Mitochondria are multifunctional cellular organelles that are major producers of reactive oxygen species (ROS) in eukaryotes; to maintain the redox balance, they are supplemented with different ROS ...scavengers, including mitochondrial peroxiredoxins (Prdxs). Mitochondrial Prdxs have physiological and pathological significance and are associated with the initiation and progression of various cancer types. In this review, we have focused on signaling involving ROS and mitochondrial Prdxs that is associated with cancer development and progression. An upregulated expression of Prdx3 and Prdx5 has been reported in different cancer types, such as breast, ovarian, endometrial, and lung cancers, as well as in Hodgkin's lymphoma and hepatocellular carcinoma. The expression of Prdx3 and Prdx5 in different types of malignancies involves their association with different factors, such as transcription factors, micro RNAs, tumor suppressors, response elements, and oncogenic genes. The microenvironment of mitochondrial Prdxs plays an important role in cancer development, as cancerous cells are equipped with a high level of antioxidants to overcome excessive ROS production. However, an increased production of Prdx3 and Prdx5 is associated with the development of chemoresistance in certain types of cancers and it leads to further complications in cancer treatment. Understanding the interplay between mitochondrial Prdxs and ROS in carcinogenesis can be useful in the development of anticancer drugs with better proficiency and decreased resistance. However, more targeted studies are required for exploring the tumor microenvironment in association with mitochondrial Prdxs to improve the existing cancer therapies and drug development.
Left untreated, malignant pleural mesothelioma (MPM) is associated with uniformly poor prognosis. Better survival has been reported with surgery-based multimodality therapy, but to date, no trial has ...demonstrated survival benefit of surgery over other therapies. We evaluated whether cancer-directed surgery influenced survival independently from other predictors in a large population-based dataset.
The SEER database was explored from 1973 to 2009 to identify all cases of pathologically-proven MPM. Age, sex, race, year of diagnosis, histology stage, cancer-directed surgery, radiation, and vital status were analyzed. The association between prognostic factors and survival was estimated using Cox regression and propensity matched analysis.
There were 14,228 patients with pathologic diagnosis of MPM. On multivariable analysis, female gender, younger age, early stage, and treatment with surgery were independent predictors of longer survival. In comparison to no treatment, surgery alone was associated with significant improvement in survival adjusted hazard ratio (adj HR) 0.64 (0.61-0.67), but not radiation adj HR 1.15 (1.08-1.23). Surgery and radiation combined had similar survival as surgery alone adj HR 0.69 (0.64-0.76). Results were similar when cases diagnosed between 1973 and 1999 were compared to cases diagnosed between 2000 and 2009.
Despite developments in surgical and radiation techniques, the prognosis for MPM patients has not improved over the past 4 decades. Cancer-directed surgery is independently associated with better survival, suggesting that multimodal surgery-based therapy can benefit these patients. Further research in adjuvant treatment is necessary to improve prognosis in this challenging disease.
In this paper, we propose an amount estimation method for food intake based on both color and depth images. Two pairs of color and depth images are captured pre- and post-meals. The pre- and ...post-meal color images are employed to detect food types and food existence regions using Mask R-CNN. The post-meal color image is spatially transformed to match the food region locations between the pre- and post-meal color images. The same transformation is also performed on the post-meal depth image. The pixel values of the post-meal depth image are compensated to reflect 3D position changes caused by the image transformation. In both the pre- and post-meal depth images, a space volume for each food region is calculated by dividing the space between the food surfaces and the camera into multiple tetrahedra. The food intake amounts are estimated as the difference in space volumes calculated from the pre- and post-meal depth images. From the simulation results, we verify that the proposed method estimates the food intake amount with an error of up to 2.2%.
In this paper, we propose an intra-picture prediction method for depth video by a block clustering through a neural network. The proposed method solves a problem that the block that has two or more ...clusters drops the prediction performance of the intra prediction for depth video. The proposed neural network consists of both a spatial feature prediction network and a clustering network. The spatial feature prediction network utilizes spatial features in vertical and horizontal directions. The network contains a 1D CNN layer and a fully connected layer. The 1D CNN layer extracts the spatial features for a vertical direction and a horizontal direction from a top block and a left block of the reference pixels, respectively. 1D CNN is designed to handle time-series data, but it can also be applied to find the spatial features by regarding a pixel order in a certain direction as a timestamp. The fully connected layer predicts the spatial features of the block to be coded through the extracted features. The clustering network finds clusters from the spatial features which are the outputs of the spatial feature prediction network. The network consists of 4 CNN layers. The first 3 CNN layers combine two spatial features in the vertical and horizontal directions. The last layer outputs the probabilities that pixels belong to the clusters. The pixels of the block are predicted by the representative values of the clusters that are the average of the reference pixels belonging to the clusters. For the intra prediction for various block sizes, the block is scaled to the size of the network input. The prediction result through the proposed network is scaled back to the original size. In network training, the mean square error is used as a loss function between the original block and the predicted block. A penalty for output values far from both ends is introduced to the loss function for clear network clustering. In the simulation results, the bit rate is saved by up to 12.45% under the same distortion condition compared with the latest video coding standard.
