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Ganpu vine tea is a new type of health care citrus fruit tea made from citrus shell, Pu-er tea, and vine tea baked as raw materials. In this study, the in vitro uric acid synthase inhibition system and hyperuric acid cell model were constructed to appraise the uric acid lowering efficacy of Ganpu vine tea, traditional Ganpu tea, and vine tea. Results showed that in the uric acid synthase inhibition system, the aqueous extract can inhibite the puric metabolically related enzymes, such as adenosine deaminase (ADA), purine nucleoside phosphorylase (PNP), and xanthine oxidase (XOD). The ability of the aqueous extract to inhibit the above enzyme was as follows: vine tea > Ganpu vine tea > Ganpu tea; all teas had a strong effect on XOD inhibition. The hyperuric acid cell model test showed that the aqueous extract inhibited uric acid production through accumulating inosine and hypoxanthine and hindering xanthine synthesis. The uric acid reductive ability was as follows: Vine tea > Ganpu vine tea > Ganpu tea. The inhibition of enzymes related to uric acid synthesis and the inhibition of uric acid production were significantly enhanced through adding vine tea to Ganpu tea. It also shows that flavonoids are the main factor driving this ability because they are the main active ingredients in these botanical drinks.
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Acute respiratory failure and sudden cardiac arrest caused by acute intrathoracic infection is a fatal clinical condition with a low resuscitation success rate. The present study describes the case of a patient with acute empyema secondary to an acute lung abscess rupture, complicated by acute respiratory failure and sudden cardiac arrest caused by severe hypoxemia. The patient recovered well through the administration of multiple therapeutic measures, including medication and closed chest drainage, cardiopulmonary resuscitation, extracorporeal membrane oxygenation combined with continuous renal replacement therapy, and minimally invasive surgical resection of the lung lesion with persistent alveolar fistula as the clinical manifestation. To the best of our knowledge, the treatment of such a severe condition combined with thoracoscopic surgery has rarely been reported before, and the present study may provide insight regarding therapeutic schedules for acute respiratory failure by intrathoracic infection, and excision of ruptured lung abscess.
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Polyphenol oxidase (PPO) is a metalloenzyme with a type III copper core that is abundant in nature. As one of the most essential enzymes in the tea plant (Camellia sinensis), the further regulation of PPO is critical for enhancing defensive responses, cultivating high-quality germplasm resources of tea plants, and producing tea products that are both functional and sensory qualities. Due to their physiological and pharmacological values, the constituents from the oxidative polymerization of PPO in tea manufacturing may serve as functional foods to prevent and treat chronic non-communicable diseases. However, current knowledge of the utilization of PPO in the tea industry is only available from scattered sources, and a more comprehensive study is required to reveal the relationship between PPO and tea obviously. A more comprehensive review of the role of PPO in tea was reported for the first time, as its classification, catalytic mechanism, and utilization in modulating tea flavors, compositions, and nutrition, along with the relationships between PPO-mediated enzymatic reactions and the formation of functional constituents in tea, and the techniques for the modification and application of PPO based on modern enzymology and synthetic biology are summarized and suggested in this article.
Assuntos
Camellia sinensis , Catecol Oxidase/metabolismo , Oxirredução , CháRESUMO
BACKGROUND: Somatic cell nuclear transfer (SCNT) is used widely in cloning, stem cell research, and regenerative medicine. The type of donor cells is a key factor affecting the SCNT efficiency. OBJECTIVES: This study examined whether urine-derived somatic cells could be used as donors for SCNT in pigs. METHODS: The viability of cells isolated from urine was assessed using trypan blue and propidium iodide staining. The H3K9me3/H3K27me3 level of the cells was analyzed by immunofluorescence. The in vitro developmental ability of SCNT embryos was evaluated by the blastocyst rate and the expression levels of the core pluripotency factor. Blastocyst cell apoptosis was examined using a terminal deoxynucleotidyl transferase dUTP nick end-labeling assay. The in vivo developmental ability of SCNT embryos was evaluated after embryo transfer. RESULTS: Most sow urine-derived cells were viable and could be cultured and propagated easily. On the other hand, most of the somatic cells isolated from the boar urine exhibited poor cellular activity. The in vitro development efficiency between the embryos produced by SCNT using porcine embryonic fibroblasts (PEFs) and urine-derived cells were similar. Moreover, The H3K9me3 in SCNT embryos produced from sow urine-derived cells and PEFs at the four-cell stage showed similar intensity. The levels of Oct4, Nanog, and Sox2 expression in blastocysts were similar in the two groups. Furthermore, there is a similar apoptotic level of cloned embryos produced by the two types of cells. Finally, the full-term development ability of the cloned embryos was evaluated, and the cloned fetuses from the urine-derived cells showed absorption. CONCLUSIONS: Sow urine-derived cells could be used to produce SCNT embryos.
