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1.
J Exp Clin Cancer Res ; 40(1): 220, 2021 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-34210327

RESUMO

BACKGROUND: Metastasis is a major challenge in cervical cancer treatment. Previous studies have shown that the dual functional protein apurinic/apyrimidinic endonuclease 1 (APE1) promotes tumor metastasis and is overexpressed in cervical cancer. However, the biological role and mechanism of APE1 in cervical cancer metastasis have rarely been studied. METHODS: We used gene set enrichment analysis (GSEA) to determine the APE1-related signaling pathways in cervical cancer. To investigate the role and mechanism of APE1 in cervical cancer metastasis and invasion, immunohistochemistry, immunofluorescence, western blotting, secondary structure prediction, coimmunoprecipitation, luciferase reporter, and electrophoretic mobility shift assays were performed. The inhibitory effects of the APE1 redox function inhibitor APX3330 on cervical cancer metastasis were evaluated using animal models. RESULTS: Clinical data showed that high expression of APE1 was associated with lymph node metastasis in cervical cancer patients. GSEA results showed that APE1 was associated with epithelial to mesenchymal transition (EMT) in cervical cancer. Ectopic expression of APE1 promoted EMT and invasion of cervical cancer cells, whereas inhibition of APE1 suppressed EMT and invasion of cervical cancer cells in a redox function-dependent manner. Notably, APE1 redox function inhibitor APX3330 treatment dramatically suppressed cervical cancer cell lymph node and distant metastasis in vivo. Furthermore, we found that APE1 enhanced the interaction between ZEB1 and the E-cadherin promoter by binding to ZEB1, thereby suppressing the expression of E-cadherin, a negative regulator of EMT. CONCLUSION: Our findings help to elucidate the role played by APE1 in cervical cancer metastasis and targeting APE1 redox function may be a novel strategy for inhibiting cervical cancer metastasis.

2.
Cell Res ; 2021 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-34239070

RESUMO

Glioblastoma (GBM) is a prevalent and highly lethal form of glioma, with rapid tumor progression and frequent recurrence. Excessive outgrowth of pericytes in GBM governs the ecology of the perivascular niche, but their function in mediating chemoresistance has not been fully explored. Herein, we uncovered that pericytes potentiate DNA damage repair (DDR) in GBM cells residing in the perivascular niche, which induces temozolomide (TMZ) chemoresistance. We found that increased pericyte proportion correlates with accelerated tumor recurrence and worse prognosis. Genetic depletion of pericytes in GBM xenografts enhances TMZ-induced cytotoxicity and prolongs survival of tumor-bearing mice. Mechanistically, C-C motif chemokine ligand 5 (CCL5) secreted by pericytes activates C-C motif chemokine receptor 5 (CCR5) on GBM cells to enable DNA-dependent protein kinase catalytic subunit (DNA-PKcs)-mediated DDR upon TMZ treatment. Disrupting CCL5-CCR5 paracrine signaling through the brain-penetrable CCR5 antagonist maraviroc (MVC) potently inhibits pericyte-promoted DDR and effectively improves the chemotherapeutic efficacy of TMZ. GBM patient-derived xenografts with high CCL5 expression benefit from combined treatment with TMZ and MVC. Our study reveals the role of pericytes as an extrinsic stimulator potentiating DDR signaling in GBM cells and suggests that targeting CCL5-CCR5 signaling could be an effective therapeutic strategy to improve chemotherapeutic efficacy against GBM.

