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1.
Bioresour Technol ; : 126367, 2021 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-34801717

RESUMO

Cosolvent Enhanced Lignocellulosic Fractionation (CELF) is an emerging solvolysis pretreatment to fractionate lignocellulosic biomass. Herein, the bioconversion performance of CELF lignin was fully evaluated for the first time. Results showed that CELF lignin possessed higher content of carboxylic acid OH, lower molecular weight, and disappeared ß-O-4 and ß-5 linkages compared to other two technical lignins including a conventional ethanol organosolv lignin (EOL) and a kraft lignin (KL). Rhodococcus opacus PD630 cell count from CELF lignin fermentation reached the highest value of 3.9 × 107 CFU/mL, representing a 62.5% and 77.3% improvement over EOL and KL, respectively. Correspondingly, lipid yield reached 143 mg/L from CELF lignin, which was 36.2% and 26.5% higher than from EOL and KL, respectively. Principal component analysis (PCA) revealed that more carboxylic acid groups and lower molecular weight contributed to the enhanced bioconversion performance of CELF lignin. This study demonstrates that CELF lignin is a promising candidate for bioconversion.

2.
Artigo em Inglês | MEDLINE | ID: mdl-34567221

RESUMO

Background: Parkinson's disease (PD) is the second most common neurodegenerative disease worldwide, which currently lacks disease-modifying therapy to slow down its progression. Idebenone, a coenzyme Q10 (CQ10) analogue, is a well-known antioxidant and has been used to treat neurological disorders. However, the mechanism of Idebenone on PD has not been fully elucidated. This study aims to predict the potential targets of Idebenone and explore its therapeutic mechanism against PD. Method: We obtained potential therapeutic targets through database prediction, followed by Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis. Next, we constructed and analyzed a protein-protein interaction network (PPI) and a drug-target-pathway-disease network. A molecular docking test was conducted to identify the interactions between Idebenone and potential targets. Lastly, a PD cell line of SH-SY5Y overexpressing mutant α-synuclein was used to validate the molecular mechanism. Result: A total of 87 targets were identified based on network pharmacology. The enrichment analysis highlighted manipulation of MAP kinase activity and the PI3K-AKT signaling pathway as potential pharmacological targets for Idebenone against PD. Additionally, molecular docking showed that AKT and MAPK could bind tightly with Idebenone. In the cell model of PD, Idebenone activated autophagy and promoted α-synuclein degradation by suppressing the AKT/mTOR pathway. Pretreating cells with chloroquine (CQ) to block autophagic flux could diminish the pharmacological effect of Idebenone to clear α-synuclein. Conclusion: This study demonstrated that Idebenone exerts its anti-PD effects by enhancing autophagy and clearance of α-synuclein, thus providing a theoretical and experimental basis for Idebenone therapy against PD.

3.
Aging Cell ; 20(10): e13483, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34587364

RESUMO

The senescence-associated secretory phenotype (SASP) is a striking characteristic of senescence. Accumulation of SASP factors causes a pro-inflammatory response linked to chronic disease. Suppressing senescence and SASP represents a strategy to prevent or control senescence-associated diseases. Here, we identified a small molecule SR9009 as a potent SASP suppressor in therapy-induced senescence (TIS) and oncogene-induced senescence (OIS). The mechanism studies revealed that SR9009 inhibits the SASP and full DNA damage response (DDR) activation through the activation of the NRF2 pathway, thereby decreasing the ROS level by regulating the expression of antioxidant enzymes. We further identified that SR9009 effectively prevents cellular senescence and suppresses the SASP in the livers of both radiation-induced and oncogene-induced senescence mouse models, leading to alleviation of immune cell infiltration. Taken together, our findings suggested that SR9009 prevents cellular senescence via the NRF2 pathway in vitro and in vivo, and activation of NRF2 may be a novel therapeutic strategy for preventing cellular senescence.

