miR-218-5p promotes hepatic lipogenesis through targeting Elovl5 in non-alcoholic fatty liver disease.

Investigating and identifying pathogenic molecules of non-alcoholic fatty liver disease (NAFLD) has become imperative, which would serve as effective targets in the future. We established high-fat diet (HFD)-induced NAFLD model in mice and palmitic acid (PA)-induced model in mouse AML12 cells. The level of miR-218-5p was examined by qRT-PCR, and Elovl5 was identified as the potential target gene of miR-218-5p. The binding relationship between miR-218-5p and Elovl5 was validated by double luciferase reporter gene assay, and inhibition/overexpression of miR-218-5p in vitro. The functional mechanisms of miR-218-5p/Elovl5 in regulating lipogenesis in NAFLD were investigated in vivo and in vitro through gain- and loss-of-function studies. MiR-218-5p was significantly increased, and Elovl5 was decreased in model group. According to the double luciferase reporter and gene interference experiments in AML12 cells, Elovl5 was a target gene of miR-218-5p and its expression was regulated by miR-218-5p. The SREBP1-mediated lipogenesis signaling pathway regulated by Elovl5 was upregulated in model group. Moreover, silencing of miR-218-5p significantly upregulated Elovl5 expression, and suppressed SREBP1 signaling pathway in PA-induced AML-12 cells. Correspondingly, the cell injury, elevated TC, TG contents and lipid droplet accumulation were ameliorated. Furthermore, the effect of miR-218-5p on lipogenesis in vitro and in vivo was obstructed by si-Elovl5, implicating that miR-218-5p promotes lipogenesis by targeting ELOVL5 in NAFLD. miR-218-5p could promote fatty acid synthesis by targeting Elovl5, thereby accelerating the development of NAFLD, which is one of the key pathogenic mechanisms of NAFLD and provides a new molecular target for the management of NAFLD.

Fixation technique of biodegradable magnesium alloy suture anchor in the rotator cuff repair of the shoulder in a goat model: a technical note.

BACKGROUND: Shoulder disorders, particularly rotator cuff tears, are prevalent musculoskeletal conditions related to aging. Although the widely used suture anchor technique provides strong mechanical support to the tendon, it is associated with a risk of postoperative tendon retearing. The conventionally used titanium alloys can affect the interpretation of magnetic resonance imaging. Degradable magnesium alloys possess excellent biocompatibility, similar mechanical property to the bone, and stimulating bone formation ability from Mg2+. The purpose of this experiment was to develop innovative magnesium-based suture anchors to enhance rotator cuff repair by improving fixation materials, and to evaluate their feasibility in a goat model. METHODS: We developed fluoridized ZK60 suture anchors as the implantation material for two goats, who underwent rotator cuff repair surgery on both shoulders. Computed tomography (CT) and histological analysis were performed at 12 weeks postoperatively, and the results were compared between the magnesium and titanium alloy groups. Additionally, a hematological examination was conducted, which included assessments of red blood cells, white blood cells, platelets, coagulation function, liver function, kidney function, and magnesium ion concentration. RESULTS: The 12-week postoperative CT images showed intact MgF2 ZK60 suture anchors, effectively reconnecting the infraspinatus tendon to the humeral head. The anchors became less visible on CT scans, indicating absorption by surrounding tissues. New bone formation in the MgF2 group surpassed that in the Ti group, demonstrating superior osseointegration. The similarity between cortical bone and magnesium reduced stress-shielding and promoted bone regeneration. Histological analysis revealed successful tendon healing with MgF2 anchors, while the Ti group showed discontinuous interfaces and reduced collagen secretion. Hematological examination showed stable liver, renal function, and magnesium ion levels. CONCLUSIONS: The findings indicate that MgF2-coated suture anchors are feasible for rotator cuff repair and potentially other orthopedic applications. We hope that magnesium alloy anchors can become the solution for rotator cuff tendon repair surgery.

Finite Element Analysis Model for Assessing Expansion Patterns from Surgically Assisted Rapid Palatal Expansion.

