Biological activity of the essential oil of Drimys winteri.

In the Chilean indigenous culture, the tree Drimys winteri (Winteraceae) Canelo is of great importance and is considered the sacred Mapuche tree. It has antibacterial and disinfectant properties and is used in the treatment of various diseases, such as fevers, ulcers, cancers, and respiratory tract problems. The essential oil obtained from D. winteri, DW_EO, is bioactive, possesses insecticidal and repellent properties against pests, and shows activity toward plant growth regulators. It also has a phytotoxic effect against the growth and germination of weeds. The essential oil obtained from the leaves and bark of Drimys winteri has demonstrated antifungal, immunomodulatory, anti-inflammatory, and anticancer properties in in vitro and in vivo studies. It also possesses antioxidant activity and antibacterial effects. The essential oil contains monoterpenes such as zafrol, pinenes, and linalool, among others, that contribute to its bioactivity. The DW_EO and bioactive compounds have great potential in various applications in medicine, industrial food, sanitizer, and other areas.

Primeras recomendaciones de consenso SLANH - COLABIOCLI / Primeiras Recomendações de Consenso SLANH - COLABIOCLI / (Sociedad Latinoamericana de Nefrología e Hipertensión - Confederación Latinoamericana de Bioquímica Clínica) / Informe de la tasa de filtración glomerular estimada junto a la determinación de la creatininemia en población adulta / First SLANH-COLABIOCLI Consensus Recommendations

Resumen La enfermedad renal crónica (ERC) es de alta prevalencia en América Latina y en todo el mundo. Se estima que entre 10 y 20% de la población adulta es portadora de ERC y su prevalencia va en aumento. La ERC progresa en forma silenciosa. Su diagnóstico temprano y oportuno permite iniciar un tratamiento efectivo, en la mayoría de los casos, para detener la enfermedad. Desde hace mucho tiempo, el análisis de la creatininemia es la principal prueba utilizada para valorar la función renal, pero su confiabilidad es limitada. De acuerdo con las recomendaciones de las GUIAS KDOQI del año 2002 la tasa de filtración glomerular estimada (TFGe) obtenida a través de fórmulas, se estableció como una de las herramientas principales para detectar la enfermedad renal de manera precoz, ya que alerta de forma precisa al médico y al equipo de salud sobre el nivel de función renal del paciente. La detección de una TFGe disminuida (menor de 60 mL/min/1,73 m2) es clínicamente relevante, ya que permite establecer el diagnóstico de enfermedad renal en adultos. En el año 2022, en una encuesta realizada por SLANH y COLABIOCLI dirigida a los laboratorios de análisis clínicos de América Latina (n: 237), el 49% de los mismos no informaban la TFGe rutinariamente. En base a esta realidad SLANH y COLABIOCLI elaboraron estas recomendaciones de consenso en referencia al uso de la TFGe.

Abstract Chronic kidney disease (CKD) has a high prevalence worldwide and in Latin America (10 to 20% of the adult population) and is increasing. CKD progresses silently. Opportune diagnosis and treatment are effective in most cases to improve outcomes. Serum creatinine was the main test to assess kidney function, but its reliability is limited. Through the KDOQI Guidelines 2002, the estimated glomerular filtration rate (eGFR) obtained from equations was established as one of the main tools for the early detection of kidney disease in clinical practice. The detection of a decreased eGFR (less than 60 mL/min/1.73 m2) is clinically relevant. This cut-off level establishes the diagnosis of kidney disease in adults. In 2022 SLANH and COLABIOCLI conducted a survey among the clinical laboratories from Latin America. The survey included 237 laboratories, 49% of which did not routinely report the eGFR. Based on this situation, SLANH and COLABIOCLI have elaborated the following consensus recommendations regarding the use of eGFR.

Resumo A doença renal crônica (DRC) é altamente prevalente na América Latina e em todo o mundo. Estima-se que entre 10 e 20% da população adulta seja portadora de DRC e sua prevalência esteja aumentando. A DRC progride silenciosamente. Seu diagnóstico precoce e oportuno permite iniciar um tratamento eficaz, na maioria dos casos, para estancar a doença. Faz muito tempo, a análise da creatinina tem sido o principal teste usado para avaliar a função renal mas sua confiabilidade é limitada. De acordo com as recomendações dos GUIAS KDOQI do ano de 2002, a estimativa da taxa de filtração glomerular (eGFR), obtida por meio de fórmulas, consolidou-se como uma das principais ferramentas para a detecção precoce da doença renal, visto que alerta com precisão ao médico e ao equipe de saúde sobre o nível de função renal do paciente. A detecção de uma eGFR diminuída (inferior a 60 mL/min/1,73 m2) é clinicamente relevante, pois permite estabelecer o diagnóstico de doença renal em adultos. No ano de 2022, em pesquisa realizada pela SLANH e COLABIOCLI dirigida a laboratórios de análises clínicas da América Latina (n: 237), 49% deles não relataram rotineiramente eGFR. Com base nessa realidade, SLANH e COLABIOCLI prepararam essas recomendações de consenso sobre o uso de eGFR.

