Knockout of PERK protects rat Müller glial cells against OGD-induced endoplasmic reticulum stress-related apoptosis.

BACKGROUND: The pathological basis for many retinal diseases, retinal ischemia is also one of the most common causes of visual impairment. Numerous ocular diseases have been linked to Endoplasmic reticulum(ER)stress. However, there is still no clear understanding of the relationship between ER stress and Müller glial cells during retinal ischemia and hypoxia. This study examined the effects of ER stress on autophagy and apoptosis-related proteins, as well as the microtubule-related protein tau in rMC-1 cells. METHODS: rMC-1 cells were cultured in vitro. RT-PCR、immunofluorescence and Western blotting revealed the expression levels of associated mRNAs and proteins, and the CCK-8 and flow cytometry assays detected cell apoptosis. RESULTS: The results showed that under OGD(Oxygen-glucose deprivation) conditions, the number of rMC-1 cells was decreased, the PERK/eIF2a pathway was activated, and the expressions of p-tau, LC3、Beclin1 and Caspase-12 proteins were increased. After the PERK knockout, the expression of the above proteins was decreased, and the apoptosis was also decreased. CONCLUSION: According to the findings of this study, specific downregulation of PERK expression had an anti-apoptotic effect on OGD-conditioned rMC-1 cells. There is a possibility that this is one of the mechanisms of MG cell apoptosis during retinal ischemic injury.

Identification of Graves' ophthalmology by laser-induced breakdown spectroscopy combined with machine learning method.

Diagnosis of the Graves' ophthalmology remains a significant challenge. We identified between Graves' ophthalmology tissues and healthy controls by using laser-induced breakdown spectroscopy (LIBS) combined with machine learning method. In this work, the paraffin-embedded samples of the Graves' ophthalmology were prepared for LIBS spectra acquisition. The metallic elements (Na, K, Al, Ca), non-metallic element (O) and molecular bands ((C-N), (C-O)) were selected for diagnosing Graves' ophthalmology. The selected spectral lines were inputted into the supervised classification methods including linear discriminant analysis (LDA), support vector machine (SVM), k-nearest neighbor (kNN), and generalized regression neural network (GRNN), respectively. The results showed that the predicted accuracy rates of LDA, SVM, kNN, GRNN were 76.33%, 96.28%, 96.56%, and 96.33%, respectively. The sensitivity of four models were 75.89%, 93.78%, 96.78%, and 96.67%, respectively. The specificity of four models were 76.78%, 98.78%, 96.33%, and 96.00%, respectively. This demonstrated that LIBS assisted with a nonlinear model can be used to identify Graves' ophthalmopathy with a higher rate of accuracy. The kNN had the best performance by comparing the three nonlinear models. Therefore, LIBS combined with machine learning method can be an effective way to discriminate Graves' ophthalmology.

Pantoprazole, an FDA-approved proton-pump inhibitor, suppresses colorectal cancer growth by targeting T-cell-originated protein kinase.

T-cell-originated protein kinase (TOPK) is highly expressed in several cancer cells and promotes tumorigenesis and progression, and therefore, it is an important target for drug treatment of tumor. Pantoprazole (PPZ) was identified to be a TOPK inhibitor from FDA-approved drug database by structure based virtual ligand screening. Herein, the data indicated that pantoprazole inhibited TOPK activities by directly binding with TOPK in vitro and in vivo. Ex vivo studies showed that pantoprazole inhibited TOPK activities in JB6 Cl41 cells and HCT 116 colorectal cancer cells. Moreover, knockdown of TOPK in HCT 116 cells decreased their sensitivities to pantoprazole. Results of an in vivo study demonstrated that i.p. injection of pantoprazole in HCT 116 colon tumor-bearing mice effectively suppressed cancer growth. The TOPK downstream signaling molecule phospho-histone H3 in tumor tissues was also decreased after pantoprazole treatment. In short, pantoprazole can suppress growth of colorectal cancer cells as a TOPK inhibitor both in vitro and in vivo.