ABSTRACT
Background: In Mexico and the world, breast cancer is the cancer type with the highest incidence and mortality for women. Its incidence has increased due to a higher life expectancy and a higher exposure to risk factors. Screening is done by mammography using the BIRADS (Breast Imaging Reporting and Data System) system, the standard for mammography screening report which classifies lesions assigning recommendations for patient follow-up. The system goes from 0 (not conclusive) to 6 (demonstrated malignancy), being of interest for this study the BIRADS 0 category. Objective: To describe patients classified as BIRADS 0 by mammography and their reclassification in a first-level hospital during 2021. Material and methods: Retrospective, descriptive, cross-sectional, observational study. Women over 40 years with a BIRADS 0 result were studied. The following databases were used: Institutional Cancer Registry, Family Medicine Information System, Electronic Clinical File, and the mammography and patient list from preventive medicine. Results: Reclassification by ultrasound (US) was achieved in 100% of patients, in all of the BIRADS US categories. In 3.8% of BIRADS 0 patients, ductal adenocarcinoma was found and confirmed by histological testing. Conclusion: All of the reassessed lesions with US were adequately reclassified.
Introducción: en México y el mundo, el cáncer de mama causa la mayor mortalidad por cáncer en mujeres. Su incidencia ha incrementado por una mayor esperanza de vida y exposición a factores de riesgo. El tamizaje de esta enfermedad se hace mediante mastografía, y para la estratificación de las lesiones se utiliza el sistema BIRADS (Breast Imaging Reporting and Data System), que estandariza el informe, categoriza las lesiones según el grado de sospecha y asigna recomendaciones a seguir. Dicho sistema va desde 0 (no concluyente) hasta 6 (lesión con malignidad demostrada) y es de interés para este estudio la categoría 0. Objetivo: describir la reclasificación de pacientes con reporte BIRADS 0 por mastografía durante 2021 en una unidad de primer nivel de atención. Material y métodos: estudio retrospectivo, descriptivo, transversal, observacional. Se estudiaron mujeres mayores de 40 años con resultado BIRADS 0. Se utilizaron las siguientes bases de datos: Registro Institucional de Cáncer, Sistema de Información de Medicina Familiar, Expediente Clínico Electrónico y lista nominal de mastografías y censo de pacientes sospechosos de medicina preventiva. Resultados: la reclasificación con ultrasonido (US) se logró en el 100% de pacientes, en todas las categorías de BIRADS US. En el 3.8% se confirmó carcinoma ductal por histología en las pacientes inicialmente categorizadas como BIRADS 0. Conclusiones: la totalidad de lesiones reevaluadas con US fueron reclasificadas satisfactoriamente.
Subject(s)
Breast Neoplasms , Mammography , Humans , Cross-Sectional Studies , Female , Retrospective Studies , Breast Neoplasms/diagnostic imaging , Breast Neoplasms/diagnosis , Breast Neoplasms/classification , Mammography/standards , Middle Aged , Adult , Aged , Mexico , Ultrasonography, Mammary , Aged, 80 and over , Early Detection of Cancer/methods , Early Detection of Cancer/standardsABSTRACT
Parasites have been associated with possible anticancer activity, including Trypanosoma cruzi, which has been linked to inhibiting the growth of solid tumors. To better understand this antitumor effect, we investigated the association of anti-T. cruzi antibodies with B cells of the acute lymphoblastic leukemia (ALL) SUPB15 cell line. The antibodies were generated in rabbits. IgGs were purified by affinity chromatography. Two procedures (flow cytometry (CF) and Western blot(WB)) were employed to recognize anti-T. cruzi antibodies on SUPB15 cells. We also used CF to determine whether the anti-T. cruzi antibodies could suppress SUPB15 cells. The anti-T. cruzi antibodies recognized 35.5% of the surface antigens of SUPB15. The complement-dependent cytotoxicity (CDC) results demonstrate the cross-suppression of anti-T. cruzi antibodies on up to 8.4% of SUPB15 cells. For the WB analysis, a band at 100 kDa with high intensity was sequenced using mass spectrometry, identifying the protein as nucleolin. This protein may play a role in the antitumor effect on T. cruzi. The anti-T. cruzi antibodies represent promising polyclonal antibodies that have the effect of tumor-suppressive cross-linking on cancer cells, which should be further investigated.
