Search

Yuri Kwon,1 Sang Hoon Park,1 Ji-Won Kim,1 Yeji Ho,1 Hyeong-Min Jeon,1 Min-Jung Bang,1 Gu-In Jung,1 Seon-Min Lee,3 Gwang-Moon Eom,1,2 Seong-Beom Koh,3 Jeong-Whan Lee,1,2 Heung Seok Jeon41Biomedical Engineering, 2Research Institute of Biomedical Engineering, Konkuk University, Chungju, Korea; 3Department of Neurology, Korea University College of Medicine, Seoul, Korea; 4Department of Computer Engineering, Konkuk University, Chungju, KoreaPurpose: Freezing of gait (FOG), increasing the fall risk and limiting the quality of life, is common at the advanced stage of Parkinson’s disease, typically in old ages. A simple and unobtrusive FOG detection system with a small calculation load would make a fast presentation of on-demand cueing possible. The purpose of this study was to find a practical FOG detection system.Patients and methods: A sole-mounted sensor system was developed for an unobtrusive measurement of acceleration during gait. Twenty patients with Parkinson’s disease participated in this study. A simple and fast time-domain method for the FOG detection was suggested and compared with the conventional frequency-domain method. The parameters used in the FOG detection were optimized for each patient.Results: The calculation load was 1,154 times less in the time-domain method than the conventional method, and the FOG detection performance was comparable between the two domains (P=0.79) and depended on the window length (P

Background and Objectives: We assessed the ability of positron emission tomography-computed tomography (PET/CT) to detect synchronous colonic pathology and determined the significance of 18F-fluorodeoxyglucose (18F-FDG) activity in the colon of gastric cancer patients.Methods: A total of 239 gastric cancer patients who underwent PET/CT and colonoscopy preoperatively were included. FDG uptake patterns on PET/CT were classified as (1) group A, focal; (2) group B, diffuse; and (3) group C, no uptake. The PET/CT findings were compared with the results of concurrent colonoscopy.Results: In group A, a total of 123 polyps of >0 mm were observed. Of these, nine polyps were colonic adenocarcinomas and six were high-grade dysplasia. The incidence of colonic adenocarcinomas was significantly higher in group A than in the other two groups (p = 0.037). There was a significant correlation between SUVmax values and incidence of colonic polyps of >10 mm (r = 0.471, p = 0.04). The distribution pattern of SUVmax in polyps with adenoma (>10 mm) was less homogenous than in polyps (>10 mm) with adenocarcinoma.Conclusions: The focal colonic FDG uptake in PET/CT requires colonoscopic confirmation. The suspicion of colonic malignancy increased in the presence of polyps >10 mm that showed a positive correlation with the SUVmax. [ABSTRACT FROM AUTHOR]

Glioblastoma multiforme (GBM) is the most fatal form of brain cancer in humans, with a dismal prognosis and a median overall survival rate of less than 15 months upon diagnosis. Glioma stem cells (GSCs), have recently been identified as key contributors in both tumor initiation and therapeutic resistance in GBM. Both public dataset analysis and direct differentiation experiments on GSCs have demonstrated that CREB5 is more highly expressed in undifferentiated GSCs than in differentiated GSCs. Additionally, gene silencing by short hairpin RNA (shRNA) of CREB5 has prevented the proliferation and self-renewal ability of GSCs in vitro and decreased their tumor forming ability in vivo. Meanwhile, RNA-sequencing, luciferase reporter assay, and ChIP assay have all demonstrated the closely association between CREB5 and OLIG2. These findings suggest that targeting CREB5 could be an effective approach to overcoming GSCs., (© 2024. The Author(s).)

Glioblastoma (GBM) is the most lethal brain cancer with a dismal prognosis. Stem-like GBM cells (GSCs) are a major driver of GBM propagation and recurrence; thus, understanding the molecular mechanisms that promote GSCs may lead to effective therapeutic approaches. Through in vitro clonogenic growth-based assays, we determined mitogenic activities of the ligand molecules that are implicated in neural development. We have identified that semaphorin 3A (Sema3A), originally known as an axon guidance molecule in the CNS, promotes clonogenic growth of GBM cells but not normal neural progenitor cells (NPCs). Mechanistically, Sema3A binds to its receptor neuropilin-1 (NRP1) and facilitates an interaction between NRP1 and TGF-β receptor 1 (TGF-βR1), which in turn leads to activation of canonical TGF-β signaling in both GSCs and NPCs. TGF-β signaling enhances self-renewal and survival of GBM tumors through induction of key stem cell factors, but it evokes cytostatic responses in NPCs. Blockage of the Sema3A/NRP1 axis via shRNA-mediated knockdown of Sema3A or NRP1 impeded clonogenic growth and TGF-β pathway activity in GSCs and inhibited tumor growth in vivo. Taken together, these findings suggest that the Sema3A/NRP1/TGF-βR1 signaling axis is a critical regulator of GSC propagation and a potential therapeutic target for GBM.

This study compared the condylar volume, length, and articular eminence (AE) characteristics of normal individuals to those with unilateral and bilateral juvenile idiopathic osteoarthritis (JOA). The 116 patients were divided into four groups: Control (n = 16), affected condyle of unilateral JOA (Aff-Uni) (n = 36), non-affected condyle of JOA (NonAff-uni) (n = 36), and bilateral JOA (Bilateral) (n = 28). The differences in condyle volume and length and AE were analyzed using ANOVA and Bonferroni post-hoc tests. The results showed that Bilateral had a significantly different condylar volume, especially in the condylar head ( p < 0.01), specifically the middle, anterior, and medial parts ( p < 0.05). Condylar length also differed among the groups, with differences observed between the control group and the other three groups, as well as between the bilateral group and the other three groups ( p < 0.01). AE total volume differed between the control group and Aff-Uni. In the detailed comparison, Aff-Uni and NonAff-Uni were smaller than the control group in the posterior, lateral, and medial sections ( p < 0.05). In conclusion, depending on the involvement of unilateral or bilateral JOA, there were differences in condylar volume and AE when compared to the normal control group. Therefore, a prognosis should be evaluated by distinguishing between patients with unilateral and bilateral JOA.

Radiation therapy (RT) provides therapeutic benefits for patients with glioblastoma (GBM), but inevitably induces poorly understood global changes in GBM and its microenvironment (TME) that promote radio-resistance and recurrence. Through a cell surface marker screen, we identified that CD142 (tissue factor or F3) is robustly induced in the senescence-associated β-galactosidase (SA-βGal)-positive GBM cells after irradiation. F3 promotes clonal expansion of irradiated SA-βGal + GBM cells and orchestrates oncogenic TME remodeling by activating both tumor-autonomous signaling and extrinsic coagulation pathways. Intratumoral F3 signaling induces a mesenchymal-like cell state transition and elevated chemokine secretion. Simultaneously, F3-mediated focal hypercoagulation states lead to activation of tumor-associated macrophages (TAMs) and extracellular matrix (ECM) remodeling. A newly developed F3-targeting agent potently inhibits the aforementioned oncogenic events and impedes tumor relapse in vivo. These findings support F3 as a critical regulator for therapeutic resistance and oncogenic senescence in GBM, opening potential therapeutic avenues., Competing Interests: Declaration of interests H-M.J. and J.L. are co-inventors on a filed patent application for the use of truncated F7 recombinant protein to treat cancer., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Recent studies indicate that signaling molecules traditionally associated with central nervous system function play critical roles in cancer. Dopamine receptor signaling is implicated in various cancers including glioblastoma (GBM) and it is a recognized therapeutic target, as evidenced by recent clinical trials with a selective dopamine receptor D2 (DRD2) inhibitor ONC201. Understanding the molecular mechanism(s) of the dopamine receptor signaling will be critical for development of potent therapeutic options. Using the human GBM patient-derived tumors treated with dopamine receptor agonists and antagonists, we identified the proteins that interact with DRD2. DRD2 signaling promotes glioblastoma (GBM) stem-like cells and GBM growth by activating MET. In contrast, pharmacological inhibition of DRD2 induces DRD2-TRAIL receptor interaction and subsequent cell death. Thus, our findings demonstrate a molecular circuitry of oncogenic DRD2 signaling in which MET and TRAIL receptors, critical factors for tumor cell survival and cell death, respectively, govern GBM survival and death. Finally, tumor-derived dopamine and expression of dopamine biosynthesis enzymes in a subset of GBM may guide patient stratification for DRD2 targeting therapy., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Inc.)

