Host miR-146a-3p Facilitates Replication of Infectious Hematopoietic Necrosis Virus by Targeting WNT3a and CCND1.

Infectious hematopoietic necrosis virus (IHNV) is a serious pathogen that causes great economic loss to the salmon and trout industry. Previous studies showed that IHNV alters the expression patterns of splenic microRNAs (miRNAs) in rainbow trout. Among the differentially expressed miRNAs, miRNA146a-3p was upregulated by IHNV. However, it is unclear how IHNV utilizes miRNA146a-3p to escape the immune response or promote viral replication. The present study suggested that one multiplicity of infection (MOI) of IHNV induced the most significant miR-146a-3p expression at 1 day post infection (dpi). The upregulation of miR-146a-3p by IHNV was due to viral N, P, M, and G proteins and relied on the interferon (IFN) signaling pathway. Further investigation revealed that Wingless-type MMTV integration site family 3a (WNT3a) and G1/S-specific cyclin-D1-like (CCND1) are the target genes of miRNA-146a-3p. The regulation of IHNV infection by miRNA-146a-3p is dependent on WNT3a and CCND1. MiRNA-146a-3p was required for the downregulation of WNT3a and CCND1 by IHNV. Moreover, we also found that WNT3a and CCND1 are novel proteins that induce the type-I IFN response in RTG-2 cells, and both of them could inhibit the replication of IHNV. Therefore, IHNV-induced upregulation of miRNA-146a-3p promotes early viral replication by suppressing the type-I IFN response by targeting WNT3a and CCND1. This work not only reveals the molecular mechanism of miRNA-146a-3p during IHNV infection but also provides new antiviral targets for IHNV.

ABA-importing transporter (AIT1) synergies enhances exogenous ABA minimize heavy metals accumulations in Arabidopsis.

Exogenous abscisic acid (ABA) presents a novel approach to mitigate heavy metal (HM) accumulation in plants, yet its efficacy against multiple HMs and potential enhancement methods remain underexplored. In this study, we demonstrated that the exogenous ABA application simultaneously decreased Zn, Cd and Ni accumulation by 22-25 %, 27-39 % and 60-62 %, respectively, in wild-type (WT) Arabidopsis. Conversely, ABA reduced Pb in shoots but increased its root concentration. ABA application also modulated the expression of HM uptake genes, inhibiting IRT1, NRAMP1, NRAMP4, and HMA3, and increasing ZIP1 and ZIP4 expressions. Further analysis revealed that overexpressing the ABA-importing transporter (AIT1) in plants intensified the reduction of Cd, Zn, and Ni, compared to WT. However, the inhibitory effect of exogenous ABA on Pb accumulation was mitigated in shoots with higher AIT1 expression. Furthermore, HMs-induced growth inhibition and the damage to photosynthesis were also alleviated with ABA treatment. Conclusively, AIT1's synergistic effect with ABA effectively reduces Cd, Zn and Ni accumulation, offering a synergistic approach to mitigate HM stress in plants.

Chinese medicine in the treatment of non-alcoholic fatty liver disease based on network pharmacology: a review.

Non-alcoholic fatty liver disease (NAFLD) is a clinicopathological syndrome characterized by abnormalities in hepatic fat deposition, the incidence of which has been increasing year by year in recent years. It has become the largest chronic liver disease globally and one of the important causes of cirrhosis and even primary liver cancer formation. The pathogenesis of NAFLD has not yet been fully clarified. Modern medicine lacks targeted clinical treatment protocols for NAFLD, and most drugs lack efficacy and have high side effects. In contrast, Traditional Chinese Medicine (TCM) has significant advantages in the treatment and prevention of NAFLD, which have been widely recognized by scholars around the world. In recent years, through the establishment of a "medicine-disease-target-pathway" network relationship, network pharmacology can explore the molecular basis of the role of medicines in disease prevention and treatment from various perspectives, predicting the pharmacological mechanism of the corresponding medicines. This approach is compatible with the holistic view and treatment based on pattern differentiation of TCM and has been widely used in TCM research. In this paper, by searching relevant databases such as PubMed, Web of Science, and Embase, we reviewed and analyzed the relevant signaling pathways and specific mechanisms of action of single Chinese medicine, Chinese medicine combinations, and Chinese patent medicine for the treatment of NAFLD in recent years. These related studies fully demonstrated the therapeutic characteristics of TCM with multi-components, multi-targets, and multi-pathways, which provided strong support for the exact efficacy of TCM exerted in the clinic. In conclusion, we believe that network pharmacology is more in line with the TCM mindset of treating diseases, but with some limitations. In the future, we should eliminate the potential risks of false positives and false negatives, clarify the interconnectivity between components, targets, and diseases, and conduct deeper clinical or experimental studies.

