miRNAs as Interconnectors between Obesity and Cancer.

Obesity and cancer are a concern of global interest. It is proven that obesity may trigger the development or progression of some types of cancer; however, the connection by non-coding RNAs has not been totally explored. In the present review, we discuss miRNAs and lncRNAs dysregulation involved in obesity and some cancers, shedding light on how these conditions may exacerbate one another through the dysregulation of ncRNAs. lncRNAs have been reported as regulating microRNAs. An in silico investigation of lncRNA and miRNA interplay is presented. Our investigation revealed 44 upregulated and 49 downregulated lncRNAs in obesity and cancer, respectively. miR-375, miR-494-3p, miR-1908, and miR-196 were found interacting with 1, 4, 4 and 4 lncRNAs, respectively, which are involved in PPARγ cell signaling regulation. Additionally, miR-130 was found to be downregulated in obesity and reported as modulating 5 lncRNAs controlling PPARγ cell signaling. Similarly, miR-128-3p and miR-143 were found to be downregulated in obesity and cancer, interacting with 5 and 4 lncRNAs, respectively, associated with MAPK cell signaling modulation. The delicate balance between miRNA and lncRNA expression emerges as a critical determinant in the development of obesity-associated cancers, presenting these molecules as promising biomarkers. However, additional and deeper studies are needed to reach solid conclusions about obesity and cancer connection by ncRNAs.

Differential Effect of 4H-Benzo[d] [1, 3]oxazines on the Proliferation of Breast Cancer Cell Lines.

BACKGROUND: A family of 4H-benzo[d][1,3]oxazines were obtained from a group of N-(2-alkynyl)aryl benzamides precursors via gold(I) catalysed chemoselective 6-exo-dig C-O cyclization. METHOD: The precursors and oxazines obtained were studied in breast cancer cell lines MCF-7, CAMA-1, HCC1954 and SKBR-3 with differential biological activity showing various degrees of inhibition with a notable effect for those that had an aryl substituted at C-2 of the molecules. 4H-benzo[d][1,3]oxazines showed an IC50 rating from 0.30 to 157.4 µM in MCF-7, 0.16 to 139 in CAMA-1, 0.09 to 93.08 in SKBR-3, and 0.51 to 157.2 in HCC1954 cells. RESULTS: We observed that etoposide is similar to benzoxazines while taxol effect is more potent. Four cell lines responded to benzoxazines while SKBR-3 cell line responded to precursors and benzoxazines. Compounds 16, 24, 25 and 26 have the potent effect in cell proliferation inhibition in the 4 cell lines tested and correlated with oxidant activity suggesting a possible mechanism by ROS generation. CONCLUSION: These compounds represent possible drug candidates for the treatment of breast cancer. However, further trials are needed to elucidate its full effect on cellular and molecular features of cancer.

Knowledge, attitudes and perceptions of Latin American healthcare workers relating to antibiotic stewardship and antibiotic use: a cross-sectional multi-country study.

BACKGROUND: The burden of antimicrobial resistance (AMR) in Latin America is high. Little is known about healthcare workers' (HCWs) knowledge, attitudes, and perceptions of antimicrobial stewardship (AS), AMR, and antibiotic use (AU) in the region. METHODS: HCWs from 42 hospitals from 5 Latin American countries were invited to take an electronic, voluntary, anonymous survey regarding knowledge, attitudes, and perceptions of AS, AMR, and AU between March-April 2023. FINDINGS: Overall, 996 HCWs completed the survey (52% physicians, 32% nurses, 11% pharmacists, 3% microbiologists, and 2% "other"). More than 90% of respondents indicated optimizing AU was a priority at their healthcare facility (HCF), 69% stated the importance of AS was communicated at their HCF, and 23% were unfamiliar with the term "antibiotic stewardship". Most (> 95%) respondents acknowledged that appropriate AU can reduce AMR; however, few thought AU (< 30%) or AMR (< 50%) were a problem in their HCF. Lack of access to antibiogram and to locally endorsed guidelines was reported by 51% and 34% of HCWs, respectively. Among prescribers, 53% did not consider non-physicians' opinions to make antibiotic-related decisions, 22% reported not receiving education on how to select antibiotics based on culture results and 60% stated patients and families influence their antibiotic decisions. CONCLUSIONS: Although HCWs perceived improving AU as a priority, they did not perceive AU or AMR as a problem in their HCF. AS opportunities include improved access to guidelines, access to AMR/AU data, teamwork, and education on AS for HCWs and patients and families.