3.
J Mol Med (Berl) ; 2021 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-34232352

RESUMO

Zinc finger and BTB domain-containing protein 20 (ZBTB20) play an important role in glucose and lipid homeostasis. ZBTB20 was shown to be a crucial protein for the maintenance of cardiac contractile function. However, the role of ZBTB20 in cardiac response remodeling has not been elucidated. Thus, this study aimed to explore the role of ZBTB20 in cardiac remodeling following angiotensin II insult. Mice were subjected to angiotensin II infusion to induce a cardiac adverse remodeling model. An adeno-associated virus (AAV) 9 system was used to deliver ZBTB20 to the mouse heart. Here, we demonstrate that ZBTB20 expression is elevated in angiotensin II-induced cardiac remodeling and in response to cardiomyocyte insults. Furthermore, AAV9-mediated overexpression of ZBTB20 caused cardiac wall hypertrophy, chamber dilation, increased fibrosis, and reduced ejection fraction. Additionally, ZBTB20 siRNA protected cardiomyocytes from angiotensin II-induced hypertrophy. Mechanistically, ZBTB20 interferes with EGFR and Akt signaling and modulates the remodeling response. Overexpression of constitutively active Akt counteracts ZBTB20 knockdown-mediated protection of adverse cardiac remodeling. These findings illustrate the role of ZBTB20 in the transition of adverse cardiac remodeling toward heart failure and provide evidence for the molecular programs inducing adverse cardiac remodeling. KEY MESSAGES: ZBTB20 is a transcription factor from the POK family. ZBTB20 is upregulated in heart tissue treated with angiotensin II. ZBTB20 influences cardiomyocyte hypertrophy via the EGFR-Akt pathway. Akt continuous activation leads to similar results to ZBTB20 overexpression.

4.
Sci China Life Sci ; 2021 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-34236584

RESUMO

Male sterility is an essential trait in hybrid seed production, especially for monoclinous and autogamous food crops. Soybean male-sterile ms1 mutant has been known for more than 50 years and could be instrumental in making hybrid seeds. However, the gene responsible for the male-sterile phenotype has remained unknown. Here, we report the map-based cloning and characterization of the MS1 gene in soybean. MS1 encodes a kinesin protein and localizes to the nucleus, where it is required for the male meiotic cytokinesis after telophase II. We further substantiated that MS1 colocalizes with microtubules and is essential for cell plate formation in soybean male gametogenesis through immunostaining. Both ms1 and CRISPR/Cas9 knockout mutants show complete male sterility but are otherwise phenotypically normal, making them perfect tools for producing hybrid seeds. The identification of MS1 has the practical potential for assembling the sterility system and speeding up hybrid soybean breeding.

5.
Adv Sci (Weinh) ; 8(13): 2100104, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34258160

RESUMO

Addressing the high false-positive rate of conventional low-dose computed tomography (LDCT) for lung cancer diagnosis, the efficacy of incorporating blood-based noninvasive testing for assisting practicing clinician's decision making in diagnosis of pulmonary nodules (PNs) is investigated. In this prospective observative study, next generation sequencing- (NGS-) based cell-free DNA (cfDNA) mutation profiling, NGS-based cfDNA methylation profiling, and blood-based protein cancer biomarker testing are performed for patients with PNs, who are diagnosed as high-risk patients through LDCT and subsequently undergo surgical resections, with tissue sections pathologically examined and classified. Using pathological classification as the gold standard, statistical and machine learning methods are used to select molecular markers associated with tissue's malignant classification based on a 98-patient discovery cohort (28 benign and 70 malignant), and to construct an integrative multianalytical model for tissue malignancy prediction. Predictive models based on individual testing platforms have shown varying levels of performance, while their final integrative model produces an area under the receiver operating characteristic curve (AUC) of 0.85. The model's performance is further confirmed on a 29-patient independent validation cohort (14 benign and 15 malignant, with power > 0.90), reproducing AUC of 0.86, which translates to an overall sensitivity of 80% and specificity of 85.7%.

6.
PLoS One ; 16(7): e0253429, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34214081

RESUMO

Porcine reproductive and respiratory syndrome (PRRS) is a disease caused by the PRRS virus (PRRSV) that has spread globally in the last 30 years and causes huge economic losses every year. This research aims to 1) investigate the relationship between the PRRSV detection in two age categories (wean-to-market and adult/sow farm), and 2) examine the extent to which the wean-to-market PRRSV positive rate forecasts the adult/sow farm PRRSV positive rate. The data we used are the PRRSV RNA detection results between 2007 and 2019 integrated by the US Swine Disease Reporting System project that represent 95% of all porcine submissions tested in the US National Animal Health Network. We first use statistical tools to investigate to what extent the increase in PRRSV positive submissions in the wean-to-market is related to the PRRSV increase in adult/sow farms. The statistical analysis confirms that an increase in the PRRSV positive rate of wean-to-market precedes the increase in the adult/sow farms to a large extent. Then we create the dynamic exponentially weighted moving average control charts to identify out-of-control points (i.e., signals) in the PRRSV rates for both wean-to-market and adult/sow farms. This control-chart-based analysis finds that 78% of PRRSV signals in the wean-to-market are followed by a PRRSV rate signal in the adult/sow farms within eight weeks. We expect that our findings will help the producers and veterinarians to justify and reinforce the implementation of bio-security and bio-contaminant practices to curb disease spread across farms.

