Can inspiratory muscle training benefit patients with COVID-19? A systematic review and meta-analysis.

The possible benefits of inspiratory muscle training (IMT) on mechanical and clinical outcomes in patients with Coronavirus disease-2019 (COVID-19) remain controversial. We conducted a meta-analysis to evaluate the effect of IMT in the rehabilitation strategy of patients with COVID-19. The Pubmed, Embase, Web of Science (WOS), and Cochrane Central Register of Controlled Trials (CENTRAL) were searched to identify trials evaluating the efficacy of IMT in the treatment of patients with COVID-19. The primary outcome included change from baseline of VO2 max, maximal inspiratory pressure (PImax), 6-min walk test(6MWT), forced expiratory volume in the first second predicted (FEV1%pred), and quality of life (QOL). Six studies with 349 participants were analyzed. Significant improvements were found in change from baseline of VO2 max (MD: 4.54, 95% confidence interval [CI]: 1.79-7.30, Z = 3. 32, I2 = 0, p = 0.001), PImax (MD: 21.43, 95% CI: 1.33-41.52, Z = 2.09, I2 = 90%, p = 0.04), 6MWD (MD: 40.13, 95% CI: 24.92-55.35, Z = 5.17, I2 = 0, p < 0.00001) and FEV1%pred (MD: 8.73, 95% CI 3.07-14.39, Z = 3.02, p = 0.002) while no statistical improvements were found in QOL (SMD: 0.70, 95% CI: 0.37-1.03, Z = 4.15, I2 = 89% p = 0.32) between IMT group and control group. The application of IMT might elicit mechanical and clinical improvement in patients with COVID-19. IMT could be recommended as an effective strategy of pulmonary rehabilitation for COVID-19. However, the proper timing, optimal duration, as well as appropriate frequency and intensity of IMT remain uncertain and further studies are needed.

Pinoresinol diglucoside (PDG) attenuates cardiac hypertrophy via AKT/mTOR/NF-κB signaling in pressure overload-induced rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Pinoresinol diglucoside (PDG), the active compound extracted from Eucommia ulmoides, Styrax sp. and Forsythia suspensa, plays the roles in regulating hypertension, inflammation and oxidative stress. AIMS: Considering that hypertension and inflammation has been proved to contribute to cardiac remodeling, we tested the effects of PDG on cardiac hypertrophy (CM). METHODS: Male Sprague Dawley (SD) rats were used to construct hypertrophic rats by partial abdominal aortic constriction (AAC)-surgery. PDG solution (2 mg/ml) was used to treat AAC-induced rats by intraperitoneal injection at low dose (L-PDG, 2.5 mg/kg per day), medium dose (M-PDG, 5 mg/kg per day), and high dose (H-PDG, 7.5 mg/kg per day) for 3 weeks post AAC-surgery. CM was evaluated by the ratio of left ventricular weight to body weight ratio (LVW/BW), left ventricular wall thickness by H&E staining, and collagen content deposit by Masson's staining. Further, isoproterenol (ISO) and phenylephrine (PE) were used to produce cellular models of CM in neonatal rat ventricular cardiomyocytes (NRVMs). PDG pre-treated NRVMs 2 h at low dose (L-PDG, 2.5 µg/ml), medium dose (M-PDG, 5 µg/ml), and high dose (H-PDG, 7.5 µg/ml) for 24 h with or without PE- and ISO-stimulation. CM was evaluated by the expressions of hypertrophic biomarkers. Next, the hypertrophic biomarkers and pro-inflammatory cytokines were measured using quantitative real-time PCR (qRT-PCR), the expressions of protein kinase B (AKT)/mammalian target of rapamycin (mTOR)/transcription factor nuclear factor-kappa B (NF-kB) signaling pathway were determined by Western blotting. RESULTS: PDG treatment prevented cardiac histomorphology damages, decreased upregulations of hypertrophic biomarkers, and prevented fibrosis and inflammation after pressure overload resulting from AAC-surgery. Consistently, PDG remarkably inhibited the changes of cardiomyocyte hypertrophic biomarkers and inflammatory responses in cellular models of CM. Interestingly, PDG administration inhibited the activation of AKT/mTOR/NF-kB signaling pathway both in vivo and in vitro. CONCLUSIONS: PDG prevents AAC-induced CM in vivo, PE- and ISO-induced CM in vitro. The AKT/mTOR/NF-kB signaling pathway could be the potential therapeutic target involved in the protection of PDG. These findings provide novel evidence that PDG might be a promising therapeutic strategy for CM.