Targeting DNMT3A-mediated oxidative phosphorylation to overcome ibrutinib resistance in mantle cell lymphoma.

The use of Bruton tyrosine kinase (BTK) inhibitors such as ibrutinib achieves a remarkable clinical response in mantle cell lymphoma (MCL). Acquired drug resistance, however, is significant and affects long-term survival of MCL patients. Here, we demonstrate that DNA methyltransferase 3A (DNMT3A) is involved in ibrutinib resistance. We find that DNMT3A expression is upregulated upon ibrutinib treatment in ibrutinib-resistant MCL cells. Genetic and pharmacological analyses reveal that DNMT3A mediates ibrutinib resistance independent of its DNA-methylation function. Mechanistically, DNMT3A induces the expression of MYC target genes through interaction with the transcription factors MEF2B and MYC, thus mediating metabolic reprogramming to oxidative phosphorylation (OXPHOS). Targeting DNMT3A with low-dose decitabine inhibits the growth of ibrutinib-resistant lymphoma cells both in vitro and in a patient-derived xenograft mouse model. These findings suggest that targeting DNMT3A-mediated metabolic reprogramming to OXPHOS with decitabine provides a potential therapeutic strategy to overcome ibrutinib resistance in relapsed/refractory MCL.

Bioactive Compounds from Pigmented Corn (Zea mays L.) and Their Effect on Health.

Pigmented corn is a gramineae food of great biological, cultural and nutritional importance for many Latin American countries, with more than 250 breeds on the American continent. It confers a large number of health benefits due to its diverse and abundant bioactive compounds. In this narrative review we decided to organize the information on the nutrients, bioactive compounds and phytochemicals present in pigmented corn, as well as their effects on human health. Phenolic compounds and anthocyanins are some of the most studied and representative compounds in these grasses, with a wide range of health properties, mainly the reduction of pro-oxidant molecules. Carotenoids are a group of molecules belonging to the terpenic compounds, present in a large number of pigmented corn breeds, mainly the yellow ones, whose biological activity incorporates a wide spectrum. Bioactive peptides can be found in abundance in corn, having very diverse biological effects that include analgesic, opioid and antihypertensive activities. Other compounds with biological activity found in pigmented corn are resistant starches, some fatty acids, phytosterols, policosanols, phospholipids, ferulic acid and phlobaphenes, as well as a great variety of vitamins, elements and fibers. This review aims to disseminate and integrate the existing knowledge on compounds with biological activity in pigmented corn in order to promote their research, interest and use by scientists, nutrition professionals, physicians, industries and the general population.

Mechanistic insights into the antitumoral potential and in vivo antiproliferative efficacy of a silver-based core@shell nanosystem.

This study delves into the biomolecular mechanisms underlying the antitumoral efficacy of a hybrid nanosystem, comprised of a silver core@shell (Ag@MSNs) functionalized with transferrin (Tf). Employing a SILAC proteomics strategy, we identified over 150 de-regulated proteins following exposure to the nanosystem. These proteins play pivotal roles in diverse cellular processes, including mitochondrial fission, calcium homeostasis, endoplasmic reticulum (ER) stress, oxidative stress response, migration, invasion, protein synthesis, RNA maturation, chemoresistance, and cellular proliferation. Rigorous validation of key findings substantiates that the nanosystem elicits its antitumoral effects by activating mitochondrial fission, leading to disruptions in calcium homeostasis, as corroborated by RT-qPCR and flow cytometry analyses. Additionally, induction of ER stress was validated through western blotting of ER stress markers. The cytotoxic action of the nanosystem was further affirmed through the generation of cytosolic and mitochondrial reactive oxygen species (ROS). Finally, in vivo experiments using a chicken embryo model not only confirmed the antitumoral capacity of the nanosystem, but also demonstrated its efficacy in reducing cellular proliferation. These comprehensive findings endorse the potential of the designed Ag@MSNs-Tf nanosystem as a groundbreaking chemotherapeutic agent, shedding light on its multifaceted mechanisms and in vivo applicability.

