Expression of Tripartite Motif-Containing Proteactiin 11 (TRIM11) is Associated with the Progression of Human Prostate Cancer and is Downregulated by MicroRNA-5193.

BACKGROUND Tripartite motif-containing protein 11 (TRIM11), encoded by the TRIM11 gene, has been studied in some human malignant tumors. MicroRNA-5193 (miRNA-5193) was predicted to target TRIM11, according to bioinformatics data from TargetScan. However, the roles of TRIM11 and miRNA-5193 in prostate cancer remain unknown. This study aimed to investigate the regulatory effects of miRNA-5193 on the expression of TRIM11 in prostate cancer tissues compared with adjacent normal prostate, and in human prostate cancer cell lines, PC3 and DU145 in vitro. MATERIAL AND METHODS Prostate tumor tissue and adjacent normal tissue from 137 patients with stage T1c (n=66), stage T2 (n=48), and stage T3 (n=23) prostate cancer were studied. Expression levels of the TRIM 11 protein and the TRIM11 gene in prostate cancer, normal prostate tissue, and human prostate cancer cell lines, PC3 and DU145, were measured by Western blot and quantitative real-time polymerase chain reaction (qRT-PCR), respectively. Transfection with TRIM11 small interfering RNA (siRNA) resulted in gene knockdown. Transfection with a miR-5193 mimic resulted in overexpression of miR-5193. Proliferation and invasion assays were performed for PC3 and DU145 cells in vitro. RESULTS TRIM11 expression was upregulated in prostate cancer specimens compared with normal prostate tissue and was significantly correlated with reduced outcome. In human prostate cancer cell lines, PC3 and DU145, TRIM11 overexpression promoted cell proliferation. Upregulation of miR-5193 downregulated the expression of TRIM11. CONCLUSIONS TRIM11 was upregulated in prostate cancer tissue and was associated with reduced prognosis. TRIM11 expression increased cell proliferation in vitro and was downregulated by miR-5193.

CMS-NET: deep learning algorithm to segment and quantify the ciliary muscle in swept-source optical coherence tomography images.

Background: The ciliary muscle plays a role in changing the shape of the crystalline lens to maintain the clear retinal image during near work. Studying the dynamic changes of the ciliary muscle during accommodation is necessary for understanding the mechanism of presbyopia. Optical coherence tomography (OCT) has been frequently used to image the ciliary muscle and its changes during accommodation in vivo. However, the segmentation process is cumbersome and time-consuming due to the large image data sets and the impact of low imaging quality. Objectives: This study aimed to establish a fully automatic method for segmenting and quantifying the ciliary muscle on the basis of optical coherence tomography (OCT) images. Design: A perspective cross-sectional study. Methods: In this study, 3500 signed images were used to develop a deep learning system. A novel deep learning algorithm was created from the widely used U-net and a full-resolution residual network to realize automatic segmentation and quantification of the ciliary muscle. Finally, the algorithm-predicted results and manual annotation were compared. Results: For segmentation performed by the system, the total mean pixel value difference (PVD) was 1.12, and the Dice coefficient, intersection over union (IoU), and sensitivity values were 93.8%, 88.7%, and 93.9%, respectively. The performance of the system was comparable with that of experienced specialists. The system could also successfully segment ciliary muscle images and quantify ciliary muscle thickness changes during accommodation. Conclusion: We developed an automatic segmentation framework for the ciliary muscle that can be used to analyze the morphological parameters of the ciliary muscle and its dynamic changes during accommodation.

Reduced Radial Peripapillary Capillary in Pathological Myopia Is Correlated With Visual Acuity.

