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1.
Commun Biol ; 7(1): 583, 2024 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-38755265

RESUMO

Tumor-associated macrophages of the M2 phenotype promote cancer initiation and progression. Importantly, M2 macrophage-derived exosomes play key roles in the malignancy of cancer cells. Here, we report that circTMCO3 is upregulated in ovarian cancer patients, and its high expression indicates poor survival. M2-derived exosomes promote proliferation, migration, and invasion in ovarian cancer, but these effects are abolished by knockdown of circTMCO3. Furthermore, circTMCO3 functions as a competing endogenous RNA for miR-515-5p to reduce its abundance, thus upregulating ITGA8 in ovarian cancer. miR-515-5p inhibits ovarian cancer malignancy via directly downregulating ITGA8. The decreased oncogenic activity of circTMCO3-silencing exosomes is reversed by miR-515-5p knockdown or ITGA8 overexpression. Exosomal circTMCO3 promotes ovarian cancer progression in nude mice. Thus, M2 macrophage-derived exosomes promote malignancy by delivering circTMCO3 and targeting the miR-515-5p/ITGA8 axis in ovarian cancer. Our findings not only provide mechanistic insights into ovarian cancer progression, but also suggest potential therapeutic targets.


Assuntos
Exossomos , Camundongos Nus , MicroRNAs , Neoplasias Ovarianas , Feminino , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/patologia , Neoplasias Ovarianas/metabolismo , Humanos , Exossomos/metabolismo , Exossomos/genética , MicroRNAs/genética , MicroRNAs/metabolismo , Animais , Camundongos , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica , Macrófagos/metabolismo , RNA Circular/genética , RNA Circular/metabolismo , Proliferação de Células , Cadeias alfa de Integrinas/genética , Cadeias alfa de Integrinas/metabolismo , Movimento Celular
2.
J Transl Med ; 22(1): 46, 2024 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-38212795

RESUMO

BACKGROUND: Ovarian cancer (OC) is a malignant neoplasm that displays increased vascularization. Angiopoietin-like 4 (ANGPTL4) is a secreted glycoprotein that functions as a regulator of cell metabolism and angiogenesis and plays a critical role in tumorigenesis. However, the precise role of ANGPTL4 in the OC microenvironment, particularly its involvement in angiogenesis, has not been fully elucidated. METHODS: The expression of ANGPTL4 was confirmed by bioinformatics and IHC in OC. The potential molecular mechanism of ANGPTL4 was measured by RNA-sequence. We used a series of molecular biological experiments to measure the ANGPTL4-JAK2-STAT3 and ANGPTL4-ESM1 axis in OC progression, including MTT, EdU, wound healing, transwell, xenograft model, oil red O staining, chick chorioallantoic membrane assay and zebrafish model. Moreover, the molecular mechanisms were confirmed by Western blot, Co-IP and molecular docking. RESULTS: Our study demonstrates a significant upregulation of ANGPTL4 in OC specimens and its strong association with unfavorable prognosis. RNA-seq analysis affirms that ANGPTL4 facilitates OC development by driving JAK2-STAT3 signaling pathway activation. The interaction between ANGPTL4 and ESM1 promotes ANGPTL4 binding to lipoprotein lipase (LPL), thereby resulting in reprogrammed lipid metabolism and the promotion of OC cell proliferation, migration, and invasion. In the OC microenvironment, ESM1 may interfere with the binding of ANGPTL4 to integrin and vascular-endothelial cadherin (VE-Cad), which leads to stabilization of vascular integrity and ultimately promotes angiogenesis. CONCLUSION: Our findings underscore that ANGPTL4 promotes OC development via JAK signaling and induces angiogenesis in the tumor microenvironment through its interaction with ESM1.


