Identification of novel biomarkers in the early diagnosis of malignant melanoma by untargeted liquid chromatography coupled to high-resolution mass spectrometry-based metabolomics: a pilot study.

BACKGROUND: Malignant melanoma (MM) is a highly aggressive form of skin cancer whose incidence continues to rise worldwide. If diagnosed at an early stage, it has an excellent prognosis, but mortality increases significantly at advanced stages after distant spread. Unfortunately, early detection of aggressive melanoma remains a challenge. OBJECTIVES: To identify novel blood-circulating biomarkers that may be useful in the diagnosis of MM to guide patient counselling and appropriate disease management. METHODS: In this study, 105 serum samples from 26 healthy patients and 79 with MM were analysed using an untargeted approach by liquid chromatography coupled to high-resolution mass spectrometry (LC-HRMS) to compare the metabolomic profiles of both conditions. Resulting data were subjected to both univariate and multivariate statistical analysis to select robust biomarkers. The classification model obtained from this analysis was further validated with an independent cohort of 12 patients with stage I MM. RESULTS: We successfully identified several lipidic metabolites differentially expressed in patients with stage I MM vs. healthy controls. Three of these metabolites were used to develop a classification model, which exhibited exceptional precision (0.92) and accuracy (0.94) when validated on an independent sample. CONCLUSIONS: These results demonstrate that metabolomics using LC-HRMS is a powerful tool to identify and quantify metabolites in bodily fluids that could serve as potential early diagnostic markers for MM.

Melanoma is a type of skin cancer that can be deadly if it is not detected at an early stage. Unfortunately, the early detection of melanoma is challenging. Our team has developed a model that could be used to predict whether a person has stage I malignant melanoma based on blood serum analysis. The model was trained on data from a group of people with melanoma and it was found to be accurate in predicting melanoma at an early stage. This means that the model could be used to identify people who have skin cancer before it progresses and becomes more complicated to treat. Although the researchers recommend that further studies are conducted to validate the model in a larger population of people, this research could help with the early diagnosis of melanoma and work toward improving survival rates.

Assessment of Untargeted Metabolomics by Hydrophilic Interaction Liquid Chromatography-Mass Spectrometry to Define Breast Cancer Liquid Biopsy-Based Biomarkers in Plasma Samples.

An early diagnosis of cancer is fundamental not only in regard to reducing its mortality rate but also in terms of counteracting the progression of the tumor in the initial stages. Breast cancer (BC) is the most common tumor pathology in women and the second deathliest cancer worldwide, although its survival rate is increasing thanks to improvements in screening programs. However, the most common techniques to detect a breast tumor tend to be time-consuming, unspecific or invasive. Herein, the use of untargeted hydrophilic interaction liquid chromatography-mass spectrometry analysis appears as an analytical technique with potential use for the early detection of biomarkers in liquid biopsies from BC patients. In this research, plasma samples from 134 BC patients were compared with 136 from healthy controls (HC), and multivariate statistical analyses showed a clear separation between four BC phenotypes (LA, LB, HER2, and TN) and the HC group. As a result, we identified two candidate biomarkers that discriminated between the groups under study with a VIP > 1 and an AUC of 0.958. Thus, targeting the specific aberrant metabolic pathways in future studies may allow for better molecular stratification or early detection of the disease.

Integration of network-based approaches for assessing variations in metabolic profiles of alkalized and non-alkalized commercial cocoa powders.

Cocoa can undergo an alkalization process to enhance its color and solubility. It reduces astringency and alters its composition, particularly in the phenolic compound content, which is related to cocoa health benefits. This study aimed to investigate the impact of alkalization on the composition of seven commercial cocoa powders. A liquid chromatography-based metabolomic approach was employed to assess the metabolic differences between alkalized and non-alkalized cocoa powders. Supervised orthogonal partial least squares discriminant analysis (OPLS-DA) was used to identify the most discriminating variables between groups. A feature-based molecular network (FBMN) was used to explore the chemical space. Three hundred forty-seven metabolites were obtained as the most discriminant, among which 60 were tentatively annotated. Phenolic compounds, lysophosphatidylethanolamines, amino acids, and their derivatives were significantly reduced in alkalized cocoas. In contrast, fatty acids and their derivatives significantly increased with alkalization. Despite the variability among commercial cocoas, chemometrics allowed the elucidation of alterations induced specifically by alkalization in their composition.

Evaluation of pro-regenerative and anti-inflammatory effects of isolecanoric acid in the muscle: Potential treatment of Duchenne Muscular Dystrophy.

Duchenne muscular dystrophy (DMD) is a devastating degenerative disease of skeletal muscles caused by loss of dystrophin, a key protein that maintains muscle integrity, which leads to progressive muscle degeneration aggravated by chronic inflammation, muscle stem cells' (MuSCs) reduced regenerative capacity and replacement of muscle with fibroadipose tissue. Previous research has shown that pharmacological GSK-3ß inhibition favors myogenic differentiation and plays an important role in modulating inflammatory processes. Isolecanoric acid (ILA) is a natural product isolated from a fungal culture displaying GSK-3ß inhibitory properties. The present study aimed to investigate the proregenerative and anti-inflammatory properties of this natural compound in the DMD context. Our results showed that ILA markedly promotes myogenic differentiation of myoblasts by increasing ß-Catenin signaling and boosting the myogenic potential of mouse and human stem cells. One important finding was that the GSK-3ß/ß-Catenin pathway is altered in dystrophic mice muscle and ILA enhances the myofiber formation of dystrophic MuSCs. Treatment with this natural compound improves muscle regeneration of dystrophic mice by, in turn, improving functional performance. Moreover, ILA ameliorates the inflammatory response in both muscle explants and the macrophages isolated from dystrophic mice to, thus, mitigate fibrosis after muscle damage. Overall, we show that ILA modulates both inflammation and muscle regeneration to, thus, contribute to improve the dystrophic phenotype.