Enhancing antioxidant properties of CeO2 nanoparticles with Nd3+ doping: structural, biological, and machine learning insights.

The antioxidant capabilities of nanoparticles are contingent upon various factors, including their shape, size, and chemical composition. Herein, novel Nd-doped CeO2 nanoparticles were synthesized and the neodymium content was varied to investigate the synergistic impact on the antioxidant properties of CeO2 nanoparticles. Incorporating Nd3+ induced changes in lattice parameters and significantly altered the morphology from nanoparticles to nanorods. The biological activity of Nd-doped CeO2 was examined against pathogenic bacterial strains, breast cancer cell lines, and antioxidant models. The antibacterial and anticancer activities of nanoparticles were not observed, which could be associated with the Ce3+/Ce4+ ratio. Notably, the incorporation of neodymium improved the antioxidant capacity of CeO2. Machine learning techniques were employed to forecast the antioxidant activity to enhance understanding and predictive capabilities. Among these models, the random forest model exhibited the highest accuracy at 96.35%, establishing it as a robust computational tool for elucidating the biological behavior of Nd-doped CeO2 nanoparticles. This study presents the first exploration of the influence of Nd3+ on the structural, optical, and biological attributes of CeO2, contributing valuable insights and extending the application of machine learning in predicting the therapeutic efficacy of inorganic nanomaterials.

Clinically Effective Molecules of Natural Origin for Obesity Prevention or Treatment.

The prevalence and incidence of obesity and the comorbidities linked to it are increasing worldwide. Current therapies for obesity and associated pathologies have proven to cause a broad number of adverse effects, and often, they are overpriced or not affordable for all patients. Among the alternatives currently available, natural bioactive compounds stand out. These are frequently contained in pharmaceutical presentations, nutraceutical products, supplements, or functional foods. The clinical evidence for these molecules is increasingly solid, among which epigallocatechin-3-gallate, ellagic acid, resveratrol, berberine, anthocyanins, probiotics, carotenoids, curcumin, silymarin, hydroxy citric acid, and α-lipoic acid stand out. The molecular mechanisms and signaling pathways of these molecules have been shown to interact with the endocrine, nervous, and gastroenteric systems. They can regulate the expression of multiple genes and proteins involved in starvation-satiety processes, activate the brown adipose tissue, decrease lipogenesis and inflammation, increase lipolysis, and improve insulin sensitivity. This review provides a comprehensive view of nature-based therapeutic options to address the increasing prevalence of obesity. It offers a valuable perspective for future research and subsequent clinical practice, addressing everything from the molecular, genetic, and physiological bases to the clinical study of bioactive compounds.

NCAPH drives breast cancer progression and identifies a gene signature that predicts luminal a tumour recurrence.

BACKGROUND: Luminal A tumours generally have a favourable prognosis but possess the highest 10-year recurrence risk among breast cancers. Additionally, a quarter of the recurrence cases occur within 5 years post-diagnosis. Identifying such patients is crucial as long-term relapsers could benefit from extended hormone therapy, while early relapsers might require more aggressive treatment. METHODS: We conducted a study to explore non-structural chromosome maintenance condensin I complex subunit H's (NCAPH) role in luminal A breast cancer pathogenesis, both in vitro and in vivo, aiming to identify an intratumoural gene expression signature, with a focus on elevated NCAPH levels, as a potential marker for unfavourable progression. Our analysis included transgenic mouse models overexpressing NCAPH and a genetically diverse mouse cohort generated by backcrossing. A least absolute shrinkage and selection operator (LASSO) multivariate regression analysis was performed on transcripts associated with elevated intratumoural NCAPH levels. RESULTS: We found that NCAPH contributes to adverse luminal A breast cancer progression. The intratumoural gene expression signature associated with elevated NCAPH levels emerged as a potential risk identifier. Transgenic mice overexpressing NCAPH developed breast tumours with extended latency, and in Mouse Mammary Tumor Virus (MMTV)-NCAPHErbB2 double-transgenic mice, luminal tumours showed increased aggressiveness. High intratumoural Ncaph levels correlated with worse breast cancer outcome and subpar chemotherapy response. A 10-gene risk score, termed Gene Signature for Luminal A 10 (GSLA10), was derived from the LASSO analysis, correlating with adverse luminal A breast cancer progression. CONCLUSIONS: The GSLA10 signature outperformed the Oncotype DX signature in discerning tumours with unfavourable outcomes, previously categorised as luminal A by Prediction Analysis of Microarray 50 (PAM50) across three independent human cohorts. This new signature holds promise for identifying luminal A tumour patients with adverse prognosis, aiding in the development of personalised treatment strategies to significantly improve patient outcomes.

