Microarrays and NGS for Drug Discovery

Novel technologies and state of the art platforms developed and launched over the last two decades such as microarrays, next-generation sequencing, and droplet PCR have provided the medical field many opportunities to generate and analyze big data from the human genome, particularly of genomes altered by different diseases like cancer, cardiovascular, diabetes and obesity. This knowledge further serves for either new drug discovery or drug repositioning. Designing drugs for specific mutations and genotypes will dramatically modify a patient’s response to treatment. Among other altered mechanisms, drug resistance is of concern, particularly when there is no response to cancer therapy. Once these new platforms for omics data are in place, available information will be used to pursue precision medicine and to establish new therapeutic guidelines. Target identification for new drugs is necessary, and it is of great benefit for critical cases where no alternatives are available. While mutational status is of highest importance as some mutations can be pathogenic, screening of known compounds in different preclinical models offer new and quick strategies to find alternative frameworks for treating more diseases with limited therapeutic options

MicroRNAs expression profile in chemotherapy-induced cardiotoxicity in non-small cell lung cancer using a co-culture model

Clinical application of chemotherapy in lung cancer is constrained by side effects, notably cardiotoxicity, the mechanisms of which remain elusive. This study assessed the potential of specific microRNAs (miRNAs) as biomarkers for chemotherapy-induced cardiotoxicity in lung cancer. We employed two lung adenocarcinoma cell lines (Calu6 and H1792) and ventricular normal human cardiac fibroblasts (NHCF-V) in single and co-culture experiments. Functional tests were conducted using 100 µM carboplatin and 1µM vinorelbine doses. The effects of carboplatin and vinorelbine, both individually and in combination, were evaluated at cellular and molecular levels 48h post-therapy for both mono- and co-cultures. miR-205-5p, miR-21-5p, and miR-30a-5p, modulated by anticancer treatments and influencing cardiotoxicity, were analyzed. Vinorelbine and carboplatin treatment promoted apoptosis and autophagy in lung cancer cells and cardiac fibroblasts more than in controls. Western blot analyses revealed BCL2 and p53 protein upregulation. Using qRT-PCR, we investigated the expression dynamics of miR-21-5p, miR-30c-5p, and miR-205-5p in co-cultured cardiomyocytes and lung cancer cells, revealing altered miRNA patterns from vinorelbine and carboplatin treatment. Our findings underscore the intricate relationship between chemotherapy, miRNA regulation, and cardiotoxicity, highlighting the importance of cardiac health in lung cancer treatment decisions

Synthèse stéréosélective d'hétéroaryl alcools et alanines

This PhD thesis presents the stereoselecticve synthesis of several novel amino acids and secondary alcohols using biocatalysis. The work is divided in two main parts.The first part is dedicated to the stereoselective synthesis of novel heteroaryl alanines using two different biocatalysts with the same enantiopreference, the aminoacylase I and the baker's yeast (Saccharomyces cerevisiae). Using these two biocatalysts the L-alanines were obtained with a high enantiometric excess and yields.The second part is dedicated to the syntehsis of the txo enantiomers of the novel (hetero)aryl secondary alcohols using lipases as the biocatalysts. This part is divided in two sub-chapters, one for the stereoselective synthesis of (S)- and (R)-1-aryl-3-chloro propanols and the other for the streoselective synthesis of different (thiazole-2-yl)-methanols C-substituted and their acylated derivatives. These compounds were obtained by the stereoselective enzymatic acylation of the racemic alcohols and the enzymatic hydrolisis ot their acylatic derivatives.Cette thèse présente la synthèse stéréosélective de plusieurs nouveaux acides aminés et alcools secondaires en utilisant la biocatalyse. Le travail est divisé en deux parties principales. La première partie est consacrée à la synthèse stéréosélective des alanines hétéroaryles en utilisant deux différents biocatalyseurs avec le même énantiopréférence, l'aminocatalyse I et la levure de boulanger (Saccharomyces cerevisiae). A l'aide de ces deux biocatalyseurs, les L-alanines ont été obtenus avec des excès énantiomériques et rendements élevé. La deuxième partie est consacrée à la synthèse des deux énantiomètres des alcools secondaires (hétéro)aryles en utilisant les lipases comme biocatalyseurs. Cette partie est divisée en deux sous-chapitres, un pour la synthèse stéréosélective de différents (thiazole-2-yl) - méthanols C-substitués et leurs dérivés acylés. Ces composés ont été obtenus par l'acylation enzymatique stéréosélective des alcools racémiques et par l'hydrolise enzymatique de leurs dérivés acylés

