RESUMO
An electro-triggered cascade cyclization strategy was disclosed with concomitant phosphinylation and N-heterocycle construction. It provides a novel and environmentally friendly approach to access phosphinyl-substituted N-heterocycles with no external metal catalyst, oxidant, or heating. Mechanistic studies have revealed that anodic oxidation of H-phosphorus compounds occurs first to generate the key P-centered radical directly and cathodic reduction leads to the concurrent release of molecular hydrogen or methane. This protocol features simple operation, broad substrate scope, clean and mild conditions, and atom and step economy to form heterocycle-containing organophosphorus scaffolds.
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NF-YA is considered as a crucial regulator for the maintenance of cancer stem cell (CSC) and involved in various types of malignant tumours. However, the exact function and molecular mechanisms of NF-YA in the progression of cervical cancer remains poorly understood. Here, the expression of NF-YA detected by immunohistochemistry was gradually increased from normal cervical tissues, to the high-grade squamous intraepithelial lesions, and then to cervical cancer tissues. NF-YA promoted the cell proliferation and tumorigenic properties of cervical cancer cells as well as tumorsphere formation and chemoresistance in vitro. The luciferase reporter assay combined with mutagenesis analyses and Western blotting showed that NF-YA trans-activated the expression of SOX2 in cervical cancer. Furthermore, quantitative chromatin immunoprecipitation (qChIP) and electrophoretic mobility shift assay (EMSA) confirmed that NF-YA protein directly bound to the CCAAT box region located upstream of the SOX2 promoter. Together, our data demonstrated that NF-YA was highly expressed in cervical cancer and promoted the cell proliferation, tumorigenicity and CSC characteristic by trans-activating the expression of SOX2.
Assuntos
Fator de Ligação a CCAAT/metabolismo , Regulação Neoplásica da Expressão Gênica , Fatores de Transcrição SOXB1/metabolismo , Neoplasias do Colo do Útero/metabolismo , Animais , Carcinoma de Células Escamosas/metabolismo , Linhagem Celular Tumoral , Proliferação de Células , Separação Celular , Sobrevivência Celular , Feminino , Humanos , Camundongos , Camundongos Nus , Células-Tronco Neoplásicas/metabolismo , Ativação Transcricional , Displasia do Colo do Útero/metabolismoRESUMO
Ticks are the vectors of various pathogens, threatening human health and animal production across the globe. Here, for the first time we detected Ricketssia spp., Borrelia spp. and protozoan in ticks from Poyang Lake region in Ji- angxi Province of eastern China. In 3 habitat categories and on 12 host species, 311 ticks from 11 species were collected. Haemaphysalis longicornis was the predominant species, accounting for 55.63%, followed by Rhipicephalus microplus, Haemaphysalis flava and Ixodes granulatus. Of the collected ticks, 7.07% were positive for tick-borne pathogens, and H. longicornis and H. flava were found to be co-infected with Ricketssia spp. and protozoan. H. flava was the most detected positive for tick-borne pathogens, whereas H. longicornis had the lowest infection rate, and the difference in infection rates between tick species was significant (χ2=61.24, P<0.001). Furthermore, adult ticks demonstrated remarkably greater infection rate than immature ticks (χ2=10.12, P=0.018), meanwhile ticks on Erinaceidae showed significantly higher positivity than ticks collected on other host species (χ2=108.44, P<0.001). Genetic fragment sequencing and analyses showed at least 4 pathogen species presence in ticks, namely Borrelia yangtzensis, Rickettsia slovaca or Rickettsia raoultii related genospecies, Babesia vogeli and Hepatozoon canis or Hepatozoon felis related genospecies. The finding indicates that the abundant ticks can carry diverse pathogens in Poyang Lake region, and pathogen infection is highly related to species, vertebrate hosts and life stages of ticks.