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Clonagem de Organismos , Técnicas de Transferência Nuclear , Animais , Blastocisto , Clonagem de Organismos/veterinária , Transferência Embrionária/veterinária , Feminino , Fibroblastos , Masculino , Técnicas de Transferência Nuclear/veterinária , SuínosRESUMO
Fu brick tea (FBT) is a microbial-fermented tea, which is produced by the solid-state fermentation of tea leaves. Previous studies have proved that FBT aqueous extracts could attenuate obesity and gut microbiota dysbiosis. However, the bioactive components in FBT that contribute to these activities remain unclear. In this study, we aimed to investigate the effects of FBT polyphenols (FBTPs) on obesity, gut microbiota, and gut microbiota-related intestinal oxidative stress and barrier function and to further investigate whether the antiobesity effect of FBTPs was dependent on the alteration of gut microbiota. The results showed that FBTP supplementation effectively attenuated obesity in high-fat diet (HFD)-fed rats. FBTP supplementation improved the intestinal oxidative stress and intestinal barrier function, including intestinal inflammation and the integrity of the intestinal barrier. Furthermore, FBTP intervention significantly attenuated HFD-induced gut microbiota dysbiosis, characterized by increased phylogenetic diversity and decreased Firmicutes/Bacteroidetes ratio. Certain core microbes, including Akkermansia muciniphila, Alloprevotella, Bacteroides, and Faecalibaculum, were also found to be improved by FBTPs. Moreover, the antiobesity effect of FBTPs was gut microbiota-dependent, as demonstrated by a fecal microbiota transplantation experiment. Collectively, we concluded that FBTPs reduced obesity by modulating the gut microbiota and gut microbiota-related intestinal oxidative stress and barrier function. Therefore, FBTPs may be used as prebiotic agents to treat obesity and gut microbiota dysbiosis in obese individuals.
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Microbioma Gastrointestinal , Animais , Camundongos , Camundongos Endogâmicos C57BL , Obesidade/tratamento farmacológico , Estresse Oxidativo , Filogenia , Polifenóis , Ratos , CháRESUMO
EGCG, as a dietary-derived antioxidant, has been extensively studied for its beneficial health effects. Nevertheless, it induces the transient increase in ROS and leads to the hormetic extension of lifespan. How exactly biology-benefiting effects with the minimum severe adverse are realized remains unclear. Here, we showed that physiological dose of EGCG could help moderate remission in health side effects exposed to high doses, including shortened lifespan, reduced body size, decreased pharyngeal pumping rate, and dysfunctional body movement in C. elegans. Furthermore, we found this result was caused by the physiological dose of EGCG to block the continued ROS accumulation and triggered acclimation responses after stressor removal. Also, in this process, we observed that EGCG downregulated the key redox protein MEMO-1 to activate the feedback loop of NADPH oxidase-mediated redox signaling. Our data indicates that the feedback signal induced by NADPH oxidase may contribute to the health-protective mechanism of dietary polyphenols in vivo.
