Anti-inflammatory effects of hinokitiol on human corneal epithelial cells: an in vitro study

Purpose

This study assessed the anti-inflammatory effect and mechanism of action of hinokitiol in human corneal epithelial (HCE) cells.

Methods

HCE cells were incubated with different concentrations of hinokitiol or dimethylsulfoxide (DMSO), which served as a vehicle control. Cell viability was evaluated using Cell Counting Kit-8 (CCK-8) assay. After polyriboinosinic:polyribocytidylic acid (poly(I:C)) stimulus, cells with or without hinokitiol were evaluated for the mRNA and protein levels of interleukin-8 (IL-8), interleukin-6 (IL-6), and interleukin-1β (IL-1β) using real-time PCR analysis and an enzyme-linked immunosorbent assay (ELISA), respectively. Nuclear and cytoplasmic levels of nuclear factor kappa B (NF-κB) p65 protein and an inhibitor of NF-κB α (IκBα) were evaluated using western blotting.

Results

There were no significant differences among the treatment concentrations of hinokitiol compared with cells incubated in medium only. Incubating with 100 μM hinokitiol significantly decreased the mRNA levels of IL-8 to 58.77±10.41% (P<0.01), IL-6 to 64.64±12.71% (P<0.01), and IL-1β to 54.19±8.10% (P<0.01) compared with cells stimulated with poly(I:C) alone. The protein levels of IL-8, IL-6, and IL-1β had similar trend. Further analysis revealed that hinokitiol maintained the levels of IκBα and significantly reduced NF-κB p65 subunit translocation to the nucleus which significantly inhibiting the activation of the NF-κB signal pathway.

Conclusion

Hinokitiol showed a significant protective effect against ocular surface inflammation through inhibiting the NF-κB pathway, which may indicate the possibility to relieve the ocular surface inflammation of dry eye syndrome (DES).     

Gene–gene interaction of CFH,ARMS2, and ARMS2/HTRA1 on the risk of neovascular age-related macular degeneration and polypoidal choroidal vasculopathy in Chinese population

Purpose

To evaluate the association and interaction of five single-nucleotide polymorphisms (SNPs) in three genes (CFH, ARMS2, and ARMS2/HTRA1) with neovascular age-related macular degeneration (nAMD) and polypoidal choroidal vasculopathy (PCV) in Chinese population.

Methods

A total of 300 nAMD and 300 PCV patients and 301 normal subjects participated in the present study. The allelic variants of rs800292, rs2274700, rs3750847, rs3793917, and rs1065489 were determined by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS). Gene–gene interactions were evaluated by the data mining approach multifactor-dimensionality reduction (MDR) method.

Results

The risk alleles of CFH rs800292, rs2274700, ARMS2 rs3057847, and ARMS2/HTRA1 rs3793917 showed significant difference between nAMD or PCV patients and controls (all P<0.01). The homozygosity of risk alleles for rs800292, rs2274700, rs3750847, and rs3793917 were significantly different between nAMD patients and controls (all P<0.01), and predisposed to PCV patients (all P<0.01). After cross-validation consistency (CVC) and permutation tests, the two-locus model rs2274700_rs3750847 has a balanced accuracy of 64.37% in predicting nAMD disease risk. The one-marker model, rs3750847, and two-locus model rs2274700_rs3750847 has a balanced accuracy of 66.07% and 65.89% in predicting PCV disease risk, respectively. Furthermore, CFH rs1065489 did not show significant association with nAMD (P>0.01), but was strongly associated with PCV in Chinese patients (P<0.001).

Conclusions

In this study, we found that the interaction of ARMS2 and ARMS2/HTRA1 is significantly associated with nAMD, and the interaction of CFH and ARMS2 is pronounced in PCV development in Chinese population.     

Observing implantable collamer lens dislocation by panoramic ultrasound biomicroscopy

Purpose

Observe the image characteristics and dislocation of implantable collamer lenses (ICL) following their use to correct high myopia.

Methods

A total of 127 patients (242 eyes); 64 females (50.3%) and 63 males (49.7%) were included in this retrospective study with ICL V4 implantation and mean spherical equivalent −9.08±2.04 diopters (D). Panoramic ultrasound biomicroscopy (UBM) was utilized to observe anterior segment morphology and ICL location at various follow-up periods (1 week preoperative, followed by 1, 3, 6, and yearly postoperative).

Results

Twenty-eight ICL eyes (11.2%) were noted to have abnormal postoperative positioning. The central vault of 12 eyes was too high with ICL decentration, mean central vault 1.14±0.39 mm; 10 eyes were too low but without ICL decentration, mean central vault 0.13±0.11 mm. The remaining subjects were only ICL decentration without abnormal central vault, mean central vault was 0.54±0.28 mm.