An injectable signal-amplifying device elicits a specific immune response against malignant glioblastoma.

Despite exciting achievements with some malignancies, immunotherapy for hypoimmunogenic cancers, especially glioblastoma (GBM), remains a formidable clinical challenge. Poor immunogenicity and deficient immune infiltrates are two major limitations to an effective cancer-specific immune response. Herein, we propose that an injectable signal-amplifying nanocomposite/hydrogel system consisting of granulocyte-macrophage colony-stimulating factor and imiquimod-loaded antigen-capturing nanoparticles can simultaneously amplify the chemotactic signal of antigen-presenting cells and the "danger" signal of GBM. We demonstrated the feasibility of this strategy in two scenarios of GBM. In the first scenario, we showed that this simultaneous amplification system, in conjunction with local chemotherapy, enhanced both the immunogenicity and immune infiltrates in a recurrent GBM model; thus, ultimately making a cold GBM hot and suppressing postoperative relapse. Encouraged by excellent efficacy, we further exploited this signal-amplifying system to improve the efficiency of vaccine lysate in the treatment of refractory multiple GBM, a disease with limited clinical treatment options. In general, this biomaterial-based immune signal amplification system represents a unique approach to restore GBM-specific immunity and may provide a beneficial preliminary treatment for other clinically refractory malignancies.

Drag reduction using bionic groove surface for underwater vehicles.

Introduction: The reduction of drag is a crucial concern within the shipping industry as it directly influences energy consumption. This study addresses this issue by proposing a novel approach inspired by the unique ridge structure found on killer whale skin. The objective is to develop a non-smooth surface drag reduction method that can effectively decrease drag and improve energy efficiency for ships. Methods: The study introduces a technique involving the creation of transverse bionic groove surfaces modeled after the killer whale skin's ridge structure. These grooves are aligned perpendicular to the flow direction and are intended to modify the behavior of turbulent boundary layer flows that form around the ship's hull. Numerical simulations are employed using the Shear Stress Transport k-ω model to analyze the effects of the proposed groove surface across a wide range of flow conditions. The research investigates the impact of various parameters, such as the width-to-depth ratio (λ/A), groove depth, and inlet velocity, on the drag reduction performance of the bionic groove surface. Results: The study reveals several key findings. Optimal shape parameters for the bionic groove surface are determined, enabling the most effective drag reduction. The numerical simulations demonstrate that the proposed groove surface yields notable drag reduction benefits within the velocity range of 2∼12 m/s. Specifically, the friction drag reduction ratio is measured at 26.91%, and the total drag reduction ratio at 9.63%. These reductions signify a substantial decrease in the forces opposing the ship's movement through water, leading to enhanced energy efficiency. Discussion: Comparative analysis is conducted between the performance of the bionic groove surface and that of a smooth surface. This investigation involves the examination of velocity gradient, streamwise mean velocity, and turbulent intensity. The results indicate that the bionic groove structure effectively mitigates viscous stress and Reynolds stress, which in turn reduces friction drag. This reduction in drag is attributed to the alteration in flow behavior induced by the non-smooth surface. Conclusion: The study proposes a novel approach for drag reduction in the shipping industry by emulating the ridge structure of killer whale skin. The transverse bionic groove surface, aligned perpendicular to flow direction, demonstrates promising drag reduction outcomes across diverse flow conditions. Through systematic numerical simulations and analysis of key parameters, the research provides insights into the drag reduction mechanism and identifies optimal design parameters for the groove surface. The potential for significant energy savings and improved fuel efficiency in maritime transportation underscores the practical significance of this research.