Subject(s)
Antibodies, Protozoan , Precursor Cell Lymphoblastic Leukemia-Lymphoma , Trypanosoma cruzi , Trypanosoma cruzi/immunology , Precursor Cell Lymphoblastic Leukemia-Lymphoma/immunology , Humans , Cell Line, Tumor , Animals , Rabbits , Antibodies, Protozoan/immunology , RNA-Binding Proteins/immunology , RNA-Binding Proteins/metabolism , Nucleolin , Phosphoproteins/immunology , Phosphoproteins/metabolismABSTRACT
Background: Arterial hypertension is highly prevalent in Mexico; nevertheless, there are limited insights regarding its management during the COVID-19 pandemic. Here, we estimate the prevalence of clinical and treatment profiles of arterial hypertension and explore associated factors for undiagnosed and uncontrolled hypertension using a cross-sectional survey endorsed by the Collaborative Group on Arterial Hypertension from the Mexican Institute of Social Security. Methods: Our survey was conducted from May to November 2021 using the May-Measurement Month 2021 protocols of the International Society of Hypertension. Arterial hypertension (defined as: blood pressure [BP] ≥140/90 mmHg, previous diagnosis, or taking antihypertensives) and its clinical and treatment profiles were classified according to the World Hypertension League Expert Committee. Mixed-effects logistic regression models were used to explore associated factors for undiagnosed and uncontrolled hypertension. Results: Among 77,145 screened participants (women: 62.4%; median age: 46 [IQR: 32-59] years), the prevalence of arterial hypertension was 35.7% (95% CI: 35.3-36.0, n = 27,540). Among participants with arterial hypertension, 30.9% (95% CI: 30.4-31.5, n = 8,533) were undiagnosed, 6.6% (95% CI: 6.3%-6.9%, n = 1,806) were diagnosed but untreated, 43.4% (95% CI: 42.9-44.0, n = 11,965) had uncontrolled hypertension, and only 19% (95% CI: 18.6%-19.5%, n = 5,236) achieved hypertension control (BP < 130/80 mmHg). Explored associated factors for undiagnosed and uncontrolled hypertension include being men, living in the central and southern regions, lower educational attainments, higher use of pharmacological agents, and previous COVID-19 infection. Conclusion: Our findings suggest that adverse arterial hypertension profiles, mainly undiagnosed and uncontrolled hypertension, were highly prevalent during the context of the COVID-19 pandemic in Mexico.
Subject(s)
Antihypertensive Agents , COVID-19 , Hypertension , Humans , Mexico/epidemiology , Cross-Sectional Studies , Hypertension/epidemiology , Female , COVID-19/epidemiology , Male , Middle Aged , Adult , Prevalence , Antihypertensive Agents/therapeutic use , SARS-CoV-2 , Pandemics , Surveys and QuestionnairesABSTRACT
Chagas disease, caused by the protozoan Trypanosoma cruzi, remains a major public health challenge affecting millions in Latin America and worldwide. Although significant progress has been made in vector control, no vaccine exists to prevent infection or mitigate disease pathogenesis. We developed a rationally designed chimeric protein vaccine, N-Tc52/TSkb20, incorporating immunodominant epitopes from two T. cruzi antigens, the amino-terminal portion of Tc52 and the TSkb20 epitope derived from trans-sialidase. The objectives of this study were to construct and characterize the antigen and evaluate its protective potential in an immunoprophylactic murine model of T. cruzi infection. The N-Tc52/TSkb20 protein was recombinantly expressed in E. coli and its identity was confirmed using mass spectrometry and Western blotting. Immunization with the chimeric protein significantly controlled parasitemia and reduced the heart, colon, and skeletal muscle parasite burdens compared to non-vaccinated mice. Protection was superior to vaccination with the individual parental antigen components. Mechanistically, the vaccine induced potent CD8+ T-cell and IFNγ responses against the incorporated epitopes and a protective IgG antibody profile. A relatively low IL-10 response favored early parasite control. These results validate the promising multi-epitope approach and support the continued development of this type of rational vaccine design strategy against Chagas disease.
