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1.
Neurochem Res ; 49(5): 1291-1305, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38424396

RESUMO

Parkinson's Disease (PD) is characterized by the loss of dopaminergic neurons, with ferroptosis playing a significant role. Salidroside (SAL) has shown neuroprotective potential, this study aims to explore its capacity to mitigate ferroptosis in PD, focusing on the modulation of the Nuclear Factor E2-Related Factor 2 (Nrf2)/ Glutathione Peroxidase 4 (GPX4) pathway. Male C57BL/6 mice were subjected to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) to induce PD-like symptoms, followed by SAL and Nrf2 inhibitor administration. Then behavioral tests, immunohistochemical staining, transmission electron microscopy, and Western blot analysis were conducted to assess motor functions, pathological changes, ferroptosis, and related protein expressions. In vitro, SH-SY5Y cells were treated with erastin to induce ferroptosis to assess the protective effects of SAL. Additionally, A53T-α-synuclein (α-syn) was used to stimulate the PD model, SAL and a Nrf2 inhibitor (ML385) was utilized to elucidate the role of the Nrf2/GPX4 pathway in mitigating ferroptosis in PD. In vivo, SAL significantly improved motor functions and reduced the expression of α-syn, while increasing tyrosine hydroxylase (TH) expression of PD mice. Additionally, SAL treatment notably enhanced the levels of antioxidants and reduced MDA and iron content in the substantia nigra of PD mice. In vitro, SAL treatment increased the TH, GPX4, Nrf2 expression, and mitochondrial membrane potential whereas alleviated ferroptosis through the Nrf2/GPX4 pathway, as evidenced in erastin-induced and α-syn overexpressing SH-SY5Y cells. While these effects were reversed upon Nrf2 inhibition. SAL demonstrates significant potential in mitigating PD pathology and ferroptosis, positioning the Nrf2/GPX4 pathway as a promising therapeutic target. However, future studies should focus on the long-term effects of SAL, its pharmacokinetics, addressing the multifactorial nature of PD pathogenesis.


Assuntos
Ferroptose , Glucosídeos , Neuroblastoma , Doença de Parkinson , Fenóis , Masculino , Humanos , Camundongos , Animais , Fator 2 Relacionado a NF-E2/metabolismo , Transdução de Sinais , Camundongos Endogâmicos C57BL
2.
Nucleic Acids Res ; 50(4): 2223-2239, 2022 02 28.
Artigo em Inglês | MEDLINE | ID: mdl-35104889

RESUMO

N 6-Threonylcarbamoyladenosine (t6A) is a universal and pivotal tRNA modification. KEOPS in eukaryotes participates in its biogenesis, whose mutations are connected with Galloway-Mowat syndrome. However, the tRNA substrate selection mechanism by KEOPS and t6A modification function in mammalian cells remain unclear. Here, we confirmed that all ANN-decoding human cytoplasmic tRNAs harbor a t6A moiety. Using t6A modification systems from various eukaryotes, we proposed the possible coevolution of position 33 of initiator tRNAMet and modification enzymes. The role of the universal CCA end in t6A biogenesis varied among species. However, all KEOPSs critically depended on C32 and two base pairs in the D-stem. Knockdown of the catalytic subunit OSGEP in HEK293T cells had no effect on the steady-state abundance of cytoplasmic tRNAs but selectively inhibited tRNAIle aminoacylation. Combined with in vitro aminoacylation assays, we revealed that t6A functions as a tRNAIle isoacceptor-specific positive determinant for human cytoplasmic isoleucyl-tRNA synthetase (IARS1). t6A deficiency had divergent effects on decoding efficiency at ANN codons and promoted +1 frameshifting. Altogether, our results shed light on the tRNA recognition mechanism, revealing both commonality and diversity in substrate recognition by eukaryotic KEOPSs, and elucidated the critical role of t6A in tRNAIle aminoacylation and codon decoding in human cells.


Assuntos
Eucariotos , RNA de Transferência de Isoleucina , Adenosina/genética , Animais , Códon , Eucariotos/genética , Células HEK293 , Humanos , Mamíferos/genética , Conformação de Ácido Nucleico , RNA de Transferência/genética , RNA de Transferência de Metionina
3.
Nucleic Acids Res ; 50(22): 12951-12968, 2022 12 09.
Artigo em Inglês | MEDLINE | ID: mdl-36503967

