FANCD2 deficiency sensitizes SHH medulloblastoma to radiotherapy via ferroptosis.

Radiotherapy is one of the standard therapeutic regimens for medulloblastoma (MB). Tumor cells utilize DNA damage repair (DDR) mechanisms to survive and develop resistance during radiotherapy. It has been found that targeting DDR sensitizes tumor cells to radiotherapy in several types of cancer, but whether and how DDR pathways are involved in the MB radiotherapy response remain to be determined. Single-cell RNA sequencing was carried out on 38 MB tissues, followed by expression enrichment assays. Fanconi anemia group D2 gene (FANCD2) expression was evaluated in MB samples and public MB databases. The function of FANCD2 in MB cells was examined using cell counting assays (CCK-8), clone formation, lactate dehydrogenase activity, and in mouse orthotopic models. The FANCD2-related signaling pathway was investigated using assays of peroxidation, a malondialdehyde assay, a reduced glutathione assay, and using FerroOrange to assess intracellular iron ions (Fe2+ ). Here, we report that FANCD2 was highly expressed in the malignant sonic hedgehog (SHH) MB subtype (SHH-MB). FANCD2 played an oncogenic role and predicted worse prognosis in SHH-MB patients. Moreover, FANCD2 knockdown markedly suppressed viability, mobility, and growth of SHH-MB cells and sensitized SHH-MB cells to irradiation. Mechanistically, FANCD2 deficiency led to an accumulation of Fe2+ due to increased divalent metal transporter 1 expression and impaired glutathione peroxidase 4 activity, which further activated ferroptosis and reduced proliferation of SHH-MB cells. Using an orthotopic mouse model, we observed that radiotherapy combined with silencing FANCD2 significantly inhibited the growth of SHH-MB cell-derived tumors in vivo. Our study revealed FANCD2 as a potential therapeutic target in SHH-MB and silencing FANCD2 could sensitize SHH-MB cells to radiotherapy via inducing ferroptosis. © 2024 The Pathological Society of Great Britain and Ireland.

Effects of UV/H2O2 Degradation on the Physicochemical and Antibacterial Properties of Fucoidan.

The applications of fucoidan in the food industry were limited due to its high molecular weight and low solubility. Moderate degradation was required to depolymerize fucoidan. A few studies have reported that fucoidan has potential antibacterial activity, but its antibacterial mechanism needs further investigation. In this study, the degraded fucoidans were obtained after ultraviolet/hydrogen peroxide treatment (UV/H2O2) at different times. Their physicochemical properties and antibacterial activities against Staphylococcus aureus and Escherichia coli were investigated. The results showed that the average molecular weights of degraded fucoidans were significantly decreased (up to 22.04 times). They were mainly composed of fucose, galactose, and some glucuronic acid. Fucoidan degraded for 90 min (DFuc-90) showed the strongest antibacterial activities against Staphylococcus aureus and Escherichia coli, with inhibition zones of 27.70 + 0.84 mm and 9.25 + 0.61 mm, respectively. The minimum inhibitory concentrations (MIC) were 8 mg/mL and 4 mg/mL, respectively. DFuc-90 could inhibit the bacteria by damaging the cell wall, accumulating intracellular reactive oxygen species, reducing adenosine triphosphate synthesis, and inhibiting bacterial metabolic activity. Therefore, UV/H2O2 treatment could effectively degrade fucoidan and enhance its antibacterial activity.

The application of blended teaching in medical practical course of clinical skills training.

