What Is the Impact of Bariatric Surgery on Erectile Function? A Systematic Review and Meta-Analysis.

INTRODUCTION: Obesity is a worldwide public health issue that has severe psychological and social implications. Erectile dysfunction also is a prevalent clinical situation, and obesity is one of the primary risk factors for its development. AIM: To determine whether bariatric surgery can lessen erectile dysfunction in obese men because of evidence showing that weight loss in obese men contributes to decreasing erectile dysfunction and bariatric surgery contributes to significant weight loss. METHODS: A search was conducted using Medline, LILACS, Cochrane, Scopus, CINAHL, Embase, Web of Science, Eric, and EBM up to April 13, 2016. The authors selected by title, abstract, and full text. Scottish Intercollegiate Guidelines Network checklists were used for comparative studies to show the limitations and biases of each article. RevMan 5.3 software from the Cochrane Library was used for meta-analyses. Results were demonstrated with forest plots. MAIN OUTCOME MEASURES: The outcome selected was resolution of erectile dysfunction, which was analyzed by improvement in the International Index of Erectile Function (IIEF) score. RESULTS: Of 185 articles analyzed, 7 were selected for systematic review. Meta-analysis of two articles that evaluated erectile function showed a 5.66-point increase in the five-item IIEF score of patients who underwent bariatric surgery (95% CI = 7.88-3.45, I2 = 35%, P < .00001), demonstrating statistical significance. Meta-analysis of three articles showed a 4.10-point increase in the IIEF erectile function score of patients who underwent bariatric surgery (95% CI = 6.10-2.10, I2 = 0%, P < .0001), demonstrating statistical significance. CONCLUSION: Bariatric surgery leads to an improvement of erectile function. Glina FPI, de Freitas Barboza JW, Nunes VM, et al. What Is the Impact of Bariatric Surgery on Erectile Function? A Systematic Review and Meta-Analysis. Sex Med Rev 2017;5:393-402.

The adaptor-related protein complex 2, alpha 2 subunit (AP2α2) gene is a peroxisome proliferator-activated receptor cardiac target gene.

A peroxisome proliferator-actived receptor (PPAR) response element (RE) in the promoter region of the adaptor-related protein complex 2, alpha 2 subunit (AP2α2) of mouse heart has been identified. The steroid hormone nuclear PPARs and the retinoid X receptors (RXRs) are important transcriptional factors that regulate gene expression, cell differentiation and lipid metabolism. They form homo- (RXR) and hetero- (PPAR-RXR) dimers that bind DNA at various REs. The AP2α2 gene is part of complex and process that transports lipids and proteins from the plasma membrane to the endosomal system. A PPAR activator (Wy14643) and DMSO (vehicle) was introduced into control and δ337T thyroid hormone receptor (TRß1) transgenic mice. Heart tissue was extracted and AP2α2 gene expression was compared using Affymetrix expression arrays and qRT PCR among four groups [control, control with Wy14643, δ337T TRß1 and δ337T TRß1 with Wy14643]. The gene expression of AP2α2 in the Wy14643 control and transgenic mouse groups was significantly up regulated over the vehicle mouse groups in both the array (p < 0.01) and qRT PCR (p < 0.01) studies. Duplex oligo DNAs containing the PPAR/RXR motif (AGGTCA/TCCAGT) from the AP2α2 promoter were used in EMSA to verify binding of the PPAR and RXR receptors to their REs. pGL4.0 [Luc] constructs of the AP2α2 promoter with and without the PPAR/RXR motifs were co-transfected with mouse PPARα, ß or γ1 into HepG2 cells and used in lucerifase assays to verify gene activation. In conclusion our study revealed that PPARα regulates the mouse cardiac AP2α2 gene in both the control and transgenic mouse.

The IkappaBalpha gene is a peroxisome proliferator-activated receptor cardiac target gene.