COVID-19 is a highly contagious respiratory infection caused by the SARS-CoV-2 virus. The infected lung epithelial cells secrete a group of chemokines and cytokines, which triggers harmful cytokine storms and hyper-thrombotic responses. Recent studies have proposed that viral-induced senescence is responsible for cytokine release and inflammation in COVID-19 patients. However, it is unknown whether cellular senescence is commonly triggered after viral infection and how inflammation and thrombosis, hyper-activated in these patients, are functionally connected. To address these questions, we conducted a bioinformatics-based meta-analysis using single-cell and bulk RNA sequencing datasets obtained from human patient studies, animal models, and cell lines infected with SARS-CoV-2 and other respiratory viruses. We found that the senescence phenotype is robustly upregulated in most SARS-CoV-2-infected patients, especially in the infected lung epithelial cells. Notably, the upregulation of Tissue factor (F3), a key initiator of the extrinsic blood coagulation pathway, occurs concurrently with the upregulation of the senescence-associated secretory phenotype (SASP) factors. Furthermore, F3 levels are positively correlated with the senescence and hyper-coagulation gene signatures in COVID-19 patients. Together, these data demonstrate the prevalence of senescence in respiratory viral infection and suggest F3 as a critical link between inflammation, thrombosis, and senescence in these disease states., (© 2022. The Author(s).)

Lymph node fibroblastic reticular cells (LN-FRCs) provide functional structure to LNs and play important roles in interactions between T cells and antigen-presenting cells. However, the direct impact of LN-FRCs on naive CD4+ T cell differentiation has not been explored. Here, we show that T cell zone FRCs of LNs (LN-TRCs) express CD25, the α chain of the IL-2 receptor heterotrimer. Moreover, LN-TRCs trans-present IL-2 to naive CD4+ T cells through CD25, thereby facilitating early IL-2-mediated signaling. CD25-deficient LN-TRCs exhibit attenuated STAT5 phosphorylation in naive CD4+ T cells during T cell differentiation, promoting T helper 17 (Th17) cell differentiation and Th17 response-related gene expression. In experimental autoimmune disease models, disease severity was elevated in mice lacking CD25 in LN-TRCs. Therefore, our results suggest that CD25 expression on LN-TRCs regulates CD4+ T cell differentiation by modulating early IL-2 signaling of neighboring, naive CD4+ T cells, influencing the overall properties of immune responses., (© 2022 Kim et al.)

Poly(A)-binding protein (PABP) is a translation initiation factor that interacts with the poly(A) tail of mRNAs. PABP bound to poly(A) stimulates translation by interacting with the eukaryotic initiation factor 4G (eIF4G), which brings the 3' end of an mRNA close to its 5' m7G cap structure through consecutive interactions of the 3'-poly(A)-PABP-eIF4G-eIF4E-5' m7G cap. PABP is a highly abundant translation factor present in considerably larger quantities than mRNA and eIF4G in cells. However, it has not been elucidated how eIF4G, present in limited cellular concentrations, is not sequestered by mRNA-free PABP, present at high cellular concentrations, but associates with PABP complexed with the poly(A) tail of an mRNA. Here, we report that RNA-free PABPs dimerize with a head-to-head type configuration of PABP, which interferes in the interaction between PABP and eIF4G. We identified the domains of PABP responsible for PABP-PABP interaction. Poly(A) RNA was shown to convert the PABP-PABP complex into a poly(A)-PABP complex, with a head-to-tail-type configuration of PABP that facilitates the interaction between PABP and eIF4G. Lastly, we showed that the transition from the PABP dimer to the poly(A)-PABP complex is necessary for the translational activation function., (© The Author(s) 2021. Published by Oxford University Press on behalf of Nucleic Acids Research.)

The skin is subject to both intrinsic aging caused by metabolic processes in the body and extrinsic aging caused by exposure to environmental factors. Intrinsic aging is an important obstacle to in vitro experimentation as its long-term progression is difficult to replicate. Here, we accelerated aging of a full-thickness skin equivalent by applying periodic mechanical stimulation, replicating the circadian rhythm for 28 days. This aging skin model was developed by culturing a full-thickness, three-dimensional skin equivalent with human fibroblasts and keratinocytes to produce flexible skin-on-a-chip. Accelerated aging associated with periodic compressive stress was evidenced by reductions in the epidermal layer thickness, contraction rate, and secretion of Myb. Increases in β-galactosidase gene expression and secretion of reactive oxygen species and transforming growth factor-β1 were also observed. This in vitro aging skin model is expected to greatly accelerate drug development for skin diseases and cosmetics that cannot be tested on animals.

Purpose: Microbiota manipulation through selected probiotics may be a promising tool to prevent cancer development as well as onset, to improve clinical efficacy for cancer treatments. The purpose of this study was to evaluate change in microbiota composition after-probiotics supplementation and assessed the efficacy of probiotics in improving quality of life (QOL) in postoperative cancer patients., Methods: Stool samples were collected from 30 cancer patients from February to October 2020 before (group I) and after (group II) 8 weeks of probiotics supplementation. We performed 16S ribosomal RNA gene sequencing to evaluate differences in gut microbiota between groups by comparing gut microbiota diversity, overall composition, and taxonomic signature abundance. The health-related QOL was evaluated through the EORTC Quality of life Questionnaire Core 30 questionnaire., Results: Statistically significant differences were noted in group II; increase of Shannon and Simpson index (P = 0.004 and P = 0.001), decrease of Bacteroidetes and Fusobacteria at the phylum level (P = 0.032 and P = 0.014, retrospectively), increased of beneficial bacteria such as Weissella (0.096% vs. 0.361%, P < 0.004), Lactococcus (0.023% vs. 0.16%, P < 0.001), and Catenibacterium (0.0% vs. 0.005%, P < 0.042) at the genus level. There was a significant improvement in sleep disturbance (P = 0.039) in group II., Conclusion: Gut microbiota in cancer patients can be manipulated by specific probiotic strains, result in an altered microbiota. Microbiota modulation by probiotics can be considered as part of a supplement that helps to increase gut microbiota diversity and improve QOL in cancer patients after surgery., Competing Interests: Conflict of Interest: No potential conflict of interest relevant to this article was reported., (Copyright © 2021, the Korean Surgical Society.)

