Activity

The current manuscript describes two molecules that were designed against PPARγ and GPR40 receptors. The preparation of the compounds was carried out following a synthetic route of multiple steps. Then, the mRNA expression levels of PPARγ, GLUT4, and GPR40 induced by compounds were measured and quantified in adipocyte and β-pancreatic cell cultures. The synthesized compound 1 caused an increase in the 4-fold expression of mRNA of PPARγ regarding the control and had a similar behavior to the pioglitazone, while compound 2 only increased 2-fold the expression. Also, the compound 1 increased to 7-fold the GLUT4 expression levels, respect to the control and twice against the pioglitazone. GW2580 On the other hand, the 1 increase 3-fold GPR40 expression, and compound 2 had a minor activity. Besides, 1 and 2 showed a moderated increase on insulin secretion and calcium mobilization versus the glibenclamide. Based on the molecular docking studies, the first compound had a similar conformation to co-crystal ligands into the binding site of both receptors. The poses were docked keeping the most important interactions and maintaining the interaction along the Molecular Dynamics simulation (20 ns). Finally, compound (1) showed an antihyperglycemic effect at 5 mg/kg, however at higher doses of 25 mg/kg it controlled blood glucose levels associated with feeding intake and without showing the adverse effects associated with insulin secretagogues (hypoglycemia). For these reasons, we have concluded that molecule 1 acts as a dual PPARγ and GPR40 agonist offering a better glycemic control than current treatments.Hepatocellular carcinoma (HCC) is one of the most common types of liver cancer with high incidence and metastatic rate. Recent studies have shown that the high metastasis of HCC is closely related to the acidic microenvironment of HCC cells. Acid-sensing ion Channel 1a (ASIC1a) plays an important role in HCC development, which can mediate tumor cell migration and invasion. However, the underlying mechanism of how ASIC1a promotes HCC cell migration and invasion in acidic microenvironments remains unclear, while autophagy may act as a mechanism for tumor cells to adapt to acidic microenvironment. Therefore, this study aims to investigate whether ASIC1a mediates autophagy and its effects on the migration and invasion of HCC cells. Interestingly, our study has shown that ASIC1a and autophagy were increased in HepG2 cells in acidic microenvironment, and both of them can promote HCC cells migration and invasion. Moreover, inhibition of ASIC1a with PcTx1 or ASIC1a ShRNA reduced the autophagy flux. Collectively, ASIC1a can promote acidic microenvironment-induced HepG2 cells migration and invasion by inducing autophagy, which may be correlated with Ca2+ influx.The evolution of ultrasound and the introduction of 3- and 4-dimensional ultrasound techniques led to a shift in the perception and usage of ultrasound in fetal medicine. The biplane mode might help in multiple fetal procedures, including but not limited to basic intrauterine thoracocentesis, thoracoamniotic shunting, amnioreduction, amnioinfusion, cordocentesis, intraumbilical infusion, and umbilical cord coagulation, with a possible reduction in the complication rate. Despite its theoretical usefulness, more studies are required to assess the clinical importance of this technique.

Evidence for the association between prenatal antidepressant use and the development of hypertensive disorders of pregnancy is inconsistent. Previous studies have reported that antidepressant use during pregnancy increases the risk for gestational hypertension and preeclampsia, but the results of these studies are potentially confounded by important methodologic limitations. Furthermore, it remains unknown whether a higher cumulative dose of antidepressant increases the risk for hypertensive disorders of pregnancy.

This study aimed to investigate the association between prenatal antidepressant use and the risk for hypertensive disorders of pregnancy and the potential effect of a higher cumulative antidepressant dose.

This retrospective cohort study used data from the Health and Welfare Database in Taiwan. Pregnant women with depression aged 18 to 49 years were enrolled as part of the study population. Prenatal antidepressant use was defined as at least 1 dispensing record of an antidepressant between thants.

Phosphodiesterase-5 inhibitors have recently been used for the treatment of severe early onset pre-eclampsia and fetal growth restriction. There are however concerns that they may increase the risk of neonatal morbidity and mortality. The aim of this systematic review was to assess the safety profile and clinical outcomes of phosphodiesterase-5 inhibitors use in pregnancy.

We searched Embase, PubMed, CENTRAL, Prospero and Google Scholar to identify randomised controlled trials (RCTs) reporting the use of phosphodiesterase-5 inhibitors in human pregnancy up to November 2020.

Inclusion criteria included RCTs reporting obstetric or perinatal outcomes or maternal adverse outcomes in women taking phosphodiesterase-5 inhibitors in pregnancy. Outcomes of interest included maternal side effects, obstetric, intrapartum and perinatal outcomes.

Risk ratios and 95% confidence intervals were calculated and pooled for analysis. Where possible, analyses were stratified by type of phosphodiesterase-5 inhibitors and i early onset fetal growth restriction may increase the risk of persistent pulmonary hypertension of the newborn and neonatal death.In the United States, it is estimated that 1% to 4% of pregnant women are infected with hepatitis C virus, which carries approximately a 5% risk of transmission from mother to infant. Hepatitis C virus can be transmitted to the infant in utero or during the peripartum period, and infection during pregnancy is associated with an increased risk of adverse fetal outcomes, including fetal growth restriction and low birthweight. The purpose of this document is to discuss the current evidence, provide updated recommendations regarding screening, review treatment, and address management of hepatitis C virus during pregnancy. The following are the Society for Maternal-Fetal Medicine’s recommendations (1) We suggest that third trimester assessment of fetal growth may be performed, but antenatal testing is not indicated in the setting of hepatitis C virus diagnosis alone (GRADE 2C); (2) we suggest screening for viral hepatitis in patients with a diagnosis of intrahepatic cholestasis of pregnancy at an early gestational age or with high levels of bile acids (GRADE 2C); (3) we recommend that obstetrical providers screen all pregnant patients for hepatitis C virus by testing for anti-hepatitis C virus antibodies in every pregnancy (GRADE 1B); (4) we suggest that obstetrical care providers screen hepatitis C virus-positive pregnant patients for other sexually transmitted infections (if not done previously), including human immunodeficiency virus, syphilis, gonorrhea, chlamydia, and hepatitis B virus (GRADE 2C); (5) we recommend vaccination against hepatitis A and B viruses (if not immune) for patients with hepatitis C virus (GRADE 1B); (6) we recommend that direct-acting antiviral regimens only be initiated in the setting of a clinical trial during pregnancy and that people who become pregnant while taking a direct-acting antiviral should be counseled in a shared decision-making framework about the risks and benefits of continuation (GRADE 1C); (7) we suggest that if prenatal diagnostic testing is requested, patients are counseled that data regarding the risk of vertical transmission are reassuring but limited (GRADE 2C); (8) we recommend against cesarean delivery solely for the indication of hepatitis C virus (GRADE 1B); (9) we suggest that obstetrical care providers avoid internal fetal monitors and early artificial rupture of membranes when managing labor in patients with hepatitis C virus unless necessary in the course of management (ie, when unable to trace the fetal heart rate with external monitors and the alternative is proceeding with cesarean delivery) (GRADE 2B); (10) we recommend that hepatitis C virus status not alter standard breastfeeding counseling and recommendations unless nipples are cracked or bleeding (GRADE 1A).