Assuntos
Cistadenocarcinoma Seroso , Janus Quinase 2 , Neoplasias Ovarianas , Fator de Transcrição STAT3 , Animais , Feminino , Humanos , Microambiente Tumoral , Simulação de Acoplamento Molecular , Angiogênese , Peixe-Zebra/metabolismo , Carcinogênese , Proliferação de Células , Carcinoma Epitelial do Ovário , Neoplasias Ovarianas/genética , Linhagem Celular Tumoral , Proteína 4 Semelhante a Angiopoietina/genética , Proteínas de Neoplasias , Proteoglicanas
3.
Sci Rep ; 13(1): 19474, 2023 11 09.
Artigo em Inglês | MEDLINE | ID: mdl-37945610

RESUMO

Gynecological cancers are a leading cause of mortality for women, including ovarian cancer (OC), cervical squamous cell carcinoma (CESC), and uterine corpus endometrial carcinoma (UCEC). Nevertheless, these gynecological cancer types have not elucidated the role of cuproptosis and the correlated tumor microenvironment (TME) infiltration features. CRGs had important potential molecular functions and prognostic significance in gynecological cancers, especially in UCEC. Hub CRG, FDX1, was correlated with the CD8+ T cell immune infiltration in UCEC and CESC. FDX1 OE could significantly repress the proliferation ability in UCEC cells by MTT, EdU, and clone formation. High levels of FDX1 could repress ATP and lactic acid but enhance ROS and glucose levels by metabolism assay. The xenograft tumor model indicated that FDX1 OE significantly inhibited the growth of UCEC and attenuated the PCNA, HK2, PKM2, and Ki-67 expression. These CRGs are significant roles that could be potential markers and treatment targets to optimize the TME immune cell infiltration features for gynecological cancer types. FDX1 is a hub CRGs in UCEC to promote immune infiltration and attenuate proliferation and metabolism.


Assuntos
Apoptose , Carcinoma Endometrioide , Carcinoma de Células Escamosas , Neoplasias Ovarianas , Neoplasias do Colo do Útero , Animais , Feminino , Humanos , Bioensaio , Modelos Animais de Doenças , Neoplasias Ovarianas/genética , Microambiente Tumoral/genética , Neoplasias do Colo do Útero/genética , Cobre
4.
BMC Pediatr ; 23(1): 239, 2023 05 13.
Artigo em Inglês | MEDLINE | ID: mdl-37173671

RESUMO

BACKGROUND: D40LG-associated X-linked hyper-IgM syndrome with pulmonary alveolar proteinosis has rarely been reported, and its genotype-phenotypic correlation remains elusive. CASE PRESENTATION: We describe a five-month-old boy with CD40LG mutation (c.516T > A, p.Tyr172Ter) X-linked hyper-IgM syndrome with pulmonary alveolar proteinosis as the first manifestation. The patient completely recovered after immunotherapy and allogeneic hematopoietic stem cell transplantation. In addition, four previously reported patients with CD40LG mutation with pulmonary alveolar proteinosis were also analyzed. All of these patients presented with early onset of pulmonary infections and a good response to immunotherapy. The structural model of CD40LG indicated that all mutations caused the X-linked hyper-IgM syndrome with pulmonary alveolar proteinosis to be located within the tumor necrosis factor homology domain. CONCLUSIONS: A case was presented, and the characteristics of four cases of CD40LG-associated X-linked hyper-IgM syndrome with pulmonary alveolar proteinosis were summarized. The variant locations may explain the phenotypic heterogeneity of patients with the CD40LG mutation.


Assuntos
Síndrome de Imunodeficiência com Hiper-IgM Tipo 1 , Síndrome de Imunodeficiência com Hiper-IgM , Proteinose Alveolar Pulmonar , Masculino , Humanos , Lactente , Proteinose Alveolar Pulmonar/diagnóstico , Proteinose Alveolar Pulmonar/genética , Proteinose Alveolar Pulmonar/terapia , Mutação , Síndrome de Imunodeficiência com Hiper-IgM Tipo 1/complicações , Síndrome de Imunodeficiência com Hiper-IgM Tipo 1/diagnóstico , Síndrome de Imunodeficiência com Hiper-IgM Tipo 1/genética , Ligante de CD40/genética
5.
Ecotoxicol Environ Saf ; 259: 115064, 2023 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-37229873