4.
Toxicol Appl Pharmacol ; 426: 115641, 2021 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-34242568

RESUMO

Bisphenol-A (BPA) is an environmental endocrine disruptor and impairs learning and memory. However, the direct evidence for BPA exposure affecting neural circuits has been limited. In this study, a virus tracing assay has been established to explore the brain's neural circuits. Thy1-Cre mice were used to investigate the effects of BPA on the neural projection of glutamatergic pyramidal neurons in hippocampal CA1 based on Thy1 promoter. These transgenic mice were orally exposed to BPA (0, 0.5 mg/kg/day) from postnatal day (PND) 0 to PND60 and then subjected to behavioral tests. Morris water maze(MWM)and Barnes maze's showed that the spatial memory was seriously impaired in BPA exposed Thy1-Cre mice. Virus tracing assay indicated that CA1 pyramidal neurons mainly received neural inputs from hippocampal CA3, entorhinal cortex (EC), and medial septum (MS). The analysis showed that BPA reduced the number of RV+ neurons in CA3 and EC but not MS. The immunohistochemistry experiment displayed that BPA decreased the percentage of CaMKIIRV+ cells in CA3 and EC. The results demonstrated that the synaptic connection of upstream glutamatergic neurons and CA1 pyramidal cells was weakened by BPA exposure. These point to potentially detrimental effects of BPA exposure on the excitatory neural circuit of CA3-CA1 and EC-CA1 in memory formation. Thus, our findings revealed that the decrease in excitatory neural circuits of CA3-CA1 and EC-CA1 contribute to the BPA-induced spatial memory deficits in Thy1-Cre mice.


Assuntos
Compostos Benzidrílicos/toxicidade , Disruptores Endócrinos/toxicidade , Hipocampo/efeitos dos fármacos , Transtornos da Memória/induzido quimicamente , Fenóis/toxicidade , Memória Espacial/efeitos dos fármacos , Animais , Feminino , Hipocampo/fisiologia , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Neurônios/efeitos dos fármacos , Sinapses/efeitos dos fármacos
5.
Nat Commun ; 12(1): 3912, 2021 06 23.
Artigo em Inglês | MEDLINE | ID: mdl-34162838

RESUMO

Biological lignin valorization has emerged as a major solution for sustainable and cost-effective biorefineries. However, current biorefineries yield lignin with inadequate fractionation for bioconversion, yet substantial changes of these biorefinery designs to focus on lignin could jeopardize carbohydrate efficiency and increase capital costs. We resolve the dilemma by designing 'plug-in processes of lignin' with the integration of leading pretreatment technologies. Substantial improvement of lignin bioconversion and synergistic enhancement of carbohydrate processing are achieved by solubilizing lignin via lowering molecular weight and increasing hydrophilic groups, addressing the dilemma of lignin- or carbohydrate-first scenarios. The plug-in processes of lignin could enable minimum polyhydroxyalkanoate selling price at as low as $6.18/kg. The results highlight the potential to achieve commercial production of polyhydroxyalkanoates as a co-product of cellulosic ethanol. Here, we show that the plug-in processes of lignin could transform biorefinery design toward sustainability by promoting carbon efficiency and optimizing the total capital cost.


Assuntos
Carbono/metabolismo , Lignina/metabolismo , Poli-Hidroxialcanoatos/metabolismo , Bioengenharia/economia , Bioengenharia/métodos , Carboidratos/química , Hidrólise , Microbiologia Industrial/economia , Microbiologia Industrial/métodos , Pseudomonas putida/genética , Pseudomonas putida/metabolismo
6.
Sci Rep ; 11(1): 11152, 2021 05 27.
Artigo em Inglês | MEDLINE | ID: mdl-34045597

RESUMO

A significant proportion of the land area of Heilongjiang Province, China, is composed of saline-alkaline soil, which severely inhibits maize growth. Although Trichoderma treatment is widely regarded as a promising strategy for improving the soil environment and promoting plant growth, the mechanism through which Trichoderma asperellum enhances maize resistance to saline-alkaline stress is not clear. In this study, we explored the effect of T. asperellum application at different concentrations to soil saline-alkaline environment on the seedlings of two maize cultivars, assessing the biochemical parameters related to oxidation resistance. Increasing spore densities of T. asperellum suspension effectively regulated the soil ion balance in the rhizosphere of maize seedlings, reduced the soil pH by 2.15-5.76% and sodium adsorption ratios by 22.70-54.13%, increased soil nutrient content and enzyme activity, and improved the soil environment for seedling growth. Additionally, T. asperellum treatment increased the maize seedling content of osmo-regulating substances and rate of glutathione:oxidised glutathione (43.86-88.25%) and ascorbate:oxidised ascorbate (25.26-222.32%) by affecting the antioxidant enzyme activity in the roots, increasing reactive oxygen species scavenging, and maintaining the osmotic balance and metabolic homeostasis under saline-alkaline stress. T. asperellum also improved the saline-alkaline tolerance of maize seedlings by improving the root growth characteristics. Moreover, results showed that Trichoderma applied at high concentration had the greatest effect. In conclusion, improvement in the saline-alkaline tolerance of maize seedlings by T. asperellum under saline-alkaline soil conditions may be achieved through diverse effects that vary among maize cultivars.