Over‐activation of microglia cells in the brain contributes to neurodegenerative processes promoted by the production of various neurotoxic factors including pro‐inflammatory cytokines and nitric ...oxide. Recently, accumulating evidence has suggested that mitochondrial dynamics are an important constituent of cellular quality control and function. However, the role of mitochondrial dynamics in microglial activation is still largely unknown. In this study, we determined whether mitochondrial dynamics are associated with the production of pro‐inflammatory mediators in lipopolysaccharide (LPS)‐stimulated immortalization of murine microglial cells (BV‐2) by a v‐raf/v‐myc carrying retrovirus (J2). Excessive mitochondrial fission was observed in lentivirus‐transfected BV‐2 cells stably expressing DsRed2‐mito following LPS stimulation. Furthermore, mitochondrial localization of dynamin‐related protein 1 (Drp1) (a key regulator of mitochondrial fission) was increased and accompanied by de‐phosphorylation of Ser637 in Drp1. Interestingly, inhibition of LPS‐induced mitochondrial fission and reactive oxygen species (ROS) generation by Mdivi‐1 and Drp1 knock‐down attenuated the production of pro‐inflammatory mediators via reduced nuclear factor kappa‐light‐chain‐enhancer of activated B cells (NF‐κB) and mitogen‐activated protein kinase (MAPK) signaling. Our results demonstrated for the first time that mitochondrial fission regulates mitochondrial ROS production in activated microglial cells and influences the expression of pro‐inflammatory mediators through the activation of NF‐κB and MAPK. We therefore suggest that mitochondrial dynamics may be essential for understanding pro‐inflammatory mediator expression in activated microglial cells. This could represent a new therapeutic approach for preventing neurodegenerative diseases.
LPS induced excessive mitochondrial fission through mitochondrial localization of de‐phosphorylation of Ser637 Drp1. Interestingly, inhibition of LPS‐induced mitochondrial fission and mitochondrial ROS generation by Mdivi‐1 and Drp1 shRNA attenuate the production of pro‐inflammatory mediators via reduced NF‐κB and MAPK signaling. Our results suggest that mitochondrial dynamics may be essential for understanding pro‐inflammatory mediator expression in activated microglial cells.
LPS induced excessive mitochondrial fission through mitochondrial localization of de‐phosphorylation of Ser637 Drp1. Interestingly, inhibition of LPS‐induced mitochondrial fission and mitochondrial ROS generation by Mdivi‐1 and Drp1 shRNA attenuate the production of pro‐inflammatory mediators via reduced NF‐κB and MAPK signaling. Our results suggest that mitochondrial dynamics may be essential for understanding pro‐inflammatory mediator expression in activated microglial cells.
Drug resistance in epithelial ovarian cancer (EOC) is reportedly attributed to the existence of cancer stem cells (CSC), because in most cancers, CSCs still remain after chemotherapy. To overcome ...this limitation, novel therapeutic strategies are required to prevent cancer recurrence and chemotherapy-resistant cancers by targeting cancer stem cells (CSCs). We screened an FDA-approved compound library and found four voltage-gated calcium channel blockers (manidipine, lacidipine, benidipine, and lomerizine) that target ovarian CSCs. Four calcium channel blockers (CCBs) decreased sphere formation, viability, and proliferation, and induced apoptosis in ovarian CSCs. CCBs destroyed stemness and inhibited the AKT and ERK signaling pathway in ovarian CSCs. Among calcium channel subunit genes, three L- and T-type calcium channel genes were overexpressed in ovarian CSCs, and downregulation of calcium channel genes reduced the stem-cell-like properties of ovarian CSCs. Expressions of these three genes are negatively correlated with the survival rate of patient groups. In combination therapy with cisplatin, synergistic effect was shown in inhibiting the viability and proliferation of ovarian CSCs. Moreover, combinatorial usage of manidipine and paclitaxel showed enhanced effect in ovarian CSCs xenograft mouse models. Our results suggested that four CCBs may be potential therapeutic drugs for preventing ovarian cancer recurrence.