BACKGROUND: Blended teaching is an effective approach that combines online and offline teaching methods, leading to improved outcomes in medical education compared to traditional offline teaching. In this study, we examined the impact of blended teaching in clinical skills training, a medical practice course. METHODS: This study involved forty-eight undergraduate students studying clinical medicine in the fifth semester at Wuhan University of Science and Technology. The students were divided into two groups: the control group, which received traditional offline teaching, and the experimental group, which received hybrid teaching. Following the completion of the 4-month course, both groups underwent the Objective Structured Clinical Examination (OSCE) to evaluate their proficiency in clinical skills. Furthermore, the experimental group was given a separate questionnaire to gauge their feedback on the Blended Teaching approach. RESULTS: Based on the OSCE scores, the experimental group outperformed the control group significantly (P<0.05). The questionnaire results indicated that a majority of students (54.2%, 3.71 ± 1.06) believed that blended teaching is superior to traditional offline teaching, and a significant number of students (58.3%, 3.79 ± 1.15) expressed their willingness to adopt blended teaching in other courses. Furthermore, students in the experimental group displayed varying levels of interest in different teaching contents, with emergency medicine (79.2%), internal medicine (70.8%), and surgery (66.7%) being the most popular among them. CONCLUSIONS: This research demonstrates for the first time that blended teaching can achieve a good pedagogical effectiveness in the medical practice course, clinical skills training and practice. Moreover, in different teaching contents, the teaching effects are different. In the content of Emergency Medicine and Surgery, which is more attractive to students, the application of blended teaching could result in a better pedagogical outcome than other contents.

RUNX1 knockdown induced apoptosis and impaired EMT in high-grade serous ovarian cancer cells.

Ovarian cancer is the leading cause of death from gynecologic illnesses worldwide. High-grade serous ovarian cancer (HGSOC) is a gynecological tumor that accounts for roughly 70% of ovarian cancer deaths in women. Runt-related transcription factor 1(RUNX1) proteins were identified with overexpression in the HGSOC. However, the roles of RUNX1 in the development of HGSOC are poorly understood. In this study, combined with whole-transcriptome analysis and multiple research methods, RUNX1 was identified as vital in developing HGSOC. RUNX1 knockdown inhibits the physiological function of ovarian cancer cells and regulates apoptosis through the FOXO1-Bcl2 axis. Down-regulated RUNX1 impairs EMT function through the EGFR-AKT-STAT3 axis signaling. In addition, RUNX1 knockdown can significantly increase the sensitivity to clinical drug therapy for ovarian cancer. It is strongly suggested that RUNX1 work as a potential diagnostic and therapeutic target for HGSOC patients with better prognoses and treatment options. It is possible to generate novel potential targeted therapy strategies and translational applications for serous ovarian carcinoma patients with better clinical outcomes.

Lymph Node Metastases in Surgically Resected Solitary Ground-Glass Opacities: A Two-Center Retrospective Cohort Study and Pooled Literature Analysis.

BACKGROUND: An increasing body of evidence supports the noninferiority of sublobar resection compared with lobectomy in terms of survival for patients with early-stage lung cancer with ground-glass opacities (GGOs). However, few studies have focused on the incidence of lymph node (LN) metastases in these patients. We aimed to analyze N1 and N2 lymph node involvement in patients with non-small cell lung cancer (NSCLC) with GGO components stratified with different consolidation tumor ratio (CTR). PATIENTS AND METHODS: We performed two-center studies by retrospectively reviewing a total of 864 patients with NSCLC with semisolid or pure GGO manifestation (diameter ≤ 3 cm). Clinicopathologic features and outcomes were analyzed. We also reviewed 35 studies to characterize the patient with NSCLC population with the GGO manifestation. RESULTS: In both cohorts, there was no LN involvement for pure GGO NSCLC, while solid predominant GGO exhibited a relatively high LN involvement rate. On the basis of a pooled literature analysis, the incidence of pathologic mediastinal LN was 0% and 3.8% for pure and semisolid GGOs, respectively. GGO NSCLCs with CTR ≤ 0.5 also had rare LN involvement (0.1%). CONCLUSIONS: From two cohorts and pooled literature analysis, LN involvement was not observed in patients with pure GGO, and very few patients with semisolid GGO NSCLC with CTR ≤ 0.5 had LN involvement, revealing that it may be unnecessary to perform lymphadenectomy for pure GGOs, while mediastinal lymph node sampling (MLNS) is enough for semisolid GGOs with CTR ≤ 0.5. For the patients with GGO CTR > 0.5, mediastinal lymphadenectomy (MLD) or MLNS should be considered.

A map of the spatial distribution and tumour-associated macrophage states in glioblastoma and grade 4 IDH-mutant astrocytoma.