RESUMO

Mitochondrial RNA metabolism is suggested to occur in identified compartmentalized foci, i.e. mitochondrial RNA granules (MRGs). Mitochondrial aminoacyl-tRNA synthetases (mito aaRSs) catalyze tRNA charging and are key components in mitochondrial gene expression. Mutations of mito aaRSs are associated with various human disorders. However, the suborganelle distribution, interaction network and regulatory mechanism of mito aaRSs remain largely unknown. Here, we found that all mito aaRSs partly colocalize with MRG, and this colocalization is likely facilitated by tRNA-binding capacity. A fraction of human mitochondrial AlaRS (hmtAlaRS) and hmtSerRS formed a direct complex via interaction between catalytic domains in vivo. Aminoacylation activities of both hmtAlaRS and hmtSerRS were fine-tuned upon complex formation in vitro. We further established a full spectrum of interaction networks via immunoprecipitation and mass spectrometry for all mito aaRSs and discovered interactions between hmtSerRS and hmtAsnRS, between hmtSerRS and hmtTyrRS and between hmtThrRS and hmtArgRS. The activity of hmtTyrRS was also influenced by the presence of hmtSerRS. Notably, hmtSerRS utilized the same catalytic domain in mediating several interactions. Altogether, our results systematically analyzed the suborganelle localization and interaction network of mito aaRSs and discovered several mito aaRS-containing complexes, deepening our understanding of the functional and regulatory mechanisms of mito aaRSs.


Assuntos
Aminoacil-tRNA Sintetases , Aminoacilação de RNA de Transferência , Humanos , Aminoacil-tRNA Sintetases/metabolismo , Grânulos de Ribonucleoproteínas Citoplasmáticas/metabolismo , RNA Mitocondrial/metabolismo , RNA de Transferência/metabolismo
4.
Nucleic Acids Res ; 50(7): 4012-4028, 2022 04 22.
Artigo em Inglês | MEDLINE | ID: mdl-35357504

RESUMO

METTL8 has recently been identified as the methyltransferase catalyzing 3-methylcytidine biogenesis at position 32 (m3C32) of mitochondrial tRNAs. METTL8 also potentially participates in mRNA methylation and R-loop biogenesis. How METTL8 plays multiple roles in distinct cell compartments and catalyzes mitochondrial tRNA m3C formation remain unclear. Here, we discovered that alternative mRNA splicing generated several isoforms of METTL8. One isoform (METTL8-Iso1) was targeted to mitochondria via an N-terminal pre-sequence, while another one (METTL8-Iso4) mainly localized to the nucleolus. METTL8-Iso1-mediated m3C32 modification of human mitochondrial tRNAThr (hmtRNAThr) was not reliant on t6A modification at A37 (t6A37), while that of hmtRNASer(UCN) critically depended on i6A modification at A37 (i6A37). We clarified the hmtRNAThr substrate recognition mechanism, which was obviously different from that of hmtRNASer(UCN), in terms of requiring a G35 determinant. Moreover, SARS2 (mitochondrial seryl-tRNA synthetase) interacted with METTL8-Iso1 in an RNA-independent manner and modestly accelerated m3C modification activity. We further elucidated how nonsubstrate tRNAs in human mitochondria were efficiently discriminated by METTL8-Iso1. In summary, our results established the expression pattern of METTL8, clarified the molecular basis for m3C32 modification by METTL8-Iso1 and provided the rationale for the involvement of METTL8 in tRNA modification, mRNA methylation or R-loop biogenesis.


Assuntos
Metiltransferases/metabolismo , Mitocôndrias/metabolismo , RNA de Transferência , Processamento Alternativo , Humanos , Metiltransferases/genética , Mitocôndrias/genética , RNA Mensageiro , RNA de Transferência/genética , RNA de Transferência/metabolismo , RNA de Transferência de Treonina/genética
5.
Artigo em Inglês | MEDLINE | ID: mdl-39034823

RESUMO

Transfer RNAs (tRNAs) play central roles in protein biosynthesis. Post-transcriptional RNA modifications affect tRNA function and stability. Among these modifications, RNA editing is a widespread RNA modification in three domains of life. Proteins of the adenosine deaminase acting on tRNA (ADAT) family were discovered more than 20 years ago. They catalyze the deamination of adenosine to inosine (A-to-I) or cytidine to uridine (C-to-U) during tRNA maturation. The most studied example is the TadA- or ADAT2/3-mediated A-to-I conversion of the tRNA wobble position in the anticodon of prokaryotic or eukaryotic tRNAs, respectively. This review provides detailed information on A-to-I and C-to-U editing of tRNAs in different domains of life, presents recent new findings on ADATs for DNA editing, and finally comments on the association of mutations in the ADAT3 gene with intellectual disability.

