Celastrol nanoparticles inhibit corneal neovascularization induced by suturing in rats

Zhanrong Li1, Lin Yao1, Jingguo Li2, Wenxin Zhang1, Xianghua Wu1, Yi Liu1, Miaoli Lin1, Wenru Su1, Yongping Li1, Dan Liang11State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-Sen University, 2School of Chemistry and Chemical Engineering, Sun Yat-Sen University, Guangzhou, People's Republic of ChinaPurpose: Celastrol, a traditional Chinese medicine, is widely used in anti-inflammation and anti-angiogenesis research. However, the poor water solubility of celastrol restricts its further application. This paper aims to study the effect of celastrol nanoparticles (CNPs) on corneal neovascularization (CNV) and determine the possible mechanism.Methods: To improve the hydrophilicity of celastrol, celastrol-loaded poly(ethylene glycol)-block-poly(ε-caprolactone) nanopolymeric micelles were developed. The characterization of CNPs was measured by dynamic light scattering and transmission electron microscopy analysis. Celastrol loading content and release were assessed by ultraviolet-visible analysis and high performance liquid chromatography, respectively. In vitro, human umbilical vein endothelial cell proliferation and capillary-like tube formation were assayed. In vivo, suture-induced CNV was chosen to evaluate the effect of CNPs on CNV in rats. Immunohistochemistry for CD68 assessed the macrophage infiltration of the cornea on day 6 after surgery. Real-time quantitative reverse transcription-polymerase chain reaction and enzyme-linked immunosorbent assay were used to evaluate the messenger ribonucleic acid and protein levels, respectively, of vascular endothelial growth factor, matrix metalloproteinase 9, and monocyte chemoattractant protein 1 in the cornea.Results: The mean diameter of CNPs with spherical shape was 48 nm. The celastrol loading content was 7.36%. The release behavior of CNPs in buffered solution (pH 7.4) showed a typical two-phase release profile. CNPs inhibited the proliferation of human umbilical vein endothelial cells in a dose-independent manner and suppressed the capillary structure formation. After treatment with CNPs, the length and area of CNV reduced from 1.16 ± 0.18 mm to 0.49 ± 0.12 mm and from 7.71 ± 0.94 mm2 to 2.29 ± 0.61 mm2, respectively. Macrophage infiltration decreased significantly in the CNP-treated corneas. CNPs reduced the expression of vascular endothelial growth factor, matrix metalloproteinase 9, and monocyte chemoattractant protein 1 in the cornea on day 6 after suturing.Conclusion: CNPs significantly inhibited suture-induced CNV by suppressing macrophage infiltration and the expression of vascular endothelial growth factor and matrix metalloproteinase 9 in the rat cornea.Keywords: celastrol, PEG-b-PCL nanopolymeric micelles, corneal neovascularization, macrophages, VEGF, MMP-

Efficacy of Subantimicrobial Dose Doxycycline for Moderate-to-Severe and Active Graves’ Orbitopathy

Aim. To study the efficacy and safety of subantimicrobial dose (SD) doxycycline(50 mg/d) in patients with active and moderate-to-severe Graves’ orbitopathy (GO). Methods. Thirteen patients with active and moderate-to-severe GO received once daily oral doxycycline (50 mg/d) for 12 wk. Treatment response at 24 wk was used as the primary outcome, measured by a composite of improvement in Clinical Activity Score (CAS), diplopia, motility, soft tissue swelling, proptosis, and eyelid aperture. Secondary outcome was the change of quality of life score (QoL, including visual functioning subscale and appearance subscale). Adverse events were also recorded. Results. Overall improvement was noted in eight out of 13 patients (61.5%, 95% CI 31.6%–86.1%). Both CAS and soft tissue swelling significantly ameliorated in eight patients at 24 wk. Five patients (38.5%) had improvement in ocular motility of ≥8 degrees. Eyelid aperture (46.2%) also decreased remarkably. For QoL, a significant improvement in appearance subscale (P=0.008) was noted during the study, whereas no difference was observed in visual functioning subscale (P=0.21). Two patients reported mild stomachache at 12 wk. Conclusions. SD doxycycline appears to be effective and safe for the treatment of active and moderate-to-severe GO. It might serve as a new promising therapeutic strategy for GO. This trial is registered with NCT01727973