7.
Cancer Cytopathol ; 129(9): 693-700, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33826796

RESUMO

BACKGROUND: Cervical cytology screening is usually laborious with a heavy workload and poor diagnostic consistency. The authors have developed an artificial intelligence (AI) microscope that can provide onsite diagnostic assistance for cervical cytology screening in real time. METHODS: A total of 2167 cervical cytology slides were selected from a cohort of 10,601 cases from Shenzhen Maternity and Child Healthcare Hospital, and the training data set consisted of 42,073 abnormal cervical epithelial cells. The recognition results of an AI technique were presented in a microscope eyepiece by an augmented reality technique. Potentially abnormal cells were highlighted with binary classification results in a 10× field of view (FOV) and with multiclassification results according to the Bethesda system in 20× and 40× FOVs. In addition, 486 slides were selected for the reader study to evaluate the performance of the AI microscope. RESULTS: In the reader study, which compared manual reading with AI assistance, the sensitivities for the detection of low-grade squamous intraepithelial lesions and high-grade squamous intraepithelial lesions were significantly improved from 0.837 to 0.923 (P < .001) and from 0.830 to 0.917 (P < .01), respectively; the κ score for atypical squamous cells of undetermined significance (ASCUS) was improved from 0.581 to 0.637; the averaged pairwise κ of consistency for multiclassification was improved from 0.649 to 0.706; the averaged pairwise κ of consistency for binary classification was improved from 0.720 to 0.798; and the averaged pairwise κ of ASCUS was improved from 0.557 to 0.639. CONCLUSIONS: The results of this study show that an AI microscope can provide real-time assistance for cervical cytology screening and improve the efficiency and accuracy of cervical cytology diagnosis.

8.
Med Image Anal ; 70: 102006, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33690025

RESUMO

Cervical cancer causes the fourth most cancer-related deaths of women worldwide. Early detection of cervical intraepithelial neoplasia (CIN) can significantly increase the survival rate of patients. World Health Organization (WHO) divided the CIN into three grades (CIN1, CIN2 and CIN3). In clinical practice, different CIN grades require different treatments. Although existing studies proposed computer aided diagnosis (CAD) systems for cervical cancer diagnosis, most of them are fail to perform accurate separation between CIN1 and CIN2/3, due to the similar appearances under colposcopy. To boost the accuracy of CAD systems, we construct a colposcopic image dataset for GRAding cervical intraepithelial Neoplasia with fine-grained lesion Description (GRAND). The dataset consists of colposcopic images collected from 8,604 patients along with the pathological reports. Additionally, we invite the experienced colposcopist to annotate two main clues, which are usually adopted for clinical diagnosis of CIN grade, i.e., texture of acetowhite epithelium (TAE) and appearance of blood vessel (ABV). A multi-rater model using the annotated clues is benchmarked for our dataset. The proposed framework contains several sub-networks (raters) to exploit the fine-grained lesion features TAE and ABV, respectively, by contrastive learning and a backbone network to extract the global information from colposcopic images. A comprehensive experiment is conducted on our GRAND dataset. The experimental results demonstrate the benefit of using additional lesion descriptions (TAE and ABV), which increases the CIN grading accuracy by over 10%. Furthermore, we conduct a human-machine confrontation to evaluate the potential of the proposed benchmark framework for clinical applications. Particularly, three colposcopists on different professional levels (intern, in-service and professional) are invited to compete with our benchmark framework by investigating a same extra test set-our framework achieves a comparable CIN grading accuracy to that of a professional colposcopist.


