Bioactivity of Fractions and Pure Compounds from Jatropha cordata (Ortega) Müll. Arg. Bark Extracts.

Medicines for chronic inflammation can cause gastric ulcers and hepatic and renal issues. An alternative treatment for chronic inflammation is that of natural bioactive compounds, which present low side effects. Extracts of Jatropha cordata (Ortega) Müll. Arg. have been evaluated for their cytotoxicity and anti-inflammatory activity; however, testing pure compounds would be of greater interest. Campesteryl palmitate, n-heptyl ferulate, palmitic acid, and a mixture of sterols, i.e., brassicasterol, campesterol, ß-sitosterol, and stigmasterol, were obtained from an ethyl acetate extract from J. cordata (Ortega) Müll. Arg. bark using column chromatography. The toxicity and in vitro anti-inflammatory activities were evaluated using RAW 264.7 murine macrophage cells. None of the products assessed exhibited toxicity. The sterol mixture exhibited greater anti-inflammatory activity than the positive control, and nitric oxide (NO) inhibition percentages were 37.97% and 41.68% at 22.5 µg/mL and 30 µg/mL, respectively. In addition, n-heptyl ferulate decreased NO by 30.61% at 30 µg/mL, while campesteryl palmitate did not show anti-inflammatory activity greater than the positive control. The mixture and n-heptyl ferulate showed NO inhibition; hence, we may conclude that these compounds have anti-inflammatory potential. Additionally, further research and clinical trials are needed to fully explore the therapeutic potential of these bioactive compounds and their efficacy in treating chronic inflammation.

Short-Term Thermal Effect of Continuous Ultrasound from 3 MHz to 1 and 0.5 W/cm2 Applied to Gastrocnemius Muscle.

Continuous ultrasound is recognized for its thermal effect and use in the tissue repair process. However, there is controversy about its dosage and efficacy. This study used infrared thermography, a non-invasive technique, to measure the short-term thermal effect of 3 MHz continuous ultrasound vs. a placebo, referencing the intensity applied. It was a single-blind, randomized clinical trial of 60 healthy volunteers (19-24 years old) divided into three equal groups. Group 1:1 W/cm2 for 5 min; Group 2: 0.5 W/cm2 for 10 min; and Group 3: the placebo for 5 min. The temperature was recorded through five thermographic images per patient: pre- and post-application, 5, 10, and 15 min later. After statistical analysis, a more significant decrease in temperature (p<0.05 ) was observed in the placebo group compared with the remaining groups after the application of continuous ultrasound. Group 1 was the one that generated the highest significant thermal effect (p<0.001), with an increase of 3.05 °C at 15 min, compared with the other two groups. It is concluded that to generate a thermal effect in the muscle, intensities of ≥1 W/cm2 are required, since the dosage maintained a temperature increase for more than 5 min.

Design, synthesis, in silico, and in vitro evaluation of benzylbenzimidazolone derivatives as potential drugs on α-glucosidase and glucokinase as pharmacological targets.

Benzimidazolones have shown biological activities, including antihyperglycemic and hypoglycemic, by inhibiting or activating of α-glu and GK. The aim of this study is the rational design of compounds using in silico assays to delimitate the selection of structures to synthesize and the in vitro evaluation of benzimidazolone derivatives in blood glucose control. A docking of 23 benzimidazolone derivatives was performed; selecting the compounds with better in silico profiles to synthesize by microwave-irradiation/conventional heat and evaluate in enzymatic in vitro evaluation. Compounds 2k, 2m, 2r, and 2s presented the best in silico profiles, showing good affinity energy (-10.9 to -8.6 kcal mol-1) and binding with catalytic-amino acids. They were synthesized at 70 °C and 24 h using DMF as the solvent and potassium carbonate (yield: 22-38%). The results with α-glu showed moderate inhibition of 2k (14 ± 1.23-29 ± 0.45), 2m (12 ± 2.21-36 ± 0.30), 2r (7 ± 2.21-13 ± 1.34), and 2s (11 ± 0.74-35 ± 2.95) at evaluated concentrations (0.1 to 100 µg mL-1). The GK activation assay showed an enzymatic activity increase; compound 2k increased 1.31 and 2.83 more than normal activity, 2m (2.13-fold), 2s (2.86 and 3.74-fold) at 100 and 200 µg mL-1 respectively. The present study showed that the 2s derivative presents moderate potential as an α-glu inhibitor and a good activator potential of GK, suggesting that this compound is a good candidate for blood glucose control through antihyperglycemic and hypoglycemic mechanisms.