Conclusions

This study shows the abnormal characteristics regarding ICL locations. The ICL dislocation closely correlates with the central vault. The ICL dislocation is the primary cause of several postoperative complications. Panoramic UBM is one of the most effective imaging means to observe the ICL positioning and its stability after implantable surgery.     

A smoking cessation intervention among tuberculosis patients in rural China

Objective: To assess the integration of a smoking cessation intervention into routine tuberculosis (TB) services.Method: Consecutive TB patients registered from 1 March to 31 August 2010 were enrolled in an intervention for self-reported smoking to promote tobacco cessation during treatment for TB. Information on the harmful health effects of tobacco smoke and smoking and TB were provided to TB patients who self-reported as current smokers. Smoking status was reassessed at every follow-up visit during anti-tuberculosis treatment with reinforced health messages and advice to quit.Results: Of 800 TB patients enrolled, 572 (71.5%) were male and 244 (30.5%) were current smokers. Females were more likely to be non-smokers (100% vs. 35.8%, P < 0.001). Of the 244 current smokers, 144 (59.0%) started smoking at <20 years, 197 (80.7%) consumed ⩾20 cigarettes per day, 211 (86.5%) had perceived smoking dependence and 199 (81.6%) had made no attempt to quit before the diagnosis of TB. Of the 244 current smokers, 234 (95.9%) were willing to quit, and 156 (66.7%) reported abstinence at month 6. Challenges to implementing smoking cessation intervention were identified.Conclusion: The majority of current smokers among TB patients were willing to quit and remained abstinent at the end of anti-tuberculosis treatment. This intervention should be scaled up nationwide.     

An efficient access to β-ketosulfones via β-sulfonylvinylamines: metal–organic framework catalysis for the direct C–S coupling of sodium sulfinates with oxime acetates

A copper-based framework Cu₂(OBA)₂(BPY) was synthesized and used as a recyclable heterogeneous catalyst for the synthesis of β-sulfonylvinylamines from sodium sulfinates and oxime acetates via direct C–S coupling reaction. The transformation was remarkably affected by the solvent, and chlorobenzene emerged as the best option. This Cu-MOF displayed higher activity than numerous conventional homogeneous and MOF-based catalysts. The catalyst was reutilized many times in the synthesis of β-sulfonylvinylamines without considerably deteriorating in catalytic efficiency. These β-sulfonylvinylamines were readily converted to the corresponding β-ketosulfones via a hydrolysis step with aqueous HCl solution. To the best of our knowledge, this direct C–S coupling reaction to achieve β-sulfonylvinylamines was not previously conducted with a heterogeneous catalyst.

Cu₂(OBA)₂(BPY) was used as catalyst for the synthesis of β-sulfonylvinylamines from sodium sulfinates and oxime acetates. These β-sulfonylvinylamines were readily converted to corresponding β-ketosulfones via a hydrolysis step.     

Individualized dosing guidelines for PEGasparaginase and factors influencing the clearance: a population pharmacokinetic model

Considerable inter- and intra-patient variability exist in serum activity levels of PEGasparaginase, essential for pediatric acute lymphoblastic leukemia (ALL) treatment. A population pharmacokinetic (popPK) model was developed, identifying patient characteristics that explain these variabilities. Patients (n=92) were treated according to the Dutch Childhood Oncology Group (DCOG) ALL-11 protocol, using therapeutic drug monitoring to individualize PEGasparaginase doses. Non-linear mixed effects modeling (NONMEM) was used to analyze popPK evaluating several covariates. The final model was validated using an independent database (n=28). Guidelines for starting doses and dose adjustments were developed. A one-compartment model with timedependent clearance was adequately described in popPK. Normalization of clearance and volume of distribution by body surface area reduced inter-individual variability. Clearance was 0.084 L/day/m² for 12.7 days, increasing by 0.082 L/day/m²/day thereafter. Clearance was 38% higher during an infection, and 11-19% higher during induction treatment than during intensification and maintenance (P<0.001). In order to target an asparaginase activity level of 100 IU/L, a loading dose of 800 IU/m² (induction) and 600 IU/m² (intensification) is advised. In conclusion, variability of PEGasparaginase activity levels can be explained by body surface area, the treatment phase and the occurrence of an infection. With this popPK model, PEGasparaginase treatment can be individualized further, taking into account the covariates and the dosing guidelines provided. (clinicaltrials gov. Identifier [CCMO register]: NL50250.078.14).