In Silico and In Vivo Evaluation of the Maqui Berry (Aristotelia chilensis (Mol.) Stuntz) on Biochemical Parameters and Oxidative Stress Markers in a Metabolic Syndrome Model.

Metabolic syndrome (MetS) is a complex disease that includes metabolic and physiological alterations in various organs such as the heart, pancreas, liver, and brain. Reports indicate that blackberry consumption, such as maqui berry, has a beneficial effect on chronic diseases such as cardiovascular disease, obesity, and diabetes. In the present study, in vivo and in silico studies have been performed to evaluate the molecular mechanisms implied to improve the metabolic parameters of MetS. Fourteen-day administration of maqui berry reduces weight gain, blood fasting glucose, total blood cholesterol, triacylglycerides, insulin resistance, and blood pressure impairment in the diet-induced MetS model in male and female rats. In addition, in the serum of male and female rats, the administration of maqui berry (MB) improved the concentration of MDA, the activity of SOD, and the formation of carbonyls in the group subjected to the diet-induced MetS model. In silico studies revealed that delphinidin and its glycosylated derivatives could be ligands of some metabolic targets such as α-glucosidase, PPAR-α, and PPAR-γ, which are related to MetS parameters. The experimental results obtained in the study suggest that even at low systemic concentrations, anthocyanin glycosides and aglycones could simultaneously act on different targets related to MetS. Therefore, these molecules could be used as coadjuvants in pharmacological interventions or as templates for designing new multitarget molecules to manage patients with MetS.

In Combo Studies for the Optimization of 5-Aminoanthranilic Acid Derivatives as Potential Multitarget Drugs for the Management of Metabolic Syndrome.

Metabolic syndrome is a set of risk factors that consist of abdominal obesity, arterial hypertension, alterations in the lipid profile, and hyperglycemia. The current therapeutic strategy includes polypharmacy, using three or more drugs to control each syndrome component. However, this approach has drawbacks that could lead to therapeutic failure. Multitarget drugs are molecules with the ability to act on different targets simultaneously and are an attractive alternative for treating complex diseases such as metabolic syndrome. Previously, we identified a triamide derivative of 5-aminoanthranilic acid that exhibited hypoglycemic, hypolipemic, and antihypertensive activities simultaneously. In the present study, we report the synthesis and in combo evaluation of new derivatives of anthranilic acid, intending to identify the primary structural factors that improve the activity over metabolic syndrome-related parameters. We found that substitution on position 5, incorporation of 3,4-dimethoxyphenyl substituents, and having a free carboxylic acid group lead to the in vitro inhibition of HMG-CoA reductase, and simultaneously the diminution of the serum levels of glucose, triglycerides, and cholesterol in a diet-induced in vivo model.

Frequency of Candida spp. in the Oral Cavity of Asymptomatic Preschool Mexican Children and Its Association with Nutritional Status.

Malnutrition is a public health problem in developing countries, affecting the child population, which favors the appearance of infections such as oral candidiasis. In Mexico, information on the presence of oral colonization by Candida spp. in asymptomatic children is scarce. The present study aimed to determine the presence of Candida spp. in the oral cavity of asymptomatic preschool Mexican children and its association with their nutritional status. A sample of oral mucosa was obtained using a sterile swab and then inoculated in Sabouraud dextrose agar with antibiotics, and the yeast growth was phenotypically identified. The anthropometric profile of children was performed based on the guidelines of the International Society for the Advancement of Kinanthropometry. In addition, eating habits were investigated. The possible associations between the variables were determined through the chi-square test (IC95%, p < 0.05) (GraphPad Prism 8.0). Among the 743 assessed children (403 boys and 340 girls), the average age was 4.6 years, and the average nutritional status was normal (53.7%), followed by undernutrition (28.4%), overweight (12.4%) and obesity (5.5%). In 52 children, Candida was isolated, and the identified species were C. albicans (87.8%), C. glabrata (11.5%), C. krusei (5.8%) and C. parapsilosis (1.9%). The frequency of colonization was greater in males of six years (69.23%). There was no significant association between the colonization by Candida spp. and the nutritional status; however, a relation was observed with a high intake of simple carbohydrates.

High Fructose and High Fat Diet Impair Different Types of Memory through Oxidative Stress in a Sex- and Hormone-Dependent Manner.

Metabolic syndrome (MetS) contributes to the spread of cardiovascular diseases, diabetes mellitus type 2, and neurodegenerative diseases. Evaluation of sex- and hormone-dependent changes in body weight, blood pressure, blood lipids, oxidative stress markers, and alterations in different types of memory in Sprague-Dawley rats fed with a high fat and high fructose (HFHF) diet were evaluated. After 12 weeks of feeding the male and female rats with HFHF, body weight gain, increase in blood pressure, and generation of dyslipidemia compared to the animals fed with chow diet were observed. Regarding memory, it was noted that gonadectomy reverted the effects of HFHF in the 24 h novel object recognition task and in spatial learning/memory analyzed through Morris water maze, males being more affected than females. Nevertheless, gonadectomy did not revert long-term memory impairment in the passive avoidance task induced by HFHF nor in male or female rats. On the other hand, sex-hormone-diet interaction was observed in the plasma concentration of malondialdehyde and nitric oxide. These results suggest that the changes observed in the memory and learning of MetS animals are sex- and hormone-dependent and correlate to an increase in oxidative stress.

Does the Fetus Limit Antibiotic Treatment in Pregnant Patients with COVID-19?

