Ultraviolet B radiation induces oxidative stress and apoptosis in human lens epithelium cells by activating NF-κB signaling to down-regulate sodium vitamin C transporter 2 (SVCT2) expression.

Ultraviolet B (UVB) exposure is reported to cause cataract formation by inducing excessive reactive oxygen species (ROS) and apoptosis in human lens epithelial cells (HLECs). Sodium-dependent Vitamin C transports-2 (SVCT2) is a ascorbic acid (AsA) transporter for that can protect cells and tissues from oxidative stress. Here, we focus on the functional characterization and mechanism analysis of SVCT2 in UVB-treated HLECs. The results showed a significant reduction of SVCT2 expression in HLECs treated with UVB. SVCT2 abated apoptosis and Bax expression and increased Bcl-2 expression. Moreover, SVCT2 decreased ROS accumulation and MDA level, but increased the activities of antioxidant enzymes (SOD and GSH-PX). NF-κB inhibitor (PDTC) alleviated ROS production and apoptosis, and promoted SVCT2 expression in UVB-treated HLECs. Additionally, ROS inhibitor (NAC) suppressed oxidative stress, apoptosis, and induced SVCT2 expression in UVB-treated HLECs, while these effects were significantly abated due to the activation of NF-κB signaling. Furthermore, SVCT2 facilitated 14C-AsA absorption in UVB-treated HLECs. Together, our findings demonstrated that UVB exposure-induced ROS generation, which further activated NF-κB signaling to down-regulate SVCT2 expression in HLECs. Then, downregulated SVCT2 promoted ROS accumulation and induced apoptosis by decreasing AsA uptake. Our data reveal a novel NF-κB/SVCT2/AsA regulatory pathway and suggest the therapeutic potential of SVCT2 in UVB-induced cataract.

Vascular endothelial cell-derived exosomal miR-1246 facilitates posterior capsule opacification development by targeting GSK-3ß in diabetes mellitus.

Posterior capsule opacification (PCO) is a serious complication after cataract surgery. Diabetes could increase the occurrence of PCO, but the mechanism is still unclear. The purpose of this study is to investigate the role of small extracellular vesicles (sEVs) derived from diabetic aqueous humor in PCO process. Intraoperatively-derived aqueous humor sEVs from patients with diabetic related cataract (DRC) promoted the epithelial-mesenchymal transition (EMT) and metastasis of human lens epithelial cells (LECs). Via mouse PCO surgical model and DiI labeled fluorescence detection of sEVs, the sEVs derived from vascular endothelium were discovered directly contacting with LECs. Furthermore, we demonstrated that high-glucose-cultured human umbilical vein endothelial cells (HUVEC) -derived sEVs facilitated EMT process of HLE-B3 using co-culture model in vitro. miRNA-seq data and GEO datasets analysis revealed that miR-1246 was essential in EMT process with diabetes. The miR-1246 was highly expressed in diabetic aqueous humor sEVs and high-glucose-treated vascular-endothelial-cell-derived sEVs. Moreover, miR-1246 promoted the metastasis and EMT process of HLE-B3 cells by directly targeting GSK-3ß. Inhibiting miR-1246 could negatively regulated EMT. This finding might serve as a potential therapy for diabetic PCO.

Surgical resection and orbital iodine-125 brachytherapy for orbital malignancy: a novel treatment for orbital lymphoma.

OBJECTIVES: Orbital lymphoma is one of the most common adult orbital malignancies, accounting for approximately 10% of all orbital tumors. This study aimed to analyze the effects of surgical resection and orbital iodine-125 brachytherapy implantation for orbital lymphoma. PATIENTS AND METHODS: This was a retrospective study. Clinical data of 10 patients were collected from October 2016 to November 2018 and followed up to March 2022. Patients underwent the primary surgery for maximal safe removal of the tumor. After a pathologic diagnosis of a primary orbital lymphoma was established, iodine-125 seed tubes were designed based on the tumor size and invasion range, and direct vision was placed into the nasolacrimal canal or/and under the orbital periosteum around the resection cavity during the secondary surgery. Then, follow-up data, including the general situation, ocular condition, and tumor recurrence, were recorded. RESULTS: Of the 10 patients, the pathologic diagnoses included extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (6 cases), small lymphocytic lymphoma (1 case), mantle cell lymphoma (2 cases), and diffuse large B-cell lymphoma (1 case). The number of seeds implanted ranged from 16 to 40. The follow-up period ranged between 40 and 65 months. All patients in this study were alive and well had tumors that were completely controlled. No tumor recurrences or metastases occurred. Three patients had dry eye syndrome and two patients had abnormal facial sensation. No patient had radiodermatitis involving the skin around the eye, and no patient had radiation-related ophthalmopathy. CONCLUSIONS: Based on preliminary observations, iodine-125 brachytherapy implantation appeared to be a reasonable alternative to external irradiation for orbital lymphoma.

