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1.
Diagnostics (Basel) ; 14(4)2024 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-38396428

RESUMO

Major depressive disorder (MDD) and bipolar disorder (BD) share clinical features, which complicates their differentiation in clinical settings. This study proposes an innovative approach that integrates structural connectome analysis with machine learning models to discern individuals with MDD from individuals with BD. High-resolution MRI images were obtained from individuals diagnosed with MDD or BD and from HCs. Structural connectomes were constructed to represent the complex interplay of brain regions using advanced graph theory techniques. Machine learning models were employed to discern unique connectivity patterns associated with MDD and BD. At the global level, both BD and MDD patients exhibited increased small-worldness compared to the HC group. At the nodal level, patients with BD and MDD showed common differences in nodal parameters primarily in the right amygdala and the right parahippocampal gyrus when compared with HCs. Distinctive differences were found mainly in prefrontal regions for BD, whereas MDD was characterized by abnormalities in the left thalamus and default mode network. Additionally, the BD group demonstrated altered nodal parameters predominantly in the fronto-limbic network when compared with the MDD group. Moreover, the application of machine learning models utilizing structural brain parameters demonstrated an impressive 90.3% accuracy in distinguishing individuals with BD from individuals with MDD. These findings demonstrate that combined structural connectome and machine learning enhance diagnostic accuracy and may contribute valuable insights to the understanding of the distinctive neurobiological signatures of these psychiatric disorders.

2.
Environ Res ; 236(Pt 2): 116771, 2023 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-37516267

RESUMO

The state of growth of invasive species has a significant impact on the microbial regulation of the soil carbon (C) cycle. This study focused on the growth of Spartina alterniflora treated with imazapyr in the Tiaozini wetland of Jiangsu Province, China. The changes in soil bacterial structure, bacterial C metabolic activity, soil C, and regulation mechanism of soil C metabolic activity by biotic and abiotic factors were investigated. The results showed that soil bacterial diversity eventually decreased significantly (p < 0.05) along with significant changes in microbial structure (p < 0.05). Significant changes in soil physicochemical properties due to S. alterniflora growth inhibition were the key factors affecting the changes in the soil bacterial taxa composition (p < 0.05). Abiotic factors showed a greater effect on metabolic activities related to C fixation and biosynthesis of bacterial taxa than biotic factors (self-regulation). Additionally, bacterial taxa regulated soil C emission and degradation to a greater extent than abiotic factors. This study provides important information for understanding the regulators of C cycling in coastal wetland soil during the control of S. alterniflora invasion by imazapyr; moreover, it provides a scientific basis for the government to establish a prevention and control policy for S. alterniflora invasion. Understanding the complex interplay between abiotic and biotic factors is essential for developing effective strategies to manage soil C and mitigate the impacts of climate change.

3.
J Mol Neurosci ; 72(11): 2345-2359, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36203072

RESUMO

Cerebral small vessel disease is a common neurological disease, and its incidence is increasing year by year worldwide. In recent years, research on cerebral small vessel disease has gained more and more attention. Our research aims to visualize publications to identify the hotspots and frontiers of cerebral small vessel disease research, and to provide reference and guidance for further research. Publications related to cerebral small vessel disease were searched from the Web of Science Core Collection and screened according to inclusion criteria. CiteSpace 5.8.R3 was used to evaluate and visualize results, including generating web maps and analyzing annual publications, countries, institutions, bibliographic and co-cited references, and keywords; in this article, we use CiteSpace and VOSviewer for the 2012 Cerebral small vessel disease and bibliometric analysis from January 1, 2022 to April 30, 2022. A total of 3037 papers related to cerebral small vessel disease were retrieved, and the number of published papers showed a steady upward trend. Among them, Neuroimaging standards for research into small vessel disease and its contribution to ageing and neurodegeneration, the most symbolic references in the field of cerebral small vessel disease have been cited a total of 438 times. Stroke is the most active journal (227 articles) and USA publishes up to 800 articles. Harvard Med SchUniv Edinburgh (133 papers) and Charidimou (85 papers) are the institutions and authors who have made the most contributions in this field, respectively. Among the keywords, most of them are related to the pathogenesis of cerebral small vessel disease. After 2018, gut-brain axis and cortex are the keywords with the strongest number of cited outbreaks. There is increasing evidence that cerebral small vessel disease is a research frontier and may remain a research hotspot in the future.