Assuntos
Neoplasia Intraepitelial Cervical , Neoplasias do Colo do Útero , Benchmarking , Neoplasia Intraepitelial Cervical/diagnóstico por imagem , Colposcopia , Feminino , Humanos , Gravidez , Neoplasias do Colo do Útero/diagnóstico por imagem
9.
BMC Pediatr ; 21(1): 87, 2021 02 17.
Artigo em Inglês | MEDLINE | ID: mdl-33596858

RESUMO

BACKGROUND: Cornell assessment of pediatric delirium (CAPD) showed advantage in diagnosis of pediatric delirium in Chinese critically ill patients. But its performance in surgical patients is still unclear. The present study was designed to validate the diagnostic performance of CAPD in surgical pediatric patients. METHODS: This is a prospective validation study. Pediatric patients who underwent selective surgery and general anesthesia were enrolled. Primary outcome was the incidence of delirium within postoperative three days. CAPD Chinese version was used to evaluate if the patient had delirium one time per day. At the meantime, a psychiatrist employed Diagnostic and Statistical Manual of Mental Disorders fifth edition to diagnose delirium, which was the "gold standard", and the result was considered as reference standard. Sensitivity, specificity and area under receiver operating characteristic (ROC) curve were calculated to investigate the performance of CAPD. RESULTS: A total of 170 patients were enrolled. Median age was 4 years old. As diagnosed by psychiatrist, 23 (13.5 %) patients experienced at least one episode of delirium during the follow-up period. When diagnostic threshold was set at 9, CAPD showed the optimal sensitivity (87.0 %, 95 %CI 65.3 %-96.6 %) and specificity (98.0 %, 95 %CI 93.7 %-99.5 %) in comparison with other diagnostic thresholds. ROC analysis showed that CAPD was a good delirium assessment instrument with area under curve of 0.911 (95 % CI 0.812 to 1.000, P < 0.001). Agreement between CAPD and reference standard was 0.849 (Kappa coefficient, P < 0.001). CONCLUSIONS: This study found that Cornell assessment of pediatric delirium could be used as an effective instrument in diagnosis of delirium in pediatric surgical patients. TRIAL REGISTRATION: www.chictr.org.cn Identifier: ChiCTR-DDD-17,012,231, August 3, 2017.


Assuntos
Delírio , Criança , Pré-Escolar , Estado Terminal , Delírio/diagnóstico , Manual Diagnóstico e Estatístico de Transtornos Mentais , Humanos , Estudos Prospectivos , Reprodutibilidade dos Testes
10.
Int J Cancer ; 148(6): 1419-1427, 2021 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-32895912

RESUMO

Thermal ablation is a point-of-care ablative treatment technique for cervical intraepithelial neoplasia (CIN). However, limited information is available about its efficacy in low- and middle-income countries. We evaluated the efficacy of thermal ablation in treatment of CIN detected through high-risk human papillomavirus (HPV) screening in China. Women positive on high-risk HPV and having colposcopically suspected lesions eligible for ablation underwent colposcopy, biopsy and thermal ablation in one visit. Women ineligible were recalled for large loop excision of transformation zone (LLETZ) when histopathology results were high-grade CIN. Posttreatment follow-up at 6 months or more was with HPV test and cytology followed by colposcopy and biopsy for HPV and/or cytology-positive women. Cure was defined as either negative cytology and HPV test or absence of histopathology proved CIN in any positive women. Of total 218 HPV-positive women treated with thermal ablation (n = 170) or LLETZ (n = 48), 196 reported for follow-up evaluation. For women with histologically confirmed CIN at baseline (thermal ablation-104; LLETZ-38), cure rates were 84.6% for thermal ablation and 86.8% for LLETZ. Cure rates after thermal ablation were 90.3% for CIN grade one (CIN1) and 76.2% for CIN grade two or worse (CIN2+). HPV clearance rate was 80.4% in women undergoing thermal ablation, which was lower for HPV16/18 compared to other oncogenic types (67.6% vs 85.7%). HPV test had a negative predictive value (NPV) of 98.7% to detect CIN2+ at follow-up and the positive predictive value (PPV) was 40.4%. Thermal ablation is effective to treat CIN as well as to clear the high-risk HPV infection. HPV test has high PPV and NPV in following up patients posttreatment.


