Potential Benefits of Statin Therapy in Reducing Osteoarthritis Risk: A Mendelian Randomization Study.

OBJECTIVE: The purpose of this study was to determine the causal effect of statins on osteoarthritis (OA) risk using Mendelian randomization (MR). METHODS: Single nucleotide polymorphism-based genome-wide association analyses of statins were collected from the UK Biobank and FinnGen dataset, and OA data were collected from the UK Biobank and Arthritis Research UK Osteoarthritis Genetics (arcOGEN) study. Two-sample MR analyses were performed using the inverse-variance weighted (IVW) technique. MR-Egger, weighted median, and weighted mode served as supplementary analyses. MR-Egger regression, Cochran's Q test, and Mendelian Randomization Pleiotropy Residual Sum and Outlier analysis were performed as sensitivity analyses. Hydroxymethylglutaryl-coenzyme A reductase (HMGCR) expression and OA risk were evaluated using summary data-based MR (SMR). RESULTS: MR analyses consistently supported a causal connection between statin use and OA risk. A causal effect was observed for atorvastatin (IVW: ß = -2.989, P = 0.003) and rosuvastatin (IVW: ß = -14.141, P = 0.006) treatment on hip OA. Meta-analysis showed the association between atorvastatin and knee OA was statistically significant (odds ratio 0.15; P = 0.004). Simvastatin use exhibited a protective effect against knee (IVW: ß = -1.056, P = 0.004) and hip OA (IVW: ß = -1.405, P = 0.001). Statin medication showed a protective effect on hip OA (IVW: ß = -0.054, P = 0.013). HMGCR correlated significantly with a reduced risk of knee OA (ß = -0.193, PSMR = 0.017), rather than hip OA (ß = 0.067, PSMR = 0.502), which suggested that statins' protective effect on OA may not be related to its lipid-lowering effect. CONCLUSION: This MR study provides compelling evidence that statin treatment may be a protective factor for OA. Further research is required to clarify its underlying mechanism.

Activating biomass carbon with metallurgical slag by pyrolysis in molten salt for high-performance supercapacitors.

Pyrolysis of sustainable biomass to advanced carbon materials for energy storage is key-enabling in energy and environmental sustainability. However, obtaining carbon materials with well-defined microstructure and composition for high-performance energy storage is extremely challenging. Herein, efficient activation of biomass carbon is realized by introducing extra metallurgical slag during pyrolysis of coconut shell in Na2CO3-K2CO3 molten salt. The molten salt guides the formation of carbon with a hierarchical honeycomb-like nanostructure, while the metallurgical slag facilitates enhanced doping of the heteroatom species, conjointly contributing to the increase of the specific surface area of carbon materials from 424 m2 g-1 to 1451 m2 g-1 and the extension of the single N dopant to multiple dopants of N, P, Zn and Co. Such adequate tuning of the microstructure and composition in the pyrolysis product increases the capacitance for supercapacitors from 30 F g-1 to 135 F g-1 at 0.5 A g-1. The results can provide new insights for the controllable upgradation of both biomass and waste industrial slag toward enhanced energy storage.

LRRC superfamily expression in stromal cells predicts the clinical prognosis and platinum resistance of ovarian cancer.

BACKGROUND: Leucine-rich repeat sequence domains are known to mediate protein‒protein interactions. Recently, some studies showed that members of the leucine rich repeat containing (LRRC) protein superfamily may become new targets for the diagnosis and treatment of tumours. However, it is not known whether any of the LRRC superfamily genes is expressed in the stroma of ovarian cancer (OC) and is associated with prognosis. METHODS: The clinical data and transcriptional profiles of OC patients from the public databases TCGA (n = 427), GTEx (n = 88) and GEO (GSE40266 and GSE40595) were analysed by R software. A nomogram model was also generated through R. An online public database was used for auxiliary analysis of prognosis, immune infiltration and protein‒protein interaction (PPI) networks. Immunohistochemistry and qPCR were performed to determine the protein and mRNA levels of genes in high-grade serous ovarian cancer (HGSC) tissues of participants and the MRC-5 cell line induced by TGF-ß. RESULTS: LRRC15 and LRRC32 were identified as differentially expressed genes from the LRRC superfamily by GEO transcriptome analysis. PPI network analysis suggested that they were most enriched in TGF-ß signalling. The TCGA-GTEx analysis results showed that only LRRC15 was highly expressed in both cancer-associated fibroblasts (CAFs) and the tumour stroma of OC and was related to clinical prognosis. Based on this, we developed a nomogram model to predict the incidence of adverse outcomes in OC. Moreover, LRRC15 was positively correlated with CAF infiltration and negatively correlated with CD8 + T-cell infiltration. As a single indicator, LRRC15 had the highest accuracy (AUC = 0.920) in predicting the outcome of primary platinum resistance. CONCLUSIONS: The LRRC superfamily is related to the TGF-ß pathway in the microenvironment of OC. LRRC15, as a stromal biomarker, can predict the clinical prognosis of HGSC and promote the immunosuppressive microenvironment. LRRC15 may be a potential therapeutic target for reversing primary resistance in OC.