Assuntos
Doenças de Pequenos Vasos Cerebrais , Humanos , Bibliometria , Córtex Cerebral , Neuroimagem
4.
J Pain Res ; 15: 1813-1823, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35784110

RESUMO

Background: Neuropathic pain (NP) after spinal cord injury (SCI-evoked NP) is clinically challenging; the underlying mechanisms are not fully understood, leading to a lack of promising treatment options. NP occurs in only a subset of patients with SCI. The injured spinal cord exhibits a series of histopathological changes, and the complement system has been shown to play an important role in these processes. In addition, NMDA receptor subunit 2B (NR2B) is involved in the development and maintenance of NP. This preliminary study was performed to investigate the correlations of the complement receptor 3/complement component 3 (CR3/C3) pathway and NR2B with SCI-evoked NP. Methods: A trauma-induced SCI animal model was established and SCI-evoked NP was evaluated by behavioural analysis. Transcriptome analysis was performed to identify genes in the CR3/C3 pathway related to synaptic modification, while the expression and distribution of NR2B in the injured spinal cord, and the relation to NP, were examined by immunohistochemical analysis. Results: Nine of seventeen SCI rats (52.9%) developed NP. C3 mRNA expression was significantly decreased in SCI-evoked NP rats and significantly increased in the non-NP SCI rats. C1q mRNA and CR3 mRNA expression were significantly increased in all SCI rats, but higher levels of expression were observed in the non-NP SCI rats. NR2B mRNA expression was significantly increased in the SCI-evoked NP rats and significantly decreased in the non-NP SCI rats. In addition, significantly elevated expression of NR2B-positive cells was seen in lamina II of the superficial dorsal horn in SCI-evoked NP rats in comparison with non-NP SCI rats. Conclusion: NP occurred in only a subset of SCI rats, and the CR3/C3 pathway and NR2B were involved in SCI-evoked NP. Further studies are required to determine the mechanisms underlying the SCI-evoked NP associated with the CR3/C3 pathway and NR2B.

5.
Recent Pat Anticancer Drug Discov ; 17(4): 387-395, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35023460

RESUMO

BACKGROUND: Therapeutic resistance is a frequent problem of cancer treatment and a leading cause of mortality in patients with metastatic colorectal cancer (CRC). Recent insight into the mechanisms that confer multidrug resistance has elucidated that the ATP-binding cassette (ABC) superfamily G member 2 (ABCG2) assists cancer cells in escaping therapeutic stress caused by toxic chemotherapy. Therefore, it is necessary to develop ABCG2 inhibitors. OBJECTIVES: In the present study, we investigated the inhibitory effect of KU55933 on ABCG2 in CRC. METHODS: The cytotoxicity assay and drug accumulation assay were used to examine the inhibitory effect of KU55933 on ABCG2. The protein expressions were detected by Western blot assay. The docking assay was performed to predict the binding site and intermolecular interactions between KU55933 and ABCG2. RESULTS: KU55933 was more potent than the known ABCG2 inhibitor fumitremorgin C to enhance the sensitivity of mitoxantrone and doxorubicin and the intracellular accumulation of mitoxantrone, doxorubicin and rhodamine 123 inside CRC cells with ABCG2 overexpression. Moreover, KU55933 did not affect the protein level of ABCG2. Furthermore, the docking data showed that KU55933 was tightly located in the drug-binding pocket of ABCG2. CONCLUSION: In summary, our data presented that KU55933 could effectively inhibit the drug pump activity of ABCG2 in colorectal cancer, which is further supported by the predicted model that showed the hydrophobic interactions of KU55933 within the drug-binding pocket of ABCG2. KU55933 can potently inhibit the activity of ABCG2 in CRC.


Assuntos
Membro 2 da Subfamília G de Transportadores de Cassetes de Ligação de ATP , Antineoplásicos , Neoplasias Colorretais , Membro 2 da Subfamília G de Transportadores de Cassetes de Ligação de ATP/antagonistas & inibidores , Membro 2 da Subfamília G de Transportadores de Cassetes de Ligação de ATP/genética , Membro 2 da Subfamília G de Transportadores de Cassetes de Ligação de ATP/metabolismo , Antineoplásicos/química , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/genética , Doxorrubicina/farmacologia , Resistencia a Medicamentos Antineoplásicos , Humanos , Mitoxantrona/farmacologia , Morfolinas/farmacocinética , Proteínas de Neoplasias/antagonistas & inibidores , Proteínas de Neoplasias/genética , Proteínas de Neoplasias/metabolismo , Pironas/farmacologia
6.
Kaohsiung J Med Sci ; 38(4): 367-377, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-34962339

RESUMO

The specific mechanism of gingerol in cerebral ischemia remains unknown. A neuroprotective function for miR-210 in cerebral ischemia has been identified. The brain-derived neurotrophic factor (BDNF)-mediated signaling pathway protects against cerebral ischemic injury. This investigation aimed to determine whether gingerol plays a neuroprotective role in cerebral ischemia via the miR-210/BDNF axis. N2a cells subjected to 10 h of hypoxia and 4 h of reoxygenation were treated with 5, 10, or 20 µmol/L gingerol. The levels of viability, apoptosis, and proteins in N2a cells were determined using MTT assays, flow cytometry, and western blotting, respectively. The binding relationship between BDNF and miR-210 was studied using a dual luciferase reporter assay. The expression levels of miR-210 and BDNF were determined using qPCR. Gingerol repressed the increase in apoptosis and decrease in viability observed in response to hypoxia/reoxygenation. Gingerol increased Bcl-2, BDNF, and TrkB levels and reduced Bax and cleaved caspase 3 levels after hypoxia/reoxygenation. Gingerol evoked decreased expression of miR-210. Inhibition of miR-210 resulted in increased viability and reduced apoptosis along with increased levels of Bcl-2, BDNF, and TrkB and reduced levels of Bax and cleaved caspase 3 after hypoxia/reoxygenation. Additionally, the miR-210 mimic reversed changes induced by gingerol. The cotransfection of the miR-210 mimic and wild type BDNF led to decreased luciferase activity. BDNF was negatively regulated by miR-210. BDNF siRNA reversed these changes evoked by miR-210 inhibition. Gingerol ameliorated hypoxia/reoxygenation-stimulated neuronal damage by regulating the miR-210/BDNF axis, indicating that gingerol is worthy of further application in cerebral ischemia therapy.