Objective: To evaluate the efficacy and safety of treatment for neurogenic heterotopic ossification (NHO) using extracorporeal shock wave therapy (ESWT) in persons with spinal cord injury (SCI). Design: Single case report. Setting: Department of Physical Medicine and Rehabilitation, Veterans Health Service Medical Center. Participants: A 55-year-old male with cervical SCI, who developed painful NHO around the right hip joint. Interventions: Ultrasound-guided ESWT that used 4,000 shocks at the rate of 3 Hz and the energy flux density between 0.056 and 0.068 mJ/mm 2 was applied to the NHO region a total of 7 times, weekly. Outcome Measures: We assessed the treatment outcomes using a visual analog scale (VAS) score, wheelchair sitting time and size of NHO. Result : After 7 weeks of ESWT treatment, his pain reduced from a VAS score of 7-8 to 3 and his wheelchair sitting time increased. However, there was no significant change of size of NHO. Conclusion: The application of ESWT could be a possible alternative to other treatments for NHO in persons with SCI. Clinical Trial Registry Number : 2019-03-003.

Background: Joint loads in different walking strategies during stair descent have been investigated in terms of the joint moment in association with the risk of osteoarthritis. However, the absorption mechanisms of the potential energy loss are not known., Objective: This study aims to compare the mechanical energy absorptions in lower limb joints in different initial foot contact strategies., Methods: Nineteen young subjects walked down on instrumented stairs with two different strategies, i.e., forefoot and rearfoot strike. Power and energy at lower limb joints during stance phase were compared between strategies., Results: Lower limb joints absorbed 73 ± 11% of the potential energy released by descending stairs and there was no difference between strategies. Rearfoot strategy absorbed less energy than forefoot strategy at the ankle joint in the 1st phase, which was compensated mainly by more energy absorption at the knee in the 2nd phase and less energy generation at the hip joints in the 3rd phase., Conclusion: The results suggest that a leg absorbs most of the potential energy while descending stairs irrespective of the walking strategies and that any reduction of energy absorption at one joint is compensated by other joints. Greater energy absorption at the knee joint compared to the other joints suggests high burden of knee joint muscles and connective tissues during stair-descent, which is even more significant for the rearfoot strike strategy.

Gait modification strategies are effective in reducing knee joint loads, which are associated with the development and progression of knee osteoarthritis (OA). However, the effect of modification of the initial foot contact method in high-loading descending task was not investigated. Here, we show that the initial foot contact strategy significantly alters knee joint moments during descending tasks. We found that the second peak flexion moment was lower for the forefoot strike (FFS) than for the rearfoot strike (RFS) in both stair and ramp descent. As for the peak adduction moment, the second peak was lower for the FFS in stair descent, but two peaks were inconsistent in ramp descent. Our results demonstrate that the knee joint loads can be reduced by simple modification of the initial foot contact strategy. In both descending modalities, the FFS may benefit people with early OA in the patellofemoral joint, whose progression is associated with the peak flexion moment. Likewise, the FFS during stair descent may benefit people with early OA in the medial knee, whose progression is associated with the peak adduction moment. The results would be helpful for prevention and rehabilitation programmes of knee OA.

Purpose: Many studies have shown that the enhanced recovery after surgery (ERAS) protocols improve postoperative surgical outcomes. The purpose of this study was to observe the effects on postoperative inflammatory markers and to explore the effects of a high degree of compliance and the use of epidural anesthesia on inflammation and surgical outcomes., Methods: Four hundred patients underwent colorectal cancer surgery at 2 hospitals during 2 different periods, namely, from January 2006 to December 2009 and from January 2017 to July 2017. Data related to the patient's clinicopathological features, inflammatory markers, percentage of compliance with elements of the ERAS protocol, and use of epidural anesthesia were collected from a prospectively maintained database., Results: The complication rate and the length of hospital stay (LOS) were less in the ERAS group than in the conventional group (P = 0.005 and P ≤ 0.001, respectively). The postoperative white blood cell count and the duration required for leukocytes to normalize were reduced in patients following the ERAS protocol (P ≤ 0.001). Other inflammatory markers, such as lymphocyte count (P = 0.008), neutrophil/lymphocyte ratio (P = 0.032), and C-reactive protein level (P ≤ 0.001), were lower in the ERAS protocol group. High compliance ( ≥ 70%) was strongly associated with the complication rate and the LOS (P = 0.008 and P ≤ 0.001, respectively)., Conclusion: ERAS protocols decrease early postoperative inflammation and improves short-term postoperative recovery outcomes such as complication rate and the LOS. High compliance ( ≥ 70%) with the ERAS protocol elements accelerates the positive effects of ERAS on surgical outcomes; however, the effect on inflammation was very small.

The in vitro tests in current research employ simple culture methods that fail to mimic the real human tissue. In this study, we report drug testing with a 'pumpless skin-on-a-chip' that mimics the structural and functional responses of human skin. This model is a skin equivalent constituting two layers of the skin, dermis and epidermis, developed using human primary fibroblasts and keratinocytes. Using the gravity flow device system, the medium was rotated at an angle of 15 degrees on both sides so as to circulate through the pumpless skin-on-a-chip microfluidic channel. This pumpless skin-on-a-chip is composed of upper and lower chips, and is manufactured using porous membranes so that medium can be diffused and supplied to the skin equivalent. Drug testing was performed using Curcuma longa leaf extract (CLLE), a natural product cosmetic ingredient, to evaluate the usefulness of the chip and the efficacy of the cosmetic ingredient. It was found that the skin barrier function of the skin epidermis layer is enhanced to exhibit antiaging effects. This result indicates that the pumpless skin-on-a-chip model can be potentially used not only in the cosmetics and pharmaceutical industries but also in clinical applications as an alternative to animal studies.

Purpose: Osteoarthritis (OA) of the temporomandibular joint (TMJ) elicits cartilage and subchondral bone defects. Growth hormone (GH) promotes chondrocyte growth. The aim of this study was to evaluate the efficacy of intra-articular injections of GH to treat TMJ-OA., Materials and Methods: Monosodium iodoacetate (MIA) was used to induce OA in the TMJs of rats. After confirming the induction of OA, recombinant human GH was injected into the articular cavities of rats. Concentrations of GH and IGF-1 were measured in the blood and synovial fluid, and OA grades of cartilage and subchondral bone degradation were recorded by histological examination and micro-computed tomography., Results: MIA-induced OA in the rat TMJ upregulated insulin-like growth factor-1 (IGF-1) rather than GH levels. GH and IGF-1 concentrations were increased after local injection of GH, compared with controls. Locally injected GH lowered osteoarthritic scores in the cartilage and subchondral bone of the TMJ., Conclusion: Intra-articular injection of GH improved OA scores in rat TMJs in both cartilage and subchondral bone of the condyles without affecting condylar bone growth. These results suggest that intra-articular injection of human GH could be a suitable treatment option for TMJ-OA patients in the future., Competing Interests: The authors have no potential conflicts of interest to disclose., (© Copyright: Yonsei University College of Medicine 2020.)