Comprehensive analysis of novel prognosis-related proteomic signature effectively improve risk stratification and precision treatment for patients with cervical cancer.

OBJECTIVE: Cervical cancer (CC) is one of the most common types of malignant female cancer, and its incidence and mortality are not optimistic. Protein panels can be a powerful prognostic factor for many types of cancer. The purpose of our study was to investigate a proteomic panel to predict the survival of patients with common CC. METHODS AND RESULTS: The protein expression and clinicopathological data of CC were downloaded from The Cancer Proteome Atlas and The Cancer Genome Atlas database, respectively. We selected the prognosis-related proteins (PRPs) by univariate Cox regression analysis and found that the results of functional enrichment analysis were mainly related to apoptosis. We used Kaplan-Meier analysis and multivariable Cox regression analysis further to screen PRPs to establish a prognostic model, including BCL2, SMAD3, and 4EBP1-pT70. The signature was verified to be independent predictors of OS by Cox regression analysis and the area under curves. Nomogram and subgroup classification were established based on the signature to verify its clinical application. Furthermore, we looked for the co-expressed proteins of three-protein panel as potential prognostic proteins. CONCLUSION: A proteomic signature independently predicted OS of CC patients, and the predictive ability was better than the clinicopathological characteristics. This signature can help improve prediction for clinical outcome and provides new targets for CC treatment.

Membranous and nuclear staining of CLDN18 in HPV-independent and HPV-associated endocervical adenocarcinomas.

OBJECTIVES: A classification system for endocervical adenocarcinoma (ECA) based on high-risk human papillomavirus (HPV) status has been established; however, the immunohistochemical markers distinguishing HPV-independent and HPV-associated ECAs have not been fully described. Here, we aimed to characterize ECA immunopathological features. METHODS: We evaluated the immunohistochemical profile of CLDN18, CDX2, PAX8, p16, p53, and CEA in 60 ECAs comprising 10 HPV-independent ECAs and 50 HPV-associated ECAs. Both the membranous and nuclear expression levels of CLDN18 were analyzed. RESULTS: Membranous CLDN18 (CLDN18 [M]) was found to be expressed in the mucinous epithelium of all HPV-independent ECAs, including eight gastric-type ECAs (G-ECAs), one endometrioid ECA, and one clear cell ECA, but no nuclear CLDN18 (CLDN18 [N]) expression was detected in HPV-independent ECAs. Among HPV-associated ECAs, CLDN18 (M) expression levels in intestinal-type (I-ECAs) and usual-type ECAs (U-ECAs) were significantly different from those in invasive stratified mucin-producing (iSMILE) carcinomas (p = 0.036). Positive CLDN18 (M) staining was present in 55.6% (5/9) of intestinal-type and 39.4% (13/33) of usual-type ECAs and was not present in iSMILE ECAs. Silva pattern C cancers expressed higher levels of CLDN18 (M) than Silva pattern A and B cancers (p = 0.004), whereas the CLDN18 (N) expression levels in cancers showing Silva pattern A were significantly higher than those in cancers exhibiting Silva patterns B and C (p < 0.001). CONCLUSION: Membranous CLDN18 is expressed in ECAs and is particularly frequently expressed in HPV-independent ECAs, and membranous CLDN18 expression has potential as a therapeutic target. Nuclear staining of CLDN18 is a new immunohistochemical marker for diagnosing Silva pattern A HPV-associated ECAs and is associated with a good prognosis. Further studies should investigate the therapeutic and prognostic significance of membranous and nuclear CLDN18 expression and develop a related test that can be implemented in the clinical evaluation of ECAs.

Serum free fatty acid elevation is related to acute kidney injury in primary nephrotic syndrome.