6.
J Environ Manage ; 358: 120921, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38652992

RESUMO

Ecological vulnerability and poverty are interrelated and must be addressed together. The resolution of this issue will help us to meet the challenges during the process of implementing concrete actions for realizing the 2030 UN sustainable development goals (SDGs). Ecological restoration projects (ERPs) can enhance ecosystem services (ESs) while providing policy support for improving people's livelihoods. However, processes and mechanisms of ERPs on the ecological environment and socioeconomic development in poverty-stricken and ecologically fragile areas have rarely been studied. To address these issues, we conducted a comparative analysis on the changes of land use and land cover (LULC), ecosystem services (ESs), and socioeconomic development in Bijie City, a karst rocky desertification area in southwest China, before and after the implementation of ERPs in 2000, as well as the complex relationship between these factors. ERPs have affected LULCs, ESs, socioeconomics, and poverty reduction significantly since 2000. Specifically, the total ecosystem service value (ESV) in the study area has increased by more than 3 times in the past 30 years, with the ESV of tourism services and carbon storage increasing the most, from CNY 0.001 and 337.07 billion in 1990 to CNY 11.07 and 108.97 billion in 2019, respectively. The correlation between ESs is mainly synergistic, while the tradeoff between carbon storage and water yield is in a fluctuating upward trend. LULC conversion of cropland to green, and cropland to water, wetland and shrubs has positive effects on carbon storage and water yield, respectively. During study period, GDP, urbanization increased by over 70 times, 5 times, respectively, whereas poverty population, poverty incidence, and employment rate of various sectors (i.e., agriculture, forest, animal, and fishery, or AFAF) decreased by 96.4%, 97.7%, and 18.24%, respectively. Our findings emphasized that ERPs can effectively help poor and ecologically fragile areas to get out of the poverty trap and achieve the "win-win" goals of ecological and socio-economic sustainable development. These results have profound environmental management references to China and other developing countries around the world in realizing ecological restoration, poverty reduction, and the SDGs.


Assuntos
Conservação dos Recursos Naturais , Ecossistema , Pobreza , China , Desenvolvimento Sustentável , Ecologia , Humanos
7.
Small ; 19(33): e2207330, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37078831

RESUMO

Electrospinning technology has attracted extensive attention in recent decades and is widely used to prepare nanofiber membranes from hundreds of polymers. Polyvinyl formal acetal (PVFA), as a polymer with excellent properties such as high strength and heat resistance, is not reported on the electrospun water treatment membrane. In this paper, the preparation process of electrospun PVFA nanofiber membrane is optimized, and the effect of sodium chloride (NaCl) addition on the physical and mechanical properties and microfiltration performance of nanofiber membrane is also explored. And the hydrophobic PVFA nanofiber filter layer is then combined with a hydrophilic nonwoven support layer to construct a composite micro/nanofiber membrane with a pore-size gradient structure and a hydrophilic/hydrophobic asymmetric structure. Finally, unidirectional water transport and water treatment performance are further investigated. The results show that the tensile breaking strength of the composite membrane can reach up to 37.8 MPa, the retention rate for particles with the size of 0.1-0.3 µm is 99.7%, and the water flux is 513.4 L m-2 h-1 under the hydrostatic pressure. Moreover, it still has a retention of more than 98% after three repeated uses. Therefore, the electrospun PVFA composite membrane has a great potential in microfiltration.

8.
Nucleic Acids Res ; 49(14): 8309-8323, 2021 08 20.
Artigo em Inglês | MEDLINE | ID: mdl-34268557

RESUMO

tRNAs harbor the most diverse posttranscriptional modifications. The 3-methylcytidine (m3C) is widely distributed at position C32 (m3C32) of eukaryotic tRNAThr and tRNASer species. m3C32 is decorated by the single methyltransferase Trm140 in budding yeasts; however, two (Trm140 and Trm141 in fission yeasts) or three enzymes (METTL2A, METTL2B and METTL6 in mammals) are involved in its biogenesis. The rationale for the existence of multiple m3C32 methyltransferases and their substrate discrimination mechanism is hitherto unknown. Here, we revealed that both METTL2A and METTL2B are expressed in vivo. We purified human METTL2A, METTL2B, and METTL6 to high homogeneity. We successfully reconstituted m3C32 modification activity for tRNAThr by METT2A and for tRNASer(GCU) by METTL6, assisted by seryl-tRNA synthetase (SerRS) in vitro. Compared with METTL2A, METTL2B exhibited dramatically lower activity in vitro. Both G35 and t6A at position 37 (t6A37) are necessary but insufficient prerequisites for tRNAThr m3C32 formation, while the anticodon loop and the long variable arm, but not t6A37, are key determinants for tRNASer(GCU) m3C32 biogenesis, likely being recognized synergistically by METTL6 and SerRS, respectively. Finally, we proposed a mutually exclusive substrate selection model to ensure correct discrimination among multiple tRNAs by multiple m3C32 methyltransferases.