Background: Developing personalized strategies for cancer has shown good efficacies., Methods: We assessed the molecular targets programmed death ligand 1 (PD-L1), microsatellite instability (MSI), and PIK3CA. Seventy-four patients with liposarcomas who underwent curative resection were assessed for PD-L1 expression in the tumor and tumor-infiltrating lymphocytes (TILs), mismatch repair proteins (MLH1, PMS2, MSH2, and MSH6) by immunohistochemistry, MSI using polymerase chain reaction, and PIK3CA mutation/amplification using pyrosequencing and fluorescence in situ hybridization., Results: Seventeen (23%) cases were TIL+ (≥1 + expression) and associated with longer 5-year overall survival than those with TIL- tumors (84.4 vs. 60.8%, p = 0.007). Six (35.3%) PD-L1+ tumors were detected only in TIL+ cases, with none detected in tumor cells. Two well-differentiated liposarcomas showed MSI, one low and one high with concurrent loss of MLH1, MSH6, and PMS2. PIK3CA mutation was detected in 7 (9.5%) [exon 9 (n = 4) and exon 20 (n = 3)] and only 1 Q546K mutation was a PD-L1+ tumor. PIK3CA copy number gain was detected in 18 (24.4%) and was associated with TIL+ tumors (p = 0.045)., Conclusions: Our comprehensive immuno-molecular panel suggests that liposarcoma should be categorized based on the molecular genomic subtype for precision medicine., (© 2020 S. Karger AG, Basel.)

Background: Bone loss is highly prevalent after gastrectomy in gastric cancer patients. Therefore, the efficacy of medical treatment should be evaluated in patients undergoing gastrectomy., Methods: We conducted an unblinded, randomized controlled trial of patients who underwent gastrectomy to treat gastric cancer. The intention-to-treat participants (n = 107) were randomly assigned to receive either alendronate at a weekly dose of 70 mg and daily elemental calcium (500 mg) with cholecalciferol (1000 IU) or daily elemental calcium (500 mg) with cholecalciferol (1000 IU) only. The primary endpoint was defined by the changes in bone mineral density of four measurement sites: the lumbar spine, femur neck, total hip, and trochanter. Changes in bone turnover markers, osteocalcin and collagen I carboxyterminal telopeptide were also observed., Results: At baseline, there were no differences between the two groups in bone mineral density. In the lumbar spine and trochanter, there were no significant percentage changes compared with the baseline in the alendronate group, but a significant decrease was noted in the control group (p < 0.001 for both lumbar spine and trochanter). In the femur neck and total hip, a larger decrease was observed compared with the baseline in the control group (p < 0.001 for both femur neck and total hip). Significant percentage increases in serum osteocalcin compared with baseline were noted in the control group (p for trend <0.001), but there was no change in the alendronate group (p for trend = 0.713). Collagen I carboxyterminal telopeptide significantly declined in the alendronate group over 12 months (p for trend <0.001)., Conclusions: Prevention and treatment with bisphosphonate effectively reduces bone loss by suppressing bone resorption in gastric cancer patients undergoing gastrectomy., (Copyright © 2019. Published by Elsevier Inc.)

Interleukin (IL)-15 is an essential immune-modulator with high potential for use in cancer treatment. Natural IL-15 has a low biological potency because of its short half-life and difficulties in mass-production. IL-15Rα, a member of the IL-15 receptor complex, is famous for its high affinity to IL-15 and its ability to lengthen the half-life of IL-15. We have double-transfected IL-15 and its truncated receptor IL-15Rα into CT26 colon cancer cells to target them for intracellular assembly. The secreted IL-15:IL-15Rα complexes were confirmed in ELISA and Co-IP experiments. IL-15:IL15Rα secreting clones showed a higher anti-tumor effect than IL-15 secreting clones. Furthermore, we also evaluated the vaccine and therapeutic efficacy of the whole cancercell vaccine using mitomycin C (MMC)-treated IL-15:IL15Rα secreting CT26 clones. Three sets of experiments were evaluated; (1) therapeutics, (2) vaccination, and (3) longterm protection. Wild-type CT26-bearing mice treated with a single dose of MMC-inactivated secreted IL-15:IL-15Rα clones prolonged survival compared to the control group. Survival of MMC-inactivated IL-15:IL-15Rα clone-vaccinated mice (without any further adjuvant) exceeded up to 100%. This protection effect even lasted for at least three months after the immunization. Secreted IL-15:IL-15Rα clones challenging trigger anti-tumor response via CD4 + T, CD8 + T, and natural killer (NK) cell-dependent cytotoxicity. Our result suggested that cell-based vaccine secreting IL-15:IL-15Rα, may offer the new tools for immunotherapy to treat cancer.

Higd-1a/HIMP1-a/HIG1, a mitochondrial inner membrane protein, promotes cell survival under low glucose and hypoxic conditions. We previously reported that it interacts with Opa1, a factor involved in mitochondrial fusion, to regulate mitochondrial homeostasis. In the present study, we found that depletion of Higd-1a inhibited the proliferation of pancreatic cancer cells in vitro and in mice xenografts. Higd-1a knockdown did not itself lead to cell death but it caused cell cycle arrest through induction of p27 KIP1 and hypo-phosphorylation of RB protein. Knockdown of Higd-1a also induced cellular senescence as shown by increased granularity and SA-β-galactosidase activity. We further showed that the mitochondrial stress induced by Higd-1a led to reduced ERK phosphorylation. Inhibition of the ERK pathway with U0126 induced p27 KIP1 expression in the pancreatic cancer cells, confirming that the cell cycle retardation was the result of inhibition of the ERK pathway. Array analysis of human pancreatic cancers revealed that expression of Higd-1a was significantly elevated in pancreatic cancer tissues compared to normal tissue. Collectively, our results demonstrate that Higd-1a plays an important role in the proliferation of pancreatic cancer cells by regulating the pERK/p27 KIP1 /pRB signaling pathway., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Reactive oxygen species (ROS) are important cellular second messengers involved in various aspects of cell signaling. ROS are elevated in multiple types of cancer cells, and this elevation is known to be involved in pathological processes of cancer. Although high levels of ROS exert cytotoxic effects on cancer cells, low levels of ROS stimulate cell proliferation and survival by inducing several pro‑survival signaling pathways. In addition, ROS have been shown to induce epithelial‑mesenchymal transition (EMT), which is essential for the initiation of metastasis. However, the precise mechanism of ROS‑induced EMT remains to be elucidated. In the present study, it was indicated that ROS induce EMT by activating Snail expression, which then represses E‑cadherin expression in MCF‑7 cells. It was further indicated that distal‑less homeobox‑2 (Dlx‑2), one of the human Dlx gene family proteins involved in embryonic development, acts as an upstream regulator of ROS‑induced Snail expression. It was also revealed that ROS treatment induces the glycolytic switch, a phenomenon whereby cancer cells primarily rely on glycolysis instead of mitochondrial oxidative phosphorylation for ATP production, even in the presence of oxygen. In addition, ROS inhibited oxidative phosphorylation and caused cytochrome c oxidase inhibition via the Dlx‑2/Snail cascade. These results suggest that ROS induce EMT, the glycolytic switch and mitochondrial repression by activating the Dlx‑2/Snail axis, thereby playing crucial roles in MCF‑7 cancer cell progression.