Curcumin combining temozolomide formed localized nanogel for inhibition of postsurgical chemoresistant glioblastoma.

Aim: To investigate the use of nanoparticle (NP)-encapsulated injectable thermosensitive hydrogel-formed nanogel for inhibition of postsurgical residual temozolomide (TMZ)-resistant glioblastoma (GBM) recurrence. Materials & methods: Curcumin (Cur) was coloaded with TMZ into PEG-PLGA NPs, then NPs were further encapsulated into a thermosensitive hydrogel to form a nanogel, which was injected into the resection cavity of the GBM postsurgery. Results: The prepared nanogel displayed excellent drug-loading capacity and long-term drug release. Estimated survival characteristics demonstrated that the nanogel could play a significant role in TMZ-resistant tumor inhibition with low drug-induced toxicity. The originally designed ratio of Cur/TMZ was sustained, making it an effective therapeutic outcome. Conclusion: Cur-combined TMZ-formed nanogels can be a promising candidate for the local inhibition of GBM recurrence.

In this study, the animal model used was rats suffering residual brain tumor after resection. The selected drugs were temozolomide, a first-line chemotherapeutic drug for the clinical treatment of glioma, and curcumin, an extract from the ginger plant. With the use of temozolomide, brain glioma cells gradually develop resistance, resulting in poor efficacy of temozolomide. Therefore, the purpose of this study was to construct a drug-delivery system for temozolomide-resistant brain glioma residual tumor after surgery, namely, a temperature-sensitive gel containing drug-carrying nanopreparations ­ the so-called nanogels. This drug-delivery system can directly deliver drugs to residual tumor cells in situ after surgery. In situ drug-delivery systems can reduce the dose of drugs consumed and increase their potency compared to oral or intravenous administration.

Amino Acid-Assisted Sand-Milling Exfoliation of Boron Nitride Nanosheets for High Thermally Conductive Thermoplastic Polyurethane Composites.

Boron nitride nanosheets (BNNSs) show excellent thermal, electrical, optical, and mechanical properties. They are often used as fillers in polymers to prepare thermally conductive composites, which are used in the production of materials for thermal management, such as electronic packaging. Aside from the van der Waals force, there are some ionic bond forces between hexagonal boron nitride (h-BN) layers that result in high energy consumption and make BNNSs easily agglomerate. To overcome this issue, L-lysine (Lys) was first employed as a stripping assistant for preparing graft-functionalized BNNSs via mechanical sand-milling technology, and the obtained Lys@BNNSs can be added into thermoplastic polyurethane (TPU) by solution mixing and hot-pressing methods to prepare thermally conductive composites. This green and scalable method of amino acid-assisted sand-milling can not only exfoliate the bulk h-BN successfully into few-layer BNNSs but also graft Lys onto the surface or edges of BNNSs through Lewis acid-base interaction. Furthermore, benefiting from Lys's highly reactive groups and biocompatibility, the compatibility between functionalized BNNSs and the TPU matrix is significantly enhanced, and the thermal conductivity and mechanical properties of the composite are remarkably increased. When the load of Lys@BNNSs is 3 wt%, the thermal conductivity and tensile strength of the obtained composites are 90% and 16% higher than those of the pure TPU, respectively. With better thermal and mechanical properties, Lys@BNNS/TPU composites can be used as a kind of heat dissipation material and have potential applications in the field of thermal management materials.

Application of network pharmacology in the study of mechanism of Chinese medicine in the treatment of ulcerative colitis: A review.

