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1.
Artigo em Inglês | MEDLINE | ID: mdl-34806331

RESUMO

Progesterone is an important natural hormone regulating ovulation and menstruation. The present study aimed to investigate the pharmacokinetics and safety of two formulations of progesterone in Chinese postmenopausal females under fasting and fed conditions. The study adopted a single-dose, open-label, randomized, three-period bioequivalence design. A total of 96 subjects were enrolled and randomly assigned to the fasting cohort or fed cohort. A high-fat meal (890 kcal) was used in the fed study. The reference-scaled average bioequivalence method was used for bioequivalence evaluation. A high-fat meal led to a 22-fold higher peak concentration (Cmax ) and a 7-fold higher area under the curve (AUC) while time to reach Cmax and half-life was not significantly affected. The concentration-time curve displayed double peaks suggesting the existence of enterohepatic circulation. The test/reference geometric mean ratios for Cmax and AUC under fasting and fed conditions are all within the range of 80% to 125%. All adverse events (AEs) that occurred during the trial were mild and did not cause drop-out, though these AEs occurred more frequently under fed state. In conclusion, the two formulations of progesterone are bioequivalent in Chinese subjects under fasting and fed conditions. Drug label modification regarding food effects needs further discussion.

2.
Front Cell Dev Biol ; 9: 736298, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34616742

RESUMO

Immunotherapy is a novel clinical approach that has shown clinical efficacy in multiple cancers. However, only a fraction of patients respond well to immunotherapy. Immuno-oncological studies have identified the type of tumors that are sensitive to immunotherapy, the so-called hot tumors, while unresponsive tumors, known as "cold tumors," have the potential to turn into hot ones. Therefore, the mechanisms underlying cold tumor formation must be elucidated, and efforts should be made to turn cold tumors into hot tumors. N6-methyladenosine (m6A) RNA modification affects the maturation and function of immune cells by controlling mRNA immunogenicity and innate immune components in the tumor microenvironment (TME), suggesting its predominant role in the development of tumors and its potential use as a target to improve cancer immunotherapy. In this review, we first describe the TME, cold and hot tumors, and m6A RNA modification. Then, we focus on the role of m6A RNA modification in cold tumor formation and regulation. Finally, we discuss the potential clinical implications and immunotherapeutic approaches of m6A RNA modification in cancer patients. In conclusion, m6A RNA modification is involved in cold tumor formation by regulating immunity, tumor-cell-intrinsic pathways, soluble inhibitory mediators in the TME, increasing metabolic competition, and affecting the tumor mutational burden. Furthermore, m6A RNA modification regulators may potentially be used as diagnostic and prognostic biomarkers for different types of cancer. In addition, targeting m6A RNA modification may sensitize cancers to immunotherapy, making it a promising immunotherapeutic approach for turning cold tumors into hot ones.

3.
Ecotoxicol Environ Saf ; 227: 112901, 2021 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-34673408

RESUMO

Several studies found that reduction of 5-hydroxymethylcytosine (5hmC), a marker of DNA hydroxymethylation highly enriched in developing brain, is associated with anxiety-like behaviors. This study aimed to investigate whether gestational arsenic (As) exposure induces anxiety-like behaviors in adult offspring by reducing DNA hydroxymethylation in the developing brain. The dams drank ultrapure water containing NaAsO2 (15 mg/L) throughout pregnancy. Anxiety-like behaviors were evaluated and developing brain 5hmC was detected. Results showed that anxiety-like behaviors were observed in As-exposed adult offspring. In addition, 5hmC content was reduced in As-exposed fetal brain. Despite no difference on Tet1, Tet2 and Tet3 expression, TET activity was suppressed in As-exposed fetal brain. Mechanistically, alpha-ketoglutarate (α-KG), a cofactor for TET dioxygenases, was reduced and Idh2, a key enzymatic gene for mitochondrial α-KG synthesis, was downregulated in As-exposed fetal brain. Of interest, ascorbic acid, a cofactor for TET dioxygenases, reversed As-induced suppression of TET activity. Moreover, ascorbic acid attenuated As-induced reduction of 5hmC in fetal brain. In addition, ascorbic acid alleviated As-induced anxiety-like behaviors in adult offspring. Taken together, these results suggest that gestational As exposure induces anxiety-like behaviors in adult offspring, possibly at part, by inhibiting DNA hydroxymethylation in developing brain.


