Sepsis often causes diaphragm contractile dysfunction. Endoplasmic reticulum (ER) stress has been implicated in muscle contractile dysfunction. However, it remains unknown if ER stress occurs in the diaphragm during sepsis. In the present study, rats were divided into 4 groups and received placebo or one of three durations of endotoxin treatment (24, 48 h and 7 days). Isometric contractile force of the diaphragm was measured and lung wet-to-dry ratio (W/D) was calculated. Hematoxylin and eosin (H&E) staining of lung tissue was performed and electron microscopy assessed ER damage in the diaphragm during sepsis. The mRNA and protein expression of glucose‑regulated protein 78 kDa (GRP78), glucose-regulated protein 94 kDa (GRP94), C/EBP homologous protein (CHOP), endoplasmic reticulum protein 44 (ERP44), protein disulfide-isomerase like protein (ERP57) and protein disulfide isomerase family A member 4 (ERP72) in diaphragm muscles were measured using reverse transcription‑quantitative polymerase chain reaction and western blot analysis. The level of cleaved caspase-12 was analyzed by western blot analysis. The results demonstrated that sepsis increased lung W/D. H&E staining revealed that sepsis caused alveolar congestion, hemorrhage and rupture. Swollen and distended ER was observed using electron microscopy during sepsis and decreased diaphragm contractile function was also observed. The expression levels of ER stress markers (GRP78, GRP94, CHOP, ERP44, ERP57 and ERP72) and the level of cleaved caspase‑12 were significantly elevated in septic rats compared with control rats, particularly in the 48 h group. In conclusion, the present study indicated that weakened diaphragm contraction and damaged ER in septic rats was associated with increased expression of ER stress markers.

Weakened diaphragm contraction in the septic rats was associated with reduced mRNA and protein expression of DHPRα1s and RyR1, the isoforms of skeletal muscles.

Information on the interactive effects of methylprednisolone, controlled mechanical ventilation (CMV), and assisted mechanical ventilation (AMV) on diaphragm function is sparse. Sedated rabbits received 2 days of CMV, AMV, and spontaneous breathing (SB), with either methylprednisolone (MP; 60 mg/kg/day intravenously) or saline. There was also a control group. In vitro diaphragm force, myofibril ultrastructure, αII-spectrin proteins, insulin-like growth factor-1 (IGF-1), and muscle atrophy F-box (MAF-box) mRNA were measured. Maximal tetanic tension (P(o)) decreased significantly with CMV. Combined MP plus CMV did not decrease P(o) further. With AMV, P(o) was similar to SB and controls. Combined MP plus AMV or MP plus SB decreased P(o) substantially. Combined MP plus CMV, MP plus AMV, or MP plus SB induced myofibrillar disruption that correlated with the reduced P(o). αII-spectrin increased, IGF-1 decreased, and MAF-box mRNA increased in both the CMV group and MP plus CMV group. Short-term, high-dose MP had no additive effects on CMV-induced diaphragm dysfunction. Combined MP plus AMV impaired diaphragm function, but AMV alone did not. We found that acute, high-dose MP produces diaphragm dysfunction depending on the mode of mechanical ventilation.

1. Paraquat (PQ) is an organic nitrogen heterocyclic herbicide that is widely used in agriculture throughout the world. Numerous studies have reported PQ intoxication on humans. 2. In this study, we established a rat lung injury model induced by PQ and evaluated the intervention effect of rapamycin on the model, exploring the pathogenesis of PQ on lung injury as well as therapeutic effects of rapamycin on PQ-induced lung injury. 3. A rat lung injury model was established by gavage of PQ, and rapamycin was used to treat the model animals with PQ-induced lung injury. Different physiological indices were measured through Western blot and real-time polymerase chain reaction to evaluate the effect of rapamycin on the PQ-induced lung injury. 4. The analyses showed that application of rapamycin could significantly reduce the lung injury damage caused by PQ, with lung tissue wet-dry weight ratio, pathological features, compositions in serum, protein in bronchoalveolar lavage fluid and other indices being significantly improved after the injection of rapamycin. 5. It was inferred that the use of rapamycin could improve the PQ-induced lung injury through inhibiting the activity of mTOR. And we expected the use of rapamycin to be a potential treatment method for the PQ intoxication in future.

Drug combination therapies are common practice in the treatment of cancer. Cisplatin is the most active chemotherapeutic agent for lung cancer treatment. Osthole is a natural compound extracted from a number of medicinal plants. To determine whether osthole enhances the anticancer effect of cisplatin in human lung cancer, we treated NCI-H460 cells with osthole alone or in combination with cisplatin and evaluated cell growth and apoptosis using 3-(4,5-dimethyl thiazol-2yl)-2,5-diphenyltetrazolium bromide (MTT) assay, flow cytometry and fluorescence microscopy. The results showed that, in comparison with single agent treatment, the combination of osthole and cisplatin resulted in greater efficacy in growth inhibition and apoptosis induction. Western blot analysis revealed that the combination effect of osthole and cisplatin was due to regulation of the Bcl-2 family proteins. Findings of this investigation suggested that osthole combined with cisplatin is a potential clinical chemotherapeutic approach in human lung cancer.