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Progesterone is an endogenous hormone, produced by the adrenal cortex, the gonads and in women, its source is the corpus luteum. Progesterone is produced in the late phase of the menstrual cycle, when implantation of the zygote does not occur, the corpus luteum involutes and the release of progesterone is suppressed, thus initiating menstruation. Progestogen Hypersensitivity were initially identified as hormone allergy and were related to endogenous reactions to hormones and alteration of ovarian function. Skin manifestations such as dermatitis or urticaria were initially reported and described as progesterone autoimmune dermatitis, although the immune-mediated mechanism was not clear. Currently there is no standardization for in vivo or in vitro tests for Progestogen Hypersensitivity diagnosis. In this review, we will address the different diagnostic methods of this disease.
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Stanhopea tigrina Bateman ex Lindl. (Orchidaceae) is an orchid endemic to Mexico, known as "Calavera" or "calaverita", in the Huasteca Potosina (central region of Mexico). This plant species is used for the folk treatment of mental disorders and urological kidney disorders, according to the ethnomedicinal information obtained in this study. Ethanolic extracts of leaves (HE) and pseudobulb (PE) were obtained by microwave-assisted extraction (MAE). Gas Chromatography coupled with Mass Spectrometry (GC-MS) was used to carry out the chemical characterization of HE and PE. The pharmacological effects (antioxidant, diuretic, anxiolytic, locomotor, hypnotic, and sedative) of HE and PE were evaluated. The possible mechanism of action of the anxiolytic-like activity induced by HE was assessed using inhibitors of the GABAergic, adrenergic, and serotonergic systems. The possible mechanism of the diuretic action of HE was assessed using prostaglandin inhibitory antagonists and nitric oxide synthase (NOS) blockers. HE at 50 and 100 mg/kg exerted anxiolytic-like activity without inducing hypnosis or sedation. Flumazenil, prazosin, and ketanserin inhibited the anxiolytic-like activity shown by HE, which suggests the participation of GABA, α1-adrenergic receptors, and 5-HT2 receptors, respectively. The diuretic effect was reversed by the non-selective NOS inhibitor L-NAME, which caused the reduction in nitric oxide (NO). These results demonstrate that the ethanolic extract of S. tigrina leaves exhibited anxiolytic-like activity and diuretic effects without inducing hypnosis or sedation. This work validates the medicinal uses of this orchid species.
ABSTRACT
There is scarce evidence on sociodemographic and lifestyle characteristics that may explain adherence to different dietary patterns (DPs) during pregnancy. Our aims were to identify dietary patterns in a sample of pregnant Mexican women and to describe their association with selected sociodemographic and lifestyle characteristics. This is a secondary cross-sectional analysis of 252 mothers of children that participated as controls in a hospital-based case-control study of childhood leukemia. We obtained parents' information about selected sociodemographic characteristics, as well as alcohol and tobacco consumption. We also obtained dietary information during pregnancy. We identified DPs using cluster and factor analyses and we estimated their association with characteristics of interest. We identified two DPs using cluster analysis, which we called "Prudent" and "Non healthy", as well as three DPs through factor analysis, namely "Prudent", "Processed foods and fish", and "Chicken and vegetables". Characteristics associated with greater adherence to "Prudent" patterns were maternal education, older paternal age, not smoking, and being a government employee and/or uncovered population. Likewise, the "Processed foods and fish" pattern was associated with greater maternal and paternal education, as well as those with less household overcrowding. We did not identify sociodemographic variables related to the "Chicken and Vegetables" pattern. Our results may be useful to identify target populations that may benefit from interventions aimed to improve individual dietary decisions during pregnancy.
