The pathogenesis of neonatal meconium aspiration syndrome (MAS) may involve inactivation of endogenous surfactant, and data from clinical pilot studies indicate that treatment with exogenous surfactant may alleviate respiratory failure in babies with MAS. We studied ventilation efficiency after treatment with a modified porcine surfactant in experimental meconium aspiration. Adult rats were anesthetized and tracheotomized, and received via a tracheal cannula from 4 to 6 ml/kg body weight of a saline suspension of human meconium (25 mg [dry weight]/ml). After 30 min of ventilation with 100% oxygen, the animals were in respiratory failure, with dynamic lung-thorax compliance < 0.5 ml/cm H2O/kg and PaO2 < 8 kPa (60 mm Hg). Animals were then allocated to: (1) immediate treatment with surfactant (200 mg/kg); (2) treatment with surfactant (200 mg/kg 3 h later; or (3) a control group not receiving surfactant. All animals were ventilated for 6 h with variable FIO2 and peak inspiratory/positive end-expiratory pressure (PIP/PEEP). In the control group, six of 12 animals died of respiratory failure with hypoxemia and acidosis despite ventilation with 100% oxygen and high mean airway pressure (> 20 cm H2O). The lungs of all animals in this group showed severe atelectasis, influx of neutrophils, edema, and hyaline membranes. In contrast, animals allocated to immediate or late surfactant treatment had lower mortality (one of seven and two of eight, respectively), a reduction of oxygen supply by 30%, and a decrease in mean airway pressure of 3 to 4 cm H2O. This was associated with a > 50% increase in static lung volume at 40 cm H2O inflation and 10 cm H2O deflation pressure and improved alveolar expansion in histologic sections. Hyaline membranes tended to be less prominent in surfactant-treated animals than in controls. We conclude that both early and late treatment with surfactant is effective in this animal model of MAS.
A novel and ten known diterpenoids were isolated from the ethanolic crude extract of the fresh tubers of Sagittaria trifolia L. Compound 11 exhibited strong inhibitory activity on Hct-116 cancer cells by blocking the NF-κB signaling pathway.
Objective
To investigate the correlative of autophagy flux and hydrogen sulfide postconditioning protecting against myocardial ischemia reperfusion (I/R) injury in type 2 diabetic rats in vivo.
Methods
Sixty adult male Sprague-Dawley rats were randomly divided into five groups (n=12): sham group, I/R group, chloroquine (CQ) group, sodium hydrosulfide (NaHS) group and CQ + NaHS group. Rats in the sham group only gave thoracotomy and separation of the left anterior descending coronary artery; In the I/R group rats were occluded the left anterior descending coronary artery for 30 min, followed by 4 h of reperfusion; In the CQ group rats received CQ 10 mg/kg by intraperitoneal injection at 1 h before the I/R operation; In the NaHS group rats were injected NaHS 0.05 mg/kg intravenously within 1 min after releasing the left anterior descending coronary artery undergoing 30 min occlusion, then followed by 4 h of reperfusion; and in the CQ + NaHS group rats received CQ 10 mg/kg by intraperitoneal injection at 1 h before the I/R operation additionally on the basis of NaHS group. The heart rate, mean arterial pressure and rate-pressure product (RPP) were detected and recorded at 15 min of balance period, ischemic period, and 1, 2, 4 h after reperfusion. After reperfusion for 4 h, the rats were sacrificed and the hearts were used to calculate the range of myocardial infarction and the express of microtubule-associated protein 1 light chain 3 (LC3), Cathepsin B, Beclin-1 and P62 were determined by Western blotting.
Results
The heart rates in the five groups had no siginficant differences at each time point (F=0.854, P=0.512), but the mean arterial pressure and RPP showed siginficant differences among the five groups at each time point (F=5.182, P=0.007; F=5.082, P=0.008). Furthermore, the mean arterial pressure[(87 ± 8) mmHg vs. (72 ± 10) mmHg, (91±10) mmHg vs. (63 ± 6) mmHg] and RPP [(35.4 ± 4.6)·103 mmHg·beat/min vs. (28.7 ± 5.8)·103 mmHg·beat/min, (36.2 ± 5.8)·103 mmHg·beat/min vs. (26.8 ± 3.8)·103 mmHg·beat/min] in the NaHS group at 2, 4 h after reperfusion were much higher than those in the I/R group (all P<0.05). The range of myocardial infarction and the express of LC3, Cathepsin B, Beclin-1 and P62 at 4 h after reperfusion all had statistical significance obviously among five groups (F=96.907, 71.164, 43.594, 57.180, 35.967, all P<0.05) , and above indicators in the NaHS group were much lower than those in the I/R group, CQ group and CQ + NaHS group (all P<0.05).