Assuntos
Arsênio , 5-Metilcitosina , Ansiedade/induzido quimicamente , Arsênio/toxicidade , Encéfalo/metabolismo , DNA , Metilação de DNA , Proteínas de Ligação a DNA/genética , Proteínas Proto-Oncogênicas/genética , Proteínas Proto-Oncogênicas/metabolismo
4.
Front Cell Dev Biol ; 9: 700029, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34322486

RESUMO

Long non-coding RNAs (lncRNAs) play important roles during the initiation and progression of cancer. We identified DiGeorge Syndrome Critical Region Gene 5 (DGCR5) as a clear cell renal cell carcinoma (ccRCC) cancer- and lineage-specific lncRNA. Agarose gel electrophoresis analysis and sanger sequencing verified two main isoforms of DGCR5 in ccRCC patient tissues and cell lines. Quantitative polymerase chain reaction further demonstrated that the expression level of DGCR5 major isoform (isoform-1) was higher in ccRCC tissues than that in papillary/chromophobe RCC and other multiple solid malignant tumors. We investigate the biological functions of DGCR5 isoform-1 in ccRCC and show that DGCR5 isoform-1 exerts a tumor-promoting effect in ccRCC. DGCR5 isoform-1 is localized in cytoplasm and shares the same binding sequence to the tumor-suppressive miR-211-5p with the epithelial-to-mesenchymal transition key component SNAI. Furthermore, cellular and molecular experiments demonstrate that DGCR5 isoform-1 could sequester miR-211-5p, leading to the elevation of Snail protein and downregulation of its downstream targets and further promoting ccRCC cell proliferation and migration. Thus, our study indicates that DGCR5 isoform-1 could contribute to ccRCC progression by sponging miR-211-5p through regulating the expression of Snail protein and could serve as a reliable diagnostic biomarker in ccRCC.

5.
Plant Physiol Biochem ; 162: 656-666, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33780739

RESUMO

The growth of Dendrobium nobile is often influenced by zinc. Here, D. nobile was regularly sprayed with different concentrations (0, 50, 100, 200, 400, 800, 1000, 2000 µmol L-1) of zinc to study its effect on the growth and biosynthesis of medicinal components. Samples were taken at 0, 7, 14, and 21 days to detect physiological and medicinal components. The results showed that the net photosynthetic rate, transpiration rate, stomatal conductance, and Chl A and Chl B levels of leaves first increased and then decreased as the concentration of zinc increased. At 400 µmol L-1 concentration, these parameters reached their maximum values. Thus, a certain dose of zinc could promote the photosynthesis of D. nobile. There was an obvious increase in the synthesis of superoxide dismutase (SOD), while the content of ascorbate peroxidase and ascorbic acid (AsA) were the highest after treatment with 400 µmol L-1 zinc. Maximum levels of polysaccharides and polyphenols were observed on day 7 and 14, respectively, at a zinc concentration of 400 µmol L-1. These results suggest that exogenous zinc may promote the accumulation of medicinal components in D. nobile. It was also found that polysaccharides could combine well with zinc to form a polysaccharide-zinc chelate and transform inorganic zinc into organic form, which is stored in the form of polysaccharide-Zn and is known to reduce the damage induced by Zn stress.


Assuntos
Dendrobium , Fotossíntese , Folhas de Planta , Polissacarídeos , Zinco/farmacologia
6.
Front Pharmacol ; 11: 1281, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33013364

