mir-22-mediated-regulation-wnt-catenin-signaling-curcumin

miR-22-Mediated Regulation of Wnt/&#946;-Catenin Signaling by Curcumin in Retinoblastoma

Retinoblastoma (RB) is a common intraocular malignant tumor affecting infants and children, yet its precise etiology and pathogenesis remain incompletely ...

Tianjin Eye Hospital

We investigated the effect of epidermal growth factor receptor (EGFR) siRNA on human lens epithelium (HLE) cells and the development of posterior capsular opacity (PCO).

SiRNA targeting EGFR effectively prevents posterior capsular opacification after cataract surgery.

Shikonin is a compound from the herbal plant Lithospermum erythrorhizon that has been proved to possess powerful anti-proliferative effect on many kinds of cancers and to be safe in in vivo study. Posterior capsular opacification (PCO), the most frequent complication of cataract surgery, is mainly caused by the uncontrolled proliferation of retained human lens epithelial cells (HLEs). In this study, we investigated the effect of shikonin on the proliferation of HLEs and explored its underlying mechanism of action. Shikonin significantly inhibited the proliferation of HLEs in a dose- and time-dependent manner. Its anti-proliferative effect was exerted through induction of apoptosis. Reactive oxygen species (ROS) generation played an essential role in this apoptotic process. Interestingly, scavenging of ROS completely blocked the apoptosis induced by shikonin. In addition, the treatment of shikonin in HLEs significantly increased the ratio of Bax/Bcl-2, disrupted mitochondria membrane potential (MMP) and activated caspases. The inhibition of caspase largely blocks the apoptosis. The changes of MAPK pathway were also demonstrated. Shikonin effectively inhibited the phosphorylation of ERK, while it activated the phosphorylation of JNK and p38. These results suggested that shikonin inhibited the proliferation of HLEs by inducing apoptosis through ROS generation and the caspase-dependent pathway and the MAPK pathway was also involved.

Shikonin inhibits the proliferation of human lens epithelial cells by inducing apoptosis through ROS and caspase-dependent pathway.

BACKGROUND In view of the high incidence of posterior capsule opacification (PCO) and the effects of TGF-β signaling on the epithelial-mesenchymal transition (EMT) of human lens epithelial cells (LECs), our study aimed to explore the mechanism of the function of TGF-β signaling in LECs EMT. MATERIAL AND METHODS Human lens epithelial cells (HLEC-h3) were treated with TGF-β, ILK siRNA, ILK inhibitor, and NF-κB inhibitor to study the effects of TGF-β, ILK, and NF-κB on cell migration and EMT. Cell migration assay was used to measure cell migration ability. Western blot was performed to detect the expression of ILK, E-cadherin, and a-SMA at the protein level. QRT-PCR was used to detect the expression of ILK at the mRNA level. RESULTS Compared with control cells, TGF-β treatment increased the expression level of ILK HLEC-h3, promoted migration of HLEC-h3 cells, increased the expression level of E-cadherin protein, and decreased the expression level of a-SMA protein. However, treatment with ILK siRNA, ILK inhibitor, and NF-κB inhibitor reversed the effects of TGF-β on HLEC-h3 cells. CONCLUSIONS TGF-β-stimulated ILK regulates the migration and EMT of human LECs via NF-κB.

Transforming Growth Factor β1 (TGF-β1)-Stimulated Integrin-Linked Kinase (ILK) Regulates Migration and Epithelial-Mesenchymal Transition (EMT) of Human Lens Epithelial Cells via Nuclear Factor κB (NF-κB).

Posterior capsular opacification (PCO) remains a major complication of cataract surgery and is the most common reason for loss of vision. PCO is primarily associated with uncontrolled proliferation of residual human lens epithelial cells (HLEs). Sanguinarine is a type of benzophenanthridine alkaloid extracted from the herbaceous plant Sanguinaria canadensis, which is widely used for its anti‑microbial, anti‑inflammatory, anti‑oxidative and anti‑proliferative properties. However, studies examining the effect of sanguinarine on HLEs and the underlying mechanism are scarce. The present study aimed to investigate the effects of sanguinarine on HLEs. An MTT assay was used to determine the effect of sanguinarine on cell viability. Flow cytometry was used to evaluate cell apoptosis, and the mitochondrial membrane potential and reactive oxygen species (ROS) levels. A caspase 3/7 activity assay was also used to evaluate cell apoptosis, while western blotting was performed to determine protein levels. The results demonstrated that sanguinarine exerted an anti‑proliferative effect by inducing ROS, and caused cell apoptosis via mitochondrial and caspase‑dependent pathways. Treatment with sanguinarine led to the loss of mitochondrial membrane potential. Sanguinarine also significantly increased the phosphorylation levels of c‑Jun N‑terminal kinase and p38, which indicated the involvement of the mitogen‑activated protein kinase signaling pathway. These results suggested that sanguinarine may have a noteworthy pro‑apoptotic effect on HLEs, and may be used as a potential drug for PCO or even cataract prevention.