Tumour-associated macrophages (TAMs) abundantly infiltrate high-grade gliomas and orchestrate immune response, but their diversity in isocitrate dehydrogenase (IDH)-differential grade 4 gliomas remains largely unknown. This study aimed to dissect the transcriptional states, spatial distribution, and clinicopathological significance of distinct monocyte-derived TAM (Mo-TAM) and microglia-derived TAM (Mg-TAM) clusters across glioblastoma-IDH-wild type and astrocytoma-IDH-mutant-grade 4 (Astro-IDH-mut-G4). Single-cell RNA sequencing was performed on four cases of human glioblastoma and three cases of Astro-IDH-mut-G4. Cell clustering, single-cell regulatory network inference, and gene set enrichment analysis were performed to characterize the functional states of myeloid clusters. The spatial distribution of TAM subsets was determined in human glioma tissues using multiplex immunostaining. The prognostic value of different TAM-cluster specific gene sets was evaluated in the TCGA glioma cohort. Profiling and unbiased clustering of 24,227 myeloid cells from glioblastoma and Astro-IDH-mut-G4 identified nine myeloid cell clusters including monocytes, six Mo/Mg-TAM subsets, dendritic cells, and proliferative myeloid clusters. Different Mo/Mg-TAM clusters manifest functional and transcriptional diversity controlled by specific regulons. Multiplex immunostaining of subset-specific markers identified spatial enrichment of distinct TAM clusters at peri-vascular/necrotic areas in tumour parenchyma or at the tumour-brain interface. Glioblastoma harboured a substantially higher number of monocytes and Mo-TAM-inflammatory clusters, whereas Astro-IDH-mut-G4 had a higher proportion of TAM subsets mediating antigen presentation. Glioblastomas with a higher proportion of monocytes exhibited a mesenchymal signature, increased angiogenesis, and worse patient outcome. Our findings provide insight into myeloid cell diversity and its clinical relevance in IDH-differential grade 4 gliomas, and may serve as a resource for immunotherapy development. © 2022 The Pathological Society of Great Britain and Ireland.

Learning 3D Bipedal Walking with Planned Footsteps and Fourier Series Periodic Gait Planning.

Reinforcement learning provides a general framework for achieving autonomy and diversity in traditional robot motion control. Robots must walk dynamically to adapt to different ground environments in complex environments. To achieve walking ability similar to that of humans, robots must be able to perceive, understand and interact with the surrounding environment. In 3D environments, walking like humans on rugged terrain is a challenging task because it requires complex world model generation, motion planning and control algorithms and their integration. So, the learning of high-dimensional complex motions is still a hot topic in research. This paper proposes a deep reinforcement learning-based footstep tracking method, which tracks the robot's footstep position by adding periodic and symmetrical information of bipedal walking to the reward function. The robot can achieve robot obstacle avoidance and omnidirectional walking, turning, standing and climbing stairs in complex environments. Experimental results show that reinforcement learning can be combined with real-time robot footstep planning, avoiding the learning of path-planning information in the model training process, so as to avoid the model learning unnecessary knowledge and thereby accelerate the training process.

Uneven Terrain Walking with Linear and Angular Momentum Allocation.

Uneven terrain walking is hard to achieve for most child-size humanoid robots, as they are unable to accurately detect ground conditions. In order to reduce the demand for ground detection accuracy, a walking control framework based on centroidal momentum allocation is studied in this paper, enabling a child-size humanoid robot to walk on uneven terrain without using ground flatness information. The control framework consists of three controllers: momentum decreasing controller, posture controller, admittance controller. First, the momentum decreasing controller is used to quickly stabilize the robot after disturbance. Then, the posture controller restores the robot posture to adapt to the unknown terrain. Finally, the admittance controller aims to decrease contact impact and adapt the robot to the terrain. Note that the robot uses a mems-based inertial measurement unit (IMU) and joint position encoders to calculate centroidal momentum and use force-sensitive resistors (FSR) on the robot foot to perform admittance control. None of these is a high-cost component. Experiments are conducted to test the proposed framework, including standing posture balancing, structured non-flat ground walking, and soft uneven terrain walking, with a speed of 2.8 s per step, showing the effectiveness of the momentum allocation method.

Overexpression of carnitine palmitoyltransferase 1A promotes mitochondrial fusion and differentiation of glioblastoma stem cells.