Subject(s)
Diet , Life Style , Humans , Female , Mexico , Pregnancy , Adult , Cross-Sectional Studies , Diet/statistics & numerical data , Socioeconomic Factors , Feeding Behavior , Sociodemographic Factors , Case-Control Studies , Young Adult , Maternal Nutritional Physiological Phenomena , Dietary PatternsABSTRACT
The beneficial effects of increasing histamine levels on memory have acquired special interest due to their applicability to psychiatric conditions that cause memory impairments. In addition, by employing drug repurposing approaches, it was demonstrated that dihydroergotamine (DHE), an FDA drug approved to treat migraines, inhibits Histamine N Methyl Transferase (HNMT), the enzyme responsible for the inactivation of histamine in the brain. For this reason, in the present work, the effect of DHE on histamine levels in the hippocampus and its effects on memory was evaluated, employing the scopolamine-induced amnesia model, the Novel Object Recognition (NOR) paradigm, and the Morris Water Maze (MWM). Furthermore, the role of histamine 1 receptor (H1R) and histamine 2 receptor (H2R) antagonists in the improvement in memory produced by DHE in the scopolamine-induced amnesia model was evaluated. Results showed that the rats that received DHE (10 mg/kg, i.p.) showed increased histamine levels in the hippocampus after 1 h of administration but not after 5 h. In behavioral assays, it was shown that DHE (1 mg/kg, i.p.) administered 20 min before the training reversed the memory impairment produced by the administration of scopolamine (2 mg/kg, i.p.) immediately after the training in the NOR paradigm and MWM. Additionally, the effects in memory produced by DHE were blocked by pre-treatment with pyrilamine (20 mg/kg, i.p.) administered 30 min before the training in the NOR paradigm and MWM. These findings allow us to demonstrate that DHE improves memory in a scopolamine-induced amnesia model through increasing histamine levels at the hippocampus due to its activity as an HNMT inhibitor.
Subject(s)
Dihydroergotamine , Scopolamine , Animals , Rats , Histamine , Amnesia/chemically induced , Amnesia/drug therapy , Brain , Memory Disorders/chemically induced , Memory Disorders/drug therapy , Histamine H2 AntagonistsABSTRACT
Background: Obesity is characterized as a low-grade chronic inflammatory state, marked by elevated inflammatory biomarkers. Breast milk (BM) is rich in nutritional elements, vitamins, minerals, immunological factors, and bioactive components. These bioactive components, capable of influencing biological processes, may vary in concentration based on maternal body composition. Research Aim/Question(s): This study aimed to explore the association between pro-inflammatory cytokine levels (interleukin-1 beta [IL-1ß], interleukin-6 [IL-6], and tumor necrosis factor-alpha [TNF-α]) in human colostrum and maternal body composition, as analyzed through bioelectrical impedance vector analysis (BIVA). Method: In this cross-sectional study, 117 healthy postpartum participants were included, with each group (normal weight, overweight, and obese) comprising 39 individuals, as classified by BIVA. Colostrum samples were collected within the first 24 hours postpartum. Results: IL-1ß levels did not significantly differ across the groups, with concentrations of 69.5 ± 103 pg/mL in normal-weight, 79.7 ± 97.9 pg/mL in overweight, and 68.7 ± 108 pg/mL in obese women. IL-6 levels were significantly higher in the overweight group (55 ± 72.4 pg/mL) than in the normal-weight (48.1 ± 74.1 pg/mL) and obese groups (28.9 ± 36.2 pg/mL) (p = 0.02). Similarly, TNF-α levels were higher in the overweight group, with concentrations of 58.7 ± 74.9 pg/mL, than in the normal-weight group, with concentrations of 38.6 ± 95.4 pg/mL, and 52.6 ± 115 pg/mL in obese women (p = 0.02). Conclusion: This study shows that IL-6 and TNF-α concentrations were statistically higher in the colostrum of overweight women, suggesting that maternal body composition may influence the inflammatory profile of BM.
Subject(s)
Body Composition , Colostrum , Interleukin-1beta , Interleukin-6 , Obesity , Postpartum Period , Tumor Necrosis Factor-alpha , Humans , Female , Colostrum/chemistry , Adult , Cross-Sectional Studies , Tumor Necrosis Factor-alpha/analysis , Tumor Necrosis Factor-alpha/metabolism , Interleukin-6/metabolism , Interleukin-6/analysis , Interleukin-1beta/analysis , Interleukin-1beta/metabolism , Obesity/metabolism , Overweight/metabolism , Pregnancy , Milk, Human/chemistry , Biomarkers/analysis , Young AdultABSTRACT
Rheumatoid arthritis (RA) and osteoarthritis (OA) are the most common arthritic diseases. Medical ozone has demonstrated its effectiveness in combination therapy with methotrexate or non-steroidal anti-inflammatory drugs for RA and OA, respectively. Although RA and OA have been compared from different points of view, few studies have considered their redox status in spite of the oxidative processes that are involved in both diseases. The aim of this study was to compare RA with OA, evaluating their redox status and the effects of ozone on their clinical response to combined therapy with ozone. The redox status of 80 patients was determined: antioxidant defenses, injury markers, two subjective variables (pain and disability), and levels of antibodies against cyclic citrullinated peptides were evaluated. Oxidative stress and clinical response to combined therapy with ozone was higher than in the case of RA. After medical ozone treatment, there was an increase in antioxidant defense and a decrease in injury markers as well as pain, disability, and autoantibody concentrations. Redox biomarkers were able to differentiate between both arthritic diseases and combined therapy with ozone (methotrexate + ozone), showing a therapeutic selectivity for RA in comparison with OA.
