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1.
Artigo em Inglês | MEDLINE | ID: mdl-38489081

RESUMO

Gastric cancer (GC) treatment regimens are still unsatisfactory. Recently, Urolithin A (UroA) has gained tremendous momentum due to its anti-tumor properties. However, the therapeutic effect and underlying mechanisms of UroA in GC are unclear. We explored the effects and related mechanisms of UroA on GC both in vivo and in vitro. A Cell Counting Kit-8 was used to determine the influence of UroA on the proliferation of GC cell lines. The Autophagy inhibitor 3-methyladenine (3MA) was employed to clarify the role of autophagy in the anti-tumor effect of UroA. Simultaneously, we detected the core-component proteins involved in autophagy and its downstream pathways. Subsequently, the in vivo anti-tumor effect of UroA was determined using a xenograft mouse model. Western blotting was used to detect the core protein components of the anti-tumor pathways, and 16S rDNA sequencing was used to detect the effect of UroA on the gut microbiota. We found that UroA suppressed tumor progression. The use of 3MA undermined the majority of the inhibitory effect of UroA on tumor cell proliferation, further confirming the importance of autophagy in the anti-tumor effect of UroA. Invigorating of autophagy activated the downstream Hippo pathway, thereby inhibiting the Warburg effect and promoting cell apoptosis. In addition, UroA modulated the composition of the gut microbiota, as indicated by the increase of probiotics and the decrease of pathogenic bacteria. Our research revealed new anti-tumor mechanisms of UroA, which may be a promising candidate for GC treatment.

2.
J Agric Food Chem ; 72(15): 8550-8568, 2024 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-38546976

RESUMO

Pathogenic fungi pose a significant threat to crop yields and human healthy, and the subsequent fungicide resistance has greatly aggravated these agricultural and medical challenges. Hence, the development of new fungicides with higher efficiency and greater environmental friendliness is urgently required. In this study, luvangetin, isolated and identified from the root of Zanthoxylum avicennae, exhibited wide-spectrum antifungal activity in vivo and in vitro. Integrated omics and in vitro and in vivo transcriptional analyses revealed that luvangetin inhibited GAL4-like Zn(II)2Cys6 transcriptional factor-mediated transcription, particularly the FvFUM21-mediated FUM cluster gene expression, and decreased the biosynthesis of fumonisins inFusarium verticillioides. Moreover, luvangetin binds to the double-stranded DNA helix in vitro in the groove mode. We isolated and identified luvangetin, a natural metabolite from a traditional Chinese edible medicinal plant and uncovered its multipathogen resistance mechanism. This study is the first to reveal the mechanism underlying the antifungal activity of luvangetin and provides a promising direction for the future use of plant-derived natural products to prevent and control plant and animal pathogenic fungi.


Assuntos
Fumonisinas , Fungicidas Industriais , Fusarium , Zanthoxylum , Animais , Humanos , Fungicidas Industriais/farmacologia , Fungicidas Industriais/metabolismo , Antifúngicos/farmacologia , Antifúngicos/metabolismo , Zanthoxylum/metabolismo , Fumonisinas/metabolismo
3.
Cell Rep Methods ; 4(3): 100721, 2024 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-38452769

RESUMO

Ribose 2'-O-methylation is involved in critical biological processes, but its biological functions and significance in mRNAs remain underexplored. We have developed NJU-seq, a sensitive method for unbiased 2'-O-methylation (Nm) profiling, and Nm-VAQ, a site-specific quantification tool. Using these tools in tandem, we identified thousands of Nm sites on mRNAs of human and mouse cell lines, of which 68 of 84 selected sites were further validated to be more than 1% 2'-O-methylated. Unlike rRNA, most mRNA Nm sites were from 1% to 30% methylated. In addition, mRNA Nm was dynamic, changing according to the circumstance. Furthermore, we show that fibrillarin is involved as a methyltransferase. By mimicking the detected Nm sites and the context sequence, the RNA fragments could be 2'-O-methylated and demonstrated higher stability but lower translation efficiency. Last, profiling of Nm sites in lung surgery samples revealed common signatures of lung cancer pathogenesis, providing potential new diagnostic markers.