Proof-of-Concept in Developing a 45% Drug Loaded Amorphous Nanoparticle Formulation.

Amorphous solid dispersion (ASD) is an enabling approach utilized to deliver poorly soluble compounds. ASDs can spontaneously generate drug-rich amorphous nanoparticles upon dissolution, which can act as a reservoir for maintaining supersaturation during oral absorption. But, conventional ASDs are often limited in drug loadings to < 20 %. For indications where the dose is high, this can translate into a significant pill burden. The aim of this research was to develop a high drug loading (DL) amorphous nanoparticle (ANP) formulation that can release the drug-rich nanoparticles into solution upon contact with aqueous environment. Nanoparticles were directly engineered using solvent/anti-solvent precipitation. The obtained nanoparticle suspension was then concentrated followed by solidification to a re-dispersible amorphous dosage form using spray drying or lyophilization. The impact of process variables was studied using dynamic light scattering (DLS), scanning electron microscopy (SEM), high performance liquid chromatography (HPLC), nuclear magnetic resonance (NMR) and differential scanning calorimetry (DSC). It was observed that spray drying led to a non-re-dispersible formulation. Sucrose and trehalose containing lyocakes resulted in re-dispersible formulations. The trehalose containing lyocakes, in a dog study, gave comparable performance to the reference tablet in the fasted state but lower area under the curve (AUC) in fed state.

POTEE promotes breast cancer cell malignancy by inducing invadopodia formation through the activation of SUMOylated Rac1.

The small GTPase Rac1 (Ras-related C3 botulinum toxin substrate 1) has been implicated in cancer progression and in the poor prognosis of various types of tumors. Rac1 SUMOylation occurs during epithelial-mesenchymal transition (EMT), and it is required for tumor cell migration and invasion. Here we identify POTEE (POTE Ankyrin domain family member E) as a novel Rac1-SUMO1 effector involved in breast cancer malignancy that controls invadopodium formation through the activation of Rac1-SUMO1. POTEE activates Rac1 in the invadopodium by recruiting TRIO-GEF (triple functional domain protein), and it induces tumor cell proliferation and metastasis in vitro and in vivo. We found that the co-localization of POTEE with Rac1 is correlated with more aggressive breast cancer subtypes. Given its role in tumor dissemination, the leading cause of cancer-related deaths, POTEE could represent a potential therapeutic target for these types of cancer.

Chemometric Evaluation of RI-Induced Phytochemicals in Phaseolus vulgaris Seeds Indicate an Improvement on Liver Enzymes in Obese Rats.

Liver enzymes alterations (activity or quantity increase) have been recognized as biomarkers of obesity-related abnormal liver function. The intake of healthy foods can improve the activity of enzymes like aspartate and alanine aminotransferases (AST, ALT), γ-glutaminyl transferase (GGT), and alkaline phosphatase (ALP). Beans have a high concentration of several phytochemicals; however, Restriction Irrigation (RI) during plant development amends their synthesis. Using chemometric tools, we evaluated the capacity of RI-induced phytochemicals to ameliorate the high activity of liver enzymes in obese rats. The rats were induced with a high-fat diet for 4 months, subsequently fed with 20% cooked beans from well-watered plants (100/100), or from plants subjected to RI at the vegetative or reproduction stage (50/100, 100/50), or during the whole cycle (50/50) for 3 months. A partial least square discriminant analysis indicated that mostly flavonols have a significant association with serum AST and ALT activity, while isoflavones lowered GGT and ALP. For AST and ALT activity in the liver, saponins remained significant for hepatocellular protection and flavonoids remained significant as hepatobiliary protectants by lowering GGT and ALP. A principal component analysis demonstrated that several flavonoids differentiated 100/50 treatment from the rest, while some saponins were correlated to 50/100 and 50/50 treatments. The intake of beans cultivated under RI improves obesity-impaired liver alterations.

[Depression in health personnel associated with exposure to COVID-19]. / Depresión en personal de salud asociado a la exposición de la COVID-19.