Surgically assisted rapid palatal expansion (SARPE) was introduced to release bony resistance to facilitate skeletal expansion in skeletally mature patients. However, asymmetric expansion between the left and right sides has been reported in 7.52% of all SARPE patients, of which 12.90% had to undergo a second surgery for correction. The etiologies leading to asymmetric expansion remain unclear. Finite element analysis has been used to evaluate the stress associated with SARPE in the maxillofacial structures. However, as a collision of the bone at the LeFort I osteotomy sites occurs only after a certain amount of expansion, most of the existing models do not truly represent the force distribution, given that the expansion amount of these existing models rarely exceeds 1 mm. Therefore, there is a need to create a novel finite element model of SARPE that could perform a clinically required amount of expander activation for further analysis of the expansion patterns of the hemimaxillae in all three dimensions. A three-dimensional (3D) skull model from cone beam computed tomography (CBCT) was imported into Mimics and converted into mathematical entities to segment the maxillary complex, maxillary first premolars, and maxillary first molars. These structures were transferred into Geomagic for surface smoothing and cancellous bone and periodontal ligament creation. The right half of the maxillary complex was then retained and mirrored to create a perfectly symmetrical model in SolidWorks. A Haas expander was constructed and banded to the maxillary first premolars and first molars. Finite element analysis of various combinations of buccal osteotomies at different angles with 1 mm clearance was performed in Ansys. A convergence test was conducted until the desired amount of expansion on both sides (at least 6 mm in total) was achieved. This study lays the foundation for evaluating how buccal osteotomy angulation influences the expansion patterns of SARPE.

Effects of exercise on circadian rhythms in humans.

The biological clock system is an intrinsic timekeeping device that integrates internal physiology and external cues. Maintaining a healthy biological clock system is crucial for life. Disruptions to the body's internal clock can lead to disturbances in the sleep-wake cycle and abnormalities in hormone regulation, blood pressure, heart rate, and other vital processes. Long-term disturbances have been linked to the development of various common major diseases, including cardiovascular diseases, metabolic disorders, tumors, neuropsychiatric conditions, and so on. External factors, such as the diurnal rhythm of light, have a significant impact on the body's internal clock. Additionally, as an important non-photic zeitgeber, exercise can regulate the body's internal rhythms to a certain extent, making it possible to become a non-drug intervention for preventing and treating circadian rhythm disorders. This comprehensive review encompasses behavioral, physiological, and molecular perspectives to provide a deeper understanding of how exercise influences circadian rhythms and its association with related diseases.

Single-Cell and Transcriptome-Based Immune Cell-Related Prognostic Model in Clear Cell Renal Cell Carcinoma.

Traditional studies mostly focus on the role of single gene in regulating clear cell renal cell carcinoma (ccRCC), while it ignores the impact of tumour heterogeneity on disease progression. The purpose of this study is to construct a prognostic risk model for ccRCC by analysing the differential marker genes related to immune cells in the single-cell database to provide help in clinical diagnosis and targeted therapy. Single-cell data and ligand-receptor relationship pair data were downloaded from related publications, and ccRCC phenotype and expression profile data were downloaded from TCGA and CPTAC. Based on the DEGs of each cluster acquired from single-cell data, immune cell marker genes, and ligand-receptor gene data, we constructed a multilayer network. Then, the genes in the network and the genes in TCGA were used to construct the WGCNA network, which screened out prognosis-associated genes for subsequent analysis. Finally, a prognostic risk scoring model was obtained, and CPTAC data showed that the effectiveness of this model was good. A nomogram based on the predictive model for predicting the overall survival was established, and internal validation was performed well. Our findings suggest that the predictive model built and based on the immune cell scRNA-seq will enable us to judge the prognosis of patients with ccRCC and provide more accurate directions for basic relevant research and clinical practice.

Three-Dimensional Physical Model in Urologic Cancer.

Three-dimensional (3D) printing, as an evolving technology, enables the creation of patient-specific physical models with high precision; thus, it is widely used in various clinical practices, especially urologic cancer. There is an increasing need to clarify the contribution of 3D printing in the practice of urological cancer in order to identify various applications and improve understanding its benefits and challenges in clinical practice. Researches have focused on the use of 3D-printed models in patient and trainee education, surgical simulation, as well as surgical planning and guidance. This mini review will present the most recently published studies on the topic, including the applications of 3D-printed models, feasibility of performed procedures, possible simulated organs, application outcomes, and challenges involved in urologic cancer, to provide potential directions for future research.