RESUMO

Pomacea canaliculata is a malignant invasive aquatic snail found worldwide, and niclosamide (NS) is one of the primary agents used for its control. NS applied to water will exist in non-lethal concentrations for some time due to degradation or water exchange, thus resulting in sublethal effects on environmental organisms. To identify sublethal effects of NS on Pomacea canaliculata, we studied the aspects of histopathology, oxygen-nitrogen ratio (RO∶N), enzyme activity determination, and gene expression. After LC30 NS treatment (0.310 g/L), many muscle fibers of the feet degenerated and some acinar vesicles of the hepatopancreas collapsed and dissolved. The oxygen-nitrogen ratio (RO∶N) decreased significantly from 15.0494 to 11.5183, indicating that NS had changed the metabolic mode of Pomacea canaliculata and shifted it primarily to protein catabolism. Transcriptome analysis identified the sublethal effects of LC30 NS on the snails at the transcriptional level. 386, 322, and 583 differentially expressed genes (DEGs) were identified in the hepatopancreas, gills, and feet, respectively. GO (Gene Ontology) functional analysis and KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway annotations showed that DEGs in the hepatopancreas were mainly enriched for sugar metabolism, protein biosynthesis, immune response, and amino acid metabolism functional categories; DEGs in the gills were mainly enriched for ion transport and amino acid metabolism; DEGs in the feet were mainly enriched for transmembrane transport and inositol biosynthesis. In the future, we will perform functional validation of key genes to further explain the molecular mechanism of sublethal effects.


Assuntos
Alimentos , Niclosamida , Animais , Niclosamida/toxicidade , Metabolismo dos Carboidratos , Água , Aminoácidos
6.
Adv Mater ; 35(12): e2210179, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36630669

RESUMO

Phototheranostics have emerged and flourished as a promising pattern for cancer theranostics owing to their precise photoinduced diagnosis and therapeutic to meet the demands of precision medicine. The diagnosis information and therapeutic effect are directly determined by the fluorescence imaging ability and photothermal conversion efficiency (PCE) of phototheranostic agents. Hence, how to balance the competitive radiative and nonradiative processes of phototheranostic agents is the key factor to evaluate the phototheranostic effect. Herein, molecules named ICRs with high photostaibility  are rationally designed, exhibiting fluorescence emission in the second near-infrared window (NIR-II, 1000-1700 nm) and high PCE, which are related to the strong donor-acceptor (D-A) interaction and high reorganization energy Noteworthily, ICR-Qu with stronger D-A interaction and a large-sized conjugated unit encapsulated in nanoparticles exhibits high PCE (81.1%). In addition, ICR-QuNPs are used for fluorescence imaging (FLI), photoacoustic imaging (PAI), and photothermal imaging (PTI) to guide deep-tissue photonic hyperthermia, achieving precise removal and inhibition of breast cancer. Furthermore, combined with α-PD-1, ICR-QuNPs show huge potential to be a facile and efficient tool for photo-immunotherapy. More importantly, this study not only reports an "all-in-one" polymethine-based phototheranostic agent, but also sheds light on the exploration of versatile organic molecules for future practical applications.


Assuntos
Neoplasias da Mama , Nanopartículas , Neoplasias , Técnicas Fotoacústicas , Humanos , Feminino , Fototerapia/métodos , Nanomedicina Teranóstica/métodos , Neoplasias/diagnóstico por imagem , Neoplasias/terapia , Corantes , Nanopartículas/uso terapêutico , Imunoterapia , Técnicas Fotoacústicas/métodos
7.
Immunobiology ; 227(6): 152290, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-36279621

RESUMO

PURPOSE: To determine the association of a combined ratio change of inflammatory biomarkers at 72 h after admission on sepsis severity and prognosis from pulmonary infections. METHODS: Data on adult patients diagnosed with sepsis, or septic shock were retrospectively analyzed. Patients were divided into two groups, according to their outcome of hospitalization. Blood specimens were obtained on admission (T0) and 72 h (T72) after therapy. Acute Physiology And Chronic Health Evaluation Score (APACHEII) and Sequential Organ Failure Assessment Score (SOFA) were statistically analyzed on admission. Survivors discharged from hospital were classified into different subgroups according to the change in biomarkers at T72, and compared for different clinical prognosis. RESULTS: Our study showed that IL-6, IL-8, IL-10 and TNF-a could predict the severity of sepsis at T0, since they showed a positive correlation with APACHEII or SOFA score. Another important finding was that survivors discharged from hospital whose ratio change with IL-10, i.e: IL-10/IL-6, IL-10/IL-8, IL-10/TNF-a ≤ 0 exhibited significantly greater 9-month overall survival. We also observed that patients with increased IL-6 after 72 h showed similar improved survival. CONCLUSION: Our findings suggested that a combined ratio change of inflammatory biomarkers was an effective predictor for sepsis severity and prognosis.