Background: There are many working factors to do with depression. Objective: To determine the association between the exposure to COVID-19 and depression in physicians and nurses from the four hospitals at "Centro Médico Nacional Siglo XXI" (CMN SXXI) took part in: Oncology, Specialties, Cardiology and Pediatrics. Material and Methods: A cross-sectional study of 856 participants took place in January 2022, excluding workers, such as physicians and nurses from the CMN SXXI, disabled workers, staff with a union agreement, support staff and/or staff with less than one year of work labour. Through a self-administered questionnaire, the degree of occupational exposure to patients care with COVID-19, a history of COVID-19 infection, and the patient's health quiz were asked (PHQ-9). The analysis included simple frequency measurements, odds ratio (OR), Chi squared and multiple logistics regression with p ≤ 0.05. Results: The prevalence of depression in the medical and nursing staff at CMN SXXI was 32.2% (moderate to severe degree); In the multiple regression, an association was identified with not identifying support by the Institute (OR: 1.60, CI95%: 1.08-2.39, p = 0.02), high occupational exposure (OR: 8.35, CI95%: 3.02-23.09, p ˂ 0.0001), and more than 5 working days a week serving the COVID-19 patients (OR: 2.51, CI95%: 1.35-4.49, p = 0.004) and as a protective factor the fact that they have never had the COVID-19 (OR: 0.61, CI95%: 0.43-0.86, p = 0.01). Conclusions: The prevalence of depression was higher than expected being associated with the degree of occupational exposure in the COVID-19 patients´ assistance.

Introducción: existen factores laborales que influyen en la presencia de la depresión. Objetivo: determinar la asociación entre la exposición a la COVID-19 y la depresión en médicos y enfermeras de los cuatro hospitales del Centro Médico Nacional Siglo XXI (CMN SXXI): Oncología, Especialidades, Cardiología y Pediatría. Material y métodos: se realizó un estudio transversal, en enero del 2022, con 870 participantes pertenecientes a la población de médicos y enfermeras que laboraban en el CMN SXXI, se excluyó a los trabajadores que se encontraban con incapacidad, al personal temporal y/o con menos de un año de antigüedad laboral. A través de un cuestionario autoaplicable se interrogó sobre el grado de exposición laboral a la atención de pacientes con COVID-19, antecedentes de infección por la COVID-19 y el cuestionario de salud del paciente (PHQ-9). El análisis incluyo medidas de frecuencia simple y razón de Momios (RM), Chi cuadrada y regresión logística múltiple con p ≤ 0.05. Resultados: la prevalencia de depresión en personal médico y de enfermería del CMN SXXI fue del 32.2% (grado moderado a severo). En la regresión múltiple se encontró asociación con no identificar apoyo por parte del Instituto (RM: 1.60, IC95%: 1.08-2.39, p = 0.02), alta exposición laboral (RM: 8.35, IC95%: 3.02-23.09, p ˂ 0.0001) y más de 5 días laborados a la semana atendiendo pacientes con la COVID-19 (RM: 2.51, IC95%: 1.35-4.49, p = 0.004) y como factor protector el que nunca hayan enfermado de la COVID-19 (RM: 0.61, IC95%: 0.43-0.86, p = 0.01). Conclusiones: la prevalencia de depresión fue mayor a la esperada y se asoció con el grado de exposición laboral en la atención de pacientes con la COVID-19.

[Procalcitonin as sepsis predictor in cardiovascular surgery with cardiopulmonary bypass]. / Procalcitonina como predictor de sepsis en cirugía cardiovascular con circulación extracorpórea.

Background: Cardiopulmonary bypass generates an exacerbated response that may lead to sepsis. Objective: To describe the association between procalcitonin levels and sepsis diagnosis in cardiovascular surgery subjects with cardiopulmonary bypass. Methods: A case-series study was conducted in 142 patients. Serum procalcitonin levels were measured at 24 hours and at 72 hours after surgery using a point of care testing based on quantitative immunochromatographic method. To assess association between procalcitonin levels and sepsis status, we calculated area under the curve (AUC) and sensitivity, specificity, and predictive values for the best cut-off point. Results: From 142 patients studied, 7 developed sepsis after surgery (4.9%). For 24-hours procalcitonin levels AUC was 0.921 and best cut-off point was 3.8 ng/mL (sensitivity 0.857 and specificity 0.904). In the case of 72-hours procalcitonin levels, we observed a value of 0.868 for AUC and best cut-off point was 8.4 ng/mL (sensitivity 0.86 and specificity 0.97). Conclusions: Procalcitonin levels at 24 and 72 hours after cardiovascular surgery with cardiopulmonary bypass are associated with sepsis presence at cut-off points of 3.8 and 8.4 ng/mL respectively.

