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1.
Circ Res ; 135(1): 76-92, 2024 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-38747146

RESUMO

BACKGROUND: Hypoxia and oxidative stress contribute to the development of pulmonary hypertension (PH). tRNA-derived fragments play important roles in RNA interference and cell proliferation, but their epitranscriptional roles in PH development have not been investigated. We aimed to gain insight into the mechanistic contribution of oxidative stress-induced 8-oxoguanine in pulmonary vascular remodeling. METHODS: Through small RNA modification array analysis and quantitative polymerase chain reaction, a significant upregulation of the 8-oxoguanine -modified tRF-1-AspGTC was found in the lung tissues and the serum of patients with PH. RESULTS: This modification occurs at the position 5 of the tRF-1-AspGTC (5o8G tRF). Inhibition of the 5o8G tRF reversed hypoxia-induced proliferation and apoptosis resistance in pulmonary artery smooth muscle cells. Further investigation unveiled that the 5o8G tRF retargeted mRNA of WNT5A (Wingless-type MMTV integration site family, member 5A) and CASP3 (Caspase3) and inhibited their expression. Ultimately, BMPR2 (Bone morphogenetic protein receptor 2) -reactive oxygen species/5o8G tRF/WNT5A signaling pathway exacerbated the progression of PH. CONCLUSIONS: Our study highlights the role of site-specific 8-oxoguanine-modified tRF in promoting the development of PH. Our findings present a promising therapeutic avenue for managing PH and propose 5o8G tRF as a potential innovative marker for diagnosing this disease.


Assuntos
Biomarcadores , Receptores de Proteínas Morfogenéticas Ósseas Tipo II , Hipertensão Pulmonar , Artéria Pulmonar , Hipertensão Pulmonar/metabolismo , Hipertensão Pulmonar/genética , Hipertensão Pulmonar/etiologia , Humanos , Receptores de Proteínas Morfogenéticas Ósseas Tipo II/metabolismo , Receptores de Proteínas Morfogenéticas Ósseas Tipo II/genética , Animais , Biomarcadores/metabolismo , Biomarcadores/sangue , Artéria Pulmonar/metabolismo , Proteína Wnt-5a/metabolismo , Proteína Wnt-5a/genética , Guanina/análogos & derivados , Guanina/metabolismo , Masculino , Estresse Oxidativo , Caspase 3/metabolismo , Miócitos de Músculo Liso/metabolismo , Proliferação de Células , Apoptose , Células Cultivadas , Remodelação Vascular , Feminino , Ratos , Espécies Reativas de Oxigênio/metabolismo , Músculo Liso Vascular/metabolismo
2.
Prep Biochem Biotechnol ; 53(4): 401-411, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-35792938

RESUMO

Few studies expressed the ß-galactosidase encoding gene from L. plantarum in E. coli so far. In the present study, the recombinant ß-galactosidase from L. plantarum FMNP01 was used as a catalyst in transgalactosylation to form tri-GOS and lactosucrose. In the presence of lactose and sucrose, six transfer products were formed in the transgalactosylation reaction with recombinant ß-galactosidase L.pFMNP01Gal as a catalyst. Three transfer products were tri-galacto-oligosaccharides (tri-GOS), lactosucrose, and lactulose; the other three transfer products needed to be identified further. Based on a single factor test and response surface methodological approach, the optimal transgalactosylation conditions of the production of tri-GOS and lactosucrose were determined as initial sugar concentration of 50%, lactose: sucrose ratio of 1:2, enzyme concentration of 3 U/mL, and reaction time of 6 h at 50 °C resulting in a maximum tri-GOS concentration of 47.69 ± 1.36 g/L and a maximum lactosucrose concentration of 8.18 ± 0.97 g/L.


Assuntos
Lactose , Sacarose , Escherichia coli/genética , Oligossacarídeos , beta-Galactosidase/genética
3.
Pharmacology ; 106(3-4): 202-210, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-32998136

