We investigated the cardioprotective effect of melatonin (Mel) and exendin-4 (Ex4) treatment in a rat model of cardiorenal syndrome (CRS). Adult male SD rats (n=48) were randomly and equally divided into sham control (SC), dilated cardiomyopathy (DCM) (doxorubicin 7 mg/kg i.p. every five days/4 doses), CRS (defined as DCM+CKD) only, CRS-Mel (20 mg/kg/d), CRS-Ex4 (10 μg/kg/d), and CRS-Mel-Ex4 groups. In vitro results showed protein expressions of oxidative stress (NOX-1/NOX-2/oxidized protein), DNA/mitochondrial damage (γ-H2AX/cytosolic cytochrome c), apoptosis (cleaved caspase-3/PARP), and senescence (β-galactosidase cells) biomarkers were upregulated, whereas mitochondrial ATP level was decreased in doxorubicin/p-cresol-treated H9c2 cells that were revised by Mel and Ex4 treatments (all P<.001). By day 60, LVEF was highest in the SC and lowest in the CRS, significantly lower in the DCM than in other treatment groups, lower in the CRS-Mel and CRS-Ex4 than in the CRS-Mel-Ex4, and lower in the CRS-Mel than in the CRS-Ex4, whereas LV chamber size and histopathology score showed a pattern opposite to that of LVEF among all groups (all P<.001). Plasma creatinine level was highest in the CRS and lowest in the SC and progressively decreased from the CRS-Mel, CRS-Ex4, CRS-Mel-Ex4 to DCM (P<.0001). Protein expressions of inflammation (TNF-α/NF-κB/MMP-2/MMP-9/IL-1β), apoptosis/DNA damage (Bax/c-caspase-3/c-PARP/γ-H2AX), fibrosis (Smad3/TGF-β), oxidative stress (NOX-1/NOX-2/NOX-4/oxidized protein), cardiac hypertrophy/pressure overload (BNP/β-MHC), and cardiac integrity (Cx43/α-MHC) biomarkers in LV myocardium showed an opposite pattern compared to that of LVEF among all groups (all P<.001). Fibrotic area, DNA damage (γ-H2AX /53BP1 CD90 /XRCC1 CD90 ), and inflammation (CD14 /CD68 ) biomarkers in LV myocardium displayed a pattern opposite to that of LVEF among all groups (all P<.001). Combined melatonin and exendin-4 treatment suppressed CRS-induced deterioration of LVEF and LV remodeling.
This study tested the hypothesis that xenogeneic human umbilical cord-derived mesenchymal stem cell (HUCDMSC) therapy would improve survival rates in rats with acute respiratory distress-syndrome (ARDS, induction by 48 h inhalation of 100% oxygen) and sepsis-syndrome (SS, induction by cecal-ligation and puncture) (ARDS-SS). Adult-male Sprague-Dawley rats were categorized into group 1 (sham-controls), group 2 (ARDS-SS), group 3 [ARDS-SS+HUCDMSC (1.2 ×106 cells administered 1 h after SS-induction)], and group 4 [ARDS-SS+HUCDMSC (1.2 ×106 cells administered 24 h after SS-induction)]. The mortality rate was higher in groups 2 and 4 than in groups 1 and 3 (all p<0.0001). The blood pressure after 28 h was lower in groups 2, 3 and 4 (p<0.0001) than in group 1. Albumin levels and percentages of inflammatory cells in broncho-alveolar lavage fluid, and the percentages of inflammatory and immune cells in circulation, were lowest in group 1, highest in group 2, and higher in group 3 than group 4 (all p<0.0001). The percentages of inflammatory cells in ascites and kidney parenchyma showed identical patterns, as did kidney injury scores (all p<0.0001). EarlyHUCDMSC therapy reduced rodent mortality after induced ARDS-SS.
Objective: To compare the postoperative outcomes of inspiratory muscle training and aerobic exercise, along with standard care, on lung cancer patients undergoing video-assisted thoracoscopic surgery (VATS). Design: A parallel-group, single-blind randomized clinical trial Setting: Thoracic surgery ward and outpatient clinic in a teaching hospital Subjects: Overall 63 patients underwent VATS were randomly assigned to a triaging (TG, n = 32) or control group (CG, n = 31). A total of 54 patients (TG, n = 26; CG, n = 28) completed the study. Intervention: TG: six-week threshold inspiratory muscle training and aerobic exercise. CG: standard care. Main measures: Maximum inspiratory pressure (PImax), maximum expiratory pressure (PEmax) lung expansion volume, and 6-min walking test (6MWT) were performed on the day of chest tube removal (baseline), and 2, 6, and 12 weeks postoperatively. Results: The TG showed significant improvement in PImax at week 6 (71.6 ± 34.9 vs. 94.3 ± 32.8 cmH2O, P = 0.018), PEmax at week 2 (70.9 ± 24.3 vs. 90.9 ± 28.2 cmH2O, P = 0.015) and week 12 (76.1 ± 20.2 vs. 98.6 ± 35.3 cmH2O, P = 0.012), the lung expansion volume at week 2 (1080 ± 433 vs 1457 ± 624 mL, P = 0.02) and week 12 (1200 ± 387 vs 1885 ± 678 mL, P < 0.001), in addition to the 6MWT at week 2 (332 ± 78 vs 412 ± 74 m, P = 0.002), week 6 (360 ± 70 vs 419 ± 60 m, P = 0.007) and week 12 (360 ± 58 vs 402 ± 65 m, P = 0.036). Conclusion: A six weeks of inspiratory muscle training and aerobic exercise had improved respiratory muscle strength and aerobic exercise postoperatively in lung cancer patients after VATS as early as 2 weeks.
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