Effect of verapamil on bronchial goblet cells of asthma: an experimental study on sensitized animals

IntroductionGoblet cell hyperplasia (GCH) and mucus hypersecretion in the airway is recognized as an important contributor to morbidity and mortality in asthma and COPD. Verapamil is a calcium channel blocker that binds to the alpha-subunit of L-type calcium channels and inhibits the mucin gene via the calmodulin and CaM kinase pathway. The objective of this study was to determine the in vivo effect of verapamil on GCH and eosinophilic inflammation in sensitized mice.MethodsMale BALB/c mice were sensitized to ovalbumin using the standard method. Two groups of animals were received verapamil via an intramuscular injection: 1-low dose (0.5 mg/kg/day for two weeks), 2-high dose (1.5 mg/kg/day for two weeks). Serum and bronchoalveolar lavage fluid (BALF) was collected and analyzed for inflammatory cells, interferon-γ and IL-4. The left lung was sent for histopathological evaluation, especially for periodic acid-Schiff (PAS), to identify goblet cells in the epithelium. The degree of inflammatory cell infiltration, including eosinophils, mucus plugging, and smooth muscle thickness of the airways were classified on a semi quantitative scale.ResultsInflammatory cell infiltration in peribronchial and perivascular areas was observed in all sensitized groups. Eosinophils percentage in the BALF significantly decreased in verapamil-treated mice compared with sensitized mice (from 19.8% in asthmatic to 5.4% for low dose and 4.4% for high dose). The ratio of airway goblet cells per epithelial cells were significantly lower in verapamil-treated mice versus sensitized mice (1.57 ± 1.30% for low dose; 1.50 ± 0.93% for high dose versus 12.93 ± 7.55%, P < 0.05, respectively). Mucus production of goblet cells decreased significantly in verapamil-treated mice versus sensitized mice (mean score was 1.45 ± 0.30 for low dose; 0.81 ± 1.00 for high dose versus 2.85 ± 0.86 in the sensitized control group, P < 0.05, respectively). The concentration of serum and BALF-IFN-γ in verapamil-treated mice markedly increased by the verapamil treatment when compared to sensitized mice (15.1 ± 0.43 versus 4.7 ± 0.96, P < 0.05 and 91.8 ± 47.7 versus 14.8 ± 4.6, P < 0.01, respectively).ConclusionVerapamil is a useful drug with therapeutic targeting on GCH and a potential way to limit mucous production and improve bronchial inflammation.     

A manganese(iii) Schiff base complex immobilized on silica-coated magnetic nanoparticles showing enhanced electrochemical catalytic performance toward sulfide and alkene oxidation

In this study, a novel Mn(iii)–Schiff base complex was synthesized and characterized. The structure of this complex was determined to be a deformed octahedral coordination sphere by single-crystal X-ray diffraction analysis. The Mn(iii)–Schiff base complex was supported on silica-coated iron magnetic nanoparticles via axial coordination by one-step complex anchoring to produce a heterogenized nanocatalyst. After this, the complex was characterized by Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), transmission electron microscopy (TEM), energy-dispersive X-ray spectroscopy (EDX), thermogravimetric analysis (TGA), vibrating sample magnetometry (VSM), and powder X-ray diffraction (XRD). Moreover, atomic absorption spectroscopy was used to determine the amount of the loaded metal. The heterogenized nanocatalyst effectively catalyzed the oxidation of a broad range of sulfides and alkenes with H₂O₂ in the presence of a glassy carbon electrode, applying voltage to the reaction mixture. The results showed that the application of a potential to the reaction mixture could significantly decrease the reaction time when compared with the case of similar chemical oxidation reactions. In addition, an excellent value of turnover frequency (17 750 h⁻¹) was achieved for the electrochemical oxidation of styrene. Moreover, the nanocatalyst showed good recoverability without significant loss of its activity within six successive runs in the electrochemical oxidation of methyl phenyl sulfide and cyclooctene. The electrochemical properties and stability of Fe₃O₄@SiO₂-[MnL(OAc)] were investigated by cyclic voltammetry measurements and chronoamperometry technique.

A Mn–Schiff base complex supported on silica-coated iron magnetic nanoparticles was used for the electrochemical oxidation of sulfides and alkenes.     