Sanguinarine induces apoptosis of human lens epithelial cells by increasing reactive oxygen species via the MAPK signaling pathway.

To evaluate the outcomes and complications of intravitreal injections of ranibizumab in patients during pars plana vitrectomy for treatment of diabetic vitreous hemorrhage. This retrospective, observational, comparative study included 103 patients (103 eyes) who underwent pars plana vitrectomy for treatment of diabetic vitreous hemorrhage. Sixty-six patients received an intravitreal injection of 0.05 mg (0.05 cc) of ranibizumab at the end of surgery. Main outcome measures were the occurrence of recurrent early vitreous hemorrhage, reoperation, intraocular pressure, best corrected visual acuity. Mean follow-up time was 6 months. The rate of rebleeding in the intravitreal ranibizumab (IVR) group was 6.1% (4 eyes), which is significantly lower than the control group (24.3%, 9 eyes, P < .01). The incidence of postoperative diabetic vitreous hemorrhage (PDVH) was significantly lower in the IVR group than the control group, OR=0.26, 95% CI= (0.06, 0.95). Visual acuity 6 months after operation was better in IVR group (P<.01) There was no difference in mean intraocular pressure between the 2 groups (P=.56). The present clinical study suggests that intravitreal injection of ranibizumab is effective in the prevention of postoperative diabetic vitreous hemorrhage in eyes undergoing pars plana vitrectomy for the treatment of diabetic vitreous hemorrhage.

Intravitreal ranibizumab injection at the end of vitrectomy for diabetic vitreous hemorrhage (Observational Study).

Vitrectomy is one of the main treatments for proliferative diabetic retinopathy (PDR). Postoperative neovascular glaucoma, in which it is difficult to obtain satisfactory results using conventional filtering surgery, is one of the most serious complications of vitrectomy. It often requires destructive surgery, such as ciliary body photocoagulation or freezing, and the outcome with regard to visual acuity (VA) is extremely poor. The purpose of this study was to evaluate the prevalence of neovascular glaucoma (NVG) after modern vitrectomy techniques and investigate how variables assessed before and after vitrectomy are associated with patients who develop NVG after PDR surgery.

Frequency and Risk Factors for Neovascular Glaucoma After Vitrectomy in Eyes with Diabetic Retinopathy: An Observational Study.

In an effort to develop a new class of potent aldose reductase inhibitors against diabetic cataracts, a series of novel 2-thioxothiazolidine-4-one derivatives was synthesized in excellent yields via a facile synthetic route. These compounds were tested against aldehyde (ALR1) and aldose reductase (ALR2) enzymes, where they showed considerable inhibitory activity. Among the tested derivatives, compound 6e showed selective and excellent inhibition of ALR2 over ALR1. The experimental diabetes was induced by the intraperitoneal administration of streptozotocin in male Wistar rats. Compound 6e showed positive modulation of body weight, blood glucose, and blood insulin levels in diabetic rats. Compound 6e also showed ALR2 inhibition as evidenced by Western blot analysis in lens homogenates of Wistar rats having cataract. The docking study of 6e was also performed inside the active site of ALR2 to enumerate the key contacts for inhibitory activity.

Article	Year
SiRNA targeting EGFR effectively prevents posterior capsular opacification after cataract surgery. Molecular vision\| PubMed ID: 21921987	2011
Shikonin inhibits the proliferation of human lens epithelial cells by inducing apoptosis through ROS and caspase-dependent pathway. Molecules (Basel, Switzerland)\| PubMed ID: 24962386	2014
Transforming Growth Factor β1 (TGF-β1)-Stimulated Integrin-Linked Kinase (ILK) Regulates Migration and Epithelial-Mesenchymal Transition (EMT) of Human Lens Epithelial Cells via Nuclear Fact... Medical science monitor : international medical journal of experimental and clinical research\| PubMed ID: 30332398	2018
Sanguinarine induces apoptosis of human lens epithelial cells by increasing reactive oxygen species via the MAPK signaling pathway. Molecular medicine reports\| PubMed ID: 30942394	2019
Intravitreal ranibizumab injection at the end of vitrectomy for diabetic vitreous hemorrhage (Observational Study). Medicine\| PubMed ID: 31096535	2019
Frequency and Risk Factors for Neovascular Glaucoma After Vitrectomy in Eyes with Diabetic Retinopathy: An Observational Study. Diabetes therapy : research, treatment and education of diabetes and related disorders\| PubMed ID: 31321746	2019
Substituted 2-thioxothiazolidin-4-one derivatives showed protective effects against diabetic cataract via inhibition of aldose reductase. Archiv der Pharmazie\| PubMed ID: 32237167	2020

Wanrong Huang

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