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Proteínas de Caenorhabditis elegans/fisiologia , Caenorhabditis elegans/fisiologia , Catequina/análogos & derivados , Peptídeos e Proteínas de Sinalização Intracelular/fisiologia , Animais , Catequina/metabolismoRESUMO
Cigarette smoke- (CS-) induced oxidative stress and inflammation in the lung are serious health problems. Primary and reprocessed tea products contain multiple antioxidants that have been reported to protect the lung against CS-induced injury. However, the beneficial effects of Eurotium cristatum fermented loose dark tea (ECT) and Eurotium cristatum particle metabolites (ECP) on CS-induced lung injury and its potential hepatic metabolic detoxification are still unclear. Therefore, sixty mice were randomly divided into six equal groups. CS-exposed mice were prevented or treated with ECP or ECT infusions for 12 or 8 weeks to determine the antioxidative stress, anti-inflammatory and potential metabolic detoxification of ECT and ECP. Thirty-six mice were randomly divided into six equal groups to observe the effects on hepatic metabolic detoxification by replacing daily drinking water with ECT. Results showed that CS significantly decreased the activities of glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) and upregulated the expressions of malondialdehyde (MDA), tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6), IL-8, and IL-1ß in serum. These adverse effects were modulated by ECP and ECT. In addition, ECT upregulated the mRNA expression of pregnane X receptor (PXR) and cytochrome P450 (CYP450) in the liver on daily free drinking ECT mice group. Western blot analysis further revealed that in CS-exposed mice, ECP and ECT significantly decreased the phosphorylation of mitogen-activated protein kinase (MAPK) in the lung but upregulated the protein expressions of PXR and aryl hydrocarbon receptor (AhR) in the liver. Overall, our findings demonstrated that ECT and ECP protected against lung injury induced by CS via MAPK pathway and enhanced hepatic metabolic detoxification via PXR and AhR pathways. Therefore, daily intake of ECT and ECP can potentially protect against CS-induced oxidative and inflammatory injuries.
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Aspergillus/classificação , Fumar Cigarros/metabolismo , Lesão Pulmonar/tratamento farmacológico , Pulmão/metabolismo , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Desintoxicação Metabólica Fase I , Extratos Vegetais/farmacologia , Receptor de Pregnano X/metabolismo , Receptores de Hidrocarboneto Arílico/metabolismo , Transdução de Sinais/efeitos dos fármacos , Animais , Fumar Cigarros/patologia , Feminino , Pulmão/patologia , Lesão Pulmonar/metabolismo , Camundongos , Extratos Vegetais/químicaRESUMO
Lung cancer, especially lung adenocarcinoma, is one of the most common neoplasms worldwide. However, the mechanisms underlying its initiation, development, and metastasis are still poorly understood. Destrin (DSTN) is a member of ADF/cofilin family. Its detailed biological function remains unknown, although it is reported that DSTN is involved in cytoskeleton remodeling and regulation of actin filament turnover. Recent evidence has shown that high expression of cofilin-1 is associated with invasion and poor prognosis of several types of human tumors, but the detailed mechanism is still entirely unclear, particularly in lung cancer tumorigenesis and malignancy. Here, we report that DSTN was highly expressed in a mouse lung cancer model induced by urethane and in clinical lung adenocarcinoma tissue samples. Its expression level was positively correlated with cancer development, as well as metastasis to the liver and lymph nodes. Consistently, it was directly associated with the poor prognosis of lung adenocarcinoma patients. Furthermore, we also found that DSTN promotes cell proliferation, invasion, and migration in vitro, and facilitates subcutaneous tumor formation and lung metastasis via intravenous injection in vivo. Mechanically, DSTN associates with and facilitates nuclear translocation of ß-catenin, which promotes epithelial-to-mesenchymal transition (EMT). Taken together, our results indicated that DSTN enhances lung cancer malignancy through facilitating ß-catenin nuclear translocation and inducing EMT. Combined with multivariate analyses, DSTN might potentially serve as a therapeutic target and an independent prognostic marker of lung adenocarcinoma. IMPLICATIONS: This finding indicates that DSTN facilitates ß-catenin nuclear translocation and promotes malignancy in lung adenocarcinoma.