Biomimetic Mineralized Fiber Bundle-Inspired Scaffolding Surface on Polyetheretherketone Implants Promotes Osseointegration.

The stress shielding effect caused by traditional metal implants is circumvented by using polyetheretherketone (PEEK), due to its excellent mechanical properties; however, the biologically inert nature of PEEK limits its application. Endowing PEEK with biological activity to promote osseointegration would increase its applicability for bone replacement implants. A biomimetic study is performed, inspired by mineralized collagen fiber bundles that contact bone marrow mesenchymal stem cells (BMMSCs) on the native trabecular bone surface. The PEEK surface (P) is first sulfonated with sulfuric acid to form a porous network structure (sP). The surface is then encapsulated with amorphous hydroxyapatite (HA) by magnetron sputtering to form a biomimetic scaffold that resembles mineralized collagen fiber bundles (sPHA). Amorphous HA simulates the composition of osteogenic regions in vivo and exhibits strong biological activity. In vitro results show that more favorable cell adhesion and osteogenic differentiation can be attained with the novelsurface of sPHA than with SP. The results of in vivo experiments show that sPHA exhibits osteoinductive and osteoconductive activity and facilitates bone formation and osseointegration. Therefore, the surface modification strategy can significantly improve the biological activity of PEEK, facilitate effective osseointegration, and inspire further bionic modification of other inert polymers similar to PEEK.

TiO2nanotubes induce early mitochondrial fission in BMMSCs and promote osseointegration.

Nanotopography can promote osseointegration, but how bone marrow mesenchymal stem cells (BMMSCs) respond to this physical stimulus is unclear. Here, we found that early exposure of BMMSCs to nanotopography (6 h) caused mitochondrial fission rather than fusion, which was necessary for osseointegration. We analyzed the changes in mitochondrial morphology and function of BMMSCs located on the surfaces of NT100 (100 nm nanotubes) and ST (smooth) by super-resolution microscopy and other techniques. Then, we found that both ST and NT100 caused a significant increase in mitochondrial fission early on, but NT100 caused mitochondrial fission much earlier than those on ST. In addition, the mitochondrial functional statuses were good at the 6 h time point, this is at odds with the conventional wisdom that fusion is good. This fission phenomenon adequately protected mitochondrial membrane potential (MMP) and respiration and reduced reactive oxygen species. Interestingly, the MMP and oxygen consumption rate of BMMSCs were reduced when mitochondrial fission was inhibited by Mdivi-1(Inhibition of dynamin-related protein 1 fission) in the early stage. In addition, the effect on osseointegration was significantly worse, and this effect did not improve with time. Taken together, the findings indicate that early mitochondrial fission plays an important role in nanotopography-mediated promotion of osseointegration, which is of great significance to the surface structure design of biomaterials.

The protective mechanism of Grx2 in ultraviolet-B (UVB)-induced cataract formation.

OBJECTIVE: We established a mouse cataract model by irradiating Grx2 knockout (KO) and knock-in (KI) genetically modified mice with UVB to explore the protective mechanism of Grx2 against UVB lens damage. METHODS: After irradiating Grx2 KO and Grx2 KI mice with UVB lamps, we observed and recorded the general physiological conditions and lens opacity of the mice. The crystalline grading system of the University of Oxford was used to classify the opacity of the lens. Lens reactive oxygen species (ROS) contents were detected using a microplate reader, western blot, and enzyme-linked immunosorbent assay (ELISA) to detect antioxidant and antioxidant enzyme contents. Statistical analysis of the recorded data was performed by using SPSS 19.0 software. RESULTS: After UVB irradiation, the weight of Grx2 KO mice was slightly lower than that of wild-type (WT) mice of the same age. Compared to WT mice, the lens opacity of Grx2 KO mice appeared earlier, the nucleus density of the lens increased, and the opacity increased in the first week after UVB irradiation. Meanwhile, the lenses of Grx2 KI mice remained transparent. The experiment showed that the content of ROS increased, the level of glutathione (GSH) decreased, the content of 8-OHdG increased, and the expression of BCL2 decreased after UVB irradiation. Compared to WT mice, these changes were more significant in Grx2 KO mice. CONCLUSION: This experiment found that knocking out the Grx2 gene accelerated the occurrence and development of UVB-induced cataracts in mice and that Grx2 plays an important role in the oxidative damage caused by UVB radiation by repairing the antioxidant enzymes of the lens. This study provides a new animal model and research ideas for the study of cataract pathogenesis.

