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In recent years, pyclen-based complexes have attracted a great deal of interest as magnetic resonance imaging (MRI) contrast agents (CAs) and luminescent materials, as well as radiopharmaceuticals. Remarkably, gadopiclenol, a Gd(III) bishydrated complex featuring a pyclen-based heptadentate ligand, received approval as a novel contrast agent for clinical MRI application in 2022. To maximize stability and efficiency, two novel chiral pyclen-based chelators and their complexes were developed in this study. Gd-X-PCTA-2 showed significant enhancements in both thermodynamic and kinetic stabilities compared to those of the achiral parent derivative Gd-PCTA. 1H NMRD profiles reveal that both chiral gadolinium complexes (Gd-X-PCTA-1 and Gd-X-PCTA-2) have a higher relaxivity than Gd-PCTA, while variable-temperature 17O NMR studies show that the two inner-sphere water molecules have distinct residence times τMa and τMb. Furthermore, in vivo imaging demonstrates that Gd-X-PCTA-2 enhances the signal in the heart and kidneys of the mice, and the chiral Gd complexes exhibit the ability to distinguish between tumors and normal tissues in a 4T1 mouse model more efficiently than that of the clinical agent gadobutrol. Biodistribution studies show that Gd-PCTA and Gd-X-PCTA-2 are primarily cleared by a renal pathway, with 24 h residues of Gd-X-PCTA-2 in the liver and kidney being lower than those of Gd-PCTA.
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Compuestos de Azabiciclo , Quelantes , Medios de Contraste , Gadolinio , Imagen por Resonancia Magnética , Medios de Contraste/química , Animales , Ratones , Quelantes/química , Quelantes/síntesis química , Gadolinio/química , Complejos de Coordinación/química , Complejos de Coordinación/síntesis química , Estructura Molecular , Estereoisomerismo , Humanos , FemeninoRESUMEN
Four new sesquiterpenoids, named artemivestinolide D-G (1-4) and three known sesquiterpenoids (5-7), were isolated from Artemisia vestita. The structures of these new compounds were determined based on extensive spectroscopic data analyses. Furthermore, the electronic circular dichroism data determined the absolute configurations of the new compounds. The antifeedant and antifungal activities of the isolates were evaluated against third-instar larvae of Plutella xylostella and three plant pathogenic fungi. Compounds 1-7 showed moderate antifeedant activities and compounds 1-4 and 6-7 exhibited antifungal activities.
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Antifúngicos/farmacología , Hongos/efectos de los fármacos , Extractos Vegetales/farmacología , Sesquiterpenos/química , Animales , Antibacterianos/química , Antibacterianos/farmacología , Antifúngicos/química , Artemisia/química , Hongos/patogenicidad , Larva/efectos de los fármacos , Lepidópteros/microbiología , Extractos Vegetales/química , Sesquiterpenos/aislamiento & purificación , Sesquiterpenos/farmacologíaRESUMEN
In this article, we report the case of a woman in whom was found an abdominal mass during pregnancy and who underwent nephrectomy and extraction of the emboli after delivery. The kidney had a volume of 15 × 10 × 8 cm and pathological diagnosis was primary Ewing's sarcoma. The patient was treated with conventional chemotherapy for 1 year after surgery, at which time multiple metastases were found. From this case, we surmise that hormonal changes that occur during pregnancy may accelerate the growth of Ewing's sarcoma of the kidney, suggesting that renal tumors in pregnant women demand serious attention and that anti-cancer treatment should begin as soon as possible.