Dioscin alleviates Alzheimer's disease through regulating RAGE/NOX4 mediated oxidative stress and inflammation.

Alzheimer's disease (AD) is a neurodegenerative disease with amyloid beta (Aß) deposition and intracellular neurofibrillary tangles (NFTs) as its characteristic pathological changes. Ameliorating oxidative stress and inflammation has become a new trend in the prevention and treatment of AD. Dioscin, a natural steroidal saponin which exists in Dioscoreae nipponicae rhizomes, displays various pharmacological activities, but its role in Alzheimer's disease (AD) is still unknown. In the present work, effect of dioscin on AD was evaluated in injured SH-SY5Y cells induced by H2O2 and C57BL/6 mice with AD challenged with AlCl3 combined with D-galactose. Results showed that dioscin obviously increased cell viability and decreased reactive oxygen species (ROS) level in injured SH-SY5Y cells. In vivo, dioscin obviously improved the spatial learning and memory abilities as well as gait and interlimb coordination disorders of mice with AD. Moreover, dioscin distinctly restored the levels of malondialdehyde (MDA), superoxide dismutase (SOD), amyloid beta 42 (Aß42), acetylcholine (ACh) and acetylcholinesterase (AChE) of mice, and reversed the histopathological changes of brain tissue. Mechanism studies revealed that dioscin markedly down-regulated the expression levels of RAGE and NOX4. Subsequently, dioscin markedly up-regulated the expression levels of Nrf2 and HO-1 related to oxidative stress, and down-regulated the levels of p-NF-κB(p-p65)/NF-κB(p65), AP-1 and inflammatory factors involved in inflammatory pathway. RAGE siRNAs transfection further clarified that the pharmacological activity of dioscin in AD was achieved by regulating RAGE/NOX4 pathway. In conclusion, dioscin showed excellent anti-AD effect by adjusting RAGE/NOX4-mediated oxidative stress and inflammation, which provided the basis for the further research and development against AD.

Immunotherapeutic Significance of a Prognostic Alternative Splicing Signature in Bladder Cancer.

Objectives: Bladder cancer is the fourth most common malignancy in men in the United States. Aberrant alternative splicing (AS) events are involved in the carcinogenesis, but the association between AS and bladder cancer remains unclear. This study aimed to construct an AS-based prognostic signature and elucidate the role of the tumor immune microenvironment (TIME) and the response to immunotherapy and chemotherapy in bladder cancer. Methods: Univariate Cox regression analysis was performed to detect prognosis-related AS events. The least absolute shrinkage and selection operator (LASSO) and multivariate Cox analyses were employed to build prognostic signatures. Kaplan-Meier survival analysis, multivariate Cox regression analysis, and receiver operating characteristic (ROC) curves were conducted to validate the prognostic signatures. Then, the Estimation of Stromal and Immune cells in MAlignant Tumor tissues using Expression data (ESTIMATE) and tumor immune estimation resource (TIMER) databases were searched and the single-sample gene set enrichment analysis (ssGSEA) algorithm and CIBERSORT method were performed to uncover the context of TIME in bladder cancer. The Tumor Immune Dysfunction and Exclusion (TIDE) web tool and pRRophetic algorithm were used to predict the response to immunotherapy and chemotherapy. Finally, we constructed a correlation network between splicing factors (SFs) and survival-related AS events. Results: A total of 4684 AS events were significantly associated with overall survival in patients with bladder cancer. Eight prognostic signatures of bladder cancer were established, and a clinical survival prediction model was built. In addition, the consolidated prognostic signature was closely related to immune infiltration and the response to immunotherapy and chemotherapy. Furthermore, the correlation identified EIF3A, DDX21, SDE2, TNPO1, and RNF40 as hub SFs, and function analysis found ubiquitin-mediated proteolysis is correlated most significantly with survival-associated AS events. Conclusion: Our findings highlight the prognostic value of AS for patients with bladder cancer and reveal pivotal players of AS events in the context of TIME and the response to immunotherapy and chemotherapy, which may be important for patient management and treatment.

Functional and structural properties of cardiotoxin isomers produced by blocking negatively charged groups.