Introducción: la circulación extracorpórea durante la cirugía cardiovascular genera una respuesta exacerbada que puede asociarse con sepsis. Objetivo: describir la asociación entre los niveles de procalcitonina y el diagnóstico de sepsis en sujetos de cirugía cardiovascular con circulación extracorpórea. Material y métodos: se realizó un estudio de serie de casos en 142 pacientes. Los niveles de procalcitonina fueron medidos a las 24 horas y a las 72 horas después de la cirugía. Para evaluar la asociación entre los niveles de procalcitonina y la identificación de sepsis, se calculó el área bajo la curva (AUC) y la sensibilidad y especificidad identificando el mejor punto de corte. Resultados: de un total de 142 pacientes estudiados, 7 desarrollaron sepsis (4.9%). En los niveles de procalcitonina en las 24 horas, el AUC fue de 0.921 y el mejor punto de corte fue 3.8 ng/mL (sensibilidad de 0.857 y especificidad de 0.904). En el caso de los niveles de procalcitonina a las 72 horas, observamos un AUC de 0.868 y el mejor punto de corte fue 8.4 ng/mL (sensibilidad de 0.86 y especificidad de 0.97). Conclusiones: los niveles de procalcitonina a las 24 y 72 horas de la cirugía cardiovascular con circulación extracorpórea se asociaron con la presencia de sepsis con los puntos de corte de 3.8 ng/mL y 8.4 ng/mL respectivamente.

Proliferation, Migration and Invasion of Breast Cancer Cell Lines Are Inhibited by 1,5-Disubstituted Tetrazol-1,2,3-triazole Hybrids through Interaction with p53.

The anticarcinogenic potential of a series of 1,5-disubstituted tetrazole-1,2,3-triazole hybrids (T-THs) was evaluated in the breast cancer (BC)-derived cell lines MCF-7 (ER+, PR+, and HER2-), CAMA-1 (ER+, PR+/-, and HER2-), SKBR-3 (ER+, PR+, and HER2+), and HCC1954 (ER+, PR+, and HER2+). The T-THs 7f, 7l, and 7g inhibited the proliferation of MCF-7 and CAMA-1, HCC1954, and SKBR-3 cells, respectively. The compounds with stronger effect in terms of migration and invasion inhibition were 7o, 7b, 7n, and 7k for the CAMA-1, MCF-7, HCC1954, and SKBR-3 cells respectively. Interestingly, these T-THs were the compounds with a fluorine present in their structures. To discover a possible target protein, a molecular docking analysis was performed for p53, p38, p58, and JNK1. The T-THs presented a higher affinity for p53, followed by JNK1, p58, and lastly p38. The best-predicted affinity for p53 showed interactions between the T-THs and both the DNA fragment and the protein. These results provide an opportunity for these compounds to be studied as potential drug candidates for breast cancer treatment.

In vitro study of miRNA-369-3p targeting TCF4 regulating the malignant biological behavior of colon cancer cells.

