ABSTRACT
The design and fabrication of high-performance, inexpensive and durable electrocatalyst toward hydrogen evolution reaction (HER) is supremely significant for alleviating energy crisis and environmental concerns, but still remaining challenging. Herein, we develop an experimental work based on etching and reduction strategy to reveal the remarkable effect of cation/anion co-doping in CoMoO4 on its intrinsic HER activity. The CoMoO4 with Fe and B incorporation (Fe/B-CoMoO4) exhibits a current density of 10 mA cm-2 with strikingly low potential of 38 mV coupling with Tafel slope of 51 mV dec-1, and manifesting a robust durability for 100 h with no attenuation, which is comparable to the state-of-the-art commercial Pt/C catalyst. The collective experimental and theoretical findings concomitantly illustrate that the enhanced performances are due to the strong synergistic effect resulting from the co-doping of Fe and B, which plays a pivotal role in finely tuning the electronic structure of CoMoO4, further optimizing the adsorption free energy of H intermediates and shifting the center of the d-band of Fe/B-CoMoO4 away from the Fermi level. This fantastic work highlights the critical role of foreign element incorporating for optimizing electronic structure of transition metal oxides toward HER, and offers valuable guiding principles for rational design of more efficient energy conversion devices.
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Malignant melanoma is a challenging problem worldwide, because the remaining tumor cells and extensive skin defects following surgical resection are difficult to treat. Biomaterial-mediated immunotherapy has emerged as a superior strategy for anti-tumor applications in recent years. Herein, a unique double-layer MNP was developed to address the problem of malignant melanoma. Hydroxyapatite (HAP) and short-chain peptides from tumor cells were self-assembled to prepare the bioinspired nano-vaccine, and then they were loaded onto the microneedle tips of methacrylated gelatin (GelMA)-based MNP. The products (dubbed HVMN) demonstrated relatively good biocompatibility and immune activity, inhibiting the proliferation and inducing apoptosis of malignant melanoma in a B16 cell-bearing model of C57BL/6 mice, and promoting skin tissue regeneration in a full thickness skin defect model of SD rats in 15 days. The putative molecular pathways were examined preliminarily. In conclusion, this research will develop a competitive microneedle patch with dual anti-tumor and pro-regenerative properties for the postoperative treatment of malignant melanoma.
Subject(s)
Melanoma , Skin Neoplasms , Mice , Rats , Animals , Melanoma/drug therapy , Nanovaccines , Rats, Sprague-Dawley , Mice, Inbred C57BL , Wound Healing , Skin Neoplasms/drug therapy , Skin Neoplasms/pathologyABSTRACT
Background: Keloid is a common condition characterized by abnormal scarring of the skin, affecting a significant number of individuals worldwide. Objective: The occurrence of keloids may be related to the reduction of cell death. Recently, a new cell death mode that relies on copper ions has been discovered. This study aimed to identify novel cuproptosis-related genes that are associated with keloid diagnosis. Methods: We utilized several gene expression datasets, including GSE44270 and GSE145725 as the training group, and GSE7890, GSE92566, and GSE121618 as the testing group. We integrated machine learning models (SVM, RF, GLM, and XGB) to identify 10 cuproptosis-related genes (CRGs) for keloid diagnosis in the training group. The diagnostic capability of the identified CRGs was validated using independent datasets, RT-qPCR, Western blotting, and IHC analysis. Results: Our study successfully categorized keloid samples into two clusters based on the expression of cuproptosis-related genes. Utilizing WGCNA analysis, we identified 110 candidate genes associated with cuproptosis. Subsequent functional enrichment analysis results revealed that these genes may play a regulatory role in cell growth within keloid tissue through the MAPK pathway. By integrating machine learning models, we identified CRGs that can be used for diagnosing keloid. The diagnostic efficacy of CRGs was confirmed using independent datasets, RT-qPCR, Western blotting, and IHC analysis. GSVA analysis indicated that high expression of CRGs influenced the gene set related to ECM receptor interaction. Conclusion: This study identified 10 cuproptosis-related genes that provide insights into the molecular mechanisms underlying keloid development and may have implications for the development of targeted therapies.