Assuntos
Neoplasia Intraepitelial Cervical/cirurgia , Técnicas de Ablação Endometrial/métodos , Sistemas Automatizados de Assistência Junto ao Leito , Neoplasias do Colo do Útero/cirurgia , Adulto , Idoso , Ablação por Cateter/métodos , China , Feminino , Humanos , Pessoa de Meia-Idade , Infecções por Papillomavirus/complicações
11.
J Asian Nat Prod Res ; 23(5): 407-413, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-32228193

RESUMO

Two new pyrrolizidine alkaloids, sclerwalins A and B (1 and 2), and one known 9-O-E-hydroxysenecioylretronecine (3) were first isolated from the seeds of Scleropyrum wallichianum. Their chemical structures were elucidated by extensive 1 D NMR and 2 D NMR (HSQC, HMBC, COSY, and ROESY), MS and IR spectra. Cytotoxicities of all isolates were evaluated against five human tumor cell lines (HL-60, A-549, SMMC-7721, MCF-7 and SW480).[Formula: see text].


Assuntos
Alcaloides de Pirrolizidina , Linhagem Celular Tumoral , Células HL-60 , Humanos , Estrutura Molecular , Sementes
12.
Cancer Epidemiol ; 70: 101861, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33310688

RESUMO

BACKGROUND: On Nov 17, 2020, WHO launched a global initiative to accelerate the elimination of cervical cancer through the implementation of HPV vaccination, cervical cancer screening and treatment for precancer and cancer. China has the largest burden of cervical cancer in the world, but only has a national cervical cancer screening program in rural areas since 2009. Here, we aimed to evaluate the effectiveness and cost-effectiveness of cervical cancer screening in urban China, using Shenzhen City as an example. METHODS: We use an extensively validated platform ('Policy1-Cervix'), calibrated to data from Shenzhen city and Guandong Province. We evaluated a range of strategies that have previously been implemented as pilot studies in China, or recommended as guidelines within China and globally, spanning primary HPV, cytology and co-testing strategies. We additionally considered alternate triaging methods, age ranges and screening intervals, resulting in 19 algorithms in total. RESULTS: Of the 19 strategies considered, the most effective approach involved primary HPV testing. At 3- to 10-yearly intervals, primary HPV testing reduced the age-standardized cancer mortality rate by 37-71 %. The most cost-effective strategy was 5-yearly primary HPV testing with partial genotyping triage for ages 25-65, discharging to 10-yearly screening for low-risk women (ICER = US$7191/QALYS using 2018 costs; willingness-to-pay threshold<1xGDP [US$9771]). This strategy gave an incidence and mortality reduction of 56 % and 63 %, respectively. This remained the most cost-effective strategy under most conditions in sensitivity analysis. CONCLUSION: Primary HPV testing would be cost-effective in Shenzhen and could more than halve cervical cancer incidence rates to 6 per 100,000 over the long term. In order to achieve rates below 4 per 100,000, the elimination threshold set by the World Health Organization, vaccination will likely also be necessary.


Assuntos
Programas de Rastreamento/economia , Infecções por Papillomavirus/virologia , Adulto , Feminino , Humanos , Anos de Vida Ajustados por Qualidade de Vida , População Urbana , Adulto Jovem
14.
ChemSusChem ; 13(20): 5423-5432, 2020 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-32750220

RESUMO

Biological lignin valorization represents a promising approach contributing to sustainable and economic biorefineries. The low level of valuable lignin-derived products remains a major challenge hindering the implementation of microbial lignin conversion. Lignin's properties play a significant role in determining the efficiency of lignin bioconversion. To date, despite significant progress in the development of biomass pretreatment, lignin fractionation, and fermentation over the last few decades, little efforts have gone into identifying the ideal lignin substrates for an efficient microbial metabolism. In this Minireview, emerging and state-of-the-art strategies for biomass pretreatment and lignin fractionation are summarized to elaborate their roles in modifying lignin structure for bioconversion. Fermentation strategies aimed at enhancing lignin depolymerization for microbial utilization are systematically reviewed as well. With an improved understanding of the ideal lignin structure elucidated by comprehensive metabolic pathways and/or big data analysis, modifying lignin chemistry could be more directional and effective. Ultimately, together with the progress of fermentation process optimization, biological lignin valorization will become more competitive in biorefineries.