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Neoplasias Renales , Neoplasias Primarias Múltiples , Células Neoplásicas Circulantes , Tumores Neuroectodérmicos Primitivos , Complicaciones Neoplásicas del Embarazo , Sarcoma de Ewing , Vena Cava Inferior , Resultado Fatal , Femenino , Humanos , Neoplasias Renales/diagnóstico , Neoplasias Renales/patología , Neoplasias Renales/cirugía , Neoplasias Primarias Múltiples/diagnóstico , Neoplasias Primarias Múltiples/cirugía , Tumores Neuroectodérmicos Primitivos/diagnóstico , Tumores Neuroectodérmicos Primitivos/secundario , Tumores Neuroectodérmicos Primitivos/cirugía , Embarazo , Complicaciones Neoplásicas del Embarazo/diagnóstico , Complicaciones Neoplásicas del Embarazo/cirugía , Sarcoma de Ewing/diagnóstico , Sarcoma de Ewing/secundario , Sarcoma de Ewing/cirugía , Adulto JovenRESUMEN
Recent studies have highlighted the lipid-lowering ability of hawthorn ethanol extract (HEE) and the role played by gut flora in the efficacy of HEE. Our study sought to explore the effects of HEE on non-alcoholic fatty liver disease (NAFLD) in normal flora and pseudo germ-free mice. The results showed that HEE effectively diminished hepatic lipid accumulation, ameliorated liver function, reduced inflammatory cytokine levels and blood lipid profiles, and regulated blood glucose levels. HEE facilitated triglyceride breakdown, suppressed fatty acid synthesis, and enhanced intestinal health by modulating the diversity of the gut microbiota and the production of short-chain fatty acids in the gut. In addition, HEE apparently helps to increase the presence of beneficial genera of bacteria, thereby influencing the composition of the gut microbiota, and the absence of gut flora affects the efficacy of HEE. These findings reveal the potential of hawthorn for the prevention and treatment of NAFLD and provide new perspectives on the study of functional plants to improve liver health.
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Crataegus , Microbioma Gastrointestinal , Metabolismo de los Lípidos , Hígado , Enfermedad del Hígado Graso no Alcohólico , Extractos Vegetales , Microbioma Gastrointestinal/efectos de los fármacos , Enfermedad del Hígado Graso no Alcohólico/tratamiento farmacológico , Enfermedad del Hígado Graso no Alcohólico/microbiología , Extractos Vegetales/farmacología , Animales , Crataegus/química , Hígado/metabolismo , Hígado/efectos de los fármacos , Ratones , Masculino , Metabolismo de los Lípidos/efectos de los fármacos , Ratones Endogámicos C57BL , Etanol , Modelos Animales de Enfermedad , Triglicéridos/sangre , Triglicéridos/metabolismo , Citocinas/metabolismo , Ácidos Grasos Volátiles/metabolismoRESUMEN
BACKGROUND: As a novel necrosis manner, ferroptosis has been increasingly reported to play a role in tumor progression and treatment, however, the specific mechanisms underlying its development in prostate cancer remain unclear. Growing evidence showed that peroxisome plays a key role in ferroptosis. Herein, we identified a novel mechanism for the involvement of ferroptosis in prostate cancer progression, which may provide a new strategy for clinical treatment of prostate cancer. METHODS: Label-Free Mass spectrometry was used to screen and identify candidate proteins after ferroptosis inducer-ML210 treatment. Immunohistochemistry was undertaken to explore the protein expression of AGPS in prostate cancer tissues compared with normal tissues. Co-immunoprecipitation and GST pull-down were used to identify the directly binding of AGPS to MDM2 in vivo and in vitro. CCK8 assay and colony formation assay were used to illustrate the key role of AGPS in the progression of prostate cancer in vitro. The xenograft model was established to verify the key role of AGPS in the progression of prostate cancer in vivo. RESULTS: AGPS protein expression was downregulated in prostate cancer tissues compared with normal tissues from the first affiliated hospital of Zhengzhou University dataset. Lower expression was correlated with poorer overall survival of patients compared to those with high expression of AGPS. In addition, AGPS can promote ferroptosis by modulating the function of peroxisome-resulting in the lower survival of prostate cancer cells. Furthermore, it was shown that AGPS can be ubiquitinated and degraded by the E3 ligase-MDM2 through the proteasomal pathway. Meanwhile, kinase TrkA can promote the combination of AGPS and MDM2 by phosphorylating AGPS at Y451 site. It was verified that kinase TrkA inhibitor-Larotrectinib can increase the susceptibility of prostate cancer cells to ferroptosis, which leads to the inhibition of prostate cancer proliferation to a great extent in vitro and in vivo. CONCLUSION: Based on these findings, we proposed the combination of ferroptosis inducer and TrkA inhibitor to synergistically exert anti-tumor effects, which may provide a new strategy for the clinical treatment of prostate cancer.