Background: Colorectal carcinoma (CRC) is a common malignant tumor of the digestive tract. It is characterized by a high degree of malignancy, early metastasis and poor prognosis. Studies have shown the effect of miR-369-3p on the biological function of a variety of tumors. However, the mechanism by which miR-369-3p and its potential target genes participate in the pathogenesis of CRC has not been elucidated. This study aims to study the relationship between miR-369-3p and transcription factor 4 (TCF4), to reveal the mechanism of the occurrence and development of CRC, and to provide a promising target for the treatment of CRC. Methods: Real-time quantitative polymerase chain reaction (RT-qPCR) was used to detect the miR-369-3p levels in CRC tissues and cells. miR-369-3p mimics and/or TCF4 overexpression vectors were transfected into SW480 cells. The expression of miR-369-3p and TCF4 mRNA was detected using RT-qPCR. Bioinformatics analysis predicted the binding site of miR-369-3p to the TCF4 3'UTR, and the targeting relationship was verified by a dual luciferase reporter gene assay. Cell proliferation and invasion were investigated by labeled immunofluorescence assay using BrdU antibody and Transwell assay. The oxidative stress ability of cells was determined by commercial kits. The levels of proteins related to cell proliferation and invasion were measured by western blotting. Results: The level of miR-369-3p was significantly down-regulated in CRC tissues and cell lines, especially in SW480 cells (P<0.05). The expression of TCF4 was negatively correlated with that of miR-369-3p. High levels of miR-369-3p targeting TCF4 suppressed cell proliferation and downregulated the protein expression of Ki67 and PCNA (P<0.05). Overexpressed miR-369-3p binding TCF4 inhibited cell invasion and decreased the protein levels of vascular endothelial growth factor (VEGF) and E-cadherin (P<0.05). Furthermore, upregulation of miR-369-3p increased the activity of superoxide dismutase (SOD) while decreasing the content of malondialdehyde (MDA) and activity of lactate dehydrogenase (LDH) by blocking the expression of TCF4 (P<0.05). Conclusions: MiR-369-3p inhibits the proliferation, invasion and oxidative stress of CRC cells by targeting TCF4, thus defining miR-369-3p as a potential target for the diagnosis and treatment of CRC.

NCAPH Drives Breast Cancer Progression and Identifies a Gene Signature that Predicts Luminal A Tumor Recurrence.

Despite their generally favorable prognosis, luminal A tumors paradoxically pose the highest ten-year recurrence risk among breast cancers. From those that relapse, a quarter of them do it within five years after diagnosis. Identifying such patients is crucial, as long-term relapsers could benefit from extended hormone therapy, whereas early relapsers may require aggressive treatment. In this study, we demonstrate that NCAPH plays a role in the pathogenesis of luminal A breast cancer, contributing to its adverse progression in vitro and in vivo. Furthermore, we reveal that a signature of intratumoral gene expression, associated with elevated levels of NCAPH, serves as a potential marker to identify patients facing unfavorable progression of luminal A breast cancer. Indeed, transgenic mice overexpressing NCAPH generated breast tumors with long latency, and in MMTV-NCAPH/ErbB2+ double-transgenic mice, the luminal tumors formed were more aggressive. In addition, high intratumoral levels of Ncaph were associated with worse breast cancer evolution and poor response to chemotherapy in a cohort of genetically heterogeneous transgenic mice generated by backcrossing. In this cohort of mice, we identified a series of transcripts associated with elevated intratumoral levels of NCAPH, which were linked to adverse progression of breast cancer in both mice and humans. Utilizing the Least Absolute Shrinkage and Selection Operator (LASSO) multivariate regression analysis on this series of transcripts, we derived a ten-gene risk score. This score is defined by a gene signature (termed Gene Signature for Luminal A 10 or GSLA10) that correlates with unfavorable progression of luminal A breast cancer. The GSLA10 signature surpassed the Oncotype DX signature in discerning tumors with unfavorable outcomes (previously categorized as Luminal A by PAM50) across three independent human cohorts. This GSLA10 signature aids in identifying patients with Luminal A tumors displaying adverse prognosis, who could potentially benefit from personalized treatment strategies.

Manilkara zapota "chicozapote" as a fruit source of health-beneficial bioactive compounds and its effects on chronic degenerative and infectious diseases, a review.

Manilkara zapota "chicozapote" is an autochthonous evergreen tree from the Southern regions of Mexico, Belize, and Guatemala. Currently, it is widely distributed and extensively grown in Mexico and Southeast Asia. Traditionally, different structures of the plant have been used for medical purposes; seeds have diuretic and purgative properties, aiding in digestive complications and eliminating bladder and kidney stones. Tree bark has antidiarrheal, antipyretic, antibiotic, and astringent properties. Fruits and leaves have been used to treat cold, cough, diarrhea, indigestion, fever, hemorrhages, wounds, and ulcers. Chicozapote fruit is yellow and brown, with an oval shape and rough peel, it is an excellent source of nutrients, such as sugars, proteins, amino acids, and minerals, and is rich in phytochemical components, such as flavonoids, phenolic acids, and tannins. These bioactive compounds exert several biological activities, i.e., as an antioxidant, antidiabetic, antimicrobial, anti-inflammatory, cytotoxic, and anti-arthritic agents, to name a few. These beneficial properties assist in preventing chronic and degenerative diseases, such as cancer, diabetes, neurological, infectious, and cardiovascular diseases. The use of chicozapote is still limited to its fresh form, and its non-edible structures produce a lot of waste. Therefore, an alternative valorizing and preserving strategy is to use the fruit as a raw source to design functional foods and pharmacological products. Here, the nutritional and phytochemical profiles and the current view regarding methodologies and conditions, for the extraction and characterization of its bioactive compounds, are described, and focus is placed on their multiple biological effects and specific functional mechanisms.