ABSTRACT
Poly-ADP-Ribose Polymerase (PARP-1) is an overexpressed enzyme in several carcinomas; consequently, the design of PARP-1 inhibitors has acquired special attention. Hence, in the present study, three compounds (8-10) were produced through a Michael addition protocol, using phenylmethanethiol, 5-fluoro-2-mercaptobenzyl alcohol, and 4-mercaptophenylacetic acid, respectively, as nucleophiles and perezone as the substrate, expecting them to be convenient candidates that inhibit PARP-1. It is convenient to note that in the first stage of the whole study, the molecular dynamics (MD) simulations and the quantum chemistry studies of four secondary metabolites, i.e., perezone (1), perezone angelate (2), hydroxyperezone (3), and hydroxyperezone monoangelate (4), were performed, to investigate their interactions in the active site of PARP-1. Complementarily, a docking study of a set of eleven sulfur derivatives of perezone (5-15) was projected to explore novel compounds, with remarkable affinity to PARP-1. The molecules 8-10 provided the most adequate results; therefore, they were evaluated in vitro to determine their activity towards PARP-1, with 9 having the best IC50 (0.317 µM) value. Additionally, theoretical calculations were carried out using the density functional theory (DFT) with the hybrid method B3LYP with a set of base functions 6-311++G(d,p), and the reactivity properties were compared between the natural derivatives of perezone and the three synthesized compounds, and the obtained results exhibited that 9 has the best properties to bind with PARP-1. Finally, it is important to mention that 9 displays significant inhibitory activity against MDA-MB-231 and MCF-7 cells, i.e., 145.01 and 83.17 µM, respectively.
Subject(s)
Cyclohexenes , Neoplasms , Poly(ADP-ribose) Polymerase Inhibitors , Sesquiterpenes , Humans , Poly(ADP-ribose) Polymerase Inhibitors/pharmacology , MCF-7 Cells , Molecular Dynamics Simulation , Neoplasms/drug therapyABSTRACT
The present study highlighted the repositioning of the drug dapsone (DDS) for cancer therapy. Due to its mechanism of action, DDS has a dual effect as an antibiotic and as an anti-inflammatory/immunomodulator; however, at high doses, it has important adverse effects. The derivative DDS-13 [N,N'-(sulfonyl bis (4,1-phenylene)) dioctanamide] was synthesized through an N-acylation reaction to compare it with DDS. Its cytotoxic effects in cancer cells (DU145 and HeLa) and non-cancer cells (HDFa) were observed at concentrations ranging 0.01-100 µM and its physicochemical/pharmacokinetic properties were analyzed using the SwissADME tool. The objectives of the present study were to evaluate the anticancer activity of both DDS and DDS-13 and to identify the physicochemical and pharmacokinetic properties of DDS-13. The results showed that DDS-13 presented a cytotoxic effect in the DU145 cell line (IC50=19.06 µM), while DDS showed a cytotoxic effect on both the DU145 (IC50=11.11 µM) and HeLa (IC50=13.07 µM) cell lines. DDS-13 appears to be a good cytotoxic candidate for the treatment of prostate cancer, while DDS appears to be a good candidate for both cervical and prostate cancer. Neither candidate showed a cytotoxic effect in non-cancerous cells. The different pharmacokinetic properties of DDS-13 make it a new candidate for evaluation in preclinical models for the treatment of cancer.