RESUMO

Nod-like receptor (NLR) family caspase activation and recruitment domain containing 5 (NLRC5) is a newly identified sub-class of the NLR family. It regulates inflammation and has a key function in innate and adaptive immunologic reactions. Autophagy has been reported to be crucially linked to the pathogenesis of endometriosis. Our recent study identify there is a negative correlation between NLRC5 and autophagy in endometriosis, indicating that NLRC5 and autophagy together act as promising predictors in endometriosis patients. However, the mechanism associating NLRC5 and autophagy in endometriosis is still not completely understood. We hypothesize that autophagy could be involved in NLRC5-mediated inflammation in endometriosis. In order to validate the assumption, we evaluate the effects of NLRC5 and autophagy in the inflammation of ectopic endometrial stromal cells (EESCs) of ovarian endometriosis patients, to specifically determine whether autophagy is involved in NLRC5-mediated inflammation in EESCs. Our results show that over-expression of NLRC5 results in the up-regulation of autophagy in EESCs and inhibition of NLRC5 restricts the level of autophagy in EESCs. Furthermore, over-expression of NLRC5 and promotion of autophagy inhibit interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) expressions, whereas inhibition of NLRC5 and autophagy up-regulate IL-6 and TNF-α expressions in EESCs. Additionally, promotion of autophagy contributes to the NLRC5-mediated inhibition of IL-6 and TNF-α expressions in EESCs; inhibition of autophagy restricts NLRC5-mediated inhibition of IL-6 and TNF-α expressions in EESCs. Our results suggest that over-expression of NLRC5 promotes autophagy, thereby inhibiting inflammation in ovarian endometriosis.

7.
Life Sci ; 261: 118358, 2020 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-32866518

RESUMO

Preeclampsia (PE) is a pregnancy-specific disorder characterized by the onset of hypertension and proteinuria with onset after the 20th week of gestation. The pathogenesis of PE is attributed to increased trophoblast cell death and poor trophoblast migration/invasiveness. This study investigates the function of microRNA-23a (miR-23a) in PE and its effects on migration and invasion of trophoblast cells HTR-8/SVneo. We found higher expression of miR-23a in placental tissue samples from PE pregnant women compared to samples from normal pregnant women. Enhancing miR-23a expression by its specific mimic reduced HTR-8/SVneo cell migration and invasion and increased HTR-8/SVneo cell apoptosis. The dual-luciferase reporter gene assay revealed miR-23a binding with HDAC2. We found that HDAC2 was poorly expressed in placental tissue samples from PE pregnant women, and its expression correlated inversely with miR-23a expression. HTR-8/SVneo cells showed diminished HDAC2 expression upon miR-23a elevation and increased HDAC2 expression upon miR-23a inhibition. Lentivirus-mediated HDAC2 knockdown mimicked the effects of miR-23a on HTR-8/SVneo cells and led to NF-κB activation. Similarly, HDAC2 overexpression and NF-κB inhibition both abrogated the effects of miR-23a on HTR-8/SVneo cells, suggesting that miR-23a reduced HTR-8/SVneo cell migration and invasion and increased HTR-8/SVneo cell apoptosis by HDAC2 inhibition and NF-κB activation. In summary, these results support a novel role of miR-23b in invasion and apoptosis of trophoblast cells, and imply that targeting miR-23b may be a new avenue for treating PE.


Assuntos
Movimento Celular/genética , Histona Desacetilase 2/metabolismo , NF-kappa B/metabolismo , Trofoblastos/citologia , Trofoblastos/metabolismo , Adulto , Sequência de Bases , Linhagem Celular , Regulação para Baixo/genética , Feminino , Humanos , Lentivirus/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Modelos Biológicos , Transdução de Sinais , Regulação para Cima/genética
8.
J Int Med Res ; 48(5): 300060520925352, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32431202

RESUMO

OBJECTIVE: NOD-like receptor family caspase recruitment domain family domain-containing 5 (NLRC5) is involved in the development of cancer. Our objective was to explore the role of NLRC5 in the progression of endometrial cancer (EC). METHODS: The roles of NLRC5 in migration and invasion of AN3CA EC cells were examined by cell wound-healing assay, Transwell migration, and invasion analysis. Overexpression of NLRC5 was achieved with NLRC5 plasmid, and knockdown of NLRC5 was achieved using small interfering (si)RNA-NLRC5 in AN3CA cells. The expression of NLRC5 was detected by immunohistochemical, western blot, and quantitative real-time PCR. LY294002 was used to inhibit the phosphatidylinositol 3-kinase (PI3K)/AKT signaling pathway. RESULTS: NLRC5 was downregulated in EC tissue compared with normal endometrium. Overexpression of NLRC5 led to upregulation of cell migration and invasion in AN3CA cells and expression of matrix metallopeptidase (MMP)-9. Inhibition of NLRC5 restricted migration and invasion of AN3CA cells and expression of MMP9. Overexpression of NLRC5 promoted the activation of PI3K/AKT signaling pathway. Inhibiting PI3K/AKT signaling pathway by using LY294002 blocked the positive role of NLRC5 in migration and invasion of AN3CA cells and expression of MMP9. CONCLUSIONS: These results demonstrate that NLRC5 promotes EC progression by activating the PI3K/AKT signaling pathway.