This retrospective study aims to investigate the proportion and characteristics of patients who perceive dental treatment (DT) as a cause of oral mucosal lesions (OMLs). A total of 2,302 patients with OMLs visited the Oral Medicine Department of Pusan National University Dental Hospital. The patients were divided into a study group (280 patients who perceived DT as a cause of OMLs) and a control group (300 randomly selected patients). Percentages of DT types, clinical characteristics, and the frequencies of diagnoses and chief complaint (CC) sites were analyzed in both groups. Among the patients with OMLs, 12.2% attributed OMLs to DT. Among the diagnoses, allergic reaction (AR) and traumatic ulcer/irritation (TU) were significantly more frequent in the study group. The DT types most frequently perceived as the cause of OMLs were implants. According to patients, TU and candida occurred most frequently following denture placement (68-79%), whereas oral lichen planus and AR occurred most commonly following implant treatment (52-53%). The gingiva was significantly more frequent as the CC site in the study group than in the control group (P < 0.05 for all outcomes). It is important to inform patients of the potential complications of DT and the importance of regular check-ups.

Background: Guardix-SG is a poloxamer-based antiadhesive agent. The aim of this study was to investigate its efficacy in preventing abdominal adhesions in gastric cancer patients undergoing gastrectomy. Few clinical studies have reported that antiadhesive agent reduces the incidence of adhesion after gastrectomy., Methods: We conducted a multicenter trial from June 2013 and August 2015 in patients with gastric adenocarcinoma undergoing radical gastrectomy. Patients were randomly assigned to the Guardix treatment or control group. Postoperative adhesions were diagnosed based on postoperative symptoms, plain x-ray films, and computed tomography. The primary endpoint of the study was the incidence of small bowel obstruction in the first postoperative year. The secondary end-point was the safety of Guardix-SG., Results: The study included 109 patients in the Guardix group and 105 patients in the control group. The groups were similarly matched with pathological stage, operation type, anastomosis method, midline incision length, and the extent of lymph node dissection. Eight in the Guardix group and 21 in the control group experienced intestinal obstruction during the 1-year follow-up period. The cumulative incidence of small bowel obstruction was significantly lower in the Guardix group compared to that seen in the control group (4.7% vs 8.6% at 6 months and 7.3% vs 20% at 1 year; P = .007, log-rank test). There were no differences in postoperative complications and adverse events., Conclusion: Guardix-SG significantly decreased the incidence of intestinal obstruction without affecting the incidence of postoperative complications.

Hemagglutinin (HA) displayed on a ferritin nano-cage has been shown to be effective in generating a potent immune response against a broad range of influenza infections. Here, we showed that conjugation of flagellin together with HA to the exterior surface of the ferritin cage greatly enhanced not only the humoral immune response in mice but also antigen-specific T cell responses that include Th1 cytokine secretion. The effect of flagellin remained essentially unchanged when the molar ratio of flagellin to HA was reduced from 1:1 to 1:3. Injection of the ferritin-HA-flagellin cage provided protection against lethal virus challenge in mice. We used a small immunoglobulin fragment V L 12.3 as a convenient method for attaching HA and flagellin to the ferritin cage. This attachment method can be used for rapid screening of a variety of protein cages and nano-assemblies to identify the most suitable carrier and adjuvant proteins for the target antigen., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: The purpose of this study was to investigate how lower extremity kinematics and kinetics change when running downhill., Methods: Fifteen male recreational runners ran on an instrumented treadmill with three different slope conditions [level (0°), moderate (-6°), and steep (-9°)] at a controlled speed of 3.2 m/s. Ten consecutive steps were selected for analysis for each of the slope conditions and the order of slope conditions was randomized. Synchonized motion analysis and force plate were used to determine joint kinematics and kinetics., Results: Compared to level running, participants demonstrated significantly larger knee flexion but smaller ankle plantar-flexion and hip flexion during downhill running (Ps < 0.05). Significantly smaller peak propulsive ground reaction forces and posterior impulses were found during downhill running (Ps < 0.05). Furthermore, participants experienced significantly larger extension moment and negative joint power at the knee (Ps < 0.05) but smaller plantar-flexion moment and negative joint power at the ankle during downhill running (Ps < 0.05). Negative net joint work increased for all joints with increased declinations and the knee joint showed the greatest increase in negative net joint work amongst the three joints (Ps < 0.05)., Significance: These findings indicate that runners modify their running mechanics resulting in greater kinetic demand on the knee during downhill running. Differences in lower extremity injury mechanisms with different running slopes may be linked to the changes in loading at the knee but further investigation using clinical trials is needed to support the potential relationship., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Metastasis is a major obstacle to the efficient and successful treatment of cancer. Initiation of metastasis requires epithelial-mesenchymal transition (EMT) that is regulated by several transcription factors, including Snail and ZEB1/2. EMT is closely linked to the acquisition of cancer stem cell (CSC) properties and chemoresistance, which contribute to tumor malignancy. Tumor suppressor p53 inhibits EMT and metastasis by negatively regulating several EMT-inducing transcription factors and regulatory molecules; thus, its inhibition is crucial in EMT, invasion, metastasis, and stemness. Metabolic alterations are another hallmark of cancer. Most cancer cells are more dependent on glycolysis than on mitochondrial oxidative phosphorylation for their energy production, even in the presence of oxygen. Cancer cells enhance other oncogenic metabolic pathways, such as glutamine metabolism, pentose phosphate pathway, and the synthesis of fatty acids and cholesterol. Metabolic reprogramming in cancer is regulated by the activation of oncogenes or loss of tumor suppressors that contribute to tumor progression. Oncogenic metabolism has been recently linked closely with the induction of EMT or CSC phenotypes by the induction of several metabolic enzyme genes. In addition, several transcription factors and molecules involved in EMT or CSCs, including Snail, Dlx-2, HIF-1 α , STAT3, TGF- β , Wnt, and Akt, regulate oncogenic metabolism. Moreover, p53 induces metabolic change by directly regulating several metabolic enzymes. The collective data indicate the importance of oncogenic metabolism in the regulation of EMT, cell invasion and metastasis, and adoption of the CSC phenotype, which all contribute to malignant transformation and tumor development. In this review, we highlight the oncogenic metabolism as a key regulator of EMT and CSC, which is related with tumor progression involving metastasis and chemoresistance. Targeting oncometabolism might be a promising strategy for the development of effective anticancer therapy.

Background: We recently reported that myeloid sirtuin 6 (Sirt6) is a critical determinant of phenotypic switching and the migratory responses of macrophages. Given the prominent role of macrophages in the pathogenesis of rheumatoid arthritis (RA), we tested whether myeloid Sirt6 deficiency affects the development and exacerbation of RA., Methods: Arthritis was induced in wild type and myeloid Sirt6 knockout (mS6KO) mice using collagen-induced and K/BxN serum transfer models. Sirt6 expression (or activity) and inflammatory activities were compared in peripheral blood mononuclear cells (PBMCs) and monocytes/macrophages obtained from patients with RA or osteoarthritis., Findings: Based on clinical score, ankle thickness, pathology, and radiology, arthritis was more severe in mS6KO mice relative to wild type, with a greater accumulation of macrophages in the synovium. Consistent with these findings, myeloid Sirt6 deficiency increased the migration potential of macrophages toward synoviocyte-derived chemoattractants. Mechanistically, Sirt6 deficiency in macrophages caused an inflammation with increases in acetylation and protein stability of forkhead box protein O1. Conversely, ectopic overexpression of Sirt6 in knockout cells reduced the inflammatory responses. Lastly, PBMCs and monocytes/macrophages from RA patients exhibited lower expression of Sirt6 than those from patients with osteoarthritis, and their Sirt6 activity was inversely correlated with disease severity., Interpretation: Our data identify a role of myeloid Sirt6 in clinical and experimental RA and suggest that myeloid Sirt6 may be an intriguing therapeutic target. FUND: Medical Research Center Program and Basic Science Research Program through the National Research Foundation of Korea., (Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.)