Assuntos
Pneumonia , Sepse , Adulto , Humanos , Interleucina-10 , Estudos Retrospectivos , Interleucina-6 , Interleucina-8 , Sepse/diagnóstico , Prognóstico , Biomarcadores , Curva ROC , Unidades de Terapia Intensiva
8.
Front Immunol ; 13: 907183, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35711411

RESUMO

The JAK/STAT pathway plays an important role in the development and immune responses of animals. In vertebrates, families of cytokines or growth factors act as activators of the JAK/STAT pathway; however, the activators for the JAK/STAT signaling pathway in arthropods are largely unknown. Herein we report a new ligand, peroxiredoxin 4 (Prx4), for the Domeless in the JAK/STAT pathway of shrimp Marsupenaeus japonicus. Prx4 was induced to secrete into the extracellular surroundings upon Vibrio challenge, which then facilitated the anti-Vibrio activity of shrimp by activating the phosphorylation and nuclear translocation of STAT and the expression of STAT-responsive antimicrobial peptides. Blocking the expression of Prx4 in vivo abrogated the activation of the JAK/STAT pathway by Vibrio infection, while injection of Prx4 protein activated the pathway. The interaction between Prx4 and Domeless was proved by immuno-precipitation and protein pull-down assays. Moreover, two cysteine residues in Prx4 that are critical for the interaction and Prx4's anti-Vibrio role were identified, and the binding site in Domeless for Prx4 was proved to be the cytokine-binding homology module fragment. Taken together, our study revealed a new function for Prx4 enzyme and established a new enzyme-type ligand for the activation of the JAK/STAT pathway in an aquatic arthropod.


Assuntos
Penaeidae , Vibrio , Animais , Antibacterianos , Imunidade , Janus Quinases/metabolismo , Ligantes , Peroxirredoxinas/metabolismo , Fatores de Transcrição STAT/metabolismo , Transdução de Sinais , Vibrio/fisiologia
9.
Photodiagnosis Photodyn Ther ; 38: 102784, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35219895

RESUMO

Inflammatory myofibroblastic tumor (IMT) is a rare intermediate tumor that exhibits both benign and malignant behaviors. Whether IMT is an inflammatory or a neoplastic disease remains controversial, and there is currently no standard treatment for this disease. The treatment strategies include surgical tumor removal and drug therapy; however, several patients experience tumor recurrence post-treatment. Herein, we report the endoscopic manifestations and treatment process in a case of IMT. We performed photodynamic therapy (PDT) after endoscopic tumor resection, and no recurrence was found in the patient's re-examination a year later. This indicates that PDT can improve IMT prognosis and reduce its local recurrence, signifying the therapy's potential application value for IMT.


Assuntos
Granuloma de Células Plasmáticas , Fotoquimioterapia , Granuloma de Células Plasmáticas/diagnóstico , Granuloma de Células Plasmáticas/patologia , Granuloma de Células Plasmáticas/cirurgia , Humanos , Fotoquimioterapia/métodos , Prognóstico
10.
Zhongguo Dang Dai Er Ke Za Zhi ; 23(8): 848-853, 2021 Aug 15.
Artigo em Inglês, Chinês | MEDLINE | ID: mdl-34511176

RESUMO

OBJECTIVES: To study the effect of gap junction blockers, quinine (QUIN) and carbenoxolone (CBX), on hippocampal ripple energy expression in rats with status epilepticus (SE). METHODS: A total of 24 rats were randomly divided into four groups: model, QUIN, valproic acid (VPA), and CBX (n=6 each). A rat model of SE induced by lithium-pilocarpine (PILO) was prepared. The QUIN, VPA, and CBX groups were given intraperitoneal injection of QUIN (50 mg/kg), VPA by gavage (200 mg/kg), and intraperitoneal injection of CBX (50 mg/kg) respectively, at 3 days before PILO injection. Electroencephalography was used to analyze the change in hippocampal ripple energy before and after modeling, as well as before and after chloral hydrate injection to control seizures. RESULTS: Ripple expression was observed in the hippocampal CA1, CA3, and dentate gyrus regions of normal rats. After 10 minutes of PILO injection, all groups had a gradual increase in mean ripple energy expression compared with 1 day before modeling, with the highest expression level before chloral hydrate injection in the model, VPA and CBX groups (P<0.05). The QUIN group had the highest expression level of mean ripple energy 60 minutes after PILO injection. The mean ripple energy returned to normal levels in the three intervention groups immediately after chloral hydrate injection, while in the model group, the mean ripple energy returned to normal levels 1 hour after chloral hydrate injection. The mean ripple energy remained normal till to day 3 after SE in the four groups. The changing trend of maximum ripple energy was similar to that of mean ripple energy. CONCLUSIONS: The change in ripple energy can be used as a quantitative indicator for early warning of seizures, while it cannot predict seizures in the interictal period. Gap junction blockers can reduce ripple energy during seizures.