Assuntos
Neoplasias do Endométrio/patologia , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Cromonas/farmacologia , Progressão da Doença , Neoplasias do Endométrio/cirurgia , Endométrio/patologia , Endométrio/cirurgia , Feminino , Humanos , Histerectomia , Metaloproteinase 9 da Matriz/metabolismo , Pessoa de Meia-Idade , Morfolinas/farmacologia , Invasividade Neoplásica/patologia , Fosfatidilinositol 3-Quinases/metabolismo , Inibidores de Fosfoinositídeo-3 Quinase/farmacologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais/efeitos dos fármacos
9.
Reprod Toxicol ; 94: 40-47, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32330513

RESUMO

Gestational vitamin D deficiency is associated with pulmonary diseases. This study aimed to investigate the effect of gestational vitamin D deficiency on fetal lung development in mice. Absolute and relative weights of fetal lungs were reduced in vitamin D deficient (VDD) group. Incrassate mesenchyme, measured by septal wall thickness, accompanied by lessened saccular space, was shown in VDD group. Numerous immature type II pneumocytes, as determined by PAS staining, were observed in VDD group. Moreover, increased Ki67-positive cells, a marker of cell proliferation, was detected in VDD group. The additional experiments showed that Sftpa, Sftpb, Sftpc and Sftpd, four surfactant genes, were downregulated and pro-surfactant protein B was reduced in VDD group. FoxA1, FoxA2 and TTF-1, three transcription factors that regulate surfactant genes, and VEGF, a key regulator for pulmonary maturation, were downregulated in VDD group. These results suggest that gestational vitamin D deficiency impairs fetal lung development partially through suppressing type II pneumocyte differentiation.


Assuntos
Células Epiteliais Alveolares/citologia , Desenvolvimento Fetal , Pulmão/crescimento & desenvolvimento , Deficiência de Vitamina D/complicações , Células Epiteliais Alveolares/metabolismo , Animais , Diferenciação Celular , Citocinas/genética , Proteínas de Ligação a DNA/genética , Feminino , Feto , Fator 3-alfa Nuclear de Hepatócito/genética , Fator 3-beta Nuclear de Hepatócito/genética , Humanos , Antígeno Ki-67/metabolismo , Masculino , Camundongos , Gravidez , Proteínas Associadas a Surfactantes Pulmonares/genética , Proteínas Associadas a Surfactantes Pulmonares/metabolismo , Fatores de Transcrição/genética , Fator A de Crescimento do Endotélio Vascular/genética , Vitamina D/sangue , Deficiência de Vitamina D/sangue , Deficiência de Vitamina D/genética , Deficiência de Vitamina D/metabolismo , Vitaminas/sangue
10.
Int J Biol Macromol ; 153: 942-950, 2020 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-31758995

RESUMO

In order to improve the hydrophilicity and immune activity of the polysaccharide from Dendrobium nobile Lindl., non-thermal plasma was used to treat the polysaccharide. It was found that the hydrophilicity of the polysaccharide plasma-treated was significantly enhanced. Infrared spectra showed that the content of OH in the molecule increased significantly, and the monosaccharide ring changed from ß-pyran sugar to ß-furan sugar. The detection of SEM, AFM and TEM showed that the degree of cross-linking of surface molecules increased, and the arrangement of the polysaccharide was more compact and orderly. In vitro cell tests showed that the polysaccharide plasma-treated significantly improve the phagocytosis ability of RAW264.7, and promote the secretion of cytokines TNF-α, IL-6, IL-1. However, the cell proliferation test indicated that the polysaccharide did not increase the concentration of cytokines by promoting cell proliferation. RT-PCR showed that the polysaccharide plasma-treated could promote the expression of IL-1ß at the transcriptional level. These results showed that non-thermal plasma treatment can effectively enhance the hydrophilicity of the polysaccharide and enhance its immune activity in vitro. Therefore, it can be inferred that the non-thermal plasma technology can be applied to the modification of active polysaccharides and will promote active polysaccharides to work better.


