Melatonin and Vitamins as Protectors against the Reproductive Toxicity of Bisphenols: Which Is the Most Effective? A Systematic Review and Meta-Analysis.

Bisphenols such as bisphenol A (BPA), S (BPS), C (BPC), F (BPF), AF (BPAF), tetrabromobisphenol, nonylphenol, and octylphenol are plasticizers used worldwide to manufacture daily-use articles. Exposure to these compounds is related to many pathologies of public health importance, such as infertility. Using a protector compound against the reproductive toxicological effects of bisphenols is of scientific interest. Melatonin and vitamins have been tested, but the results are not conclusive. To this end, this systematic review and meta-analysis compared the response of reproductive variables to melatonin and vitamin administration as protectors against damage caused by bisphenols. We search for controlled studies of male rats exposed to bisphenols to induce alterations in reproduction, with at least one intervention group receiving melatonin or vitamins (B, C, or E). Also, molecular docking simulations were performed between the androgen (AR) and estrogen receptors (ER), melatonin, and vitamins. About 1234 records were initially found; finally, 13 studies were qualified for review and meta-analysis. Melatonin plus bisphenol improves sperm concentration and viability of sperm and increases testosterone serum levels compared with control groups; however, groups receiving vitamins plus bisphenols had lower sperm concentration, total testis weight, and testosterone serum levels than the control. In the docking analysis, vitamin E had the highest negative MolDock score, representing the best binding affinity with AR and ER, compared with other vitamins and melatonin in the docking. Our findings suggest that vitamins could act as an endocrine disruptor, and melatonin is most effective in protecting against the toxic effects of bisphenols.

Differential Expression of FXR and Genes Involved in Inflammation and lipid Metabolism Indicate Adipose Tissue Dysfunction in Gestational Diabetes.

BACKGROUND: Gestational diabetes mellitus (GDM) is the most frequent metabolic alteration in pregnancy. Several abnormalities in visceral adipose tissue (VAT) have been described as part of its pathophysiology including hypertrophy, inflammation and altered lipid metabolism. Farnesoid X receptor (FXR) is involved in adipocyte physiology and inflammation, so its expression may correlate with the expression of tumor necrosis factor-alpha (TNF-α), interleukin-10 (IL-10), lipoprotein lipase (LPL), and two fatty acid transporters (SLC27A2, and SLC27A4). AIM: To compare the FXR, LPL, SLC27A2, SLC27A4, TNF-α, and IL-10 mRNA expression in VAT between women with GDM and healthy pregnant (HP) women. Secondarily, to evaluate the potential correlation between these expression levels. MATERIALS AND METHODS: Cross-sectional study of 50 GDM and 50 HP women. Conventional biochemical tests were performed and relative mRNA expression in VAT was measured by RT-qPCR. RESULTS: Gene expression levels of FXR and IL-10 were lower, whereas those of LPL, as well as the TNF-α/IL-10 ratio, were higher in women with GDM compared to HP. Pre-pregnancy BMI was the main significant independent variable for FXR levels in VAT from women with GDM. In all women, LPL expression levels correlated positively with those of SLC27A2. Only in women with GDM, IL-10 expression levels correlated negatively with those of SLC27A2, and SLC27A4. CONCLUSIONS: GDM is associated with decreased expression of FXR and IL-10 and increased expression of LPL, as well as a higher TNF/IL-10 ratio in VAT. These results suggest increased lipid storage and pro-inflammatory state indicating VAT dysfunction in this metabolic disorder.

Heparan Sulfate and Sialic Acid in Viral Attachment: Two Sides of the Same Coin?

Sialic acids and heparan sulfates make up the outermost part of the cell membrane and the extracellular matrix. Both structures are characterized by being negatively charged, serving as receptors for various pathogens, and are highly expressed in the respiratory and digestive tracts. Numerous viruses use heparan sulfates as receptors to infect cells; in this group are HSV, HPV, and SARS-CoV-2. Other viruses require the cell to express sialic acids, as is the case in influenza A viruses and adenoviruses. This review aims to present, in a general way, the participation of glycoconjugates in viral entry, and therapeutic strategies focused on inhibiting the interaction between the virus and the glycoconjugates. Interestingly, there are few studies that suggest the participation of both glycoconjugates in the viruses addressed here. Considering the biological redundancy that exists between heparan sulfates and sialic acids, we propose that it is important to jointly evaluate and design strategies that contemplate inhibiting the interactions of both glycoconjugates. This approach will allow identifying new receptors and lead to a deeper understanding of interspecies transmission.

Prognostic Value of Galectin Expression in Patients with Breast Cancer: Systematic Review and Meta-Analysis.