Stereoselective synthesis of heteroaryl alcohols and alanines

Cette thèse présente la synthèse stéréosélective de plusieurs nouveaux acides aminés et alcools secondaires en utilisant la biocatalyse. Le travail est divisé en deux parties principales. La première partie est consacrée à la synthèse stéréosélective des alanines hétéroaryles en utilisant deux différents biocatalyseurs avec le même énantiopréférence, l'aminocatalyse I et la levure de boulanger (Saccharomyces cerevisiae). A l'aide de ces deux biocatalyseurs, les L-alanines ont été obtenus avec des excès énantiomériques et rendements élevé. La deuxième partie est consacrée à la synthèse des deux énantiomètres des alcools secondaires (hétéro)aryles en utilisant les lipases comme biocatalyseurs. Cette partie est divisée en deux sous-chapitres, un pour la synthèse stéréosélective de différents (thiazole-2-yl) - méthanols C-substitués et leurs dérivés acylés. Ces composés ont été obtenus par l'acylation enzymatique stéréosélective des alcools racémiques et par l'hydrolise enzymatique de leurs dérivés acylés.This PhD thesis presents the stereoselecticve synthesis of several novel amino acids and secondary alcohols using biocatalysis. The work is divided in two main parts.The first part is dedicated to the stereoselective synthesis of novel heteroaryl alanines using two different biocatalysts with the same enantiopreference, the aminoacylase I and the baker's yeast (Saccharomyces cerevisiae). Using these two biocatalysts the L-alanines were obtained with a high enantiometric excess and yields.The second part is dedicated to the syntehsis of the txo enantiomers of the novel (hetero)aryl secondary alcohols using lipases as the biocatalysts. This part is divided in two sub-chapters, one for the stereoselective synthesis of (S)- and (R)-1-aryl-3-chloro propanols and the other for the streoselective synthesis of different (thiazole-2-yl)-methanols C-substituted and their acylated derivatives. These compounds were obtained by the stereoselective enzymatic acylation of the racemic alcohols and the enzymatic hydrolisis ot their acylatic derivatives

Synthèse stéréosélective d'hétéroaryl alcools et alanines

This PhD thesis presents the stereoselecticve synthesis of several novel amino acids and secondary alcohols using biocatalysis. The work is divided in two main parts.The first part is dedicated to the stereoselective synthesis of novel heteroaryl alanines using two different biocatalysts with the same enantiopreference, the aminoacylase I and the baker's yeast (Saccharomyces cerevisiae). Using these two biocatalysts the L-alanines were obtained with a high enantiometric excess and yields.The second part is dedicated to the syntehsis of the txo enantiomers of the novel (hetero)aryl secondary alcohols using lipases as the biocatalysts. This part is divided in two sub-chapters, one for the stereoselective synthesis of (S)- and (R)-1-aryl-3-chloro propanols and the other for the streoselective synthesis of different (thiazole-2-yl)-methanols C-substituted and their acylated derivatives. These compounds were obtained by the stereoselective enzymatic acylation of the racemic alcohols and the enzymatic hydrolisis ot their acylatic derivatives.Cette thèse présente la synthèse stéréosélective de plusieurs nouveaux acides aminés et alcools secondaires en utilisant la biocatalyse. Le travail est divisé en deux parties principales. La première partie est consacrée à la synthèse stéréosélective des alanines hétéroaryles en utilisant deux différents biocatalyseurs avec le même énantiopréférence, l'aminocatalyse I et la levure de boulanger (Saccharomyces cerevisiae). A l'aide de ces deux biocatalyseurs, les L-alanines ont été obtenus avec des excès énantiomériques et rendements élevé. La deuxième partie est consacrée à la synthèse des deux énantiomètres des alcools secondaires (hétéro)aryles en utilisant les lipases comme biocatalyseurs. Cette partie est divisée en deux sous-chapitres, un pour la synthèse stéréosélective de différents (thiazole-2-yl) - méthanols C-substitués et leurs dérivés acylés. Ces composés ont été obtenus par l'acylation enzymatique stéréosélective des alcools racémiques et par l'hydrolise enzymatique de leurs dérivés acylés

Removal of Methyl Orange from Aqueous Solutions by Using Zn-Al Layered Double Hydroxide as Photocatalyst

The Zn-Al layered double hydroxide (LDH) was prepared using co-precipitation method at constant pH and characterized from structural point of view. Due to the high concentration of ZnO obtained after LDH calcinations, the material can be used as photocatalyst in removal of organic persistent compounds from water. The photocatalytic activity of the as-synthesized and calcined materials was evaluated for the degradation of Methyl Orange dye under UV irradiation. The influence of calcination temperature, solid: liquid ratio and initial dye concentration on photocatalytic activity of LDH was studied. The increase of calcination temperature and solid: liquid ratio and the decrease of initial dye concentration leads to increasing degradation efficiency

Next Generation Sequencing Technology in Lung Cancer Diagnosis

Lung cancer is still one of the most commonly diagnosed cancers, and one of the deadliest. The high death rate is mainly due to the late stage of diagnosis and low response rate to therapy. Previous and ongoing research studies have tried to discover new reliable and useful cbiomarkers for the diagnosis and prognosis of lung cancer. Next generation sequencing has become an essential tool in cancer diagnosis, prognosis, and evaluation of the treatment response. This article aims to review the leading research and clinical applications in lung cancer diagnosis using next generation sequencing. In this scope, we identified the most relevant articles that present the successful use of next generation sequencing in identifying biomarkers for early diagnosis correlated to lung cancer diagnosis and treatment. This technique can be used to evaluate a high number of biomarkers in a short period of time and from small biological samples, which makes NGS the preferred technique to develop clinical tests for personalized medicine using liquid biopsy, the new trend in oncology

Chemoenzymatic synthesis of highly enantiomerically enriched secondary alcohols with a thiazolic core

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