Network pharmacology is a research method based on a multidisciplinary holistic analysis of biological systems, which coincides with the idea of the holistic view of traditional Chinese medicine. In this review, we summarized the use of network pharmacology technology through studying Chinese medicine single medicine or Chinese medicine compound research ideas and methods for the treatment of ulcerative colitis, based on the application of the current network pharmacology in Chinese medicine research, including the important role in the mechanism of the prediction and verification, to search for new ideas for disease diagnosis and treatment, this study summarizes the application of network pharmacology in the treatment of ulcerative colitis in traditional Chinese medicine, including monotherapy and compound therapy, and considers that relevant research studies have fully demonstrated the function characteristics of the multi-component, multi-target, and multi-pathway of traditional Chinese medicine, and can also explain the connotation of "selecting appropriate treatment methods according to the differences and similarities of pathogenesis" of traditional Chinese medicine. Finally, we raised important questions about the prospects and limitations of network pharmacology, such as differences caused by different data collection methods, a considerable lag, and so on.

Chinese Medicine in the Treatment of Ulcerative Colitis: The Mechanisms of Signaling Pathway Regulations.

Ulcerative colitis (UC) is a common clinical inflammatory bowel disease characterized by repeated attacks, difficult treatment, and great harm to the physical and mental health of the patients. The occurrence and development of UC were closely related to the physiological and pathological processes, such as intestinal inflammatory reaction, oxidizing reaction, and immune response. Treatment of ulcerative colitis using Western medicine is often associated with a number of limitations and adverse events. There is a long history of using traditional Chinese medicine in dealing with this medical condition. Commonly used traditional Chinese medicines for the treatment of UC include Caulis Sargentodoxae, Flos Lonicerae, Fructus Cnidii, etc. Additionally, classic prescriptions such as Gegen Qinlian Formulae and Zuojin Pills can also be used to treat UC. To enrich the traditional Chinese medicine theory, the cognitive theory and perspective of network pharmacology and bioinformatics research of cell signal transduction mechanism of UC are emerging rapidly. Modern pharmacological studies focus on underlying mechanisms for the management of UC with Chinese medicine monomers, single Chinese medicines, and traditional Chinese medicine formulations, alleviating the symptoms of UC, controlling the development of intestinal inflammation, and restoring intestinal function through the regulation of key molecular signaling pathways, including PI3K/Akt, NF-[Formula: see text]B, JAK/STAT, MAPK and Notch. By summarizing current research progressions, this review provides key references for the in-depth exploration of the mechanisms focused on signaling pathways for the clinical management of UC using traditional Chinese medicine.

Application of network pharmacology in the study of the mechanism of action of traditional chinese medicine in the treatment of COVID-19.

Network pharmacology was rapidly developed based on multidisciplinary holistic analysis of biological systems, which has become a popular tool in traditional Chinese medicine (TCM) research in recent years. Its characteristics of integrity and systematization provide a new approach for the study on complex TCM systems, which has many similarities with the holistic concept of TCM. It has been widely used to explain the mechanism of TCM treatment of diseases, drug repositioning, and interpretation of compatibility of TCM prescriptions, to promote the modernization of TCM. The use of TCM have provided crucial support on prevention and treatment of diseases such as the famous "three medicines and three prescriptions". Furthermore, TCM has become an important part of the treatment of COVID-19 and is one of the main contents of the "Chinese plan" to fight the epidemic. The current review demonstrated the role of TCM in treating diseases with multiple components, multiple targets, and multiple pathways, interprets the connotation of TCM treatment method selection based on pathogenesis and also discusses the application of network pharmacology in the study of COVID-19 treatment in TCM including single drug and prescription. However, there are still some shortcomings such as the lack of experimental verification and regular upgrading of the TCM pharmacology network. Therefore, we must pay attention to the characteristics of TCM and develop a network pharmacology method suitable for TCM system research when applying network pharmacology to TCM research.

Correction to: A complex mechanism for HDGF-mediated cell growth, migration, invasion, and TMZ chemosensitivity in glioma.

In the original publication, there are errors in Fig. 3D and Fig. 5C and are corrected as follows.

Genetic engineering of Bacillus sp. and fermentation process optimizing for diacetyl production.