Abastract: BACKGROUND: Despite the development of newer treatments, the prognosis for patients with stage IV gastric cancer remains grave. This study evaluated the efficacy of gastrectomy following response to chemotherapy in patients with stage IV gastric cancer., Methods: A total of 419 patients who were diagnosed with stage IV gastric cancer were identified from the multi-institutional Catholic Gastric Cancer Study Group database. The patients were divided into four groups: 212 were in the chemotherapy only (CTx) group, 124 were in the chemotherapy after palliative gastrectomy (G-CTx) group, 23 were in the radical gastrectomy after chemotherapy (CTx-G) group, and 60 were in the best supportive care group. To compensate for the effects of chemotherapy, cases of chemotherapy responsive were analyzed separately. To identify factors affecting survival rates, cure rates for surgery in the surgery group were analyzed., Results: The 3-year survival rate of the CTx-G group was significantly higher than that of the CTx group (42.8 vs. 12.0%, p = 0.001). Moreover, the CTx-G group's 3-year survival rate was greater than that of the G-CTx group (42.8 vs. 37.1%, p = 0.207). Chemotherapy-responsive patients in the CTx-G group had a better 3-year survival rate than those in the G-CTx group (46.1 vs. 18.4%, respectively, p = 0.011). In the surgery group, R0 resection led to a significantly better 3-year survival rate than palliative gastrectomy (61.1 vs. 16.2%, p = 0.003)., Conclusions: Adjuvant surgery might improve the survival rate of patients with stage IV gastric cancer, particularly in R0 resection cases.

Importance: The guidelines by the National Comprehensive Cancer Network and the American Society for Clinical Oncology recommend the routine use of thromboprophylaxis for patients with gastric adenocarcinoma. However, many physicians in Asian countries use venous thromboembolism (VTE) prophylaxis much less often because of the perceived lower VTE incidence in this population., Objectives: To evaluate the incidence of postgastrectomy VTE in Korean patients with gastric adenocarcinoma, and to identify the complications and evaluate the efficacy and safety of VTE prevention methods., Design, Setting, and Participants: The Optimal Prophylactic Method for Venous Thromboembolism After Gastrectomy in Korean Patients (PROTECTOR) randomized clinical trial was conducted between August 1, 2011, and March 31, 2015. Patients with histologically confirmed gastric adenocarcinoma presenting to a single center (Seoul St Mary's Hospital in Seoul, South Korea) were enrolled. Patients were randomized to either an intermittent pneumatic compression (IPC)-only group or an IPC+low-molecular-weight (LMW) heparin sodium group. The data were analyzed on intention-to-treat and per protocol bases. Data analysis was performed from April 1, 2016, to October 30, 2017., Main Outcomes and Measures: Venous thromboembolism incidence was the primary outcome. Postoperative complications, particularly those associated with VTE prophylaxis methods, were the secondary end point., Results: Of the 682 patients enrolled and randomized, 447 (65.5%) were male and 245 (34.5%) were female, with a mean (SD) age of 57.67 (12.94) years. Among the 666 patients included in the analysis, the overall incidence of VTE was 2.1%. The incidence of VTE was statistically significantly higher in the IPC-only group compared with the IPC+LMW heparin group (3.6%; 95% CI, 2.05%-6.14% vs 0.6%; 95% CI, 0.17%-2.18%; P = .008). Among the 14 patients (2.1%) with VTE, 13 were asymptomatic and received a deep vein thrombosis diagnosis, whereas 1 patient received a symptomatic pulmonary thromboembolism diagnosis. The overall incidence of bleeding complications was 5.1%. The incidence of bleeding complications was significantly higher in the IPC+LMW heparin group compared with the IPC-only group (9.1% vs 1.2%; P < .001). No cases of VTE-associated mortality were noted., Conclusions and Relevance: Use of IPC alone is inferior to the use of IPC+LMW heparin in preventing postoperative VTE. Because LMW heparin is associated with a high bleeding risk, further study is needed to stratify the patients at high risk for perioperative development of VTE., Trial Registration: ClinicalTrials.gov Identifier: NCT01448746.

Objective: The present study aimed to identify the brain regions involved in upper and lower limb motor and functional recovery after stroke., Methods: Twenty-five patients (mean age 73.4 years; average duration from stroke onset 50.1 months) were examined. Fractional anisotropy (FA) mapping using diffusion tensor imaging, and clinical measures, including the Fugl-Meyer motor assessment of upper and lower limbs, the Modified Barthel Index (MBI), and Functional Ambulation Category, were used for examinations. Linear regression analyses were carried out with the FA map as a dependent variable, each clinical measure as an independent variable, and patient age as a covariate., Results: FA in the internal capsule of the posterior limb of the lesioned hemisphere was significantly associated with Fugl-Meyer motor assessment scores for the upper limbs, whereas FAs in the internal capsule of the posterior limb of the lesioned hemisphere, the posterior corpus callosum of the lesioned hemisphere, and the middle cerebellar peduncle of the contralateral hemisphere were associated with Fugl-Meyer motor assessment scores for the lower limb. FA in brain regions with bilateral connection fibers was commonly associated with the score on the Korean version of the MBI and participants' functional ambulation. Furthermore, the FA in the corticospinal tract in the contralesional hemisphere was also associated with the score on the Korean version of the MBI (corrected P<0.05)., Conclusion: Motor and functional recovery of upper and lower limbs involves different brain regions. This finding is of particular relevance for treatment and recovery in stroke.

We propose a method to reconstruct damaged data based on statistical learning during data acquisition. In the process of measuring the data using a sensor, the damage of the data caused by the defect of the sensor or the environmental factor greatly degrades the performance of data classification. Instead of the traditional PCA based on L2-norm, the PCA features were extracted based on L1-norm and updated by iteratively reweighted fitting using the generalized objective function to obtain robust features for the outlier data. The damaged data samples were reconstructed using weighted linear combination using these features and the projection vectors of L1-norm based PCA. The experimental results on various types of volatile organic compounds (VOCs) data show that the proposed method can be used to reconstruct the damaged data to the original form of the undamaged data and to prevent degradation of classification performance due to data corruption through data reconstruction., Competing Interests: The authors have declared that no competing interests exist.