Phytochemical Characterization and In Vitro Anti-Inflammatory Evaluation in RAW 264.7 Cells of Jatropha cordata Bark Extracts.

The inflammatory process, although beneficial, can produce tissue damage and systemic damage when uncontrolled. Effective therapeutic alternatives with little or no side effects are of great therapeutic interest. This study aimed to determine the phytochemical composition of bark extracts from J. cordata, an endemic plant from México, and evaluate their in vitro anti-inflammatory activity. Hexane, ethyl acetate, and methanol extracts were characterized by qualitative phytochemical tests, and their bioactive groups were identified by 1H NMR and gas chromatography coupled to mass spectrometry (GC-MS). The extract's anti-inflammatory activity was evaluated as nitric oxide (NO) production and their cytotoxicity by an MTS cell proliferation assay in lipopolysaccharide (LPS)-activated RAW 264.7 cells at concentrations of 1-100 µg/mL. The hexane extract contained fatty acids, fatty esters, phytosterols, alkanes, vitamin E, and terpenoids; the ethyl acetate extract showed fatty acids, fatty esters, aromatic aldehyde, phytosterols, vitamin E, and terpenoids, while the methanolic extract showed fatty esters, fatty acid, aromatics aldehydes, and alcohol. The ethyl acetate extract showed the highest inhibition of NO production, followed by the methanolic extract and the hexane extract, without affecting the viability of RAW 264.7 macrophage cells. The results suggest that J. cordata extracts are a potential source of bioactive compounds with anti-inflammatory potential.

Luxación acromioclavicular tipo V tratada con tenosuspensión coracoclavicular y cerclaje acromioclavicular asistida por artroscopía / Type V acromioclavicular dislocation

El tratamiento de las luxaciones acromioclaviculares busca reducir y controlar la inestabilidad vertical, horizontal y rotacional. El uso de los sistemas de tenosuspensión con botones ofrece buenos resultados. A pesar de ello, se presentan molestias y dolor en la región supraclavicular, los que son motivo de consulta postquirúrgica y necesidad de revisión para retiro.Presentamos el caso de un paciente de sexo masculino, de treinta y nueve años, quien luego de una caída desde su bicicleta sufre una luxación acromioclavicular tipo V, la que fue tratada mediante sistema de tenosuspensión coracoclavicular y cerclaje acromioclavicular asistida por artroscopía, con buenos resultados. Nivel de Evidencia: IV

Treatment of acromioclavicular dislocations seeks to reduce and control vertical, horizontal, and rotational instability. The use of tenosuspension systems with buttons offers good results. Despite this, there is discomfort and pain in the supraclavicular region, which are the reason for post-surgical consultation and the need for revision for removal.We present a case of a thirty-nine-year-old male patient who suffered a type V acromioclavicular dislocation after falling from a bicycle, which was treated with a coracoclavicular tenosuspension system and arthroscopically assisted acromioclavicular cerclage with good results. Level of Evidence: IV

Pinzamiento subcoracoideo: diagnóstico e inyección guiada por ecografía en atletas lanzadores / Subcoracoid impingement. Diagnosis and ultrasound-guided injection in throwing athletes