Assuntos
Isquemia Encefálica , Fator Neurotrófico Derivado do Encéfalo , Catecóis , Álcoois Graxos , MicroRNAs , Neurônios , Fármacos Neuroprotetores , Animais , Apoptose/efeitos dos fármacos , Isquemia Encefálica/metabolismo , Fator Neurotrófico Derivado do Encéfalo/genética , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Catecóis/farmacologia , Linhagem Celular Tumoral , Álcoois Graxos/farmacologia , Camundongos , MicroRNAs/genética , MicroRNAs/metabolismo , Neurônios/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia
7.
Front Oncol ; 11: 680663, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34094985

RESUMO

Colorectal cancer is a common malignancy with the third highest incidence and second highest mortality rate among all cancers in the world. Chemotherapy resistance in colorectal cancer is an essential factor leading to the high mortality rate. The ATP-binding cassette (ABC) superfamily G member 2 (ABCG2) confers multidrug resistance (MDR) to a range of chemotherapeutic agents by decreasing their intracellular content. The development of novel ABCG2 inhibitors has emerged as a tractable strategy to circumvent drug resistance. In this study, an ABCG2-knockout colorectal cancer cell line was established to assist inhibitor screening. Additionally, we found that ataxia-telangiectasia mutated (ATM) kinase inhibitor AZ32 could sensitize ABCG2-overexpressing colorectal cancer cells to ABCG2 substrate chemotherapeutic drugs mitoxantrone and doxorubicin by retaining them inside cells. Western blot assay showed that AZ32 did not alter the expression of ABCG2. Moreover, molecule docking analysis predicted that AZ32 stably located in the transmembrane domain of ABCG2. In conclusion, our result demonstrated that AZ32 could potently reverse ABCG2-mediated MDR in colorectal cancer.

8.
Cancer Lett ; 497: 14-27, 2021 01 28.
Artigo em Inglês | MEDLINE | ID: mdl-33010383

RESUMO

Human papillomavirus (HPV) is the etiological agent of cervical cancer; however, the mechanisms underlying HPV-mediated carcinogenesis remain poorly understood. Here, we showed that nuclear receptor related-1 protein (Nurr1) was upregulated in primary cervical cancer tissue-derived spheroid cells and HPV-positive cell lines, and Nurr1 upregulation was correlated with cancer grade. Nurr1 promoted cell proliferation, migration, invasion, and anchorage-independent cell growth. In addition to its effect on cancer aggressiveness, Nurr1 enhanced the self-renewal ability of cells in vitro and in vivo, underscoring the importance of Nurr1 in maintaining the stemness of cancer stem-like cells (CSLCs). Mechanistically, Nurr1 independently activated the MEK/ERK and PI3K/Akt/mTOR signaling cascades. The MEK inhibitor trametinib (GSK) and PI3K/mTOR dual inhibitor dactolisib (BEZ) were shown to abrogate Nurr1-augmented tumorigenesis by upregulating p21 and p27 expression and by suppressing MMP9 and KLF4 expression. We provided further evidence that BEZ, but not GSK, could abolish Nurr1-enhanced radioresistance, suggesting its potential value for radiosensitizing CSLCs in the clinical setting. This study highlights the unprecedented roles of Nurr1 and elucidates mechanisms by which Nurr1 promotes tumor progression and radioresistance, providing a novel therapeutic strategy for cervical cancer treatment.


Assuntos
Biomarcadores Tumorais/metabolismo , Regulação Neoplásica da Expressão Gênica , Células-Tronco Neoplásicas/patologia , Membro 2 do Grupo A da Subfamília 4 de Receptores Nucleares/metabolismo , Proteínas Oncogênicas Virais/metabolismo , Tolerância a Radiação , Neoplasias do Colo do Útero/patologia , Animais , Apoptose , Biomarcadores Tumorais/genética , Proliferação de Células , Feminino , Humanos , Fator 4 Semelhante a Kruppel , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Proteína Quinase 1 Ativada por Mitógeno/genética , Proteína Quinase 1 Ativada por Mitógeno/metabolismo , Proteína Quinase 3 Ativada por Mitógeno/genética , Proteína Quinase 3 Ativada por Mitógeno/metabolismo , Células-Tronco Neoplásicas/metabolismo , Células-Tronco Neoplásicas/efeitos da radiação , Membro 2 do Grupo A da Subfamília 4 de Receptores Nucleares/genética , Proteínas Oncogênicas Virais/genética , Papillomaviridae/fisiologia , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/metabolismo , Infecções por Papillomavirus/virologia , Fosfatidilinositol 3-Quinases/genética , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais , Células Tumorais Cultivadas , Neoplasias do Colo do Útero/metabolismo , Neoplasias do Colo do Útero/radioterapia , Neoplasias do Colo do Útero/virologia , Ensaios Antitumorais Modelo de Xenoenxerto
9.
Cancers (Basel) ; 12(10)2020 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-33086676