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Adenocarcinoma de Pulmão/patologia , Destrina/genética , Destrina/metabolismo , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/secundário , Neoplasias Pulmonares/patologia , beta Catenina/metabolismo , Células A549 , Adenocarcinoma de Pulmão/induzido quimicamente , Adenocarcinoma de Pulmão/genética , Adenocarcinoma de Pulmão/metabolismo , Animais , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Progressão da Doença , Transição Epitelial-Mesenquimal , Feminino , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Neoplasias Pulmonares/induzido quimicamente , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Masculino , Camundongos , Transplante de Neoplasias , Prognóstico , Análise de Sobrevida , Regulação para Cima , Uretana/efeitos adversos , Via de Sinalização WntRESUMO
Processing of dark tea varieties, such as Fu brick tea, Liupao tea, Qianliang tea, and Qing brick tea, includes solid-state fermentation involving microorganisms. In this study, we analyzed the major chemical constituents of dark tea extracts and evaluated their modulatory effect on the gastrointestinal function in normal mice, including the improvement of gastrointestinal transit and intestinal microbial, as well as the attenuation of intestinal microbial dysbiosis and intestinal pathological damage, and the adjustment of immune function in antibiotic-treated mice. Substantial differences in major chemical constituents, including total polyphenols, total organic acids, water extract content, 18 free amino acids, gallic acid, and six tea catechins, were observed among Fu brick tea, Qianliang tea, Qing brick tea, and Liupao tea extracts. Extracts from the four dark tea varieties significantly promoted gastrointestinal transit and colonization of beneficial Bifidobacterium and Lactobacillus, and inhibited the growth of harmful Escherichia coli and Enterococcus in normal mice. In addition, Qianliang tea, Qing brick tea, and Liupao tea extracts significantly accelerated the reversal of the ampicillin sodium-induced pathological damage in the ileum, intestinal bacterial dysbiosis (Bifidobacterium, Lactobacillus, E. coli, and Enterococcus), and low immunity.
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Trânsito Gastrointestinal/efeitos dos fármacos , Microbiota/efeitos dos fármacos , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Chá/química , Animais , Disbiose , Masculino , CamundongosRESUMO
PURPOSE: Data from in vitro and animal studies support the preventive effect of tea (Camellia sinensis) against colorectal cancer. Further, many epidemiologic studies evaluated the association between tea consumption and colorectal cancer risk, but the results were inconsistent. We conducted a meta-analysis of prospective cohort studies to systematically assess the association between tea consumption and colorectal cancer risk. METHODS: A comprehensive literature review was conducted to identify the related articles by searching PubMed and Embase up to June, 2019. Summary relative risks (RRs) and 95% confidence intervals (CIs) were calculated using a fixed effect model. RESULTS: Twenty cohort articles were included in the present meta-analysis involving 2,068,137 participants and 21,437 cases. The combined RR of colorectal cancer for the highest vs. lowest tea consumption was determined to 0.97 (95% CI 0.94-1.01) with marginal heterogeneity (I2 = 24.0%, P = 0.093) among all studies. This indicated that tea consumption had no significant association with colorectal cancer risk. Stratified analysis showed that no significant differences were found in all subgroups. We further conducted the gender-specific meta-analysis for deriving a more precise estimation. No significant association was observed between tea consumption and colorectal cancer risk in male (combined RR = 0.97; 95% CI 0.90-1.04). However, tea consumption had a marginal significant inverse impact on colorectal cancer risk in female (combined RR = 0.93; 95% CI 0.86-1.00). Further, we found a stronger inverse association between tea consumption and risk of colorectal cancer among the female studies with no adjustment of coffee intake (RR: 0.90; 95% CI 0.82-1.00, P < 0.05) compared to the female studies that adjusted for coffee intake (RR = 0.97; 95% CI 0.87-1.09, P > 0.05). CONCLUSIONS: Our finding indicates that tea consumption has no significant impact on the colorectal cancer risk in both genders combined, but gender-specific meta-analysis shows that tea consumption has a marginal significant inverse impact on colorectal cancer risk in female.
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Neoplasias Colorretais , Chá , Café , Estudos de Coortes , Neoplasias Colorretais/epidemiologia , Neoplasias Colorretais/prevenção & controle , Feminino , Humanos , Masculino , Estudos Prospectivos , Risco , Fatores de RiscoRESUMO
OBJECTIVES: To date, many efforts have been made to establish porcine embryonic stem (pES) cells without success. Extraembryonic endoderm (XEN) cells can self-renew and differentiate into the visceral endoderm and parietal endoderm. XEN cells are derived from the primitive endoderm of the inner cell mass of blastocysts and may be an intermediate state in cell reprogramming. MATERIALS AND METHODS: Porcine XEN cells (pXENCs) were generated from porcine pluripotent stem cells (pPSCs) and were characterized by RNA sequencing and immunofluorescence analyses. The developmental potential of pXENCs was investigated in chimeric mouse embryos. RESULTS: Porcine XEN cells derived from porcine pPSCs were successfully expanded in N2B27 medium supplemented with bFGF for least 30 passages. RNA sequencing and immunofluorescence analyses showed that pXENCs expressed the murine and canine XEN markers Gata6, Gata4, Sox17 and Pdgfra but not the pluripotent markers Oct4, Sox2 and TE marker Cdx2. Moreover, these cells contributed to the XEN when injected into four-cell stage mouse embryos. Supplementation with Chir99021 and SB431542 promoted the pluripotency of the pXENCs. CONCLUSIONS: We successfully derived pXENCs and showed that supplementation with Chir99021 and SB431542 confer them with pluripotency. Our results provide a new resource for investigating the reprogramming mechanism of porcine-induced pluripotent stem cells.