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Lack of specific biomarkers and effective drug targets constrains therapeutic research in breast cancer (BC). In this regard, therapeutic modulation of damage-associated molecular patterns (DAMPs)-induced immunogenic cell death (ICD) may help improve the effect of immunotherapy in individuals with BC. The aim of this investigation was to develop biomarkers for ICD and to construct ICD-related risk estimation models to predict prognosis and immunotherapy outcomes of BC. RNA-seq transcriptome information and medical data from individuals with BC (n = 943) were obtained from TCGA. Expression data from a separate BC cohort (GEO: GSE20685) were used for validation. We identified subtypes of high and low ICD gene expression by consensus clustering and assessed the connection between ICD subtypes and tumor microenvironment (TME). In addition, different algorithms were used to construct ICD-based prognostic models of BC. BC samples were categorized into subtypes of high and low ICD expression depending on the expression of genes correlated with ICD. The subtype of ICD high-expression subtypes are correlated with poor prognosis in breast cancer, while ICD low-expression subtypes may predict better clinical outcomes. We also created and verified a predictive signature model depending on four ICD-related genes (ATG5, CD8A, CD8B, and HSP90AA1), which correlates with TME status and predicts clinical outcomes of BC patients. We highlight the connection of ICD subtypes with the dynamic evolution of TME in BC and present a novel ICD-based prognostic model of BC. In clinical practice, distinction of ICD subtype and assessment of ICD-related biomarkers should help guide treatment planning and improve the effectiveness of tumor immunotherapy.
Subject(s)
Breast Neoplasms , Humans , Female , Immunogenic Cell Death , Prognosis , Immunotherapy , Biomarkers , Tumor MicroenvironmentABSTRACT
Computer-generated holography based on neural network holds great promise as a real-time hologram generation method. However, existing neural network-based approaches prioritize lightweight networks to achieve real-time display, which limits their capacity for network fitting. Here, we propose an asymmetrical neural network with a non-end-to-end structure that enhances fitting capacity and delivers superior real-time display quality. The non-end-to-end structure decomposes the overall task into two sub-tasks: phase prediction and hologram encoding. The asymmetrical design tailors each sub-network to its specific sub-task using distinct basic net-layers rather than relying on similar net-layers. This method allows for a sub-network with strong feature extraction and inference capabilities to match the phase predictor, while another sub-network with efficient coding capability matches the hologram encoder. By matching network functions to tasks, our method enhances the overall network's fitting capacity while maintaining a lightweight architecture. Both numerical reconstructions and optical experiments validate the reliability and effectiveness of our proposed method.
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To analyze the relationship between the composition of urinary stones and various influencing factors in the Enshi region. We used FT-IR to examine the composition of 1092 stone samples. Combined with the relevant clinical materials, the data were analyzed using both one-dimensional statistical methods and multivariate statistical methods. The study included 1092 stone samples, classified as follows: 457 (41.8%) with a single component, 453 (41.5%) with two components, 149 (13.6%) with three components, and 33 (3.0%) with four components. Stones were categorized into five types: Calcium Oxalate (CaOx) (76.4%), carbapatite (CaP) (9.3%), Struvite (ST) (8.3%), Uric Acid (UA) (4.9%), and Others (1.0%). Age, gender, urinary tract infection (UTI), family history of urinary stones (FH), hyperuricemia (HUA) and stone location were significantly associated with stone type. Logistic regression revealed that females and UTI were relative risk factors for predicting CaP and ST, while FH and HUA were relative risk factors for predicting UA. Our study indicates that the overall composition of urinary tract stones in the Enshi region is consistent with that of the entire China. Additionally, the predisposing factors for stone formation vary in terms of gender, age, FH, UTI, hyperuricemia HUA, and stone location.