Glioma stem cells (GSCs) are self-renewing tumor cells with multi-lineage differentiation potential and the capacity of construct glioblastoma (GBM) heterogenicity. Mitochondrial morphology is associated with the metabolic plasticity of GBM cells. Previous studies have revealed distinct mitochondrial morphologies and metabolic phenotypes between GSCs and non-stem tumor cells (NSTCs), whereas the molecules regulating mitochondrial dynamics in GBM cells are largely unknown. Herein, we report that carnitine palmitoyltransferase 1A (CPT1A) is preferentially expressed in NSTCs, and governs mitochondrial dynamics and GSC differentiation. Expressions of CPT1A and GSC marker CD133 were mutually exclusive in human GBMs. Overexpression of CPT1A inhibited GSC self-renewal but promoted mitochondrial fusion. In contrast, disruption of CPT1A in NSTCs promoted mitochondrial fission and reprogrammed NSTCs toward GSC feature. Mechanistically, CPT1A overexpression increased the phosphorylation of dynamin-related protein 1 at Ser-637 to promote mitochondrial fusion. In vivo, CPT1A overexpression decreased the percentage of GSCs, impaired GSC-derived xenograft growth and prolonged tumor-bearing mice survival. Our work identified CPT1A as a critical regulator of mitochondrial dynamics and GSC differentiation, indicating that CPT1A could be developed as a molecular target for GBM cell-differentiation strategy.

Calcyphosine promotes the proliferation of glioma cells and serves as a potential therapeutic target.

Calcyphosine (CAPS) was initially identified from the canine thyroid. It also exists in many types of tumor, but its expression and function in glioma remain unknown. Here we explored the clinical significance and the functional mechanisms of CAPS in glioma. We found that CAPS was highly expressed in glioma and high expression of CAPS was correlated with poor survival, in glioma patients and public databases. Cox regression analysis showed that CAPS was an independent prognostic factor for glioma patients. Knockdown of CAPS suppressed the proliferation, whereas overexpression of CAPS promoted the proliferation of glioma both in vitro and in vivo. CAPS regulated the G2/M phase transition of the cell cycle, but had no obvious effect on apoptosis. CAPS affected PLK1 phosphorylation through interaction with MYPT1. CAPS knockdown decreased p-MYPT1 at S507 and p-PLK1 at S210. Expression of MYPT1 S507 phosphomimic rescued PLK1 phosphorylation and the phenotype caused by CAPS knockdown. The PLK1 inhibitor volasertib enhanced the therapeutic effect of temozolomide in glioma. Our data suggest that CAPS promotes the proliferation of glioma by regulating the cell cycle and the PLK1 inhibitor volasertib might be a chemosensitizer of glioma. © 2021 The Authors. The Journal of Pathology published by John Wiley & Sons, Ltd. on behalf of The Pathological Society of Great Britain and Ireland.

Platelet-activating factor acetyl hydrolase IB2 dysregulated cell proliferation in ovarian cancer.

BACKGROUND: Ovarian cancer is the leading cause of death from gynaecologic illnessed worldwide. Platelet-activating factor acetyl hydrolase IB2 (PAF-AH IB2) is an intracellular serine esterase that hydrolyzes platelet-activating factor, a G-protein-like trimer with two catalytic subunits and one regulatory subunit. The regulatory role of PAF-AH IB2 in the oncogenesis of ovarian cancer is not well understood. METHODS: In this study, the TCGA dataset and clinical cancer tissue microarray were utilized to investigate abnormal overexpression of PAF-AH IB2 in ovarian cancer. To investigate the impact on the cell proliferation, migration, and tumorigenicity in vitro, PAF-AH IB2 stable knocking down (KD) ovarian cancer cells were established by ShRNA. The whole transcription profiling, tyrosine kinase profiling and standard cell functional assays were integrated to explore the biological importance and mechanism of PAF-AH IB2 modulated in ovarian cancer. RESULTS: PAF-AH IB2 was identified significantly overexpression in four subtypes of ovarian cancer. In vitro, PAF-AH IB2 KD significantly inhibited cancer cell proliferation, migration, and tumorigenicity, activated caspases and caused cell cycle arrest, and made the cells more sensitive to PAF. PAF-AH 1B2 KD cells down-regulated several key regulators of the multiple tyrosine kinases-mediated signaling pathway, suggesting a novel interaction network between the growth factor receptors pathway and PAF-AH 1B2 mediated PAF signalling. CONCLUSIONS: These findings revealed a previously undiscovered role for PAF-AH IB2 as a potenial therapy target and essential signaling mediators in ovarian cancer pathogenesis, as well as new possible preventive and therapeutic strategies to inhibit this enzyme in clinical treatment for ovarian cancer.