Edible Oil Parameters during Deterioration Processes.

With the continuous increase in research on lipids, technologies and the development of chemical-analytical methods associated with the characterization and monitoring of different processes that involve modifications in edible fats are increasing. The beneficial effect of lipids, especially those essential for the health of the population, is widely known. However, degradation compounds are also produced that eventually have negative effects. In this dual context, the monitoring of the changes suffered by nutritional compounds can be obtained thanks to the development of technologies and analytical methods applied to the study of lipids. The modifications that lipids undergo can be followed by a wide variety of methods, ranging from the basic ones associated with simple chemical titrations to the more complex ones associated with sophisticated laboratory equipment. These determinations involve chemical and/or physical quantification of lipids to know an initial condition on the major and minor components. In addition to technologies that allow monitoring during more complex processes such as thermal deterioration, in multiple conditions depending on the objective of the study, this review could benefit a comprehensive understanding of lipid deterioration for future developments and research in the study of fats and oils for human consumption.

Theobroma cacao L. compounds: Theoretical study and molecular modeling as inhibitors of main SARS-CoV-2 protease.

Cocoa beans contain antioxidant molecules with the potential to inhibit type 2 coronavirus (SARS-CoV-2), which causes a severe acute respiratory syndrome (COVID-19). In particular, protease. Therefore, using in silico tests, 30 molecules obtained from cocoa were evaluated. Using molecular docking and quantum mechanics calculations, the chemical properties and binding efficiency of each ligand was evaluated, which allowed the selection of 5 compounds of this series. The ability of amentoflavone, isorhoifolin, nicotiflorin, naringin and rutin to bind to the main viral protease was studied by means of free energy calculations and structural analysis performed from molecular dynamics simulations of the enzyme/inhibitor complex. Isorhoifolin and rutin stand out, presenting a more negative binding ΔG than the reference inhibitor N-[(5-methylisoxazol-3-yl)carbonyl]alanyl-l-valyl-N~1~-((1R,2Z)-4-(benzyloxy)-4-oxo-1-{[(3R)-2-oxopyrrolidin-3-yl]methyl}but-2-enyl)-L-leucinamide (N3). These results are consistent with high affinities of these molecules for the major SARS-CoV-2. The results presented in this paper are a solid starting point for future in vitro and in vivo experiments aiming to validate these molecules and /or test similar substances as inhibitors of SARS-CoV-2 protease.

The Chemical Compositions of Essential Oils Derived from Cryptocarya alba and Laurelia sempervirens Possess Antioxidant, Antibacterial and Antitumoral Activity Potential.

Cryptocarya alba (Peumo; CA) and Laurelia sempervirens (Laurel; LS) are herbs native to the Chilean highlands and have historically been used for medicinal purposes by the Huilliches people. In this work, the essential oils were extracted using hydrodistillation in Clevenger apparatus and analyzed by GC-MS to determine their composition. The antioxidant capacity (AC) was evaluated in vitro. The cytotoxicity was determined using cell line cultures both non tumoral and tumoral. The toxicity was determined using the nematode Caenorhabditis elegans. The antimicrobial activity was evaluated against 52 bacteria using the agar disc diffusion method and the minimum inhibitory concentrations (MICs) were determined. The principal compounds found in C. alba essential oil (CA_EO) were α-terpineol (24.96%) and eucalyptol (21.63%) and were isazafrol (91.9%) in L. sempervirens essential oil (LS_EO). Both EOs showed antioxidant capacity in vitro. Both EO showed antibacterial activity against bacteria using. LS_EO showed more inhibitory effect on these cell lines respect to CA_EO. Both EOs showed toxicity against the nematode C.elegans at 3.12-50 mg/mL. The essential oils of CA and LS have an important bioactive potential in their antioxidant, antibacterial and cytotoxicity activity. Both essential oils could possibly be used in the field of natural medicine, natural food preservation, cosmetics, sanitation and plaguicides among others.

Modeling invasive lobular breast carcinoma by CRISPR/Cas9-mediated somatic genome editing of the mammary gland.