RESUMO

BACKGROUND AND OBJECTIVES: With the increasing number of patients with febrile neutropenia (FN), voriconazole (VRC) has been widely used in hospitals for first-line treatment of FN. The study was designed for evaluating the influence of FMO3 mutation on the plasma disposition and adverse reactions of VRC in FN. MATERIALS AND METHODS: A single-center observational study was conducted in the inpatient ward for 4 years. The genotypes of FMO3 and cytochrome P450 (CYP) 2C19 were detected by PCR-restriction fragment length polymorphism. Patients with neutropenia were screened according to the CYP2C19 metabolic phenotype and other inclusion criteria. Five days after empirical administration of VRC, blood concentrations of VRC and nitrogen oxides in patients' blood were determined by liquid chromatography-electrospray tandem mass spectrometry (LC-ESI MS/MS). Serum parameters and clinical adverse reaction symptoms in the medical records were collected and statistically analyzed. RESULTS: A total of 165 patients with neutropenia with the intermediate metabolic phenotype of CYP2C19 were screened. At the initial stage of oral VRC treatment, patients with the FMO3 E308G genotype had a poorer plasma disposal ability to VRC than those with the wide type of FMO3 (WT) genotype (p = 0.0005). Moreover, patients with the FMO3 E308G genotype were more likely to have adverse drug reactions and abnormal serum parameters after receiving VRC treatment. For example, the serum potassium level in the FMO3 E308G genotype group was significantly lower than that in the WT group (p = 0.028), the abnormal level of total bilirubin in the FMO3 E308G genotype group was significantly higher than that in the WT group (p = 0.049), and the aspartate aminotransferase level in the E308G group was significantly higher than that in the WT group (p = 0.05). The incidence of atopic dermatitis and visual impairment in the FMO3 E308G genotype group was 67 and 75%, respectively, and the incidences of peripheral neuroedema, headache, and diarrhea were 57, 50, and 60%, respectively, which were significantly different from those in the WT group. CONCLUSION: FMO3 E308G reduces the activity of the FMO3 enzyme by decreasing the metabolic ability of VRC, which increases the plasma concentration of VRC and may also lead to adverse reactions in patients with FN.


Assuntos
Antifúngicos/efeitos adversos , Antifúngicos/farmacocinética , Neutropenia Febril/sangue , Neutropenia Febril/tratamento farmacológico , Oxigenases/genética , Voriconazol/efeitos adversos , Voriconazol/farmacocinética , Administração Oral , Adulto , Idoso , Idoso de 80 Anos ou mais , Antifúngicos/administração & dosagem , Antifúngicos/sangue , Aspartato Aminotransferases/metabolismo , Bilirrubina/metabolismo , Citocromo P-450 CYP2C19/genética , Feminino , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Oxigenases/metabolismo , Variantes Farmacogenômicos/fisiologia , Fenótipo , Plasma/efeitos dos fármacos , Polimorfismo Genético , Potássio/metabolismo , Estudos Retrospectivos , Soro/efeitos dos fármacos , Distribuição Tecidual , Voriconazol/administração & dosagem , Voriconazol/sangue
4.
Prep Biochem Biotechnol ; 46(4): 399-405, 2016 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-26176886

RESUMO

Strains of Leuconostoc mesenteroides, Pediococcus pentosaceus, and Lactobacillus brevis were identified from mango fruits by partial 16S rDNA gene sequence. Based on the ability of producing mannitol and diacetyl, Leuconostoc mesenteroides MPL18 and MPL39 were selected within the lactic acid bacteria isolates, and used as mixed starters to ferment mango juice (MJ). Both the autochthonous strains grew well in fermented mango juice (FMJ) and remained viable at 9.81 log cfu mL(-1) during 30 days of storage at 4°C. The content of total sugar of FMJ was lower than that of MJ, while the concentration of mannitol was higher than that of MJ, and the concentration of diacetyl was 3.29 ± 0.12 mg L(-1). Among detected organic acids including citric acid, gallic acid, lactic acid, and acetic acid, only citric acid and gallic acid were found in MJ, while all detected organic acids were found in FMJ. The concentration of lactic acid of FMJ was the highest (78.62 ± 13.66 mM) among all detected organic acids. The DPPH radical scavenging capacity of FMJ was higher than that of MJ. Total phenolic compounds were better preserved in FMJ. The acidity and sweetness had a noticeable impact on the overall acceptance of the treated sample.


Assuntos
Fermentação , Lactobacillaceae/metabolismo , Mangifera/metabolismo , Probióticos , Genótipo , Lactobacillaceae/genética , Filogenia
5.
Genes (Basel) ; 15(8)2024 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-39202436