Assuntos
RNA Ribossômico , RNA , Animais , Camundongos , Humanos , RNA Mensageiro/genética , RNA/metabolismo , RNA Ribossômico/genética , Metilação , Metiltransferases/metabolismo
4.
Gut Microbes ; 16(1): 2302065, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38196273

RESUMO

Hepatic immunity is one of the driving forces for the development of nonalcoholic steatohepatitis (NASH), and targeting gut microbiota is believed to affect the hepatic immune constitution. Here, we aimed to investigate the hepatic immunological state in NASH, with a specific emphasis on natural killer (NK) cells. In addition, we aimed to identify the contributing species that target hepatic immunity to provide new directions and support the feasibility of immunotherapy for NASH. A possible NASH population was determined by combination of long-term severe fatty liver, metabolic disorders and increased serum CK18 to detect serum immune factors and gut microbiota. NASH was induced in mice fed a high-fat diet to verify the prophylactic effect of the functional species on the immunopathology and development of NASH. Hepatic immunologic state was examined, and the effector functions of NK cells were detected. Hepatic transcriptome, proteomic, and fecal metagenome were performed. We observed a statistical increase in serum IL-10 (p < 0.001) and non-statistical decrease in interferon-γ and IL-6 in NASH population, hinting at the possibility of immune tolerance. Fecal Bacteroides uniformis and Bifidobacterium bifidum were abundant in healthy population but depleted in NASH patients. In NASH mice, hepatic CD8+T cells, macrophages, and dendritic cells were increased (p < 0.01), and NK cells were inhibited, which were identified with decreased granzyme B (p < 0.05). Bacteroides uniformis and Bifidobacterium bifidum improved hepatic pathological and metabolic cues, increased hepatic NK cells and reduced macrophages (p < 0.05). Bacteroides uniformis also restored hepatic NK cell function, which was identified as increased CD107a (p < 0.05). Transcriptional and translational profiling revealed that the functional species might restore the function of hepatic NK cells through multiple pathways, such as reduction of inhibitory molecules in NK cells. Bacteroides uniformis and Bifidobacterium bifidum are novel prophylactics for NASH that restore the impaired function of hepatic NK cells.


Assuntos
Bifidobacterium bifidum , Microbioma Gastrointestinal , Hepatopatia Gordurosa não Alcoólica , Humanos , Animais , Camundongos , Hepatopatia Gordurosa não Alcoólica/etiologia , Hepatopatia Gordurosa não Alcoólica/prevenção & controle , Dieta Hiperlipídica/efeitos adversos , Proteômica , Células Matadoras Naturais , Tolerância Imunológica
5.
Cell Mol Biol (Noisy-le-grand) ; 69(10): 121-128, 2023 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-37953575

RESUMO

Gut microbiota dysbiosis is an essential factor contributing to non-alcoholic fatty liver disease (NAFLD), in which the gut-liver axis plays a crucial role. Peroxisome proliferator-activated receptor δ (PPARδ) is considered a new direction for the research on NAFLD due to its positive regulation of glucose and lipid metabolism. Our experiment aimed to investigate the effect of PPARδ gene deletion on gut microbiota and NAFLD through the gut-liver axis. PPARδ-/- mice and wild-type mice were randomly divided into high-fat diet(HFD) groups and normal diet groups. In each group, six mice were sacrificed at weeks 4, 8, and 12. Metabolic indicators and inflammation indicators were measured, and the degree of liver steatosis and the ileum mucosa integrity were evaluated. Additionally, fecal samples were subjected to 16S rDNA gene sequencing and analysis of gut microbiota. Deletion of the PPARδ gene exhibited exacerbated effects on HFD-induced NAFLD and displayed more severe liver inflammation and intestinal mucosal barrier injuries. The HFD reduced the abundance of short-chain fatty acid (SCFA)-producing bacteria and increased the abundance of intestinal endotoxin-rich bacteria in mice. Deletion of the PPARδ gene exacerbated this trend, resulting in decreased abundances of norank_f__Eubacterium_coprostanoligenes_group and Alloprevotella and increased abundances of Acidibacter, unclassified_f__Comamonadaceae, unclassified_c__Alphaproteobacteria, unclassified_f__Beijerinckiaceae, unclassified_f__Caulobacteraceae, unclassified_c__Bacteroidia and Bosea. Spearman's correlation analysis found Lachnoclostridium, unclassified_f__Rhizobiaceae, Allobaculum, Acinetobacter, Romboutsia, norank_f__Muribaculaceae and Dubosiella showed some correlations with metabolic indicators, inflammation indicators, NAS and occludin. Deletion of the PPARδ gene exacerbated HFD-induced gut microbiota dysbiosis and affected NAFLD through the gut-liver axis.