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Endoderma/citologia , Endoderma/embriologia , Suínos/embriologia , Animais , Técnicas de Cultura de Células , Diferenciação Celular , Linhagem Celular , Técnicas de Cocultura , Cães , Células-Tronco Embrionárias/citologia , Células-Tronco Embrionárias/metabolismo , Endoderma/metabolismo , Expressão Gênica , Camundongos , Células-Tronco Pluripotentes/citologia , Células-Tronco Pluripotentes/metabolismo , Análise de Sequência de RNA , Transdução de Sinais , Suínos/genética , Suínos/metabolismo , Quimeras de TransplanteRESUMO
Epigallocatechin-3-O-(3-O-methyl) gallate (EGCG3"Me) in tea (Camellia sinensis (L.) O. Kuntze) is a major source of O-methylated catechin and renowned for a wide range of health effects. However, the transcriptional regulation mechanisms of EGCG3"Me biosynthesis remain unclear. In the present work, the basic Helix-Loop-Helix (bHLH) transcription factor, designated as CsbHLH62, belonging to GBOF group of bHLH families, was isolated and characterized from Camellia sinensis. CsbHLH62 contains an Open Reading Frame of 1662â¯bp and encodes a polypeptide of 553 amino acids. Subcellular location and transcriptional activity analysis showed it as a nucleus protein and possessed transcriptional inhibition activity. Furthermore, the expression of CsbHLH62 was decreased during EGCG3"Me accumulation. More importantly, E-box motifs (5'-CANNTG-3') were found in the promoters of CCoAOMT, CsLAR, and CsDFR, and further transient expression assays showed that CsbHLH62 repressed the transcription of CCoAOMT, CsLAR, and CsDFR. Collectively, these results suggest that CsbHLH62 acts as a transcriptional repressor that might be negatively affecting the accumulation of EGCG3"Me. These findings provide novel insights into the regulatory mechanism of EGCG3"Me biosynthesis, which might help to breed high EGCG3"Me-content tea plants.
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Camellia sinensis/genética , Ácido Gálico/análogos & derivados , Proteínas de Plantas/genética , Transcrição Gênica/genética , Catequina/genética , Ácido Gálico/metabolismo , Regulação da Expressão Gênica de Plantas/genética , Metiltransferases/metabolismo , Fases de Leitura Aberta/genética , Folhas de Planta/genética , Folhas de Planta/metabolismo , Regiões Promotoras Genéticas/genética , Chá/genética , Chá/metabolismoRESUMO
Human genetic and pharmacological studies have demonstrated that voltage-gated sodium channels (VGSCs) are promising therapeutic targets for the treatment of pain. Spider venom contains many toxins that modulate the activity of VGSCs. To date, only 0.01% of such spider toxins has been explored, and thus there is a great potential for discovery of novel VGSC modulators as useful pharmacological tools or potential therapeutics. In the current study, we identified a novel peptide, µ-TRTX-Ca1a (Ca1a), in the venom of the tarantula Cyriopagopus albostriatus. This peptide consisted of 38 residues, including 6 cysteines, i.e. IFECSISCEIEKEGNGKKCKPKKCKGGWKCKFNICVKV. In HEK293T or ND7/23 cells expressing mammalian VGSCs, this peptide exhibited the strongest inhibitory activity on Nav1.7 (IC50 378 nM), followed by Nav1.6 (IC50 547 nM), Nav1.2 (IC50 728 nM), Nav1.3 (IC50 2.2 µM) and Nav1.4 (IC50 3.2 µM), and produced negligible inhibitory effect on Nav1.5, Nav1.8, and Nav1.9, even at high concentrations of up to 10 µM. Furthermore, this peptide did not significantly affect the activation and inactivation of Nav1.7. Using site-directed mutagenesis of Nav1.7 and Nav1.4, we revealed that its binding site was localized to the DIIS3-S4 linker region involving the D816 and E818 residues. In three different mouse models of pain, pretreatment with Cala (100, 200, 500 µg/kg) dose-dependently suppressed the nociceptive responses induced by formalin, acetic acid or heat. These results suggest that Ca1a is a novel neurotoxin against VGSCs and has a potential to be developed as a novel analgesic.
