Gestational diabetes mellitus: genetic factors, epigenetic alterations, and microbial composition.

Gestational diabetes mellitus (GDM) is a common metabolic disorder, usually diagnosed during the third trimester of pregnancy that usually disappears after delivery. In GDM, the excess of glucose, fatty acids, and amino acids results in foetuses large for gestational age. Hyperglycaemia and insulin resistance accelerate the metabolism, raising the oxygen demand, and creating chronic hypoxia and inflammation. Women who experienced GDM and their offspring are at risk of developing type-2 diabetes, obesity, and other metabolic or cardiovascular conditions later in life. Genetic factors may predispose the development of GDM; however, they do not account for all GDM cases; lifestyle and diet also play important roles in GDM development by modulating epigenetic signatures and the body's microbial composition; therefore, this is a condition with a complex, multifactorial aetiology. In this context, we revised published reports describing GDM-associated single-nucleotide polymorphisms (SNPs), DNA methylation and microRNA expression in different tissues (such as placenta, umbilical cord, adipose tissue, and peripheral blood), and microbial composition in the gut, oral cavity, and vagina from pregnant women with GDM, as well as the bacterial composition of the offspring. Altogether, these reports indicate that a number of SNPs are associated to GDM phenotypes and may predispose the development of the disease. However, extrinsic factors (lifestyle, nutrition) modulate, through epigenetic mechanisms, the risk of developing the disease, and some association exists between the microbial composition with GDM in an organ-specific manner. Genes, epigenetic signatures, and microbiota could be transferred to the offspring, increasing the possibility of developing chronic degenerative conditions through postnatal life.

Global DNA methylation and miR-126-3p expression in Mexican women with gestational diabetes mellitus: a pilot study.

BACKGROUND: Gestational diabetes mellitus (GDM), a type of diabetes that occurs for the first time during pregnancy, may predispose the development of chronic degenerative diseases and metabolic alterations in mother and offspring. DNA methylation and microRNA (miRNA) expression are regulatory mechanisms of gene expression that may contribute to the pathogenesis of GDM. Therefore, we determined global DNA methylation and miR-126-3p expression levels in 8 and 7 Mexican women with and without GDM, respectively. METHODS AND RESULTS: Global DNA methylation was assessed by measuring the percentage of 5-methylcytosine (5-mC) in placenta, umbilical cord, and plasma DNA samples, whereas miR-126-3p expression was quantified by real-time PCR using the 2-ΔCt method of the corresponding RNA samples. A significant increase in the percentage of 5-mC was detected in placenta samples from GDM patients compared to healthy women, while plasma samples showed a significant decrease. Conversely, miR-126-3p expression levels were significantly higher in plasma from the GDM group, while placenta and umbilical cord samples showed no significant differences across experimental groups. Furthermore, DNA methylation correlated significantly with glucose levels in placenta and plasma. Likewise, miR-126-3p expression correlated significantly with plasma glucose, in addition to maternal body mass index (BMI at first trimester). CONCLUSION: The results indicate that GDM is associated with alterations in global DNA methylation levels and miR-126-3p expression in placenta and/or plasma, providing insights into future novel approaches to diagnose and/or prevent this pathology.

Capsaicinoids and Their Effects on Cancer: The "Double-Edged Sword" Postulate from the Molecular Scale.

