RESUMEN
The mechanisms underlying autophagic defects in nonalcoholic steatohepatitis (NASH) remain largely unknown. We aimed to elucidate the roles of hepatic cyclooxygenase 1 (COX1) in autophagy and the pathogenesis of diet-induced steatohepatitis in mice. Human nonalcoholic fatty liver disease (NAFLD) liver samples were used to examine the protein expression of COX1 and the level of autophagy. Cox1Δhepa mice and their wildtype littermates were generated and fed with 3 different NASH models. We found that hepatic COX1 expression was increased in patients with NASH and diet-induced NASH mice models accompanied by impaired autophagy. COX1 was required for basal autophagy in hepatocytes and liver specific COX1 deletion exacerbated steatohepatitis by inhibiting autophagy. Mechanistically, COX1 directly interacted with WD repeat domain, phosphoinositide interacting 2 (WIPI2), which was crucial for autophagosome maturation. Adeno-associated virus (AAV)-mediated rescue of WIPI2 reversed the impaired autophagic flux and improved NASH phenotypes in Cox1Δhepa mice, indicating that COX1 deletion-mediated steatohepatitis was partially dependent on WIPI2-mediated autophagy. In conclusion, we demonstrated a novel role of COX1 in hepatic autophagy that protected against NASH by interacting with WIPI2. Targeting the COX1-WIPI2 axis may be a novel therapeutic strategy for NASH.
RESUMEN
Objective To investigate the prevalence of musculoskeletal disorders (MSD) in dentists and to analyze the risk factors of MSD to provide suggestions for preventing and reducing MSD in dentists. Methods Through stratified cluster random sampling, 373 dentists were selected from one Hospital of Stomatolagy and five general hospitals among Three-A hospitals in Wuhan as the research objects. The prevalence of MSD was surveyed using the Nordic musculoskeletal disorders standard questionnaire (NMQ) and Numerical Rating Scale (NRS) of pain measurement, and the risk factors of MSD was analyzed with binary Logistic regression. Results The total MSD annual prevalence rate of dentists was 93.3%, with a prevalence rate in neck, shoulder and back, waist and wrist at 78.3%, 70.0%, 56.0% and 36.2% respectively. Through Binary Logistic regression analysis, it was found that the risk factors associated with neck MSD were work fatigue（χ2=24.00，P=0.000）, neck hunching（χ2=23.55，P=0.000）, and shoulder side lift（χ2=24.52，P=0.000）. The risk factors associated with MSD in shoulder and back were work fatigue（χ2=34.64，P=0.000）, neck twisting（χ2=21.68，P=0.000） and wrist bending（χ2=45.87，P=0.000）. The risk factors associated with waist MSD were age（χ2=29.83，P=0.000）, majors（χ2=16.68，P=0.028）, work fatigue（χ2=21.08，P=0.000）, waist bending（χ2=22.88，P=0.000）. The risk factors associated with wrist MSD were gender（χ2=4.17，P=0.041）, majors（χ2=23.47，P=0.001）, working years（χ2=11.63，P=0.009）, physical activities（χ2=9.14，P=0.028）, number of patient visits per day（χ2=18.41，P=0.000）, bending and twisting（χ2=24.12，P=0.000）, wrist twisting（χ2=34.41，P=0.000）, and prevalence of microscope using（χ2=12.09，P=0.020）, while physical exercise was a protective factor for wrist MSD.The differences of the above-mentioned risk factors were statistically significant (P<0.05). Conclusion The prevalence of MSD in dentists is relatively high, and hospital management should strengthen organizational training to help dentists to realize the importance of adopting correct operating posture, a 5-minute breaks during work, prevent MSD at an early stage.