Chemical and Bioactive Properties of Red Rice with Potential Pharmaceutical Use.

Red rice has been proposed as a super-food. Accordingly, the nutritional properties (AOAC), as well as its chemical composition, including sugars (HPLC-RI), organic acids (UFLC-PDA), tocopherols (HPLD-FD), and phenolic compounds (LC-DAD-ESI/MSn), together with the main bioactive properties (antioxidant, cytotoxic, antiproliferative, and antibacterial activities), were evaluated to access its nutritional benefits and health improvement potential. The most abundant macronutrients found were carbohydrates (87.2 g/100 g dw), proceeded by proteins (9.1 g/100 g dw), fat (2.6 g/100 g dw), and ash (1.1 g/100 g dw). Sucrose and raffinose were the only detected sugars, with sucrose presenting the maximum concentration (0.74 g/100 g dw). MUFAs and PUFAs were the predominant fatty acids (40.7% and 31%, respectively). Among the two detected tocopherol isoforms, γ-tocopherol (0.67 mg/100 g dw) predominated over α-tocopherol. The phenolic compounds profile, majorly composed of flavan-3-ols, should be associated with the detected bioactivities, which may provide biological benefits to human health beyond the primary nutritional effect. Overall, the bioactive potential of red rice was comprehensively accessed.

Podophyllic Aldehyde, a Podophyllotoxin Derivate, Elicits Different Cell Cycle Profiles Depending on the Tumor Cell Line: A Systematic Proteomic Analysis.

When new antitumor therapy drugs are discovered, it is essential to address new target molecules from the point of view of chemical structure and to carry out efficient and systematic evaluation. In the case of natural products and derived compounds, it is of special importance to investigate chemomodulation to further explore antitumoral pharmacological activities. In this work, the compound podophyllic aldehyde, a cyclolignan derived from the chemomodulation of the natural product podophyllotoxin, has been evaluated for its viability, influence on the cell cycle, and effects on intracellular signaling. We used functional proteomics characterization for the evaluation. Compared with the FDA-approved drug etoposide (another podophyllotoxin derivative), we found interesting results regarding the cytotoxicity of podophyllic aldehyde. In addition, we were able to observe the effect of mitotic arrest in the treated cells. The use of podophyllic aldehyde resulted in increased cytotoxicity in solid tumor cell lines, compared to etoposide, and blocked the cycle more successfully than etoposide. High-throughput analysis of the deregulated proteins revealed a selective antimitotic mechanism of action of podophyllic aldehyde in the HT-29 cell line, in contrast with other solid and hematological tumor lines. Also, the apoptotic profile of podophyllic aldehyde was deciphered. The cell death mechanism is activated independently of the cell cycle profile. The results of these targeted analyses have also shown a significant response to the signaling of kinases, key proteins involved in signaling cascades for cell proliferation or metastasis. Thanks to this comprehensive analysis of podophyllic aldehyde, remarkable cytotoxic, antimitotic, and other antitumoral features have been discovered that will repurpose this compound for further chemical transformations and antitumoral analysis.

Unveiling the metabolites underlying the skin anti-ageing properties of Cytinus hypocistis (L.) L. through a biochemometric approach.

BACKGROUND: The genus Cytinus, recognised as one of the most enigmatic in the plant kingdom, has garnered attention for its bioactive potential, particularly its skin anti-ageing properties. Despite this recognition, much remains to be accomplished regarding deciphering and isolating its most active compounds. HYPOTHESIS: This study aimed to identify the compounds responsible for C. hypocistis skin anti-ageing potential. METHODS: Using multivariate analysis, a biochemometric approach was applied to identify the discriminant metabolites by integrating extracts' chemical profile (Liquid Chromatography-High-Resolution Mass Spectrometry, LCHRMS) and bioactive properties. The identified bioactive metabolite was structurally elucidated by 1D and 2D Nuclear Magnetic Resonance (NMR). RESULTS: Among the studied bioactivities, the anti-elastase results exhibited a significant variation among the samples from different years. After the biochemometric analysis, the compound 2,3:4,6-bis(hexahydroxydiphenoyl)glucose, with a molecular mass of 784.075 Da, was structurally elucidated as the discriminant feature responsible for the outstanding human neutrophil elastase inhibition. Remarkably, the subfraction containing this compound exhibited a tenfold improvement in neutrophil elastase inhibition efficacy compared to the crude extract; its effectiveness fell within the same range as SPCK, a potent irreversible neutrophil elastase inhibitor. Moreover, this subfraction displayed no cytotoxicity or phototoxicity and excellent efficacy for the tested anti-ageing properties. CONCLUSIONS: Hydrolysable tannins were confirmed as the metabolites behind C. hypocistis skin anti-ageing properties, effectively mitigating critical molecular mechanisms that influence the phenotypically distinct ageing clinical manifestations. Pedunculagin was particularly effective in inhibiting neutrophil elastase, considered one of the most destructive enzymes in skin ageing.