7.
Sci Total Environ ; 795: 148870, 2021 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-34243009

RESUMO

Traditional lake phytoplankton diversity studies do not take into account the impact of ecological protection and restoration project policies. Here, a difference-in-differences (DID) model, which is commonly used to analyze the relative importance of economic factors, was used to evaluate the impact of such policies on phytoplankton diversity in lakes. Dongping Lake was used as the experimental group, and the upstream Nansi Lake was used as the control group. The phytoplankton diversity index of the experimental group and the control group was used as the explanatory variable of the DID model. Six environmental and socioeconomic factors, temperature and precipitation, were used as control variables in the DID model. The effects of ecological protection and restoration project policy on phytoplankton diversity in lakes were analyzed. Under the influence of policy implementation, the phytoplankton diversity in the experimental lake was improved by 2.79% compared with that in the control lake. Temperature and precipitation were the main factors affecting phytoplankton diversity in the two connected shallow lakes in the Shandong Peninsula. This study verified that DID models can be used to quantitatively analyze the impact of ecological protection and restoration project policies on phytoplankton diversity in lakes.

8.
Food Chem ; 363: 130298, 2021 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-34237557

RESUMO

Ferulic acid (FA) and tetramethyl pyrazine (TMP) are intrinsic bioactive compounds in baijiu, and kafirin is the major protein of sorghum, which is the raw material of baijiu. In this study, the interactions of kafirin-FA and kafirin-TMP were investigated by multiple spectroscopic and molecular modeling techniques. Fluorescence spectra showed that intrinsic fluorescence of kafirin drastically quenched because of the formations of kafirin-FA and kafirin-TMP complexes. The CD studies indicated that the combination with FA or TMP decreased the α-helix content of kafirin slightly. The shifts and intensity changes of UV-Vis, FTIR and fluorescence spectra confirmed the formations of complexes. Moreover, the molecular docking and molecular dynamics studies showed that hydrophobic interactions and hydrogen bonds played major roles in the formations of kafirin-FA and kafirin-TMP complexes, and the formations of complexes made kafirin structures more compact. This work is of great importance for further quality improvement in baijiu and alcoholic beverages.

9.
Comp Biochem Physiol C Toxicol Pharmacol ; 249: 109131, 2021 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-34246797

RESUMO

Trimethyltin chloride (TMT) is a highly toxic substance produced by organotin heat stabilizers in the synthesis of polyvinyl chloride (PVC) products. TMT is widely used in industry and agriculture. The aim of this study was to investigate the effects of TMT-induced cytotoxicity in intestinal porcine epithelial cells (IPEC-J2). Our study showed that TMT induced a decline in cell viability of IPEC-J2, caused cell shrinkage and rounded cell morphology, reduced the number of proliferating cells and the expression of proliferating cell nuclear antigen (PCNA), and increased lactate dehydrogenase (LDH) activity in cell supernatants. Simultaneously, TMT lowered the mRNA expression of Cyclin B1, and Cyclin D1, but increased P21 and P27 expression. The cell cycle progression was arrested from the G1 to the S phase. Furthermore, the mRNA expression of Bax/Bcl-2 ratio and the protein expression of cleaved Caspase-9 and cleaved Caspase-3 were significantly increased after TMT treatment, while the ratio of advanced apoptotic cells was elevated. These results indicated that TMT blocked the cell cycle, inhibited IPEC-J2 proliferation, and induced apoptosis.