Diacetyl, an important flavor extensively used in the food industry, can be produced from the non-enzymatic oxidative decarboxylation of α-acetolactate in bacteria fermentation. In previous work, we obtained a strain of Bacillus sp. DL01-ΔalsD with low diacetyl accumulation. The strain was engineered and optimized for improving the production of diacetyl in this study. First, deletion of the gene encoding phosphotransacetylase (pta), by homologous recombination with high temperature sensitive shuttle plasmid vector pKS1, led to a reduction of acetate and 130% increase of diacetyl production in B. sp. DL01-ΔalsD-Δpta. Then overexpression of α-acetolactate synthase (ALS) from B. subtilis 168 in B. sp. DL01-ΔalsD-Δpta resulted in efficient diacetyl production with a titer of 5.43 g/L. To further increase diacetyl production, single factor and orthogonal experimental data were used to predict the optimal fermentation conditions by Back Propagation neural network. Optimal value of KLa (Dissolved oxygen volume coefficient) was 12.4 h-1 with fermentation parameters of aeration rate 0.66 vvm, agitation speed 179 rpm and temperature 35.7 ℃. A titer of 11.18 g/L diacetyl, the highest reported diacetyl production, was achieved by fed-batch fermentation at the optimal condition using the metabolic engineered strain of B. sp. DL01-ΔalsD-Δpta-als168. These results are of great importance as a new way for the efficient production of diacetyl by food-safety bacteria.

Flot2 targeted by miR-449 acts as a prognostic biomarker in glioma.

Flotillin-2 (FLOT2) was reported as oncogene and involves in the pathogenic process of several cancers, yet the precise mechanism of FLOT2 in glioma is still limited. In this study, we demonstrated that FLOT2 expression levels were greatly upregulated in glioma tissues and cell lines, and the FLOT2 expression in glioma tissue was markedly associated with tumour stage and size. Overexpression of FLOT2 was correlated with poor prognosis of glioma patients. The functional assay revealed that silenced FLOT2 repressed the viability, migration, and invasion of glioma cells. And then, we detected the relationship between miR-449 and FLOT2. Luciferase reporter assay and Western blot results showed that miR-449 directly binding the 3'UTR sequence of FLOT2 and regulated FLOT2 expression in glioma cells. Finally, we detected the expression levels of miR-449 in glioma tissue and cell lines and found that miR-449 was significantly downregulated in glioma tissues and cell lines. In conclusion, we demonstrated that overexpression FLOT2 was associated with poor prognosis of glioma patients and involved in the progression of glioma, identifying a novel prognostic biomarker and therapeutic target for glioma progression.

The long non-coding RNA PTTG3P promotes cell growth and metastasis via up-regulating PTTG1 and activating PI3K/AKT signaling in hepatocellular carcinoma.

BACKGROUND: Dysfunctions of long non-coding RNA (lncRNAs) have been associated with the initiation and progression of hepatocellular carcinoma (HCC), but the clinicopathologic significance and potential role of lncRNA PTTG3P (pituitary tumor-transforming 3, pseudogene) in HCC remains largely unknown. METHODS: We compared the expression profiles of lncRNAs in 3 HCC tumor tissues and adjacent non-tumor tissues by microarrays. In situ hybridization (ISH) and quantitative real-time polymerase chain reaction (qRT-PCR) were applied to assess the level of PTTG3P and prognostic values of PTTG3P were assayed in two HCC cohorts (n = 46 and 90). Artificial modulation of PTTG3P (down- and over-expression) was performed to explore the role of PTTG3P in tumor growth and metastasis in vitro and in vivo. Involvement of PTTG1 (pituitary tumor-transforming 1), PI3K/AKT signaling and its downstream signals were validated by qRT-PCR and western blot. RESULTS: We found that PTTG3P was frequently up-regulated in HCC and its level was positively correlated to tumor size, TNM stage and poor survival of patients with HCC. Enforced expression of PTTG3P significantly promoted cell proliferation, migration, and invasion in vitro, as well as tumorigenesis and metastasis in vivo. Conversely, PTTG3P knockdown had opposite effects. Mechanistically, over-expression of PTTG3P up-regulated PTTG1, activated PI3K/AKT signaling and its downstream signals including cell cycle progression, cell apoptosis and epithelial-mesenchymal transition (EMT)-associated genes. CONCLUSIONS: Our findings suggest that PTTG3P, a valuable marker of HCC prognosis, promotes tumor growth and metastasis via up-regulating PTTG1 and activating PI3K/AKT signaling in HCC and might represent a potential target for gene-based therapy.