Assuntos
Estado Epiléptico , Animais , Junções Comunicantes , Hipocampo , Pilocarpina , Ratos , Convulsões , Estado Epiléptico/tratamento farmacológico
11.
J Transl Med ; 19(1): 155, 2021 04 16.
Artigo em Inglês | MEDLINE | ID: mdl-33874953

RESUMO

BACKGROUND: Modification of the gut microbiota by antibiotics may influence the disease susceptibility and immunological responses. Infants in the neonatal intensive care unit (NICU) subjected to frequent antibiotics and oxygen therapies, which may give rise to local and systemic inflammatory reactions and progression of bronchopulmonary dysplasia (BPD). This study aimed to investigate the role of intestinal dysbacteriosis by antibiotic therapy before hyperoxia exposure in the progression of BPD. METHODS: Mice had been exposed to hyperoxia (85% O2) since postnatal day 3 until day 16 for the BPD model establishment, treated with antibiotics from postnatal day 2 until day 8. Treated mice and appropriate controls were harvested on postnatal day 2 or 10 for 16S rRNA gene sequencing, or postnatal day 17 for assessment of alveolar morphometry and macrophages differentiation. RESULTS: Antibiotic-induced intestinal dysbacteriosis before hyperoxia exposure gave rise to deterioration of BPD evidenced by reduced survival rates and alveolarization. Moreover, antibiotic-induced intestinal dysbacteriosis resulted in increased M1 macrophage maker (iNOS) and decreased M2 macrophage maker (Arg-1) levels in lung homogenates. CONCLUSION: Broad-spectrum antibiotic-induced intestinal dysbacteriosis may participate in BPD pathogenesis via alteration of the macrophage polarization status. Manipulating the gut microbiota may potentially intervene the therapy of BPD.


Assuntos
Displasia Broncopulmonar , Hiperóxia , Animais , Animais Recém-Nascidos , Antibacterianos/efeitos adversos , Modelos Animais de Doenças , Disbiose/induzido quimicamente , Disbiose/complicações , Humanos , Recém-Nascido , Pulmão , Camundongos , RNA Ribossômico 16S/genética
12.
Risk Manag Healthc Policy ; 13: 833-845, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32765138

RESUMO

BACKGROUND: Coronavirus disease 2019 (COVID-19) is a worldwide pandemic outbreak with a high mortality. Prognostic factors of critically ill patients with COVID-19 have not been fully elucidated yet. METHODS: In the present study, 59 patients with COVID-19 from the intensive care unit of the Caidian Branch of Tongji Hospital were enrolled. Epidemiological, demographic, clinical, laboratory, radiological, treatment data, and clinical outcomes were collected. Prognostic factors were statistically defined. RESULTS: Of the 59 patients studied (67.4±11.3 years), 38 patients were male, 51 had underlying diseases, and 41 patients died during admission. Compared with the survivors, the deceased patients were of older age, had more smoking history, severer fatigue, and diarrhea, a higher incidence of multiple organ injuries, more deteriorative lymphopenia and thrombocytopenia, remarkably impaired cellular immune response, and strengthened cytokine release. Age higher than 70 (OR=2.76, 95% CI=1.45-5.23), arrhythmia (OR=4.76, 95% CI=1.59-14.25), and a Sequential Organ Failure Assessment (SOFA) score above 4 (OR=5.16, 95% CI=1.29-20.55) were identified as risk factors for mortality of patients. CONCLUSION: Critically ill COVID-19 patients aged higher than 70, arrhythmia, or a SOFA score above 4 have a high risk of mortality, and need prior medical intervention.