Subject(s)
Hyperuricemia , Urinary Calculi , Urolithiasis , Female , Humans , Spectroscopy, Fourier Transform Infrared , East Asian People , Ethnic and Racial Minorities , Ethnicity , Retrospective Studies , Minority GroupsABSTRACT
OBJECTIVE: The effectiveness of arthroscopic rotator cuff repair (ARCR) on rheumatoid arthritis (RA) patients remains a controversial topic. This study investigates the mid-term outcomes of ARCR in RA patients and identifies the factors influencing clinical efficacy. METHODS: This retrospective study enrolled RA patients with small or medium rotator cuff tears (RCTs) between February 2014 and February 2019. Visual Analog Scale (VAS), American Shoulder and Elbow Surgeons (ASES), and Constant-Murley scores were collected at each follow-up time. Ultimately, magnetic resonance imaging (MRI) and X-ray were employed to assess rotator cuff integrity and progression of shoulder bone destruction, respectively. Statistical methods used two-way repeated-measures ANOVA or generalized estimation equations. RESULTS: A total of 157 patients were identified and divided into ARCR (n = 75) and conservative treatment (n = 82) groups. ARCR group continued to be divided into small tear (n = 35) and medium tear (n = 40) groups. At the final, all scores were better in ARCR group than in the conservative treatment group (p < 0.05). A radiographic evaluation of the final follow-up demonstrated that the progression rate in ARCR group (18.67%) was significantly lower than that of the conservative treatment group (39.02%, p < 0.05). In the comparison of the small tear and medium tear groups, all scores increased significantly after surgery (p < 0.05), and the final follow-up scores were better than preoperative scores (p < 0.05) but worse than those of the 6-month postoperative follow-up (p < 0.05). Comparison between the two groups revealed that all scores of the small tear group were significantly better than those of the medium tear group at 6-month postoperative follow-up (p < 0.05). Although the scores of small tear group remained better than those of the medium group at the final postoperative follow-up, the difference was not statistically significant (p > 0.05). Radiographic assessment of the final follow-up demonstrated that the progression rate in the small tear group (8.57%) was significantly lower than that in the medium group (27.50%, p < 0.05), and the retear rate of small tear group (14.29%) was significantly lower than that of the medium tear group (35.00%, p < 0.05). CONCLUSION: ARCR could effectively improve the quality of life for RA patients with small or medium RCTs, at least in the medium term. Despite the progression of joint destruction in some patients, postoperative retear rates were comparable to those in the general population. ARCR is more likely to benefit RA patients than conservative treatment.
Subject(s)
Arthritis, Rheumatoid , Rotator Cuff Injuries , Humans , Rotator Cuff/diagnostic imaging , Rotator Cuff/surgery , Rotator Cuff Injuries/diagnostic imaging , Rotator Cuff Injuries/surgery , Rupture/surgery , Arthroscopy/methods , Treatment Outcome , Retrospective Studies , Arthritis, Rheumatoid/surgery , Magnetic Resonance Imaging , Range of Motion, ArticularABSTRACT
In recent years, as a green renewable energy production technology, electrochemical water splitting has demonstrated high development potential. Many materials have been reported as successful catalysts in the water-splitting field. However, it is still a huge challenge to produce bifunctional electrocatalysts for the efficient and sustainable generation of hydrogen and oxygen simultaneously. Herein, we successfully developed oxygen vacancies abundant CuCo layered double oxide (Ov-CuCo-LDO) hollow nanotube arrays (HNTAs) loaded on nickel foam as advanced electrocatalysts for total water splitting. When the current density was 10 mA cm-2, the Ov-CuCo-LDO HNTAs exhibited outstanding onset overpotentials of 53.9 and 72.5 mV for the hydrogen evolution and oxygen evolution reactions (HER and OER) in alkaline medium, respectively, because of the bimetallic synergistic effect between the cobalt and copper and the unique hollow porous structure. In addition, an as-assembled Ov-CuCo-LDO||Ov-CuCo-LDO electrolytic cell showed a small potential of 1.55 V to deliver a current density of 10 mA cm-2. Moreover, it also showed remarkable durability after long-term overall water splitting for more than 20 h. The research results in this paper are of great interest to practical applications of the water decomposition process, providing clear and in-depth insights into preliminary robust and efficient multifunctional electrocatalysts for overall water splitting.