RESUMO

Nuclear receptor related-1 protein (Nurr1), coded by an early response gene, is involved in multiple cellular and physiological functions, including proliferation, survival, and self-renewal. Dysregulation of Nurr1 has been frequently observed in many cancers and is attributed to multiple transcriptional and post-transcriptional mechanisms. Besides, Nurr1 exhibits extensive crosstalk with many oncogenic and tumor suppressor molecules, which contribute to its potential pro-malignant behaviors. Furthermore, Nurr1 is a key player in attenuating antitumor immune responses. It not only potentiates immunosuppressive functions of regulatory T cells but also dampens the activity of cytotoxic T cells. The selective accessibility of chromatin by Nurr1 in T cells is closely associated with cell exhaustion and poor efficacy of cancer immunotherapy. In this review, we summarize the reported findings of Nurr1 in different malignancies, the mechanisms that regulate Nurr1 expression, and the downstream signaling pathways that Nurr1 employs to promote a wide range of malignant phenotypes. We also give an overview of the association between Nurr1 and antitumor immunity and discuss the inhibition of Nurr1 as a potential immunotherapeutic strategy.

10.
Huan Jing Ke Xue ; 41(2): 895-904, 2020 Feb 08.
Artigo em Chinês | MEDLINE | ID: mdl-32608751

RESUMO

Soil enzymes play key roles in the construction and succession of coastal wetland communities, while the driving mechanism of their activities under water and salt stress conditions is still unclear. The activities and distributions of sucrase, phosphatase, catalase, and urease in the rhizosphere and non-rhizosphere soils of Suaeda salsa, Phragmites australis, and Tamarix chinensis communities were studied in the Yellow River Delta. Moreover, the changes in soil enzyme activities and their influencing factors during the succession of halophytic plant communities were discussed in combination with changes in the physicochemical properties of soil. The results showed significantly higher soil enzyme activities and soil fertility parameters in the rhizosphere soils of S. salsa, P. australis, and T. chinensis communities than those in the non-rhizosphere soils (P<0.05). In the rhizosphere soils, the activities of phosphatase and catalase increased in the order of S. salsa < P. australis < T. chinensis, while they increased in the order of T. chinensis < S. salsa < P. australis for sucrase activity, and S. salsa < T. chinensis < P. australis for urease activity. Further, significant differences were found in the physicochemical properties of rhizosphere soils between different halophyte communities (P<0.05), which indicated that plant types and their rhizosphere effects could affect soil enzyme activities and fertility characteristics. Furthermore, a two-way analysis of variance showed that the rhizosphere effect was greater than that of vegetation type. The soil sucrase activity was significantly positively correlated with available potassium (AK), available phosphorus (AP), and ammonium nitrogen (NH4+-N) (P<0.05). Meanwhile, urease activity was significantly positively correlated with total nitrogen (TN), organic matter (SOM), AK, AP, NH4+-N, and nitrate nitrogen (NO3--N) (P<0.01). Both of the two enzymes were negatively correlated with soil electrical conductivity (EC) (P<0.01). The phosphatase and catalase activities were found to be significantly positively correlated with soil water content (MC), total carbon (TC), TN, total phosphorus (TP), SOM, AK, and NH4+-N (P<0.05). Additionally, parameters of pH, total potassium (TK), and NO3--N were also significantly associated with catalase activity. Finally, the redundancy analysis (RDA) revealed that main factors affecting the overall soil enzyme activity were TC (P<0.01), SOM (P<0.01), MC (P<0.01), TN (P<0.05), NH4+-N (P<0.05), and EC (P<0.05). The findings suggested that soil fertility, water, and salinity are the most influential factors of soil enzyme activity in different halophytic plant communities of the Yellow River Delta.


Assuntos
Enzimas/análise , Rizosfera , Solo/química , Áreas Alagadas , Chenopodiaceae , China , Nitrogênio , Rios , Plantas Tolerantes a Sal , Tamaricaceae
11.
Br J Cancer ; 123(5): 833-843, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32507856