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Neoplasias de la Próstata , Humanos , Masculino , Próstata , Neoplasias de la Próstata/genética , Proteínas Proto-Oncogénicas c-mdm2/genética , Proteínas Tirosina Quinasas Receptoras , Ubiquitina , UbiquitinaciónRESUMEN
Cuproptosis is a new Cu-dependent programmed cell death manner that has shown regulatory functions in many tumor types, however, its mechanism in bladder cancer remains unclear. Here, we reveal that Phosphodiesterase 3B (PDE3B), a cuproptosis-associated gene, could reduce the invasion and migration of bladder cancer. PDE3B is downregulated in bladder cancer tissues, which is correlated with better prognosis. Conversely, overexpression of PDE3B in bladder cancer cell could significantly resist invasion and migration, which is consistent with the TCGA database results. Future study demonstrate the anti-cancer effect of PDE3B is mediated by Keratin 6B (KRT6B) which leads to the keratinization. Therefore, PDE3B can reduce KRT6B expression and inhibit the invasion and migration of bladder cancer. Meanwhile, increased expression of PDE3B was able to enhance the sensitivity of Cuproptosis drug thiram. This study show that PDE3B/KRT6B is a potential cancer therapeutic target and PDE3B activation is able to increase the sensitivity of bladder cancer cells to copper ionophores.
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Movimiento Celular , Cobre , Fosfodiesterasas de Nucleótidos Cíclicos Tipo 3 , Queratina-6 , Neoplasias de la Vejiga Urinaria , Humanos , Neoplasias de la Vejiga Urinaria/patología , Neoplasias de la Vejiga Urinaria/genética , Neoplasias de la Vejiga Urinaria/metabolismo , Neoplasias de la Vejiga Urinaria/tratamiento farmacológico , Línea Celular Tumoral , Cobre/metabolismo , Movimiento Celular/efectos de los fármacos , Fosfodiesterasas de Nucleótidos Cíclicos Tipo 3/metabolismo , Fosfodiesterasas de Nucleótidos Cíclicos Tipo 3/genética , Queratina-6/metabolismo , Queratina-6/genética , Invasividad Neoplásica , Regulación Neoplásica de la Expresión GénicaRESUMEN
Sharply increased reactive oxygen species (ROS) are thought to induce oxidative stress, damage cell structure and cause cell death; however, its role in prostate cancer remains unclear. Enzalutamide is a widely used anti-prostate cancer drug that antagonizes androgen binding with its receptor. Further exploration of the mechanism and potential application strategies of enzalutamide is crucial for the treatment of prostate cancer. Here, we confirmed PEX10 can be induced by ROS activators while reduce ROS level in prostate cancer cells, which weakened the anti-tumor effect of ROS activators. The androgen receptor (AR) can promote the expression of PEX10 by acting as an enhancer in cooperation with FOXA1. The anti-tumor drug enzalutamide inhibits PEX10 by inhibiting the function of AR, and synergize with ROS activators ML210 or RSL3 to produce a stronger anti-tumor effect, thereby sensitizing cells to ROS activators. This study reveals a previously unrecognized function of enzalutamide and AR by regulating PEX10 and suggests a new strategy of enzalutamide application in prostate cancer treatment.