Assuntos
Hepatopatia Gordurosa não Alcoólica , PPAR delta , Animais , Camundongos , Dieta Hiperlipídica/efeitos adversos , Disbiose/metabolismo , Inflamação/genética , Inflamação/metabolismo , Fígado/metabolismo , Camundongos Endogâmicos C57BL , Hepatopatia Gordurosa não Alcoólica/genética , PPAR delta/genética , PPAR delta/metabolismo
6.
Front Biosci (Landmark Ed) ; 28(9): 224, 2023 09 26.
Artigo em Inglês | MEDLINE | ID: mdl-37796712

RESUMO

BACKGROUND: Considering the remarkable heterogeneity of biological features of renal cell carcinoma (RCC), the current clinical classification that only relies on classic clinicopathological features is in urgent need of improvement. Herein, we aimed to conduct DNA methylation modification patterns in RCC. METHODS: We retrospectively curated multiple RCC cohorts, comprising TCGA-KIRC, TCGA-KICH, TCGA-KIRP, and E-MTAB-1980. DNA methylation modification patterns were proposed with an unsupervised clustering algorithm based on 20 DNA methylation regulators. Immunological features were characterized using tumor-infiltrating immune cells and immunomodulators. Sensitivity to immuno- or targeted therapy was estimated with submap and Genomics of Drug Sensitivity in Cancer (GDSC). DNA methylation score (DMS) was developed with principal component analysis. RESULTS: Three DNA methylation modification patterns were conducted across RCC patients, namely C1, C2 and C3. Among them, C3 displayed the most remarkable survival advantage. The three patterns presented in agreement with immune phenotypes: immune-desert, immune-excluded, and immune-inflamed, respectively. These patterns displayed distinct responses to anti-PD-1 and targeted drugs. DMS enabled the quantification of DNA methylation status individually as an alternative tool for prognostic estimation. CONCLUSIONS: The DNA methylation molecular patterns we proposed are an innovative complement to the traditional classification of RCC, which might contribute to precision medicine.


Assuntos
Carcinoma de Células Renais , Neoplasias Renais , Humanos , Carcinoma de Células Renais/tratamento farmacológico , Carcinoma de Células Renais/genética , Metilação de DNA , Estudos Retrospectivos , Imunoterapia , Neoplasias Renais/tratamento farmacológico , Neoplasias Renais/genética
7.
BMC Endocr Disord ; 23(1): 201, 2023 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-37726718

RESUMO

PURPOSE: To determine the population attributable fraction (PAF) of fatty liver disease (FLD) for type 2 diabetes mellitus (T2DM) and compare it to the PAFs of other metabolic abnormalities. METHODS: We conducted a 10-year retrospective cohort study of 33,346 individuals in Karamay Central Hospital of Xinjiang. Individuals were followed up for T2DM occurrence based on FBS. The PAFs of FLD were calculated generally and respectively in different sex and age groups. A comparison of the PAF of FLD and that of other metabolic abnormalities, as well as the PAFs of FLD in different groups classified based on age and sex, was performed using Cox regression. RESULTS: During an average follow-up period of 3.71 years, 1486 T2DM were diagnosed. The incidence density of T2DM was 1.2/100 person-years, and cumulative incidence rate was 4456.31/100,000 person-years. Partial PAF (PAFp) of FLD in the entire population was 23.11%. In the male population, PAFp was higher at 30-40 years old. In the female population, it was higher when age ≥ 60 years old. In multivariable Cox regression model, FLD, male sex, age ≥ 45 years old, overweight, hypertriglyceridaemia, and systolic hypertension were independent risk factors for T2DM, with corresponding PAFp of 25.00%, 24.99%, 36.47%, 24.96%, 5.71%, and 6.76%, respectively. Age ≥ 45 years old showed the highest PAFp and adjusted hazard ratio, followed by FLD. CONCLUSIONS: FLD contributes more to T2DM incidence than other metabolic disorders. Particular attention should be given to male populations of 30-40 and female populations above 60 for FLD prevention and treatment.