The aim of this research was to examine the clinical characteristics of acute kidney injury (AKI) in primary nephrotic syndrome (NS) and discuss the relationship between serum lipids and AKI. A total of 1028 patients diagnosed with primary NS with renal biopsy results were enrolled in this study. The patients were divided into AKI (n = 81) and non-AKI (n = 947) groups, and their characteristics were compared using a propensity score analysis for the best matching. Serum free fatty acid (FFA) was an independent predictor for AKI in the postmatch samples (p = 0.011). No significant difference in FFA levels was observed among AKI stages or different pathological types in the AKI and non-AKI groups. The AUC (area under the ROC curve) was 0.63 for FFA levels to distinguish AKI. In primary NS, elevated FFA levels tend to be related to a high risk of AKI. FFAs have diagnostic value and may serve as biomarkers for AKI in NS.

Serum Free Fatty Acids and G-Coupled Protein Receptors Are Associated With the Prognosis of Epithelial Ovarian Cancer.

Purpose: Fatty acid metabolism plays key role in cancer development, and free fatty acid receptors (FFARs) are involved in many cancers. However, the correlation between serum free fatty acids (FFAs)/FFARs levels and ovarian cancer (OC) prognosis remains largely unclear. Methods: A retrospective review of 534 primary OC patients and 1049 women with benign ovarian tumors was performed. Serum FFA levels data were extracted from the electronic medical record system. Repeated FFA results of 101 OC patients treated with standard chemotherapy were collected. The effects of FFAs on cells migration were evaluated in OC cell lines by Transwell assay. Gene Expression Profiling Interactive Analysis (GEPIA) was used to compare FFAR mRNA expression levels in cancer and noncancer tissues. Kaplan-Meier (KM) plotter was employed to analyze their prognostic values. SPSS 23.0 and Graphpad prism 7.0 software was used for analysis and graph construction. Results: FFA levels in the serum of epithelial ovarian cancer (EOC) women were higher than in women with benign ovarian tumors independent of pathology, tumor stage,and grade. FFA levels decreased gradually after chemotherapy. FFAs enhanced the migration of OVCAR3 cells. FFAR1 mRNA expression was lower in OC cells than in control cells. FFAR3 was related to a better prognosis, and FFAR4 was related to poor prognosis in TP-53wild-type and mutated type OC, while FFAR1 and FFAR2 were related to a better prognosis in TP53 wild-type OC but FFAR2 was related to a poor prognosis in TP53-mutant OC. Conclusion: The FFA levels are increased in OC and decreased with chemotherapy. High expression of FFARs was related to the prognosis of OC. The prognostic value of different FFARs differs depending on whether it is a TP53 wild or TP53 mutant ovarian cancer.Targeting FFARs may be an attractive treatment strategy for EOC.

Underwater Submarine Path Planning Based on Artificial Potential Field Ant Colony Algorithm and Velocity Obstacle Method.

Navigating safely in complex marine environments is a challenge for submarines because proper path planning underwater is difficult. This paper decomposes the submarine path planning problem into global path planning and local dynamic obstacle avoidance. Firstly, an artificial potential field ant colony algorithm (APF-ACO) based on an improved artificial potential field algorithm and improved ant colony algorithm is proposed to solve the problem of submarine underwater global path planning. Compared with the Optimized ACO algorithm proposed based on a similar background, the APF-ACO algorithm has a faster convergence speed and better path planning results. Using an inflection point optimization algorithm greatly reduces the number and length of inflection points in the path. Using the Clothoid curve fitting algorithm to optimize the path results, a smoother and more stable path result is obtained. In addition, this paper uses a three-dimensional dynamic obstacle avoidance algorithm based on the velocity obstacle method. The experimental results show that the algorithm can help submarines to identify threatening dynamic obstacles and avoid collisions effectively. Finally, we experimented with the algorithm in the submarine underwater semi-physical simulation system, and the experimental results verified the effectiveness of the algorithm.

A Low-Cost and Air-Stable Rechargeable Aluminum-Ion Battery.