Purpose: To quantify the radial peripapillary capillary (RPC) density and the peripapillary retinal nerve fiber layer (pRNFL) thickness in pathological myopia and examine associations among these factors and best-corrected visual acuity (BCVA). Methods: The cohort was composed of 41 eyes as control and 79 eyes with high myopia (59 simple high myopia, 20 pathological myopia). Optical coherence tomography angiography was done to obtain RPC density and pRNFL thickness, superficial retinal capillary plexus (SRCP), and deep retinal capillary plexus (DRCP) density. The axial length (AL) was measured. Correlations among BCVA, RPC density, pRNFL thickness, AL, and other parameters were determined. Results: For pathological myopia, the densities of RPC, SRCP, and DRCP were significantly less than those of the control and simple high myopia groups (p ≤ 0.005). There was no statistical difference in pRNFL thickness between pathological myopia and simple high myopia (p = 0.063), whereas there was significant difference in global pRNFL thickness between pathological myopia and control (p = 0.008). The global RPC density showed the greatest area under the curve (AUC = 0.962, sensitivity = 94.74%, specificity = 90.00%, cutoff value = 47.8%) for pathological myopia, whereas the AUC of pRNFL thickness, SRCP, and DRCP were only 0.675, 0.824, and 0.865, respectively. The univariate and multiple linear regression models showed that RPC density, SRCP density, and AL were correlated with BCVA (All p < 0.05). In the final BCVA model with multiple generalized estimating equation analysis, AL, RPC density and interaction between RPC and AL were shown (all p < 0.03). For an eye with AL ≥ 27.94 mm, global RPC density was predicted to be less than 48.77% with a high risk of visual impairment. Conclusion: Peripapillary alterations, both the decreasing RPC density and pRNFL thickness, occurred in pathological myopia compared with the control. The RPC density was associated with BCVA, and this relationship was affected by AL.

STAT3 activation by catalpol promotes osteogenesis-angiogenesis coupling, thus accelerating osteoporotic bone repair.

BACKGROUND: Bone fracture repair has gained a lot of attention due to the high incidence of delayed union or even nonunion especially in osteoporotic patients, resulting in a dreadful impact on the quality of life. However, current therapies involve the costly expense and hence become unaffordable strategies for fracture recovery. Herein, developing new strategies for better bone repair is essential and urgent. Catalpol treatment has been reported to attenuate bone loss and promote bone formation. However, the mechanisms underlying its effects remain unraveled. METHODS: Rat bone marrow mesenchymal stem cells (BMSCs) were isolated from rat femurs. BMSC osteogenic ability was assessed using ALP and ARS staining, immunofluorescence, and western blot analysis. BMSC-mediated angiogenic potentials were determined using the western blot analysis, ELISA testing, scratch wound assay, transwell migration assay, and tube formation assay. To investigate the molecular mechanism, the lentivirus transfection was used. Ovariectomized and sham-operated rats with calvaria defect were analyzed using micro-CT, H&E staining, Masson's trichrome staining, microfil perfusion, sequential fluorescent labeling, and immunohistochemistry assessment after administrated with/without catalpol. RESULTS: Our results manifested that catalpol enhanced BMSC osteoblastic differentiation and promoted BMSC-mediated angiogenesis in vitro. More importantly, this was conducted via the JAK2/STAT3 pathway, as knockdown of STAT3 partially abolished beneficial effects in BMSCs. Besides, catalpol administration facilitated bone regeneration as well as vessel formation in an OVX-induced osteoporosis calvarial defect rat model. CONCLUSIONS: The data above showed that catalpol could promote osteogenic ability of BMSC and BMSC-dependent angiogenesis through activation of the JAK2/STAT3 axis, suggesting it may be an ideal therapeutic agent for clinical medication of osteoporotic bone fracture.

Therapeutic effect of SIRT3 on glucocorticoid-induced osteonecrosis of the femoral head via intracellular oxidative suppression.

Glucocorticoid-induced osteonecrosis of the femoral head (GIONFH) is a serious complication after long-term or excess administration of clinical glucocorticoids intervention, and the pathogenic mechanisms underlying have not been clarified yet. Oxidative stress is considered as a major cause of bone homeostasis disorder. This study is aimed to explore the potential relevance between SIRT3 and GIONFH, as well as the effect of resveratrol, which has been reported for its role in SIRT3 activation, on dexamethasone-induced oxidative stress and mitochondrial compromise in bone marrow stem cells (BMSCs). In this study, our data showed that SIRT3 level was declined in GIONFH rat femoral head, corresponding to a resultant decrease of SIRT3 expression in dexamethasone-treated BMSCs in vitro. We also found that dexamethasone could result in oxidative injury in BMSCs, and resveratrol treatment reduced this deleterious effect via a SIRT3-dependent manner. Moreover, our results demonstrated that rewarding effect of resveratrol on BMSCs osteogenic differentiation was via activation of AMPK/PGC-1α/SIRT3 axis. Meanwhile, resveratrol administration prevented the occurrence of GIONFH, enhanced SIRT3 expression and reduced oxidative level in GIONFH model rats. Therefore, our study provides basic evidence that SIRT3 may be a promising therapeutic target for GIONFH treatment and resveratrol could be an ideal agent for clinical uses.