In this study, we investigated the functional roles of Asp40, Asp57, and C-terminal Asn60 in Naja atra cardiotoxin 3 (CTX3) structure and function by modifying these three carboxyl groups with semicarbazide. The conjugation of the carboxyl groups with semicarbazide produced two conformational isomers whose gross and fine structures were different from those of CTX3. The blocking of the carboxyl groups increased the structural flexibility of CTX3 in response to trifluoroethanol-induced effect. Despite presenting modest to no effect on decreasing the induction of permeability in zwitterionic phospholipid vesicles, the carboxyl group-modified CTX3 showed a marked reduction in its permeabilizing effect on anionic phospholipid vesicles in comparison to that of the native protein. Compared with native CTX3, carboxyl group-modified CTX3 exhibited lower activity in inducing membrane leakage in U937 cells. The CD spectra of lipid-bound toxins and the color transition of polydiacetylene/lipid assay showed that the membrane interaction mode of CTX3 was distinctly changed by the modification in the carboxyl groups. Given that the selective modification of Asp40 does not cause the conformational isomerization of CTX3, our data indicate that the carboxyl groups in Asp57 and Asn60 are essential in maintaining the structural topology of CTX3. Furthermore, modification of carboxyl groups changes the interdependence between the infrastructure and the global conformation of CTX3 in modulating membrane permeabilizing activity.

ADNP prompts the cisplatin-resistance of bladder cancer via TGF-ß-mediated epithelial-mesenchymal transition (EMT) pathway.

Activity-dependent neuroprotective protein (ADNP) is vital for embryonic development and brain formation. Besides, the upregulated expression of ADNP enhances tumorigenesis in some human tumors like bladder cancer (BC). However, the potential roles of ADNP in drug resistance and the related mechanisms in BC is unknown. We performed this study to elucidate the influence of ADNP in the chemoresistance of BC and tried to explore the underlying molecular mechanism. The expressions of ADNP in BC from progression and non-progression patient specimens were measured by quantitative real-time PCR (qRT-PCR) and immunohistochemistry (IHC). In vitro experiments including colony formation, cell counting kit-8 (CCK-8), wound healing, and in vivo tumorigenesis assay were performed to explore the effects of ADNP on chemoresistance of BC. The impacts of ADNP on TGF-ß/Smad signaling pathways were explored by western blot. Our results showed that the expression of ADNP mRNA and protein were significantly upregulated in BC tissues of the patients who suffered tumor-progression via RT-PCR and western blot. Cox regression survival analysis revealed that patients with high ADNP expression closely linked to shorter tumor-free survival. ADNP downregulation in BC showed more sensitive to cisplatin in vivo, while ADNP overexpression showed the opposite results. Additionally, we confirmed that ADNP promoted cell migration and EMT, thereby inducing cisplatin resistance, which may be related to TGF-ß / Smad signaling pathway.

An Immune-Related lncRNA Signature to Predict Survival In Glioma Patients.

Glioma is the most common and fatal primary brain tumor in human. Long non-coding RNA (lncRNA), which are characterized by regulation of gene expression and chromatin recombination play an important role in glioma, and immunotherapy is a promising cancer treatment. Therefore, it is necessary to identify Immune-related lncRNAs in glioma. In this study,we collected and evaluated the RNA-seq data of The Cancer Genome Atlas (TCGA, https://www.ncbi.nlm.nih.gov/ ) and Chinese Glioma Genome Atlas (CGGA, https://www.cgga.org.cn/ ) glioma patients and immune-related lncRNAs were screened. Cox regression and LASSO analysis were performed to construct a risk score formula to explor the different overall survival between high- and low-risk groups in TCGA and verified with CGGA. Gene ontology (GO) and pathway-enrichment analysis (KEGG) were performed to identify the function of screened genes. Co-expression network were performed of these genes for further analysis. Eleven immune-related lncRNAs were concerned to be involved in survival and adopted to construct the risk score formula. Patients with high-risk score held poor survival both in TCGA and CGGA. Compared with current clinical data, the Area Under Curve (AUC) of different years and Principal components analysis (PCA) suggested that the formula had better predictive power. Functional Annotation of immune-related lncRNAs showed that the differences overall survival of high and low RS group might be caused by the cell differentiation, microtubule polymerization, etc. We successfully constructed an immune-related lncRNAs formula with powerful predictive function, which provides certain guidance value to the analysis of glioma pathogenesis and clinical treatment, and potential therapeutic targets for glioma treatment.

Wnt signalling pathway in bladder cancer.

