time of the last measurement and from time 0 extrapolated to infinity, and lower values of clearance of the fraction dose absorbed compared with homozygous carriers (P<0.05). Only the C/C genotype of BDKRB2 was associated with the fast metabolizer phenotype. These data suggest that AGTR1 and BDKRB2 are involved in ATV pharmacokinetics; a novel finding that requires confirmation in further studies

The dawn of the liquid biopsy in the fight against cancer

ABSTRACT Cancer is a molecular disease associated with alterations in the genome, which, thanks to the highly improved sensitivity of mutation detection techniques, can be identified in cell-free DNA (cfDNA) circulating in blood, a method also called liquid biopsy. This is a non-invasive alternative to surgical biopsy and has the potential of revealing the molecular signature of tumors to aid in the individualization of treatments. In this review, we focus on cfDNA analysis, its advantages, and clinical applications employing genomic tools (NGS and dPCR) particularly in the field of oncology, and highlight its valuable contributions to early detection, prognosis, and prediction of treatment response

History and progress of antiviral drugs: from acyclovir to direct-acting antiviral agents (DAAs) for Hepatitis C

The development of antiviral drugs is a very complex process. Currently, around 50 drugs have been approved for human use against viruses such as HSV, HIV-1, the cytomegalo virus, the influenza virus, HBV and HCV. Advancements in this area have been achieved through efforts and technical breakthroughs in different scientific fields. The improvement in the treatment of HCV infection is a good example of what is needed for efficient antiviral therapy. A thorough description of the events that lead to the development of specifically targeted antiviral therapy or HCV (STAT-C) could be useful to further improve research for treating many other viral diseases in the future. Similar to HIV-1 and HBV treatment, combination therapy along with personalized medicine approaches have been necessary to successfully treat HCV patients. This review is focused on what has been done to develop a successful HCV therapy and the drawbacks along the wa

El etanol aumenta la replicación y expresión génica del VHC

El etanol acelera la progresión del daño hepático en los pacientes con hepatitis C crónica. Se utilizó el sistema de replicones subgenómicos del VHC para evaluar el efecto del etanol en la replicación y expresión génica del VHC. Se observó que el etanol aumentó los niveles del RNA y de las proteínas virales. Se observó que el etanol aumentó la expresión y actividad de la proteína COX-2 en las células Huh7 replicón, mientras que el AAS bloqueó dicho efecto. Lo que sugiere que, probablemente, la COX-2 modula el efecto del etanol en la replicación del VHC

The atorvastatin metabolic phenotype shift is influenced by interaction of drug-transporter polymorphisms in Mexican population: results of a randomized trial

Atorvastatin (ATV) is a blood cholesterol-lowering drug used to prevent cardiovascular events, the leading cause of death worldwide. As pharmacokinetics, metabolism and response vary among individuals, we wanted to determine the most reliable metabolic ATV phenotypes and identify novel and preponderant genetic markers that affect ATV plasma levels. A controlled, randomized, crossover, single-blind, three-treatment, three-period, and six-sequence clinical study of ATV (single 80-mg oral dose) was conducted among 60 healthy Mexican men. ATV plasma levels were measured using high-performance liquid chromatography mass spectrometry. Genotyping was performed by real-time PCR with TaqMan probes. Four ATV metabolizer phenotypes were found: slow, intermediate, normal and fast. Six gene polymorphisms, SLCO1B1-rs4149056, ABCB1-rs1045642, CYP2D6-rs1135840, CYP2B6-rs3745274, NAT2-rs1208, and COMT- rs4680, had a significant effect on ATV pharmacokinetics (P < 0.05). The polymorphisms in SLCO1B1 and ABCB1 seemed to have a greater effect and were especially important for the shift from an intermediate to a normal metabolizer. This is the first study that demonstrates how the interaction of genetic variants affect metabolic phenotyping and improves understanding of how SLCO1B1 and ABCB1 variants that affect statin metabolism may partially explain the variability in drug response. Notwithstanding, the influence of other genetic and non-genetic factors is not ruled out.Fil: León Cachón, Rafael B. R.. Universidad de Monterrey.; MéxicoFil: Bamford, Aileen Diane. Universidad de Monterrey.; MéxicoFil: Meester, Irene. Universidad de Monterrey.; MéxicoFil: Barrera Saldaña, Hugo Alberto. Vitagenesis S.A.; México. Innbiogem S.C.; MéxicoFil: Gómez Silva, Magdalena. Universidad Autonoma de Nuevo Leon.; MéxicoFil: Garcia Bustos, Maria Fernanda. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Salta. Instituto de Patología Experimental. Universidad Nacional de Salta. Facultad de Ciencias de la Salud. Instituto de Patología Experimental; Argentin