10.
Molecules ; 26(13)2021 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-34209485

RESUMO

(-)-Epigallocatechin-3-O-gallate (EGCG), the most abundant component of catechins in tea (Camellia sinensis (L.) O. Kuntze), plays a role against viruses through inhibiting virus invasiveness, restraining gene expression and replication. In this paper, the antiviral effects of EGCG on various viruses, including DNA virus, RNA virus, coronavirus, enterovirus and arbovirus, were reviewed. Meanwhile, the antiviral effects of the EGCG epi-isomer counterpart (+)-gallocatechin-3-O-gallate (GCG) were also discussed.

11.
Nucleic Acids Res ; 2021 Jul 15.
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.

12.
J Cancer Res Ther ; 17(3): 664-670, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34269297

RESUMO

Objective: The objective of this study was to perform a meta-analysis comparing the efficiency of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) with chemotherapy to EGFR TKI treatment alone in patients with EGFR mutation-positive non-small cell lung cancer (NSCLC). Materials and Methods: Following keyword queries in databases and identification of randomized control trials for inclusion, hazard ratios (HRs), relative risks (RRs), and associated 95% confidence intervals (95% CIs) were determined. Results: Ten randomized controlled trials involving 1354 participants with NSCLC were evaluated. We found that a combined approach of chemotherapy with EGFR TKIs significantly improved overall survival (OS) compared with EGFR TKI alone in our patient cohort (HR = 0.47, 95% CI = 0.31-0.72). In addition, a higher overall response rate (ORR) was found for patients who received combined treatment compared to chemotherapy alone (RR = 2.17, 95% CI = 1.51-3.12). Furthermore, concomitant use of chemotherapy with TKIs significantly improved the progression-free survival (PFS) when compared to the use of TKIs alone (HR = 0.68, 95% CI = 0.49-0.95). Moreover, there was a higher ORR among patients who received combined treatment as compared to those who were managed using TKIs only (RR=1.17, 95%CI=1.09-1.25). Conclusion: Our meta-analysis shows that EGFR TKIs with chemotherapy confer better OS and ORR compared to either treatment alone, similarly, the combined treatment showed better PFS and ORR profiles than the use of TKI alone.

13.
Front Med ; 2021 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-34241787

RESUMO

Consecutively hospitalized patients with confirmed coronavirus disease 2019 (COVID-19) in Wuhan, China were retrospectively enrolled from January 2020 to March 2020 to investigate the association between the use of renin-angiotensin system inhibitor (RAS-I) and the outcome of this disease. Associations between the use of RAS-I (angiotensin-converting enzyme inhibitor (ACEI) or angiotensin receptor blocker (ARB)), ACEI, and ARB and in-hospital mortality were analyzed using multivariate Cox proportional hazards regression models in overall and subgroup of hypertension status. A total of 2771 patients with COVID-19 were included, with moderate and severe cases accounting for 45.0% and 36.5%, respectively. A total of 195 (7.0%) patients died. RAS-I (hazard ratio (HR)= 0.499, 95% confidence interval (CI) 0.325-0.767) and ARB (HR = 0.410, 95% CI 0.240-0.700) use was associated with a reduced risk of all-cause mortality among patients with COVID-19. For patients with hypertension, RAS-I and ARB applications were also associated with a reduced risk of mortality with HR of 0.352 (95% CI 0.162-0.764) and 0.279 (95% CI 0.115-0.677), respectively. RAS-I exhibited protective effects on the survival outcome of COVID-19. ARB use was associated with a reduced risk of all-cause mortality among patients with COVID-19.

14.
Molecules ; 26(13)2021 Jun 29.
Artigo em Inglês | MEDLINE | ID: covidwho-1288963

RESUMO

(-)-Epigallocatechin-3-O-gallate (EGCG), the most abundant component of catechins in tea (Camellia sinensis (L.) O. Kuntze), plays a role against viruses through inhibiting virus invasiveness, restraining gene expression and replication. In this paper, the antiviral effects of EGCG on various viruses, including DNA virus, RNA virus, coronavirus, enterovirus and arbovirus, were reviewed. Meanwhile, the antiviral effects of the EGCG epi-isomer counterpart (+)-gallocatechin-3-O-gallate (GCG) were also discussed.

