Modifications on the Tetrahydroquinoline Scaffold Targeting a Phenylalanine Cluster on GPER as Antiproliferative Compounds against Renal, Liver and Pancreatic Cancer Cells

The implementation of chemo- and bioinformatics tools is a crucial step in the design of structure-based drugs, enabling the identification of more specific and effective molecules against cancer without side effects. In this study, three new compounds were designed and synthesized with suitable absorption, distribution, metabolism, excretion and toxicity (ADME-tox) properties and high affinity for the G protein-coupled estrogen receptor (GPER) binding site by in silico methods, which correlated with the growth inhibitory activity tested in a cluster of cancer cell lines. Docking and molecular dynamics (MD) simulations accompanied by a molecular mechanics/generalized Born surface area (MMGBSA) approach yielded the binding modes and energetic features of the proposed compounds on GPER. These in silico studies showed that the compounds reached the GPER binding site, establishing interactions with a phenylalanine cluster (F206, F208 and F278) required for GPER molecular recognition of its agonist and antagonist ligands. Finally, a 3-(4,5-dimethylthiazol-2- yl)2,5-diphenyltetrazolium bromide (MTT) assay showed growth inhibitory activity of compounds 4, 5 and 7 in three different cancer cell lines—MIA Paca-2, RCC4-VA and Hep G2—at micromolar concentrations. These new molecules with specific chemical modifications of the GPER pharmacophore open up the possibility of generating new compounds capable of reaching the GPER binding site with potential growth inhibitory activities against nonconventional GPER cell models.CONACYT (Grants: CB-254600, APN-782 and SEP-CONACYT-ANUIES-ECOS Francia: 296636)Instituto Politécnico Nacional (Grant: Proyectos Insignia IPN-2015)COFAA-SIP/IP

Hydroxamic acid derivatives as HDAC1, HDAC6 and HDAC8 inhibitors with antiproliferative activity in cancer cell lines

Histone deacetylases (HDACs) belong to a family of enzymes that remove acetyl groups from the ɛ-amino of histone and nonhistone proteins. Additionally, HDACs participate in the genesis and development of cancer diseases as promising therapeutic targets to treat cancer. Therefore, in this work, we designed and evaluated a set of hydroxamic acid derivatives that contain a hydrophobic moiety as antiproliferative HDAC inhibitors. For the chemical structure design, in silico tools (molecular docking, molecular dynamic (MD) simulations, ADME/Tox properties were used to target Zn2+ atoms and HDAC hydrophobic cavities. The most promising compounds were assayed in diferent cancer cell lines, including hepatocellular carcinoma (HepG2), pancreatic cancer (MIA PaCa-2), breast cancer (MCF-7 and HCC1954), renal cancer (RCC4-VHL and RCC4-VA) and neuroblastoma (SH-SY5Y). Molecular docking and MD simulations coupled to the MMGBSA approach showed that the target compounds have afnity for HDAC1, HDAC6 and HDAC8. Of all the compounds evaluated, YSL-109 showed the best activity against hepatocellular carcinoma (HepG2 cell line, IC50=3.39µM), breast cancer (MCF-7 cell line, IC50=3.41µM; HCC1954 cell line, IC50=3.41µM) and neuroblastoma (SH-SY5Y cell line, IC50=6.42µM). In vitro inhibition assays of compound YSL-109 against the HDACs showed IC50 values of 259.439µM for HDAC1, 0.537nM for HDAC6 and 2.24µM for HDAC8.Consejo Nacional de Ciencia y Tecnologia (CONACyT) CB-254600 SEP-CONACYT-ANUIES-ECOS Francia: 296636Instituto Politecnico Nacional Proyectos Insignia IPN-201

Screening of antibacterial activity in marine green and brown macroalgae from the coast of Morocco

Antibacterial activity of methanolic extracts from 32 macroalgae (13 Chlorophyta and 19 Phaeophyta) from the Atlantic and Mediterranean coast of Morocco were evaluated for the production of antibacterial compounds against Escherichia coliATCC 25922, Staphylococcus aureus ATCC 25923, Enterococcus faecalis ATCC 29212, Klebsiella pnomeuniae ATCC 700603 and E. faecalis ATCC 29213. Our results indicate that these species of seaweed collected from the Atlantic and Mediterranean coast of Morocco present a significant capacity of antibacterial activities, which makes them interesting for screening for natural products.This work is partially supported by the Spanish Agency of International Cooperation and Development of the Foreign Ministry (AECID) (A/ 3952/05, A/ 5583/06)

Absorción de CO2 en columna de burbujeo por reacción con álcalis

El presente estudio analiza el proceso de captura de gases ácidos mediante absorción gas-líquido con reacción química, en disolución acuosa y medio básico. El medio básico procede de la disolución de diferentes álcalis. El dispositivo experimental utilizado para poner en contacto las distintas fases fue una columna de burbujeo. Se estudió la influencia de la concentración de los distintos solutosy el caudal de gas alimentado al equipo de contacto sobre el proceso global de captura

Analysis of Immunotherapy in hepatocellular carcinoma

One reason immunotherapy is important for Hepatocellular carcinoma, it’s because there are many immune cells in that organ. Because HCC is very aggressive, immunotherapy must be applied correctly. There are a lot of immunotherapies for all cancers, nevertheless, some has been tested for specific organs or tissues, and probably in the future, this organ-specific treatments can be applied in other tumor tissues.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech

Analysis of Immunotherapy in Lung cancer

There are many ways of immunotherapy for lung cancer, and that includes the use of drugs, molecular treatment, and even the combination with radiotherapy. But also, it’s important to investigate in the future the adverse effects of immunotherapy in Lung cancer to avoid breathing complications, and a way to prevent those effects.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech

