Increased flux through the mevalonate pathway mediates fibrotic repair without injury
Macrophages are important in mounting an innate immune response to injury as well as in repair of injury. Gene expression of Rho proteins is known to be increased in fibrotic models; however, the role of these proteins in idiopathic pulmonary fibrosis (IPF) is not known. Here, we show that BAL cells from patients with IPF have a profibrotic phenotype secondary to increased activation of the small GTPase Rac1. Rac1 activation requires a posttranslational modification, geranylgeranylation, of the C-terminal cysteine residue. We found that by supplying more substrate for geranylgeranylation, Rac1 activation was substantially increased, resulting in profibrotic polarization by increasing flux through the mevalonate pathway. The increased flux was secondary to greater levels of acetyl-CoA from metabolic reprogramming to β oxidation. The polarization mediated fibrotic repair in the absence of injury by enhancing macrophage/fibroblast signaling. These observations suggest that targeting the mevalonate pathway may abrogate the role of macrophages in dysregulated fibrotic repair.
CONCLUSION: The etiology of chronic groin pain post hernia repair is related in part to nerve injury. This is supported by the high frequency of sensory symptoms and numbness in these patients. However other factors including the role of tissue injury and inflammatory postoperative changes need to be considered. KEY WORDS: Chronic postoperative pain, Inguinal hernia repair, Open surgery, Laparoscopic surgery. PMID: 31719216 [PubMed - as supplied by publisher]
Abstract Regulatory T cells (Tregs) are important for limiting inflammation-dependent damage in neural tissue. However, Tregs have also been shown to inhibit neural repair associated with type 2 (anti-inflammatory/wound healing) immune responses. Recently, it was demonstrated that Sirtuins, a family of proteins that contribute to the control of cellular responses to metabolic stimuli, influence the functions of Tregs. Specifically, SIRT4 was found to suppress the anti-neuroinflammatory activity of Tregs infiltrating the spinal cord following injury; when SIRT4 expression was genetically suppressed, Tregs made more...
This study offers a great potential for ECL as an alternative safer radiosensitizer for increasing the RT efficiency against NSCLC. PMID: 31727206 [PubMed - as supplied by publisher]
So I have abandoned most of my hopes of garnering any MD interviews. I don't care MD or DO for the most part past the realities of the Advantages career-wise of one over the other I just want to be a doctor. I submitted in mid to late August and haven't heard anything from 22 schools except for three rejections pre II with a Goro Fata school list. I am a non-trad reinvention student with solid ECS a disaster of a transcript (F's (3) w's (20) before my DIY transcript repair of 70 credits at a... How long after DO sumbmission on average should you expect to get a notification as an outlier?
CONCLUSIONS: Precise information of the characteristics, morphometric data and coordinates of attachment sites of SPR are essential for surgical procedures and reconstruction. PMID: 31724148 [PubMed - as supplied by publisher]
Publication date: Available online 16 November 2019Source: Orthopaedics &Traumatology: Surgery &ResearchAuthor(s): Christophe Mathoulin, Mathilde GrasAbstractScapholunate ligament tear is most frequently encountered in the aftermath of trauma in supination and extension of the wrist. It generates chronic instability, leading to osteoarthritis. It may be associated with fracture of the distal epiphysis of the radius or of the scaphoid. These lesions are often difficult to diagnose, especially in early stages. Treatment of chronic scapholunate ligament lesions before onset of osteoarthritis is a challenge for the sur...
This article describes the relevant anatomy, biomechanics, and classification system, and provides an up-to-date literature-based review of treatment options, including acute repair and various reconstruction techniques. It also helps guide surgeons in making decisions regarding a systematic treatment algorithm for these injuries.
Successful closure of gastrointestinal defects is one of the most important goals for therapeutic endoscopy. Historically, surgical repair was the mainstay of treatment for any gastrointestinal defect; however, surgery is associated with high morbidity and mortality. Endoscopic management of gastrointestinal defects has developed rapidly in recent years and has become more effective, reducing the morbidity and mortality rates, and avoiding surgical interventions. Appropriate use of endoscopic techniques requires extensive knowledge of the devices and their advantages and limitations during practical applications.
The objective of this study was to test the hypothesis that comorbid type 2 immune diseases confer protection against morbidity and mortality due to acute infection. Design: Retrospective cohort study of patients hospitalized with an acute infection between November 2008 and January 2016 using electronic health record data. Setting: Single tertiary-care academic medical center. Patients: Admissions to the hospital through the emergency department with likely infection at the time of admission who may or may not have had a type 2 immune-mediated disease, defined as asthma, allergic rhinitis, atopic dermatitis, or f...
This study contributes to a better understanding of the IL-4/13A system in salmon, which as a key axis for Th2 response may be involved not only in pathogen elimination but also in adaptive immune repair that seems critical tolerance to infectious diseases.