RESUMO

BACKGROUND: CD109 was involved in the tumorigenesis and progression of various cancers via TGF-ß1 signalling and STAT3 activation. As CD109 is strongly expressed in cervical squamous cell carcinoma, this study was conducted to investigate its functional characteristics in cervical cancer. METHODS: CD109 expression was examined by immunohistochemistry (IHC) with cervical tissue microarray. The effects of CD109 expression were examined on migration, cell proliferation, spheroid formation and soft-agar colony-formation assay. Meanwhile, cervical cancer cell lines with high CD109 expression were chosen for the functional study using siRNA knockdown and CRISPR/Cas9 knockout. RESULTS: IHC demonstrated an upregulation of CD109 in the cell membrane of cervical squamous cell carcinoma. CD109( + ) cells isolated by flow-cytometric sorting displayed enhanced migration, cell proliferation, sphere-forming and anchorage-independent cell growth ability. In contrast, silencing of CD109 expression could reverse the in vitro and in vivo tumorigenic and aggressive properties. Furthermore, CD109 induced EGFR-mediated STAT3 phosphorylation known to be responsible for cell migration, proliferation and maintenance of CSC phenotype. CONCLUSION: Abundant CD109( + ) populations in cervical cancer cells potentially contributed to carcinogenesis and aggressiveness, whereas silencing of CD109 expression could reverse those properties. CD109 mediates cervical tumorigenicity and aggressiveness via CD109/EGFR/STAT3 signalling.


Assuntos
Antígenos CD/metabolismo , Carcinoma de Células Escamosas/metabolismo , Proteínas de Neoplasias/metabolismo , Fator de Transcrição STAT3/metabolismo , Neoplasias do Colo do Útero/metabolismo , Animais , Antígenos CD/biossíntese , Antígenos CD/genética , Sequência de Bases , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/patologia , Linhagem Celular Tumoral , Receptores ErbB/metabolismo , Feminino , Proteínas Ligadas por GPI/biossíntese , Proteínas Ligadas por GPI/genética , Proteínas Ligadas por GPI/metabolismo , Técnicas de Inativação de Genes , Xenoenxertos , Humanos , Imuno-Histoquímica , Camundongos Endogâmicos BALB C , Camundongos Nus , Proteínas de Neoplasias/biossíntese , Proteínas de Neoplasias/genética , Fosforilação , RNA Interferente Pequeno/administração & dosagem , RNA Interferente Pequeno/genética , Transdução de Sinais , Neoplasias do Colo do Útero/genética , Neoplasias do Colo do Útero/patologia
12.
Sci Total Environ ; 740: 140144, 2020 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-32562999

RESUMO

Soil microorganisms play a key role in regulating the biogeochemical cycles of ecosystems. However, studies that quantitatively examine bacterial metabolic groups to predict the environmental and biological impacts are limited. In this research, we employed 16S rRNA gene sequencing on an Illumina MiSeq platform to analyze bacterial diversity, structure, function, and driving factors of Suaeda salsa in rhizosphere and non-rhizosphere soils in intertidal and supratidal habitats in the Yellow River Delta, China. Results showed that bacterial richness and Shannon diversity index of the rhizosphere soil were greater in the intertidal than in the supratidal habitat. Although the bacteria of the two habitats changed extremely in community structure, the bacterial groups related to carbohydrate metabolism (CM) and amino acid metabolism (AAM) had higher abundance than the other groups in both habitats. Furthermore, they were higher in the supratidal than the intertidal habitats, and bacterial groups associated with energy metabolism (EM) are opposite. Furthermore, bacterial diversity showed no significant difference between the rhizosphere and non-rhizosphere soils. In the intertidal habitat, the rhizosphere soil had higher EM but lower AAM and CM than the non-rhizosphere soil, which indicated that bacterial structure and function were obviously influenced by the root exudates of S. salsa under flooding and salt stresses. Redundancy analysis showed that the dominant phyla were significantly affected by available phosphorus (51.0%), total potassium (32.2%), moisture content (28.1%), available potassium (25.3%), electrical conductivity (24.2%), total nitrogen (22.8%), total carbon (21.9%), and soil organic matter (21.0%). Overall, the findings provide important insights into the roles of bacterial groups in coastal wetland under climate changes.


Assuntos
Chenopodiaceae , Rizosfera , Bactérias/genética , China , Ecossistema , RNA Ribossômico 16S , Rios , Solo , Microbiologia do Solo
13.
Br J Cancer ; 123(2): 275-287, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32390009

RESUMO

BACKGROUND: Ovarian cancer is characterised by frequent recurrence due to persistent presence of residual cancer stem cells (CSCs). Here, we identify and characterise tumour subsets from ascites-derived tumour cells with stemness, metastasis and metabolic switch properties and to delineate the involvement of pyruvate dehydrogenase kinase 4 (PDK4) in such process. METHODS: Ovarian cancer cells/cell lines derived from ascites were used for tumourspheres/ALDH+CD44+ subset isolation. The functional roles and downstream signalling of PDK4 were explored. Its association with clinical outcome of ovarian cancer was analysed. RESULTS: We demonstrated enhanced CSC characteristics of tumour cells derived from ovarian cancer ascites, concomitant with ALDH and CD44 subset enrichment and high PDK4 expression, compared to primary tumours. We further showed tumourspheres/ALDH+CD44+ subsets from ascites-derived tumour cells/cell lines with CSC properties and enhanced glycolysis. Clinically, PDK4 expression was correlated with aggressive features. Notably, blockade of PDK4 in tumourspheres/ALDH+CD44+ subsets led to inhibition of CSC characteristics, glycolysis and activation of STAT3/AKT/NF-κB/IL-8 (signal transducer and activator of transcription 3/protein kinases B/nuclear factor-κB/interleukin-8) signalling. Conversely, overexpression of PDK4 in ALDH-CD44- subsets exerted the opposite effects. CONCLUSION: Ascites-derived ALDH+CD44+ tumour cell subsets endow stemness, metastatic and metabolic switch properties via PDK4-mediated STAT3/AKT/NF-κB/IL-8 signalling, suggesting PDK4 as a viable therapeutic molecular target for ovarian cancer management.