Assuntos
Babesia/isolamento & purificação , Borrelia/isolamento & purificação , Coccídios/isolamento & purificação , Ixodidae/microbiologia , Ixodidae/parasitologia , Rickettsia/isolamento & purificação , Animais , China/epidemiologia , Ixodidae/crescimento & desenvolvimento , Infestações por Carrapato/parasitologia , Infestações por Carrapato/veterináriaRESUMO
Collective atomic excitation can be realized by the Raman scattering. Such a photon-atom interface can form an SU(1,1)-typed atom-light hybrid interferometer, where the atomic Raman amplification processes take the place of the beam splitting elements in a traditional Mach-Zehnder interferometer. We numerically calculate the phase sensitivities and the signal-to-noise ratios (SNRs) of this interferometer with the method of homodyne detection and intensity detection, and give their differences of the optimal phase points to realize the best phase sensitivities and the maximal SNRs from these two detection methods. The difference of the effects of loss of light field and atomic decoherence on measure precision is analyzed.
RESUMO
A new sesquiterpene lactone glycoside (1) and a new quinic acid methyl ester (2) were isolated from Patrinia villosa, together with another two known compounds chlorogenic acid n-butyl ester (3), 3, 4-di-O-caffeoylquinic acid methyl ester (4). Their structures were established using 1D/2D-NMR spectroscopy, mass spectrometry, and comparing with spectroscopic data reported in the literature.
Assuntos
Medicamentos de Ervas Chinesas/isolamento & purificação , Glicosídeos/isolamento & purificação , Lactonas/isolamento & purificação , Patrinia/química , Ácido Quínico/análogos & derivados , Sesquiterpenos/isolamento & purificação , Ácido Clorogênico , Medicamentos de Ervas Chinesas/química , Glicosídeos/química , Lactonas/química , Estrutura Molecular , Ressonância Magnética Nuclear Biomolecular , Ácido Quínico/química , Ácido Quínico/isolamento & purificação , Sesquiterpenos/químicaRESUMO
Arctic fjords are hotspots of marine carbon burial, with diatoms playing an essential role in the biological carbon pump. Under the background of global warming, the proportion of diatoms in total phytoplankton communities has been declining in many high-latitude fjords due to increased turbidity and oligotrophication resulting from glacier melting. However, due to the habitat heterogeneity among Svalbard fjords, diatom responses to glacier melting are also expected to be complex, which will further lead to changes in the biological carbon pumping and carbon sequestration. To address the complexity, three short sediment cores were collected from three contrasting fjords in Svalbard (Krossfjorden, Kongsfjorden, Gronfjorden), recording the history of fjord changes in recent decades during significant glacier melting. The amino acid molecular indicators in cores K4 and KF1 suggested similar organic matter degradation states between these two sites. In contrast to the turbid Kongsfjorden and Gronfjorden, preserved fucoxanthin in Krossfjorden indicated a continuous increase in diatoms since the mid-1980s, corresponding to a 59â¯% increase in biological carbon pumping, as quantified by the δ13C of sedimentary organic carbon. The increasing biological carbon pumping in Krossfjorden is further attributed to its hard rock types in the glacier basin, compared to Kongsfjorden and Gronfjorden, which are instead covered by soft rocks, as confirmed by a one-dimensional model. Given the distribution of rock types among basins in Svalbard, we extrapolate our findings and propose that approximately one-fifth of Svalbard's fjords, especially those with hard rock basins and persistent marine-terminated glaciers, still have the potential for an increase in diatom fractions and efficient biological carbon pumping. Our findings reveal the complexity of fjord phytoplankton responses and biological carbon pumping to increasing glacier melting, and underscore the necessity of modifying Arctic marine carbon feedback to climate change based on results from fjords underlain by hard rocks.