Assuntos
Dendrobium/química , Fatores Imunológicos/química , Fatores Imunológicos/farmacologia , Gases em Plasma/química , Polissacarídeos/química , Polissacarídeos/farmacologia , Proliferação de Células/efeitos dos fármacos , Citocinas/genética , Citocinas/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Regulação da Expressão Gênica/imunologia , Macrófagos/citologia , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo
11.
Org Lett ; 21(6): 1794-1798, 2019 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-30802068

RESUMO

Guided by our biosynthetic hypothesis, pericoannosins C-F, four new PKS-NRPS hybrid metabolites, were discovered from the endophytic fungus Periconia sp. F-31. Their structures and absolute configurations were elucidated by extensive spectroscopic data and electronic circular dichroism analyses. Preliminary biological evaluation revealed that pericoannosins C-D exhibited anti-HIV activities with IC50 values of 15.5 and 13.5 µM. Furthermore, the bioinspired syntheses of pericoannosins C-E have also been completed with high efficiency.


Assuntos
Fármacos Anti-HIV/farmacologia , Ascomicetos/química , Policetídeo Sintases/metabolismo , Fármacos Anti-HIV/química , Dicroísmo Circular , Estrutura Molecular , Policetídeo Sintases/química
12.
Zhonghua Wei Zhong Bing Ji Jiu Yi Xue ; 30(8): 783-789, 2018 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-30220282

RESUMO

OBJECTIVE: To comprehensively evaluate the clinical efficacy of hemoperfusion (HP) combined with continuous veno-venous hemofiltration (CVVH) on acute paraquat poisoning (APP). METHODS: Literatures of Chinese and English randomized controlled trials (RCTs), case control and cohort study on HP combined with CVVH in the treatment of APP from the PubMed, Embase, Wanfang, and CNKI up to November 2017 were enrolled (the subjects were > 16 years old). The obtained literatures were strictly screened and evaluated in quality, and data such as mortality, the life time of dead patients, inefficiency rate, incidence of multiple organ dysfunction syndrome (MODS) and acute respiratory distress syndrome (ARDS) were extracted. Meta-analysis was performed by RevMan 5.3. RESULTS: Twenty-one studies were included with 2 222 subjects, among whom 976 subjects were in HP combined with CVVH group (experimental group) and 1 246 subjects in HP group (control group). Compared with control group, the mortality in experimental group were significantly decreased [43.77% (362/827) vs. 55.26% (604/1 093), odds ratio (OR) = 0.68, 95% confidential interval (95%CI) = 0.56-0.82, P = 0.000 1], the life time of death patients was significantly prolonged [mean difference (MD) = 4.63, 95%CI = 2.60-6.66, P < 0.000 01], incidence of MODS [25.93% (70/270) vs. 55.36% (155/280), OR = 0.26, 95%CI = 0.14-0.49, P < 0.000 1], and incidence of ARDS [30.37% (82/270) vs. 51.07% (143/280), OR = 0.42, 95%CI = 0.30-0.61, P < 0.000 01], and inefficiency rate [8.72% (13/149) vs. 34.64% (53/153), OR = 0.17, 95%CI = 0.09-0.34, P < 0.000 01] were significantly reduced. Funnel chart showed that except the publication bias of mortality rate, there were less publication bias about other indicators among studies. CONCLUSIONS: HP combined with CVVH can significantly reduce the mortality of patients with APP compared with HP alone on the whole, prolong the life time and reduce the occurrence of MODS and ARDS, thus improving the treatment efficiency.


Assuntos
Hemoperfusão , Adolescente , Estudos de Coortes , Hemofiltração , Humanos , Paraquat , Diálise Renal
13.
Chem Commun (Camb) ; 53(87): 11873-11876, 2017 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-29043306

RESUMO

Pd-Catalyzed denitrogenative functionalizations of benzotriazoles with alkenes and 1,3-dienes have been developed, which enable the rapid access of diverse ortho-amino styrenes and 2-vinylindolines, respectively. This study shows the great potential of benzotriazoles as a [1C]-synthon in cross-coupling reactions and an aza-[3C]-synthon in cycloaddition reactions.