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Analgésicos/farmacologia , Proteínas de Artrópodes/farmacologia , Neurotoxinas/farmacologia , Venenos de Aranha/farmacologia , Aranhas/química , Sequência de Aminoácidos , Analgésicos/isolamento & purificação , Analgésicos/metabolismo , Animais , Proteínas de Artrópodes/isolamento & purificação , Proteínas de Artrópodes/metabolismo , Linhagem Celular Tumoral , Gânglios Espinais/efeitos dos fármacos , Células HEK293 , Humanos , Camundongos Endogâmicos C57BL , Canal de Sódio Disparado por Voltagem NAV1.7/genética , Canal de Sódio Disparado por Voltagem NAV1.7/metabolismo , Neurônios/efeitos dos fármacos , Neurotoxinas/isolamento & purificação , Neurotoxinas/metabolismo , Periplaneta , Ligação Proteica , Venenos de Aranha/isolamento & purificação , Venenos de Aranha/metabolismo , Bloqueadores do Canal de Sódio Disparado por Voltagem/isolamento & purificação , Bloqueadores do Canal de Sódio Disparado por Voltagem/metabolismo , Bloqueadores do Canal de Sódio Disparado por Voltagem/farmacologiaRESUMO
With the rapid development of stem cell research, the demands for high quality stem cells in cell differentiation studies, cell therapy and clinical applications increase significantly. Human umbilical cord mesenchymal stem cells (hUCMSCs) hold great potentials in these applications due to its wide availability, self-renewal capacity, good pluripotency, and in particular, self-immunomodulation ability. However, the conventional adherent culture system remains challenging in mass production of high-quality stem cells. In this study, we set up a 3D suspension culture system by using spinner flasks added with microcarrier. By optimizing the seeding density and rotation speed, we achieved a cell density as higher as 7×10 8cells/L per vessel. The cultured MSCs had good viability, and the expression levels of the MSC markers were similar to those of 2D-cultured MSCs. After being transferred back into a 2D culture system, the MSCs still maintained normal morphology and proliferation ability. These results indicated that the 3D suspension culture system established in this study provides a fundamental basis for mass production of high-quality MSCs for future research and clinical applications.
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Técnicas de Cultura de Células , Células-Tronco Mesenquimais/citologia , Cordão Umbilical/citologia , Diferenciação Celular , Proliferação de Células , Células Cultivadas , HumanosRESUMO
The epithelial-mesenchymal transition (EMT) is a multifunctional cell process involved in the pathogenesis of numerous conditions, including fibrosis and cancer. Idiopathic pulmonary fibrosis (IPF) is a progressive and fatal disease characterized by fibroblast accumulation and collagen deposition in the lungs. The fibroblasts involved in this process partially originate from lung epithelial cells via the EMT. Evidence suggests that the EMT contributes to progression, invasion, and metastasis of various types of cancer. We screened a series of 80 compounds for the ability to interfere with the EMT and potentially be applied as a therapeutic for IPF and/or lung cancer. We identified 2-aminopurine (2-AP), a fluorescent analog of guanosine and adenosine, as a candidate in this screen. Herein, we demonstrate that 2-AP can restore E-cadherin expression and inhibit fibronectin and vimentin expression in TGF-ß1-treated A549 lung cancer cells. Moreover, 2-AP can inhibit TGF-ß1-induced metastasis of A549 cells. This compound significantly attenuated bleomycin (BLM)-induced pulmonary inflammation, the EMT, and fibrosis. In addition, 2-AP treatment significantly decreased mortality in a mouse model of pulmonary fibrosis. Collectively, we determined that 2-AP could inhibit metastasis in vitro by suppressing the TGF-ß1-induced EMT and could attenuate BLM-induced pulmonary fibrosis in vivo. Results of this study suggest that 2-AP may have utility as a treatment for lung cancer and pulmonary fibrosis.