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Liposomes containing phosphatidylserine (PS) are engulfed by phagocytes including macrophages, microglia, and dendritic cells. PS liposomes (PSLs) mimic the effects of apoptotic cells on these phagocytes to induce the secretion of anti-inflammatory molecules and to inhibit the maturation of dendritic cells. However, the effects of PSLs on osteoclasts, which are also differentiated from the common myeloid precursors, remain to be determined. This study investigated the effects of PSLs on the osteoclastogenesis. In the rat bone marrow culture system, osteoclast precursors phagocytosed PSLs to secrete TGF-beta1 and PGE(2), which in turn inhibited osteoclastogenesis through the downregulation of receptor activator for NF-kappaB ligand, receptor activator of NF-kappaB, ICAM-1, and CD44. Consistent with these in vitro observations, i.m. injection of PSLs significantly increased the plasma level of TGF-beta1 and PGE(2) and decreased the expression of receptor activator for NF-kappaB ligand, receptor activator of NF-kappaB, and ICAM-1 in the skeletal tissues of ankle joints of rats with adjuvant arthritis (AA). A quantitative analysis using microcomputed tomography revealed that PSLs as well as TGF-beta1 together with PGE(2) significantly inhibited AA-induced trabecular bone loss. These observations strongly suggest that PSLs generate TGF-beta1 and PGE(2) release, leading to inhibit osteoclastogenesis and AA-induced trabecular bone loss. Because PS is a component of the cell membrane, PSLs therefore can be a potentially effective pharmacological intervention against abnormal bone loss, such as osteoporosis without deleterious side effects.
Assuntos
Reabsorção Óssea/prevenção & controle , Diferenciação Celular/imunologia , Regulação para Baixo/imunologia , Inibidores do Crescimento/administração & dosagem , Inibidores do Crescimento/fisiologia , Osteoclastos/imunologia , Fosfatidilserinas/administração & dosagem , Fosfatidilserinas/fisiologia , Animais , Artrite Experimental/imunologia , Artrite Experimental/metabolismo , Artrite Experimental/patologia , Artrite Experimental/prevenção & controle , Reabsorção Óssea/imunologia , Reabsorção Óssea/metabolismo , Reabsorção Óssea/patologia , Células Cultivadas , Dinoprostona/metabolismo , Modelos Animais de Doenças , Feminino , Receptores de Hialuronatos/biossíntese , Molécula 1 de Adesão Intercelular/biossíntese , Lipossomos , Osteoclastos/metabolismo , Osteoclastos/patologia , Ligante RANK/antagonistas & inibidores , Ligante RANK/biossíntese , Ratos , Ratos Endogâmicos Lew , Receptor Ativador de Fator Nuclear kappa-B/antagonistas & inibidores , Receptor Ativador de Fator Nuclear kappa-B/biossíntese , Células-Tronco/citologia , Células-Tronco/imunologia , Células-Tronco/metabolismo , Fator de Crescimento Transformador beta1/metabolismoRESUMO
The purpose of this study was to investigate preparation, characterization and tumor-targeted effect of pH-sensitive niosomes, composed of a nonionic surfactant mixed with cholesteryl hemisuccinate (CHEMS), a derivative of cholesterol (CHOL), as a pH-sensitive molecule. CHEMS was synthesized with CHOL and succinic acid, the structure of which was analyzed by Mass spectrometry (MS) and ¹H Nuclear magnetic resonance (¹H NMR) spectrum. Niosomes were prepared via film hydration-probe ultrasound method. Both normal niosomes and pH-sensitive niosomes showed spherical morphology under transmission electron microscope (TEM) with a average particle sizes of 172 ± 6.2 nm and 153 ± 4.7 nm, respectively. The thermotropic behavior, structure changes and interaction of 5-fluorouracil (5-Fu) with other materials were characterized by differential scanning calorimetry (DSC), and the disappearance of the melting peak of drug revealed the fact that drug was encapsulated in niosomes. Bulk-equilibrium reverse-dialysis method was chosen to investigate the behavior of drug release from normal niosomes and pH-sensitive niosomes in different pH medium, and the results showed that the noisome containing CHEMS had a pH-sensitive property. Tumor-targeted effect was proved by the fact that pH-sensitive niosomes showed a remarkable high concentration in tumor site of the mice transplanted with tumor cell.