15.
Bioconjug Chem ; 2021 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-34260853

RESUMO

Targeted radionuclide therapy (TRT) provides new and safe opportunities for cancer treatment and management with high precision and efficiency. Here we have designed a novel semiconducting polymer nanoparticle (SPN)-based radiopharmaceutical (211At-MeATE-SPN-GIP) for TRT against glucose-dependent insulinotropic polypeptide receptor (GIPR)-positive cancers to further explore the applications of nanoengineered TRT. 211At-MeATE-SPN-GIP was engineered via nanoprecipitation, followed by its functionalization with a glucose-dependent insulinotropic polypeptide (GIP) to target GIPR and deliver 211At for α therapy. The therapeutic effect and biological safety of 211At-MeATE-SPN-GIP were investigated using GIPR-overexpressing human pancreatic cancer CFPAC-1 cells and CFPAC-1-bearing mice. In this work, 211At-MeATE-SPN-GIP was produced with a radiochemical yield of 43% and radiochemical purity of 98%, which exhibited a specifically high uptake in CFPAC-1 cells, inducing cell cycle arrest at the G2/M phase and extensive DNA damage. In the CFPAC-1-bearing tumor model, 211At-MeATE-SPN-GIP exhibited high therapeutic efficiency, with no obvious side effects. The GIPR-specific binding of 211At-MeATE-SPN-GIP combined with effective inhibition of tumor growth and fewer side effects compared to control suggests that 211At-MeATE-SPN-GIP TRT holds great potential as a novel nanoengineered TRT strategy for patients with GIPR-positive cancer.

16.
J Med Chem ; 2021 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-34261320

RESUMO

Previous studies have reported the stepwise nature of human immunodeficiency virus type 1 (HIV-1) entry and the pivotal role of coreceptor CCR5 and the gp41 N-terminal heptad repeat (NHR) region in this event. With this in mind, we herein report a dual-targeted drug compound featuring bifunctional entry inhibitors, consisting of a piperidine-4-carboxamide-based CCR5 antagonist, TAK-220, and a gp41 NHR-targeting fusion-inhibitory peptide, C34. The resultant chimeras were constructed by linking both pharmacophores with a polyethylene glycol spacer. One chimera, CP12TAK, exhibited exceptionally potent antiviral activity, about 40- and 306-fold over that of its parent inhibitors, C34 and TAK-220, respectively. In addition to R5-tropic viruses, CP12TAK also strongly inhibited infection of X4-tropic HIV-1 strains. These data are promising for the further development of CP12TAK as a new anti-HIV-1 drug. Results show that this strategy could be extended to the design of therapies against infection of other enveloped viruses.

17.
BMJ Open ; 11(7): e047743, 2021 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-34261685

RESUMO

OBJECTIVE: To describe the relationship between long-term weight loss (LTWL) success and lifestyle behaviours among US adults. DESIGN: Serial cross-sectional data from National Health and Nutrition Examination Survey cycles 2007-2014. SETTING AND PARTICIPANTS: Population-based nationally representative sample. The analytic sample included 3040 adults aged 20-64 years who tried to lose weight in the past year. MEASURES: Participants were grouped into five LTWL categories (<5%, 5%-9.9%, 10%-14.9%, 15%-19.9% and ≥20%). Lifestyle-related behaviours included the following: alcohol intake, physical activity, smoking, fast-food consumption, dietary quality (Healthy Eating Index (HEI)) and caloric intake. Multivariable regression was employed adjusting for age, sex, race/ethnicity, marital status, education, household income and size, current body mass index and self-reported health status. RESULTS: Individuals in the 15%-19.9% LTWL group differed significantly from the reference group (<5% LTWL) in their physical activity and dietary quality (HEI) but not caloric intake. Specifically, they had a higher HEI score (ß=3.19; 95% CI 0.39 to 5.99) and were more likely to meet physical activity guidelines (OR=1.99; 95% CI 1.11 to 3.55). In comparison, the ≥20% LTWL group was significantly more likely to smoke (OR=1.63; 95% CI 1.03 to 2.57) and to consume lower daily calories (ß=-202.91; 95% CI -345.57 to -60.25) than the reference group; however, dietary quality and physical activity did not significantly differ. CONCLUSION: Among a national sample of adults, a higher level of LTWL success does not necessarily equate to healthy weight loss behaviours. Future research should attempt to design interventions aimed at facilitating weight loss success while encouraging healthy lifestyle behaviours.