Capsaicinoids are a unique chemical species resulting from a particular biosynthesis pathway of hot chilies (Capsicum spp.) that gives rise to 22 analogous compounds, all of which are TRPV1 agonists and, therefore, responsible for the pungency of Capsicum fruits. In addition to their human consumption, numerous ethnopharmacological uses of chili have emerged throughout history. Today, more than 25 years of basic research accredit a multifaceted bioactivity mainly to capsaicin, highlighting its antitumor properties mediated by cytotoxicity and immunological adjuvancy against at least 74 varieties of cancer, while non-cancer cells tend to have greater tolerance. However, despite the progress regarding the understanding of its mechanisms of action, the benefit and safety of capsaicinoids' pharmacological use remain subjects of discussion, since CAP also promotes epithelial-mesenchymal transition, in an ambivalence that has been referred to as "the double-edge sword". Here, we update the comparative discussion of relevant reports about capsaicinoids' bioactivity in a plethora of experimental models of cancer in terms of selectivity, efficacy, and safety. Through an integration of the underlying mechanisms, as well as inherent aspects of cancer biology, we propose mechanistic models regarding the dichotomy of their effects. Finally, we discuss a selection of in vivo evidence concerning capsaicinoids' immunomodulatory properties against cancer.

Comparison of Phytochemical Composition and Untargeted Metabolomic Analysis of an Extract from Cnidoscolus aconitifolius (Mill.) I. I. Johnst and Porophyllum ruderale (Jacq.) Cass. and Biological Cytotoxic and Antiproliferative Activity In Vitro.

Cnidoscolus aconitifolius (CA) and Porophyllum ruderale (PR) are representative edible plants that are a traditional food source in Mexico. This research aimed to analyze the phytochemical composition and untargeted metabolomics analysis of CA and PR and evaluate their antiproliferative effect in vitro. The phytochemical composition (UPLC-DAD-QToF/MS-ESI) identified up to 38 polyphenols and selected organic acids that were clustered by the untargeted metabolomics in functional activities linked to indolizidines, pyridines, and organic acids. Compared with PR, CA displayed a higher reduction in the metabolic activity of human SW480 colon adenocarcinoma cells (LC50: 10.65 mg/mL), and both extracts increased the total apoptotic cells and arrested cell cycle at G0/G1 phase. PR increased mRNA Apc gene expression, whereas both extracts reduced mRNA Kras expression. Rutin/epigallocatechin gallate displayed the highest affinity to APC and K-RAS proteins in silico. Further research is needed to experiment on other cell lines. Results suggested that CA and PR are polyphenol-rich plant sources exhibiting antiproliferative effects in vitro.

Bean Leaves Ameliorate Lipotoxicity in Fatty Liver Disease.

Bioactive compounds in plant-based food have protective effects against metabolic alterations, including non-alcoholic fatty liver disease (NAFLD). Bean leaves are widely cultivated in the world and are a source of dietary fiber and polyphenols. High fat/high fructose diet animal models promote deleterious effects in adipose and non-adipose tissues (lipotoxicity), leading to obesity and its comorbidities. Short-term supplementation of bean leaves exhibited anti-diabetic, anti-hyperlipidemic, and anti-obesity effects in high-fat/high-fructose diet animal models. This study aimed to evaluate the effect of bean leaves supplementation in the prevention of lipotoxicity in NAFLD and contribute to elucidating the possible mechanism involved for a longer period of time. During thirteen weeks, male Wistar rats (n = 9/group) were fed with: (1) S: Rodent Laboratory Chow 5001® (RLC); (2) SBL: 90% RLC+ 10% dry bean leaves; (3) H: high-fat/high-fructose diet; (4) HBL: H+ 10% of dry bean leaves. Overall, a HBL diet enhanced impaired glucose tolerance and ameliorated obesity, risk factors in NAFLD development. Additionally, bean leaves exerted antioxidant (↑serum GSH) and anti-inflammatory (↓mRNA TNFα in the liver) effects, prevented hepatic fat accumulation by enhanced ↑mRNA PPARα (ß oxidation), and enhanced lipid peroxidation (↓liver MDA). These findings suggest that bean leaves ameliorated hepatic lipotoxicity derived from the consumption of a deleterious diet.

EGFR and p38MAPK Contribute to the Apoptotic Effect of the Recombinant Lectin from Tepary Bean (Phaseolus acutifolius) in Colon Cancer Cells.

