Osteoarthritis, as a degenerative disease, is a common problem and results in high socioeconomic costs and rates of disability. The most commonly affected joint is the knee and characterized by progressive destruction of articular cartilage, loss of extracellular matrix, and progressive inflammation. Mesenchymal stromal cell (MSC)-based therapy has been explored as a new regenerative treatment for knee osteoarthritis in recent years. However, the detailed functions of MSC-based therapy and related mechanism, especially of cartilage regeneration, have not been explained. Hence, this review summarized how to choose, authenticate, and culture different origins of MSCs and derived exosomes. Moreover, clinical application and the latest mechanistical findings of MSC-based therapy in cartilage regeneration were also demonstrated.
BackgroundCurrent guidelines emphasize an active lifestyle in the management of knee osteoarthritis (OA), but up to 90% of patients with OA are inactive. In a previous study, we demonstrated that an 8-week physiotherapist (PT)-led counseling intervention, with the use of a Fitbit, improved step count and quality of life in patients with knee OA, compared with a control.ObjectiveThis study aimed to examine the effect of a 12-week, multifaceted wearable-based program on physical activity and patient outcomes in patients with knee OA.MethodsThis was a randomized controlled trial with a delay-control design. The immediate group (IG) received group education, a Fitbit, access to FitViz (a Fitbit-compatible app), and 4 biweekly phone calls from a PT over 8 weeks. Participants then continued using Fitbit and FitViz independently up to week 12. The delay group (DG) received a monthly electronic newsletter in weeks 1 to 12 and started the same intervention in week 14. Participants were assessed in weeks 13, 26, and 39. The primary outcome was time spent in daily moderate-to-vigorous physical activity (MVPA; in bouts ≥10 min) measured with a SenseWear Mini. Secondary outcomes included daily steps, time spent in purposeful activity and sedentary behavior, Knee Injury and OA Outcome Score, Patient Health Questionnaire-9, Partners in Health Scale, Theory of Planned Behavior Questionnaire, and Self-Reported Habit Index.ResultsWe enrolled 51 participants (IG: n=26 and DG: n=25). Compared with the IG, the DG accumulated significantly more MVPA time at baseline. The adjusted mean difference in MVPA was 13.1 min per day (95% CI 1.6 to 24.5). A significant effect was also found in the adjusted mean difference in perceived sitting habit at work (0.7; 95% CI 0.2 to 1.2) and during leisure activities (0.7; 95% CI 0.2 to 1.2). No significant effect was found in the remaining secondary outcomes.ConclusionsA 12-week multifaceted program with the use of a wearable device, an app, and PT counseling improved physical activity in people with knee OA.Trial RegistrationClinicalTrials.gov NCT02585323; https://clinicaltrials.gov/ct2/show/NCT02585323
The methylcitrate cycle metabolizes propionyl-CoA, a toxic metabolite, into pyruvate. Pyricularia oryzae (syn. Magnaporthe oryzae) is a phytopathogenic fungus that causes a destructive blast disease in rice and wheat. We characterized the essential roles of the methylcitrate cycle in the development and virulence of P. oryzae using functional genomics. In P. oryzae, the transcript levels of MCS1 and MCL1, which encode a 2-methylcitrate synthase and a 2-methylisocitrate lyase, respectively, were upregulated during appressorium formation and when grown on propionyl-CoA-producing carbon sources. We found that deletion of MCS1 and MCL1 inhibited fungal growth on media containing both glucose and propionate, and media using propionate or propionyl-CoA-producing amino acids (valine, isoleucine, methionine, and threonine) as the sole carbon or nitrogen sources. The Δmcs1 mutant formed sparse aerial hyphae and did not produce conidia on complete medium (CM), while the Δmcl1 mutant showed decreased conidiation. The aerial mycelium of Δmcs1 displayed a lowered NAD+/NADH ratio, reduced nitric oxide content, and downregulated transcription of hydrophobin genes. Δmcl1 showed reduced appressorium turgor, severely delayed plant penetration, and weakened virulence. Addition of acetate recovered the growth of the wild type and Δmcs1 on medium containing both glucose and propionate and recovered the conidiation of both Δmcs1 and Δmcl1 on CM by reducing propionyl-CoA formation. Deletion of MCL1 together with ICL1, an isocitrate lyase gene in the glyoxylate cycle, greatly reduced the mutant’s virulence as compared with the single-gene deletion mutants (Δicl1 and Δmcl1). This experimental evidence provides important information about the role of the methylcitrate cycle in development and virulence of P. oryzae by detoxification of propionyl-CoA and 2-methylisocitrate.
Objective
FibroTouch is a newly developed device to assess ultrasound attenuation parameter (UAP) and liver stiffness measurement to quantify hepatic steatosis and fibrosis, respectively. However, there is currently a lack of defined thresholds of UAP to diagnose different stages of hepatic steatosis. We aimed to assess the optimal thresholds of UAP for hepatic steatosis in individuals with biopsy-proven fatty liver disease (FLD).
Methods
We enrolled 497 adults with FLD undergoing FibroTouch and liver biopsy. Area under the receiver operating characteristic curve (AUROC) was performed to calculate the performance of UAP in staging hepatic steatosis. Hepatic steatosis >33% was defined as significant steatosis. We determined the optimal cutoff values of UAP and the sensitivity or specificity higher than 90%. Sensitivity, specificity, positive predictive value and negative predictive value were subsequently calculated.
Results
The median UAP for the enrolled patients was 308 dB/m. Multivariable logistic regression analysis showed that UAP was associated with significant steatosis [adjusted-odds ratio 1.05, 95% confidence interval (CI), 1.02–1.09; P = 0.001]. The AUROCs for S ≥ 1, S ≥ 2 and S = 3 were 0.88 (95% CI, 0.84–0.91), 0.77 (95% CI, 0.73–0.81), and 0.70 (95% CI, 0.63–0.77), respectively. The optimal UAP cutoffs were 295 dB/m for S ≥ 1, 314 dB/m for S ≥ 2, and 324 dB/m for S = 3. Almost identical results were observed in the subgroup of patients with biopsy-confirmed nonalcoholic fatty liver disease (n = 435).
Conclusion
We found that the AUROC values of UAP by FibroTouch were ranging from 0.70 to 0.88 for assessing hepatic steatosis severity. These UAP cutoffs could be applicable for clinical use.
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