Assuntos
Diabetes Mellitus Tipo 2 , Hepatopatia Gordurosa não Alcoólica , Humanos , Feminino , Masculino , Pessoa de Meia-Idade , Adulto , Diabetes Mellitus Tipo 2/epidemiologia , Estudos Retrospectivos , Fatores de Risco , Hospitais
8.
Mar Environ Res ; 190: 106115, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37540963

RESUMO

Ballast water is one of the main vectors for the spread of harmful organisms among geologically isolated waters. However, the successional processes of microbial functions and assembly processes in ballast water during the long-term shipping voyage remain unclear. In this study, the compositions, ecological functions, community assembly, and potential environmental drivers of bacteria and microeukaryotes were investigated in simulated ballast water microcosms for 120 days. The results showed that the diversity and compositions of the bacterial and microeukaryotic communities varied significantly in the initial 40 days (T0∼T40 samples) and then gradually converged. The relative abundance of Proteobacteria showed a distinct tendency to decrease (87.90%-41.44%), while that of Ascomycota exhibited an increasing trend (6.35%-62.12%). The functional groups also varied significantly over time and could be related to the variations of the microbial community. The chemoheterotrophy and aerobic chemoheterotrophy functional groups for bacteria decreased from 44.80% to 28.02% and from 43.77% to 25.39%, respectively. Additionally, co-occurrence network analysis showed that the structures of the bacterial community in T60∼T120 samples were more stable than those in T0∼T40 samples. Stochastic processes also significantly affected the community assembly of bacteria and microeukaryotes. pH played the most significant role in driving the structures and assembly processes of the bacterial and microeukaryotic communities. The results of this study could aid in the understanding of variations in the functions and ecological processes of bacterial and microeukaryotic communities in ballast water over time and provide a theoretical basis for its management.


Assuntos
Microbiota , Água , Bactérias
9.
Mar Pollut Bull ; 194(Pt B): 115336, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37542926

RESUMO

Accurate detecting bacterial communities in ballast water and sediments supports risk management. This study uses full-length 16S rRNA gene sequencing to investigate the bacterial communities in ballast water and sediments, focusing on detecting pathogens. The results indicate that full-length sequencing more accurately reveals the species diversity. There is a significant difference (P < 0.05) in bacterial communities between ballast water and sediments, despite both being dominated by the Proteobacteria phylum. Thirty human and fish pathogens were identified by full-length sequencing, yet only five pathogens were detected from V3-V4 sequencing. Notably, emerging pathogens such as Citrobacter freundii and Nocardia nova are detected in samples, which are harmful to aquaculture and human health. Several opportunistic pathogens were also identified. In summary, this study provides important insights into the bacterial communities in ballast water and sediments, highlighting the need for strict management.


Assuntos
Navios , Água , Humanos , RNA Ribossômico 16S/genética , Genes de RNAr , Bactérias/genética
10.
Exp Ther Med ; 26(3): 420, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37602313

RESUMO

N6-methyladenosine (m6A) serves a critical role in regulating gene expression and has been associated with various diseases; however, its role in the differentiation of endothelial progenitor cells (EPCs) remains unclear. The present study used liquid chromatography with tandem mass spectrometry and immunofluorescence assays to quantify the levels of m6A in human peripheral blood-derived EPCs (HPB-EPCs) before and after differentiation into mature cells. The present study performed Cell Counting Kit 8, Transwell, and tube formation assays to determine the effects of overexpression and knockdown of Wilms' tumor 1-associated protein (WTAP) on HPB-EPCs. The results revealed that the level of m6A modification was significantly increased during HPB-EPCs differentiation, and WTAP exhibited the most significant alteration among the enzymes involved in m6A regulation. When WTAP was overexpressed in HPB-EPCs, cell proliferation, invasion, and the formation of tubes were improved, whereas WTAP knockdown yielded the opposite effects. In conclusion, the present study highlighted the involvement of m6A in regulating EPC differentiation, with WTAP acting as a promoter of EPC differentiation.