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Inflammation is a core mechanism for oncogenesis. Chemokines act as important mediators of chronic inflammation and the tumour inflammatory response. However, there is limited information on chemokines in hepatocellular carcinoma (HCC), a disease for which almost all cases are derived from chronic liver inflammation. Here, we explored the protumor effects of CXCL1, a commonly elevated inflammatory chemokine in cirrhosis, in HCC. The protumor role was confirmed in clinical samples from HCC patients. CXCL1 enhanced tumorigenesis in the hepatic inflammatory microenvironment directly by acting on tumour cells and indirectly through promoting the recruitment of macrophages. The increase in the number of macrophages in the tumour microenvironment (TME) promoted tumour cell epithelial-mesenchymal transition (EMT) and significantly increased CXCL1 levels in the TME partly through NF-κB/IL-1ß activation. To investigate the potential therapeutic value of CXCL1 in HCC with an inflammatory background, an antibody blocking CXCL1 was used alone or combined with the chemotherapy agent doxorubicin (DOX), with the goal of reshaping the TME. It has been shown that blocking CXCL1-CXCR2 inhibits tumour progression and reduces macrophage recruitment in the TME. The combination regimen has been shown to synergistically reduce the number of pro-tumour macrophages in the TME and suppress tumour progression. This provides insight into therapeutic strategies for treating HCC patients with high CXCL1 expression.
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PURPOSE: Several modifications to the anterior component separation technique (ACST) have been reported to facilitate the closure of abdominal wall defects. In this study, the external oblique (EO) muscle flap for modified ACST during major abdominal wall defect reconstructions has been described. METHODS: A retrospective review of consecutive patients undergoing modified ACST was conducted. The clinical data were collected and retrospectively analyzed. RESULTS: Among the 36 patients admitted to our hospital from December 2014 to December 2020, 9 cases had rectus abdominis tumors, 1 case had rectus abdominis trauma, and 26 cases had incisional hernias. The average age was 61.17 ± 13.76 years, and the mean BMI was 24.25 ± 3.18 kg/m2. The average width of the defect was 14.33 ± 2.90 cm. Unilateral EO muscle flap technique was used to reconstruct the abdominal wall. 3 cases of surgical site infection (8.3%), 4 cases of grade III or IV seroma (11.1%) and 2 cases of intestinal obstruction (5.5%)were reported postoperatively. Ischemic necrosis of the abdominal EO muscle flap, incision dehiscence, intestinal fistula, or other complications were not observed. 1 case of incisional hernia recurrence (2.8%) was reported. Recurrence of tumors or abdominal wall bulging were not noted during the follow-up period of 32.53 ± 14.21 months. CONCLUTIONS: The EO muscle flap technique is associated with low postoperative morbidity and recurrence rate, which approves it a reliable technique for selected groups of patients. Further research are needed to confirm the effectiveness of this technique.
Subject(s)
Abdominal Wall , Hernia, Ventral , Incisional Hernia , Plastic Surgery Procedures , Humans , Middle Aged , Aged , Abdominal Muscles/surgery , Abdominal Wall/surgery , Retrospective Studies , Abdominal Oblique Muscles/surgery , Hernia, Ventral/surgery , Incisional Hernia/surgery , Postoperative Complications/epidemiology , Postoperative Complications/surgeryABSTRACT
Breast cancer is one of the most common cancers affecting females worldwide. Early detection and diagnosis of breast cancer may aid in timely treatment, reducing the mortality rate to a great extent. To diagnose breast cancer, computer-aided diagnosis (CAD) systems employ a variety of imaging modalities such as mammography, computerized tomography, magnetic resonance imaging, ultrasound, and histological imaging. CAD and breast-imaging specialists are in high demand for early detection and diagnosis. This system has the potential to enhance the partiality of traditional histopathological image analysis. This review aims to highlight the recent advancements and the current state of CAD systems for breast cancer detection using different modalities.