Conclusion
Hydrogen sulfide postconditioning play a protective role through repairinng autophagy flux in type 2 diabetic rats with I/R injury.
Key words:
Hydrogen sulfide; Ischemic postconditioning; Myocardial reperfusion injury; Diabetes mellitus, type 2; Autophagy; Rats
Extracellular vesicles (EVs) are important intercellular mediators regulating health and diseases. Conventional methods for EV surface marker profiling, which was based on population measurements, masked the cell-to-cell heterogeneity in the quantity and phenotypes of EV secretion. Herein, by using spatially patterned antibody barcodes, we realized multiplexed profiling of single-cell EV secretion from more than 1,000 single cells simultaneously. Applying this platform to profile human oral squamous cell carcinoma (OSCC) cell lines led to a deep understanding of previously undifferentiated single-cell heterogeneity underlying EV secretion. Notably, we observed that the decrement of certain EV phenotypes (e.g., CD63+EV) was associated with the invasive feature of both OSCC cell lines and primary OSCC cells. We also realized multiplexed detection of EV secretion and cytokines secretion simultaneously from the same single cells to investigate the multidimensional spectrum of cellular communications, from which we resolved tiered functional subgroups with distinct secretion profiles by visualized clustering and principal component analysis. In particular, we found that different cell subgroups dominated EV secretion and cytokine secretion. The technology introduced here enables a comprehensive evaluation of EV secretion heterogeneity at single-cell level, which may become an indispensable tool to complement current single-cell analysis and EV research.
The management of early gastric cancer (EGC) has witnessed a rise in the utilization of endoscopic submucosal dissection (ESD) as a treatment modality, although prognostic markers are needed to guide management strategies. This study investigates the prognostic implications of lymphovascular invasion (LVI) in ESD-eligible EGC patients, specifically its implications for subsequent radical surgery.
Type II alveolar epithelial cells have potential for lung growth and reparation. Extracorporeal membrane oxygenation is used as life support for lung impairment resulting from acute respiratory distress syndrome. We hypothesized that intratracheal transplantation of isogeneic primary type II alveolar epithelial cells in combination with extracorporeal membrane oxygenation may facilitate lung reparation for acute lung injury (ALI).A randomized, controlled experiment.An animal laboratory in a university pediatric center.Twenty-eight 4- to 6-week young piglets, weighing 7-8 kg.Type II alveolar epithelial cells from neonatal male piglet lungs were isolated, purified, cultured, and labeled with chemical stain PKH26. After 3-6 hours of induction of ALI by IV endotoxin and mechanical ventilation (MV), young female piglets were allocated to five groups (n = 5): ALI-MV, ALI treated with MV; ALI-EC, ALI treated with both MV and venovenous extracorporeal membrane oxygenation; ALI-EC-T, ALI-EC protocol plus intratracheal type II alveolar epithelial cell transplant; CON-MV, healthy animals treated with MV; and CON-EC-T, healthy animals treated with venovenous extracorporeal membrane oxygenation. After 24 hours, animals were weaned from treatment for recovery in the ensuing 14 days, with their lungs assessed for injury and reparation.Lung injury for animals in ALI-MV was moderate to severe, whereas much milder injuries in ALI-EC-T and ALI-EC were found. More PKH26-labeled type II alveolar epithelial cells were detected by fluorescence in the lungs of ALI-EC-T than in CON-EC-T as further verified by the expression of messenger RNA of sex-determining region of Y chromosome. Electromicroscopically intact type II alveolar epithelial cells and prominent lattice-like tubular myelin were also found in ALI-EC-T and CON-MV but not in ALI-EC. The hydroxyproline level in lung tissue was significantly lower in ALI-EC-T than in ALI-EC and ALI-MV, with most of the lung histopathologic and pathobiologic manifestations in favor of ALI-EC-T.The preliminary data suggested that type II alveolar epithelial cell transplant facilitated lung reparation for ALI in this model.
Overcoming drug resistance in cancer therapies remains challenging, and the tumor microenvironment plays an important part in it. Microvesicles (MVs) are functional natural carriers of cellular information, participate in intercellular communication, and dynamically regulate the tumor microenvironment. They contribute to drug resistance by transferring functional molecules between cells. Conversely, due to their specific cell or tissue targeting ability, MVs are considered as carriers for therapeutic molecules to reverse drug resistance. Thus, in this mini-review, we aim to highlight the crucial role of MVs in cell-to-cell communication and therefore their diverse impact mainly on liver cancer progression and treatment. In addition, we summarize the possible mechanisms for sorafenib resistance (one of the main hurdles in hepatocellular carcinoma treatments) and recent advances in using MVs to reverse sorafenib resistance in liver cancer therapies. Identifying the functional role of MVs in cancer therapy might provide a new aspect for developing precise novel therapeutics in the future.
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