Assuntos
Conformação de Ácido Nucleico , RNA de Transferência/genética , tRNA Metiltransferases/genética , Anticódon/genética , Citidina/análogos & derivados , Citidina/genética , Humanos , RNA/genética , RNA de Transferência/ultraestrutura , Serina-tRNA Ligase/genética , Especificidade por Substrato
9.
Int J Clin Pract ; 2023: 8244545, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38187354

RESUMO

Background: Acute kidney injury (AKI) was a common and serious complication in patients with acute myocardial infarction (AMI). Novel biomarkers and therapies were deficient and imperative for AKI's early diagnosis and therapy after AMI. α-Klotho was considered as an early biomarker and potential therapy for AKI recently. Previous studies reported that the expression of α-Klotho was decreased in AKI rodents, and supplement of α-Klotho alleviated kidney injury. Nevertheless, its effect has not been studied in patients presenting with AMI. Methods: A total of 155 consecutive diagnosed with AMI at emergency department whose eGFR >60 ml/min ∗ 1.73 m2 were enrolled in this prospective observational cohort study which conducted between May 2016 and April 2019 in Peking University People's Hospital. AKI was defined according to the KDIGO criteria in 2012. At admission, the clinical data of patients were collected and serum α-Klotho was tested by ELISA. The relationship between α-Klotho, serum creatinine, eGFR, systolic pressure, BNP, LVEF, and Hgb of AKI were analyzed and their discrimination performances were compared. The association variables were calculated (adjusted odds ratio) with a confidence interval (CI) of 95% by binary logistic regression. And, we followed up the incidence of CKD and rehospitalization after patients' discharge in one year. Our study was approved by the ethics committee (no. 2016PHB042-01). Results: AKI incidence was 17.4% (27/155) during hospitalization. Compared to patients without AKI, the AKI group had obviously higher mortality and was more female and had higher incidence of chronic kidney disease, worse cardiac function, more cardiac complications, larger doses of diuretics, and less use of angiotensin-converting enzyme inhibitors/angiotensin receptor blocker. By contrary to previous animal experiments, we found serum α-Klotho levels were increased significantly in AKI patients (740.2 ± 306.8 vs. 419.0 ± 272.6 pg/mL, p < 0.001). And, the areas under the receiver operating curves indicated serum α-Klotho levels had a superior discriminative power for predicting AKI after AMI compared with other risk factors (0.792, 95% CI, 0.706-0.878, p < 0.001). Meanwhile, logistic regression model indicates extensive anterior myocardial infarction, Killip classification ≥2 grade, α-Klotho ≥516.9 pg/mL, eGFR (decrease per 10 ml/min ∗ 1.73 m2), Hgb, and nonuse of ACEI/ARB were the risk factors of AKI after AMI. Moreover, one-year follow-up presented AMI patients developed CKD had higher α-Klotho levels (739.7 ± 315.2 vs. 443.8 ± 292.5 pg/mL, p = 0.001), but no significant difference in rehospitalization. And, patients with α-Klotho ≥516.9 pg/ml was 6.699 times more likely to develop CKD than those with α-Klotho <516.9 pg/ml (relative risk 6.699, 95% CI 1.631-27.519, p = 0.007). Conclusion: Compared with traditional cardiac and renal biomarkers, serum α-Klotho could be a more appropriate predict biomarker for AKI after AMI in patients' eGFR >60 ml/min ∗ 1.73 m2. Higher α-Klotho levels are related to the development of AKI during hospitalization and suggest a higher prevalence of CKD after discharge. By contrary to animal experiments, whether the increased expression of α-Klotho could be a protective factor secreted by AKI after AMI, is remained to be further studied.


Assuntos
Injúria Renal Aguda , Infarto do Miocárdio , Insuficiência Renal Crônica , Humanos , Injúria Renal Aguda/etiologia , Antagonistas de Receptores de Angiotensina , Inibidores da Enzima Conversora de Angiotensina , Biomarcadores , Infarto do Miocárdio/complicações , Estudos Prospectivos
10.
FASEB J ; 35(4): e21454, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33749945