Assuntos
Interleucina-8/genética , Recidiva Local de Neoplasia/genética , Neoplasias Ovarianas/genética , Piruvato Desidrogenase Quinase de Transferência de Acetil/genética , Fator de Transcrição STAT3/genética , Aldeído Desidrogenase/genética , Ascite/metabolismo , Ascite/patologia , Linhagem Celular Tumoral , Feminino , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Receptores de Hialuronatos/genética , NF-kappa B/genética , Metástase Neoplásica , Recidiva Local de Neoplasia/metabolismo , Recidiva Local de Neoplasia/patologia , Células-Tronco Neoplásicas/metabolismo , Células-Tronco Neoplásicas/patologia , Proteína Oncogênica v-akt/genética , Neoplasias Ovarianas/patologia , Receptores de Interleucina-8A/genética , Transdução de Sinais/genética
14.
PLoS One ; 15(2): e0229047, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32049992

RESUMO

Water-salt stress and nutrient limitation may affect leaf economic spectrum of halophytes and confuse our understanding on plant physiological principles in a changing world. In this study, three halophytic plant communities of Phragmites australis, Suaeda salsa, and Tamarix chinensis, were selected in two sites (sites 1 and 2) on the west coast of Bohai Sea. The net photosynthetic rate (Pn), transpiration rate (Tr), stomatal conductance (Gs), leaf vapor pressure deficit (VPDleaf) and their influencing factors were studied to test the possible carbon assimilation strategies of the halophytes. P. australis had higher Pn, Tr, and Gs than S. salsa and T. chinensis in both sites. Similar trends were found for leaf P and photosynthetic N and P efficiency (PNUE and PPUE, respectively) in one or both sites. By contrast, the leaf dry mass per area (LMA) increased in the order of P. australis < S. salsa < T. chinensis in both sites. For identical species in different sites, Pn, leaf P, and PNUE were lower but Tr, VPDleaf, leaf N, leaf N:P, and PPUE were higher in site 1 than in site 2 for one or more halophytes. Although soil physicochemical properties in different sites explained several variations among the halophytes, two-way ANOVA indicated that the species can explain most of the leaf traits compared with the site. LMA also had significant nonlinear relationships with Pn, Tr, Gs, and VPDleaf. PNUE and PPUE showed positive correlation with Pn in both sites, but they decreased in the power-law function with increasing LMA. Overall, the redundancy analysis showed that the gas exchange capacity of the halophytic plant communities was significantly affected by PPUE (60.0% of explanation), PNUE (57.1%), LMA (35.0%), leaf P (22.0%), and soil N (15.8%).


Assuntos
Fotossíntese , Fenômenos Fisiológicos Vegetais , Plantas/genética , Plantas/metabolismo , China , Ecossistema , Nutrientes , Oceanos e Mares , Folhas de Planta/fisiologia , Solo/química
15.
RSC Adv ; 9(53): 30615-30627, 2019 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-35529360

RESUMO

The heavy metals Al, Cr, Cu, Ni, Pb, Zn, Fe, Mn, As, and Cd in the rainfall-driven supratidal wetlands along the west coast of the Bohai Sea (the areas are named site 1, site 2, site 3, and site 4 from south to north in the gradient in this study) are tested for their accumulation risks and sources. Results show that the distribution and enrichment of the heavy metals in the supratidal wetlands are lower in site 1 than in sites 2-4. The risk indices (RIs) of all sites are less than 150, indicating low-moderate risk. However, the RI values are primarily dominated by the risk indices (E r i ) of As and Cd. The accumulative contribution values of E r i -As and E r i -Cd in sites 1, 2, 3, and 4 are 79.05%, 77.80%, 80.54%, and 76.43%, respectively. Additionally, the contamination degree (C d) and the Nemero comprehensive pollution index (PN) of the supratidal wetland in site 1 are 6.86 and 0.74 respectively, indicating a low-risk state. By contrast, the C d and PN values of the other three supratidal wetlands are higher than those of site 1, suggesting an increasing accumulation risk for heavy metals in sites 2, 3 and 4. Our analysis indicates that the heavy metals Al, Cr, Mn, and Fe in all the supratidal wetlands mainly originate from the weathering of rocks and their parent materials. Pb is significantly correlated with anthropogenic activities, while Cu, As, and Cd are likely induced by anthropogenic activities and atmospheric deposition. The sources of Ni and Zn should be determined on the basis of the situation of the wetland and its surrounding areas. For example, Ni is mainly affected by anthropogenic activities in site 2, whereas the origins of Ni are soil parent materials or atmospheric depositions in sites 1, 3, and 4. Our results can provide data to support the utilization strategy and sustainable development plans for marine space resources on the coast of the Bohai Sea.