Bladder cancer (BC) is one of the most common tumours of the urinary system and is also known as a highly malignant tumour. In addition to conventional diagnosis and treatment methods, recent research has focused on studying the molecular mechanisms related to BC, in the hope that new, less toxic and effective targeted anticancer drugs and new diagnostic markers can be discovered. It is known that the Wingless (Wnt) signalling pathway and its related genes, proteins and other substances are involved in multiple biological processes of various tumours. Clarifying the contribution of the Wnt signalling pathway in bladder tumours will help establish early diagnosis indicators, develop new therapeutic drugs and evaluate the prognosis for BC. This review aims to summarise previous studies related to BC and the Wnt signalling pathway, with a focus on exploring the participating substances and their mechanisms in the regulation of the Wnt signalling pathway to better determine how to promote new chemotherapeutic drugs, potential therapeutic targets and diagnostic biomarkers.

Identification of unique long non-coding RNAs as putative biomarkers for chromophobe renal cell carcinoma.

Aim: To investigate whether long non-coding RNAs (lncRNAs) can be utilized as molecular biomarkers in predicting the occurrence and progression of chromophobe renal cell carcinoma. Methods & results: Genetic and related clinical traits of chromophobe renal cell carcinoma were downloaded from the Cancer Genome Atlas and used to construct modules using weighted gene coexpression network analysis. In total, 44,889 genes were allocated into 21 coexpression modules depending on intergenic correlation. Among them, the green module was the most significant key module identified by module-trait correlation calculations (R2 = 0.43 and p = 4e-04). Gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses demonstrated that genes in the green module were enriched in many pathways. Coexpression, protein-protein interaction networks, screening for differentially expressed genes, and survival analysis were used to select hub lncRNAs. Five hub lncRNAs (TTK, CENPE, KIF2C, BUB1, and RAD51AP1) were selected out. Conclusion: Our findings suggest that the five lncRNAs may act as potential biomarkers for chromophobe renal cell carcinoma progression and prognosis.

A Systematic Review and Meta- Analysis of Green-Light Laser Vaporization for Superficial Bladder.

PURPOSE: The related research of green-light laser vaporization in the treatment of non-muscle invasive bladder cancer (NMIBC) is limited. This study focused on analyzing the effectiveness and safety of it from the perspective of an extensive literature review. METHODS: A comprehensive search of CNKI, WanFang, VIP, PubMed, Embase, and CENTRAL databases for photoselective vaporization of bladder tumor and transurethral resection of bladder tumor treatment of non-muscle invasive bladder cancer (NMIBC). The search included studies from January 1996 to December 2019. Two reviewers independently screened literature, extracted data, assessed the risk of bias of included studies. RevMan 5.3 software was used for Meta-analysis. RESULTS: A total of 18 RCTs involving 1648 patients met the predefined criteria. Meta-analysis data demonstrated that the PVBT group exhibited a significant advantage over the TURBT group in intraoperative obturator nerve reflex (RR = 0.09, 95% CI [0.04, 0.18], P< 0.001)and bladder perforation (RR = 0.14, 95% CI [0.07, 0.28], P< 0.001) and postoperative 1-year recurrence (RR = 0.52, 95% CI [0.40, 0.67], P< 0.001). The PVBT procedure has advantages over TURBT in the amount of surgical bleeding (MD = -17.27, 95% CI [-24.73, -9.81], P< 0.001) and the length of hospital stay (MD = -2.80, 95% CI [-3.82, -1.87], P< 0.001), bladder irrigation time (MD = -0.95, 95% CI [-1.49, -0.42], P< 0.001), and catheter indwelling time (MD = -2.60, 95% CI [-3.30, -1.90], P< 0.001). There was no difference between the two types of surgery in the incidence of postoperative urethral stricture (RR = 0.53, 95% CI [0.15, 1.83], P = 0.32) and the length of surgery (MD = -2.46, 95% CI [-5.37, 0.46], P = 0.10). CONCLUSION: Our systematic review and meta-analysis suggests that PVBT is better than TURBT as an alternative treatment for patients with NMIBC in safe aspect. However, whether it is equally effective in terms of oncological control remains to be elucidated, and additional high quality RCTs are needed to confirm our findings.