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The green tea polyphenol epigallocatechin-3-gallate (EGCG) is widely consumed as a dietary supplement. Its potential properties include slowing aging and extending lifespan, although how exactly this is achieved remains unclear. Here, we report that EGCG promoted healthy lifespan in Caenorhabditis elegans when administered throughout or only at early-to-mid adulthood. Specifically, EGCG extended lifespan in an inverted U-shaped dose-response manner. The life-extending mechanism was stimulated by EGCG-induced production of reactive oxygen species (ROS). Additionally, EGCG triggered mitochondrial biogenesis to restore mitochondrial function. The EGCG-induced increase in lifespan depends on known energy sensors such as AMPK/AAK-2, as well as SIRT1/SIR-2.1 and FOXO/DAF-16. Interestingly, aging decreased the response to EGCG and progressively neutralized its beneficial effects on longevity. Collectively, our findings link EGCG to the process of mitohormesis and suggest an inducible, AMPK/SIRT1/FOXO-dependent redox signaling module that could be invoked in different contexts to extend healthy lifespan. Its effectiveness is higher in younger adults and declines with age.
Assuntos
Caenorhabditis elegans/efeitos dos fármacos , Catequina/análogos & derivados , Longevidade/efeitos dos fármacos , Envelhecimento/efeitos dos fármacos , Animais , Caenorhabditis elegans/fisiologia , Catequina/química , Catequina/farmacologia , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Biogênese de Organelas , Espécies Reativas de Oxigênio/metabolismo , Chá/químicaRESUMO
The antibacterial effects of tea polyphenol epigallocatechin gallate (EGCG), a common phytochemical with a number of potential health benefits, are well known. However, the mechanism of its bactericidal action remains unclear. Using E. coli as a model organism, it is argued here that H2O2 synthesis by EGCG is not attributed to its inhibitory effects. In contrast, the bactericidal action of EGCG was a result of increased intracellular reactive oxygen species and blunted adaptive oxidative stress response in E. coli due to the co-administration of antioxidant N-acetylcysteine, and not on account of exogenous catalase. Furthermore, we noted a synergistic bactericidal effect for EGCG when combined with paraquat. However, under anaerobic conditions, the inhibitory effect of EGCG was prevented. In conclusion, EGCG caused an increase in endogenous oxidative stress in E. coli, thereby inhibiting its growth, and hence the use of EGCG as a prooxidant is supported by this study.
Assuntos
Catequina/análogos & derivados , Escherichia coli/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Polifenóis/farmacologia , Chá/química , Acetilcisteína/farmacologia , Antioxidantes/farmacologia , Catalase/metabolismo , Catequina/farmacologia , Peróxido de Hidrogênio/química , Espécies Reativas de Oxigênio/metabolismoRESUMO
OBJECTIVE: To investigate the clinical application value of 8.5/11.5 F transurethral seminal vesiculoscopy in the diagnosis and treatment of refractory hematospermia. METHODS: We retrospectively analyzed 78 cases of refractory hematospermia diagnosed and treated by 8.5/11.5 F transurethral seminal vesiculoscopy from June 2012 to June 2014. The patients underwent serum PSA examination, transrectal ultrasonography, seminal vesicle ultrasonography, and pelvis CT or MRI before surgery, and all received transurethral seminal vesiculoscopy under the 8.5/11.5 F rigid ureteroscope. RESULTS: Operations were all successfully accomplished, which revealed abnormal opening of the ejaculatory duct in 5 cases, mucosal inflammatory hyperemia in the prostatic utricle and seminal vesicle in 78, dark red mucilage substance in the seminal vesicle in 34, seminal vesicle stones in 19, small polyp in the seminal vesicle in 2, and ejaculatory duct or seminal vesicle cyst in 4. All the patients received symptomatic treatment during the surgery. After surgery, hematouria was found in 13 cases, which disappeared within 2 weeks, pelvic hematoma in 1 case, which was cured by conservative treatment within 3 months, and epididymitis in 2 cases, which was controlled by anti-infection treatment. Hematospermia recurred in 3 cases during the 1-year postoperative follow-up. CONCLUSION: 8.5/11.5 F transurethral seminal vesiculoscopy, with its advantages of easy operation, wide field of vision, large channel for operation, and few complications, deserves general clinical application in the diagnosis and treatment of refractory hematospermia.