Generating Human Pancreatic Tissue Slices to Study Endocrine and Exocrine Pancreas Physiology.

It is crucial to study the human pancreas to understand the pathophysiological mechanisms associated with type 1 (T1D) and 2 diabetes (T2D) as well as the pancreas endocrine and exocrine physiology and interplay. Much has been learned from the study of isolated pancreatic islets, but this prevents examining their function and interactions in the context of the whole tissue. Pancreas slices provide a unique opportunity to explore the physiology of normal, inflamed, and structurally damaged islets within their native environment, in turn allowing the study of interactions between endocrine and exocrine compartments to better investigate the complex dynamics of pancreatic tissue. Thus, the adoption of the living pancreas slice platform represents a significant advancement in the field. This protocol describes how to generate living tissue slices from deceased organ donors by tissue embedding in agarose and vibratome slicing as well as their utilization to assess functional readouts such as dynamic secretion and live cell imaging.

Cytotoxic Cyclolignans Obtained by the Enlargement of the Cyclolignan Skeleton of Podophyllic Aldehyde, a Selective Podophyllotoxin-Derived Cyclolignan.

Podophyllotoxin, a cyclolignan natural product, has been the object of extensive chemomodulation to obtain better chemotherapeutic agents. Among the obtained podophyllotoxin derivatives, podophyllic aldehyde showed very interesting potency and selectivity against several tumoral cell lines, so it became our lead compound for further modifications, as described in this work, oriented toward the enlargement of the cyclolignan skeleton. Thus, modifications performed at the aldehyde function included nucleophilic addition reactions and the incorporation of the aldehyde carbon into several five-membered rings, such as thiazolidinones and benzo-fused azoles. The synthesized derivatives were evaluated against several types of cancer cells, and although some compounds were cytotoxic at the nanomolar range, most of them were less potent and less selective than the parent compound podophyllic aldehyde, with the most potent being those having the lactone ring of podophyllotoxin. In silico ADME evaluation predicted good druggability for most of them. The results indicate that the γ-lactone ring is important for potency, while the α,ß-unsaturated aldehyde is necessary to induce selectivity in these cyclolignans.

Aspectos médico legales en mastología. Demora en el diagnóstico de cáncer de mama como motivo de conflicto legal. / Medical legal aspects in mastology. Delay in the diagnosis of breast cancer as a reason for legal conflict.

Pocas situaciones generan mayor angustia en el profesional médico como la de recibir una demanda por mala praxis. Los reclamos medico legales en cáncer de mama están centrados, de acuerdo a la mayor parte de la bibliografía internacional, en el retraso en el diagnóstico de cáncer de mama, si bien existen reclamos legales en el ámbito del tratamiento, estos son menos frecuentes. En EEUU la primera causa de juicios por mala praxis son los daños obstétricos, y la segunda causa es el retraso en el diagnóstico de la patología oncológica, estando en primer lugar el cáncer de mama; el riesgo de reclamo médico legal se calcula en 1/1000 canceres de mama; no hay estadísticas fiables en nuestro país pero extrapolando estos resultados seria esperable unas 20 demandas anuales. El perfil de riesgo es una paciente joven, premenopausica, con una masa autopercibida que es subestimada en la consulta clínica y/o por los estudios por imágenes. Una buena relación médico-paciente y una correcta documentación de la historia clínica es la mejor prevención, trabajando en forma normatizada y de acuerdo a guías nacionales e internacionales. Fomentar el trabajo en equipo y la formación de Unidades de Mastología en las instituciones es una forma de trabajo multidisciplinario que resulta en beneficio tanto de la paciente como de los profesionales.