ABSTRACT
Autonomic innervation is important to regulate homeostasis in every organ of the body. The sympathetic nervous system controls several organs associated with metabolism and reproduction, including adipose tissue, the liver, and the ovaries. The sympathetic nervous system is controlled within the central nervous system by neurons located in the hypothalamus, which in turn are regulated by hormones like leptin. Leptin action in the hypothalamus leads to increased sympathetic activity in the adipose tissue. In this short report, we propose that leptin action in the brain also controls the sympathetic innervation of other organs like the liver and the ovary. We performed two experiments: We performed an intracerebroventricular (ICV) injection of leptin and measured norepinephrine levels in several organs, and we used a validated model of overnutrition and obesity to evaluate whether an increase in leptin levels coexists with high levels of norepinephrine in the liver and ovaries. Norepinephrine was measured by ELISA in adipose tissue and by HPLC-EC in other tissues. Leptin was measured by ELISA. We found that the ICV injection of leptin increases norepinephrine levels in several organs, including the liver and ovaries. Also, we found that diet-induced obesity leads to an increase in leptin levels while inducing an increase in norepinephrine levels in the liver and ovaries. Finally, since hyperactivity of the sympathetic nervous system is observed both in non-alcoholic fatty liver disease and polycystic ovary syndrome, we think that an increase in norepinephrine levels induced by hyperleptinemia could be involved in the pathogenesis of both diseases.
Subject(s)
Leptin , Norepinephrine , Female , Adipose Tissue/metabolism , Diet , Leptin/metabolism , Norepinephrine/metabolism , Obesity/metabolism , Sympathetic Nervous System , Animals , RatsABSTRACT
Introducción: durante diciembre de 2019 se identificó en Wuhan, China, un nuevo coronavirus, denominado SARS-CoV-2 por el Comité Internacional de Taxonomía de Virus. Después de haber presentado esta enfermedad se han encontrado secuelas como ansiedad y depresión. Objetivo: determinar el nivel de ansiedad y depresión en los pacientes post-COVID-19 en primer nivel de atención. Material y métodos: estudio observacional, descriptivo, transversal, unicéntrico, homodémico, prospectivo, prolectivo. Se realizó en una Unidad de Primer Nivel de Atención del Instituto Mexicano del Seguro Social, en el periodo de enero de 2021 a enero de 2022. Se aplicó la Escala de Hamilton para la Ansiedad y el Inventario de Beck para Depresión. Se realizó un análisis estadístico en el programa SPSS 25, los datos se expresaron como media ± desviación estándar o mediana, según la distribución. Las variables cualitativas se expresaron en frecuencias y porcentajes. Resultados: el promedio de edad fue de 27 años; con predominio del sexo femenino (62.4%), presentaron depresión moderada 6%, depresión grave 1.5%, ansiedad leve 20.9% y ansiedad moderada o grave 9.8%. Conclusión: existe una asociación entre el nivel de depresión y ansiedad en los pacientes post-COVID-19, con una p significativa (AU)
Introduction: during December 2019, a new coronavirus, named SARSCoV-2, by the International Committee on Taxonomy of Viruses, was identified in Wuhan, China. After presenting with this disease, sequelae such as anxiety and depression have been found. Objective: determine the level of anxiety and depression in post-COVID-19 patients of the Family Medicine Unit No. 34. Material and methods: observational, descriptive, cross-sectional, unicentric, homodemic, prospective, prolective study. It was conducted in a first level unit of the Mexican Institute of Social Security, in the period from January 2021 to January 2022. The Hamilton Anxiety Scale and the Beck Depression Inventory were applied. Statistical analysis was performed in the SPSS 25 program, data were expressed as mean ± standard deviation or median, according to the distribution. Qualitative variables were expressed as frequencies and percentages. Results: the mean age was 27 years; with a predominance of females (62.4%), 6% presented moderate depression, 1.5% severe depression, 20.9% mild anxiety and 9.8% moderate or severe anxiety. Conclusions: there is an association between the level of depression and anxiety in post-COVID-19 patients, with a significant p (AU)
Subject(s)
Humans , Male , Female , Adult , Middle Aged , Anxiety Disorders/etiology , Primary Health Care/methods , Depression/etiology , Post-Acute COVID-19 Syndrome/complications , Epidemiology, Descriptive , Cross-Sectional Studies , Prospective Studies , Data Interpretation, Statistical , Academies and Institutes , Mexico/epidemiologyABSTRACT
Pre-eclampsia (PE) is a disorder characterized by hypertension in the second trimester of pregnancy that results from abnormal placentation affecting fetal development and maternal health. Previous studies have shown the role of serotonin (5-HT) that leads to poor placental perfusion, where S/S and S/L polymorphisms promote the solute carrier family 6 member 4 (SLC6A4) gene associated with the risk of developing changes in the microvasculature of the placenta. This study looked at the association between the gene variant 5-HTTLPR (serotonin-transporter-linked promoter region) of the SLC6A4 gene and the occurrence of PE. A total of 200 women were included: 100 cases (pregnant with PE) and 100 controls (pregnant without complications). Genotyping of the 5-HTTLPR variant was performed using polymerase chain reaction (PCR). Associations between the presence of the genetic variant of interest and PE and other clinical features were evaluated statistically. The frequencies of S/S, S/L, and L/L genotypes were 32%, 53%, and 15% for the cases and 55%, 25%, and 20% in the control group. Compared to the controls, the genotype frequencies S/S vs. S/L + L/L (recessive model) in the cases group were different (p = 0.002). The S/S genotype decreased the probability of PE (OR = 0.39, 95% IC: 0.22-0.69, p = 0.002) and PE with severity criteria (OR = 0.39, 95% IC: 0.17-0.91, p = 0.045). The 5-HTTLPR gene variant of the SLC6A4 gene modifies the risk of PE development among the studied population.