16.
J Obstet Gynaecol Res ; 44(9): 1705-1711, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29974571

RESUMO

AIM: The aim of the present study was to investigate the safety and efficacy of low-dose mifepristone combined with self-administered misoprostol for termination of early pregnancy. METHODS: A total of 533 women seeking medical abortion in early pregnancy (≤49 days since the last menstrual period) were divided randomly into hospital- (H-Mis, 250) and self- (S-Mis, 283) administered misoprostol groups. Women in two groups took 100 mg of oral mifepristone in hospital followed by 200 µg of sublingual misoprostol 24 h later in hospital or home. The primary outcome parameter was complete abortion without surgical intervention. Secondary outcomes were uterine bleeding, return of regular menses, side effects and patient acceptability. RESULTS: High rates of complete abortion were observed for both the H-Mis group (243/250; 94.8%) and the S-Mis group (266/283; 94.0%). No significant differences in outcomes (complete abortion/failure rates) or side effects were observed between the two groups. General satisfaction rates were similar for the two groups (H-Mis, 231/250, 92.4%; S-Mis, 263/283, 92.9%; P > 0.05). Higher convenience of administration (H-Mis, 211/250, 84.4%; S-Mis, 270/283, 95.4%; P < 0.05) and privacy protection (H-Mis, 214/250, 85.6%; S-Mis, 267/283, 94.3%; P < 0.05) satisfaction rates were obtained for the S-Mis group than for the H-Mis group. CONCLUSION: Self-administered sublingual misoprostol is as safe and effective as hospital-administered misoprostol following low-dose mifepristone to terminate early pregnancy (≤49 days of amenorrhoea) with fewer side effects.


Assuntos
Abortivos/farmacologia , Aborto Induzido/métodos , Mifepristona/farmacologia , Misoprostol/farmacologia , Avaliação de Resultados em Cuidados de Saúde , Abortivos/administração & dosagem , Abortivos/efeitos adversos , Aborto Induzido/efeitos adversos , Aborto Induzido/normas , Adulto , Quimioterapia Combinada , Feminino , Humanos , Mifepristona/administração & dosagem , Mifepristona/efeitos adversos , Misoprostol/administração & dosagem , Misoprostol/efeitos adversos , Autoadministração , Adulto Jovem
17.
Org Lett ; 20(12): 3527-3530, 2018 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-29798675

RESUMO

A variety of 2-aminobenzonitriles were prepared from 2-arylindoles in good to excellent yields through tert-butylnitrite (TBN)-mediated nitrosation and sequential iron(III)-catalyzed C-C Bond cleavage in a one-pot fashion. The 2-aminobenzonitriles can be used to rapidly synthesize benzoxazinones by intramolecular condensation. The present method features an inexpensive iron(III) catalyst, gram scalable preparations, and novel C-C bond cleavage of indoles.

18.
Molecules ; 22(6)2017 Jun 09.
Artigo em Inglês | MEDLINE | ID: mdl-28598407

RESUMO

In this study, the ultrasound-assisted extraction of polysaccharides (PSA) from Pinelliae Rhizoma Praeparatum Cum Alumine (PRPCA) was optimized by response surface methodology (RSM). The structural characteristics of PSA were analyzed by UV-vis spectroscopy, infrared spectroscopy, scanning electron microscopy, high performance gel permeation chromatography and high performance liquid chromatography, respectively. In addition, antioxidant and antimicrobial activities of PSA were studied by different in vitro assays. Results indicated that the optimal extraction conditions were as follows: the ratio of water to raw of 30 mL/g, extraction time of 46.50 min, ultrasonic temperature of 72.00 °C, and ultrasonic power of 230 W. Under these conditions, the obtained PSA yield (13.21 ± 0.37%) was closely agreed with the predicted yield by the model. The average molecular weights of the PSA were estimated to be 5.34 × 10³ and 6.27 × 105 Da. Monosaccharide composition analysis indicated that PSA consisted of mannose, galactose uronic acid, glucose, galactose, arabinose with a molar ratio of 1.83:0.55:75.75:1.94:0.45. Furthermore, PSA exhibited moderate antioxidant and antibacterial activities in vitro. Collectively, this study provides a promising strategy to obtain bioactive polysaccharides from processed products of herbal medicines.