Glioma stem-like cells (GSCs) contribute to tumor initiation, progression, and therapeutic resistance, but their cellular origin remains largely unknown. Here, using a stem/progenitor cell-fate tracking reporter system in which eGFP is expressed by promoter of OCT4 that is activated in stem/progenitor cells, we demonstrate that eGFP-negative glioma cells (GCs) became eGFP-positive-GCs in both in vitro cultures and in vivo xenografts. These eGFP-positive-GCs exhibited GSC features and primarily localized to the perivascular region in tumor xenografts, similar to the existence of OCT4-expressing GCs in the perivascular region of human glioblastoma specimens. Angiocrine factors, including nitric oxide (NO), converted eGFP-negative-GCs into eGFP-positive-GCs. Mechanistically, NO signaling conferred GSC features to GCs by increasing OCT4 and NOTCH signaling via ID4. NO signaling blockade and a suicide gene induction prevented tumorigenicity with a decrease in eGFP-positive-GCs in the perivascular region. Taken together, our results reveal the molecular mechanism underlying GSCs generation by cancer cell dedifferentiation., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Rapidly growing malignant tumors frequently encounter hypoxia and nutrient (e.g., glucose) deprivation, which occurs because of insufficient blood supply. This results in necrotic cell death in the core region of solid tumors. Necrotic cells release their cellular cytoplasmic contents into the extracellular space, such as high mobility group box 1 (HMGB1), which is a nonhistone nuclear protein, but acts as a proinflammatory and tumor-promoting cytokine when released by necrotic cells. These released molecules recruit immune and inflammatory cells, which exert tumor-promoting activity by inducing angiogenesis, proliferation, and invasion. Development of a necrotic core in cancer patients is also associated with poor prognosis. Conventionally, necrosis has been thought of as an unregulated process, unlike programmed cell death processes like apoptosis and autophagy. Recently, necrosis has been recognized as a programmed cell death, encompassing processes such as oncosis, necroptosis, and others. Metabolic stress-induced necrosis and its regulatory mechanisms have been poorly investigated until recently. Snail and Dlx-2, EMT-inducing transcription factors, are responsible for metabolic stress-induced necrosis in tumors. Snail and Dlx-2 contribute to tumor progression by promoting necrosis and inducing EMT and oncogenic metabolism. Oncogenic metabolism has been shown to play a role(s) in initiating necrosis. Here, we discuss the molecular mechanisms underlying metabolic stress-induced programmed necrosis that promote tumor progression and aggressiveness.

Background: The sitting in an awkward posture for a prolonged time may lead to spinal or musculoskeletal disease. It is important to investigate the joint loads at spine while sitting., Objective: The purpose of this study was to investigate the joint moment and antero-posterior (AP) reaction force at cervico-thoracic and lumbosacral joint for various sitting postures., Methods: Twenty healthy males participated in this study. Six sitting postures were defined from three spinal curvatures (slump, flat, and lordosis) and two arm postures (arms-on-chest and arms-forward). Kinematic and kinetic data were measured in six sitting postures from which joint moment and AP reaction force were calculated by inverse dynamics., Results: In the cervico-thoracic joint, joint moment and AP reaction force were greater in slump than the flat and lordosis postures (p< 0.001) and also in arms-forward posture compared to arms-on-chest posture. In the lumbosacral joint, joint moment and AP reaction force were greater in slump than flat and lordotic posture (p< 0.001) but there was no difference between different arm postures. The joint loads (moment and AP reaction force) at the cervico-thoriacic joint were closely related to the head flexion angle (r> 0.86) while those at the lumbosacral joint were correlated to the trunk flexion angle (r> 0.77). In slump posture, the joint moments were close to or over the extreme of the daily life such as sit-to-stand and walking. Consequently, if the slump is continued for a long time, it may cause pain and diseases at the cervico-thoracic and lumbosacral joints., Conclusions: The results of the study indicated that the lordosis or flat would be better spinal postures. Also, keeping arms close to body would be desirable to reduce joint loads.

Low-loss magnetization dynamics and strong magnetoelastic coupling are generally mutually exclusive properties due to opposing dependencies on spin-orbit interactions. So far, the lack of low-damping, magnetostrictive ferrite films has hindered the development of power-efficient magnetoelectric and acoustic spintronic devices. Here, magnetically soft epitaxial spinel NiZnAl-ferrite thin films with an unusually low Gilbert damping parameter (<3 × 10 -3 ), as well as strong magnetoelastic coupling evidenced by a giant strain-induced anisotropy field (≈1 T) and a sizable magnetostriction coefficient (≈10 ppm), are reported. This exceptional combination of low intrinsic damping and substantial magnetostriction arises from the cation chemistry of NiZnAl-ferrite. At the same time, the coherently strained film structure suppresses extrinsic damping, enables soft magnetic behavior, and generates large easy-plane magnetoelastic anisotropy. These findings provide a foundation for a new class of low-loss, magnetoelastic thin film materials that are promising for spin-mechanical devices., (© 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Purpose: The purpose of the present study was to perform a pattern analysis in patients with temporomandibular disorder (TMD) resulting from unilateral mastication due to chronic periodontitis., Methods: Thirty participants with signs or symptoms of TMD who engaged in unilateral mastication due to periodontitis-related discomfort (test group) were selected. Another 30 subjects exhibiting signs or symptoms of TMD resulting from unilateral mastication not due to chronic periodontitis (control group) were also recruited. An interview-based questionnaire was administered, and an examination of the temporomandibular joint (TMJ) with determination of periodontal status was performed., Results: The duration of unilateral mastication was significantly longer in the control group than in the test group. There was a significant negative correlation between the duration of unilateral mastication and the Community Periodontal Index score. Using the Research Diagnostic Criteria for TMD (RDC/TMD) axis I algorithms, all the subjects were assigned to 3 main groups. The test group exhibited significantly a higher diagnostic distribution of group III (arthralgia, osteoarthritis, or osteoarthrosis), and in both the test and control groups, the number of diagnoses was larger for the non-chewing side. The control group showed a significantly higher diagnostic distribution of group I (myofacial pain), and in both the test and control groups, the number of diagnoses was larger for the chewing side., Conclusions: The results of the present study indicate that unilateral mastication due to chronic periodontitis could induce not only pain but also structural TMJ changes if adequate treatment is not administered and supported within a short time from the onset of the condition. Therefore, immediate treatment of chronic periodontitis is recommended to prevent not only the primary progress of periodontal disease, but also secondary TMJ-related problems. Furthermore, subjects who have suffered chronic long-term periodontitis without treatment should be urged to undergo a TMJ examination., Competing Interests: Conflict of Interest: No potential conflict of interest relevant to this article was reported.

Background: Previous studies have shown that duodenojejunal bypass (DJB) resolves type 2 diabetes. However, this finding has been contradicted by several experimental and human trials and therefore needs to be clarified., Methods: Otsuka Long-Evans Tokushima Fatty (OLETF) rats randomly underwent a sham operation or DJB. Thereafter, we measured daily body weight, serum levels of glucose and gut hormones such as glucagon-like peptide-1, insulin, and leptin., Results: There was no significant difference in weight loss between rats in the DJB and sham-operated groups. There were also no differences in the area under the curve of glucose tolerance between the DJB and sham-operated groups (32466 ± 2261 mg/dL·min vs. 26319 ± 427 mg/dL·min; p = 0.35). Duodenojejunal bypass did not affect plasma concentrations of various gut hormones such as glucagon-like peptide-1, insulin, and leptin., Conclusions: We have shown that DJB alone does not improve glucose tolerance in obese, diabetic OLETF rats. Therefore, it may be that DJB alone is insufficient for diabetic control in obese diabetic rats. The addition of a restrictive component such as sleeve gastrectomy, or a new drug may be necessary for achieving diabetes reversal., (Copyright © 2016. Published by Elsevier Taiwan.)