Identified Three Interferon Induced Proteins as Novel Biomarkers of Human Ischemic Cardiomyopathy.

Ischemic cardiomyopathy is the most frequent type of heart disease, and it is a major cause of myocardial infarction (MI) and heart failure (HF), both of which require expensive medical treatment. Precise biomarkers and therapy targets must be developed to enhance improve diagnosis and treatment. In this study, the transcriptional profiles of 313 patients' left ventricle biopsies were obtained from the PubMed database, and functional genes that were significantly related to ischemic cardiomyopathy were screened using the Weighted Gene Co-Expression Network Analysis and protein-protein interaction (PPI) networks enrichment analysis. The rat myocardial infarction model was developed to validate these findings. Finally, the putative signature genes were blasted through the common Cardiovascular Disease Knowledge Portal to explore if they were associated with cardiovascular disorder. Three interferon stimulated genes (IFIT2, IFIT3 and IFI44L), as well as key pathways, have been identified as potential biomarkers and therapeutic targets for ischemic cardiomyopathy, and their alternations or mutations have been proven to be strongly linked to cardiac disorders. These novel signature genes could be utilized as bio-markers or potential therapeutic objectives in precise clinical diagnosis and treatment of ischemic cardiomyopathy.

Exosome-mediated transfer of miR-1260b promotes cell invasion through Wnt/ß-catenin signaling pathway in lung adenocarcinoma.

Increasing evidence confirms that exosome-mediated transfer of microRNAs can influence cancer progression including tumor cell invasion, cell proliferation, and drug resistance via cell-cell communication. However, the potential role of exosomal-miR-1260b in lung adenocarcinoma (LAC) remains poorly understood. Thus, this study focused on investigating the function of exosomal-miR-1260b on cell invasion. Exosomal-miR-1260b was found to be higher in plasma of patients with LAC than that of healthy persons via quantitative real-time polymerase chain reaction assay. The sensitivity and specificity of exosomal-miR-1260b (cutoff point: 2.027) were 72% and 86%, and area under the curve of 0.845 (95% CI = 0.772-0.922). Elevated expression of miR-1260b in LAC tissues was positively correlated with exosomal-miR-1260b in plasma (r = .642, p < .05). Furthermore, ceramide biosynthesis regulated exosomal-miR-1260b secretion. Exosome-mediated transfer of miR-1260b promoted A549 cell invasion and was still functional inside A549 cells. Moreover, exosomal-miR-1260b regulated Wnt/ß-catenin signaling pathway by inhibiting sFRP1 and Smad4. This study identified a new regulation mechanism involving in cell invasion by exosome-mediated tumor-cell-to-tumor-cell communication. Targeting exosome-microRNAs may provide new insights into the diagnosis and treatment of LAC.

A nuclear transport-related gene signature combined with IDH mutation and 1p/19q codeletion better predicts the prognosis of glioma patients.