Rechargeable aluminum-ion batteries (AIBs) are promising for large-scale energy storage due to the abundant reserves, low cost, and high capacity of the Al anode. However, the development of AIBs is currently hindered by the usage of AlCl3 /1-ethyl-3-methylimidazolium chloride electrolyte, which is expensive, highly corrosive, and extremely air-sensitive. Herein, a new hydrated eutectic electrolyte (HEE) composed of hydrated aluminum perchlorate and succinonitrile for low-cost, noncorrosive, and air-stable AIBs is reported. Crystal water in the hydrated aluminum perchlorate plays a vital role in forming the HEE, in which one H2 O and five succinonitrile molecules coordinate with one Al3+ ion. The optimized ratio of Al(ClO4 )3 ·9H2 O to succinonitrile is 1:12. When combining with the self-doped polyaniline cathode, the associated AIB delivers a high discharge capacity of 185 mAh g-1 over 300 cycles; and the charge/discharge mechanism in the HEE is studied experimentally and theoretically. The HEE is nonflammable, air-stable, and noncorrosive, thus enabling good air tolerance and facile fabrication of AIBs.

Molten Salt Electrochemical Modulation of Iron-Carbon-Nitrogen for Lithium-Sulfur Batteries.

Sulfur hosts with rationally designed chemistry to confine and convert lithium polysulfides are of prime importance for high-performance lithium-sulfur batteries. A molten salt electrochemical modulation of iron-carbon-nitrogen is herein demonstrated as formation of hollow nitrogen-doped carbon with grafted Fe3 C nanoparticles (Fe3 C@C@Fe3 C), which is rationalized as an excellent sulfur host for lithium-sulfur batteries. Fe3 C over nitrogen-doped carbon contributes to enhanced adsorption and catalytic conversion of lithium polysulfides. The sulfur-loaded Fe3 C@C@Fe3 C electrodes hence show a high capacity, good cyclic stability, and enhanced rate performance. This work highlights the unique chemistry of metal carbides on facilitating adsorption-conversion process of lithium polysulfides, and also extends the scope of molten salt electrolysis to elaboration of energy materials.

PD-L1, PARP1, and MMRs as potential therapeutic biomarkers for neuroendocrine cervical cancer.

OBJECTIVE: Neuroendocrine cervical cancer (NECC) is a rare cervical cancer with high aggressivity that causes poor prognosis even in the early stage. Given other neuroendocrine carcinomas and other types of cervical cancer have been proved to have expression of programmed cell death protein 1 ligand 1(PD-L1) and poly ADP-ribose polymerase-1(PARP1), we would measure and analyze these proteins in this invasive cancer. The purpose of this study is to investigate the application value of PD-1/PD-L1 and PARP1 inhibitors in NECC. METHODS: The NECC cases in our center with formalin-fixed paraffin-embedded tissue blocks were collected, and immunohistochemical (IHC) staining of PD-L1, PARP1, Mismatch repair proteins (MMRs), and P53 was performed. Chi-square test was used to analyze associations between various protein expressions. We analyzed the efficacy of immunotherapy in a recent patient with secondary recurrence after two courses of chemotherapy. RESULTS: After rigorous screening, 20 cases were finally included. Three cases did not undergo surgical treatment because of their advanced stage. Twelve (60%) developed distant metastases or relapsed within five years, and most of them within two years. The positive rate of PD-L1 and PARP1 were 70% and 75% respectively. Among all the cases, microsatellite instability (MSI) was seen in six cases (30%) and abnormal p53 expression was in 15 patients (75%). PD-L1 was associated with PARP1 expression in the MSI subgroup. The patient treated with chemotherapy + VEGF inhibitor (VEGFi) + programmed cell death protein 1(PD-1) inhibitor had an excellent improvement in clinical symptoms, tumor markers, and mass size. CONCLUSION: The IHC results of PD-L1, PARP1, and MMRs suggested that NECC was the target of immunotargeted therapy. Our case confirmed that immune checkpoint therapy was effective in patients with PD-L1 positive and MMRs loss. Considering the clinical practicability, more cases should be collected, and effective biomarkers still need to be further searched.

Integrating Network Pharmacology and Experimental Models to Investigate the Mechanism of Huanglian Jiedu Decoction on Inflammatory Injury Induced by Cerebral Ischemia.