Assuntos
Técnicas de Cultura de Células/métodos , Lignina/química , Lignina/metabolismo , Biomassa , Fermentação , Glucose/química , Redes e Vias Metabólicas , Estrutura Molecular , Polimerização , Solventes/química , Xilose/química
15.
Chin Med J (Engl) ; 133(19): 2353-2358, 2020 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-32541360

RESUMO

This review summarizes recent evidences regarding the potential influences of epidural labor analgesia (ELA) on the outcomes of neonates and children. Terms and relevant words including "ELA," "ELA and neonatal outcomes," "ELA and children's development," and "ELA and children's neurocognitive development" were used to search articles published in PubMed database up to October 2019. Original articles and reviews regarding potential influences of ELA on neonates and children were identified. Relevant references of the selected articles were also screened. The anesthetics used during ELA can be absorbed, enter the fetus, and produce neonatal depression; however, these effects are less severe than those during systematic opioid analgesia. The impact of anesthetic exposure during ELA on children's neurodevelopment has not been fully studied, but would be mild if any. ELA increases the risk of intrapartum maternal fever; the latter may be harmful to neonatal outcomes. The use of ELA may increase birth injury by increasing instrumental delivery, although long-term adverse events are rare. On the other hand, ELA may reduce maternal depression and, thus, produce favorable effects on neurocognitive development in childhood; but evidences are still lacking in this aspect. ELA may produce both favorable and unfavorable effects on neonates and children. These effects should be discussed with parturient women before making decisions. The potential harmful effects should be carefully managed. The overall impacts of ELA on neonatal and children's outcomes need to be studied further.


Assuntos
Analgesia Epidural , Analgesia Obstétrica , Trabalho de Parto , Analgesia Epidural/efeitos adversos , Analgesia Obstétrica/efeitos adversos , Criança , Parto Obstétrico , Feminino , Febre , Humanos , Recém-Nascido , Gravidez
16.
EBioMedicine ; 53: 102689, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32114396

RESUMO

BACKGROUND: How the oncoprotein epidermal growth factor receptor (EGFR) evades proteolytic degradation and accumulates in non-small cell lung cancer (NSCLC) remains unclear, and ubiquitin pathway genes (UPGs) that are critical to NSCLC needs to be systematically identified. METHODS: A total of 696 UPGs (including E1, E2, E3, and deubiquitinases) were silenced by small interfering RNA (siRNA) library in NSCLC cells, the candidates were verified, and their significance was evaluated in patients with NSCLC. The effects of a candidate gene on EGFR were investigated in vitro and in vivo. FINDINGS: We report 31 candidates that are required for cell proliferation, with the E2 ubiquitin conjugase CDC34 as the most significant one. CDC34 is elevated in tumor tissues in 76 of 114 (66.7%) NSCLCs and inversely associated with prognosis, is higher in smoker patients than nonsmoker patients, and is induced by tobacco carcinogens in normal human lung epithelial cells. Forced expression of CDC34 promotes, whereas knockdown of CDC34 inhibits, NSCLC cell proliferation in vitro and in vivo. CDC34 competes with c-Cbl to bind Y1045 to inhibit polyubiquitination and degradation of EGFR. In EGFR-L858R and EGFR-T790M/Del (exon 19)-driven lung tumor growth in mouse models, knockdown of CDC34 significantly inhibits tumor formation. INTERPRETATION: These results demonstrate that an E2 enzyme is capable of competing with E3 ligase to stabilize substrates, and CDC34 represents an attractive therapeutic target for NSCLCs. FUNDING: National Key Research and Development Program of China, National Natural Science Foundation of China, and the CAMS Innovation Fund for Medical Sciences.