Previous works showed that a Tepary bean lectin fraction (TBLF) induced apoptosis on colon cancer cells and inhibited early colonic tumorigenesis. One Tepary bean (TB) lectin was expressed in Pichia pastoris (rTBL-1), exhibiting similarities to one native lectin, where its molecular structure and in silico recognition of cancer-type N-glycoconjugates were confirmed. This work aimed to determine whether rTBL-1 retained its bioactive properties and if its apoptotic effect was related to EGFR pathways by studying its cytotoxic effect on colon cancer cells. Similar apoptotic effects of rTBL-1 with respect to TBLF were observed for cleaved PARP-1 and caspase 3, and cell cycle G0/G1 arrest and decreased S phase were observed for both treatments. Apoptosis induction on SW-480 cells was confirmed by testing HA2X, p53 phosphorylation, nuclear fragmentation, and apoptotic bodies. rTBL-1 increased EGFR phosphorylation but also its degradation by the lysosomal route. Phospho-p38 increased in a concentration- and time-dependent manner, matching apoptotic markers, and STAT1 showed activation after rTBL-1 treatment. The results show that part of the rTBL-1 mechanism of action is related to p38 MAPK signaling. Future work will focus further on the target molecules of this recombinant lectin against colon cancer.

Characterization and cytotoxicity assessment of cadmium sulfide quantum dots synthesized with Fusarium oxysporum f. sp. lycopersici.

The potential of CdS quantum dots for biomedical and bioimaging applications depends on their cytotoxicity, which can be modulated by coating molecules. Using sulfur as a precursor can be used along with cadmium nitrate to synthesize CdS quantum dots with the fungus Fusarium oxysporum f. sp. lycopersici. The latter replaces pure chemical sulfur as a precursor for CdS quantum dot synthesis, thus transforming waste into a value-added product, increasing sustainability, reducing the environmental impact of the process through the implementation of green synthesis techniques, and contributing to the circular economy. Therefore, we compared the cytotoxicity on HT-29 cells of biogenic, and chemical CdSQDs, synthesized by a chemical method using pure sulfur. Biogenic and chemical CdSQDs had diameters of 4.08 ± 0.07 nm and 3.2 ± 0.20 nm, Cd/S molar ratio of 43.1 and 1.1, Z-potential of - 14.77 ± 0.64 mV and - 5.52 ± 1.11 mV, and hydrodynamic diameters of 193.94 ± 3.71 nm and 152.23 ± 2.31 nm, respectively. The cell viability improved 1.61 times for biogenic CdSQDs over chemical CdSQDs, while cytotoxicity, measured as IC50, diminished 1.88-times. The lower cytotoxicity of biogenic CdSQDs was attributed to their organic coating consisting of lipids, amino acids, proteins, and nitrate groups that interacted with CdS through -OH and -SH groups. Therefore, the biogenic synthesis of CdSQDs has repurposed a pathogenic fungus, taking advantage of the biomolecules it secretes, to transform hazardous sulfur waste and metal ions into stable CdSQDs with advantageous structural and cytotoxic properties for their potential application in biomedicine and bioimaging.

Effect of Foliar Application of Hydrogen Peroxide Macroconcentrations on Growth Parameters, Phenolic Compounds and Antioxidant Capacity in the Leaves and Seeds of Amaranthus hypochondriacus L.