13.
Front Pediatr ; 8: 595157, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33614540

RESUMO

Background: Bronchopulmonary dysplasia (BPD) is a common pulmonary complication in preterm infants. Acetate is a metabolite produced by the gut microbiota, and its anti-inflammatory function is well known. The role of acetate in BPD has not been studied. Here, we investigate the effects of acetate on lung inflammation and damage in mice model of BPD. Objective: To investigate the role of acetate in the development of BPD. Methods: C57BL/6 mice were randomly divided into three groups on the 3rd day after birth: room air group, hyperoxia group, and hyperoxia + acetate (250 mM, 0.02 ml/g) group. The expression of inflammatory factors was determined by ELISA and RT-PCR, and NLRP3 and caspase-1 were detected by Western blot. High-throughput sequencing was used to detect bacterial communities in the mice intestines. Results: After acetate treatment, the expression levels of TNF-α, IL-1ß, IL-18, NLRP3, and caspase-1 were significantly reduced, while the expression of GPR43 was increased. In the BPD mice treated with acetate, the proportion of Escherichia-Shigella was lower than in placebo-treated BPD mice, while the abundance of Ruminococcus was increased. Conclusions: These results indicate that acetate may regulate intestinal flora and reduce inflammatory reactions and lung injury in BPD. Therefore, acetate may be an effective drug to protect against neonatal BPD.

14.
Molecules ; 24(21)2019 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-31671631

RESUMO

Tagetespatula L. is a widely cultivated herbal medicinal plant in China and other countries. In this study, two new 2, 3-dihydrobenzofuran glucosides (1, 2) and fourteen known metabolites (3-16) were isolated from the stems and leaves of T. patula (SLT). The chemical structures of the isolated compounds were characterized comprehensively based on one- and two-dimensional NMR spectroscopy and high resolution mass spectrometry. Absolute configurations of compounds 1 and 2 were determined by ECD calculations. Compounds 1 and 2 exhibited moderate in vitro inhibitory activities against human gastric cancer cell lines (AGS) with IC50 values of 41.20 µmol/L and 30.43 µmol/L, respectively. The fingerprint profiles of stems and leaves of T. patula with three color types of flowers (Janie Yellow Bright, Jinmen Orange, Shouyao Red and Yellow color) were established by high-performance liquid chromatography (HPLC). Ten different batches of stems and leaves were examined as follow: Shouyao Red and Yellow color (1, 2, 3), Janie Yellow Bright (4, 5, 6, 7) and Jinmen Orange (8, 9, 10). Twenty-two common peaks were identified with similarity values ranging from 0.910 to 0.977. Meanwhile, the average peak area of SLT in the three types of flowers was different and it was the highest in Janie Yellow Bright.


Assuntos
Compostos Fitoquímicos/análise , Folhas de Planta/química , Caules de Planta/química , Tagetes/química , Espectroscopia de Ressonância Magnética Nuclear de Carbono-13 , Morte Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Cromatografia Líquida de Alta Pressão/métodos , Humanos , Compostos Fitoquímicos/química , Compostos Fitoquímicos/isolamento & purificação , Compostos Fitoquímicos/farmacologia
15.
Cancer Manag Res ; 11: 6215-6227, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31308756

RESUMO

BACKGROUND/AIMS: Circular RNAs (circRNAs), a class of newly discovered endogenous noncoding RNAs, have shown large capabilities in gene regulation. Patients with the grade 3 endometrial cancer (EC) have a generally poor prognosis, and the specific role of circRNAs in the grade 3 EC remains unclear. This study aims to investigate the roles of circRNAs in the grade 3 EC. METHODS: In the current study, we screened the expression profiles of circRNAs taken from two women with the grade 3 EC and adjacent non-cancerous endometrial tissue using circRNAs sequencing. Bioinformatic analyses were applied to study these differentially expressed circRNAs. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) of six dysregulated circRNAs was performed to validate the sequencing results. Bioinformatic analyses, including the negative correlation network analyses of circRNAs-microRNAs (miRNAs)-messenger RNAs (mRNAs) and the Cytoscape, were used to delineate the interaction of circRNAs/miRNAs of the entire network. RESULTS: Data of circRNA sequencing showed a significant change in 75,928 unique circRNAs (P<0.05). The upregulated hsa_circ_0039569 and hsa_circ_0001610 and downregulated hsa_circ_0000437, hsa_circ_0001776, and hsa_circ_0009043 were validated by qRT-PCR analysis. Using bioinformatical methods, we found that hsa_circ_0039569 has the MRE of hsa-miR-542-3p and hsa-let-7c-5p. Hsa-miR-542-3p and hsa-let-7c-5p were downregulated in the grade 3 EC validated by qRT-PCR analysis. In the clinicopathological parameters, the expression level of hsa_circ_0039569 was significantly correlated with tumor differentiation (P=0.001). CONCLUSION: This is the first study demonstrated that there were a lot of differences between the tissue of the grade 3 EC and adjacent non-cancerous endometrial in circRNA expression and may offer novel molecular candidates for diagnosis and clinical treatment of the grade 3 EC.