RESUMO

Milk contains about 4% fat globules with its surface covered by polar lipids. Despite the abundant consumption of dairy products, the biological effects of dietary milk polar lipids on metabolic health have only been sparsely examined. Maternal obesity results in neurodevelopmental disorders and cognitive impairment in offspring. Considering the importance of maternal nutrition, the effects of polar lipids-enriched milk fat globule membrane (MFGM-PL) supplementation to dams during pregnancy and lactation on neurodevelopment and its long-term programming effects on offspring cognition were examined. Female Sprague-Dawley rats consumed 8-week control diet (CON) or high-fat diet (HFD) to induce obesity before mating. Then, female rats were fed CON or HFD with or without the supplementation of 400 mg/kg body weight MFGM-PL during pregnancy and lactation. The offspring were fed 11-week HFD after weaning. MFGM-PL supplementation to obese dams suppressed body weight gain and hyperinsulinemia in both dams and offspring. Offspring born to obese dams displayed delayed neurological reflexes development, impaired neurogenesis before weaning, and cognitive impairment in adulthood, which were recovered by maternal MFGM-PL supplementation. Insulin resistance and aberrant brain-derived neurotrophic factor signaling were induced in the hippocampus of neonatal and adult offspring due to maternal and progeny HFD, but recovered by maternal MFGM-PL administration. This study demonstrates that maternal MFGM-PL supplementation can promote neurodevelopment and exert long-term effects against HFD-induced cognitive impairment in offspring via alleviating hippocampal insulin resistance. Hence, MFGM-PL is a promising ingredient for exerting beneficial programming effects on the brain health of offspring.


Assuntos
Sistema Nervoso Central/crescimento & desenvolvimento , Cognição/efeitos dos fármacos , Suplementos Nutricionais , Lipídeos/farmacologia , Leite/química , Obesidade , Animais , Fator Neurotrófico Derivado do Encéfalo/genética , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/genética , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/metabolismo , Dieta Hiperlipídica/efeitos adversos , Feminino , Regulação da Expressão Gênica no Desenvolvimento/efeitos dos fármacos , Lipídeos/administração & dosagem , Masculino , Gravidez , Fenômenos Fisiológicos da Nutrição Pré-Natal , Ratos , Ratos Sprague-Dawley , Receptor trkB/genética , Receptor trkB/metabolismo
11.
Crit Rev Food Sci Nutr ; 62(13): 3437-3452, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-33393366

RESUMO

Cancer is one of the most devastating diseases, and recently, a variety of natural compounds with preventive effects on cancer developments have been reported. Sulforaphane (SFN) is a potent anti-cancer isothiocyanate originating from Brassica oleracea (broccoli). SFN, mainly metabolized via mercapturic acid pathway, has high bioavailability and absorption. The present reviews mainly discussed the metabolism and absorption of SFN and newly discovered mechanistic understanding recent years for SFN's anti-cancer effects including promoting autophagy, inducing epigenetic modifications, suppressing glycolysis and fat metabolism. Moreover, its inhibitory effects on cancer stem cells and synergetic effects with other anti-cancer agents are also reviewed along with the clinical trials in this realm.


Assuntos
Brassica , Neoplasias , Humanos , Isotiocianatos/farmacologia , Neoplasias/tratamento farmacológico , Sulfóxidos
12.
BMC Gastroenterol ; 22(1): 155, 2022 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-35350979

RESUMO

PURPOSES: In this study, we aimed to identify the distribution of presenting laboratory and nonenhanced computed tomography (CT) imaging features within 48 h before percutaneous cholecystostomy (PC) and create a model to appropriately guide the diagnosis of acute suppurative cholecystitis (ASC). METHODS: The study population included 204 acute cholecystitis patients who underwent PC. Based on the timing of the last laboratory and CT examinations before PC, the patients were divided into two groups: within 48 h before PC (Group 1, n = 138) and over 48 h before PC (Group 2, n = 63). The clinical features of the ASC patients in the two groups were compared. A multivariable model for the diagnosis of ASC in the patients in Group 1 was developed. RESULTS: Thirty-nine patients in Group 1 had ASC (28.3%). Gallbladder stones, common bile duct stones, gallbladder wall thickness > 2.85 mm, and neutrophil granulocytes > 82.55% were confirmed to be independent risk factors for ASC. The receiver operating characteristic curve of the recurrence prediction model verified its accuracy (area under the curve: 0.803). Compared with the ASC patients in Group 2, the ASC patients in Group 1 had a higher proportion of pericholecystic exudation or fluid (P = 0.013) and thicker gallbladder walls (P = 0.033). CONCLUSIONS: Using nonenhanced CT imaging features and cutoffs for neutrophil granulocytes, we were able to identify a simple algorithm to discriminate ASC. The degree of local inflammation of the gallbladder in ASC patients progressively increases over time, and these changes can be observed on nonenhanced CT images. However, the symptoms of abdominal pain are of little help in estimating the disease duration in elderly patients.