BACKGROUND: The nuclear transport system has been proposed to be indispensable for cell proliferation and invasion in cancers. Prognostic biomarkers and molecular targets in nuclear transport systems have been developed. However, no systematic analysis of genes related to nuclear transport in gliomas has been performed. An integrated prognostic classification involving mutation and nuclear transport gene signatures has not yet been explored. METHODS: In the present study, we analyzed gliomas from a training cohort (TCGA dataset, n = 660) and validation cohort (CGGA dataset, n = 668) to develop a prognostic nuclear transport gene signature and generate an integrated classification system. Gene set enrichment analysis (GSEA) showed that glioblastoma (GBM) was mainly enriched in nuclear transport progress compared to lower-grade glioma (LGG). Then, we developed a nuclear transport risk score (NTRS) for gliomas with a training cohort. NTRS was significantly correlated with clinical and genetic characteristics, including grade, age, histology, IDH status and 1p/19q codeletion, in the training and validation cohorts. RESULTS: Survival analysis revealed that patients with a higher NTRS exhibited shorter overall survival. NTRS showed better prognostic value compared to classical molecular markers, including IDH status and 1p/19q codeletion. Furthermore, univariate and multivariate analyses indicated that NTRS was an independent prognostic factor for gliomas. Enrichment map and Gene Ontology analysis demonstrated that signaling pathways related to the cell cycle were enriched in the NTRSHigh group. Subgroup survival analysis revealed that NTRS could differentiate the outcomes of low- and high-risk patients with wild-type IDH or mutant IDH and 1p/19q non-codeletion. CONCLUSIONS: NTRS is associated with poor outcomes and could be an independent prognostic marker in diffuse gliomas. Prognostic classification combined with IDH mutation, 1p/19q codeletion and NTRS could better predict the survival of glioma patients.

Microvascular fractal dimension predicts prognosis and response to chemotherapy in glioblastoma: an automatic image analysis study.

The microvascular profile has been included in the WHO glioma grading criteria. Nevertheless, microvessels in gliomas of the same WHO grade, e.g., WHO IV glioblastoma (GBM), exhibit heterogeneous and polymorphic morphology, whose possible clinical significance remains to be determined. In this study, we employed a fractal geometry-derived parameter, microvascular fractal dimension (mvFD), to quantify microvessel complexity and developed a home-made macro in Image J software to automatically determine mvFD from the microvessel-stained immunohistochemical images of GBM. We found that mvFD effectively quantified the morphological complexity of GBM microvasculature. Furthermore, high mvFD favored the survival of GBM patients as an independent prognostic indicator and predicted a better response to chemotherapy of GBM patients. When investigating the underlying relations between mvFD and tumor growth by deploying Ki67/mvFD as an index for microvasculature-normalized tumor proliferation, we discovered an inverse correlation between mvFD and Ki67/mvFD. Furthermore, mvFD inversely correlated with the expressions of a glycolytic marker, LDHA, which indicated poor prognosis of GBM patients. Conclusively, we developed an automatic approach for mvFD measurement, and demonstrated that mvFD could predict the prognosis and response to chemotherapy of GBM patients.

MicroRNA-124 Functions as a Tumor Suppressor by Regulating CDH2 and Epithelial-Mesenchymal Transition in Non-Small Cell Lung Cancer.

BACKGROUND/AIMS: Abnormal expression of microRNA-124 (miR-124) was found in non-small cell lung cancer (NSCLC). However, the association between miR-124 and CDH2 has not been reported yet. This study aims to reveal the inhibiting effects of miR-124 on the expression of CDH2 in NSCLC. METHODS: Quantitative real-time polymerase chain reaction was used to evaluate the expression of miR-124 and CDH2 in NSCLC tissues. Cell viability, apoptosis and invasion assays were carried out in NSCLC cell lines after transfection. The regulation mechanism was confirmed by luciferase report assay and western blot (WB). RESULTS: Significantly decreased expression of miR-124 was found in NSCLC specimens and cell lines. Overexpression of miR-124 apparently suppressed the proliferation and invasion of NSCLC cell lines in vitro. Luciferase report assay and WB revealed that CDH2 was a target gene of miR-124. Furthermore, results of WB showed that epithelial-mesenchymal transition (EMT) could be inhibited by up-regulation of miR-124. CONCLUSIONS: Taken together, our findings present the first evidence that miR-124 could suppress the expression of CDH2 and regulate EMT, which might lead to a potential therapeutic strategy focusing on miR-124 and CDH2 for human lung cancer.

Activation of LXR attenuates collagen-induced arthritis via suppressing BLyS production.