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BACKGROUND: PDZ-binding kinase/T-lymphokine-activated killer cell-derived protein kinase (PBK/TOPK) is a potential prognostic indicator for patients with breast cancer. The objective of the present study was to explore the relationship between PBK/TOPK expression and clinicopathological indicators as well as the survival of patients with breast cancer. METHODS: Immunohistochemical staining was used to detect the expression of PBK/TOPK in 202 cases of breast cancer tissues. The relationship between PBK/TOPK and clinicopathological parameters was evaluated using Spearman's rank-order correlation. The difference in PBK/TOPK expression among different molecular types was analyzed with the chi-square test. Kaplan-Meier analysis was used to create a survival curve and the log rank test was used to analyze the overall survival (OS) and disease-free survival (DFS). Prognostic correlation was assessed using univariate and multivariate Cox regression analyses. RESULTS: Among 202 breast cancer samples, PBK/TOPK was expressed ("+" and "++") in 182 samples (90.1%). In addition, the histological grade, TNM stages, lymph node metastasis, estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER-2), and Ki-67 were positively associated with PBK/TOPK expression. With regard to the molecular type, the expression of PBK/TOPK is different. The expression level of PBK/TOPK was negatively correlated with both the OS and DFS of breast cancer patients. The difference in the above results is meaningful (P < 0.05). CONCLUSIONS: PBK/TOPK is overexpressed in breast cancer, and the expression is closely related to the clinicopathological characteristics of the disease. Breast cancer patients with high expression of PBK/TOPK have a poor prognosis. Therefore, healthcare providers can optimize breast cancer management using this indicator.
Subject(s)
Breast Neoplasms , Receptors, Progesterone , Female , Humans , Ki-67 Antigen , Mitogen-Activated Protein Kinase Kinases/metabolism , Prognosis , Receptors, Estrogen , Retrospective StudiesABSTRACT
BACKGROUND: State-of-art non-invasive diagnosis processes for bladder cancer (BLCA) harbour shortcomings such as low sensitivity and specificity, unable to distinguish between high- (HG) and low-grade (LG) tumours, as well as inability to differentiate muscle-invasive bladder cancer (MIBC) and non-muscle-invasive bladder cancer (NMIBC). This study investigates a comprehensive characterization of the entire DNA methylation (DNAm) landscape of BLCA to determine the relevant biomarkers for the non-invasive diagnosis of BLCA. METHODS: A total of 304 samples from 224 donors were enrolled in this multi-centre, prospective cohort study. BLCA-specific DNAm signature discovery was carried out with genome-wide bisulfite sequencing in 32 tumour tissues and 12 normal urine samples. A targeted sequencing assay for BLCA-specific DNAm signatures was developed to categorize tumour tissue against normal urine, or MIBC against NMIBC. Independent validation was performed with targeted sequencing of 259 urine samples in a double-blinded manner to determine the clinical diagnosis and prognosis value of DNAm-based classification models. Functions of genomic region harbouring BLCA-specific DNAm signature were validated with biological assays. Concordances of pathology to urine tumour DNA (circulating tumour DNA [ctDNA]) methylation, genomic mutations or other state-of-the-art diagnosis methods were measured. RESULTS: Genome-wide DNAm profile could accurately classify LG tumour from HG tumour (LG NMIBC vs. HG NMIBC: p = .038; LG NMIBC vs. HG MIBC, p = .00032; HG NMIBC vs. HG MIBC: p = .82; Student's t-test). Overall, the DNAm profile distinguishes MIBC from NMIBC and normal urine. Targeted-sequencing-based DNAm signature classifiers accurately classify LG NMIBC tissues from HG MIBC and could detect tumours in urine at a limit of detection of less than .5%. In tumour tissues, DNAm accurately classifies pathology, thus outperforming genomic mutation or RNA expression profiles. In the independent validation cohort, pre-surgery urine ctDNA methylation outperforms fluorescence in situ hybridization (FISH) assay to detect HG BLCA (n = 54) with 100% sensitivity (95% CI: 82.5%-100%) and LG BLCA (n = 26) with 62% sensitivity (95% CI: 51.3%-72.7%), both at 100% specificity (non-BLCA: n = 72; 95% CI: 84.1%-100%). Pre-surgery urine ctDNA methylation signature correlates with pathology and predicts recurrence and metastasis. Post-surgery urine ctDNA methylation (n = 61) accurately predicts recurrence-free survival within 180 days, with 100% accuracy. CONCLUSION: With the discovery of BLCA-specific DNAm signatures, targeted sequencing of ctDNA methylation outperforms FISH and DNA mutation to detect tumours, predict recurrence and make prognoses.