RESUMO

This study investigated the transcriptomic mechanisms underlying melatonin accumulation and the enhancement of salt tolerance in hull-less barley seeds subjected to zinc sulphate stress. Following zinc sulphate treatment, hull-less barley seeds demonstrated increased melatonin accumulation and improved salt tolerance. Through transcriptome analysis, the study compared gene expression alterations in seeds (using the first letter of seed, this group is marked as 'S'), seeds treated with pure water (as the control group, is marked as 'C'), and germinated seeds exposed to varying concentrations of zinc sulphate (0.2 mM and 0.8 mM, the first letter of zinc sulphate, 'Z', is used to mark groups 'Z1' and 'Z2'). The analysis revealed that 8176, 759, and 622 differentially expressed genes (DEGs) were identified in the three comparison groups S.vs.C, C.vs.Z1, and C.vs.Z2, respectively. Most of the DEGs were closely associated with biological processes, including oxidative-stress response, secondary metabolite biosynthesis, and plant hormone signaling. Notably, zinc sulphate stress influenced the expression levels of Tryptophan decarboxylase 1 (TDC1), Acetylserotonin O-methyltransferase 1 (ASMT1), and Serotonin N-acetyltransferase 2 (SNAT2), which are key genes involved in melatonin synthesis. Furthermore, the expression changes of genes such as Probable WRKY transcription factor 75 (WRKY75) and Ethylene-responsive transcription factor ERF13 (EFR13) exhibited a strong correlation with fluctuations in melatonin content. These findings contribute to our understanding of the mechanisms underlying melatonin enrichment in response to zinc sulphate stress.


Assuntos
Regulação da Expressão Gênica de Plantas , Hordeum , Melatonina , Proteínas de Plantas , Transcriptoma , Sulfato de Zinco , Melatonina/farmacologia , Melatonina/biossíntese , Hordeum/genética , Hordeum/efeitos dos fármacos , Hordeum/metabolismo , Hordeum/crescimento & desenvolvimento , Regulação da Expressão Gênica de Plantas/efeitos dos fármacos , Sulfato de Zinco/farmacologia , Transcriptoma/efeitos dos fármacos , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Perfilação da Expressão Gênica/métodos , Sementes/genética , Sementes/efeitos dos fármacos , Sementes/crescimento & desenvolvimento , Sementes/metabolismo , Germinação/efeitos dos fármacos , Germinação/genética , Tolerância ao Sal/genética
6.
Acta Pharm Sin B ; 13(12): 4840-4855, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38045055

RESUMO

Pulmonary hypertension (PH) is an extremely malignant pulmonary vascular disease of unknown etiology. ADAR1 is an RNA editing enzyme that converts adenosine in RNA to inosine, thereby affecting RNA expression. However, the role of ADAR1 in PH development remains unclear. In the present study, we investigated the biological role and molecular mechanism of ADAR1 in PH pulmonary vascular remodeling. Overexpression of ADAR1 aggravated PH progression and promoted the proliferation of pulmonary artery smooth muscle cells (PASMCs). Conversely, inhibition of ADAR1 produced opposite effects. High-throughput whole transcriptome sequencing showed that ADAR1 was an important regulator of circRNAs in PH. CircCDK17 level was significantly lowered in the serum of PH patients. The effects of ADAR1 on cell cycle progression and proliferation were mediated by circCDK17. ADAR1 affects the stability of circCDK17 by mediating A-to-I modification at the A5 and A293 sites of circCDK17 to prevent it from m1A modification. We demonstrate for the first time that ADAR1 contributes to the PH development, at least partially, through m1A modification of circCDK17 and the subsequent PASMCs proliferation. Our study provides a novel therapeutic strategy for treatment of PH and the evidence for circCDK17 as a potential novel marker for the diagnosis of this disease.

7.
Front Genet ; 13: 936658, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35991573

RESUMO

Objective: Based on TCGA database, a prediction model for 1-, 3-, and 5-year overall survival rates of gastric cancer (GC) patients was constructed by analyzing the critical risk factors affecting the prognosis of gastric cancer patients. Method: Clinicopathological features as well as gene signature of GC patients were obtained from TCGA database. Patients were randomly divided into a training cohort and an internal validation cohort. Independent predictors of GC prognosis were analyzed by univariate and multivariate Cox analyses to construct nomogram. The accuracy and reliability of the model was further validated by calibration curves, ROC curves, and C-indexes, and the clinical utility of the model was analyzed by decision analysis curves. Result: Age, sex, N stage, M stage, METTL16, RBM15, FMR1, IGFBP1, and FTO were significantly associated with the prognosis of GC patients, and these predictors were further included in the construction of nomogram. The C-indexes for the training cohort and validation set were 0.735 and 0.688, respectively. The results of the ROC curve analysis indicated that the area under the curve (AUC) exceeded 0.6 in training and validation sets at 1, 3, and 5 years. Conclusion: We have constructed and validated a nomogram that provides individual survival condition prediction for GC patients. The prognostic model integrating gene signatures and clinicopathological characteristics would help clinicians determine the prognosis of patients with GC and develop individualized treatment plans.

8.
Genome Announc ; 2(6)2014 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-25428967

RESUMO

Lactobacillus plantarum strain FMNP01 is a new strain with probiotic properties that was isolated from fresh mango from Guangzhou, China. Here, we report the complete genome of this organism.

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