Strontium-loaded titanium implant with rough surface modulates osseointegration by changing sfrp4 in canonical and noncanonical Wnt signaling pathways.

A rough morphology and strontium (Sr) can activate the Wnt pathway to regulate bone mesenchymal stem cells (rBMSCs) osteogenic differentiation, but the mechanism remains unclear. We constructed smooth Ti (ST) surfaces, rough Ti (RT) surfaces subjected to hydrofluoric acid etching, strontium-loaded smooth Ti (ST-Sr) surfaces subjected to magnetron sputtering, and rough strontium-loaded Ti (RT-Sr) surfaces. We systematically studied thein vitroosteogenic differentiation of rBMSCs on these four surfaces by alkaline phosphatase measurement, Alizarin Red staining and polymerase chain reaction (PCR). We also investigated whether crosstalk of the canonical and noncanonical Wnt signaling pathways regulated by sfrp4, which is an inhibitor of canonical and noncanonical Wnt, is the underlying mechanism via PCR on rBMSCs in different stages of osteogenic differentiation. We confirmed the effect of sfrp4 through anin vivosfrp4-siRNA test. Thein vitroosteogenic differentiation of rBMSCs decreased in the order RT-Sr, RT, ST-Sr, and ST. Regarding the mechanism, rough morphology and Sr both enhanced the canonical Wnt pathway to promote osseointegration. Additionally, rough morphology can inhibit sfrp4 to activate the noncanonical Wnt pathway, and then, the activated noncanonical Wnt pathway can suppress the canonical Wnt pathway at the early stage of osteogenic differentiation. Sr continuously enhanced sfrp4 to inhibit the canonical Wnt pathway instead of activating the noncanonical Wnt pathway. Interestingly, the effect of rough morphology on sfrp4 changed from inhibition to enhancement, and the enhancing effect of Sr on sfrp4 was gradually attenuated. The results of thein vivosfrp4-siRNA test showed that osseointegration decreased in the order RT-Sr, RT-Sr-siRNA, and ST. Our results suggest that the lack of sfrp4 could suppress osseointegration, indicating that sfrp4 acts as a crucial regulatory molecule for the canonical and noncanonical Wnt pathways during the response of rBMSCs to rough morphology and Sr.

Iodine-125 interstitial brachytherapy for malignant lacrimal sac tumours: an innovative technique.

OBJECTIVES: Primary malignant tumours of the lacrimal sac are rare, surgery and radiotherapy may induce substantial side effects for patients. Here, this article reports an innovative technique of interstitial brachytherapy developed for the treatment of malignant lacrimal sac tumours. PATIENTS AND METHODS: Four patients (male 3, female 1), with an average age of 52.7 years (range 41-72 years), were individually diagnosed with squamous cell carcinoma, adenocarcinoma, adenoid cystic carcinoma and lymphoma. All patients received Iodine-125 interstitial brachytherapy after surgical resection for malignant lacrimal sac tumours. Visual function examination (vision, intraocular tension, fundus photography, fluorescein angiography, and optical coherence tomography) and CT/MRI/PET-MRI were performed to look for signs of recurrent tumours or metastasis. RESULTS: Four patients were followed for an average of 28 months (range, 23-37 months). All patients were free from local disease. Their visual function was normal, and CT/MRI did not reveal any tumour recurrence. CONCLUSIONS: Iodine-125 interstitial brachytherapy can be used as an alternative to wide excision or exenteration of these tumours. There was good local control, reasonable maintenance of vision, and good cosmesis.

Adjustment of IOL power for the second eye based on refractive error of the first-operated eye.

This study was to estimate refractive status of the second eye of those undergo bilateral cataract surgery based on the first-operated eye, and to evaluate the refractive error (RE) in the second eye after correcting 50% of the first-operated eye's error when it exceeded ±0.50 diopter (D). In this prospective study, 80 patients were scheduled for cataract surgery in the second eye, who underwent cataract surgery in first eye 1-3mo previously. The RE of each eye postoperatively was determined according to SRK/T formula. When the first-eye refractive error (FERE) exceeded ±0.5 D, the intraocular lens (IOL) power of the second eye was adjusted 50% of the FERE. The second-eye refractive error (SERE) was measured 1mo after surgery. The FERE exceeded -0.50 D in 12 eyes (-0.675±0.16 D), and the adjusted SERE was -0.322±0.73 D (P<0.05). The FERE exceeded +0.50 D in 8 eyes (1.533±1.14 D), and the adjusted SERE was 0.168±1.36 D (P<0.05). The unadjusted SERE in 60 cases remained -0.38 to 0.42 D when the FERE within ±0.05 D. This prospective study confirmed that the prediction of the second eye could be improved by correcting 50% of FERE when this error exceeded ±0.50 D.