The diagnostic value of preoperative inflammatory markers in craniopharyngioma: a multicenter cohort study.

To compare the different levels of preoperative inflammatory markers in peripheral blood samples between craniopharyngioma (CP) and other sellar region tumors so as to explore their differential diagnostic value. The level of white blood cell (WBC), neutrophil, lymphocyte, monocyte, platelet, albumin, neutrophil lymphocyte ratio (NLR), derived NLR (dNLR), platelet lymphocyte ratio (PLR), monocyte lymphocyte ratio (MLR) and prognostic nutritional index (PNI) were compared between the CP and other sellar region tumors. A receiver operating characteristics (ROC) curve analysis was performed to evaluate the diagnostic significance of the peripheral blood inflammatory markers and their paired combinations for CP including its pathological types. Patients with CP had higher levels of pre-operative WBC, lymphocyte and PNI. The papillary craniopharyngioma (PCP) group had higher neutrophil count and NLR than the adamantinomatous craniopharyngioma (ACP) and healthy control groups whereas the ACP group had higher platelet count and PNI than the PCP and healthy control groups. There were not any significant differences in preoperative inflammatory markers between the primary and recurrent CP groups. The AUC values of WBC, neutrophil, NLR + PLR and dNLR + PLR in PCP were all higher than 0.7. Inflammation seems to be closely correlated with CP's development. The preoperative inflammatory markers including WBC, neutrophil, NLR + PLR and dNLR + PLR may differentially diagnose PCP, pituitary tumor (PT) and Rathke cleft cyst (RCC). In addition, some statistical results in this study indirectly proved previous experimental conclusions and strictly matched CP's biological features.

Diagnostic value of preoperative inflammatory markers in patients with glioma: a multicenter cohort study.

OBJECTIVE Glioma is the most common form of brain tumor and has high lethality. The authors of this study aimed to elucidate the efficiency of preoperative inflammatory markers, including neutrophil/lymphocyte ratio (NLR), derived NLR (dNLR), platelet/lymphocyte ratio (PLR), lymphocyte/monocyte ratio (LMR), and prognostic nutritional index (PNI), and their paired combinations as tools for the preoperative diagnosis of glioma, with particular interest in its most aggressive form, glioblastoma (GBM). METHODS The medical records of patients newly diagnosed with glioma, acoustic neuroma, meningioma, or nonlesional epilepsy at 3 hospitals between January 2011 and February 2016 were collected and retrospectively analyzed. The values of NLR, dNLR, PLR, LMR, and PNI were compared among patients suffering from glioma, acoustic neuroma, meningioma, and nonlesional epilepsy and healthy controls by using nonparametric tests. Correlations between NLR, dNLR, PLR, LMR, PNI, and tumor grade were analyzed. Receiver operating characteristic (ROC) curve analysis was performed to evaluate the diagnostic significance of NLR, dNLR, PLR, LMR, PNI, and their paired combinations for glioma, particularly GBM. RESULTS A total of 750 patients with glioma (Grade I, 81 patients; Grade II, 208 patients; Grade III, 169 patients; Grade IV [GBM], 292 patients), 44 with acoustic neuroma, 271 with meningioma, 102 with nonlesional epilepsy, and 682 healthy controls were included in this study. Compared with healthy controls and patients with acoustic neuroma, meningioma, or nonlesional epilepsy, the patients with glioma had higher values of preoperative NLR and dNLR as well as lower values of LMR and PNI, whereas PLR was higher in glioma patients than in healthy controls and patients with nonlesional epilepsy. Subgroup analysis revealed a positive correlation between NLR, dNLR, PLR, and tumor grade but a negative correlation between LMR, PNI, and tumor grade in glioma. For glioma diagnosis, the area under the curve (AUC) obtained from the ROC curve was 0.722 (0.697-0.747) for NLR, 0.696 (0.670-0.722) for dNLR, 0.576 (0.549-0.604) for PLR, 0.760 (0.738-0.783) for LMR, and 0.672 (0.646-0.698) for PNI. The best diagnostic performance was obtained with the combination of NLR+LMR and dNLR+LMR, with AUCs of 0.777 and 0.778, respectively. Additionally, NLR (AUC 0.860, 95% CI 0.832-0.887), dNLR (0.840, 0.810-0.869), PLR (0.678, 0.641-0.715), LMR (0.837, 0.811-0.863), and PNI (0.740, 0.706-0.773) had significant predictive value for GBM compared with healthy controls and other disease groups. As compared with the Grade I-III glioma patients, the GBM patients had an AUC of 0.811 (95% CI 0.778-0.844) for NLR, 0.797 (0.763-0.832) for dNLR, 0.662 (0.622-0.702) for PLR, 0.743 (0.707-0.779) for LMR, and 0.661(0.622-0.701) for PNI. For the paired combinations, NLR+LMR demonstrated the highest accuracy. CONCLUSIONS The NLR+LMR combination was revealed as a noninvasive biomarker with relatively high sensitivity and specificity for glioma diagnosis, the differential diagnosis of glioma from acoustic neuroma and meningioma, GBM diagnosis, and the differential diagnosis of GBM from low-grade glioma.