11.
Obes Facts ; 16(6): 548-558, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37640023

RESUMO

INTRODUCTION: The prevalence of metabolic dysfunction-associated fatty liver disease (MAFLD) with renal insufficiency in recent years and the association between MAFLD and renal insufficiency are not entirely clear, especially in overweight/obesity. The aim of this study was to analyze the prevalence and risk factors of MAFLD with renal insufficiency in overweight/obese adults. METHODS: Individuals who attended checkup at the Second Affiliated Hospital of Xi'an Jiaotong University from 2016 to 2021 were included. The prevalence of MAFLD with renal insufficiency (estimated glomerular filtration rate ≤90 mL/min/1.73 m2) in overweight/obesity was estimated. Propensity score-matched analysis, univariate and multivariate analyses were used to determine the risk factors for MAFLD with renal insufficiency. RESULTS: From 2016 to 2021, the prevalence of MAFLD in overweight/obesity reached its highest of 44.7% in 2017 and its lowest of 36.9% in 2018; and 33.9% in 2021 and 21.8% in 2019 is the highest and lowest prevalence of MAFLD with renal insufficiency, respectively. MAFLD was more common in men, old individuals, and persons with a higher body mass index (BMI) and was characterized by significant renal insufficiency. MAFLD with renal insufficiency was more common in women, old individuals, and persons with a higher BMI and was characterized by significant metabolic dysfunction and liver fibrosis. Multivariable analysis showed that BMI, uric acid, and fibrosis (evaluated with noninvasive liver fibrosis score [fibrosis-4]) were independent risk factors for MAFLD with renal insufficiency. CONCLUSION: The prevalence of MAFLD with renal insufficiency in overweight/obese adults is quite high in the last 5 years. BMI, uric acid, and fibrosis are independent risk factors for MAFLD with renal insufficiency.


Assuntos
Hepatopatia Gordurosa não Alcoólica , Insuficiência Renal , Masculino , Adulto , Feminino , Humanos , Sobrepeso/complicações , Sobrepeso/epidemiologia , Prevalência , Ácido Úrico , Obesidade/complicações , Obesidade/epidemiologia , Fatores de Risco , Hepatopatia Gordurosa não Alcoólica/complicações , Hepatopatia Gordurosa não Alcoólica/epidemiologia , Cirrose Hepática , Insuficiência Renal/epidemiologia , Insuficiência Renal/etiologia
12.
J Clin Transl Hepatol ; 11(4): 763-776, 2023 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-37408808

RESUMO

Background and aims: Non-alcoholic fatty liver disease (NAFLD) is closely associated with gut microbiota and has become the most common chronic liver disease worldwide, but the relationship between specific strains and NAFLD has not been fully elucidated. We aimed to investigate whether Akkermansia muciniphila and Bifidobacterium bifidum could prevent NAFLD, the effects of their action alone or in combination, possible mechanisms, and modulation of the gut microbiota. Methods: Mice were fed with high-fat diets (HFD) for 20 weeks, in which experimental groups were pretreated with quadruple antibiotics and then given the corresponding bacterial solution or PBS. The expression of the glycolipid metabolism indicators, liver, and intestinal farnesol X receptors (FXR), and intestinal mucosal tight junction proteins were detected. We also analyzed the alterations of inflammatory and immune status and the gut microbiota of mice. Results: Both strains were able to attenuate mass gain (p<0.001), insulin resistance (p<0.001), and liver lipid deposition (p<0.001). They also reduced the levels of the pro-inflammatory factors (p<0.05) and the proportion of Th17 (p<0.001), while elevating the proportion of Treg (p<0.01). Both strains activated hepatic FXR while suppressing intestinal FXR (p<0.05), and elevating tight junction protein expression (p<0.05). We also perceived changes in the gut microbiota and found both strains were able to synergize beneficial microbiota to function. Conclusions: Administration of A. muciniphila or B. bifidum alone or in combination was protective against HFD-induced NAFLD formation and could be used as alternative treatment strategy for NAFLD after further exploration.