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Background: Childhood cancer is the leading cause of disease-related mortality among children aged 5-14 years in Mexico, with acute leukemia being the most common cancer among infants. Examining the overall dietary patterns allows for a comprehensive assessment of food and nutrient consumption, providing a more predictive measure of disease risk than individual foods or nutrients. This study aims to evaluate the association between maternal dietary patterns during pregnancy and the risk of acute leukemia in Mexican infants. Methods: A hospital-based case-control study was conducted, comparing 109 confirmed acute leukemia cases with 152 age-matched controls. All participants (≤24 months) were identified at hospitals in Mexico City between 2010 and 2019. Data on a posteriori dietary patterns and other relevant variables were collected through structured interviews and dietary questionnaires. Multivariate logistic regression was employed to estimate the association between maternal dietary patterns during pregnancy and the risk of acute leukemia in infants. Results: The "Balanced & Vegetable-Rich" pattern, characterized by a balanced consumption of various food groups and higher vegetable intake, exhibited a negative association with acute leukemia when compared to the "High Dairy & Cereals" Pattern (adjusted odds ratio [OR] = 0.51; 95% confidence interval [CI]: 0.29, 0.90). We observed that mothers who gave birth to girls and adhered to a healthy dietary pattern during pregnancy exhibited significantly lower odds of their children developing AL compared to those who gave birth to boys [OR = 0.32 (95% CI 0.11, 0.97)]. Our results underscore the significance of maternal nutrition as a modifiable factor in disease prevention and the importance of prenatal health education.
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Enolase proteins play a significant role as moonlighting proteins. In their role as surface-associated enolase, they have multiple functions as they interact with extracellular matrix proteins. Type I and III collagens are the major constituents of this extracellular matrix, and collagen is one of the targets of interaction with the enolase of many pathogens, thereby helping the colonization process and promoting the subsequent invasion of the host. This work aimed to determine the participation of non-typeable H. influenzae enolase as a collagen-binding protein. In this study, through the use of in vitro tests it was demonstrated that recombinant enolase of non-typeable H. influenzae (rNTHiENO) strongly binds to type I collagen. Using molecular docking, the residues that could take part in the interaction of non-typeable H. influenzae enolase-type I collagen (NTHiENO-Cln I) and non-typeable H. influenzae enolase-type III collagen (NTHiENO-Cln III) were identified. However, in vitro assays show that NTHiENO has a better affinity to interact with Cln I, concerning type Cln III. The interaction of NTHiENO with collagen could play a significant role in the colonization process; this would allow H. influenzae to increase its virulence factors and strengthen its pathogenesis.