Assuntos
Antimetabólitos Antineoplásicos/administração & dosagem , Sistemas de Liberação de Medicamentos , Excipientes/química , Fluoruracila/administração & dosagem , Neoplasias/metabolismo , Animais , Antimetabólitos Antineoplásicos/química , Antimetabólitos Antineoplásicos/farmacocinética , Linhagem Celular Tumoral , Química Farmacêutica , Ésteres do Colesterol/química , Fluoruracila/química , Fluoruracila/farmacocinética , Humanos , Concentração de Íons de Hidrogênio , Lipossomos , Camundongos , Camundongos Endogâmicos , Conformação Molecular , Neoplasias/tratamento farmacológico , Tamanho da Partícula , Distribuição Aleatória , Solubilidade , Propriedades de Superfície , Tensoativos/química , Distribuição Tecidual , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
Two new compounds 1,3-O-[5-(hydroxymethyl)-furan-2-yl]methenyl-2-n-butyl-α-fructofuranoside and n-butyl-3,4-dihydroxyl-5-hydroxymethyl-4-O-[5-(hydroxymethyl)-furan-2-yl]-tetrahydrofuran-2-carboxylate were isolated from the fruits of Trichosanthes kirilowii Maxim, and their structures were established on the basis of spectroscopic methods.
Assuntos
Medicamentos de Ervas Chinesas/isolamento & purificação , Furanos/isolamento & purificação , Glicosídeos/isolamento & purificação , Plantas Medicinais/química , Trichosanthes/química , Medicamentos de Ervas Chinesas/química , Frutas/química , Furanos/química , Glicosídeos/química , Ressonância Magnética Nuclear BiomolecularRESUMO
Two new compounds, 1-deoxy-1-[2'-oxo-1'-pyrrolidinyl]-2-n-butyl-α-fructofuranoside and isoarvenin III, were isolated from the fruits of Trichosanthes kirilowii Maxim, and their structures were established on the basis of spectroscopic methods.
Assuntos
Medicamentos de Ervas Chinesas/isolamento & purificação , Furanos/isolamento & purificação , Glicosídeos/isolamento & purificação , Pirrolidinas/isolamento & purificação , Saponinas/isolamento & purificação , Trichosanthes/química , Triterpenos/isolamento & purificação , Medicamentos de Ervas Chinesas/química , Frutas/química , Furanos/química , Glicosídeos/química , Estrutura Molecular , Ressonância Magnética Nuclear Biomolecular , Pirrolidinas/química , Saponinas/química , Triterpenos/químicaRESUMO
OBJECTIVE: To evaluate the current evidence of pregnancy outcomes among couples with recurrent pregnancy loss (RPL) with abnormal karyotypes vs. those with normal karyotypes and among couples with RPL and abnormal karyotypes after receiving expectant management vs. preimplantation genetic diagnosis (PGD). DESIGN: Systematic review and meta-analysis. SETTING: Academic medical centers. PATIENT(S): Pregnancy outcomes in 6,301 couples with RPL who conceived without medical intervention in 11 studies were analyzed. However, only 2 studies addressed the outcomes of couples with RPL and abnormal karyotypes after expectant management (75 cases) vs. PGD (50 cases). INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): The pregnancy outcomes in couples with RPL with abnormal and normal karyotypes across included studies were evaluated. RESULT(S): Compared with those with a normal karyotype, a significantly lower first pregnancy live birth rate (LBR) was found in couples with RPL with abnormal karyotypes (58.5% vs. 71.9%; odds ratio [OR], 0.55; 95% confidence interval [CI], 0.46-0.65; I2 =27%). A markedly decreased first pregnancy LBR was found in couples with a translocation (52.9% vs. 72.4%; OR, 0.44; 95% CI, 0.31-0.61; I2 =33%) but not in couples with an inversion. However, the differences in accumulated LBR (81.4% vs. 74.8%; OR, 0.96; 95% CI, 0.90-1.03; I2 = 0) were nonsignificant, whereas the miscarriage rate was distinctly higher in couples with RPL and abnormal karyotypes (53.0% vs. 34.7%; OR, 2.21; 95% CI, 1.69-2.89; I2 = 0). Compared with those who chose expectant management, differences in accumulated LBR were nonsignificant (60% vs. 68%; OR, 0.55; 95% CI, 0.11-2.62; I2 =71%), whereas the miscarriage rate (24% vs. 65.3%; OR, 0.15; 95% CI, 0.04-0.51; I2 = 45) was markedly low in couples with RPL and abnormal karyotypes who chose PGD. CONCLUSION(S): Couples with RPL and abnormal karyotypes had a higher miscarriage rate than couples with normal karyotypes but achieved a noninferior accumulated LBR through multiple conception attempts. In couples with RPL and abnormal karyotypes, PGD treatment did not increase the accumulated LBR but markedly reduced miscarriage rate compared with expectant management.