Long non-coding RNA UBE2CP3 promotes tumor metastasis by inducing epithelial-mesenchymal transition in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is a highly aggressive, solid malignancy that has a poor prognosis. Long non-coding RNAs (lncRNAs) have been found to be dysregulated in various cancers, including HCC. However, the molecular mechanism involving lncRNAs in HCC remains largely unknown. In this study, lncRNAs differentially expressed between HCC and corresponding non-cancerous tissue were identified by microarray analysis. A specific differentially expressed lncRNA UBE2CP3 (ubiquitin conjugating enzyme E2 C pseudogene 3) was identified. LncRNA UBE2CP3 was frequently up-regulated in HCC samples as assessed by quantitative real-time polymerase chain reaction (qRT-PCR) and in situ hybridization (ISH) experiments. Clinical data showed that high levels of lncRNA UBE2CP3 were correlated with poor prognosis in HCC patients. Functional studies demonstrated that over-expression of lncRNA UBE2CP3 promoted cell invasion and migration in vitro and in vivo. Mechanistically, enhanced expression of lncRNA UBE2CP3 increased the expression of Snail1 and N-cadherin, but decreased the expression of E-cadherin, thus promoting the process of epithelial to mesenchymal transition (EMT) and finally inducing cell invasion and migration. Furthermore, serum levels of lncRNA UBE2CP3 were increased in HCC patients and decreased after surgery. Our results suggest that lncRNA UBE2CP3 promotes the metastasis of HCC and that serum lncRNA UBE2CP3 may be a new biomarker for the diagnosis of HCC.

Hypoxia-induced PLOD2 promotes proliferation, migration and invasion via PI3K/Akt signaling in glioma.

Gliomas are the most common form of malignant primary brain tumors with poor 5-year survival rate. Dysregulation of procollagen-lysine, 2-oxoglutarate 5-dioxygenase 2 (PLOD2) was observed in gliomas, but the specific role and molecular mechanism of PLOD2 in glioma have not been reported yet. In this study, PLOD2 was found to be frequently up-regulated in glioma and could serve as an independent prognostic marker to identify patients with poor clinical outcome. Knockdown of PLOD2 inhibited proliferation, migration and invasion of glioma cells in vitro and in vivo. Mechanistically, inhibition of PLOD2 inactivated PI3K/AKT signaling pathway and thus regulated the expression of its downstream epithelial-mesenchymal transition (EMT)-associated regulators, including E-cadherin, vimentin, N-cadherin, ß-catenin, snail and slug in glioma cells. Moreover, PLOD2 could be induced by hypoxia-inducible factor-1α (HIF-1α) via hypoxia, thereby promoting hypoxia-induced EMT in glioma cells. Our data suggests that PLOD2 may be a potential therapeutic target for patients with glioma.