The purpose of this study was to provide a better understanding of the regulatory role of the nuclear steroid receptor on the nuclear factor of kappa light polypeptide gene enhancer in B cells (NFkappaB) in mouse heart. NFkappaB regulates many nuclear genes and has been associated with many human cardiac diseases. NFkappaB's protein regulator gene, nuclear factor of kappa light polypeptide gene enhancer in B cells inhibitor alpha gene (IkappaBalpha), was found in this study to be regulated by peroxisome proliferator-activated receptors (PPARs). PPARs, retinoid X receptors (RXRs) and thyroid hormone receptors (THRs) are members of the nuclear receptor superfamily, which consists of a large number of transcription factors whose activities are regulated by their cognate ligands. These steroid hormone receptors are important regulators of gene expression and differentiation in the heart. These receptors form homo-(RXR, THR) and hetero-(PPAR-RXR, RXR-THR) dimers that bind DNA at various response elements (PPAR, RXR and THR) in the promoter regions of target genes. The PPAR/RXR response elements in the promoter of IkappaBalpha are described in this article. A known PPAR activator (Wy14643) and dimethylsulfoxide (vehicle) were introduced into control (FVB) and delta337T thyroid hormone receptor (TRbeta) transgenic mice. The delta337T TRbeta transgenic mouse has a resistance to the thyroid hormone (RTH) phenotype. Affymetrix 430_2 chip gene expression was examined for four study groups (control, control with Wy14643, delta337T TRbeta and delta337T TRbeta with Wy14643), consisting of seven mice each. IkappaBalpha mRNA expression in the Wy14643 control and in transgenic mice was upregulated significantly in microarray (P < 0.05) and quantitative RT-PCR (P < 0.01) analyses. The increase in mRNA level was also accompanied by an increase in IkappaBalpha protein in cells, as measured by Western blot analysis. Duplex oligo-DNAs containing the putative PPAR/RXR motif (AGGTCA/TCCAGT) from the IkappaBalpha promoter were used in gel shift assays to verify the binding of PPAR and RXR to their response elements. pGL4.0 [Luc] constructs of the IkappaBalpha promoter, with and without the PPAR/RXR motifs, were co-transfected with mouse PPAR alpha, beta and gamma(1) into HepG2 cells and used in luciferase assays to verify gene activation. In conclusion, our study revealed that PPAR regulates the mouse cardiac IkappaBalpha gene in both control and transgenic mouse heart. The implications of this finding are discussed in relation to possible changes in cardiac function.

Novel signal transducer and activator of transcription 3 (STAT3) mutations, reduced T(H)17 cell numbers, and variably defective STAT3 phosphorylation in hyper-IgE syndrome.

BACKGROUND: Hyper-IgE syndrome (HIES) is a rare, autosomal-dominant immunodeficiency characterized by eczema, Staphylococcus aureus skin abscesses, pneumonia with pneumatocele formation, Candida infections, and skeletal/connective tissue abnormalities. Recently it was shown that heterozygous signal transducer and activator of transcription 3 (STAT3) mutations cause autosomal-dominant HIES. OBJECTIVE: To determine the spectrum and functional consequences of heterozygous STAT3 mutations in a cohort of patients with HIES. METHODS: We sequenced the STAT3 gene in 38 patients with HIES (National Institutes of Health score >40 points) from 35 families, quantified T(H)17 cells in peripheral blood, and evaluated tyrosine phosphorylation of STAT3. RESULTS: Most STAT3 mutations in our cohort were in the DNA-binding domain (DBD; 22/35 families) or Src homology 2 (SH2) domain (10/35) and were missense mutations. We identified 2 intronic mutations resulting in exon skipping and in-frame deletions within the DBD. In addition, we identified 2 mutations located in the transactivation domain downstream of the SH2 domain: a 10-amino acid deletion and an amino acid substitution. In 1 patient, we were unable to identify a STAT3 mutation. T(H)17 cells were absent or low in the peripheral blood of all patients who were evaluated (n = 17). IL-6-induced STAT3-phosphorylation was consistently reduced in patients with SH2 domain mutations but comparable to normal controls in patients with mutations in the DBD. CONCLUSION: Heterozygous STAT3 mutations were identified in 34 of 35 unrelated HIES families. Patients had impaired T(H)17 cell development, and those with SH2 domain mutations had reduced STAT3 phosphorylation.