Expression and localization of the AT1 and AT2 angiotensin II receptors and α1A and α1D adrenergic receptors in aorta of hypertensive and diabetic rats

Hypertension and diabetes are multifactorial diseases that frequently coexist and exacerbate each another. During the development of diabetes, the impairment of noradrenergic and renin-angiotensin systems has been reported in the response mediated by α1-AR and AT1 receptors. Although their participation in the development of cardiovascular complications is still controversial, some studies have found increased or diminished response to the vasoconstrictive effect of noradrenaline or angiotensin II in a time-dependent manner of diabetes. Thus, the aim of this work was to investigate the possible changes in the expression or localization of α1-AR (α1A and α1D) and angiotensin II receptors (AT1 and AT2) in aorta of rats after 4 weeks of the onset of diabetes. In order to be able to examine the expression of these receptors, immunofluorescence procedure was performed in tunica intima and tunica media of histological sections of aorta. Fluorescence was detected by a confocal microscopy. Our results showed that the receptors are expressed in both tunics, where adrenergic receptors have a higher density in tunica intima and tunica media of SHR compared with WKY; meanwhile, the expression of angiotensin II receptors is not modified in both groups of rats. On the other hand, the results showed that diabetes produced an increase or a decrease in the expression of receptors that is not associated to a specific type of receptor, vascular region, or strain of rat. In conclusion, diabetes and hypertension modify the expression of the receptors in tunica intima and tunica media of aorta in a different way

Human Health Risk Assessment of Arsenic and Other Metals in Herbal Products Containing St. John’s Wort in the Metropolitan Area of Mexico City

Consumption of St. John’s wort plant is high worldwide due to its various medicinal properties. However, herbal products containing St. John’s wort may be contaminated with toxic metals. This is often related to contamination of both water and the atmosphere, lack of proper cultivation methods, and inadequate plant storage conditions, as well as a lack of stricter sanitary supervision. A safety assessment of copper (Cu), lead (Pb), cadmium (Cd) and arsenic (As) content in 23 products containing St. John’s wort (pharmaceutical herbal products, food supplements and traditional herbal remedies) sold in the metropolitan area of Mexico City was conducted. The analysis of metals was determined using a graphite-furnace atomic absorption spectrometer. All herbal products were contaminated with Cu, Pb, Cd and As. The pharmaceutical herbal items showed less contamination by metals. The daily human intake (DHI) values for Pb exceeded the permissible limits in the group of traditional herbal remedies. The DHI calculation for As exceeded the permitted intake values for all items in the group of traditional herbal remedies, five food supplements and one pharmaceutical herbal product. The hazard indicator calculation of the non-carcinogenic cumulative risk values for traditional herbal remedies was greater than 1, suggesting a risk to human health

Chronic Consumption of Sweeteners and Its Effect on Glycaemia, Cytokines, Hormones, and Lymphocytes of GALT in CD1 Mice

Background. The consumption of sweeteners has increased in recent years, being used to control body weight and blood glucose. However, they can cause increased appetite, modification of immune function, and secretion of hormones in the GALT. Objective. To assess the effect of chronic sweetener consumption on glycaemia, cytokines, hormones, and GALT lymphocytes in CD1 mice. Material and Methods. 72 CD1 mice divided into 3 groups were used: (a) baseline, (b) middle, and (c) final. Groups (b) and (c) were divided into 4 subgroups: (i) Control, (ii) Sucrose, (iii) Sucralose, and (iv) Stevia. The following were determined: body weight, hormones (GIP, insulin, and leptin), lymphocytes CD3+T cells and CD19+B cells, IgA+ plasma cells, and cytokines (IL-4, IL-5, IFN-γ, and TNF-α). Results. Sucralose reduces secretion of GIP and glycaemia but does not modify insulin concentration, increases body weight, and reduces food intake. Stevia increases the secretion of GIP, insulin, leptin, body weight, and glycaemia but keeps food consumption normal. Sucralose and Stevia showed a higher percentage of CD3+T cells, CD19+B cells, and IgA+ plasma cells in Peyer’s patches, but only Stevia in lamina propria. Conclusion. Sweeteners modulate the hormonal response of cytokines and the proliferation of lymphocytes in the intestinal mucosa

Virtual and In Vitro Screens Reveal a Potential Pharmacophore that Avoids the Fibrillization of Aβ1-42.

Among the multiple factors that induce Alzheimer's disease, aggregation of the amyloid β peptide (Aβ) is considered the most important due to the ability of the 42-amino acid Aβ peptides (Aβ1-42) to form oligomers and fibrils, which constitute Aβ pathological aggregates. For this reason, the development of inhibitors of Aβ1-42 pathological aggregation represents a field of research interest. Several Aβ1-42 fibrillization inhibitors possess tertiary amine and aromatic moieties. In the present study, we selected 26 compounds containing tertiary amine and aromatic moieties with or without substituents and performed theoretical studies that allowed us to select four compounds according to their free energy values for Aβ1-42 in α-helix (Aβ-α), random coil (Aβ-RC) and β-sheet (Aβ-β) conformations. Docking studies revealed that compound 5 had a higher affinity for Aβ-α and Aβ-RC than the other compounds. In vitro, this compound was able to abolish Thioflavin T fluorescence and favored an RC conformation of Aβ1-42 in circular dichroism studies, resulting in the formation of amorphous aggregates as shown by atomic force microscopy. The results obtained from quantum studies allowed us to identify a possible pharmacophore that can be used to design Aβ1-42 aggregation inhibitors. In conclusion, compounds with higher affinity for Aβ-α and Aβ-RC prevented the formation of oligomeric species