[EFFECTS OF TOURNIQUET USE ON PERIOPERATIVE OUTCOME IN TOTAL KNEE ARTHROPLASTY].

OBJECTIVE: To clarify the effects of tourniquet use on pain, early rehabilitation, blood loss, incidence rate of thrombosis in primary total knee arthroplasty (TKA) through a randomized controlled trial. METHODS: Between Janurary 2014 and August 2015, 168 patients with knee osteoarthritis undergoing primary TKA were randomly allocated to tourniquet group (n = 84) or non-tourniquet group (n = 82). There was no significant difference in gender, age, body mass index, affected side, osteoarthritis grading, disease duration, preoperative range of motion (ROM), visual analogue scale (VAS), Hospital for Special Surgery (HSS) score, and hemoglobin (Hb) between 2 groups (P > 0.05). The operation time, hospitalization time, 90° knee flexion time, straight leg lifting time, and ambulation time were compared between 2 groups. Intraoperative blood loss, Hb decrease, postoperative VAS score, HSS score, ROM, and postoperative complications were recorded and compared. RESULTS: There was no significant difference in operation time (t = -1.353, P = 0.178). The patients were followed up 3-20 months (mean, 12 months) in tourniquet group, and 3-22 months (mean, 13 months) in non-tourniquet group. No significant difference was found in Hb decrease (t = -1.855, P = 0.066) and transfusion rate (23.81% of tourniquest group vs. 25.61% of non-tourniquest group) (χ² = 0.072, P = 0.788) between 2 groups. Significant difference was found in the incidence rate of thrombosis between tourniquet and non-tourniquet groups (10.71% vs. 2.44%) (χ² = 4.592, P = 0.032), and the intraoperative blood loss of tourniquet group was significantly less than that of non-tourniquet group (t = -16.066, P = 0.000). The 90° knee flexion time, straight leg lifting time, ambulation time, and hospitalization time of tourniquet group were significantly later than those of non-tourniquet group (P < 0.05). The tourniquet group had significantly higher VAS score at 3, 5, 7, and 14 days after operation (P < 0.05) and lower HSS score at 28 days after operation (t = -4.192, P = 0.000) than non-tourniquet group, but there was no significant difference in the ROM between 2 groups (t = 0.676, P = 0.500). CONCLUSION: The use of a tourniquet during TKA will increase knee pain and thrombotic events, but can not decrease total blood loss and transfusion rate. A tourniquet use during TKA is unfavorable for early rehabilitation progress.

Periostin activates pathways involved in epithelial-mesenchymal transition in adamantinomatous craniopharyngioma.

Periostin (POSTN) is an extracellular matrix protein (ECM) critical for epithelial-mesenchymal transitions (EMT) in several kinds of tumor cells. Previous studies have indicated that EMT exists in craniopharyngioma (CP), and expression of POSTN is a significant factor in the prognosis of CP. However, it has never been explored whether POSTN exists in CP, or how it activates CP's EMT. The expression of POSTN was examined in adamantinomatous craniopharyngioma (ACP) primary cells and tissues by immunohistochemistry, PCR and Western blot, respectively. The effects and mechanisms of POSTN on ACP cells' EMT were also analyzed. It was found that POSTN expression increased in ACP-associated fibroblasts. Overexpressed POSTN significantly elevated the EMT of ACP cells by regulating the expression of associated genes. More importantly, our further study revealed that the upregulated POSTN activated Akt signaling pathway to regulate the EMT. This study showed that POSTN is responsible for the EMT of ACP cells, and POSTN might be a potential molecular therapeutic target for ACP treatment in future.