Assuntos
Colecistite Aguda , Colecistostomia , Cálculos Biliares , Idoso , Colecistite Aguda/diagnóstico por imagem , Colecistite Aguda/cirurgia , Colecistostomia/métodos , Humanos , Estudos Retrospectivos , Tomografia Computadorizada por Raios X/métodos
13.
Nano Lett ; 21(22): 9419-9425, 2021 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-34729985

RESUMO

Herein, we present a facile reinforcement method for the large-scale fabrication of highly flexible, mechanically stable, temperature-resistant ceramic lightweight membranes based on the cross-linked assembly of zirconia-silica (ZrO2-SiO2) nanofibrous and montmorillonite (MMT) nanosheets through electrospinning and a subsequent calcination process. The resulting MMT@ZrO2-SiO2 membranes exhibit high flexibility with a bending rigidity of 0.2 cN mm-1, robust mechanical performance with a tensile strength of up to 1.83 MPa, robust fire resistance, and temperature-invariant mechanical stability from -196 to 1000 °C. The thermal superinsulation with a thermal conductivity as low as 0.026 W m-1 K-1 and the improved mechanical strength can be attributed to the cross-linked interfacial interaction between the ZrO2-SiO2 nanofibers and the MMT nanosheets. Additionally, a firefighter uniform with MMT@ZrO2-SiO2 membranes inside features a superior thermal protective property up to the A2 level (combined flame and radiant exposure) and an excellent fire resistance of up to 1000 °C, which is ideal for next-generation firefighter uniform manufacturing.

14.
BMC Surg ; 21(1): 439, 2021 Dec 27.
Artigo em Inglês | MEDLINE | ID: mdl-34961498

RESUMO

BACKGROUND: In this study, we aimed to investigate risk factors for the relapse of moderate and severe acute acalculous cholecystitis (AAC) patients after initial percutaneous cholecystostomy (PC) and to identify the predictors of patient outcomes when choosing PC as a definitive treatment for AAC. MATERIALS AND METHODS: The study population comprised 44 patients (median age 76 years; range 31-94 years) with moderate or severe AAC who underwent PC without subsequent cholecystectomy. According to the results of follow-up (followed for a median period of 17 months), the data of patients with recurrence versus no recurrence were compared. Patients were divided into the death and non-death groups based on patient status within 60 days after PC. RESULTS: Twenty-one (47.7%) had no recurrence of cholecystitis during the follow-up period after catheter removal (61-1348 days), six (13.6%) experienced recurrence of cholecystitis after PC, and 17 (38.6%) patients died during the indwelling tube period (5-60 days). The multivariate analysis showed that coronary heart disease (CHD) or congestive heart failure (odds ratio [OR] 26.50; 95% confidence interval [CI] 1.21-582.06; P = 0.038) was positively correlated with recurrence. The age-adjusted Charlson comorbidity index (OR 1.53; 95% CI 1.08-2.17; P = 0.018) was independently associated with 60-day mortality after PC. CONCLUSIONS: Our results suggest that CHD or congestive heart failure was an independent risk factor for relapse in moderate and severe AAC patients after initial PC. AAC patients with more comorbidities had worse outcomes.


Assuntos
Colecistite Acalculosa , Colecistite Aguda , Colecistite , Colecistostomia , Colecistite Acalculosa/epidemiologia , Colecistite Acalculosa/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Colecistite Aguda/cirurgia , Humanos , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento
15.
Crit Rev Food Sci Nutr ; 60(5): 810-825, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-30632783

RESUMO

Breast cancer is a common malignancy with poor prognosis. Cancer cells are heterogeneous and cancer stem cells (CSCs) are primarily responsible for tumor relapse, treatment-resistance and metastasis, so for breast cancer stem cells (BCSCs). Diets are known to be associated with carcinogenesis. Food-derived polyphenols are able to attenuate the formation and virulence of BCSCs, implying that these compounds and their analogs might be promising agents for preventing breast cancer. In the present review, we summarized the origin and surface markers of BCSCs and possible mechanisms responsible for the inhibitory effects of polyphenols on BCSCs. The suppressive effects of common dietary polyphenols against BCSCs, such as curcumin, epigallocatechin gallate (EGCG) and related polyphenolic compounds were further discussed.