Amaranth has many interesting features, both nutritional and otherwise, that make it attractive as a food crop. Plants grown in greenhouses have higher yields but lower nutritional value compared to those grown in open fields. This prompted an interest in studying viable elicitors for the production of amaranth. Small hydrogen peroxide (H2O2) concentrations for foliar spraying from 0 to 18 mM have been used in greenhouse amaranth cultivation. The objective of this work was to evaluate the effect of foliar application of H2O2 megadoses on growth parameters, total phenolic compounds, condensed tannins, anthocyanins, and the antioxidant capacity of leaves and seeds of amaranth grown in a greenhouse setting. The seed of the Amaranthus hypochondriacus L. species was used. The concentrations of H2O2 analyzed were 0, 125, 250 and 400 mM, with 11 applications throughout the growing cycle. The variable data were subjected to an analysis of variance (ANOVA), followed by a Tukey's post hoc test (95% CI, p < 0.05). The results on chlorophyll, growth parameters and proximal chemical analysis showed no statistical difference between the control group versus the treatment groups. A greater number of favorable changes in the different variables studied were observed with the 125 mM H2O2 treatment, including the increase in antioxidant capacity measured by FRAP. The seed showed a considerable increase in TFC with all treatments and responded better to the 250 mM H2O2 treatment in the case of DPPH (an increase of 30%) and TPC (an increase of 44%). A 28% increase in anthocyanin content was observed with the treatment of 400 mM H2O2. The use of H2O2 may be an appropriate strategy to enhance the production of antioxidant compounds in amaranth without affecting growth or its basic proximal chemical composition. More studies are required in this regard.

Perceived Stress Is Directly Associated with Major Consumption of Sugar-Sweetened Beverages among Public University Students.

Stress is a condition that has been related to the development of risk behaviors for health such as sugar-sweetened beverages (SSBs) consumption. The aim of this study was to examine the link between SSBs consumption and perceived stress level in university students. This was an observational, cross-sectional and single-time-point study where the subjects were recruited as a non-probabilistic sample of first-year university students. The students reported their SSBs consumption through a validated questionnaire, as well as their perceived stress level, evaluated through the Cohen scale. Comparisons were made between the means of all variables. Factorial analysis of variance was conducted to explore the effect of the variables' interaction on the stress level. One-way analysis of variance was performed to assess differences between the sexes. Men consumed more SSBs (6101.17 ± 3772.50 mL/week) compared to women (4294.06 ± 3093.8 mL/week). However, women had higher scores of perceived stress and showed a strong association of stress with the SSBs consumption pattern (r and p-value). This study shows for the first time the association that exists between stress and SSBs consumption and indicates that it is related to sex in the young population.

Identification and Association of Single Nucleotide Polymorphisms of the FTO Gene with Indicators of Overweight and Obesity in a Young Mexican Population.

(1) Background: obesity is a global public health problem; various factors have been associated with this disease, and genetic factors play a very important role. Previous studies in multiple populations have associated a gene with fat mass and obesity (FTO). Thus, the present work aims to identify and determine associations between genetic variants of FTO with indicators of overweight and obesity in the Mexican population. (2) Methods: a total of 638 subjects were evaluated to compile data on body mass index (BMI), the percentage of body fat (%BF), the waist circumference (WC), the serum levels of triglycerides (TG), and food consumption. A total of 175 genetic variants in the FTO gene were sampled by a microarray in the evaluated population, followed by association statistical analyses and comparisons of means. (3) Results: a total of 34 genetic variants were associated with any of the 6 indicators of overweight and obesity, but only 15 showed mean differences using the recessive model after the Bonferroni correction. The present study shows a wide evaluation of FTO genetic variants associated with a classic indicator of overweight and obesity, which highlights the importance of genetic analyses in the study of obesity.

Comparative study, homology modelling and molecular docking with cancer associated glycans of two non-fetuin-binding Tepary bean lectins.