During pregnancy, there is a state of immune tolerance that predisposes them to viral infection, causing maternal-fetal vulnerability to the adverse effects of COVID-19. Bacterial coinfections significantly increase the mortality rate for COVID-19. However, it is known that all drugs, including antibiotics, will enter the fetal circulation in a variable degree despite the role of the placenta as a protective barrier and can cause teratogenesis or other malformations depending on the timing of exposure to the drug. Also, it is important to consider the impact of the indiscriminate use of antibiotics during pregnancy can alter both the maternal and fetal-neonatal microbiota, generating future repercussions in both. In the present study, the literature for treating bacterial coinfections in pregnant women with COVID-19 is reviewed. In turn, we present the findings in 50 pregnant women hospitalized diagnosed with SARS-CoV-2 without previous treatment with antibiotics; moreover, a bacteriological culture of sample types was performed. Seven pregnant women had coinfection with Staphylococcus haemolyticus, Staphylococcus epidermidis, Streptococcus agalactiae, Escherichia coli ESBL +, biotype 1 and 2, Acinetobacter jahnsonii, Enterococcus faecium, and Clostridium difficile. When performing the antibiogram, resistance to multiple drugs was found, such as macrolides, aminoglycosides, sulfa, dihydrofolate reductase inhibitors, beta-lactams, etc. The purpose of this study was to generate more scientific evidence on the better use of antibiotics in these patients. Because of this, it is important to perform an antibiogram to prevent abuse of empirical antibiotic treatment with antibiotics in pregnant women diagnosed with SARS-CoV-2.

In Silico-Based Design and In Vivo Evaluation of an Anthranilic Acid Derivative as a Multitarget Drug in a Diet-Induced Metabolic Syndrome Model.

Metabolic syndrome (MetS) is a complex disease that affects almost a quarter of the world's adult population. In MetS, diabetes, obesity, hyperglycemia, high cholesterol, and high blood pressure are the most common disorders. Polypharmacy is the most used strategy for managing conditions related to MetS, but it has drawbacks such as low medication adherence. Multitarget ligands have been proposed as an interesting approach to developing drugs to treat complex diseases. However, suitable preclinical models that allow their evaluation in a context closer to a clinical situation of a complex disease are needed. From molecular docking studies, compound 1b, a 5-aminoanthranilic acid derivative substituted with 4'-trifluoromethylbenzylamino and 3',4'-dimethoxybenzamide moieties, was identified as a potential multitarget drug, as it showed high in silico affinity against targets related to MetS, including PPAR-α, PPAR-γ, and HMG-CoA reductase. It was evaluated in a diet-induced MetS rat model and simultaneously lowered blood pressure, glucose, total cholesterol, and triglyceride levels after a 14-day treatment. No toxicity events were observed during an acute lethal dose evaluation test at 1500 mg/kg. Hence, the diet-induced MetS model is suitable for evaluating treatments for MetS, and compound 1b is an attractive starting point for developing multitarget drugs.

Sex differences in the performance of cognitive tasks in a murine model of metabolic syndrome.

The metabolic syndrome includes changes in blood glucose levels, arterial hypertension, triglycerides, dyslipidemia and central obesity. Countless reports have described the correlation between the metabolic syndrome and cognitive impairment. However, only a few reports have assessed cognitive impairment associated with the metabolic syndrome in animals of both sexes. For this purpose, Sprague-Dawley male and female rats were fed either with a hypercaloric diet as model of the metabolic syndrome or with a standard chow diet as controls. Subsequently, spatial learning and memory (Morris water maze) as well as short- and long-term memory (passive avoidance task) were evaluated. Body weight, blood pressure, triglycerides, and total cholesterol significantly increased (F(1, 36) = 94.89, p < .001) in rats fed with hypercaloric diet compared to control rats. Furthermore, cognitive impairment was observed in spatial learning and spatial memory on male rats but not on female rats fed with hypercaloric diet. In addition, a long-term memory impairment was observed in both groups fed with hypercaloric diet in comparison to their respective control group (F(1, 32) = 10.61, p = .0027). Immunohistochemistry results showed no changes in the number of positive cells for NeuN, GFAP and Ox-42. In males fed with a hypercaloric diet, a decrease in testosterone levels was observed, whereas estradiol levels decreased in females when compared with their respective control group (p < .0001). In this MetS animal model, metabolic and cognitive differences were observed in males and females, which demonstrates that sex hormones play a significant role in metabolic regulation and neuroprotection related to the CA1 region of the hippocampus.

miRNA expression profile in multicellular breast cancer spheroids.

Multicellular Tumor Spheroids develop a heterogeneous micromilieu and different cell populations, thereby constituting a cancer model with intermediate characteristics between in vitro bi-dimensional cultures and in vivo tumors. Multicellular Tumor Spheroids also acquire tumor aggressiveness features due to transcription modulation of coding and non-coding RNA. Utilizing microarray analyses, we evaluated the microRNAs expression profile in MCF-7 breast cancer cells cultured as Multicellular Tumor Spheroids. The expression data was used to predict associated cellular and molecular functions using different software tools. The biological importance of two dysregulated miRNAs (miR-221-3p and miR-187) was studied by functional assays. Finally, the clinical relevance of these dysregulated miRNAs was explored using previously reported data. Thirty-three dysregulated microRNAs were found in MCF-7 Multicellular Tumor Spheroids. miRNA expression changes were closely linked with growth, proliferation, and cell development. miRNA-221-3p and miR-187 were implicated in the acquisition of migration/invasion capacities, sensitivity to the deprivation of growth factors, cell cycle phase regulation, and cell death. A panel of 5 miRNAs, including miR-187, showed a good predictive value in discriminating between low and high-risk groups of breast cancer.