Assuntos
Aborto Habitual , Diagnóstico Pré-Implantação , Gravidez , Feminino , Humanos , Resultado da Gravidez/epidemiologia , Aborto Habitual/diagnóstico , Aborto Habitual/genética , Cariótipo Anormal , PaisRESUMO
Hepatocyte nuclear factor 4 alpha (HNF4A) is a transcriptional factor which plays an important role in the development of the liver, kidney, and intestines. Nevertheless, its role in cervical cancer and the underlying mechanism remain unknown. In this study, both immunohistochemistry and western blotting revealed that the expression of HNF4A was downregulated in cervical cancer. Xenograft assays suggested that HN4A could inhibit tumorigenic potential of cervical cancer in vivo. Functional studies illustrated that HNF4A also inhibited the proliferation and viability of cervical cancer cells in vitro. In addition, FACS analysis implied that HNF4A could induce cell cycle arrest from the G0/G1 phase to S phase. Further studies suggested that HNF4A downregulated the activity of the Wnt/ß-catenin pathway. Altogether, our data demonstrated that HNF4A inhibited tumor formation and proliferation of cervical cancer cells through suppressing the activity of the Wnt/ß-catenin pathway.
Assuntos
Carcinogênese/metabolismo , Proliferação de Células/genética , Fator 4 Nuclear de Hepatócito/metabolismo , Neoplasias do Colo do Útero/metabolismo , Proteínas Wnt/metabolismo , Via de Sinalização Wnt/genética , beta Catenina/metabolismo , Animais , Carcinogênese/genética , Estudos de Casos e Controles , Pontos de Checagem do Ciclo Celular/genética , Sobrevivência Celular/genética , Regulação para Baixo/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Células HeLa , Fator 4 Nuclear de Hepatócito/genética , Humanos , Camundongos , Camundongos Nus , Transfecção , Carga Tumoral/genética , Regulação para Cima/genética , Neoplasias do Colo do Útero/genética , Neoplasias do Colo do Útero/patologia , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
Because of swainonine-producing endophytic fungal, Oxytropis glacialis is one of the main poisonous weeds in the alpine grassland and desert grassland of the Qinghai-Tibet Plateau (QTP). It has a severe impact on grassland degradation on the QTP. In this manuscript, the Internally Transcribed Spacer (ITS) region of fungal communities in the soil of the O. glacialis root system was sequenced by high-throughput sequencing and analyzed by bioinformatics methods. The physical and chemical properties of the soil samples were analyzed in combination with the fungal diversity and its relationship with the soil physical and chemical factors. The results showed that the soil fungal community in the O. glacialis root system are rich in diversity in different ecological environments and are most affected by the soil pH value and organic matter. The swainonine-producing fungal Embellisia oxytropis was first detected in the soil of the O. glacialis root system. This finding provides data to support the next step in demonstrating the horizontal spread of swainone-producing fungal from O. glacialis to soil. In addition, a stable network of core flora has a facilitating effect on the formation of O. glacialis as a dominant species in alpine ecosystems.
RESUMO
Phosphatidylserine (PS)-containing liposomes (PSLs) strongly inhibit inflammatory bone loss in adjuvant arthritic (AA) rats. This effect was attributed to the inhibition of osteoclastogenesis through the secretion of prostaglandin E(2) and transforming growth factor-ß1 by osteoclast precursors after the phagocytosis of PSLs. However, infiltrated macrophages are considered to secrete anti-inflammatory mediators after phagocytosis of PSLs, which also contribute to inhibiting osteoclastogenesis. In the present study, we have attempted to elucidate the effects of PSLs on the phenotype of infiltrated macrophages during inflammatory bone loss. In AA rats, the ankle joints swelled with the infiltration of both macrophages and helper T cells into the synovium after a complete Freund's adjuvant injection. In the ankle joints of AA rats, approximately half of the infiltrated macrophages underwent a phenotypic change from interleukin (IL)-1ß-producing to IL-10-producing cells after the phagocytosis of PSLs. In lipopolysaccharide (LPS)-stimulated macrophages, PSLs also significantly decreased IL-1ß production, but increased IL-10 production. Moreover, PSLs inhibited the rapid activation of p38 mitogen-activated protein kinases (MAPK) and nuclear factor (NF)-κB, but enhanced the delayed activation of extracellular signal-regulated kinase (ERK) in LPS-stimulated macrophages. PSL-induced different influence on the activities of p38 MAPK and ERK is a likely underlying mechanism for phenotypic change of infiltrated macrophages after the phagocytosis of PSLs. This phenotypic change may be responsible for a significant decrease in the mean mRNA level of the receptor activator of NF-κB (RANK) and the RANK ligand (RANKL) in the ankle joint of PSL-treated AA rats, resulting in the inhibition of inflammatory bone loss.