Subject(s)
Haemophilus Infections , Haemophilus influenzae , Humans , Phosphopyruvate Hydratase/genetics , Collagen Type I , Molecular Docking Simulation , Collagen/metabolism , Extracellular Matrix/metabolismABSTRACT
To aid the possible prevention of multidrug resistance in tumors and cause lower toxicity, a set of sixteen novel dihydropyridine carboxylic acids derivatives 3a-p were produced; thus, the activation of various ynones with triflic anhydride was performed, involving a nucleophilic addition of several bis(trimethylsilyl) ketene acetals, achieving good yields requiring easy workup. The target molecules were unequivocally characterized by common spectroscopic methods. In addition, two of the tested compounds (3a, and 3b) were selected to perform in silico studies due to the highest cytotoxic activity towards the HCT-15 cell line (7.94 ± 1.6 µM and 9.24 ± 0.9 µM, respectively). Employing theoretical calculations with density functional theory (DFT) using the B3LYP/6-311++G(d,p) showed that the molecular parameters correlate adequately with the experimental results. In contrast, predictions employing Osiris Property Explorer showed that compounds 3a and 3b present physicochemical characteristics that would likely make it an orally active drug. Moreover, the performance of Docking studies with proteins related to the apoptosis pathway allowed a proposal of which compounds could interact with PARP-1 protein. Pondering the obtained results (synthesis, in silico, and cytotoxic activity) of the target compounds, they can be judged as suitable antineoplastic agent candidates.
Subject(s)
Antineoplastic Agents , Dihydropyridines , Neoplasms , Humans , Cell Line , Antineoplastic Agents/chemistry , Organic Chemicals , Carboxylic Acids/pharmacology , Dihydropyridines/pharmacology , Molecular Docking Simulation , Structure-Activity Relationship , Molecular StructureABSTRACT
Equine placentitis is characterized by infection and inflammation of the placenta. Different biomarkers associated with this inflammatory response have been evaluated in experimentally induced equine placentitis, but not in pregnant mares with spontaneous placentitis. The aim of the current study was to determine the concentration of eIL-1ß and the activity of proMMP-2 and proMMP-9 in the serum of healthy mares and mares with placentitis on days 240 and 320 of gestation to explore whether these biomarkers are associated with equine maternal placentitis and/or with the birth of an infected or inviable foals. Serum samples were collected from sixteen pregnant English Thoroughbred mares, retrospectively classified as follows: (1) healthy mares with full-term gestation; and (2) mares with ultrasonographic signs of placentitis. The health of each foal was examined at birth, and it was decided to classify the cases into four groups: (1) healthy mares delivering a healthy foals (HM-HF, n = 6); (2) mares with USP delivering a healthy foal (USP-HF, n = 3); (3) mares with USP delivering a live septic foal (USP-LSeF, n = 4); and (4) mares with USP delivering a dead foal (USP-DF, n = 3). eIL-1ß was quantified by ELISA, and proMMP-2 and proMMP-9 activity by gelatin zymography electrophoresis. In healthy mares, the serum concentrations of eIL-1ß underwent a significant 16.5-fold increase from day 240 to day 320 of gestation. Although similar results were found in the mares with ultrasonographic signs of placentitis that delivered a healthy foal, those delivering a live septic or nonviable foal exhibited much higher concentrations of eIL-1ß. proMMP-2 and proMMP-9 activity was not associated with maternal placentitis, foal infection, or death. Hence, the presence of placentitis severe enough to affect the health of the foal can be confirmed or discarded by determining the eIL-1ß concentration in mares that have shown ultrasonographic signs of placentitis.
ABSTRACT
Introduction: Maternal dietary consumption during pregnancy has been inconclusively associated with acute leukemia (AL) in infants, probably because epidemiological evidence has emerged mainly from the analysis of one-by-one nutrient, which is not a real-life scenario. Our objective was to evaluate the association between AL in Mexican children under 2 years of age and their mothers' nutrients concomitant intake during pregnancy, as well as to explore whether there are differences between girls and boys. Methods: We conducted a study of 110 cases of AL and 252 hospital-based controls in the Mexico City Metropolitan area from 2010 to 2019. We obtained information on maternal intake of 32 nutrients by a food frequency questionnaire and used weighted quantile sum regression to identify nutrient concomitant intakes. Results: We found a concomitant intake of nutrients negatively associated with AL (OR 0.17; CI95% 0.03,0.88) only among girls; and we did not find a nutrient concomitant intake positively associated with AL. Discussion: This is the first study that suggests nutrients that have been individually associated with AL are not necessarily the same in the presence of other nutrients (concomitant intake); as well as that maternal diet might reduce AL risk only in girls.