14.
J Obstet Gynaecol Res ; 43(8): 1305-1316, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28586129

RESUMO

AIM: The aim of this study was to examine the reliability and validity of the Illness Perception Questionnaire-Revised (IPQ-R) in patients with stress urinary incontinence (SUI). METHODS: A total of 256 patients with SUI and 76 patients with myoma of the uterus were recruited to complete the Chinese IPQ-R. For the reliability, the key tests included Cronbach's α coefficient and intraclass correlation coefficients. For the validity, the key tests included factor analysis, Spearman's correlation coefficient, and the Student's t-test. RESULTS: Cronbach's α values ranged from 0.68 to 0.90 for each subscale and the intraclass correlation coefficients ranged from 0.80 to 0.94. The results of the confirmatory factor analysis showed that the seven-factor structure as proposed by the original IPQ-R fit the data poorly. Although removal of three items improved the model's fit, the goodness-of-fit statistics were still below acceptable standards. We identified an acceptable seven-factor solution from the 38 items on Illness Beliefs using an exploratory factor analysis (EFA), which accounted for 68.12% of the variance. For the concurrent validity, Consequences and Emotional Representation both had good correlations with anxiety and depression (r = 0.52-0.62) and better quality of life (r = 0.58-0.73). The inter-correlation coefficient of the seven factors ranged from 0.05 to 0.59, suggesting acceptable discriminant validity. There were significant differences on the scale scores of Disease Identity (t = 9.39, P < 0.01), Timeline-Acute/Chronic (t = 3.69, P < 0.01), Consequences (t = 4.53, P < 0.01), Illness Coherence (t = 7.73, P < 0.01), Timeline-Cyclical (t = 6.48, P < 0.01), Emotional Representation (t = 6.40, P < 0.01), and Cause (t = 4.29, P < 0.01) between the patients with SUI and with myoma of the uterus, which also indicated acceptable discriminant validity. CONCLUSION: The findings of this study supported the Chinese IPQ-R as being a reliable and valid tool for measuring illness perception among patients with SUI.


Assuntos
Incontinência Urinária por Estresse/psicologia , Grupo com Ancestrais do Continente Asiático , Feminino , Humanos , Pessoa de Meia-Idade , Psicometria , Inquéritos e Questionários
15.
Cell Mol Immunol ; 14(10): 850-861, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27796286

RESUMO

The role of IL-17A is important in protection against lung infection with Chlamydiae, an obligate intracellular bacterial pathogen. In this study, we explored the producers of IL-17A in chlamydial lung infection and specifically tested the role of major IL-17A producers in protective immunity. We found that γδT cells and Th17 cells are the major producers of IL-17A at the early and later stages of chlamydial infection, respectively. Depletion of γδT cells in vivo at the early postinfection (p.i.) stage, when most γδT cells produce IL-17A, failed to alter Th1 responses and bacterial clearance. In contrast, the blockade of IL-17A at the time when IL-17A was mainly produced by Th17 (day 7 p.i.) markedly reduced the Th1 response and increased chlamydial growth. The data suggest that the γδ T cell is the highest producer of IL-17A in the very early stages of infection, but the protection conferred by IL-17A is mainly mediated by Th17 cells. In addition, we found that depletion of γδ T cells reduced IL-1α production by dendritic cells, which was associated with a reduced Th17 response. This finding is helpful to understand the variable role of IL-17A in different infections and to develop preventive and therapeutic approaches against infectious diseases by targeting IL-17A.


Assuntos
Infecções por Chlamydia/imunologia , Chlamydiaceae/fisiologia , Células Dendríticas/imunologia , Interleucina-17/metabolismo , Pulmão/imunologia , Células Th1/imunologia , Células Th17/imunologia , Animais , Carga Bacteriana , Células Cultivadas , Feminino , Humanos , Imunidade Inata , Interleucina-1alfa/metabolismo , Pulmão/microbiologia , Depleção Linfocítica , Camundongos , Camundongos Endogâmicos BALB C , Receptores de Antígenos de Linfócitos T gama-delta/metabolismo
16.
Oncotarget ; 7(50): 83476-83487, 2016 Dec 13.
Artigo em Inglês | MEDLINE | ID: mdl-27825125