18.
J Med Chem ; 2021 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-34228434

RESUMO

Selective Mcl-1 inhibitors may overcome the drug resistance caused by current anti-apoptotic Bcl-2 protein inhibitors in tumors with Mcl-1 overexpression. Based on previously discovered compounds with a 3-phenylthiophene-2-sulfonamide core moiety, in this work, we have obtained new compounds with improved binding affinity and/or selectivity under the guidance of structure-based design. The most potent compounds achieved sub-micromolar binding affinities to Mcl-1 (Ki ∼ 0.4 µM) and good cytotoxicity (IC50 < 10 µM) on several tumor cells. 15N-heteronuclear single-quantum coherence NMR spectra suggested that these compounds bound to the BH3-binding groove on Mcl-1. Several cellular assays revealed that FWJ-D4 as well as its precursor FWJ-D5 effectively induced caspase-dependent apoptosis, and their target engagement at Mcl-1 was confirmed by co-immunoprecipitation experiments. Treatment with FWJ-D5 at 50 mg/kg every 2 days on an RS4;11 xenograft mouse model for 22 days led to 75% reduction in tumor volume without body weight loss.

19.
mSystems ; : e0015821, 2021 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-34282934

RESUMO

The influence of human genetic variants on the vaginal bacterial traits (VBTs) of pregnant women is still unknown. Using a genome-wide association approach based on the 16S rRNA bacteriome analysis, a total of 72 host genetic variant (single nucleotide polymorphisms [SNPs], indels, or copy number variations [CNVs])-VBT associations were found that reached the genome-wide significance level (P < 5 × 10-8) with an acceptable genomic inflation factor λ of <1.1. The majority of these SNPs that reached the genome-wide significance level had a relatively low minor allele frequency (MAF), and only seven of them had MAFs greater than 0.05. rs303212, located at the IFIT1 gene on chromosome 10, was the most eye-catching variant, which had a genome-wide association with the relative abundance (RAB) of Actinobacteria and Bifidobacteriaceae and also had a suggestive association with the RAB of a few common vaginal bacteria including Actinobacteriota, Firmicutes, Lactobacillus, and Gardnerella vaginalis and the beta diversity weighted UniFrac (P < 1 × 10-5). The findings of the study suggest that the vaginal bacteriome may be influenced by a number of genetic variants across the human genome and that interferon signaling may have an important influence on vaginal bacterial communities during pregnancy. IMPORTANCE Knowledge about the influence of host genetics on the vaginal bacteriome in pregnancy is still limited. Although a number of environmental and behavioral factors may exert influences on the structure of vaginal bacterial communities, the vaginal bacteriome often undergoes a relatively fixed transition to a more stable and less diverse state as the menstrual cycle stops, which raises questions on the effects of human genetics. We utilized a genome-wide approach to identify the associations between genetic variants and multiple VBTs and performed enrichment analyses. The human genetics during pregnancy may be involved in multiple pathways. The results may disclose innate functional factors involved in shaping the vaginal bacteriome during pregnancy and provide insight into the establishment of specific strategies for prevention and clinical treatment of pregnancy complications.

20.
Food Chem ; 365: 130545, 2021 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-34265643

RESUMO

In this study, mangosteen peel based activated carbon was prepared and first applied as adsorbent in matrix solid-phase dispersion (MSPD) for simultaneously extraction of flavonoids from Dendrobium huoshanense prior to their separation and determination by ultra-high performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry (UHPLC-Q-TOF/MS). The MSPD-UHPLC-Q-TOF/MS method was validated exhaustively. Good linearities (r2 ≥ 0.9929) were obtained for all target analytes. The limits of detection was in the range of 0.00387-0.159 µg/g. Satisfactory recoveries of six target compounds were between 80.02 and 99.49% and 85.32-99.86% for the low and high spiked level, respectively. Furthermore, relative to other common sorbent, the prepared mangosteen peel based activated carbon was less expensive and more environmentally-friendly. Consequently, the proposed method was a simple, efficient, low-cost, eco-friendly, time-saving and sensitive approach that could be successfully applied to the extraction and determination of flavonoids compounds in complex matrix.

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