El pinzamiento subcoracoideo es un cuadro poco frecuente y, por lo tanto, su diagnóstico plantea un reto al cirujano ortopédico. Se manifiesta con un dolor sordo en la región subcoracoidea y dolor a la palpación en el proceso coracoideo, como resultado del pinzamiento del músculo subescapular entre el proceso coracoideo y el troquín del húmero. El objetivo de esta nota técnica es describir una alternativa diagnóstica y la inyección guiada por ecografía para atletas lanzadores con pinzamiento subcoracoideo. Nivel de Evidencia: IV

Subcoracoid impingement is a rare condition, therefore, its diagnosis poses a challenge to the orthopedic surgeon. It manifests with dull pain in the subcoracoid region and pain on palpation in the coracoid process as a result of impingement of the subscapularis muscle between the coracoid process and the lesser tubercle of the humerus. The objective of this technical note is to describe an alternative diagnosis and ultrasound-guided injection for throwing athletes with subcoracoid impingement. Level of Evidence: IV

Role of FaSOC1 and FaCO in the seasonal control of reproductive and vegetative development in the perennial crop Fragaria × ananassa.

The diploid woodland strawberry (F. vesca) represents an important model for the genus Fragaria. Significant advances in the understanding of the molecular mechanisms regulating seasonal alternance of flower induction and vegetative reproduction has been made in this species. However, this research area has received little attention on the cultivated octoploid strawberry (F. × ananassa) despite its enormous agronomical and economic importance. To advance in the characterization of this intricated molecular network, expression analysis of key flowering time genes was performed both in short and long days and in cultivars with seasonal and perpetual flowering. Analysis of overexpression of FaCO and FaSOC1 in the seasonal flowering 'Camarosa' allowed functional validation of a number of responses already observed in F. vesca while uncovered differences related to the regulation of FaFTs expression and gibberellins (GAs) biosynthesis. While FvCO has been shown to promote flowering and inhibit runner development in the perpetual flowering H4 accession of F. vesca, our study showed that FaCO responds to LD photoperiods as in F. vesca but delayed flowering to some extent, possibly by induction of the strong FaTFL1 repressor in crowns. A contrasting effect on runnering was observed in FaCO transgenic plants, some lines showing reduced runner number whereas in others runnering was slightly accelerated. We demonstrate that the role of the MADS-box transcription factor FaSOC1 as a strong repressor of flowering and promoter of vegetative growth is conserved in woodland and cultivated strawberry. Our study further indicates an important role of FaSOC1 in the photoperiodic repression of FLOWERING LOCUS T (FT) genes FaFT2 and FaFT3 while FaTFL1 upregulation was less prominent than that observed in F. vesca. In our experimental conditions, FaSOC1 promotion of vegetative growth do not require induction of GA biosynthesis, despite GA biosynthesis genes showed a marked photoperiodic upregulation in response to long days, supporting GA requirement for the promotion of vegetative growth. Our results also provided insights into additional factors, such as FaTEM, associated with the vegetative developmental phase that deserve further characterization in the future.

Effect of 4-hydroxychalcone as preventive and curative treatment in Wistar rats with liver injury.

The increasing prevalence and complications related to liver diseases (caused by infection, toxic agents, or metabolic syndrome), together with insufficient existence of treatments, make evident the need for better therapeutic alternatives. Therefore, the aim of this study was to determine the effect of 4-hydroxychalcone (4-HC) as preventive and curative treatment in acute and chronic liver injury, respectively. Liver damage was induced with carbon tetrachloride (CCl4) in Wistar rats. Rats were divided into two groups: (1) acute liver injury and (2) chronic liver injury. In turn, each group was divided into four subgroups: (i) control (water); (ii) dimethyl sulfoxide 10%; (iii) CCl4; and (iv) 4-HC. The pre-treatment with 4-HC decreased transaminases, IL-6 serum levels, and hepatic malondialdehyde, increased IL-10 serum levels and hepatic glutathione, and decreased liver damage (necrosis, steatosis, and inflammatory infiltrate). In contrast, treatment with 4-HC after the induction of chronic liver injury decreased IL-6 serum levels and liver damage (steatosis, inflammatory infiltrate, ballooning cells, steatofibrosis, and fibrosis degree). Thus, the 4-HC treatment is proposed as a preventive treatment against acute liver injury; moreover, these results suggested the potential of 4-HC as a curative treatment against chronic liver injury, but other scheme treatments must be evaluated in future.