Galectins are a family of proteins with affinity for ß-galactosides and their expression correlates with overall survival (OS) in several cancers. However, in breast cancer their prognostic potential is unclear. In this study we performed a meta-analysis to clarify the prognostic value of galectin expression in breast cancer and to identify sources of heterogeneity. For this purpose, we performed a search of related publications in PubMed, Central-Conchrane, Web of Science database, OVID-EMBASE, Scope and EBSCOhost until November 2021.Thirteen articles were included with a total of 2700 patients. High galectin expression was found not to correlate with OS in breast cancer (HR = 1.11, 95% CI 0.93-1.31). In the case of galectin-3, correlation with OS was observed when performing subgroup analysis by cellular localization (HR = 0.59, 95% CI 0.36-0.94 for cytoplasmic and HR = 1.82, 95% CI 1.00-3.29 for cytoplasmic plus nuclear). Galectin-7 correlates with DFS/PFS/DSS (HR = 2.43; 95% CI 1.36-4.31). Finally, galectin-3 correlates with some clinicopathological features such as lymph node metastasis, estrogen receptor expression and age. In conclusion, galectin-3 correlates with OS in breast cancer when cellular localization is considered while galectin-7 correlates with DFS/PFS/DSS. The cellular localization of galectins should be as fundamental aspect to be determined in future studies.

Alteración del perfil materno de adipocinas circulantes en preeclampsia / Altered maternal adipokine profile in preeclampsia

Resumen OBJETIVOS: Evaluar las concentraciones séricas maternas de las adipocinas: adiponectina, adipsina, leptina, lipocalina-2, proteína quimioatrayente de monocitos-1, factor de crecimiento nervioso, resistina y factor de necrosis tumoral alfa y su relación con el índice de masa corporal previo al embarazo y la ganancia de peso gestacional en mujeres con preeclampsia comparadas con mujeres sanas, y hacer un análisis de la clasificación de preeclampsia en temprana y tardía. MATERIALES Y MÉTODOS: Estudio transversal, comparativo, retrolectivo, con muestreo no probabilístico por conveniencia efectuado en pacientes atendidas en el Hospital de Gineco-Obstetricia 3, Centro Médico Nacional La Raza, Instituto Mexicano del Seguro Social (IMSS). En el preoperatorio se tomó una muestra de sangre para determinar las concentraciones séricas de las adipocinas mediante ensayos multianalito. RESULTADOS: Se estudió una muestra de 75 mujeres con embarazo sano y 44 con preeclampsia (temprana n = 20, tardía n = 24). Solo las concentraciones de adipsina, leptina y factor de necrosis tumoral alfa fueron mayores en preeclampsia que en el embarazo sano [mediana (rango intercuartílico): 3.9 µg/mL (2.9-5.4) vs 2.5 µg/mL (1.9-3.1), 10.6 ng/mL (6.0-19.1) en comparación con 7.1 ng/mL (3.8-12.4), 3.6 pg/mL (2.7-5.8) vs 2.9 (2.3-3.5), respectivamente]. Las concentraciones de las adipocinas no se correlacionaron con el índice de masa corporal previo al embarazo ni con la ganancia de peso gestacional. No hubo diferencias significativas en las concentraciones entre los subtipos de preeclampsia. CONCLUSIÓN: En el tercer trimestre del embarazo la preeclampsia se asocia con un perfil sérico de adipocinas alterado, caracterizado por concentraciones elevadas de adipsina, leptina y factor de necrosis tumoral alfa, que no se relaciona con el índice de masa corporal previo al embarazo, la ganancia de peso gestacional y el subtipo de preeclampsia.

Abstract OBJECTIVES: To evaluate maternal serum concentrations of adipokines: adiponectin, adipsin, leptin, lipocalin-2, monocyte chemoattractant protein-1, nerve growth factor, resistin and tumor necrosis factor-alpha and their relationship with pre-pregnancy body mass index and gestational weight gain in women with preeclampsia compared with healthy women, and to perform an analysis classifying preeclampsia as early and late. MATERIALS AND METHODS: Cross-sectional, comparative, retrolective, non-probabilistic convenience sampling study carried out in patients attended at the Hospital de Gineco-Obstetricia 3, Centro Médico Nacional La Raza, Instituto Mexicano del Seguro Social (IMSS). Preoperatively, a blood sample was taken to determine serum adipokine concentrations by multianalyte assays. RESULTS: A sample of 75 women with healthy pregnancy and 44 with preeclampsia (early n = 20, late n = 24) was studied. Only adipsin, leptin, and tumor necrosis factor-alpha concentrations were higher in preeclampsia than in healthy pregnancy [median (interquartile range): 3. 9 µg/mL (2.9-5.4) vs. 2.5 µg/mL (1.9-3.1), 10.6 ng/mL (6.0-19.1) compared to 7.1 ng/mL (3.8-12.4), 3.6 pg/mL (2.7-5.8) vs. 2.9 (2.3-3.5), respectively]. Adipokine concentrations did not correlate with pre-pregnancy body mass index and gestational weight gain. There were no significant differences in concentrations between preeclampsia subtypes. CONCLUSION: In the third trimester of pregnancy, preeclampsia is associated with an altered serum adipokine profile, characterized by elevated concentrations of adipsin, leptin, and tumor necrosis factor-alpha, which is not related to prepregnancy body mass index, gestational weight gain, and preeclampsia subtype.