Unlike single-target Western medicines, traditional Chinese medicines (TCMs) exhibit diverse curative effects against multiple diseases through their "multicomponent" and "multitarget" manifestations. However, the material basis of the major therapeutic diseases and TCM underlying molecular mechanisms remain to be challenged. In the current study, we applied, for the first time, an integrated strategy that combines network pharmacology and experimental evaluation and explored and demonstrated the underlying possible mechanisms of a classic TCM formula, Huanglian Jiedu Decoction (HLJD), in the treatment of cerebral ischemia. First, the herb compound, protein compound, and GO-BP and KEGG pathways were constructed to predict the material basis of HLJD in the treatment of cerebral ischemia and explore the underlying molecular mechanisms. Network pharmacology analysis showed that HLJD treats cerebral ischemia mainly through its anti-inflammatory effect. We used molecular docking to verify that HLJD components have good binding activities to the arachidonic acid pathway enzymes, cyclooxylipase-2 (COX-2) and 5-lipoxygenase (5-LOX). Next, based on the prediction by the network pharmacology analysis, the rat model of middle cerebral artery occlusion (MCAO) was established to verify the efficacy of HLJD. The results showed that HLJD reduces the degree of brain injury in MCAO rats, probably by inhibiting the expression of the 5-LOX pathway and inflammatory response. In conclusion, our study demonstrates the effectiveness of integrating network pharmacology with an experimental study for material basis of the major therapeutic diseases and the underlying molecular mechanisms of TCM.

Good performance of p16/Ki-67 dual-stain cytology for detection and post-treatment surveillance of high-grade CIN/VAIN in a prospective, cross-sectional study.

BACKGROUND: The limited sensitivity of Papanicolaou (Pap) cytology and the low specificity of HPV testing in detecting cervical or vaginal lesions means that either precancers are missed or women without lesions are overtreated. To improve performance outcomes, p16/Ki-67 dual-stain cytology has been introduced as a useful biomarker. METHODS: A prospective, cross-sectional study was performed and included 599 patients. Clinical performance estimates of Pap cytology, HPV DNA assay, and p16/Ki-67 dual-stain cytology for the detection of CIN2+/VAIN2+ were determined and compared. RESULTS: The sensitivity and specificity of p16/Ki-67 dual-stain cytology in detecting histology proven CIN2+/VAIN2+ was 91.6% and 95.0%, respectively, while that of Pap cytology was 42.1% and 95.2%, respectively, and that of HPV DNA testing was 100% and 41.6%, respectively. Among the three tests, the AUC of p16/Ki-67 immunocytochemistry was the largest, both for detecting cervical lesions and vaginal lesions, at 0.932 and 0.966, respectively. Among women who were HPV 16/18 positive or 12-other hrHPV positive and Pap positive (≥ASCUS), dual staining reduced the number of unnecessary colposcopy referrals from 274 to 181. Among the women who were 12-other hrHPV positive and Pap negative, dual staining could prevent underdiagnosis in six patients with CIN2+/VAIN2+ when used as a triage marker. Dual staining also identified four women with high-grade lesions detected by diagnostic conization but with negative colposcopy-guided biopsy results. CONCLUSION: p16/Ki-67 dual staining may be a promising tool for predicting high-grade cervical and vaginal lesions.

Knockdown of enhancer of rudimentary homolog inhibits proliferation and metastasis in ovarian cancer by regulating epithelial-mesenchymal transition.

Ovarian cancer (OC) is the deadliest gynecological malignancy. The pathogenesis of molecular in epithelial ovarian cancer (EOC), main histological type of OC, has not been completely defined. Enhancer of rudimentary homolog (ERH) had been reported to participate in transcriptional regulation, mRNA splicing, DNA repair and DNA synthesis by binding a variety of proteins. In this study, immunohistochemical staining revealed that the protein expression of ERH was associated with histological type, lymph node metastasis and pathological grade in EOC patients. To verify the association of ERH with the prognosis of OC, a GSE microarray dataset was downloaded from the Gene Expression Omnibus (GEO) database. Survival analysis suggested that ERH may be associated with poor prognosis of OC. In addition, shRNA was used to knockdown the protein and mRNA expression levels of ERH in the OC cell line SKOV3. Inhibition of ERH expression slowed proliferation, promoted apoptosis and inhibited metastasis and invasion by regulating epithelial-mesenchymal transition (EMT) in SKOV3 cells. These results indicate that ERH protein promotes the development of OC and provides an experimental basis for ERH as the potential target for ovarian cancer treatment.

In-Situ Growth of Broussonetia-Like NiCo2O4 on Carbon Cloth with Tailored Aqueous Capacitance.