Assuntos
Hemospermia/diagnóstico , Hemospermia/terapia , Cálculos , Ductos Ejaculatórios , Endoscopia/métodos , Epididimite/etiologia , Humanos , Imageamento por Ressonância Magnética , Masculino , Período Pós-Operatório , Recidiva , Estudos Retrospectivos , Glândulas Seminais , Tomografia Computadorizada por Raios X , UretraRESUMO
The aim of the study was to evaluate risk factors for long-term mortality and progressive chronic kidney disease (CKD) after cardiac surgery in patients with normal preoperative renal function and postoperative acute kidney injury (AKI). From April 2009 to December 2012, we prospectively enrolled 3245 cardiac surgery patients of our hospital. The primary endpoints included survival rates and the secondary endpoint was the incidence of progressive chronic kidney disease (CKD) in a follow-up period of 2 years. Acute kidney injury was staged by KDIGO classification. Progressive CKD was defined as GFR ≤ 30âmL/min/1.73âm or end-stage renal disease (ESRD) (starting renal replacement therapy or renal transplantation).The AKI incidence was 39.9% (nâ=â1295). The 1 and 2 year overall survival (OS) rates of AKI patients were significantly lower than that for non-AKI patients (85.9% and 82.3% vs 98.1% and 93.7%, Pâ<â0.001), even after complete recovery of renal function during 2 years after intervention (Pâ<â0.001). The 2-year overall survival (OS) rates of patients with AKI stage 1, 2, and 3 were 89.9%, 78.6%, and 61.4% (Pâ<â0.001), respectively. Multivariate Cox regression analysis of factors for 2-year survival rates revealed that besides age (Pâ<â0.001), chronic cardiac failure (Pâ<â0.001), diabetes (Pâ<â0.001), cardiopulmonary bypass time (Pâ<â0.01), and length of intensive care unit (ICU) stay (Pâ=â0.004), AKI was a significant risk factor for reducing 2-year survival rates even after complete recovery of renal function (Pâ<â0.001). The accumulated progressive CKD prevalence was significantly higher in AKI than in non-AKI patients (6.8% vs 0.2%, Pâ<â0.001) in the 2 years after surgery. Even with complete recovery of renal function at discharge, AKI was still a risk factor for accumulated progressive CKD (RR 1.92, 95% CI 1.37-2.69).The 2-year mortality and progressive CKD incidence even after complete recovery of renal function were significantly increased in cardiac surgery patients with postoperative AKI.
Assuntos
Injúria Renal Aguda/etiologia , Injúria Renal Aguda/mortalidade , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Progressão da Doença , Complicações Pós-Operatórias/mortalidade , Insuficiência Renal Crônica/mortalidade , Injúria Renal Aguda/fisiopatologia , Adulto , Fatores Etários , Idoso , Comorbidade , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Duração da Cirurgia , Complicações Pós-Operatórias/fisiopatologia , Fatores de Risco , Índice de Gravidade de Doença , Fatores Sexuais , Análise de SobrevidaRESUMO
PURPOSE: To describe a new technique for staged hypospadias repair in which the urethral plate is divided and tubularized transverse island flap prefabricated partial distal urethral at the time of the first stage. MATERIALS AND METHODS: Sixteen patients with proximal hypospadias associated with severe chordee were operated on using a new staged technique. At the time of the first stage, the urethral plate was divided and chordee was corrected. Then tubularized transverse island flap was used to prefabricate partial distal urethra. The defective urethra was repaired using the Thiersch-Duplay principle at the second stage. RESULTS: All participants have completed both stages of the operation. The mean follow-up duration was 18.4 months (range from 6 to 72 months). In the first-stage surgery, the modified tabularized transverse preputial island flap was performed on 6 patients, whereas the modified preputial double-faced island flap was performed on the other 10 patients. All of the prefabricated partial distal neourethras had no evidence of stenosis or scarring. The result of the second-stage procedure was a complete penis with integrated urethral. All patients were satisfied with cosmetic and functional results. Neither stricture nor diverticula was observed. A good urinary stream during the urination was attained in 12 (75.0%) patients. Four cases (25.0%) developed urethrocutaneous fistula after the second stage repair. CONCLUSIONS: In our preliminary series, this procedure improved functional and cosmetic results. It may be applicable to most cases of proximal hypospadias. Even when complications occur, they are less severe compared to those of the traditional staged approach.