Onychocolone A produced by the fungus Onychocola sp. targets cancer stem cells and stops pancreatic cancer progression by inhibiting MEK2-dependent cell signaling.

Pancreatic cancer (PC) shows a high fatality rate that can only be faced with a combination of surgery and chemotherapy or palliative treatment in the case of advanced patients. Besides, PC tumors are enriched with subpopulations of cancer stem cells (CSCs) that are resistant to the existing chemotherapeutic agents, which raises an important need for the identification of new drugs. To fill this gap, we have tested the anti-tumoral activity of microbial extracts, which chemical diversity offers a broad spectrum of potential new bioactive compounds. Extracts derived from the fungus Onychocola sp. CF-107644 were assayed via high throughput screening followed by bioassay-guided fractionation and resulted in the identification and isolation of six benzophenone derivatives with antitumoral activity: onychocolones A-F (#1-6). The structures of the compounds were established by spectroscopic methods, including ESI-TOF MS, 1D and 2D NMR analyses and X-ray diffraction. Compounds #1-4 significantly inhibited the growth of the pancreas tumoral cell lines, with low-micromolar Median Effective Doses (ED50s). Compound #1 (onychocolone A) was prioritized for further profiling due to its pro-apoptotic effect, which was further validated on 3D spheroids and pancreatic CSCs. Protein expression assays showed that the effect was mechanistically linked to the inhibition of MEK onco-signaling pathway. The efficacy of onychocolone A was also demonstrated in vivo by the reduction of tumor growth in a pancreatic xenograft mouse model generated by CSCs. Altogether, the data support that onychocolone A is a promising new small molecule for hit-to-lead development of a new treatment for PC.

Enfrentamiento a brotes de enfermedades infecciosas en la atención primaria de salud / Tackling outbreaks of infectious diseases in primary health care

Introducción: en la actualidad las enfermedades infecciosas siguen siendo un motivo de preocupación. A pesar de los adelantos en los conocimientos médicos y el desarrollo de la atención primaria, es frecuente la ocurrencia de casos de enfermedades transmisibles. Objetivos: evaluar el nivel de conocimientos sobre enfrentamiento a brotes epidémicos en profesionales de la atención primaria de salud de la provincia La Habana, e implementar y evaluar el impacto de una estrategia de intervención utilizada con vistas a elevar los conocimientos adquiridos. Métodos: estudio cuasi experimental. El universo lo constituyeron 25 profesionales de la atención primaria de salud que laboraban en centros o unidades municipales de higiene y epidemiología de los municipios del oeste de la antigua provincia La Habana. En una primera etapa, se aplicó un cuestionario confeccionado y validado por expertos del tema, posteriormente se impartió un curso sobre enfrentamiento a brotes de enfermedades infecciosas, finalmente se evaluó el impacto de la estrategia a través del nivel de conocimientos adquirido por los profesionales. Resultados: antes de la intervención, el 52,0 por ciento de los profesionales fueron evaluados de no satisfactorios en la calificación general del examen. Después de la intervención, el 88,0 por ciento de los galenos tuvieron resultados satisfactorios, observándose un aumento general de 83,33 por ciento de respuestas satisfactorias. Al emplear la prueba de Mc Nemar de comparación de proporciones, se encontró significación estadística de forma general al obtenerse valores de p<0,05. Conclusiones: el nivel de conocimientos sobre enfrentamiento a brotes de enfermedades infecciosas en la atención primaria en salud fue no satisfactorio en la mayoría de los encuestados antes de la intervención. La estrategia de capacitación empleada resultó ser eficaz en lograr conocimientos más sólidos sobre el tema en los profesionales(AU)

Introduction: Currently, infectious diseases remain a concern. Despite advances in medical knowledge and the development of primary care, the occurrence of cases of communicable diseases is frequent. Objectives: Assess the level of knowledge on confronting outbreaks by primary health care professionals in the province of Havana, and implement and evaluate the impact of an intervention strategy used in order to raise the knowledge acquired. Method: A quasi-experimental study. Twenty-five primary care professionals made up the universe. They worked in health centers or municipal epidemiology units of the west municipalities of the former Havana province. At a first stage, a questionnaire made and tested by experts was applied, then a course of confrontation to outbreaks of infectious diseases was given, finally the impact of the strategy was evaluated through the level of knowledge acquired by professionals. Results: Before intervention, 52.0 percent of the professionals were evaluated unsatisfactory in overall test score. After the intervention, 88.0 percent of physicians had satisfactory results, showing an overall increase of 83.33 percent for satisfactory answers. By using McNemar test to compare proportions, statistical significance was found generally to the obtained values of p <0.05. Conclusions: The level of knowledge on tackling outbreaks of infectious diseases in primary health care was unsatisfactory in most of the respondents before the intervention. The training strategy used was effective in getting professionals to have sounder knowledge(AU)

Clasificación de los productos cárnicos / Classification of meat products

Se revisa brevemente la bibliografía sobre la clasificación de los productos cárnicos y se propone un agrupamiento primario basado en que los productos se sometan o no a la acción del calor. Dentro de estos 2 amplios grupos se subdividen los productos atendiendo a variantes del proceso o a una característica principal de su tecnología. Esta clasificación abarca todos los productos cárnicos cubanos así como otros importados