We present the purification and characterization of the two most abundant isoforms of lectins isolated from Tepary bean (Phaseolus acutifolius) seeds, which have been shown to differentially affect the survival of different cancer cells. They were separated by concanavalin A-affinity chromatography. After purification, to release the N-glycans, they were digested with the endoglycosidases PNGase and Glycanase A. Fractions resulted from the hydrolysis products were analyzed to determine their carbohydrate composition. Mass spectrometry data indicated that both isoforms contained high mannose glycans being mannose 6 the most abundant form. Furthermore, based on sequence Ans-X-Ser/Thr, where X is any amino acid except proline, a glycosylation site was determined on asparagine 36. When their metal requirement to preserve their biological activity was determined, the lectins showed differences. While lectin A (LA) agglutination activity was best in the presence of magnesium, lectin B (LB) was best with calcium. Additionally, only LA exhibited affinity to human type-A erythrocytes. Although both lectins showed small differences in their properties, an identical structure-model for both lectins was generated by the homology modelling process. Also, the analysis of ligand binding sites and in silico glycosylation were achieved. Molecular docking with colon adenocarcinoma associated-N-glycans revealed some highly possible interactions and, on the other hand, that N-glycan interaction zones of Tepary bean lectins is not restricted to the carbohydrate binding domain but to an extended part of their surface, which could lead new strategies to explain their biological activity.

Evaluation of the humoral and mucosal immune response of a multiepitope vaccine against COVID-19 in pigs.

Introduction: This study evaluated the immune response to a multiepitope recombinant chimeric protein (CHIVAX) containing B- and T-cell epitopes of the SARS-CoV-2 spike's receptor binding domain (RBD) in a translational porcine model for pre-clinical studies. Methods: We generated a multiepitope recombinant protein engineered to include six coding conserved epitopes from the RBD domain of the SARS-CoV-2 S protein. Pigs were divided into groups and immunized with different doses of the protein, with serum samples collected over time to determine antibody responses by indirect ELISA and antibody titration. Peptide recognition was also analyzed by Western blotting. A surrogate neutralization assay with recombinant ACE2 and RBDs was performed. Intranasal doses of the immunogen were also prepared and tested on Vietnamese minipigs. Results: When the immunogen was administered subcutaneously, it induced specific IgG antibodies in pigs, and higher doses correlated with higher antibody levels. Antibodies from immunized pigs recognized individual peptides in the multiepitope vaccine and inhibited RBD-ACE2 binding for five variants of concern (VOC). Comparative antigen delivery methods showed that both, subcutaneous and combined subcutaneous/intranasal approaches, induced specific IgG and IgA antibodies, with the subcutaneous approach having superior neutralizing activity. CHIVAX elicited systemic immunity, evidenced by specific IgG antibodies in the serum, and local mucosal immunity, indicated by IgA antibodies in saliva, nasal, and bronchoalveolar lavage secretions. Importantly, these antibodies demonstrated neutralizing activity against SARS-CoV-2 in vitro. Discussion: The elicited antibodies recognized individual epitopes on the chimeric protein and demonstrated the capacity to block RBD-ACE2 binding of the ancestral SARS-CoV-2 strain and four VOCs. The findings provide proof of concept for using multiepitope recombinant antigens and a combined immunization protocol to induce a neutralizing immune response against SARS-CoV-2 in the pig translational model for preclinical studies.

Effect of Induced Mechanical Leaf Damage on the Yield and Content of Bioactive Molecules in Leaves and Seeds of Tepary Beans (Phaseolus acutifolius).

Growing interest has recently been shown in Tepary beans (Phaseolus acutifolius) because they contain lectins and protease inhibitors that have been shown to have a specific cytotoxic effect on human cancer cells. Bean lectins offer protection against biotic and abiotic stress factors, so it is possible that mechanical foliar damage may increase lectin production. This study evaluates the effect of mechanical stress (foliar damage) on lectin and protease inhibitor content in Tepary beans. Seed yield was also analyzed, and phenolic content and antioxidant capacity (DPPH and TEAC) were determined in the leaves. An experimental design with random blocks of three treatments (T1: control group, T2: 50% mechanical foliar damage and T3: 80% mechanical foliar damage) was carried out. Mechanical foliar damage increased the amount of lectin binding units (LBUs) fivefold (from 1280 to 6542 LBUs in T3) but did not affect units of enzymatic activity (UEA) against trypsin (from 60.8 to 51 UEA in T3). Results show that controlled mechanical foliar damage could be used to induce overexpression of lectins in the seeds of Tepary beans. Mechanical foliar damage reduced seed production (-14.6%: from 1890 g to 1615 g in T3) and did not significantly increase phenolic compound levels in leaves.