Radial Retinotomies with Endodiathermy for Severe Proliferative Vitreoretinopathy: Short-Term Results

Purpose. Retinal redetachment of silicone oil-filled eyes continues to be a frustrating condition that typically requires retinectomy. We proposed radial retinotomy as a potentially less invasive surgery. Here, we preliminarily explored its feasibility, efficacy, and safety. Methods. Totally 9 eyes of 9 consecutive patients were included in a prospective noncomparative trial. A series of retinotomies were created by endodiathermy in a radial pattern to relax the foreshortened retina. The eye was refilled with fresh silicone oil. The treated eyes were examined via visual acuity (VA) tests, tonometry, slit-lamp microscopy, and fundus photography during a 6-month observation period. Results. The procedure was completed in an average of 28 minutes from silicone oil removal to fresh silicone oil placement. Fundus photography demonstrated that 7 of the 9 eyes (78%) exhibited retinal reattachment. On average, VA was significantly improved within the first 2 weeks (P=0.02) and remained stable for the following 6 months. The change in intraocular pressure was not significant (P=0.76), and no adverse event was observed (0%). Conclusion. Radial retinotomies with endodiathermy were shown to be feasible, effective, and safe in selected cases of inferior contracted retina without vitreous base fibrosis over a 6-month observation period. This trial is registered with NCT02201706

Efficacy and safety of hepatic arterial infusion chemotherapy combined with lenvatinib and sequential ablation in the treatment of advanced hepatocellular carcinoma

Abstract Purpose Evaluate the efficacy and safety of triple therapeutic method (Hepatic Aarterial Infusion Chemotherapy—HAIC, lenvatinib and sequential ablation) in the treatment for Advanced Hepatocellular carcinoma (Ad‐HCC). Materials and Methods From November 2018 to June 2021, data from 150 consecutive Ad‐HCC patients were collected. All patients received HAIC combined with lenvatinib (H‐L group, n = 97) or HAIC combined with lenvatinib and sequential ablation (H‐L‐A group, n = 53). Complications, overall survival (OS), progression‐free survival (PFS) and intrahepatic progression‐free survival (IPFS) were compared between both groups. Results No significant differences of baseline characteristics were found between groups. The time of median follow‐up was 17.8 months (range, 6.8, 37.6 months). In comparison to the H‐L group, the H‐L‐A group patients showed significantly longer median OS (>30 months vs 13.6 months, respectively; p = 0.010), PFS (12.8 vs. 5.6 months, respectively; p < 0.001), and IPFS (14.6 vs. 6.8 months, respectively; p = 0.002). According to the results from uni‐ and multivariable analyses, we considered α‐fetoprotein and treatment modality as two survival independent prognostic factors. No significant change of the complication incidences was observed between H‐L group and H‐L‐A group (12.4% vs. 11.3%, p = 0.890). Conclusion Compared to HAIC combined with lenvatinib only, HAIC combined with lenvatinib and sequential ablation was safer and more effective, improving survival outcomes of Ad‐HCC patients. A prospective study will be designed validate the retrospective results

The complete chloroplast genome sequence of Pohlia cruda (Hedw.) Lindb.

Pohlia is a genus with many taxonomic and systematic controversies. In this study, the complete chloroplast genome of Pohlia cruda (Bryales, Bryophyte) was sequenced by high-throughput sequencing technology and described. The complete chloroplast genome is 125,114 bp in length and has a quadripartite structure. The two inverted repeat (IR) regions are 9921 bp long and separated by a large single-copy (LSC) region of 86,727 bp and a small single-copy (SSC) region of 18,545 bp. Phylogenetic trees were constructed based on the complete chloroplast genome sequences of 10 bryophytes downloaded from GenBank and one acquired in this study