Mussel inspired ZIF8 microcarriers: a new approach for large-scale production of stem cells

Metal–organic frameworks (MOFs) have high porosity, large surface area, and tunable functionality and have been widely used for drug loading. The aim of this study was to exploit unique features of zeolitic imidazolate framework-8 (ZIF8) to develop an innovative composite microcarrier (MC) for human mesenchymal stem cells (hMSCs) adhesion and proliferation. ZIF8 MCs were prepared by immobilization of polydopamine/polyethyleneimine (PDA/PEI) and ZIF8 on the surface of polystyrene beads. The chemical properties of MCs such as coating stability and homogeneity were characterized by different techniques such as ATR-FTIR, XRD, EDX, SEM, and contact angle. The prepared MCs were tested using human adipose-derived mesenchymal stem cells (hADSCs) in both static and dynamic conditions, and results were compared to a commercially available MC (Star-Plus), polydopamine coated MCs and amine-functionalized MCs as a control. Results show that PDA/PEI/ZIF8 coated MCs (in short: ZIF8 MCs) provides an excellent biocompatible environment for hADSCs adhesion and growth. In conclusion, ZIF8 MCs represent suitable and low-cost support for hADSCs culture and expansion, which can maximize cell yield and viability while preserving hADSCs multipotency. The present findings have revealed this strategy has the potential for chemical and topographical modification of MCs in tissue engineering applications.

Mussel inspired ZIF8 microcarriers with high surface area, biocompatibility, and nanoscale surface roughness are applied to enhance mesenchymal stem cell attachment and proliferation in 3D cell culture.     

Long-Term Outcomes Comparing Surgery to Embolization-Ablation for Treatment of Solitary HCC <7 cm

Background

Resection has been the standard of care for patients with solitary hepatocellular carcinoma (HCC). Transarterial embolization and percutaneous ablation are alternative therapies often reserved for suboptimal surgical candidates. Here we compare long-term outcomes of patients with solitary HCC treated with resection versus combined embo-ablation.

Methods

We previously reported a retrospective comparison of resection and embo-ablation in 73 patients with solitary HCC <7 cm after a median follow-up of 23 months. This study represents long-term updated follow-up over a median of 134 months.

Results

There was no difference in survival among Okuda I patients who underwent resection versus embo-ablation (66 vs 58 months, p = .39). There was no difference between the groups in the rate of distant intrahepatic (p = .35) or metastatic progression (p = .48). Surgical patients experienced more complications (p = .004), longer hospitalizations (p < .001), and were more likely to require hospital readmission within 30 days of discharge (p = .03).

Conclusion

Over a median follow up of more than 10 years, we found no significant difference in overall survival of Okuda 1 patients with solitary HCC <7 cm who underwent surgical resection versus embo-ablation. Our data suggest that there may be a greater role for primary embo-ablation in the treatment of potentially resectable solitary HCC.     

Parkin-Knockout Mice did not Display Increased Vulnerability to Intranasal Administration of 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)

The loss of nigral dopaminergic neurons in Parkinson’s disease (PD) is believed to result from interactions between genetic susceptibility and environmental factors. Although loss-of-function mutations in the parkin gene cause early-onset familial PD, the hybrid 129Sv-C57BL/6 parkin-deficient mice did not display spontaneous degeneration of the nigrostriatal pathway or enhanced vulnerability to neurotoxicity induced by 6-hydroxydopamine (6-OHDA) or intraperitoneal 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) intoxication. We aimed to re-evaluate the role of parkin in a pure C57BL/6 background after an acute intranasal (i.n.) MPTP administration, a new route of toxin delivery to the brain that mimics environmental exposure to neurotoxins. We found that the deficiency of parkin gene modifies the d-amphetamine-induced locomotion in saline-treated animals. Intranasal MPTP induced Parkinsonism in parkin^+/+ mice, through depletion of striatal dopamine, decreased number of dopaminergic neurons in the substantia nigra, and decreased d-amphetamine-induced hyperlocomotion. Additionally, the deletion of the parkin gene in a pure C57BL/6 background did not lead to increased vulnerability to i.n. MPTP-induced neurotoxicity. Moreover, the i.n. MPTP induced nigral astrogliosis predominantly in the pars reticulata in wild type and parkin^?/? mice. Taken together, these results showed that the absence of parkin did not modify the vulnerability of nigrostriatal dopaminergic pathway after i.n. MPTP intoxication, suggesting that independently of mouse strain, the endogenous parkin is not required for protection of this system. These findings also suggest that the development of familial parkin-linked PD is not associated with exposure to environmental factors that specifically affects the dopaminergic system.