Genetic Profiling of Glucocorticoid (NR3C1) and Mineralocorticoid (NR3C2) Receptor Polymorphisms before Starting Therapy with Androgen Receptor Inhibitors: A Study of a Patient Who Developed Toxic Myocarditis after Enzalutamide Treatment.

Enzalutamide is a nonsteroidal inhibitor of the androgen receptor (AR) signaling pathway and is used to treat patients with metastatic castration-resistant prostate cancer. However, the risk of cardiovascular-related hospitalization in patients with no contraindications for the use of enzalutamide is about 1-2%. To date, the underlying molecular basis of this has not been established. The androgen receptor, glucocorticoid receptor (GR) and mineralocorticoid receptor (MR) are nuclear receptors that share structural similarities and have closely related DNA-binding sites and coregulators. In non-epithelial cells, a fine balance of the activities of these receptors is essential to ensure correct cellular function. In this study, we present a molecular characterization of these nuclear receptors in a prostate cancer patient who developed congestive heart failure after enzalutamide treatment. White cell RNAseq revealed a homozygous rs5522 MR polymorphism and both the rs143711342 and rs56149945 GR polymorphisms, carried in different alleles. No different specific splice isoforms were detected. Recent research suggests that AR inhibition by enzalutamide makes available a coregulator that specifically interacts with the rs5522-mutated MR, increasing its activity and producing adverse effects on cardiovascular health. We suggest an evaluation of the MR rs5522 polymorphism before starting therapy with AR inhibitors.

FKBP51, AmotL2 and IQGAP1 Involvement in Cilastatin Prevention of Cisplatin-Induced Tubular Nephrotoxicity in Rats.

The immunophilin FKBP51, the angiomotin AmotL2, and the scaffoldin IQGAP1 are overexpressed in many types of cancer, with the highest increase in leucocytes from patients undergoing oxaliplatin chemotherapy. Inflammation is involved in the pathogenesis of nephrotoxicity induced by platinum analogs. Cilastatin prevents renal damage caused by cisplatin. This functional and confocal microscopy study shows the renal focal-segmental expression of TNFα after cisplatin administration in rats, predominantly of tubular localization and mostly prevented by co-administration of cilastatin. FKBP51, AmotL2 and IQGAP1 protein expression increases slightly with cilastatin administration and to a much higher extent with cisplatin, in a cellular- and subcellular-specific manner. Kidney tubule cells expressing FKBP51 show either very low or no expression of TNFα, while cells expressing TNFα have low levels of FKBP51. AmotL2 and TNFα seem to colocalize and their expression is increased in tubular cells. IQGAP1 fluorescence increases with cilastatin, cisplatin and joint cilastatin-cisplatin treatment, and does not correlate with TNFα expression or localization. These data suggest a role for FKBP51, AmotL2 and IQGAP1 in cisplatin toxicity in kidney tubules and in the protective effect of cilastatin through inhibition of dehydropeptidase-I.

AmotL2, IQGAP1, and FKBP51 Scaffold Proteins in Glioblastoma Stem Cell Niches.

Glioma stem cells (GSCs) live in a continuous process of stemness reprogramming to achieve specific cell commitment within the so-called GSC niches, specifically located in periarteriolar regions. In this review, we analyze the expression levels, cellular and subcellular location, and role of three scaffold proteins (IQGAP1, FKBP51, and AmotL2) in GSC niches. Scaffold proteins contribute to cell differentiation, migration, and angiogenesis in glioblastoma. It could be of diagnostic interest for establishing stages, for therapeutic targets, and for improving glioblastoma prognosis, which is still at the experimental level.