Assuntos
Antineoplásicos/farmacologia , Neoplasias da Mama/dietoterapia , Neoplasias da Mama/prevenção & controle , Curcumina/farmacologia , Células-Tronco Neoplásicas/efeitos dos fármacos , Polifenóis/farmacologia , Antineoplásicos/administração & dosagem , Antineoplásicos/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Curcumina/administração & dosagem , Curcumina/uso terapêutico , Humanos , Polifenóis/administração & dosagem , Polifenóis/uso terapêutico
16.
Eur J Haematol ; 105(3): 326-334, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32421883

RESUMO

BACKGROUND: In multiple myeloma (MM), impact of specific chromosomal translocations involving IgH (14q21 locus, including t(4;14), t(11;14), and t(14;16)) has been explored extensively. However, over 15% MM patients harboring IgH translocation with undefined partners have long been ignored. METHODS: A prospective non-randomized cohort study with a total of 715 newly-diagnosed MM cases was conducted, 13.6% of whom were t(14;undefined) positive. The whole cohort was divided into four groups: no IgH split (47.7%); t(14;undefined) (13.6%); t(11;14) (17.6%); and t(4;14) or t(14;16) group (21.1%). RESULTS: Median OS for the four groups was 84.2, not reached (NR), 58.7, and 44.2 months, respectively, with P values for t(14;undefined) vs no IgH split, t(11;14), and t(4;14)/t(14;16) groups of 0.197, 0.022, and 0.001, respectively. In bortezomib-based group, the survival advantage gained by t(14;undefined) group was much more significant compared to t(11;14) and t(4;14)/t(14;16) groups. Importantly, t(14;undefined) turned out to be an independent predictive factor for longer OS of MM patients in multivariate analysis, especially in the context of bortezomib treatment. Similar results were also observed in the PUMCH external validation cohort. CONCLUSION: Collectively, our data confirmed and externally validated the favorable prognosis of the t(14;undefined) groups, especially in the era of novel agents.


Assuntos
Cadeias Pesadas de Imunoglobulinas/genética , Mieloma Múltiplo/genética , Mieloma Múltiplo/mortalidade , Translocação Genética , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais , Cromossomos Humanos Par 11 , Cromossomos Humanos Par 14 , Cromossomos Humanos Par 16 , Cromossomos Humanos Par 4 , Feminino , Frequência do Gene , Humanos , Hibridização in Situ Fluorescente , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/diagnóstico , Mieloma Múltiplo/terapia , Prognóstico , Modelos de Riscos Proporcionais
17.
Pestic Biochem Physiol ; 155: 81-89, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30857631

RESUMO

Sclerotinia sclerotiorum is a necrotrophic and filamentous fungus with a broad host range. Fluazinam is a pyridinamine fungicide with a broad spectrum of antifungal activity and had a strong inhibition effect on mycelial growth of S. sclerotiorum populations. But the impact of fluazinam on morphological and physiological characteristics of S. sclerotiorum is little known. In this study, the EC50 values of fluazinam to three strains of S. sclerotiorum (CZ17S, YZ55S and SA42S) were 0.0084, 0.007, 0.0065 µg/ml respectively. After fluazinam treatment, hyphae of S. sclerotiorum became thinner, hyphal offshoot of top increased, the distance between one septum and another became shorter, cell membrane permeability increased markedly, exopolysaccharide (EPS) content and oxalic acid content decreased significantly, peroxidase (POD) activity increased significantly and mycelial respiration was inhibited. While the number and dry weight of sclerotia, glycerol content in the mycelia did not significantly change. In protective activity assay on detached rapeseed leaves, application of fluazinam at 40 µg/ml and 80 µg/ml, the control efficacy reached to 41.4% and 100%, respectively. In curative activity assay, application of fluazinam at 100 µg/ml, the control efficacy reached to 61.09%. In the same concentration, protective activity of fluazinam against S. sclerotiorum was higher than curative activity. These results will contribute to us on evaluating the potential of the fungicide fluazinam for management of Sclerotinia stem rot and understanding the mode of action of fluazinam against S. sclerotiorum.


Assuntos
Aminopiridinas/farmacologia , Ascomicetos/efeitos dos fármacos , Antifúngicos/farmacologia , Micélio/efeitos dos fármacos , Doenças das Plantas/microbiologia
18.
Small ; 14(45): e1801963, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30204281

RESUMO

Inorganic luminescent materials as one of the important high-performance materials are widely used for industry and scientific research, mainly owing to their outstanding luminescence properties. However, inorganic luminescent materials are typically brittle and inelastic, which greatly limit their use in practical applications, particularly in flexible optoelectronic devices. In this work, it is shown that "plum-pudding" like CsPbBr3 /Cs4 PbBr6 perovskite crystals anchor onto Al2 O3 -La2 O3 (CCAL) nanofibrous membranes, which are synthesized via a facile electrospinning and subsequent supersaturated recrystallization process. The as-synthesized CCAL membranes exhibit outstanding mechanical flexibility and luminescence properties. Meanwhile, the crystal structure and luminous performance of the CCAL membranes are regulated by different molar ratios of CsBr/PbBr2 . The photoluminescence reaches a maximum value for the CCAL membranes produced with a CsBr/PbBr2 ratio of 1, and shows a narrow emission line-width of 18 nm. Furthermore, the potential applications of the CCAL nanofibrous membranes in green light devices through a remote nanofibrous membranes packaging approach are demonstrated. A pure green emission is achieved with the Commission Internationale de L'Eclairage color coordinates of (0.28, 0.65). This facile strategy would open a new avenue to flexible inorganic luminescent materials for the lighting and backlight display industries.