Identification of Glioma Cancer Stem Cell Characteristics Based on Weighted Gene Prognosis Module Co-Expression Network Analysis of Transcriptome Data Stemness Indices.

Glioma is the most common primary brain tumor in humans and the most deadly. Stem cells, which are characterized by therapeutic resistance and self-renewal, play a critical role in glioma, and therefore the identification of stem cell-related genes in glioma is important. In this study, we collected and evaluated the epigenetically regulated-mRNA expression-based stemness index (EREG-mRNAsi) of The Cancer Genome Atlas (TCGA, http://www.ncbi.nlm.nih.gov/ ) for glioma patient samples, corrected through tumor purity. After EREG-mRNAsi correction, glioma pathological grade and survival were analyzed. The differentially expressed gene (DEG) co-expression network was constructed by weighted gene co-expression network analysis (WGCNA) in TCGA glioma samples to find modules of interest and key genes. Gene ontology (GO) and pathway-enrichment analysis were performed to identify the function of significant genetic modules. Protein-protein interaction (PPI) and co-expression network analysis of key genes was performed for further analysis. In this experiment, we found that corrected EREG-mRNAsi was significantly up-regulated in glioma samples and increased with glioma grade, with G4 having the highest stemness index. Patients with higher corrected EREG-mRNAsi scores had worse overall survival. Fifty-one DEGs in the brown gene module were found to be positively related to EREG-mRNAsi via WGCNA. GO and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis showed that chromosome segregation and cell cycle molecular function were the major functions in key DEGs. Among these key DEGs, BUB1 showed high connectivity and co-expression, and also high connectivity in PPI. Fifty-one key genes were verified to play a critical role in glioma stem cells. These genes may serve as primary therapeutic targets to inhibit the activity of glioma stem cells.

Status of Asp29 and Asp40 in the Interaction of Naja atra Cardiotoxins with Lipid Bilayers.

It is widely accepted that snake venom cardiotoxins (CTXs) target the plasma membranes of cells. In the present study, we investigated the role of Asp residues in the interaction of Naja atra cardiotoxin 1 (CTX1) and cardiotoxin 3 (CTX3) with phospholipid bilayers using chemical modification. CTX1 contains three Asp residues at positions 29, 40, and 57; CTX3 contains two Asp residues at positions 40 and 57. Compared to Asp29 and Asp40, Asp57 was sparingly modified with semi-carbazide, as revealed by matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) mass and mass/mass analyses. Thus, semi-carbazide-modified CTX1 (SEM-CTX1) mainly contained modified Asp29 and Asp40, while SEM-CTX3 contained modified Asp40. Compared to that of native toxins, trifluoroethanol easily induced structural transition of SEM-CTX1 and SEM-CTX3, suggesting that the structural flexibility of CTXs was constrained by Asp40. Modification of Asp29 and Asp40 markedly promoted the ability of CTX1 to induce permeability of cell membranes and lipid vesicles; CTX3 and SEM-CTX3 showed similar membrane-damaging activity. Modification of Asp residues did not affect the membrane-binding capability of CTXs. Circular dichroism spectra of SEM-CTX3 and CTX3 were similar, while the gross conformation of SEM-CTX1 was distinct from that of CTX1. The interaction of CTX1 with membrane was distinctly changed by Asp modification. Collectively, our data suggest that Asp29 of CTX1 suppresses the optimization of membrane-bound conformation to a fully active state and that the function of Asp40 in the structural constraints of CTX1 and CTX3 is not important for the manifestation of membrane-perturbing activity.

NNT-AS1 enhances bladder cancer cell growth by targeting miR-1301-3p/PODXL axis and activating Wnt pathway.

As a tumor involved in the urinary system, bladder cancer (BC) seriously threatens human health. Emerging as crucial biomarkers, long noncoding RNAs (lncRNAs) play an important role in the regulation of many cancers. lncRNA NNT-AS1 has been studied in a series of cancers, whereas its role and potential molecular mechanism was poorly understood in BC. Here, we found that NNT-AS1 was upregulated in BC cells. Functionally, the silencing of NNT-AS1 inhibited cell proliferation, migration, invasion, and endothelial-mesenchymal transition. Furthermore, the apoptosis of BC cells was induced upon NNT-AS1 knockdown. Later, miR-1301-3p, the downstream gene of NNT-AS1, was found at a low level in BC cells. In addition, we found that miR-1301-3p targeted to PODXL. PODXL expression downregulated in NNT-AS1-silenced cells was restored by miR-1301-3p inhibition. Importantly, NNT-AS1 was discovered to activate Wnt pathway, and the treatment of LiCl recovered the repressive role of NNT-AS1 silencing in BC cell growth. Through restoration assays, we observed that PODXL overexpressing countervailed NNT-AS1 depletion-mediated suppression on BC cell growth and Wnt pathway. These data suggested that NNT-AS1 enhances BC cell growth and activates Wnt pathway by targeting miR-1301-3p/PODXL axis.