Synthesis of novel fluoro phenyl triazoles via click chemistry with or without microwave irradiation and their evaluation as anti-proliferative agents in SiHa cells.

AIMS: Perform the synthesis of novel fluoro phenyl triazoles via click chemistry with or without microwave irradiation and their evaluation as anti-proliferative agents in SiHa cells Background: Triazoles are heterocyclic compounds containing a five-member ring with two carbon and three nitrogen atoms. They are of great importance since many of them have shown to have biological activity as antifungal, antiviral, antibacterial, anti-HIV, anti-tuberculosis, vasodilator, and anticancer agents. OBJECTIVE: Synthesize novel fluoro phenyl triazoles via click chemistry and evaluate their anti-proliferative activity Method: First, several fluorophenyl azides were prepared. Reacting these aryl azides with phenylacetylene in the presence of Cu(I) catalyst, the corresponding fluoro phenyl triazoles were obtained by two methodologies, stirring at room temperature and under microwave irradiation at 40 ºC. In addition, their antiproliferative activity was evaluated in cervical cancer SiHa cells Result: Fluoro phenyl triazoles were obtained within minutes by means of microwave irradiation. The compound 3f, containing two fluorine atoms next to the carbon connected to the triazole ring, was the most potent among the fluoro phenyl triazoles tested in this study. Interestingly, the addition of a fluorine atom to the phenyl triazole structure in a specific site increases its antiproliferative effect as compared to parent phenyl triazole 3a without a fluorine atom. CONCLUSION: Several fluoro phenyl triazoles were obtained by reacting fluoro phenyl azides with phenylacetylene in the presence of copper sulphate, sodium ascorbate and phenanthroline. Preparation of these triazoles with MW irradiation represents a better methodology since they are obtained within minutes and higher yields of cleaner compounds are obtained. In terms of biological studies, the proximity between fluorine atom and triazole ring increases its biological activity.

Single cell metabolic imaging of tumor and immune cells in vivo in melanoma bearing mice.

Introduction: Metabolic reprogramming of cancer and immune cells occurs during tumorigenesis and has a significant impact on cancer progression. Unfortunately, current techniques to measure tumor and immune cell metabolism require sample destruction and/or cell isolations that remove the spatial context. Two-photon fluorescence lifetime imaging microscopy (FLIM) of the autofluorescent metabolic coenzymes nicotinamide adenine dinucleotide (phosphate) (NAD(P)H) and flavin adenine dinucleotide (FAD) provides in vivo images of cell metabolism at a single cell level. Methods: Here, we report an immunocompetent mCherry reporter mouse model for immune cells that express CD4 either during differentiation or CD4 and/or CD8 in their mature state and perform in vivo imaging of immune and cancer cells within a syngeneic B78 melanoma model. We also report an algorithm for single cell segmentation of mCherry-expressing immune cells within in vivo images. Results: We found that immune cells within B78 tumors exhibited decreased FAD mean lifetime and an increased proportion of bound FAD compared to immune cells within spleens. Tumor infiltrating immune cell size also increased compared to immune cells from spleens. These changes are consistent with a shift towards increased activation and proliferation in tumor infiltrating immune cells compared to immune cells from spleens. Tumor infiltrating immune cells exhibited increased FAD mean lifetime and increased protein-bound FAD lifetime compared to B78 tumor cells within the same tumor. Single cell metabolic heterogeneity was observed in both immune and tumor cells in vivo. Discussion: This approach can be used to monitor single cell metabolic heterogeneity in tumor cells and immune cells to study promising treatments for cancer in the native in vivo context.