19.
Biotechnol Lett ; 40(2): 279-284, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29119355

RESUMO

OBJECTIVES: To create a multifunctional medical material that combines the advantages of both nanofibers and macroyarns. RESULTS: A novel electrospinning-based approach was developed for creating polycaprolactone (PCL) nanofiber covered yarns (PCL-NCYs) in which polyglycolic acid multi-strand filaments (PGA-MFs) were used as the core. BALB/3T3 (mouse embryonic fibroblast cell line) cells were cultured on the PCL-NCYs substrate and cell morphology and proliferation were determined by methylthiazol tetrazolium (MTT) assay. Compared with PGA-MFs, PCL-NCYs had a higher porosity and tensile strength of 88 ± 8% and 348 ± 16 MPa and in particular, the porosity was four times higher. BALB/3T3 cells attached more easily onto the nanofiber structure and proliferated along the direction of nanofibers, indicating that PCL-NCYs can achieve better cell differentiation and proliferation. CONCLUSIONS: PCL-NCYs can be created by combining electrospinning covering and textile twisting, and have better mechanical property and higher porosity, and can be used as a novel scaffold in tissue engineering.


Assuntos
Materiais Biocompatíveis , Técnicas Eletroquímicas/métodos , Animais , Células 3T3 BALB , Materiais Biocompatíveis/síntese química , Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologia , Técnicas de Cultura de Células , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Forma Celular/efeitos dos fármacos , Técnicas Eletroquímicas/instrumentação , Desenho de Equipamento , Camundongos , Nanofibras/química , Poliésteres/química , Ácido Poliglicólico/química , Porosidade , Alicerces Teciduais/química
20.
Pestic Biochem Physiol ; 148: 8-15, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29891381

RESUMO

Fluazinam is a dinitroaniline fungicide with broad-spectrum activities. However, the activity of fluazinam against Bipolaris maydis which is the causal agent of southern corn leaf blight is unknown yet. In this study, baseline sensitivity of B. maydis to fluazinam was determined using 92 isolates collected during 2015 and 2016 from different geographical regions in Jiangsu Province of China, and the EC50 values ranged from 0.0396 to 0.9808 µg/ml with average value of 0.3853 ±â€¯0.2297 µg/ml, and 0.079 to 0.7832 µg/ml with average value of 0.3065 ±â€¯0.1384 µg/ml for mycelial growth and conidium germination respectively. Fluazinam did not affect the distribution of cell nucleus and the formation of septum of B. maydis. However, fluazinam could make mycelium of B. maydis contorted and the mycelial branches increased and inhibit the development of conidia. The result of transmission electron microscope showed that fluazinam damaged cell wall and cell membrane of mycelium, and make organelles in mycelial cell dissolved and vacuolated, and the cell almost broke up, which caused the intracellular plasma leakage increase. The protective activity test of fluazinam suggested that fluazinam had great control efficiency against B. maydis on detached corn leaves. Application of fluazinam at 10 µg/ml and 20 µg/ml, the control efficacy reached to 87.70% and 98.25% respectively. However, fluazinam had no curative activity against B. maydis on detached corn leaves. These results will contribute to us on evaluating the potential of the dinitroaniline fungicide fluazinam for management of diseases caused by B. maydis and understanding the mode of action of fluazinam against B. maydis.


Assuntos
Aminopiridinas/farmacologia , Ascomicetos/efeitos dos fármacos , Fungicidas Industriais/farmacologia , Ascomicetos/crescimento & desenvolvimento , Ascomicetos/ultraestrutura , Permeabilidade da Membrana Celular/efeitos dos fármacos , Núcleo Celular/efeitos dos fármacos , China , Meios de Cultura , Germinação , Testes de Sensibilidade Microbiana , Microscopia Eletrônica de Transmissão , Micélio/efeitos dos fármacos , Micélio/crescimento & desenvolvimento , Doenças das Plantas/microbiologia , Doenças das Plantas/prevenção & controle , Folhas de Planta/microbiologia , Esporos Fúngicos/efeitos dos fármacos , Esporos Fúngicos/crescimento & desenvolvimento , Zea mays/microbiologia
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