Assuntos
Artrite Experimental/fisiopatologia , Reabsorção Óssea/fisiopatologia , Citocinas/metabolismo , Lipossomos/metabolismo , Macrófagos/citologia , Fosfatidilserinas/metabolismo , Animais , Artrite Experimental/induzido quimicamente , Artrite Experimental/imunologia , Western Blotting , Diferenciação Celular/fisiologia , Primers do DNA/genética , Dinoprostona/metabolismo , Ensaio de Imunoadsorção Enzimática , Imunofluorescência , Adjuvante de Freund/toxicidade , Imuno-Histoquímica , Interleucina-10/metabolismo , Interleucina-1beta/metabolismo , Lipopolissacarídeos , Macrófagos/metabolismo , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Ligante RANK/metabolismo , Ratos , Receptor Ativador de Fator Nuclear kappa-B/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Células-Tronco/metabolismo , Fator de Crescimento Transformador beta1/metabolismoRESUMO
The leucine-rich repeat-containing G-protein-coupled receptor 6 (LGR6) is considered to be a stem cell marker in many normal tissues and promotes tissue development, regeneration, and repair. LGR6 is also related to the initiation and progression of some malignant tumors. However, the role of LGR6 in cervical cancer has not been reported. Here, immunohistochemistry and western blotting showed that LGR6 was significantly upregulated in cervical cancer, compared with the normal cervix. By analyzing The Cancer Genome Atlas database, LGR6 was found to be correlated with a poor prognosis of cervical cancer. Then, a small population of LGR6high cells isolated by using the fluorescence-activated cell sorting exhibited enhanced properties of cancer stem cells including self-renewal, differentiation, and tumorigenicity. Moreover, RNA sequencing revealed that LGR6 was correlated with the Wnt signaling pathway and TOP/FOP, reverse transcription-PCR, and western blotting further proved that LGR6 could activate the Wnt/ß-catenin signaling pathway. Interestingly, LGR6 upregulated the expression of TCF7L2 by activating the Wnt/ß-catenin pathway. Then, TCF7L2 combining with ß-catenin in the nucleus enhanced LGR6 transcription by binding the promoter of LGR6, which further activated the Wnt signaling to form a positive feedback loop. Thus, our study demonstrated that LGR6 activated a novel ß-catenin/TCF7L2/LGR6-positive feedback loop in LGR6high cervical cancer stem cells (CSCs), which provided a new therapeutic strategy for targeting cervical CSCs to improve the prognosis of cervical cancer patients.