Celastrol and Melatonin Modify SIRT1, SIRT6 and SIRT7 Gene Expression and Improve the Response of Human Granulosa-Lutein Cells to Oxidative Stress.

An excess of oxidative stress (OS) may affect several physiological processes fundamental to reproduction. SIRT1, SIRT6 and SIRT7 are involved in protection stress systems caused by OS, and they can be activated by antioxidants such as celastrol or melatonin. In this study, we evaluate SIRT1, SIRT6 and SIRT7 gene expression in cultured human granulosa-lutein (hGL) cells in response to OS inductors (glucose or peroxynitrite) and/or antioxidants. Our results show that celastrol and melatonin improve cell survival in the presence and absence of OS inductors. In addition, melatonin induced SIRT1, SIRT6 and SIRT7 gene expression while celastrol only induced SIRT7 gene expression. This response was not altered by the addition of OS inductors. Our previous data for cultured hGL cells showed a dual role of celastrol as a free radical scavenger and as a protective agent by regulating gene expression. This study shows a direct effect of celastrol on SIRT7 gene expression. Melatonin may protect from OS in a receptor-mediated manner rather than as a scavenger. In conclusion, our results show increased hGL cells survival with melatonin or celastrol treatment under OS conditions, probably through the regulation of nuclear sirtuins' gene expression.

Disproportion in Pericyte/Endothelial Cell Proliferation and Mechanisms of Intussusceptive Angiogenesis Participate in Bizarre Vessel Formation in Glioblastoma.

Glioblastoma (GBM) is the most malignant tumor in the brain. In addition to the vascular pattern with thin-walled vessels and findings of sprouting angiogenesis, GBM presents a bizarre microvasculature (BM) formed by vascular clusters, vascular garlands, and glomeruloid bodies. The mechanisms in BM morphogenesis are not well known. Our objective was to assess the role of pericyte/endothelial proliferation and intussusceptive angiogenic mechanisms in the formation of the BM. For this purpose, we studied specimens of 66 GBM cases using immunochemistry and confocal microscopy. In the BM, the results showed (a) transitional forms between the BM patterns, mostly with prominent pericytes covering all the abluminal endothelial cell (EC) surface of the vessels, (b) a proliferation index high in the prominent pericytes and low in ECs (47.85 times higher in pericytes than in ECs), (c) intravascular pillars (hallmark of intussusceptive angiogenesis) formed by transcapillary interendothelial bridges, endothelial contacts of opposite vessel walls, and vessel loops, and (d) the persistence of these findings in complex glomeruloid bodies. In conclusion, disproportion in pericyte/EC proliferation and mechanisms of intussusceptive angiogenesis participate in BM formation. The contributions have morphogenic and clinical interest since pericytes and intussusceptive angiogenesis can condition antiangiogenic therapy in GBM.

Molecular-Morphological Relationships of the Scaffold Protein FKBP51 and Inflammatory Processes in Knee Osteoarthritis.

Knee osteoarthritis (OA) is one of the most prevalent chronic conditions affecting the adult population. OA is no longer thought to come from a purely biomechanical origin but rather one that has been increasingly recognized to include a persistent low-grade inflammatory component. Intra-articular corticosteroid injections (IACSI) have become a widely used method for treating pain in patients with OA as an effective symptomatic treatment. However, as the disease progresses, IACSI become ineffective. FKBP51 is a regulatory protein of the glucocorticoid receptor function and have been shown to be dysregulated in several pathological scenario's including chronic inflammation. Despite of these facts, to our knowledge, there are no previous studies of the expression and possible role of FKBP51 in OA. We investigated by double and triple immunofluorescence confocal microscopy the cellular and subcellular expression of FKBP51 and its relations with inflammation factors in osteoarthritic knee joint tissues: specifically, in the tibial plateau knee cartilage, Hoffa's fat pad and suprapatellar synovial tissue of the knee. Our results show co-expression of FKBP51 with TNF-α, IL-6, CD31 and CD34 in OA chondrocytes, synovial membrane cells and adipocytes in Hoffa's fat pad. FKBP51 is also abundant in nerve fibers within the fat pad. Co-expression of FKBP51 protein with these markers may be indicative of its contribution to inflammatory processes and associated chronic pain in OA.