Clinical relevance of semaphorin-3F in patients with prostate cancer.

PURPOSE: To identify prognosis predictors for patients with prostate cancer (PCa). METHODS: Four independent PCa microarray datasets (GSE32448, GSE16560, GSE79957 and GSE17951) were reanalyzed to characterize the expression of semaphorin-3F (SEMA3F) gene between PCa patients and normal prostate tissues and the correlation between SEMA3F expression and the age, tumor/nodes/metastasis (TNM) staging, Gleason Grade Group, prostate-specific antigen level and overall survival of PCa patients. Gene set enrichment analysis was applied to investigate the potential relevant mechanisms regarding the expression of SEMA3F and the proliferation of PCa cells. RESULTS: The level of SEMA3F was significantly higher in normal prostate tissues compared with that in PCa cells (P.

Facile synthesis of fluorescent carbon dots from Prunus cerasifera fruits for fluorescent ink, Fe3+ ion detection and cell imaging.

Carbon dots (CDs) synthesized from natural products have drawn numerous attentions due to some unique properties. Here, Prunus cerasifera fruits were used as carbon source to synthesize high luminescent CDs by hydrothermal method. The obtained CDs were characterized by TEM, FTIR and XPS methods, founding the CDs were near-spherical and contained abundant nitrogen element. The CDs aqueous solution exhibited bright blue fluorescence under ultraviolet illumination, with the maximum emission at 450 nm. They could be potentially used as invisible fluorescent ink by written on the paper and irradiated by UV light, due to their fluorescent properties. Moreover, the CDs were found being selectively quenched by Fe3+ ion. The quench of CDs was linearly related to the concentration of Fe3+ ion in the range of 0-0.5 mM, meaning they could be developed as fluorescent probe of Fe3+ ion. At last, the CDs were used for cell imaging, founding they were low toxicity to HepG2 cells and exhibited blue and green fluorescence under a fluorescence microscope. In summary, the CDs prepared from Prunus cerasifera fruits exhibited excellent fluorescence properties, and could be potentially applied in the field of fluorescent ink, Fe3+ ion detection and cell imaging.

microRNA-204 modulates chemosensitivity and apoptosis of prostate cancer cells by targeting zinc-finger E-box-binding homeobox 1 (ZEB1).

Epigenetic gene inactivation by microRNAs (miRNAs) is crucial in malignant transformation, prevention of apoptosis, development of drug resistance, and metastasis. miR-204 dysregulation has been reported in prostate cancer (PC). It is considered to exert tumor suppressor functions and is associated with the development of chemoresistance. However, the detailed mechanisms underlying the role of miR-204 in PC, particularly in chemoresistance, remain to be fully elucidated. In this study, analysis using miRNA microarray showed that miR-204 is downregulated in chemoresistant PC tissues with respect to its expression in chemosensitive PC tissues and benign prostatic hyperplasia tissues. Microarray results were validated via qPCR. The changes in miR-204 expression levels were also observed in vitro. Forced overexpression of miR-204 evidently attenuated docetaxel chemoresistance and promoted apoptosis in PC-3-R cells, whereas miR-204 knockdown effectively reduced docetaxel-induced cell death and inhibited cell apoptosis. Mechanistically, miR-204 directly targets the 3'-untranslated region of zinc-finger E-box-binding homeobox 1 (ZEB1) and inhibits its protein expression via translational repression. Furthermore, suppression of ZEB1 could effectively improve miR-204 deficiency-triggered chemoresistance in PC cells. Our results collectively indicate that miR-204 expression is downregulated in chemoresistant PC tissues and cells and that miR-204/ZEB1 could potentially be used as adjunct therapy for patients with advanced/chemoresistant PC.