13.
Sci Rep ; 13(1): 11963, 2023 07 24.
Artigo em Inglês | MEDLINE | ID: mdl-37488139

RESUMO

Interferon-γ release assay (IGRA) is a widely used blood test for detecting TB infection. However, a positive result of IGRA cannot differentiate active tuberculosis (ATB) infection from inactive tuberculosis (IATB). In this study, we established a nomogram model for predictive risk of ATB, differentiated from IATB, based on the concentration of interferon-γ (IFN-γ) of QuantiFERON-TB Gold In-Tube Test (QFT-GIT) and clinical characteristics. Participants with a positive QFT-GIT result were recruited and divided into a training and validation cohort according to hospitalisation date. The nomogram model for the differential diagnosis of ATB from IATB was established according to gender, age, pleural effusion (PE), and the concentration of IFN-γ in the Nil, TB antigen, and mitogen tube of QFT-GIT in the training cohort by logistic regression and validated in the validation cohort, and then combined with adenosine deaminase (ADA) to evaluated the performance value in ATB cases with PE. The area under receiver operating characteristic curve (AUC) of the diagnostic nomogram model, which we called the NSMC-ATB model for ATB diagnosis was 0.819 (95% CI 0.797-0.841), with sensitivity 73.16% and specificity 75.95% in training cohort, and AUC was 0.785 (95% CI 0.744-0.827), with sensitivity 67.44% and specificity 75.14% in validation cohort. A combination of the NSMC-ATB model and ADA performed better than the NSMC-ATB model and ADA alone in predicting ATB cases with PE, as AUC was 0.903 (95% CI 0.856-0.950) with sensitivity 78.63% and specificity 87.50%. We established an effective diagnostic nomogram model, called the NSMC-ATB model to differentiate ATB from IATB. Meanwhile, the combination of the NSMC-ATB model and ADA improved the performance value of ATB with PE.


Assuntos
Tuberculose Latente , Derrame Pleural , Tuberculose , Humanos , Nomogramas , Testes de Liberação de Interferon-gama , Exsudatos e Transudatos , Interferon gama
14.
Biochem Biophys Res Commun ; 669: 134-142, 2023 08 20.
Artigo em Inglês | MEDLINE | ID: mdl-37271025

RESUMO

Non-alcoholic fatty liver disease (NAFLD) has become the most common chronic liver disease worldwide but still lacks specific treatment modalities. The gut microbiota and its metabolites have been shown to be intimately involved in NAFLD development, participating in and regulating disease progression. Trimethylamine N-oxide (TMAO), a metabolite highly dependent on the gut microbiota, has been shown to play deleterious regulatory roles in cardiovascular disease, but the relationship between it and NAFLD lacks validation from basic experiments. This research applied TMAO intervention by constructing fatty liver cell models in vitro to observe its effect on fatty liver cells and potential key genes and performed siRNA interference on the gene to verify the action. The results showed that TMAO intervention promoted the appearance of more red-stained lipid droplets in Oil-red O staining results, increased triglyceride (TG) levels and increased mRNA levels of liver fibrosis-related genes, and also identified one of the key genes, keratin17 (KRT17) via transcriptomics. Following the reduction in its expression level, under the same treatment, there were decreased red-stained lipid droplets, decreased TG levels, decreased indicators of impaired liver function as well as decreased mRNA levels of liver fibrosis-related genes. In conclusion, the gut microbiota metabolite TMAO could promote lipid deposition and fibrosis process via the KRT17 gene in fatty liver cells in vitro.


Assuntos
Microbioma Gastrointestinal , Hepatopatia Gordurosa não Alcoólica , Humanos , Fibrose , Metilaminas/farmacologia , Metilaminas/metabolismo , Cirrose Hepática , Lipídeos
15.
Biochimie ; 212: 106-113, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37105299

RESUMO

RNase R is a member of the RNA exonuclease family that digests RNA in the 3'-5' direction. Previous studies have identified RNase R from Mycoplasma genitalium (MgR) as the only RNA exonuclease that is sensitive to 2'-O-methylation (Nm) modification. However, the mechanism underlying this characteristic is not well understood. In this study, we aimed to explore the molecular mechanism of RNase R Nm sensitivity using an improved assay that can better evaluate Nm sensitivity. By comparing the sequences of five wild-type RNase R variants from Mycoplasma, we identified the importance of loop 18 in Nm sensitivity. Furthermore, we demonstrated the critical roles of L283, T278, and T279 within loop18. Our findings deepen the understanding of the molecular mechanism of why MgR is sensitive to Nm and provide a potential direction of protein engineering for applications.