Platelet distribution width, platelet count, and plateletcrit in diabetic retinopathy: A systematic review and meta-analysis of PRISMA guidelines.

BACKGROUND: Screening and diagnosis of diabetic retinopathy (DR) mainly depends on fundus examination, which is not an intuitive and simple screening or diagnostic method. Recently, the relationship between platelet parameters and DR has become a hot topic. Whether platelet parameters have clinical value in DR is controversial. METHODS: Literature was retrieved by formal search of electronic databases (PubMed, Embase, Cochrane library, Scopus, and CNKI) and by hand searching of reference lists of related articles from the beginning of building database to December 2017. Review manager 5.3 was utilized to deal with statistical data. This study was registered at International Prospective Register of Systematic Reviews (number: CRD42018093773). RESULTS: This study included 1720 DR patients, 1477 type 2 diabetic mellitus (T2DM) without DR patients and 1456 health controls in 21 eligible studies. We found there was significant increase of platelet distribution width (PDW) level in the comparison of DR versus Control group (standard mean difference [SMD] [95% confidence interval [CI]] = 1.04 [0.68, 1.40]) and DR versus T2DM without DR group (SMD [95% CI] = 0.68 [0.40, 0.95]). For platelet count (PLT), it showed obvious decrease in the comparison of DR versus T2DM without DR group (SMD [95% CI] = -0.26 [-0.49, -0.03]) and no difference in comparison of DR versus Control (SMD [95% CI] = -0.26 [-0.51, -0.00]). Subgroup analysis showed that significant result of PDW level appeared in China and Turkey in all comparisons, while similar results of PLT only in China. In addition, PDW level was different in various DR-subtypes, obvious high level in proliferation DR. CONCLUSIONS: We concluded that the guiding significance of PDW and PLT in diagnosis and monitor of DR, and especially, application of PDW to PDR management may have potential sense.

Anterior chamber depth - a predictor of refractive outcomes after age-related cataract surgery.

BACKGROUND: Anterior chamber depth (ACD) is becoming a hot topic and plays an important role in correcting the refractive errors (REs) after cataract surgery. The aim of this study was to assess the ACD changes and their relationship with the REs after phacoemulsification and intraocular lens (IOL) implantation in patients with age-related cataracts. METHODS: One hundred forty-five eyes of 125 age-related cataract patients from the Department of Ophthalmology, Tangdu Hospital, China, were recruited. IOL Master was used for axial length (AL) and the IOL power calculation measurements, and the Pentacam HR device was used for the ACD and lens thickness (LT) measurements. Every patient underwent uncomplicated phacoemulsification by a single surgeon using a single technique. Postoperative refraction results were obtained at 1 month. The appropriate formula used for the IOL power calculation was chosen depending on the AL, specifically the Hoffer Q (AL < 22.0 mm), SRK/T (22.0 mm ≤ AL ≤ 30.0 mm), and Haigis (AL > 30.0 mm) formulas. RESULTS: The postoperative ACD was deepened and tended to stabilize gradually after 2 weeks. A concurrent hyperopic shift (0.57 ± 0.47 D) was observed when the change in the ACD was less than 1.65 mm, whereas a myopic shift (- 0.18 ± 0.62 D) occurred contrarily, and the difference between the two groups was statistically significant (P < 0.0001). The change in ACD was significantly larger in the shallow anterior chamber (1.92 ± 0.40 mm) than in the deep chamber (1.33 ± 0.42 mm) (P < 0.0001). Similarly, the change in ACD was larger in the short AL (2.12 ± 0.37 mm) than in the long AL (1.32 ± 0.49 mm). The postoperative ACD and refractive changes were correlated with the preoperative ACD and AL (P < 0.0001), respectively. Two regression formulas were proposed: postoperative ACD = 3.524 + 0.294 × preoperative ACD and postoperative ACD = 3.361 + 0.228× (preoperative ACD + 1/2 LT). CONCLUSIONS: The results of this study showed that the ACD deepened and was associated with a concurrent RE after cataract surgery. Postoperative changes in the ACD were related to the preoperative ACD and AL, which determined the refraction status and visual quality. The regression formula of the postoperative ACD could provide a theoretical basis for predicting refractive errors in the clinic.

The relationship between mean platelet volume and diabetic retinopathy: a systematic review and meta-analysis.