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Benzamidas , Nitrilos , Feniltiohidantoína , Neoplasias de la Próstata , Especies Reactivas de Oxígeno , Humanos , Feniltiohidantoína/farmacología , Feniltiohidantoína/análogos & derivados , Masculino , Benzamidas/farmacología , Nitrilos/farmacología , Especies Reactivas de Oxígeno/metabolismo , Neoplasias de la Próstata/tratamiento farmacológico , Neoplasias de la Próstata/metabolismo , Neoplasias de la Próstata/patología , Línea Celular Tumoral , Receptores Androgénicos/metabolismo , Factor Nuclear 3-alfa del Hepatocito/metabolismo , Animales , Ratones , Proteínas de la Membrana/metabolismo , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Ratones DesnudosRESUMEN
The safety risks of gadolinium (Gd3+)-based contrast agents (GBCAs) arise from their inevitable leakage of Gd3+, and the pursuit of more stable GBCAs for magnetic resonance imaging (MRI) has drawn increasing attention. Yet, Gd-EOB-DTPA and Gd-BOPTA are the only two authorized GBCAs for liver diagnosis in spite of their weak stability. In this study, one of the pendent arms of the most inert commercial Gd-DOTA was decorated with phenyl moieties, in which obvious enhancements of both kinetic and thermodynamic stability were achieved. Gd-L4 with a para-substituted OBn group was observed with ready hepatocellular uptake, with significant contrast provided in diagnosing orthotopic hepatocellular carcinoma, and its hepatobiliary secretion accounted for more than 50% of the injection dose in mice. In this study, Gd-L4 was found with comparable performance in liver MRI diagnosis to that of commercial Gd-EOB-DTPA and was thus deemed as an ideal candidate for further clinical applications.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Animales , Ratones , Medios de Contraste , Imagen por Resonancia Magnética/métodosRESUMEN
The leakage of gadolinium ions (Gd3+) from commercial Gd3+-based contrast agents (GBCAs) in patients is currently the major safety concern in clinical magnetic resonance imaging (MRI) scans, and the lack of task-specific GBCAs limits its usage in the early detection of disease and imaging of specific biological regions. Herein, ultrastable GBCAs were constructed via decorating chiral Gd-DOTA with a phenylic analogue to one of the pendent arms, and the stability constant was determined as high as 27.08, accompanied by negligible decomplexation in 1 M of HCl over 2 years. A hepatic-specific chiral Gd-DOTA was screened out as a potential alternative to commercial Gd-EOB-DTPA, while combination with functional molecules favored chiral Gd-DOTA as tumor targeting probes. Therefore, the novel chiral Gd-DOTA is believed to be an ideal platform for designing the next generation of GBCAs for various clinical purposes due to its outstanding inert nature.
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Neoplasias Hepáticas , Compuestos Organometálicos , Humanos , Medios de Contraste , Imagen por Resonancia Magnética/métodos , Neoplasias Hepáticas/patologíaRESUMEN
Amine oxidase copper-containing 1 (AOC1) is considered an oncogene in many types of tumors. Nevertheless, there have been no investigations of AOC1 and its regulatory mechanism in prostate cancer. Here, we reveal a novel action of AOC1 and a tumor suppressor mechanism in prostate cancer. AOC1 is downregulated in prostate cancer. Abatement of AOC1 in prostate cancer tissue is positively correlated with the tumor size, lymph node metastasis, and Gleason score for prostate cancer. Conversely, high expression of AOC1 is significantly associated with reduced proliferation and migration in prostate cancer both in vitro and in vivo. We show that the anticancer effect of AOC1 is mediated by its action on spermidine which leads to the activation of reactive oxygen species and ferroptosis. AOC1 expression in prostate cancer is positively regulated by the transcription factor SOX15. Therefore, SOX15 can transcriptionally promote AOC1 expression and strengthen this effect. Targeting AOC1 and SOX15 may be promising for the treatment of prostate cancer.