Tailored broussonetia-like NiCo2O4 is grown on carbon cloth using tri-sodium citrate assisted hydrothermal method. The chelating effect of citric ions has been utilized to investigate the morphological and structural evolution of NiCo2O4 on carbon cloth, which have been illustrated by scanning electron microscopy, transmission electron microscopy, and X-ray photoelectron spectra. The results demonstrate that the morphological alteration of NiCo2O4 from single nanowire to broussonetia-like structure has been detected after the addition of tri-sodium citrate. Citric ion plays a crucial role as an electrostatic stabilizer in determining this unique structure. When used as binder-free electrode in aqueous supercapacitors, the broussonetia-like NiCo2O4 electrode exhibits a specific capacitance of 527.9 F g-1 at a current density of 0.5 A g-1. Additionally, an asymmetric supercapacitor is further assembled using NiCo2O4 as the positive electrode and activated carbon as negative electrode. The device exhibits a maximum energy of 26.4 Wh kg-1 at power density of 800 W kg-1. A long-term cycling stability with 82% capacitance retention is maintained after 20,000 cycles at a current density of 5 A g-1, indicating the practical applicability of the tested device.

A high serum-free fatty acid level is associated with cancer.

PURPOSE: The objectives of this work were to investigate whether the serum-free fatty acid (FFA) level is meaningful in cancer patients and its role in cancer diagnosis. METHODS: A total of 2206 patients were divided into a cancer group (n = 1019) and a noncancer group (n = 1187). Age, sex, body mass index (BMI), and serum FFA and serum albumin levels were collected. Cancer patients were divided into subgroups according to the location of the cancer. We then compared serum FFA levels among the tumor subgroups. A receiver operating characteristic (ROC) curve analysis was performed to further evaluate the diagnostic ability of the FFA level. SPSS 22.0 software was used to analyze the results. RESULTS: The FFA level was higher in the cancer group than in the noncancer group. According to the multivariate analysis, there was also an increased risk of cancer associated with a high FFA level after adjusting for old age, female sex, and a low BMI. In the subgroup analysis, the FFA level in patients with lung cancer, gastric cancer, thyroid cancer, rectal cancer, colon cancer, and ovarian cancer was significantly higher than that in noncancer patients. The area under the effect-time curve (AUC) of FFAs in the whole cancer group was 0.58, while the thyroid cancer, rectal cancer, and ovarian cancer subgroups had AUCs > 0.6. CONCLUSION: Our study provides clinical evidence to support that fatty acid metabolism is associated with cancers and demonstrates that a high FFA level in the serum may be an indicator of cancer.

Low-Temperature Assembly of Ultrathin Amorphous MnO2 Nanosheets over Fe2O3 Spindles for Enhanced Lithium Storage.

Carbon coating is an effective method to enhance the lithium storage of metal oxides, which, however, suffers from harsh conditions in high-temperature hydrolysis of organic mass at inert atmosphere and compromised capacity due to the presence of low-capacity carbon. We herein report a direct assembly of ultrathin amorphous MnO2 nanosheets with thickness less than 3 nm over Fe2O3 nanospindle backbones at 95 °C as a mild-condition, short-process, and upscalable alternative to the classic carbon-coating method. The assembly of the amorphous MnO2 nanosheets significantly increases the electrical conductivity of Fe2O3 nanospindles. When evaluated as an anode for lithium-ion batteries, the Fe2O3@amorphous MnO2 electrode shows enhanced capacity retention compared to that of the Fe2O3 nanospindle electrode. In situ transmission electron microscopy and in situ X-ray diffraction observations of the electrochemically driven lithiation/delithiation of the Fe2O3@amorphous MnO2 electrode indicate that the assembled amorphous MnO2 nanosheets are in situ transformed into a Fe-Mn-O protection layer for better electrical conductivity, uncompromised Li+ penetration, and enhanced structural integration. The Fe2O3@amorphous MnO2 electrode therefore has a reversible capacity of 555 mAh g-1 after 100 galvanostatic charge/discharge cycles at 1000 mA g-1, comparable with that of the Fe3O4@C electrode derived via the classic carbon-coating route.

Expression and prognostic value of lactate dehydrogenase-A and -D subunits in human uterine myoma and uterine sarcoma.