BACKGROUND: Diabetic retinopathy (DR) is one of the most common diseases causing blindness in the world, and most patients are already in advanced stage. Recent years, many studies reported mean platelet volume (MPV) may be associated with development of DR, but there was no consistent conclusion reached. METHODS: Literature was retrieved by formally searching PubMed, Embase, Cochrane library and Scopus and by hand searching of reference lists of related articles. Finally, a total of 14 literatures included, and Review manager 5.3 and STATA 14.0 statistical software were utilized for processing. RESULTS: Meta-analysis showed that MPV values in DR were significantly higher than health controls [SMD (95% CI) = 0.92 (0.60-1.24)] and type 2 diabetes mellitus without diabetic retinopathy (T2DM without DR) [SMD (95% CI) = 0.36 (0.19-0.53)]. Subgroup analysis indicated that MPV level in proliferative diabetic retinopathy (PDR) patients was higher than T2DM without DR patients [SMD (95% CI) = 0.48 (0.28, 0.68)], but this difference didn't appear in non-proliferative diabetic retinopathy (NPDR). CONCLUSIONS: The study demonstrated that increased MPV level was significant associated with the development of DR, and it might reflect the severity of DR, which could be provided to monitor development and progression of DR clinically.

Identification of H2O2 induced oxidative stress associated microRNAs in HLE-B3 cells and their clinical relevance to the progression of age-related nuclear cataract.

BACKGROUND: This study is aimed to screen out the microRNAs (miRNAs) associated with H2O2 induced oxidative stress in human lens epithelial B3 (HLE-B3) cell lines and investigate their relations with the progression of age-related nuclear cataract. METHODS: H2O2 was used to induce oxidative stress in HLE-B3 cells. A genome-wide expression profiling of miRNAs in HLE-B3 cells was performed to select the differentially expressed miRNAs before and after H2O2 treatment. The selected miRNAs were validated by RT-PCR and fluorescence in situ hybridization (FISH). Clinical specimens were divided into three groups according to the Lens Opacities Classification System III (LOCSIII) and the expression levels of the selected miRNAs were tested by RT-PCR in the three groups. Bioinformatics analyses were applied to predict the target genes of the miRNA hits and construct the miRNA regulatory network. The expression level of MAPK14 was analyzed by Western blot. RESULTS: The H2O2 induced oxidative stress model of HLE-B3 cells was established. Nineteen upregulated and 30 downregulated miRNAs were identified as differentially expressed miRNAs. Seven of the total 49 were validated in the cell model. RT-PCR of the clinical samples showed that the expression levels of miR-34a-5p, miR-630 and miR-335-3p were closely related with the severity of nuclear opacity. The images taken from FISH confirmed the results of RT-PCR. There were 172 target genes of the three miRNAs clustered in the category of response to stress. The regulatory network demonstrated that 23 target genes were co-regulated by multiple miRNAs. MAPK14 was the target gene of three miRNAs and the result were verified by Western blot. CONCLUSION: Up-regulation of miR-34a-5p and miR-630 and down-regulation of miR-335-3p are related with the progression of age-related nuclear cataract and the underlying mechanism awaits further functional research to reveal.

SIRT3 Deficiency Induces Endothelial Insulin Resistance and Blunts Endothelial-Dependent Vasorelaxation in Mice and Human with Obesity.

Recent evidence implicates the critical role of Sirtuin 3 (SIRT3) in the development of many metabolic diseases, but the contribution of SIRT3 to vascular homeostasis remains largely unknown. The aim of this study was to investigate the role of SIRT3 in endothelial insulin resistance and vascular dysfunction in obesity. We found an impaired insulin-induced mesenteric vasorelaxation and concomitant reduced vascular SIRT3 expression in morbid obese human subjects compared with the non-obese subjects. Downregulation of SIRT3 in cultured human endothelial cells increased mitochondrial reactive oxygen species (mtROS) and impaired insulin signaling as evidenced by decreased phosphorylation of Akt and endothelial nitric oxide synthase and subsequent reduced nitric oxide (NO) release. In addition, obese mice induced by 24-week high-fat diet (HFD) displayed an impaired endothelium-dependent vasorelaxation to both insulin and acetylcholine, which was further exacerbated by the gene deletion of Sirt3. Scavenging of mtROS not only restored insulin-stimulated NO production in SIRT3 knockdown cells, but also improved insulin-induced vasorelaxation in SIRT3 knockout mice fed with HFD. Taken together, our findings suggest that SIRT3 positively regulates endothelial insulin sensitivity and show that SIRT3 deficiency and resultant increased mtROS contribute to vascular dysfunction in obesity.