Large-scale sequencing studies are rapidly identifying putative oncogenic mutations in human tumors. However, discrimination between passenger and driver events in tumorigenesis remains challenging and requires in vivo validation studies in reliable animal models of human cancer. In this study, we describe a novel strategy for in vivo validation of candidate tumor suppressors implicated in invasive lobular breast carcinoma (ILC), which is hallmarked by loss of the cell-cell adhesion molecule E-cadherin. We describe an approach to model ILC by intraductal injection of lentiviral vectors encoding Cre recombinase, the CRISPR/Cas9 system, or both in female mice carrying conditional alleles of the Cdh1 gene, encoding for E-cadherin. Using this approach, we were able to target ILC-initiating cells and induce specific gene disruption of Pten by CRISPR/Cas9-mediated somatic gene editing. Whereas intraductal injection of Cas9-encoding lentiviruses induced Cas9-specific immune responses and development of tumors that did not resemble ILC, lentiviral delivery of a Pten targeting single-guide RNA (sgRNA) in mice with mammary gland-specific loss of E-cadherin and expression of Cas9 efficiently induced ILC development. This versatile platform can be used for rapid in vivo testing of putative tumor suppressor genes implicated in ILC, providing new opportunities for modeling invasive lobular breast carcinoma in mice.

Transfusion of packed red blood cells stored >14 days was associated with a higher risk of infection after hip revision arthroplasty.

PURPOSE: Transfusion of packed red blood cells (RBCs) stored for >14 days has been associated with a higher risk of infection but there is no data about the impact in revision hip arthroplasty. METHODS: We retrospectively reviewed 280 patients who underwent revision hip arthroplasty from January 2002 to May 2012. Relevant risk factors and prosthetic joint infection (PJI) rate after 100 days after surgery were collected. RESULTS: 10 patients out of 280 (3.6%) had a PJI within the first 100 days after revision surgery. The PJI rate in patients receiving an early transfusion (during surgery or within the first 12 hours) of packed RBCs with a length of storage >14 days was higher (8.0%) than the rate in nontransfused patients (1.8%) or those receiving an early transfusion of packed RBCs with a length of storage ≤14 days (2.6%, p = 0.05). A Cox regression model identified transfusion of packed RBCs stored >14 days as the only independent predictor of PJI (hazard ratio [HR] = 4.54; 95% confidence interval [CI], 1.13-18.15; p = 0.032). CONCLUSIONS: The only independent predictor of PJI was early transfusion of packed RBCs stored >14 days. Therefore, a potential way for reducing the PJI rate could be the selection of young packed RBCs.

Using the GEMM-ESC strategy to study gene function in mouse models.

Preclinical in vivo validation of target genes for therapeutic intervention requires careful selection and characterization of the most suitable animal model in order to assess the role of these genes in a particular process or disease. To this end, genetically engineered mouse models (GEMMs) are typically used. However, the appropriate engineering of these models is often cumbersome and time consuming. Recently, we and others described a modular approach for fast-track modification of existing GEMMs by re-derivation of embryonic stem cells (ESCs) that can be modified by recombinase-mediated transgene insertion and subsequently used for the production of chimeric mice. This 'GEMM-ESC strategy' allows for rapid in vivo analysis of gene function in the chimeras and their offspring. Moreover, this strategy is compatible with CRISPR/Cas9-mediated genome editing. This protocol describes when and how to use the GEMM-ESC strategy effectively, and it provides a detailed procedure for re-deriving and manipulating GEMM-ESCs under feeder- and serum-free conditions. This strategy produces transgenic mice with the desired complex genotype faster than traditional methods: generation of validated GEMM-ESC clones for controlled transgene integration takes 9-12 months, and recombinase-mediated transgene integration and chimeric cohort production takes 2-3 months. The protocol requires skills in embryology, stem cell biology and molecular biology, and it is ideally performed within, or in close collaboration with, a transgenic facility.

Hepatocyte growth factor-modulated rat Leydig cell functions.

Hepatocyte growth factor (HGF) regulates many cellular functions acting through c-Met, its specific tyrosine kinase receptor. We previously reported that in prepuberal rats HGF is secreted by the peritubular myoid cells during the entire postnatal testicular development and by the Sertoli cells only at puberty. We have also demonstrated that germ cells at different stages of development express c-Met and that HGF modulates germ cell proliferation and apoptosis. In the present article, we extend our study to the interstitial compartment of the testis and demonstrate that the c-Met protein is present on Leydig cells. The receptor is functionally active as demonstrated by the detected effects of HGF. We report in this article that HGF significantly increases the amount of testosterone secreted by the Leydig cells and decreases the number of Leydig cells undergoing apoptosis. The antiapoptotic effect of HGF is mediated by caspase-3 activity because the amount of the active fragment of the enzyme is decreased in Leydig cells cultured in the presence of HGF. However, treatment with the growth factor does not modify the expression levels of caspase-3 mRNA. These data indicate that HGF regulates the functional activities of Leydig cells. Interestingly, the steroidogenetic activity of the cells is increased by HGF in cultured explants of testicular tissues as well as the antiapoptotic effect of HGF. Therefore, our data indicate that HGF has a crucial role in the regulation of male fertility.