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Amina Oxidasa (conteniendo Cobre) , Ferroptosis , Neoplasias de la Próstata , Proliferación Celular/genética , Ferroptosis/genética , Regulación Neoplásica de la Expresión Génica , Humanos , Masculino , Neoplasias de la Próstata/genética , Neoplasias de la Próstata/patología , Factores de Transcripción SOX/genética , Factores de Transcripción SOX/metabolismoRESUMEN
Sodium alginate (SA) is an environment-friendly and low-cost polysaccharide carbohydrate extracted from seaweed. As a carbon precursor, sodium alginate has the advantages of clear molecular structure, small molecular weight, and easy controls of the structure and composition of the product, but there have been few studies for the mechanism for SA carbonization. In this work, the carbon skeleton cross-linking mode, heteroatom doping and defect generation mechanism in the process of SA pyrolysis are clarified. Subsequently, based on the understanding of the carbonization mechanism of SA-derived carbon, we have prepared a stable SA-derived interconnected porous carbon by self-template method. The materials prepared by this method possess high oxygen content (17.6 at%) and high specific surface area (384.4 m2 g-1). Zn-ion hybrid capacitors (ZICs) device assembled with SA-derived porous carbon performs superior energy densities (based on cathode mass) of 78.35 and 35.56 Wh kg-1 at the power densities of 160 and 5120 W kg-1, respectively. This work deeply explained the carbonization mechanism of sodium alginate and evaluated the application prospects of SA-based carbon in ZICs comprehensively.
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Alginatos , Carbono , Carbono/química , Electrodos , Iones , PorosidadRESUMEN
Heteroatom-rich carbon materials deliver superior potassium storage capacity owing to the abundant active sites, but their stability and conductivity are damaged because of the numerous defects and distortion of π-conjugated system. In this work, we amended the adverse influences of heteroatoms on carbon materials through the B, N stabilization effect. Due to an amending effect of B atoms on the N-doped carbon matrix, the integrity of the carbon skeleton and stability of the system are significantly enhanced, and the undesirable defects are transformed into favorable active sites, resulting in the simultaneous improvement of K+ storage capacity, rate performance and cyclic stability. The stabilized materials have a highly reversible carbon structure and fast K+ transfer kinetics, leading to high reversible capacity (300 mA h g-1 at 0.1 A g-1), good rate performance (107.2 mA h g-1 at 10 A g-1) and superior cyclic stability (75.3 % capacity retention from cycle 11 to 2000 at 1 A g-1). Consequently, the constructed devices perform excellent energy densities of 158.8 and 40.7 Wh kg-1 under power densities of 100 and 11250 W kg-1, respectively. This work proposes an effective strategy for significantly improving heteroatom-rich carbon materials, which broadens its application fields in high-performance potassium ion storage.
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Carbono , Potasio , Conductividad Eléctrica , Iones , Microesferas , Potasio/químicaRESUMEN
S doping is an effective strategy to improve the potassium-ion storage performance of carbon-based materials. However, due to the large atomic radius of S and poor thermal stability, it is challenging to synthesize carbon materials with high sulfur content by solid-phase transformation. In this work, we designed a multi-cavity structure that can confine the molten S during heat treatment and make it fully react, then achieving high S doping (7.6 at. %). As we known, S doping can also effectively increase the active sites of carbon materials to obtain higher capacity. In addition, through different ex/in-situ characterizations and DFT calculations, we confirmed that the S atoms can effectively expand the interlayer spacing of carbon, which facilitates the intercalation/deintercalation reaction of K+, thereby significantly improving the rate performance. Therefore, benefiting from the effect of S-doping, the sample exhibits high reversible specific capacity (401.0 mAh g-1 at 0.1 A/g) and rate performance (167.2 mAh g-1 at 5 A/g). The as-assembled K+ hybrid capacitor delivers both high energy density and power density (138.5 W h kg-1 and 7692.5 W kg-1, respectively). This work provides a new approach to design S content carbon-based materials for high performance K+ storage.
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Prostate cancer is currently one of the most common fatal tumor types in men. Although multiple treatments can alleviate some cases, advanced prostate cancer, especially CRPC, still has a very poor prognosis. Therefore, early detection and diagnosis of prostate cancer have a very important role in the prognosis of patients. Glycoprotein M6B (GPM6B) is a transmembrane protein that belongs to the proteolipid protein family. GPM6B has been proved and can be used as a biomarker for gynecological malignancies and breast carcinoma. However, there are no studies that explored the functions of GPM6B in PCa. We explored differentially expressed genes in prostate cancer by analyzing TCGA data and found GPM6B downregulated in PCa tissues compared to that in normal prostate tissues. The GPM6B expression in PCa patient's tumor tissues was significantly related to clinical stage, T classification, lymph node metastasis, and distant metastasis, but not significantly related to age and Gleason score. Also, patients with highGPM6B expression had a better prognosis. The overexpression of GPM6B in prostate cancer cells could inhibit cell proliferation. Serotonin treatment could enhance the proliferation of PCa cell lines; moreover, fluoxetine could reverse this result. In conclusion, we identified GPM6B as a tumor suppressor in PCa. In mechanism, it can regulate the uptaking of serotonin and inhibit the growth of prostate cancer. These results suggested the potential function of GPM6B as a diagnostic marker of PCa and provided clues for the development of new treatment targets for PCa.