Assuntos
Antibacterianos/isolamento & purificação , Antioxidantes/isolamento & purificação , Extração Líquido-Líquido/métodos , Pinellia/química , Polissacarídeos/isolamento & purificação , Sonicação/métodos , Antibacterianos/química , Antibacterianos/farmacologia , Antioxidantes/química , Antioxidantes/farmacologia , Benzotiazóis/antagonistas & inibidores , Benzotiazóis/química , Compostos de Bifenilo/antagonistas & inibidores , Compostos de Bifenilo/química , Candida albicans/efeitos dos fármacos , Candida albicans/crescimento & desenvolvimento , Escherichia coli/efeitos dos fármacos , Escherichia coli/crescimento & desenvolvimento , Análise Fatorial , Extração Líquido-Líquido/instrumentação , Testes de Sensibilidade Microbiana , Monossacarídeos/química , Picratos/antagonistas & inibidores , Picratos/química , Polissacarídeos/química , Polissacarídeos/farmacologia , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus aureus/crescimento & desenvolvimento , Ácidos Sulfônicos/antagonistas & inibidores , Ácidos Sulfônicos/química , Superóxidos/antagonistas & inibidores , Superóxidos/química , Temperatura , Ácidos Urônicos/química
19.
Reprod Sci ; 24(5): 731-737, 2017 05.
Artigo em Inglês | MEDLINE | ID: mdl-27678099

RESUMO

The aim of this study was to investigate the efficacy, safety, and acceptability of low-dose mifepristone combined with self-administered misoprostol for ultra-early medical abortion. A total of 744 women with ultra-early pregnancy (amenorrhea ≤35 days) who fulfilled the inclusion criteria were enrolled in the study. Equal numbers of participants were allocated randomly to the hospital administration and self-administration groups. All participants took 75 mg mifepristone at the initial visit and 400 µg oral misoprostol 24 hours later in the hospital or by self-administration. The primary end point was complete abortion. Secondary end points were rates of unscheduled reattendance, time required for and cost of hospital observation and follow-up, vaginal bleeding, adverse effects, menstrual disturbance in the posttreatment period, and satisfaction rating. No differences in the rates of complete abortion, unscheduled reattendance, vaginal bleeding, adverse effects, or return of posttreatment menstruation were observed. The time required for (and costs of) hospital observation and follow-up per participant was 557.82 minutes (and US$40.12) in the hospital administration group and 18.46 minutes (and US$1.96) in the self-administration group (both P < .001). Satisfaction rates were similar in both groups, but the rates of "very satisfied" responses (87.60% vs 25.41%) and follow-up compliance (loss to follow-up, 0.45% vs 7.70%) were higher in the self-administration group (both P < .001). Low-dose mifepristone combined with self-administered misoprostol for ultra-early pregnancy termination was as effective and safe as hospital administration, with greater acceptability and lower cost to the women.


Assuntos
Abortivos/administração & dosagem , Aborto Induzido/métodos , Mifepristona/administração & dosagem , Misoprostol/administração & dosagem , Abortivos/efeitos adversos , Administração Oral , Adulto , Quimioterapia Combinada , Feminino , Humanos , Mifepristona/efeitos adversos , Misoprostol/efeitos adversos , Gravidez , Primeiro Trimestre da Gravidez , Autoadministração , Resultado do Tratamento , Adulto Jovem
20.
Huan Jing Ke Xue ; 36(8): 2833-42, 2015 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-26592010

RESUMO

In order to understand the inorganic carbon cycle of the groundwater-fed reservoir in karst area, Dalongdong Reservoir, which is located at Shanglin County, Guangxi Zhuang Autonomous Region, China, was investigated from 12th to 20th July, 2014. Concentration of dissolved inorganic carbon (DIC), delta13C of DIC (delta13C(DIC)), partial CO2 pressure (pCO2) and CO2 flux across water-air interface were studied by observation in situ and high-resolution diel monitoring. Results show that: (1) DIC concentration and water pCO2 increased from upstream area to downstream area [DIC(average)): from 122.88 to 172.02 mg x L(-1), pCO2(average) : from 637.91 x 10(-6) to 1399.97 x 10(-6)], while delta13C(DIC) decreased from upstream area to downstream area [delta13C(DIC(average): from -4.34% per hundred to -6.97% per hundred] in the reservoir. (2) CO2 efflux across water-air interface varied from 7.11 to 335.54 mg x (m2 x h)(-1) with mean of 125.03 mg x (m2 x h)(-1) in Dalongdong reservoir surface-layer waters, which was the source of atmospheric CO2. CO2 effluxes across water-air interface in upstream area [mean 131.73 mg x (m2 x h)(-1)] and downstream area [mean 170.25 mg x (m2 x h)(-1)] were higher than that in middle area [mean 116.05 mg x (m2 x h))(-1)] in the reservoir. (3) Water pCO2 and CO2 efflux across water-air interface showed similar characteristics of diel variations, which decreased in daylight and increased in night and showed a negative correlation with chlorophyll a (Chla). Possible reasons of research results are found as follows: (1) DIC concentration, water pCO2 and delta13C(DIC) are influenced by biomass of phytoplankton, turbidity, conductivity, the depth of water and transparency, while CO2 efflux across water-air interface is controlled by both of biomass of phytoplankton and wind speed. (2) Photosynthesis, respiration and vertical motion of phytoplankton possibly affect diel variations of DIC cycle in the groundwater-fed reservoir in karst area.


Assuntos
Dióxido de Carbono/análise , Carbono/análise , Água/química , Biomassa , Ciclo do Carbono , Isótopos de Carbono/análise , China , Clorofila , Clorofila A , Água Subterrânea/química , Compostos Inorgânicos/análise , Fotossíntese , Fitoplâncton , Vento
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