The transversus abdominis plane block may reduce chronic postoperative pain one year after TAPP ingunial hernia repair.

INTRODUCTION: Chronic postoperative inguinal pain (CPIP) is defined as pain impacting daily activities lasting at least 3 months. With an incidence of 0.5-6.0%, chronic pain affects many patients who underwent inguinal hernia repair (IHR). Early severe postoperative pain has been described as a risk factor for CPIP. Thus, we aim to investigate the impact of the transversus abdominis plane (TAP) block on CPIP. METHODS: From 2013 to 2019 we collected data from individuals who were operated on electively in TAPP technique and who received a preoperative TAP block. RESULTS: Data from 289 patients were selected. 259 patients were male. The mean age was 59.93 years and the mean BMI was 25.72 kg/m2. 252 patients suffered from a primary inguinal hernia. No mesh fixation was conducted. 21 patients reported pain at rest, 26 pain under physical exertion and 13 patients required treatment of their pain. In 6.25% of cases patients reported CPIP. We compared our findings with data from the German Herniamed Registry (unilateral, primary IH, men, no mesh fixation; n = 8.799), because we assume that the majority of these patients did not receive a TAP block. The rate of pain under physical exertion (9.2% vs. 10.05%) and pain requiring treatment (2.45% vs. 2.95%) one year after surgery slightly differs without a statistical significance. CONCLUSIONS: We assume that the TAP block may reduce CPIP, postoperative pain during physical exertion and pain requiring treatment following IHR in TAPP technique. Additional randomized clinical trials are mandatory to evaluate the hypothesis.

O-GlcNAc transferase/host cell factor C1 complex regulates gluconeogenesis by modulating PGC-1α stability.

A major cause of hyperglycemia in diabetic patients is inappropriate hepatic gluconeogenesis. PGC-1α is a master regulator of gluconeogenesis, and its activity is controlled by various posttranslational modifications. A small portion of glucose metabolizes through the hexosamine biosynthetic pathway, which leads to O-linked ß-N-acetylglucosamine (O-GlcNAc) modification of cytoplasmic and nuclear proteins. Using a proteomic approach, we identified a broad variety of proteins associated with O-GlcNAc transferase (OGT), among which host cell factor C1 (HCF-1) is highly abundant. HCF-1 recruits OGT to O-GlcNAcylate PGC-1α, and O-GlcNAcylation facilitates the binding of the deubiquitinase BAP1, thus protecting PGC-1α from degradation and promoting gluconeogenesis. Glucose availability modulates gluconeogenesis through the regulation of PGC-1α O-GlcNAcylation and stability by the OGT/HCF-1 complex. Hepatic knockdown of OGT and HCF-1 improves glucose homeostasis in diabetic mice. These findings define the OGT/HCF-1 complex as a glucose sensor and key regulator of gluconeogenesis, shedding light on new strategies for treating diabetes.

O-GlcNAc transferase is involved in glucocorticoid receptor-mediated transrepression.

Recruitment of O-GlcNAc transferase (OGT) to promoters plays an important role in gene repression. Glucocorticoid signaling represses the transcriptional activities of NF-κB and AP-1 through direct binding, yet the molecular mechanisms remain to be elucidated. Here we report that OGT is an important component of GR-mediated transrepression. OGT associates with ligand-bound GR in a multi-protein repression complex. Overexpression of OGT potentiates the GR transrepression pathway, whereas depletion of endogenous OGT by RNA interference abolishes the repression. The recruitment of OGT by GR leads to increased O-GlcNAcylation and decreased phosphorylation of RNA polymerase II on target genes. Functionally, overexpression of OGT enhances glucocorticoid-induced apoptosis in resistant cell lines while knockdown of OGT prevents sensitive cell lines from apoptosis. These studies identify a molecular mechanism of GR transrepression, and highlight the function of O-GlcNAc in hormone signaling.