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Biomarcadores de Tumor/genética , Regulación hacia Abajo , Glicoproteínas de Membrana/genética , Proteínas del Tejido Nervioso/genética , Neoplasias de la Próstata/patología , Serotonina/metabolismo , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Fluoxetina/farmacología , Regulación Neoplásica de la Expresión Génica , Humanos , Metástasis Linfática , Masculino , Glicoproteínas de Membrana/metabolismo , Clasificación del Tumor , Proteínas del Tejido Nervioso/metabolismo , Pronóstico , Neoplasias de la Próstata/genética , Neoplasias de la Próstata/metabolismo , Serotonina/farmacologíaRESUMEN
Antisense long non-coding RNAs (AS lncRNAs) have been increasingly recognized as important regulators of gene expression and have been found to play crucial roles in the development and progression of tumors. The present study explored the roles of AS lncRNA ZNF710AS1202 in clear cell renal cell carcinoma (ccRCC). The expression levels of ZNF710AS1202 were detected in 46 human ccRCC tissues and 34 healthy adjacent renal tissues. The associations between the levels of ZNF710AS1202 expression and the clinicopathological features of the patients were evaluated by the χ2 test. Gain and lossoffunction experiments were performed to analyze the role of ZNF710AS1202 in ccRCC cell proliferation and survival in vitro. Reverse transcriptionquantitative PCR and/or western blotting were employed to detect ZNF710AS1202, zinc finger protein 710 (ZNF710) and cyclin B1 expression. The Cell Counting Kit8 and colony formation assays, as well as flow cytometry, were used to detect cell proliferation or apoptosis. The subcellular localization of ZNF710AS1202 was analyzed by RNA fluorescence in situ hybridization. The results revealed that ZNF710AS1202 was downregulated in human ccRCC tissues and was associated with the pathological grade, tumor size, local invasion and TNM stage, but not with lymph node metastasis or distant metastasis. However, ZNF710AS1202 overexpression promoted the proliferation of RCC cells and inhibited apoptosis. Opposite results were observed when ZNF710AS1202 was knocked down by small interfering RNA. Furthermore, ZNF710AS1202, which was mainly expressed in the cytoplasm of RCC cells, regulated ZNF710 mRNA and protein expression in opposing manners. In conclusion, the present study revealed that ZNF710AS1202 and ZNF710 may serve as promising therapeutic targets for ccRCC.