Assuntos
Células-Tronco Neoplásicas/metabolismo , Receptores Acoplados a Proteínas G/genética , Receptores Acoplados a Proteínas G/metabolismo , Proteína 2 Semelhante ao Fator 7 de Transcrição/metabolismo , Neoplasias do Colo do Útero/patologia , beta Catenina/metabolismo , Animais , Linhagem Celular Tumoral , Retroalimentação Fisiológica , Feminino , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Células HeLa , Humanos , Camundongos , Transplante de Neoplasias , Células-Tronco Neoplásicas/patologia , Prognóstico , Regiões Promotoras Genéticas , Análise de Sequência de RNA , Regulação para Cima , Neoplasias do Colo do Útero/genética , Neoplasias do Colo do Útero/metabolismo , Via de Sinalização WntRESUMO
OBJECTIVE: To explore the expression of CD40/CD40L in multiple myeloma(MM) patients and its influence on prognosis. METHODS: Thirty patients with MM treated in Cangzhou People's Hospital from May 2016 to June 2017 were selected and divided into MM group, then 30 healthy people with a physical examination in our hospital at the same time were selected as the normal group. The serum CD40/CD40L levels of the patients in the two groups was detected by flow cytometry, and its correlation with the lymphocyte population, pathological grade and prognostic significance of MM patients was anaysis. RESULTS: The expression of CD40 in serum of the patients in MM group was significantly higher than those in normal group (P<0.05). The expression of CD40L in serum of the patients in MM group showed no significant difference as compared with those in normal group (P>0.05). The levels of CD40 and CD40L in the patients before and after chemotherapy showed no difference(P>0.05). The levels of Ts and NK cells in the patients of MM group were lower than those in normal group (P<0.05). The proportion of total B lymphocytes, Th and Th/Ts cells between the two groups showed no significant difference (P>0.05). The CD40 level was correlated with the serum total B lymphocyte level of the patients in MM group (r=0.877, P=0.005). There was a correlation with CD40L and Th cells in the serum of MM patients (r=-0.783, P=0.035). The expression of serum CD40 in the patients at phase III-IV was higher than those of the patients at phase I-II, the levels of serum CD40L in MM patients at different periods showed no significant difference(P>0.05). The survival rate of MM patients with high CD40 expression was lower than that of MM patients with low CD40 expression (χ2=1.639, P=0.201). The high level CD40 was the main factor affecting the prognosis of MM patients (95%CI: 1.156-4.125). CONCLUSION: The increasing of CD40 level in MM patients is related to the pathological grade of the patients. Chemotherapy can reduce the level of CD40. The increasing of CD40 is an important factor for the poor prognosis of MM patients. CD40L level is not meaningful for MM treatment and prognosis.
Assuntos
Antígenos CD40 , Ligante de CD40 , Linfócitos B , Humanos , Subpopulações de Linfócitos , PrognósticoRESUMO
Arcobacter is an emerging foodborne pathogen worldwide. In this study, the prevalence, antimicrobial susceptibility and genetic characteristics of Arcobacter from different sources were investigated. Eighteen A. butzleri isolates were obtained from 60 raw chicken meat samples (16/60, 27%) and 150 patients with diarrhea (2/150, 1.3%). The resistance ratios to nalidixic acid, ciprofloxacin, clindamycin, chloramphenicol, and florfenicol were 83.33% (15/18), 38.89% (7/18), 38.89% (7/18), 33.33% (6/18) and 33.33% (6/18), respectively. We performed whole genome sequencing of the 18 isolates, and we predicted antibiotic resistance genes and virulence factors by using assembled genomes through blastx analysis. Two resistance genes, bla OXA-464 and tet(H), and the C254T mutation in gyrA, were identified in the genomes of some resistant isolates. Furthermore, virulence genes, such as flgG, flhA, flhB, fliI, fliP, motA, cadF, cjl349, ciaB, mviN, pldA and tlyA, were found in all strains, whereas hecA, hecB and iroE were found in only some strains. Phylogenetic tree analysis of A. butzleri isolates on the basis of the core-genome single nucleotide polymorphisms showed that two isolates from patients with diarrhea clustered together, separately from the isolates from raw chicken and the chicken strains. This study is the first comprehensive analysis of Arcobacter isolated in Beijing.