Assuntos
Carcinogênese/genética , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Receptores ErbB/metabolismo , Neoplasias Pulmonares/metabolismo , Enzimas de Conjugação de Ubiquitina/genética , Células Epiteliais Alveolares/efeitos dos fármacos , Células Epiteliais Alveolares/metabolismo , Animais , Carcinogênese/efeitos dos fármacos , Carcinógenos/toxicidade , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Linhagem Celular Tumoral , Proliferação de Células , Células HEK293 , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Camundongos , Camundongos SCID , Poluição por Fumaça de Tabaco/efeitos adversos , Transcriptoma , Enzimas de Conjugação de Ubiquitina/metabolismo , Ubiquitina-Proteína Ligases/genética , Ubiquitina-Proteína Ligases/metabolismo
17.
Biotechnol Biofuels ; 13: 44, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32175010

RESUMO

Background: For bioethanol production from lignocellulosic biomass, phenolics derived from pretreatment have been generally considered as highly inhibitory towards enzymatic hydrolysis and fermentation. As phenolics are produced from lignin degradation during pretreatment, it is likely that the pretreatment will exert a strong impact on the structure of phenolics, resulting in varied levels of inhibition of the bioconversion process. Despite the extensive studies on pretreatment, it remains unclear how pretreatment process affects the properties of generated phenolics and how the inhibitory effect of phenolics from different pretreatment varies on enzymatic hydrolysis and fermentation. Results: In this study, the structural properties of phenolic compounds derived from four typical pretreatment [dilute acid (DA), liquid hot water pretreatment (LHW), ammonia fiber expansion (AFEX) and alkaline pretreatment (AL)] were characterized, and their effect on both enzymatic hydrolysis and fermentation were evaluated. The inhibitory effect of phenolics on enzymatic hydrolysis followed the order: AFEX > LHW > DA > AL, while the inhibitory effect of phenolics on Zymomonas mobilis 8b strain fermentation followed the order: AL > LHW > DA > AFEX. Interestingly, this study revealed that phenolics derived from AFEX showed more severe inhibitory effect on enzymatic hydrolysis than those from the other pretreatments at the same phenolics concentrations (note: AFEX produced much less amount of phenolics compared to AL and DA), while they exhibited the lowest inhibitory effect on fermentation. The composition of phenolics from different pretreatments was analyzed and model phenolics were applied to explore the reason for this difference. The results suggested that the amide group in phenolics might account for this difference. Conclusions: Pretreatment process greatly affects the properties of generated phenolics and the inhibitory effects of phenolics on enzymatic hydrolysis and fermentation. This study provides new insight for further pretreatment modification and hydrolysate detoxification to minimize phenolics-caused inhibition and enhance the efficiency of enzymatic hydrolysis and fermentation.

18.
Int J Cancer ; 147(2): 505-518, 2020 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-32064600

RESUMO

Although early detection and systemic therapies have improved the diagnosis and clinical cure rate of breast cancer, breast cancer remains the most frequently occurring malignant cancer in women due to a lack of sufficiently effective treatments. Thus, to develop potential targeted therapies and thus benefit more patients, it is helpful to understand how cancer cells work. ZIC family members have been shown to play important roles in neural development and carcinogenesis. In our study, we found that ZIC2 is downregulated in breast cancer tissues at both the mRNA and protein levels. Low expression of ZIC2 was correlated with poor outcome in breast cancer patients and serves as an independent prognostic marker. Furthermore, overexpression of ZIC2 repressed, whereas knockdown of ZIC2 promoted, cell proliferation and colony formation ability in vitro and tumor growth in vivo. Using ChIP-seq and RNA-seq analysis, we screened and identified STAT3 as a potential target for ZIC2. ZIC2 bound to the STAT3 promoter and repressed the promoter activities of STAT3. ZIC2 knockdown induced the expression of STAT3, increasing the level of phosphorylated STAT3. These results suggest that ZIC2 regulates the transcription of STAT3 by directly binding to the STAT3 promoter. Additionally, interfering STAT3 with siRNAs or inhibitors abrogated the oncogenic effects induced by decreased ZIC2. Taken together, our results indicate that ZIC2 serves as a useful prognostic marker in breast cancer and acts as a tumor suppressor by regulating STAT3, implying that STAT3 inhibitors might provide an alternative treatment option for breast cancer patients with ZIC2 downregulation.