Phaseolus vulgaris L. Leaves Increase Short-Chain Fatty Acid (SCFA) Production, Ameliorating Early Metabolic Alterations.

High-fat/high-fructose diets promote early metabolic disorders in weight and lipid and glucose metabolism. Bioactive compounds such as polyphenols and fiber present in plant-based food prevent the development of metabolic disorders. The objective of the present study was to evaluate the effect of Phaseolus vulgaris L. Flor de Mayo Eugenia (FME) bean leaves on early metabolic alterations in male Wistar rats fed a high-fat/high-fructose diet. After proximate and chemical analysis of FME bean leaves, thirty-six male Wistar rats (ethical approval 06FCN2019 and 77FCN2019) were randomly assigned to one of four groups: 1) standard diet (S) fed with Rodent Laboratory Chow 5001®; 2) standard diet + 10% dry FME bean leaves (SBL); 3) high-fat (lard) and high-fructose diet (H); and 4) high-fat/high-fructose diet + 10% dry FME bean leaves (HBL). The study was carried out for six weeks. Group H exhibited early metabolic alterations compared to Group S: final weight gain (↑15%), abdominal fat accumulation (waist circumference, ↑11%), triglycerides (↑30%), glucose (↑16%), insulin resistance (HOMA-IR, ↑32%), and fecal triglycerides (↑284%) and decreased total short-chain fatty acids (SCFAs, ↓17%). FME bean leave supplementation (HBL) prevented body weight gain (↓12%), abdominal fat accumulation (waist circumference, ↓10%), and early insulin resistance (glucose area under the curve, ↓6%) compared to Group H. The supplementary bean leave diet increased SCFA production (↑54%), most likely mediated by the fiber and polyphenols present in the leaves. Therefore, bean leaves are a low-cost alternative for human nutritional care and prevention of early metabolic alterations.

Association between SNPs in Leptin Pathway Genes and Anthropometric, Biochemical, and Dietary Markers Related to Obesity.

Obesity is one of the main public health problems in Mexico and the world and one from which a large number of pathologies derive. Single nucleotide polymorphisms (SNPs) of various genes have been studied and proven to contribute to the development of multiple diseases. SNPs of the leptin pathway have been associated with the control of hunger and energy expenditure as well as with obesity and type 2 diabetes mellitus. Therefore, the present work focused on determining the association between anthropometric markers and biochemical and dietary factors related to obesity and SNPs of leptin pathway genes, such as the leptin gene (LEP), the leptin receptor (LEPR), proopiomelanocortin (POMC), prohormone convertase 1 (PCSK1), and the melanocortin 4 receptor (MC4R). A population of 574 young Mexican adults of both sexes, aged 19 years old on average and without metabolic disorders previously diagnosed, underwent a complete medical and nutritional evaluation, biochemical determination, and DNA extraction from the blood; DNA samples were subsequently genotyped. Association analyses between anthropometric, biochemical, and dietary variables with SNPs were performed using binary logistic regressions (p-value = 0.05). Although the sampled population did not have previously diagnosed diseases, the evaluation results showed that 33% were overweight or obese according to BMI and 64% had non-clinically elevated levels of body fat. From the 74 SNP markers analyzed from the five previously mentioned genes, 62 showed polymorphisms within the sampled population, and only 35 of these had significant associations with clinical variables. The risk associations (OR > 1) occurred between clinical markers with elevated values for waist circumference, waist−height index, BMI, body fat percentage, glucose levels, insulin levels, HOMA-IR, triglyceride levels, cholesterol levels, LDL-c, low HDL-c, carbohydrate intake, and protein intake and SNPs of the LEP, LEPR, PCSK1, and MC4R genes. On the other hand, the protective associations (OR < 1) were associated with markers including elevated values for insulin, HOMA-IR, cholesterol, c-LDL, energy intake > 2440 Kcal/day, and lipid intake and SNPs of the LEP and LEPR genes and POMC. The present study describes associations between SNPs in leptin pathway genes, revealing positive and negative interactions between reported SNPs and the clinical markers related to obesity in a sampled Mexican population. Hence, our results open the door for the further study of new genetic variants and their influence on obesity.