RESUMO

Autophagy is a conserved cellular self-digestion pathway for maintenance of homeostasis under basal and stressed conditions. Autophagy plays pivotal roles in the pathogenesis of many diseases, such as aging-related diseases, autoimmune diseases, cardiovascular diseases, and cancers. Of special note is that accumulating data suggest an intimate relationship between autophagy and ovarian carcinoma. Autophagy is well identified to act as either as a tumor-suppressor or as a tumor-promoter in ovarian carcinoma. The exact function of autophagy in ovarian carcinoma is highly dependent on the circumstances of cancer including hypoxic, nutrient-deficient, chemotherapy and so on. However, the mechanism underlying autophagy associated with ovarian carcinoma remains elusive, the precise role of autophagy in ovarian carcinoma also remains undetermined. In this review, we tried to sum up and discuss recent research achievements of autophagy in ovarian cancer. Moreover, waves of novel therapies ways for ovarian carcinoma based on the functions of autophagy were collected.


Assuntos
Antineoplásicos/uso terapêutico , Autofagia/efeitos dos fármacos , Terapia de Alvo Molecular , Neoplasias Ovarianas/tratamento farmacológico , Animais , Desenho de Fármacos , Resistencia a Medicamentos Antineoplásicos , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/metabolismo , Neoplasias Ovarianas/patologia , Transdução de Sinais/efeitos dos fármacos
17.
Pharmacogn Mag ; 12(47): 193-7, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27601849

RESUMO

OBJECTIVE: In order to investigate the antioxidant activities of polysaccharides (BPL-1 and BPL-2), one of the most important functional constituents in Brasenia schreberi was isolated from the external mucilage of B. schreberi (BPL-1) and the plant in vivo (BPL-2). This paper examines the relationship between the content of sulfuric radicals and uronic acid in BPL and the antioxidant activity of BPL. MATERIALS AND METHODS: The free radicals, 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS+) and 1,1-diphnyl-2-picrylhydrazyl (DPPH-), were used to determine the antioxidant activity of BPL. The Fourier-transform infrared spectroscopy of BPL-1 and BPL-2 revealed typical characteristics of polysaccharides. RESULTS: The two sample types had different contents. This was proved by their different adsorption peak intensities. The IC50 values of BPL-1 (31.189 mg/ml) and BPL-2 (1.863 mg/ml) showed significant DPPH radical scavenging activity. Based on the quantification of ABTS radical scavenging, the IC50 value of BPL-1 (5.460 mg/ml) was higher than that of BPL-2 (0.239 mg/ml). Therefore, in terms of the reducing power, the IC50 value of BPL-1 was too high to determine, and the IC50 value of BPL-2 was found to be 50.557 mg/ml. Hence, the antioxidant activity and total reducing power were high, and they were greater in BPL-2 than in BPL-1. In addition, BPL-2 was found to have more sulfuric radicals and uronic acid than BPL-1. CONCLUSION: The contents of sulfuric radicals and uronic acid are significantly correlated to the antioxidant activity and reducing power of BPL; the more sulfuric radicals and uronic acid, the more antioxidant activity and reducing power BPL has. SUMMARY: The water-soluble crude polysaccharides obtained from the external mucilage and the Brasenia schreberi plant in vivo were confirmed to have high contents of sulfuric radicals and uronic acidBoth BPL-1 and BPL-2 exhibited antioxidative activity and reducing power, and their antioxidative activity gradually improved with increasing concentrationsThe content of sulfuric radicals and uronic acid in BPL-1 and BPL-2 might explain their high antioxidant activity. Abbreviations used: BPL-1:Polysaccharide were isolated from the external mucilage of B. Schreberi; BPL-2: Polysaccharide were isolated from the plant in vivo of B. schreberi; BPL:Polysaccharide were isolated from B. Schreberi.

18.
Biochimie ; 123: 130-7, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26898675

RESUMO

Endometriosis is a common gynecologic disease defined as the presence of ectopic endometrial tissues on the ovaries and pelvic peritoneum, and it is a significant cause of pelvic pain, dysmenorrhea and infertility of women in their reproductive age. However, the etiology of endometriosis remains obscure. In recent years, a growing body of evidence validated that hypoxia developed a close relationship with endometriosis and the expression of hypoxia-inducible factor-1alpha (HIF-1α) was increased significantly in the development of endometriosis. Furthermore, inhibiting the expression of HIF-1α contributed to suppress endometriosis progression, suggesting HIF-1α plays a critical function in endometriosis. Nevertheless, the mechanisms by which HIF-1α associates with endometriosis are still undefined. In this brief review, we had a general understanding of HIF-1α firstly, and then we tried to sum up the collective knowledge of HIF-1α in endometriosis. Finally, we will discuss kinds of novel therapeutic approaches to endometriosis based on the functions of HIF-1α.