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Apoptosis/efectos de los fármacos , Carcinoma de Células Renales/genética , Carcinoma de Células Renales/metabolismo , Proliferación Celular/efectos de los fármacos , Neoplasias Renales/genética , Neoplasias Renales/metabolismo , ARN Largo no Codificante/farmacología , Adulto , Anciano , Línea Celular Tumoral , Progresión de la Enfermedad , Regulación hacia Abajo , Femenino , Regulación Neoplásica de la Expresión Génica , Técnicas de Silenciamiento del Gen , Humanos , Hibridación Fluorescente in Situ , Masculino , Persona de Mediana Edad , ARN Largo no Codificante/genética , ARN Mensajero , ARN Interferente Pequeño/metabolismo , TranscriptomaRESUMEN
BACKGROUND: Circular RNAs (circRNAs) are novel clusters of endogenous noncoding RNAs (ncRNAs) that are involved in the regulation of multiple biological processes in diverse types of cancers. However, the roles and precise mechanisms of circRNAs in renal cell carcinoma (RCC) occurrence and progression have not been clearly elucidated. METHODS: We identified the aberrantly expressed circRNAs in RCC by high-throughput RNA-seq assay and used qRT-PCR to test the expression level of circRNAs in RCC tissues. Loss-of-function experiments were executed to detect the biological roles of circPDK1 in the RCC cells both in vivo and in vitro. RNA Fish, luciferase reporter assays and Western blotting were used to explore the molecular mechanism of circPDK1 function. All data were expressed as the means ± standard error of the mean (SEM). Student's t-test, one-way ANOVA, Cox regression, an LSD-t-test, Pearson's chi-squared test, a Log-rank test, and linear regression analyses were used to evaluate the group differences. P < 0.05 was considered significant. RESULTS: CircPDK1 was overexpressed in RCC tissues and positively associated with patient tumor metastasis and renal cell invasion. The in vivo functional assays also revealed that circPDK1 drove RCC xenograft metastasis. CircPDK1 was mainly located in the cytoplasm, serving as a sponge of miR-377-3P to regulate RCC invasion and metastasis through NOTCH1 (Notch Homolog 1). Ectopic express of NOTCH1 in RCC cell lines will block the metastasis inhibition effect after circPDK1 knockdown. CONCLUSION: CircPDK1 is aberrantly expressed in RCC and promotes the metastasis of RCC cells mainly through sponging miR-377-3P and reducing its negative regulation of NOTCH1. Thus, circPDK1 may act as a therapeutic target and biomarker for RCC.
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AIM: To investigate the association between ocular demodex folliculorum infestation and ocular surface manifestations in meibomian gland dysfunction (MGD). METHODS: Eight-six patients with MGD were enrolled. All enrolled subjects were tested in the following sequence: ocular surface disease index (OSDI), slit-lamp biomicroscope examination, corneal surface regularity index (SRI) and surface asymmetry index (SAI), tear fluid collection, fluorescein tear film break-up time (F-BUT), corneal fluorescein staining (CFS), Schirmer I test (SIT) and demodex folliculorum counting. Tear matrix metalloproteinase (MMP)-9 activity was assessed using MMP-9 activity assay kit. RESULTS: Among 86 MGD patients, 40 were positive for demodex. The ocular demodex-positive group showed significantly increased scores of OSDI (25.96±13.74 vs 18.07±11.55, P=0.01), lid margin abnormality (2.38±0.87 vs 1.98±0.91, P=0.04) and CFS (1.28±2.00 vs 0.94±1.36, P=0.01) compared to the ocular demodex-free group. The tear MMP-9 activity was higher in the ocular demodex-positive group (102.9±32.4 ng/mL) than the ocular demodex-free group (46.2±19.2 ng/mL, P=0.03). There was no significant difference in meibum quality and expressibility, SRI, SAI, F-BUT and SIT between the two groups (P>0.05 for each). No significant correlation was noted between the number of demodex and ocular surface parameters in demodex-positive MGD group (P>0.05 for each). CONCLUSION: Ocular demodex folliculorum infestation may be associated with ocular discomfort and ocular surface damage in MGD.
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OBJECTIVES: Many adjuvant therapies have been widely used in an attempt to reduce the local recurrence or distant metastasis of locally advanced renal cell carcinoma (RCC) after surgical resection. However, the benefits of adjuvant therapy remain controversial. Thus, we performed this study to analyze the role and safety of adjuvant therapy in renal cancer setting. METHODS AND METHODS: We comprehensively searched PubMed, EMBASE, Web of Science, and the Cochrane Library for published randomized controlled trials comparing adjuvant therapy (chemotherapy, vaccine therapy, immune therapy, and targeted therapy) versus no active treatment after surgery among patients with locoregional RCC. Outcomes of interest were disease-free survival, overall survival, and severe toxicities. Different kinds of adjuvant therapy were evaluated separately. RESULTS: Twelve studies (5,936 patients) were included in the present analysis. Adjuvant therapy did not contribute to overall survival (HR = 1.04; 95% CI: 0.95-1.15; P = 0.395; I2 = 0%) or disease-free survival (HR = 1.00; 95% CI: 0.92-1.08; P = 0.971; I2 = 35%) when compared to placebo or observation. No survival benefit was observed according to subgroup analyses (targeted therapy, vaccine therapy, and immune therapy). Moreover, adjuvant therapy increased obviously the risk of toxicities. CONCLUSIONS: The addition of adjuvant therapy provided no survival benefit but increased the rates of adverse events for locally advanced RCC patients.