16.
Anal Chem ; 90(15): 9109-9116, 2018 08 07.
Artigo em Inglês | MEDLINE | ID: mdl-29974748

RESUMO

Commonly, in the artificial enzyme-involved signal amplification approach, the catalytic efficiency was limited by the relatively low binding affinity between artificial enzyme and substrate. In this work, substrate l-cysteine (l-Cys) and hemin were combined into one molecule to form l-Cys-hemin/G-quadruplex as an artificial self-catalytic complex for the improvement of the binding affinity between l-Cys-hemin/G-quadruplex and l-Cys. The apparent Michaelis-Menten constant ( Km = 2.615 µM) on l-Cys-hemin/G-quadruplex for l-Cys was further investigated to assess the affinity, which was much lower than that of hemin/G-quadruplex ( Km = 8.640 µM), confirming l-Cys-hemin/G-quadruplex possessed better affinity to l-Cys compared with that of hemin/G-quadruplex. Meanwhile, l-Cys bilayer could be further assembled onto the surface of l-Cys-hemin/G-quadruplex based on hydrogen-bond and electrostatic interaction to concentrate l-Cys around the active center, which was beneficial to the catalytic enhancement. Through this efficient electrochemical self-catalytic platform, a sensitive thrombin aptasensor was constructed. The results exhibited good sensitivity from 0.1 pM to 80 nM and the detection limit was calculated to be 0.032 pM. This self-catalytic strategy with improved binding affinity between l-Cys-hemin/G-quadruplex and l-Cys could provide an efficient approach to improve artificial enzymatic catalytic efficiency.


Assuntos
Aptâmeros de Nucleotídeos/química , Técnicas Biossensoriais/métodos , Cisteína/química , Quadruplex G , Hemina/química , Trombina/análise , Técnicas Eletroquímicas/métodos , Humanos , Ligação de Hidrogênio , Limite de Detecção , Nanoestruturas/química , Eletricidade Estática
17.
J Asian Nat Prod Res ; 20(6): 538-544, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29210302

RESUMO

The chemical constituents of 95% EtOH extract of yacon leaves were separated to yield two new sesquiterpene lactones, together with three known compounds. The two new compounds were characterized to be 8ß-angeloyloxy-13-methoxyl-11, 13-dihydromelampolid-14-oic acid methyl ester (1) and 8ß-(3-methylbut-2-enoyl) oxy-13-methoxyl-11, 13-dihydromelampolid-14-oic acid methyl ester (2) on the basis of NMR spectra, HR-MS and other spectroscopic methods. The cytotoxicity of compounds 1-5 were evaluated on human hepatoma cell Bel-7402 and all the compounds showed moderate cytotoxicity.


Assuntos
Antineoplásicos Fitogênicos/isolamento & purificação , Asteraceae/química , Lactonas , Antineoplásicos Fitogênicos/química , Linhagem Celular Tumoral , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Lactonas/química , Lactonas/isolamento & purificação , Folhas de Planta/química , Sesquiterpenos/isolamento & purificação
18.
Nat Prod Res ; 31(1): 43-49, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-27484732

RESUMO

The chemical constituents of 60% EtOH extract of yacon leaves were separated to yield a new compound, together with four known compounds, which were isolated for the first time from yacon. The new compound was characterised and named as chlorodalin (1) on the basis of NMR (1D and 2D), HR-MS and other spectral methods. The cytotoxic activities of 1-5 were evaluated on two human tumour cell lines and the new compound showed significant cytotoxic activity.