OBJECTIVE: This study aimed to determine the expression of lactate dehydrogenase (LDH)-A and LDH-D in patients with uterine myoma, cellular leiomyoma (CLM), and uterine sarcoma and to evaluate their prognostic significance. METHODS: Protein expression levels of LDH-A and LDH-D were determined in tissue samples from 86 patients (26 uterine myoma, 10 CLM, 50 uterine sarcoma) by immunohistochemistry and their associations with clinicopathologic parameters and outcomes were analyzed in patients with uterine sarcoma. RESULTS: The positivity rates for LDH-A and LDH-D were significantly higher in patients with uterine sarcoma compared with those with uterine myoma or CLM (P < .05). Patients with uterine sarcoma were classified as having uterine leiomyosarcoma (LMS), malignant endometrial stromal sarcoma, and malignant mixed Mullerian tumor, with 5-year overall survival rates of 59%, 71%, and 29%, respectively (P < .05). Univariate analysis showed that patients younger than 50 years and with stage I-II had better clinical prognoses. LDH-A-positive LMS patients had a poorer prognosis than LDH-A-negative patients (P = .03). The median survival time of LDH-A-positive patients was 35 months. CONCLUSIONS: We demonstrated that LDH-D was expressed in patients with uterine sarcoma. Furthermore, the overexpressions of LDH-A and LDH-D in uterine sarcoma patients may contribute to further understanding of the mechanism of LDH in tumor metabolism in uterine sarcoma. Positive expression of LDH-A in patients with LMS may act as a potential prognostic biomarker in these patients.

miRNA-34a decreases ovarian cancer cell proliferation and chemoresistance by targeting HDAC1.

This study aimed to explore the roles of miRNA-34a (miR-34a) in ovarian cancer (OC) cells and uncover possible mechanisms. The proliferation of OC cells was measured with an MTT assay and soft agar colony formation assay. TargetScan analysis, real-time PCR, and a luciferase reporter assay were used to demonstrate the downstream target of miR-34a in OC cells. HDAC1 expression levels were detected by immunoblot analysis. miR-34a inhibited the proliferation of SKOV3 and OVCA433 cells and enhanced cisplatin sensitivity in cisplatin-resistant SKOV3cp cells. The results of TargetScan analysis, real-time PCR, and luciferase reporter assay confirmed that miR-34a downregulated HDAC1 expression by directly targeting the 3'-UTR of HDAC1 mRNA. The overexpression of HDAC1 decreased cisplatin sensitivity and promoted proliferation in OC cells. MTT assay and soft agar colony formation assay showed that HDAC1 overexpression blocked the suppressive effects of miR-34a on SKOV3 cell proliferation. In addition, treatment with the miR-34a mimic partially recovered the cisplatin sensitivity of SKOV3cp cells, whereas HDAC1 overexpression blocked the above phenomena caused by treatment with the miR-34a mimic. miR-34a exhibited suppressive effects on OC cells via directly binding and downregulating HDAC1 expression, which subsequently decreased the resistance to cisplatin and suppressed proliferation in OC cells.

Emodin inhibits TGF-ß2 by activating the FOXD3/miR­199a axis in ovarian cancer cells in vitro.

Ovarian cancer is a highly metastatic malignancy and a leading cause of cancer-related death in postmenopausal women. Emodin is a natural anthraquinone isolated from several traditional Chinese medicines including Rhubarb and Polygonum cuspidatum. Recently, emodin was demonstrated to reduce the growth of human ovarian carcinoma cells. However, the mechanism remains unclear. In the present study, we identified that transforming growth factor (TGF)-ß2 was significantly affected by emodin treatment in A2780 cells using microarray analysis. MicroRNA (miR)-199a was predicted as a potential miRNA targeting TGF-ß2 by in silico prediction using TargetScan. The mRNA and protein levels of TGF-ß2 were both significantly reduced by miR-199a. Spearman's correlation analysis revealed a significant correlation between the expression level of miR-199a and TGF-ß2 in human ovarian cancer specimens. Silencing of miR-199a with miR-199a inhibitor significantly restored the reduction in TGF-ß2 expression induced by emodin. Additionally, cell viability and colony formation of A2780 cells were markedly inhibited by emodin treatment, which was mediated by miR-199a. We analyzed the primary mature miR-199a-1 and miR-199a-2 transcripts in A2780 cells treated with emodin or dimethyl sulfoxide (DMSO) and found that only pri-miR-199a-1 was regulated by emodin. A conserved binding site of Forkhead box D3 (FOXD3) was identified within pri-miR­199a-1. We further revealed that miR-199a expression was significantly regulated by FOXD3. Taken together, the present study demonstrated that emodin may directly promote FOXD3 expression and sequentially activates miR-199a, which in turn suppresses the expression of TGF-ß2 to reduce cell viability and colony formation of A2780 cells.