Hybridization between Crotalus aquilus and Crotalus polystictus Species: A Comparison of Their Venom Toxicity and Enzymatic Activities.

Hybridization is defined as the interbreeding of individuals from two populations distinguishable by one or more heritable characteristics. Snake hybridization represents an interesting opportunity to analyze variability and how genetics affect the venom components between parents and hybrids. Snake venoms exhibit a high degree of variability related to biological and biogeographical factors. The aim of this work is to analyze the protein patterns and enzymatic activity of some of the main hemotoxic enzymes in snake venoms, such as serine proteases (trypsin-like, chymotrypsin-like, and elastase-like), metalloproteases, hyaluronidases, and phospholipase A2. The lethal dose of 50 (LD50) of venom from the Crotalus aquilus (Cabf) and Crotalus polystictus (Cpbm) parents and their hybrids in captivity was determined, and phenetic analysis is also conducted, which showed a high similarity between the hybrids and C. polystictus. The protein banding patterns and enzymatic activity analyze by zymography resulted in a combination of proteins from the parental venoms in the hybrids, with variability among them. In some cases, the enzymatic activity is higher in the hybrids with a lower LD50 than in the parents, indicating higher toxicity. These data show the variability among snake venoms and suggest that hybridization is an important factor in changes in protein concentration, peptide variability, and enzymatic activity that affect toxicity and lethality.

Proangiogenic Effect of Affinin and an Ethanolic Extract from Heliopsis longipes Roots: Ex Vivo and In Vivo Evidence.

Angiogenesis, the formation of new blood vessels, underlies tissue development and repair. Some medicinal plant-derived compounds can modulate the angiogenic response. Heliopsis longipes, a Mexican medicinal plant, is widely used because of its effects on pain and inflammation. The main bioactive phytochemicals from H. longipes roots are alkamides, where affinin is the most abundant. Scientific studies show various medical effects of organic extracts of H. longipes roots and affinin that share some molecular pathways with the angiogenesis process, with the vasodilation mechanism of action being the most recent. This study investigates whether pure affinin and the ethanolic extract from Heliopsis longipes roots (HLEE) promote angiogenesis. Using the aortic ring rat assay (ex vivo method) and the direct in vivo angiogenesis assay, where angioreactors were implanted in CD1 female mice, showed that affinin and the HLEE increased vascular growth in a dose-dependent manner in both bioassays. This is the first study showing the proangiogenic effect of H. longipes. Further studies should focus on the mechanism of action and its possible therapeutic use in diseases characterized by insufficient angiogenesis.

Vitamin D status, proinflammatory cytokines and bone mineral density in Mexican people with multiple sclerosis.