B-lymphocyte stimulator (BLyS) plays a critical role in the pathogenesis and progression of rheumatoid arthritis (RA). Liver X receptor (LXR), a nuclear receptor, has an important anti-inflammatory effect. However, it is unclear whether the BLyS expression is regulated by LXR. In this study, we found that treatment with LXR agonist in collagen-induced arthritis (CIA) mice significantly attenuated arthritis progression, and markedly decreased BLyS production in serum and splenocytes as well as the production of serum IFNγ and TGFß. Activation of LXR in B lymphocytes dramatically suppressed the basal and IFNγ/TGFß-induced BLyS expression. Moreover, LXR agonist prominently suppressed the binding of NF-κB to BLyS promoter region, and decreased the promoter's transcriptional activity. Additionally, activation of LXR obviously repressed IFNγ-induced STAT1 activation and TGFß-induced SMAD3 activation. These results indicated that downregulation of BLyS may be a novel mechanism by which LXR ameliorates RA, and LXR/BLyS pathway may serve as a novel target for the treatment of RA.

Up-Regulation of MiR-452 Inhibits Metastasis of Non-Small Cell Lung Cancer by Regulating BMI1.

BACKGROUND/AIMS: MicroRNAs (miRNAs) have been regarded as a new class of regulators in cellular processes in non-small cell lung cancer (NSCLC). However, the relationship between miR-452 and the development of NSCLC remains unclear. METHODS: qRT-PCR was used to detect the expression of miR-452 and its target gene in NSCLC samples (n=60). The transwell assay was used to test the cell invasion capability. The regulation mechanism was confirmed by luciferase reporter assay and western blot assay. RESULTS: In the current study, a relatively lower miR-452 and higher BMI1 expression levels were confirmed to be associated with advanced tumor stage and more extent of lymph nodes metastasis. In vitro, down-regulated miR-452 could enhance cell invasion capability. Furthermore, miR-452 modulated BMI1 expression by binding to its 3'-UTR. The enhancement of cell invasion capability induced by down-regulated miR-452 was eliminated by repression of BMI1. CONCLUSIONS: Our results suggest that miR-452 plays a vital role in development of NSCLC, and this miR-452-BMI1 pathway might generate a novel insight into the treatment of NSCLC.

ITSN2L Interacts with and Negatively Regulates RABEP1.

Intersectin-2Long (ITSN2L) is a multi-domain protein participating in endocytosis and exocytosis. In this study, RABEP1 was identified as a novel ITSN2L interacting protein using a yeast two-hybrid screen from a human brain cDNA library and this interaction, specifically involving the ITSN2L CC domain and RABEP1 CC3 regions, was further confirmed by in vitro GST (glutathione-S-transferase) pull-down and in vivo co-immunoprecipitation assays. Corroboratively, we observed that these two proteins co-localize in the cytoplasm of mammalian cells. Furthermore, over-expression of ITSN2L promotes RABEP1 degradation and represses RABEP1-enhanced endosome aggregation, indicating that ITSN2L acts as a negative regulator of RABEP1. Finally, we showed that ITSN2L and RABEP1 play opposite roles in regulating endocytosis. Taken together, our results indicate that ITSN2L interacts with RABEP1 and stimulates its degradation in regulation of endocytosis.

Exopolysaccharide production by salt-tolerant bacteria: Recent advances, current challenges, and future prospects.

Natural biopolymers derived from exopolysaccharides (EPSs) are considered eco-friendly and sustainable alternatives to available traditional synthetic counterparts. Salt-tolerant bacteria inhabiting harsh ecological niches have evolved a number of unique adaptation strategies allowing them to maintain cellular integrity and assuring their long-term survival; among these, producing EPSs can be adopted as an effective strategy to thrive under high-salt conditions. A great diversity of EPSs from salt-tolerant bacteria have attracted widespread attention recently. Because of factors such as their unique structural, physicochemical, and functional characteristics, EPSs are commercially valuable for the global market and their application potential in various sectors is promising. However, large-scale production and industrial development of these biopolymers are hindered by their low yields and high costs. Consequently, the research progress and future prospects of salt-tolerant bacterial EPSs must be systematically reviewed to further promote their application and commercialization. In this review, the structure and properties of EPSs produced by a variety of salt-tolerant bacterial strains isolated from different sources are summarized. Further, feasible strategies for solving production bottlenecks are discussed, which provides a scientific basis and direct reference for more scientific and rational EPS development.