Assuntos
Arcobacter/efeitos dos fármacos , Arcobacter/genética , Galinhas , Diarreia/microbiologia , Infecções por Bactérias Gram-Negativas/microbiologia , Infecções por Bactérias Gram-Negativas/veterinária , Doenças das Aves Domésticas/microbiologia , Idoso , Animais , Farmacorresistência Bacteriana/genética , Genes Bacterianos , Humanos , Masculino , Carne , Testes de Sensibilidade Microbiana , Filogenia , Virulência , Fatores de Virulência/genéticaRESUMO
HOXA5 is considered a regulator involved in embryonic development and cellular differentiation and a tumor suppressor. Nevertheless, its biological role in cervical carcinoma is still unclear. In the present study, immunohistochemistry showed that HOXA5 expression gradually decreased as the degree of cervical lesions deepened. Ectopic expression of HOXA5 restrained cell proliferation, decreased cell viability, and inhibited tumor formation in vitro and in vivo. Furthermore, the expression of HOXA5 could arrest cell cycle from G0/G1 to S phase. RNA-seq revealed that p21 and cyclinD1 were involved in this process. Moreover, the gene set enrichment analysis and the TOP/FOP reporter assay both suggested that HOXA5 could restrain the activity of the Wnt/ß-catenin pathway. Further study using dual-luciferase reporter assay and quantitative chromatin immunoprecipitation assay demonstrated that HOXA5 could directly bind to the TAAT motif within the promoter of TP53 by its HD domain and transactivate TP53, which can upregulate p21. Altogether, our data suggest that HOXA5 inhibits the proliferation and neoplasia via repression activity of the Wnt/ß-catenin pathway and transactivating TP53 in cervical cancer.
Assuntos
Regulação para Baixo/genética , Proteínas de Homeodomínio/metabolismo , Ativação Transcricional/genética , Proteína Supressora de Tumor p53/genética , Neoplasias do Colo do Útero/genética , Neoplasias do Colo do Útero/patologia , Via de Sinalização Wnt , Animais , Carcinogênese/genética , Carcinogênese/patologia , Pontos de Checagem do Ciclo Celular/genética , Linhagem Celular Tumoral , Proliferação de Células/genética , Ciclina D1/metabolismo , Inibidor de Quinase Dependente de Ciclina p21/metabolismo , Feminino , Regulação Neoplásica da Expressão Gênica , Proteínas de Homeodomínio/genética , Humanos , Camundongos Endogâmicos BALB C , Camundongos Nus , Modelos Biológicos , Regiões Promotoras Genéticas/genética , Regulação para Cima/genética , Via de Sinalização Wnt/genéticaRESUMO
Hexokinase 2 (HK2) is a member of the hexokinases (HK) that has been reported to be a key regulator during glucose metabolism linked to malignant growth in many types of cancers. In this study, stimulation of HK2 expression was observed in squamous cervical cancer (SCC) tissues, and HK2 expression promoted the proliferation of cervical cancer cells in vitro and tumor formation in vivo by accelerating cell cycle progression, upregulating cyclin A1, and downregulating p27 expression. Moreover, transcriptome sequencing analysis revealed that MAPK3 (ERK1) was upregulated in HK2-overexpressing HeLa cells. Further experiments found that the protein levels of p-Raf, p-MEK1/2, ERK1/2, and p-ERK1/2 were increased in HK2 over-expressing SiHa and HeLa cells. When ERK1/2 and p-ERK1/2 expression was blocked by an inhibitor (FR180204), reduced cyclin A1 expression was observed in HK2 over-expressing cells, with induced p27 expression and inhibited cell growth. Therefore, our data demonstrated that HK2 promoted the proliferation of cervical cancer cells by upregulating cyclin A1 and down-regulating p27 expression through the Raf/MEK/ERK signaling pathway.
RESUMO
Mytilopsis sallei, an invasive alien species, has strong reproductive ability and high adaptability. It can severely endanger biodiversity of intertidal ecosystem after invasion. The intertidal zones and oyster breeding areas in some coastal areas of Guangdong Province have been severely invaded by M. sallei. To examine the potential habitat of M. sallei in China, we established a potential habitat prediction model of M. sallei using Maxent and ArcGIS method for China and global scales. The model was verified by the method of receiver operating characteristic curve (ROC) analysis and field investigation. The results showed that M. sallei could distribute with high probabili-ty in the area between North and South America, South India in Asia, Sri Lanka, the south coast of the Yangtze River in China, and in Van Dimen Bay of the southern hemisphere. In China, M. sallei mainly distributed in coastal provinces south of Shanghai. The main environmental factors affecting the suitable distribution areas for M. sallei were water vapor pressure, temperature, and solar radiation. After ROC detection, the AUC values of both the training and testing sets were 0.996, indicating that the prediction reached an excellent level. Our results provide theoretical basis for the risk assessment and management of M. sallei, and complement the potential habitat prediction of invasive species in China.