BACKGROUND: Vitamin D (VD) has been classically associated with calcium homeostasis and bone mineral density since it has a key role on mineralization and resorption. Immunomodulatory effects have been attributable to VD; low concentrations of VD have been associated with elevation of inflammatory markers. Inflammatory autoimmune diseases, such as multiple sclerosis (MS), a chronic neurodegenerative suffering, whose etiology is still unknown, is directly related to an increase in pro-inflammatory cytokines such as interleukin 17 and interleukin 1ß who play an important role in this physiopathology. Nowadays, even though additional studies have linked MS's clinical signs with low VD concentration, there is scarce information of this association in people from regions with sufficient sun exposure. The aim of this study was to evaluate serum VD and cytokine concentrations, and bone density, in Mexican people with MS. METHODS: Vitamin D (25OHD), interleukin 1ß, interleukin 6 and interleukin 17 concentrations of twenty-five volunteers with MS were determined by enzyme-linked immunosorbent assay. Bone mineral density and body composition assessment was performed by dual energy X-Ray absorptiometry. RESULTS: A mean concentration of 17.3 ± 4.6 ng/ml of 25OHD was obtained, in a range of 5.15 to 25.71 ng/ml; when international advisory bodies thresholds were applied 76% of the participants exhibited some degree of VD inadequacy. Pro-inflammatory markers were detectable among the participants: interleukin 1ß in 100%, interleukin 6 in 64%, whereas interleukin 17 was found in 24% of the volunteers. Bone mineral density below the expected for the age was found in 8% of the participants, with lumbar spine as the most affected anatomic region. Non-significant correlations were found between VD and bone mineral density (Z-score) or pro-inflammatory markers. CONCLUSION: Although non-significant correlations were found between VD and bone mineral density or cytokines, it is important to highlight that an important percentage of our participants exhibited some degree of VD inadequacy, an unknown fact for them, since these are not included in routine clinical evaluations. The low concentrations of VD among this sample regardless of annual UVB sun exposure may suggest the involvement of endogenous and not environmental factors. Further works are needed in order to deepen the physiological causes and effects of VD deficiency in people with MS.

Endothelial TRP channels and cannabinoid receptors are involved in affinin-induced vasodilation.

Affinin is mainly recognized by its antinociceptive effect. Recently, our research group demonstrated that this compound produces vasodilation via activation of the gasotransmitters signaling pathways. However, the molecular targets of affinin were not identified. Considering the structural similarity of this alkamide with anandamide, we hypothesized that affinin-induced vasodilation could involve participation of TRP channels and cannabinoid receptors. In this work, by using the isolated rat aorta assay, we assessed involvement of TRP channels, the cannabinoid system, and the HNO-CGRP-TRPA1 pathway on the mechanism of action of affinin. Additionally, we measured NO and H2S levels elicited by affinin on rat aorta homogenates and carried out computer simulations of molecular interactions between affinin and the TRPA1 and TRPV1 channels and the CB1 receptor. Our results indicated that affinin induces an increase in aortic NO and H2S levels. We found evidence that the vasodilator effect induced by affinin involves activation of TRPA1 and TRPV1 channels and the CB1 and eCB receptors. In silico analyses showed that affinin is able to bind with high affinity to these molecular targets. Moreover, we also proved that affinin-induced vasodilation is partly mediated via activation of the HNO-TRPA1-CGRP pathway. Based on these results we propose a novel mechanism of action to explain the vasodilatory effect of affinin, which could be developed as an alternative drug to treat cardiovascular diseases.

Rapid and reversible cell volume changes in response to osmotic stress in yeast.

Saccharomyces cerevisiae has evolved diverse mechanisms to osmotic changes: the cell wall, ion and water transport systems, and signaling cascades. At the present time, little is known about the mechanisms involved in short-term responses of osmotic stress in yeast or their physiological state during this process. We conducted studies of flow cytometry, wet weight measurements, and electron microscopy to evaluate the modifications in cell volume and the cell wall induced by osmotic stress. In response to osmotic challenges, we show very fast and drastic changes in cell volume (up to 60%), which were completed in less than eight seconds. This dramatic change was completely reversible approximately 16 s after returning to an isosmotic solution. Cell volume changes were also accompanied by adaptations in yeast metabolism observed as a reduction by 50% in the respiratory rate, measured as oxygen consumption. This effect was also fully reversible upon returning to an isosmotic solution. It is noteworthy that we observed a significant recovery in oxygen consumption during the first 10 min of the osmotic shock. The rapid adjustment of the cellular volume may represent an evolutionary advantage, allowing greater flexibility for survival.