Assuntos
Endometriose/terapia , Adulto , Feminino , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia
19.
Tumour Biol ; 37(3): 2823-31, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26749284

RESUMO

E2F is a family of transcription factors that recognized to regulate the expression of genes essential for a wide range of cellular functions, including cell cycle progression, DNA repair, DNA replication, differentiation, proliferation, and apoptosis. E2F1, the most classic member of the E2F family, exhibits a complex role in tumor development regulation. In recent years, a growing body of data suggested an intimate relationship between E2F1 and ovarian carcinoma. And E2F1 was well identified to play dual functions and serve as a useful prognostic indicator in ovarian carcinoma. However, the mechanism underlying E2F1 associated with ovarian carcinoma remains elusive. It is necessary to clarify the fundamental role of E2F1 in ovarian carcinoma. In this review, we tried to sum up the knowledge of E2F1, including its structure and related mechanism. We also attempt to absorb the research achievements and collect the mechanism of E2F1 in ovarian carcinoma.


Assuntos
Fator de Transcrição E2F1/fisiologia , Neoplasias Ovarianas/etiologia , Fator de Transcrição E2F1/química , Feminino , Genes BRCA1 , Humanos , Proteína Supressora de Tumor p53/fisiologia
20.
Int Urol Nephrol ; 47(8): 1277-95, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-26093584

RESUMO

PURPOSE: We conducted this review to summarize the short-term and long-term efficacy of several midurethral sling procedures on quality of life (QoL) improvement based on incontinence-specific QoL measures in clinical trials among women with stress urinary incontinence (SUI). METHODS: We searched MEDLINE (January 1966 to March 2015), EMBASE (January 1988 to March 2015), and the Cochrane Incontinence Group Specialised Register (March 2015). Only randomized controlled trials (RCTs) were eligible in this analysis. RESULTS: We identified 13 different condition-specific instruments in the included 31 RCTs; the Urogenital Distress Inventory (UDI), the Incontinence Impact Questionnaire (IIQ), and Pelvic Organ Prolapse/Incontinence Sexual Function Questionnaire-12 (PISQ-12) were the most frequently used methods to measure QoL among women with SUI. We found that the improvement in sexual function (as assessed by PISQ-12) score was significantly higher in the single-incision slings group than in the TO-TVT group (WMD 1.06; 95 % CI 0.58-1.54); the post-operative pain visual analogue scale scores in the single-incision slings group was significantly lower than that in the TO-TVT group (WMD -1.59; 95 % CI -2.28 to -0.89). TO-TVT-treated patients had significantly greater reductions in total UDI scores (WMD 2.28; 95 % CI 1.77-2.80) and total IIQ scores (WMD 0.89; 95 % CI 0.26-1.52) than TVT-treated patients. The reduction in the total UDI score was significantly higher in the RP-TVT group than in the TO-TVT group (WMD -1.00; 95 % CI -1.65 to -0.35). Subgroup analysis of the total UDI score showed a significantly greater improvement in TO-TVT-treated patients than in TVT after long-term follow-up (>30 months), but no differences were detected after short-term follow-up (12-15 or 6 months). CONCLUSIONS: Our meta-analysis indicated that consistent use of the UDI and IIQ with or without the PISQ-12 might promote options for comparisons between trials. Single-incision slings were associated with significantly higher improvement in sexual function and lower post-operative pain compared with standard midurethral slings, and the long-term efficacy of TO-TVT was superior to the TVT procedure in terms of reducing the distress caused by incontinence symptoms.


Assuntos
Ensaios Clínicos como Assunto/métodos , Satisfação do Paciente , Qualidade de Vida , Slings Suburetrais , Incontinência Urinária por Estresse/psicologia , Procedimentos Cirúrgicos Urológicos/métodos , Feminino , Humanos , Inquéritos e Questionários , Incontinência Urinária por Estresse/cirurgia , Procedimentos Cirúrgicos Urológicos/psicologia
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