Assuntos
Neoplasias da Mama/patologia , Regulação para Baixo , Proteínas Nucleares/genética , Proteínas Nucleares/metabolismo , Fator de Transcrição STAT3/genética , Fator de Transcrição STAT3/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Animais , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Neoplasias da Mama/genética , Neoplasias da Mama/metabolismo , Linhagem Celular Tumoral , Proliferação de Células , Sequenciamento de Cromatina por Imunoprecipitação , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Células MCF-7 , Camundongos , Transplante de Neoplasias , Fosforilação , Prognóstico , Regiões Promotoras Genéticas , Análise de Sequência de RNA , Transdução de Sinais
19.
Chemosphere ; 243: 125428, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31995880

RESUMO

Toxic elements exposure disturbs the homeostasis of essential elements in organisms, but the mechanism remains elusive. In this study, we demonstrated that Drosophila melanogaster exposed to Lead (Pb, a pervasive environmental threat to human health) exhibited various health defects, including retarded development, decreased survival rate, impaired mobility and reduced egg production. These phenotypes could be significantly modulated by either intervention of dietary iron levels or altering expression of genes involved in iron metabolism. Further study revealed that Pb exposure leads to systemic iron deficiency. Strikingly, reactive oxygen species (ROS) clearance significantly increased iron uptake by restoring the expression of iron metabolism genes in the midgut and subsequently attenuated Pb toxicity. This study highlights the role of ROS in Pb induced iron dyshomeostasis and provides unique insights into understanding the mechanism of Pb toxicity and suggests ideal ways to attenuate Pb toxicity by iron supplementation therapy or ROS clearance.


Assuntos
Anemia Ferropriva/etiologia , Drosophila melanogaster/metabolismo , Chumbo/toxicidade , Estresse Oxidativo/efeitos dos fármacos , Anemia Ferropriva/induzido quimicamente , Animais , Dieta , Drosophila melanogaster/efeitos dos fármacos , Homeostase , Humanos , Ferro/metabolismo , Chumbo/metabolismo , Espécies Reativas de Oxigênio/metabolismo
20.
Eur J Anaesthesiol ; 36(10): 745-754, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31356375

RESUMO

BACKGROUND: Severe labour pain is an important risk factor of postpartum depression, and early depression is associated with an increased risk of long-term depression; whereas the use of epidural analgesia during labour decreases the risk of postpartum depression. OBJECTIVE: To investigate whether neuraxial labour analgesia was associated with a decreased risk of 2-year depression. DESIGN: This was a multicentre, prospective, longitudinal study. SETTING: The study was performed in Peking University First Hospital, Beijing Obstetrics and Gynecology Hospital and Haidian Maternal and Child Health Hospital in Beijing, China, between 1 August 2014 and 25 April 2017. PATIENTS: Five hundred ninety-nine nulliparous women with single-term cephalic pregnancy preparing for vaginal delivery were enrolled. MAIN OUTCOME MEASURE: Depressive symptoms were screened with the Edinburgh Postnatal Depression Scale at delivery-room admission, 6-week postpartum and 2 years after childbirth. A score of 10 or higher was used as the threshold of depression. The primary endpoint was the presence of depression at 2 years after childbirth. The association between the use of neuraxial labour analgesia and the development of 2-year depression was analysed with a multivariable logistic regression model. RESULTS: Five hundred and eight parturients completed 2-year follow-up. Of these, 368 (72.4%) received neuraxial analgesia during labour and 140 (27.6%) did not. The percentage with 2-year depression was lower in those with neuraxial labour analgesia than in those without (7.3 [27/368] vs. 13.6% [19/140]; P = 0.029). After correction for confounding factors, the use of neuraxial analgesia during labour was associated with a significantly decreased risk of 2-year depression (odds ratio 0.455, 95% confidence interval 0.230 to 0.898; P = 0.023). CONCLUSION: For nulliparous women with single-term cephalic pregnancy planning for vaginal delivery, the use of neuraxial analgesia during labour was associated with a reduced risk of maternal depression at 2 years after childbirth. TRIAL REGISTRATION: www.chictr.org.cn: ChiCTR-OCH-14004888 and ClinicalTrials.gov: NCT02823418.


Assuntos
Analgesia Epidural/métodos , Analgesia Obstétrica/métodos , Depressão Pós-Parto/prevenção & controle , Adulto , Parto Obstétrico , Feminino , Seguimentos , Humanos , Trabalho de Parto , Estudos Longitudinais , Análise Multivariada , Razão de Chances , Manejo da Dor , Parto , Período Pós-Parto , Gravidez , Estudos Prospectivos , Índice de Gravidade de Doença , Inquéritos e Questionários , Adulto Jovem
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