Assuntos
Exonucleases , Exorribonucleases , Metilação , Exorribonucleases/metabolismo , Exonucleases/metabolismo , RNA/metabolismo
16.
Biomed Pharmacother ; 158: 114208, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36800265

RESUMO

The COVID-19 pandemic has affected millions of people and posed an unprecedented burden on healthcare systems and economies worldwide since the outbreak of the COVID-19. A considerable number of nations have investigated COVID-19 and proposed a series of prevention and treatment strategies thus far. The pandemic prevention strategies implemented in China have suggested that the spread of COVID-19 can be effectively reduced by restricting large-scale gathering, developing community-scale nucleic acid testing, and conducting epidemiological investigations, whereas sporadic cases have always been identified in numerous places. Currently, there is still no decisive therapy for COVID-19 or related complications. The development of COVID-19 vaccines has raised the hope for mitigating this pandemic based on the intercross immunity induced by COVID-19. Thus far, several types of COVID-19 vaccines have been developed and released to into financial markets. From the perspective of vaccine use in globe, COVID-19 vaccines are beneficial to mitigate the pandemic, whereas the relative adverse events have been reported progressively. This is a review about the development, challenges and prospects of COVID-19 vaccines, and it can provide more insights into all aspects of the vaccines.


Assuntos
Vacinas contra COVID-19 , COVID-19 , Humanos , COVID-19/epidemiologia , COVID-19/prevenção & controle , Pandemias/prevenção & controle , China/epidemiologia , Surtos de Doenças
17.
Environ Pollut ; 316(Pt 2): 120540, 2023 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-36370977

RESUMO

This study found that the cross-linkable zinc acrylic nanosphere aggregates (NAs) as precursors were successfully prepared by a simple one-step synthesis route, and Zn,O dopped-carbon nanocomposites were obtained through temperature-controllable engineering, which showed excellent adsorption capacities for perfluorooctanoic acid (PFOA). A series of experiments were performed to investigate and compare carbon materials for the efficient removal of PFOA. The maximum adsorption capacities of PFOA absorbed on carbon nanospheres aggregates (CNAs) were calculated by the Langmuir (360.98 mg/g) and Sips models (309.65 mg/g). The kinetic model indicated there was chemical adsorption and physical adsorption in the adsorption process. Van der Waals force and electrostatic interactions might be the dominant mechanism of the adsorption process. Additionally, pore-filling also played a role in the adsorption process. Furthermore, the adsorption efficiency was still above 90% after five cycles. The selective adsorption ability was tested through various pollutants (metal ions and dye solutions) absorbed by the CNAs. Our results proved that carbon nanosphere aggregates (CNAs) are expected to be outstanding adsorption materials for the decontamination of PFOA from wastewater.


Assuntos
Nanosferas , Poluentes Químicos da Água , Adsorção , Carbono , Zinco , Poluentes Químicos da Água/análise , Água/química , Cinética , Concentração de Íons de Hidrogênio
18.
Environ Res ; 218: 114990, 2023 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-36463990

RESUMO

Ballast water and sediments can serve as prominent vectors for the widespread dispersal of pathogens between geographically distant areas. However, information regarding the diversity and distribution of the bacterial pathogens in ballast water and sediments is highly limited. In this study, using high-throughput sequencing and quantitative PCR, we investigated the composition and abundance of potential pathogens, and their associations with indicator microorganisms. We accordingly detected 48 potential bacterial pathogens in the assessed ballast water and sediments, among which there were significant differences in the compositions and abundances of pathogenic bacterial communities characterizing ballast water and sediments. Rhodococcus erythropolis, Bacteroides vulgatus, and Vibrio campbellii were identified as predominant pathogens in ballast water, whereas Pseudomonas stutzeri, Mycobacterium paragordonae, and Bacillus anthracis predominated in ballast sediments. Bacteroidetes, Vibrio alginolyticus, Vibrio parahaemolyticus, and Escherichia coli were generally detected with median values of 8.54 × 103-1.22 × 107 gene copies (GC)/100 mL and 1.16 × 107-3.97 × 109 GC/100 g in ballast water and sediments, respectively. Notably, the concentrations of Shigella sp., Staphylococcus aureus, and V. alginolyticus were significantly higher in ballast sediments than in the water. In addition, our findings tend to confirm that the indicator species specified by the International Maritime Organization (IMO) might underestimate the pathogen risk in the ballast water and sediments, as these bacteria were unable to predict some potential pathogens assessed in this study. In summary, this study provides a comprehensive insight into the spectrum of the potential pathogens that transferred by ship ballast tanks and emphasizes the need for the implementation of IMO convention on ballast sediment management.