Subject(s)
Circulating Tumor DNA , Urinary Bladder Neoplasms , Biomarkers, Tumor/genetics , DNA Methylation/genetics , Humans , In Situ Hybridization, Fluorescence , Prospective Studies , Urinary Bladder Neoplasms/diagnosis , Urinary Bladder Neoplasms/genetics , Urinary Bladder Neoplasms/pathologyABSTRACT
Cylindrical holograms have been widely studied for their 360° display properties and have remained in the theoretical stage for a long time because of the difficulty to manufacture cylindrical spatial light modulators (SLMs). Recently, an optical realization of cylindrical holography using a planar SLM that converts planar holography into cylindrical holography through a conical mirror has been proposed. However, the magnification and quality improvement of the reconstruction have remained issues from the original method that still must be addressed. In this paper, a Fourier hologram optimization with stochastic gradient descent (FHO-SGD) is proposed for the magnification and quality improvement of an optical cylindrical holographic display. The reconstructed object is magnified 2.9 times by a lens with a focal length of 300 mm due to the optical properties of Fourier holograms. In addition, the quality of the reconstructed objects is significantly improved. Numerical simulation and optical experiments demonstrate the effectiveness of the proposed FHO-SGD method in the magnification and quality improvement of an optical cylindrical holographic display.
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In this study, an environmentally friendly and water-soluble nitrogen-doped carbon quantum dots (N-CQDs) with quantum yield (QY) of 8.59% were prepared by one-step hydrothermal synthesis without any chemical reagent using the leaves of prunus lannesiana as precursors. The properties and quality of N-CQDs were investigated by Ultraviolet-visible absorption spectroscopy, infrared spectroscopy, X-ray photoelectron spectroscopy, zeta potential, high-resolution transmission electron microscopy and fluorescence spectroscopy. The fluorescence of the prepared N-CQDs can be quenched by Fe3+ through the synergistic effect of the formation of non-fluorescent complex and internal filtration effect (IFE) between Fe3+ and N-CQDs. And the quenched fluorescence can be "turned on" after adding ascorbic acid (AA) because Fe3+ can be released from the surface of N-CQDs through the redox reaction between AA and Fe3+. While the restored fluorescence can be "turned off" again by hydrogen peroxide (H2O2) due to the re-oxidation of Fe2+ to Fe3+. So, the three inputs "logic gate" is achieved and the "on-off-on-off" continuous response fluorescence sensor is formed, which can be applied for the continuous detection of Fe3+, AA and H2O2 with the linear range of 40-260 µM, 10-200 µM and 40-140 µM, respectively. Finally, the sensor was successfully applied to determine Fe3+, AA and H2O2 in real samples with the satisfactory recoveries (95.35%-104.10%) and repeatability (relative standard deviation (RSD) ≤ 1.68%). The continuous response fluorescence sensor prepared by simple green synthesis route has the characteristics of fast response, acceptable sensitivity and good selectivity.