Celastrol Prevents Oxidative Stress Effects on FSHR, PAPP, and CYP19A1 Gene Expression in Cultured Human Granulosa-Lutein Cells.

Regulation of oxidative stress (OS) is important to prevent damage to female reproductive physiology. While normal OS levels may have a regulatory role, high OS levels may negatively affect vital processes such as folliculogenesis or embryogenesis. The aim of this work was to study OS induced by glucose, a reactive oxygen species generator, or peroxynitrite, a reactive nitrogen species generator, in cultured human granulosa-lutein (hGL) cells from oocyte donors, analyzing expression of genes involved in oocyte maturation (FSHR, PAPP, and CYP19A1) and OS damage response (ALDH3A2). We also evaluated the effect of celastrol as an antioxidant. Our results showed that although both glucose and peroxynitrite produce OS increments in hGL cells, only peroxynitrite treatment increases ALDH3A2 and PAPP gene expression levels and decreases FSHR gene expression levels. Celastrol pre-treatment prevents this effect of peroxynitrite. Interestingly, when celastrol alone was added, we observed a reduction of the expression of all genes studied, which was independent of both OS inductors. In conclusion, regulation of OS imbalance by antioxidant substances such as celastrol may prevent negative effects of OS in female fertility. In addition to the antioxidant activity, celastrol may well have an independent role on regulation of gene expression in hGL cells.

Bioguided isolation of N-malonyl-(+)-tryptophan from the fruit of Pithecellobium dulce (Roxb.) Benth. that showed high activity against Hymenolepis nana.

Pithecellobium dulce is distributed in America and Asia where is widely used in traditional medicine. This study describes the bioguided fractionation of the methanol extract (ME) obtained from the P. dulce fruit that showed in vitro activity against Hymenolepis nana; Artemia salina assay was used to determine toxicity; and the purified compound was computationally analysed to obtain its absorption-distribution-metabolism-excretion-and-toxicity properties (ADMET). The ME and its fractions were more active than praziquantel (PZQ), and the purified compound was characterized as N-malonyl-(+)-tryptophan (NMT). Parasites treated with NMT showed shorter paralysis and death times (5 and 7 min) than those treated with PZQ (15 and 30 min), both used at 20 mg/mL. Toxicity and ADMET prediction results supported the slight-hazardousness and efficacy of the assayed fractions/compound. This is the first report of the antiparasitary activity of both the P. dulce ME and NMT, showing their potential to treat human H. nana infections.

Synthesis of covalent bonding MWCNT-oligoethylene linezolid conjugates and their antibacterial activity against bacterial strains.

Nowadays, infectious diseases caused by drug-resistant bacteria have become especially important. Linezolid is an antibacterial drug active against clinically important Gram positive strains; however, resistance showed by these bacteria has been reported. Nanotechnology has improved a broad area of science, such as medicine, developing new drug delivery and transport systems. In this work, several covalently bounded conjugated nanomaterials were synthesized from multiwalled carbon nanotubes (MWCNTs), a different length oligoethylene chain (S n ), and two linezolid precursors (4 and 7), and they were evaluated in antibacterial assays. Interestingly, due to the intrinsic antibacterial activity of the amino-oligoethylene linezolid analogues, these conjugated nanomaterials showed significant antibacterial activity against various tested bacterial strains in a radial diffusion assay and microdilution method, including Gram negative strains as Escherichia coli (11 mm, 6.25 µg mL-1) and Salmonella typhi (14 mm, ≤0.78 µg mL-1), which are not inhibited by linezolid. The results show a significant effect of the oligoethylene chain length over the antibacterial activity. Molecular docking of amino-oligoethylene linezolid analogs shows a more favorable interaction of the S 2-7 analog in the PTC of E. coli.