Assuntos
Bacteroidetes , Água , Prevalência , Navios
19.
BMC Gastroenterol ; 22(1): 521, 2022 Dec 16.
Artigo em Inglês | MEDLINE | ID: mdl-36526962

RESUMO

OBJECTIVES: Dysglycemia promotes the occurrence of fatty liver disease (FLD). However, the process is unclear. This study aimed to analyze the median time-to-onset, cumulative prevalence and influencing factors for the occurrence of FLD in people undergoing routine screening and evaluation. METHODS: Data from Karamay Central Hospital (September 2008-April 2017) were analyzed. Survival analysis was performed to calculate the median time and cumulative prevalence of FLD associated with normal and elevated fasting blood glucose (FBG) levels. Cox proportional hazards model was used to determine risk factors. RESULTS: A total of 31,154 participants were included in the two cohorts of this study, including 15,763 men. The mean age was 41.1 ± 12.2 years. There were 2230 patients (1725 male) in the elevated FBG group, the median age was 53 years (range 21-85 years), the median time-to-onset of FLD was 5.2 years. The incidence of FLD was 121/1000 person-years, and the 1-, 3-, 5-, and 7-year prevalence rates were 4%, 30%, 49%, and 64%, respectively. The normal FBG group included 28,924 participants (14,038 male), the median age was 40 years (range 17-87 years), and the corresponding values were as follows: 8.3 years, 66/1000 person-years, and 3%, 16%, 28%, and 41%, respectively. The Cox proportional hazards analysis revealed that age, blood pressure, FBG, body mass index and triglycerides were independent influencing factors for FLD in individuals (P < 0.05). CONCLUSIONS: Elevated FBG levels increase the risk of FLD and should be treated promptly.


Assuntos
Hepatopatia Gordurosa não Alcoólica , Humanos , Masculino , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Adolescente , Hepatopatia Gordurosa não Alcoólica/epidemiologia , Hepatopatia Gordurosa não Alcoólica/diagnóstico , Índice de Massa Corporal , Fatores de Risco , Jejum , Glucose , Glicemia
20.
Front Med (Lausanne) ; 9: 1038475, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36457563

RESUMO

Objective: To analyze the prevalence, associated comorbidities, influencing factors, and identifying factors of non-obese fatty liver disease and to provide a reference for its prevention and treatment. Materials and methods: Firstly, to screen data obtained from the physical examinations of individuals conducted in the Second Affiliated Hospital of Xi'an Jiaotong University in 2021, subjects with complete data of abdominal ultrasonography, body mass index, age and sex were selected to analyze the prevalence of fatty liver disease and non-obese fatty liver disease. Secondly, to screen non-obese subjects who had data for triglycerides, fasting blood glucose, and so on, to analyze the complications, influencing factors, and identifying factors of non-obese fatty liver disease. Results: The prevalence of fatty liver disease was 27.8% (18,416/66,221), including 33.9% (11,921/35,131) in males and 20.9% (6,495/31,090) in females, revealing that the prevalence was significantly higher in males than in females (P < 0.001). There were 40,673 non-obese subjects screened in total, and the prevalence of non-obese fatty liver disease was 13.0% (5,307/40,673). The prevalence of non-obese fatty liver disease was 13.3% (2,208/16,572) in males and 12.9% (3,099/24,101) in females; the difference was not statistically significant (P = 0.17). The serum triglycerides level was elevated in 54.2% of subjects with non-obese fatty liver disease, and this was the most common abnormal metabolic index accompanying the disease. Logistic regression analysis showed that gender, age, body mass index, blood pressure, alanine aminotransferase, aspartate aminotransferase, fasting blood glucose, triglycerides, total cholesterol, and serum uric acid were independent risk factors for non-obese fatty liver disease (P < 0.001). For triglycerides, the area under the receiver operating characteristic curve in predicting non-obese fatty liver disease was the greatest (0.806). Conclusion: The prevalence of fatty liver disease and non-obese fatty liver disease determined by the physical examination of individuals was high, and the triglycerides is likely to be useful for the extensive screening of non-obese fatty liver disease.

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