There are few situations can generate distress for medical professionals like receiving a malpractice lawsuit. Medico legal issues in breast cancer are focused, according to the most international bibliography, on the delay in diagnosis of breast cancer. Even though legal claims exist concerning about treatment, those are less frequent. In USA, obstetric damages are the first cause of malpractice lawsuit and the second one is the delay in diagnosis of oncological pathology being the breast cancer at the first place. The risk of legal medical claim is calculated at 1/1000 breast cancers. There are no reliable statistic in our country but extrapolating these results, it would be expected around 20 demands per year. The risk profile is a young premenopausal patient with a breast mass self-perceived which is underrated by the doctor or imaging studies. A good doctor patient relationship and an accurate report in medical records is the best prevention, working in a standarized way according to international and national guides. We must persuit to encourage teamwork and Mastology Units organisation over all institutions is a multidisciplinary way of working toreach the patients benefit as well as professionals.

Antiproliferative potential of solidagenone isolated of Solidago chilensis

ABSTRACT Plants are considered among the main sources of biologically active chemicals. The species Solidago chilensis Meyen, Asteraceae, is native to the southern parts of South America, where the aerial parts of the plant are commonly used for the treatment of inflammatory conditions. However, the effects of S. chilensis on human cancer cells remain to be elucidated. In this study, we evaluated the antiproliferative effects of the hydroalcoholic and dichloromethane extracts of S. chilensis, as well as their chemical constituents quercitrin and solidagenone against the five human tumor cell lines in vitro. The dichloromethane extract showed a promisor antiproliferative effects in vitro, especially against glioma cell line. Besides, the hydroalcoholic extract and quercitrin were inactive. The diterpene solidagenone showed highly potent antiproliferative effects against breast (MCF-7), kidney (786-0), and prostate cancer (PC-3) cells (total growth inhibition: TGI < 6.25 µg/ml). Solidagenone meets the theoretical physico-chemical criteria for bioavailability of drugs, according to the "Rule of Five" and, by theorical studies, the observed biological effects were probably related to the interaction of the molecule with nuclear receptors and as an enzymatic inhibitor. This study contributes to chemical study and to the identification of antiproliferative molecules in S. chilensis.

Evaluación preoperatoria del estado axilar con ecografía y punción con aguja fina (paaf ) en pacientes con cáncer de mama / Preoperative evaluation of axillary status with ultrasound and fine needle aspiration (FNA) in patients with breast cancer

La estatificación axilar es uno de los más importantes factores pronósticos en pacientes con cáncer de mama. La punción con aguja fina (PAAF) guiada por ecografía de los ganglios axilares es un método técnicamente factible y de baja morbilidad para la evaluación preoperatoria del compromiso axilar, en especial cuando hay sospecha clínica o ecográfica de compromiso a ese nivel. Este procedimiento aún no es parte de la rutina en la práctica general y sus indicaciones no se han establecido claramente. Objetivos: Analizar la utilidad de la punción con aguja fina (PAAF) guiada por ecografía de los ganglios linfáticos axilares en la evaluación preoperatoria de las pacientes con cáncer de mama y sospecha de compromiso axilar clínico o por imágenes; determinar la sensibilidad y especificidad del método;comparar los resultados con la bibliografía. Material y método: Se llevó a cabo un estudio observacional, prospectivo donde se evaluaron 23 pacientes con cáncer de mama a las cuales se les realizó PAAF axilar en el Servicio de Ginecología y el Servicio de Diagnóstico por Imágenes del Hospital Interzonal General de Agudos (HIGA) de Mar del Plata, en el períodonoviembre de 2013 a agosto de 2014. Resultados: La edad promedio de las pacientes fue de 49,4 años. El tamaño tumoral promedio por imágenes fue de 31 mm y por anatomía patológica de 32,5 mm. Se realizaron 25 punciones axilares (dos casos bilaterales) con 14 resultados positivos (56%), 9 negativos (36%) y 2 (8%) insatisfactorios. La sensibilidad del método fue del 82,3% con un 17,7% de falsos negativos; la especificidad fue del 100%, el VPP del 100% y el VPN del 66,6%. No hubo diferencia significativa en la relación del tamaño tumoral con el resultado de la PAAF...

iso-Kaurenoic acid from Wedelia paludosa D.C.

A recent reinvestigation of aerial parts of Wedelia paludosa D.C. is described and reports, for the first time, the isolation of iso-kaurenoic acid from this species.

Uma recente reinvestigação das partes aéreas de Wedelia paludosa D.C. é descrita e relata, pela primeira vez, o isolamento do ácido iso-caurenóico desta espécie.