Assuntos
Asteraceae/química , Folhas de Planta/química , Sesquiterpenos/química , Antineoplásicos Fitogênicos/farmacologia , Linhagem Celular Tumoral , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Lactonas/química , Espectroscopia de Ressonância Magnética , Espectrometria de Massas , Extratos Vegetais/química , Extratos Vegetais/farmacologia
19.
Chin J Nat Med ; 11(3): 269-73, 2013 May.
Artigo em Inglês | MEDLINE | ID: mdl-23725840

RESUMO

AIM: To investigate the chemical constituents from the leaves of Broussonetia papyrifera. METHODS: The chemical constituents were isolated and purified by macroporous adsorptive resin D101, silica gel, and ODS column chromatography and preparative HPLC. Their structures were elucidated on the basis of 1D and 2D NMR analyses. In addition, their cytotoxic activity against human hepatoma carcinoma cells (HepG-2) were evaluated by the MTT method. Furthermore, RP-HPLC and colorimetric methods were used for the analysis of cosmosiin and total flavonoids. RESULTS: A new lignan, together with five known compounds were obtained, and their structures were characterized as (+)-pinoresinol-4'-O-ß-D-glucopyranosyl-4″-O-ß-D-apiofuranoside (1), cosmosiin (2), luteolin-7-O-ß-D-glucopyranoside (3), liriodendrin (4), 3, 5, 4'-trihydroxy-bibenzyl-3-O-ß-D-glucoside (5), and apigenin-6-C-ß-D-glucopyranside (6). Furthermore, RP-HPLC and colorimetric methods were established for the analysis of cosmosiin and total flavonoids. CONCLUSION: Compound 1 was a new lignan, and compounds 5 and 6 were isolated for the first time from the title plant. Compounds 1, 4 and 6 showed definite activities against HepG-2, while the other compounds didn't show inhibitory effects. The optimal harvest time of B. papyrifera (L.) Vent. is September.


Assuntos
Broussonetia/química , Citotoxinas/toxicidade , Extratos Vegetais/toxicidade , Folhas de Planta/química , Proliferação de Células/efeitos dos fármacos , Citotoxinas/química , Citotoxinas/isolamento & purificação , Células Hep G2 , Humanos , Lignanas/química , Lignanas/toxicidade , Estrutura Molecular , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação
20.
J Asian Nat Prod Res ; 14(3): 216-23, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22248215

RESUMO

Two new triterpenoid saponins (1, 2) and a known saponin (3) were isolated from the husks of Xanthoceras sorbifolia Bunge., and their structures were elucidated as 3-O-ß-D-glucopyranosyl(1 → 6)-[angeloyl(1 → 2)]-ß-D-glucopyranosyl-28-O-α-L-rhamnopyranosyl(1 → 2)-[ß-D-glucopyranosyl(1 → 6)]-ß-D-glucopyranosyl-21ß,22α-dihydroxyl-olean-12-ene (1), 3-O-ß-D-glucopyranosyl-28-O-[ß-D-glucopyranosyl(1 → 2)]-ß-D-glucopyranosyl-21ß,22α-dihydroxyl-olean-12-ene (2), and 3-O-ß-D-glucopyranosyl-28-O-[α-L-rhamnopyranosyl(1 → 2)]-ß-D-glucopyranosyl-21ß,22α-dihydroxyl-olean-12-ene (3), on the basis of the spectral analysis of NMR and chemical methods. Cytotoxic assay indicated that none of them showed obvious inhibitory effect on the proliferation of two human tumor cell lines.


Assuntos
Antineoplásicos Fitogênicos/isolamento & purificação , Medicamentos de Ervas Chinesas/isolamento & purificação , Ácido Oleanólico/análogos & derivados , Sapindaceae/química , Saponinas/isolamento & purificação , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/farmacologia , Ensaios de Seleção de Medicamentos Antitumorais , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/farmacologia , Células Hep G2 , Humanos , Ressonância Magnética Nuclear Biomolecular , Ácido Oleanólico/química , Ácido Oleanólico/isolamento & purificação , Ácido Oleanólico/farmacologia , Saponinas/química , Saponinas/farmacologia
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