Subject(s)
Prunus , Quantum Dots , Carbon , Hydrogen Peroxide , Limit of Detection , Nitrogen , Spectrometry, FluorescenceSubject(s)
Carcinoma, Transitional Cell/mortality , DNA Polymerase III/genetics , Germ-Line Mutation , Urinary Bladder Neoplasms/mortality , Carcinoma, Transitional Cell/genetics , Carcinoma, Transitional Cell/pathology , Female , Humans , Male , Pedigree , Prognosis , Survival Rate , Urinary Bladder Neoplasms/genetics , Urinary Bladder Neoplasms/pathologyABSTRACT
BACKGROUND: Novel chemotherapeutic drugs with good anti-tumor activity are of pressing need for bladder cancer treatment. In this study, plumbagin (PL), a natural plant-derived drug extracted from Chinese herbals, was identified as a promising candidate for human bladder cancer (BCa) chemotherapy. METHODS: The anti-tumor activity of PL was evaluated using a series of in vitro experiments, such as MTT, transwell assay, flow cytometry, quantitative real-time PCR (qRT-PCR) and western blotting. We established xenograft tumors in nude mice by subcutaneous injection with the human bladder cancer T24 cells. RESULTS: The results showed that PL could inhibit the proliferation, migration and survival of BCa cells (T24 and UMUC3 cells) in a time- and dose-dependent way. We found PL promotes the cell cycle arrest and apoptosis by inhibiting PI3K/AKT/mTOR signaling pathway, which inhibits cell proliferation. In vivo, anti-tumor activity of PL was further investigated using a BCa cell xenograft mice model. To simulate clinical chemotherapy, the PL were intravenously injected with a dose of 10 mg/kg for 10 times. Compared with the blank control, the tumor weight in PL treated group decreased significantly from 0.57 ± 0.04 g to 0.21 ± 0.06 g (P < 0.001). CONCLUSIONS: In our study. We found PL inhibits the proliferation of T24 and UMUC3 cells in vivo and in vitro, which may play a role through several downstream effectors of PI3K/AKT/mTOR signaling pathway to promote the cell cycle arrest and apoptosis. Meanwhile, we consider that PL may inhibit the migration of bladder cancer cells via EMT suppression and induce ROS generation to make cell apoptosis. This work screened out a novel chemotherapeutic drug (plumbagin) with relatively good anti-tumor activity, which possessed great potential in BCa chemotherapy.
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We aimed to investigate the biological function of MELK and the therapeutic potential of OTSSP167 in human bladder cancer (BCa). First, we observed overexpression of MELK in BCa cell lines and tissues and found that it was associated with higher tumour stage and tumour grade, which was consistent with transcriptome analysis. High expression of MELK was significantly correlated with poor prognosis in BCa patients, and MELK was found to have a role in the cell cycle, the G1/S transition in mitosis, and DNA repair and replication. Furthermore, BCa cells presented significantly decreased proliferation capacity following silencing of MELK or treatment with OTSSP167 in vitro and in vivo. Functionally, reduction in MELK or treatment of cells with OTSSP167 could induce cell cycle arrest and could suppress migration. In addition, these treatments could activate phosphorylation of ATM and CHK2, which would be accompanied by down-regulated MDMX, cyclin D1, CDK2 and E2F1; however, p53 and p21 would be activated. Opposite results were observed when MELK expression was induced. Overall, MELK was found to be a novel oncogene in BCa that induces cell cycle arrest via the ATM/CHK2/p53 pathway. OTSSP167 displays potent anti-tumour activities, which may provide a new molecule-based strategy for BCa treatment.