Algunos aspectos epidemiológicos de otitis media aguda en menores de dos años

Se realizó un estudio descriptivo retrospectivo con el objetivo de identificar algunos aspectos epidemiológicos de la otitis media aguda en los 60 niños menores de dos años que presentaron episodios de esta enfermedad en los consultorios médicos de la familia del área de salud, del Policlínico Docente "Noelio Capote", municipio Jaruco, durante el período comprendido desde el 1ro de enero de 1998 hasta el 31 de diciembre de 1998. La enfermedad fue más frecuente en los niños menores de un año y dentro de ellos los menores de seis meses, sexo masculino, procedencia urbana y con antecedentes personales de cuadros respiratorios a repetición.Predominó en los antecedentes familiares los cuidados diarios en el hogar y el hábito de fumar en los convivientes, así como el uso de pacificador y el tiempo de lactancia materna menor de dos meses. Se sugiere realizar actividades de educación para la salud sobre los factores de riesgo de la otitis media aguda con la comunidad en general

Clinical metagenomic analysis and Cancer

After seven years of periodic controls by the SEIMC (Spanish Society of Infectious Diseases and Clinical Microbiology), it can be affirmed that the analysis is capable of detecting microorganisms in any type of sample (Blood, CSF, Saliva, BAL, Urine, Sputum, Faeces, Tissues, Prosthetic Material, Exudates, Swabs, Etc…), it requires a small amount of sample, it identifies more than 77,000 pathogens in a single test, simultaneously detects Archaea, G+ and G- Bacteria, Fungi, Viruses, Protists and parasites, it detects nonculturable pathogens and those that revert to false negatives, it is not affected by inhibition by antibiotics or other causes, resistance to antibiotics and antimycotics are detected, results are obtained in 24 hours, it is the most sensitive and reliable direct microbial identification technique and specific today. The analysis is 87% more sensitive than a culture, 99% reliable in gender determination, 91% reliable in sensitivity, increases the rate of accurate diagnosis of infections by more than 50%, as it is NGS sequencing it is more sensitive, specific and reliable than 16s and 18s sequencing. The test is highly useful for detecting microorganisms associated with cancer.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech

Pulsed magnetic feld increases the efect of ultraviolet C radiation and thermal shock in aged yeasts

The study of the efects of the magnetic feld (MF) on living matter continues to be a dilemma. Until now, the interaction mechanisms of MF with living matter that explain the observed phenomena are unknown. Despite the existing literature and the multiple efects described to date, there are few published articles that study the combined efect of MF with other physical agents during the cellular aging process. In this sense, the aim of this work is to study whether low frequency and intensity pulsed and sinusoidal MF exposure produce alterations in the cell killing efect of ultraviolet C (UVC) radiation and thermal shock during the chronological aging of S. cerevisiae. Yeast cells were exposed to 2.45 mT (50 Hz) sinusoidal MF and 1.5 mT (25 Hz) pulsed MF, during 40 days of aging, in combination with UVC radiation (50 J/m2 ) and/or thermal shock (52°C). Cell survival was evaluated by clonogenic assay. The exposure of yeast to pulsed MF produces an acceleration of aging, which is not observed in cells exposed to sinusoidal MF. The pulsed MF modifes the cellular response to damaging agents only in aged S. cerevisiae cells. In this sense, the pulsed MF applied increases the damage induced by UVC radiation and by thermal shock. In contrast, the sinusoidal MF used has no efect.Funding for open access publishing: Universidad de Málaga/CBUA. This study was supported by the “Plan Andaluz de Investi gación, Desarrollo e Innovación (PAIDI); Junta de Andalucía”, code CTS-181

Inappropriate prescribing to the oldest old patients admitted to hospital: prevalence, most frequently used medicines, and associated factors

Background: Scientific evidence on treatments of chronic diseases in patients 85 years old or older is very limited, as is available information on inappropriate prescription (IP) and its associated factors. The study aimed to describe medicine prescription, potentially inappropriate medicines (PIM) and potentially prescribing omissions (PPO) and their associated factors on this population. Methods: In the context of an observational, prospective and multicentric study carried out in elderly patients admitted to seven Spanish hospitals for a year, a sub-analysis of those aged 85 years and over was performed. To assess PIMs, the Beers and STOPP criteria were used, and to assess PPOs, the START and the ACOVE-3 criteria were used. To assess factors associated with IP, a multivariate logistic regression analysis was performed. Patients were selected randomly every week on consecutive days from the hospitalization lists. Results: A total of 336 patients were included in the sub-analysis with a median (Q1-Q3) age of 88 (8690) years. The median medicines taken during the month prior to admission was 10 (713). Forty-seven point two per cent of patients had at least one Beers-listed PIM, 63.3% at least one STOPP-listed PIM, 53.6% at least one START-listed PPO, and 59.4% at least one ACOVE-3-listed PPO. Use of benzodiazepines in patients who are prone to falls (18.3%) and omission of calcium and vitamin D supplements in patients with osteoporosis (13.3%) were the most common PIM and PPO, respectively. The main factor associated with the Beers-listed and the STOPP-listed PIM was consumption of 10 or more medicines (OR = 5.7, 95% CI 1.8-17.9 and OR = 13.4, 95% CI 4.0-44.0, respectively). The main factors associated with the START-listed PPO was a non-community dwelling origin (OR 2.3, 95% CI 1.0-5.0), and multimorbidity (OR1.8, 95% CI 1.0-3.1). Conclusions: Prescribed medicines and PIM and PPO prevalence were high among patients 85 years and over. Benzodiazepine use in those who are prone to falls and omission of calcium and vitamin D in those with osteoporosis were the most frequent PIM and PPO, respectively. Factors associated with PIM and PPO differed with polypharmacy being the most important factor associated with PIM