Novel Linezolid analogues with antiparasitic activity against Hymenolepis nana.

The stereoselective synthesis and anti- Hymenolepis nana activity of six Linezolid-type compounds, obtained by chemical modification of l-Alanine, are reported in this work. The synthetic strategy was to prepare diasteromeric N,N-dibenzylamino oxazolidinones 1 and 2, and coupling with 4-(4-bromophenyl)morpholine (3) to obtain N,N-dibenzylamino Linezolid analogues 4 and 5. A hydrogenolysis reaction over 4 and 5 resulted in amino-free Linezolid analogues 6 and 7, which were acetylated to reach diasteromeric Linezolid analogues 8 and 9. The six Linezolid analogues 4-9 show in vitro antiparasitic activity against Hymenolepis nana cestode, but not against several bacterial strains. Interestingly, compounds 6, 7 and 9 exhibit high potency, having shorter paralysis and death times after exposure (6-10 and 18-21 min, respectively), shorter than those found with antihelmintic compound Praziquantel (20 and 30 min) at 20 mg/mL. In addition, a cytocompatibility assay of 6-9 with human cells (ARPE-19 cells) demonstrate a non-cytotoxic effect at 0.4 mM. These results show the pharmacological potential of the newly reported Linezolid-type analogues as antiparasitic agents against Hymenolepis nana.

Milk intake and IGF-1 rs6214 polymorphism as protective factors to obesity.

Mexico ranks 2nd in adult obesity and 4th in milk intake worldwide. Low levels of IGF-1 have been related to obesity and can be reverted by milk intake. The rs6214 polymorphism has been associated with an increase in the expression of IGF-1. Therefore, the aim of the study was to evaluate the association between both, rs6214 polymorphism and milk intake, and obesity. We analysed 99 adult volunteers, with and without a history of milk intake, for the presence of this polymorphism through qPCR and body composition by electro-bioimpedance. Univariate logistic regression analyses showed that TT genotype is inversely associated with obesity and body fat mass. Besides, milk intake is also related to low obesity, body fat mass and visceral fat, and high percentage of lean mass. Multivariate logistic regression analyses confirm the univariate relationships, showing a clear inverted association between TT genotype, milk intake and obesity.

Synthesis and molecular docking studies of imines as α-glucosidase and α-amylase inhibitors.

Imine functionality is found in many compounds with important biological activity. Thus, the development of novel synthetic approaches for imines is important. In this work, it is propose an easy, eco-friendly and straightforward synthesis pathway of aryl imines under microwave irradiation catalyzed by Alumina-sulfuric acid. In addition, the in vitro enzymatic inhibition, antioxidant activity and molecular docking studies were performed. The aryl imines were isolated with yields in the range of 37-94%. All aryl imines synthesized were evaluated for in vitro inhibitory potential against α-glucosidase and α-amylase enzymes and the results exhibited that the most of the compounds displayed inhibitory activity against both enzymes. The (E)-1-(4-nitrophenyl)-N-(pyridin-2-yl)methanimine (3d) was 1.15-fold more active than acarbose against α-amylase whilst the (E)-1-phenyl-N-(pyridin-2-yl)methanimine (3c) displayed similar activity that acarbose against α-glucosidase. The molecular docking studies in α-glucosidase and α-amylase reveal that aryl imines mainly establish an H-bond with the R2-subtituent and hydrophobic interactions with the R1-subtituent. The docking analysis reveals these synthetic aryl imines 3d-i interact in same active site than acarbose drug in both enzymes.