Most cancer-related signaling pathways sustain their active or inactive status via genetic mutations or various regulatory mechanisms. Previously, we demonstrated that platelet-derived growth factor (PDGF) activates Notch signaling through nitric oxide (NO)-signaling-driven activation of inhibitor of differentiation 4 (ID4) in glioblastoma (GBM) stem cells (GSCs) and endothelial cells in the vascular niche of GBM, leading to maintenance of GSC traits and GBM progression. Here, we determined that the PDGF-NO-ID4-signaling axis is constantly activated through a positive regulatory circuit. ID4 expression significantly increased PDGF subunit B expression in both in vitro cultures and in vivo tumor xenografts and regulated NO synthase 2 (NOS2) expression and NO production by activating PDGF signaling, as well as that of its receptor (PDGFR). Additionally, ectopic expression of PDGFRα, NOS2, or ID4 activated the PDGF-NO-ID4-signaling circuit and enhanced the self-renewal of GBM cell lines. These results suggested that the positive regulatory circuit associated with PDGF-NO-ID4 signaling plays a pivotal role in regulating the self-renewal and tumor-initiating capacity of GSCs and might provide a promising therapeutic target for GBM., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Aim: To evaluate the clinical outcomes of V4c implantable collamer lens (Hole ICL) implantation with regard to the optical quality assessed according to different degrees of decentering., Methods: This included 49 eyes that received conventional ICL and 94 eyes that received Hole ICL. The eyes that received Hole ICL were divided into three groups according to the degree of decentering: group 1, central hole within 1 hole diameter (HD) from the pupil center; group 2, central hole within 1 HD to 2 HD; and group 3, central hole within 2 HD to 3 HD. Visual acuity (VA), intraocular pressure (IOP), and spherical equivalent (SE) values were assessed at 1wk, 1 and 3mo after surgery. The ocular modulation transfer function, Strehl ratio, objective scattering index, and higher order aberrations (HOAs) were measured for 4-mm pupils at 3mo after surgery., Results: There were no significant differences in VA, IOP, and SE among the conventional and Hole ICL groups. With regard to HOAs, values for coma and spherical aberrations showed no differences. The total HOA and trefoil values were significantly higher in group 2 than in group 1 ( P =0.02, 0.03, respectively). There were no significant differences among groups with regard to other optical quality parameter at 3mo after surgery., Conclusion: Our results suggest that Hole ICL implantation provides satisfactory visual quality that is equivalent to that provided by conventional ICL, regardless of the presence of central hole and degree of decentering.

Background: The extent of serosal exposure varies depending on the cross-section of the stomach that is viewed, affected by the visceral peritoneum of the omentum. Although multidetector computed tomography (MDCT) is the most useful method to predict serosal exposure, the MDCT criteria for such exposure by cross-sectional location remain to be established., Methods: The MDCT of gastric cancer patients who underwent surgery, and for whom pathological reports were available, were reviewed by radiologists. The MDCT criteria for invasion depth were divided into five grades: (1) smooth margin; (2) undulating margin; (3) streaky margin within vessels; (4) nodular margin within perigastric vessels; and (5) streaky or nodular margin over the perigastric vessels. The five grades were compared in terms of pathological tumor depth by curvature and wall group., Results: A total of 125 patients of stage ≥ T2 were enrolled. The five MDCT grades correlated with tumor depth (P < 0.001). Exposed serosal lesions of grade 3 (P = 0.031) and 5 (P = 0.030) constituted significantly the largest proportion of wall and curvature cancers, respectively. The accuracy of MDCT in terms of T staging using the five grades was calculated by cross-sectional location. The highest accuracies were associated with curvature- and wall-located tumors (55.1 and 64.3%, respectively) when serosal exposure was graded 5 and 3, respectively. The highest overall accuracy for T staging was 59.2% when the various MDCT criteria were applied by reference to the cross-sectional location., Conclusions: The MDCT criteria for serosal exposure vary by the cross-sectional location of the gastric cancer.

Aim: Gastrectomy is a known risk factor for decreased bone mass. We aimed to evaluate the cumulative incidence and predictive factors of fracture in gastric cancer patients who underwent gastrectomy., Method: We retrospectively reviewed the records of 1687 patients who underwent gastrectomy for gastric cancer at our hospital between September 1991 and December 2008. The exclusion criteria were stage IV gastric cancer, history of cancer recurrence, medical conditions that cause osteoporosis and high-energy injury. Fractures at sites considered to be associated with osteoporosis were diagnosed radiologically., Results: In total, our analysis included the records of 1131 patients. The incidence of postgastrectomy fracture was 42.1 cases per 1000 person-years. Fractures typically occurred within 3.7 ± 0.5 years postoperatively. The cumulative incidence of fracture was 9.1%, 19.7%, and 37.3% by postoperative year 2, 4, and 6, respectively. During the following years, the cumulative incidence increased slowly, up to a final 40.6%. Multivariate analysis showed that older age (hazard ratio, 1.03; 95% confidence interval, 1.01-1.04) and smoking (hazard ratio, 1.35; 95% confidence interval, 1.05-1.73) were significantly associated with fracture, whereas sex, body mass index, percent weight loss, diabetes mellitus, tumour stage, and type of gastrectomy were not., Conclusion: The cumulative incidence of fracture is high in gastric cancer patients who have undergone gastrectomy, and fracture rate is higher during the early postoperative period. Old age and smoking are independent risk factors for postgastrectomy fracture in these patients. More detailed postoperative surveillance and pharmacological intervention should be considered to prevent fracture., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Radiation therapy is one of the major tools of cancer treatment, and is widely used for a variety of malignant tumours. Radiotherapy causes DNA damage directly by ionization or indirectly via the generation of reactive oxygen species (ROS), thereby destroying cancer cells. However, ionizing radiation (IR) paradoxically promotes metastasis and invasion of cancer cells by inducing the epithelial-mesenchymal transition (EMT). Metastasis is a major obstacle to successful cancer therapy, and is closely linked to the rates of morbidity and mortality of many cancers. ROS have been shown to play important roles in mediating the biological effects of IR. ROS have been implicated in IR-induced EMT, via activation of several EMT transcription factors-including Snail, HIF-1, ZEB1, and STAT3-that are activated by signalling pathways, including those of TGF-β, Wnt, Hedgehog, Notch, G-CSF, EGFR/PI3K/Akt, and MAPK. Cancer cells that undergo EMT have been shown to acquire stemness and undergo metabolic changes, although these points are debated. IR is known to induce cancer stem cell (CSC) properties, including dedifferentiation and self-renewal, and to promote oncogenic metabolism by activating these EMT-inducing pathways. Much accumulated evidence has shown that metabolic alterations in cancer cells are closely associated with the EMT and CSC phenotypes; specifically, the IR-induced oncogenic metabolism seems to be required for acquisition of the EMT and CSC phenotypes. IR can also elicit various changes in the tumour microenvironment (TME) that may affect invasion and metastasis. EMT, CSC, and oncogenic metabolism are involved in radioresistance; targeting them may improve the efficacy of radiotherapy, preventing tumour recurrence and metastasis. This study focuses on the molecular mechanisms of IR-induced EMT, CSCs, oncogenic metabolism, and alterations in the TME. We discuss how IR-induced EMT/CSC/oncogenic metabolism may promote resistance to radiotherapy; we also review efforts to develop therapeutic approaches to eliminate these IR-induced adverse effects.