Cholecystokinin Outcome on Markers of Intestinal IgA Antibody Response

Cholecystokinin 8 (CCK8) is an entero-octapeptide that participates in crosstalk with components of intestinal immunity via the CCK receptor (CCKR), but its role in modulation of the IgA response is not fully known under physiological conditions. Male eight-week-old BALB/c mice each were intraperitoneally injected once during 7 days with CCK8, devazapide (CCKR1 antagonist), L365,260 (CCKR2 antagonist) or vehicle (sham group). In intestinal lavages, total and secretory IgA (SIgA) were determined by ELISA; in lamina propria, IgA+ B lymphocytes and IgA+ plasma cells were analyzed by flow cytometry; mRNA levels of polymeric immunoglobulin receptor (pIgR) in epithelial cells and α chain, interleukins (ILs) in lamina propria cells were assessed by qRTPCR. Regarding the sham conditions, IgA+ plasma-cell percentage and IL-2, IL-5, IL-10 and transforming growth factor-β (TGF-β) mRNA levels were either increased by CCK8 or decreased by both CCKR antagonists. For IgA/SIgA responses, IL-4/IL-6 mRNA levels were decreased by all drugs and pIgR mRNA was increased by CCK8 and reduced by L365,260. IgA+ B cell percentage and α chain mRNA levels were elicited by CCK8 and L365,260. Data suggested a presumable differential role of CCK/CCKR on the IgA-response; outcome of L365,260 on the elicitation of IgA+ B cells and α chain mRNA needs further examination

Protein Phosphorylation in Serine Residues Correlates with Progression from Precancerous Lesions to Cervical Cancer in Mexican Patients

Protein phosphorylation is a posttranslational modification that is essential for normal cellular processes; however, abnormal phosphorylation is one of the prime causes for alteration of many structural, functional, and regulatory proteins in disease conditions. In cancer, changes in the states of protein phosphorylation in tyrosine residues have been more studied than phosphorylation in threonine or serine residues, which also undergo alterations with greater predominance. In general, serine phosphorylation leads to the formation of multimolecular signaling complexes that regulate diverse biological processes, but in pathological conditions such as tumorigenesis, anomalous phosphorylation may result in the deregulation of some signaling pathways. Cervical cancer (CC), the main neoplasm associated with human papillomavirus (HPV) infection, is the fourth most frequent cancer worldwide. Persistent infection of the cervix with high-risk human papillomaviruses produces precancerous lesions starting with low-grade squamous intraepithelial lesions (LSIL), progressing to high-grade squamous intraepithelial lesions (HSIL) until CC is generated. Here, we compared the proteomic profile of phosphorylated proteins in serine residues from healthy, LSIL, HSIL, and CC samples. Our data show an increase in the number of phosphorylated proteins in serine residues as the grade of injury rises. These results provide a support for future studies focused on phosphorylated proteins and their possible correlation with the progression of cervical lesions

The Role of Propolis as a Natural Product with Potential Gastric Cancer Treatment Properties: A Systematic Review

Gastric cancer is one of the most common, aggressive, and invasive types of malignant neoplasia. It ranks fifth for incidence and fourth for prevalence worldwide. Products of natural origin, such as propolis, have been assessed for use as new complementary therapies to combat cancer. Propolis is a bee product with antiproliferative and anticancer properties. The concentrations and types of secondary metabolites contained in propolis mainly vary according to the geographical region, the season of the year, and the species of bees that make it. The present study is a systematic review of the main articles related to the effects of propolis against gastric cancer published between 2011 and 2021 in the PubMed and Science Direct databases. Of 1305 articles published, only eight studies were selected; among their principal characteristics was the use of in vitro analysis with cell lines from gastric adenocarcinoma and in vivo murine models of the application of propolis treatments. These studies suggest that propolis arrests the cell cycle and inhibits proliferation, prevents the release of oxidizing agents, and promotes apoptosis. In vivo assays showed that propolis decreased the number of tumors by regulating the cell cycle and the expression of proteins related to apoptosis

Docking results between curcumin, melatonin and ThT with several Aβ_1–42 conformers.

<p>The methodology to obtain the complex is the same as mentioned above for the docking studies with the selected compounds. ΔG values were obtained through docking studies of the ligands with <b>Aβ-α</b> (circles), <b>Aβ-RC</b> (rhombuses) and <b>Aβ-β</b> (squares) (A). The binding modes of curcumin, melatonin and ThT on <b>Aβ-α</b>, <b>Aβ-RC</b>, and <b>Aβ-β</b> (B).</p

Docking results for the selected compounds with several Aβ_1–42 conformers.

<p>ΔG values were obtained through docking studies of the ligands with <b>Aβ-α</b> (circles), <b>Aβ-RC</b> (rhombuses) and <b>Aβ-β</b> (squares) (A). The binding modes of compounds 5, 8, 14, 21 and 26 on <b>Aβ-α</b>, <b>Aβ-RC</b>, and <b>Aβ-β</b> (B).</p

Proposed Aβ-α pharmacophore based on the studies with compound 5.

<p>Schematic representation of the polar and nonpolar interactions that favor the interactions with <b>Aβ-α</b> (A); distances between principal chemical groups, the protonated amine (N⁺), the aromatic ring (Ar), and Alkyl substituent (<i>Tert-B</i>) (B). The main interactions involved in the recognition of compound 5 are electrostatic interactions with Glu22 and Asp23, π-π with Phe19 and Phe20 and hydrophobic interactions with Leu17.</p