Subject(s)
Antineoplastic Agents/pharmacology , Ataxia Telangiectasia Mutated Proteins/metabolism , Cell Cycle Checkpoints , Checkpoint Kinase 2/metabolism , Protein Serine-Threonine Kinases/antagonists & inhibitors , Tumor Suppressor Protein p53/metabolism , Urinary Bladder Neoplasms/pathology , Aged , Animals , Cell Cycle Checkpoints/drug effects , Cell Line, Tumor , Cell Movement/drug effects , Cell Proliferation/drug effects , Disease Progression , Female , Gene Expression Regulation, Neoplastic/drug effects , Gene Silencing/drug effects , Humans , Male , Mice, Inbred BALB C , Middle Aged , Models, Biological , Naphthyridines/pharmacology , Prognosis , Protein Serine-Threonine Kinases/genetics , Protein Serine-Threonine Kinases/metabolism , RNA, Messenger/genetics , RNA, Messenger/metabolism , Up-Regulation/drug effects , Urinary Bladder Neoplasms/geneticsABSTRACT
@#[Abstract] Objective: To explore the effect of circ_0001429 on proliferation and apoptosis of bladder cancer cells by regulating miR-139-5p/TGF-interacting factor 1(TGIF1)axis. Methods: The expression of circ_0001429 in bladder cancer cell lines SW780, T24, 5637 and human bladder epithelial SV-HUC-1 cells were detected by RT-qPCR. Targeted regulatory relationship between circ_0001429 and miR-139-5p as well as miR-139-5p and TGIF1 was measured by Dual luciferase reporter gene assay. T24 cells were divided into NC group, sh-circ_0001429 group, miR-139-5p mimics group, sh-TGIF1 group, pcDNA-circ_0001429+sh-TGIF1 group, miR-139-5p mimics+pcDNA-TGIF1 group and sh-circ_0001429+miR-139-5p inhibitor group. Western blotting was used to detect the expression level of TGIF1 in each group. CCK-8 method, Transwell experiment and Flow cytometry were used to detect the effects of circ_ 0001429, miR-139-5p and TGIF1 on proliferation, invasion, migration and apoptosis of T24 cells, respectively. Results: Circ_0001429 was highly expressed in three bladder cancer cell lines (P<0.01). Knockdown of circ_0001429 significantly inhibited proliferation, invasion and migration of T24 cells while promoted the level of cell apoptosis (P<0.05 or P<0.01). The results of Dual luciferase reporter gene assayconfirmedthatthereisatargetingrelationshipbetweencirc_0001429andmiR-139-5p as well as between miR-139-5p and TGIF1. Overexpression of miR-139-5p significantly inhibited the proliferation, invasion and migration of T24 cells while promoted the level of cell apoptosis (all P<0.01). Recovery experiments further confirmed that the competitive binding of circ_0001429 and TGIF1 to miR-139-5p promoted the proliferation, invasion and migration of T24 cells while inhibited the level of cell apoptosis (all P<0.01). Conclusion: Circ_0001429 promotes proliferation, invasion and migration and inhibits apoptosis of bladder cancer T24 cells by competing with TGIF1 to bind to miR-139-5p.
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BACKGROUND: Locking compress plate, as external fixator, is an attractive technique for distal tibial fracture treatment. But it still remains unclear whether the external LCP has sufficient stiffness. Thus, the present study aims to make a comprehensive evaluation of the stiffness of external locking compress plate when it is used as an external fixator in distal tibial fractures treatment. METHODS: Composite tibia was used to simulate distal tibia fracture (Orthopedic Trauma Association type 43 A3 fracture). The fractures were stabilized with medial distal tibial locking compress plates (LCP group), medial distal tibial locking compress plates with 30-mm plate-bone distances (EF-tibia group), and medial distal femur locking compress plates with 30-mm plate-bone distances (EF-femur group). Stiffness of each configuration was measured under axial compression loading and in axial torsion loading directions. Compression stiffness and torsional rigidity were compared across different groups. RESULTS: Compared with LCP group, (1) EF-tibia group showed significantly lower (p < 0.001) compression stiffness and torsional rigidity; (2) EF-femur group showed significantly lower (p < 0.001) compression stiffness, but significantly higher (p < 0.001) torsional rigidity. CONCLUSIONS: The results indicated that locking compress plate as an external fixator was flexible, and the distal femur locking compress plate was preferred over the distal tibial locking compress plate to be an external fixator in distal tibia fracture treatment.