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Carcinoma de Células Renales/terapia , Neoplasias Renales/terapia , Carcinoma de Células Renales/patología , Carcinoma de Células Renales/cirugía , Quimioterapia Adyuvante/métodos , Terapia Combinada , Supervivencia sin Enfermedad , Humanos , Inmunoterapia/métodos , Neoplasias Renales/patología , Neoplasias Renales/cirugía , Terapia Molecular Dirigida/métodos , Ensayos Clínicos Controlados Aleatorios como Asunto , Vacunación/métodosRESUMEN
BACKGROUND: ATP-binding cassette transporter super-family including ABCC1 and MDR-1 were involved in multi-drug resistance (MDR) of renal cell carcinoma (RCC) patients. Several miRNAs were confirmed to promote the MDR and the survival of tumor cells. METHODS: The RCC cell lines Caki-2 with vinblastine-resistant (Caki-2/VBL) or doxorubicin-resistant (Caki-2/DOX) were constructed, respectively. The expressions of miR-210-3p, ABCC1 and MDR-1 protein were determined by qRT-PCR and Western blot assays. The viability of RCC cells was assessed by MTT assay. The regulatory relationship between miR-210-3p and ABCC1 was analyzed by Dual Luciferase assay. The effect of miR-210-3p in vivo was investigated with a tumor xenograft model in mice. RESULTS: MiR-210-3p expression was observed to significantly decrease in Caki-2/VBL and Caki-2/DOX cells. Meanwhile, ABCC1 and MDR-1 were significantly increased in Caki-2/VBL and Caki-2/DOX cells. ABCC1 was a novel target of miR-210-3p and negatively regulated by miR-210-3p. And miR-210-3p improved drug-sensitivity of RCC cells. Down-regulation of ABCC1 could reverse the effect of miR-210-3p knockdown on the drug-resistance and the level of MDR-1 in drug-sensitive RCC cells. CONCLUSION: We confirmed that down-regulation of miR-210-3p increased ABCC1 expression, thereby enhancing the MRP-1-mediated multidrug resistance of RCC cells.
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BACKGROUND: Bladder dysfunction is an important symptom of experimental autoimmune encephalomyelitis (EAE). Our previous study showed that EAE-induced upregulation of the E-prostanoid receptor 3 (EP3) and E-prostanoid receptor 4 (EP4) in the bladder was accompanied by bladder dysfunction. Although many other studies have evaluated the lower urinary tract symptoms in multiple sclerosis, the mechanism remains unclear. OBJECTIVES: To investigate the effects of interstitial cells of Cajal (ICC) on bladder dysfunction in a novel neurogenic bladder model induced by experimental autoimmune encephalomyelitis. MATERIALS AND METHODS: The EAE model was induced by a previously established method, and bladder functions in mice were evaluated. Bladders were harvested for the analysis of ICCs and the genes associated with bladder mechanosensation including pannexin 1 (Panx1) and Gja1 (encoding connexin43) by immunofluorescence and western blotting. The stem cell factor cytokine (SCF) was intraperitoneally injected at the beginning of EAE onset. RESULTS: EAE mice developed profound bladder dysfunction characterized by significant urine retention, increased micturition and decreased urine output per micturition. EAE induced a significant decrease in c-Kit expression and ICCs number. EAE also induced a significant increase in pannexin 1 and connexin43. SCF treatment could ameliorate all of these pathological changes. CONCLUSIONS: ICCs and stem cell factor play an important role in EAE-induced bladder dysfunction, which may be used as therapeutic options in treating patients with multiple sclerosis-related bladder dysfunction.