Dynamin‐related protein 1 (DRP1) is a mitochondrial membrane GTPase and regulates mitochondrial fission. In this study, we found that the cytokine RANKL increased the expression of DRP1 and its ...receptor proteins, Fis1, Mid49, and Mid 51, during osteoclast formation in mouse bone marrow‐derived macrophages. Inactivation of the kinase GSK3β appeared to induce DRP1 expression. DRP1 knockdown or the DRP1 inhibitor Mdivi1 suppressed osteoclast differentiation via downregulation of c‐Fos and NFATc1, the key transcription factor for osteoclast formation. Finally, the DRP1 inhibitor suppressed lipopolysaccharide‐induced osteoclast formation in a calvarial model and ovariectomy‐induced bone loss in vivo. Taken together, our data demonstrate that DRP1 positively contributes to RANKL‐induced osteoclast differentiation by regulating the c‐Fos–NFATc1 axis, suggesting the importance of mitochondrial DRP1 in osteoclastogenesis.
Airflow in a multi-zone building can be a major cause of pollutant transfer, excessive energy consumption, and occupants discomfort. The key to monitoring airflows and mitigating related problems is ...to obtain a comprehensive understanding of pressure relationships within the buildings. This study proposes a visualization method for representing pressure distribution within a multi-zone building by using a novel pressure-sensing system. The system consists of a Master device and a couple of Slave devices that are connected with each other by a wireless sensor network. A 4-story office building and a 49-story residential building were installed with the system to detect pressure variations. The spatial and numerical mapping relationships of each zone were further determined through grid-forming and coordinate-establishing processes for the building floor plan. Lastly, 2D and 3D visualized pressure mappings of each floor were generated, illustrating the pressure difference and spatial relationship between adjacent zones. It is expected that the pressure mappings derived from this study will allow building operators to intuitively perceive the pressure variations and the spatial layouts of the zones. These mappings also make it possible for operators to diagnose the differences in pressure conditions between adjacent zones and plan a control scheme for the HVAC system more efficiently.
Peroxiredoxins (PRDXs) are expressed in the ovary and during ovulation. PRDX1 activity related to the immuno-like response during ovulation is unknown. We investigated the roles of Prdx1 on TLR4 and ...ERK1/2 signaling from the ovulated cumulus–oocyte complex (COC) using Prdx1-knockout (K/O) and wild-type (WT) mice. Ovulated COCs were collected 12 and 16 h after pregnant mare serum gonadotropin/hCG injection. PRDX1 protein expression and COC secretion factors (Il-6, Tnfaip6, and Ptgs2) increased 16 h after ovulated COCs of the WT mice were obtained. We treated the ovulated COCs in mice with LPS (0.5 μg/mL) or hyaluronidase (Hya) (10 units/mL) to induce TLR4 activity. Intracellular reactive oxygen species (ROS), cumulus cell apoptosis, PRDX1, TLR4/P38/ERK1/2 protein expression, and COC secretion factors’ mRNA levels increased in LPS- and Hya-treated COCs. The ERK inhibitor (U0126) and Prdx1 siRNA affected TLR4/ERK1/2 expression. The number and cumulus expansion of ovulated COCs by ROS were impaired in Prdx1 K/O mice but not in WT ones. Prdx1 gene deletion induced TLR4/P38/ERK1/2 expression and cumulus expansion genes. These results show the controlling roles of PRDX1 for TLR4/P38/ERK1/2 signaling activity in ovulated mice and the interlink of COCs with ovulation.
Strategies for cancer treatment have traditionally focused on suppressing cancer cell behavior, but many recent studies have demonstrated that regulating the tumor microenvironment (TME) can also ...inhibit disease progression. Macrophages are major TME components, and the direction of phenotype polarization is known to regulate tumor behavior, with M2-like polarization promoting progression. It is also known that reactive oxygen species (ROS) in macrophages drive M2 polarization, and M2 polarization promote lung cancer progression. Lung cancer patients with lower expression of the antioxidant enzyme peroxiredoxin 5 (Prx5) demonstrate poorer survival. This study revealed that Prx5 deficiency in macrophages induced M2 macrophage polarization by lung cancer. We report that injection of lung cancer cells produced larger tumors in Prx5-deficit mice than wild-type mice independent of cancer cell Prx5 expression. Through co-culture with lung cancer cell lines, Prx5-deficient macrophages exhibited M2 polarization, and reduced expression levels of the M1-associated inflammatory factors iNOS, TNFα, and Il-1β. Moreover, these Prx5-deficient macrophages promoted the proliferation and migration of co-cultured lung cancer cells. Conversely, suppression of ROS generation by N-acetyl cysteine (NAC) inhibited the M2-like polarization of Prx5-deficient macrophages, increased expression levels of inflammatory factors, inhibited the proliferation and migration of co-cultured lung cancer cells, and suppressed tumor growth in mice. These findings suggest that blocking the M2 polarization of macrophages may promote lung cancer regression.
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•Increased lung cancer cell proliferation in Prx5 -/- mice.•Deficiency of Prx5 in macrophages increased susceptibility to M2 macrophage polarization by lung cancer cells.•Deficiency of Prx5 in macrophages promoted lung cancer development.•Macrophage Prx5 has a pivotal role in macrophage polarization.
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