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1.
Artigo em Inglês | MEDLINE | ID: mdl-39009501

RESUMO

BACKGROUND: Oxidized forms of low-density lipoproteins (ox-LDL)-associated endothelial dysfunction and subsequent monocyte adhesion play an important role in the development of atherosclerosis (AS). Bezafibrate (BEZ) is a peroxisome proliferator-activated receptor (pan-PPAR) agonist licensed as a hypolipidemic drug. However, the effects of BEZ on endothelial dysfunction are less reported. OBJECTIVES: In this study, we aim to investigate the protective effects of BEZ on ox-LDL-challenged vascular endothelial cells to evaluate its potential value in treating AS. METHODS: Human aortic endothelial cells (HAECs) and THP-1 cells were used to establish an In Vitro AS model. Cell Counting Kit-8 (CCK-8) assay, Real-time PCR, Western blot analysis, and Enzyme-linked immunosorbent assay (ELISA) were used to test the data. RESULTS: As expected, treatment with BEZ suppressed the expression of vascular endothelial growth factor A (VEGF-A), tissue factor (TF), Interleukin 12 (IL-12), tumor necrosis factor (TNF-α), and monocyte chemoattractant protein-1 (MCP-1). BEZ was also found to inhibit ox-LDL-induced expression of the endothelial adhesion molecules vascular cellular adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1) in HAECs. Correspondingly, BEZ prevented attachment of THP-1 monocytes to ox-LDL-incubated HAECs. Mechanically, BEZ was found to prevent NF-κB activation by reducing the levels of nuclear NF-κB p65 and inhibiting luciferase activity of NF-κB. CONCLUSION: Our study revealed the pharmacological function of BEZ in protecting endothelial dysfunction against ox-LDL, which may provide valuable insight for the clinical application of BEZ.

2.
Biomacromolecules ; 25(5): 2852-2862, 2024 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-38574372

RESUMO

Albumin nanoparticles are widely used in biomedicine due to their safety, low immunogenicity, and prolonged circulation. However, incorporating therapeutic molecules into these carriers faces challenges due to limited binding sites, restricting drug conjugation efficiency. We introduce a universal nanocarrier platform (X-UNP) using polyphenol-based engineering to incorporate phenolic moieties into albumin nanoparticles. Integration of catechol or galloyl groups significantly enhances drug binding and broadens the drug conjugation possibilities. Our study presents a library of X-UNP nanoparticles with improved drug-loading efficiency, achieving up to 96% across 10 clinically used drugs, surpassing conventional methods. Notably, ibuprofen-UNP nanoparticles exhibit a 5-fold increase in half-life compared with free ibuprofen, enhancing in vivo analgesic and anti-inflammatory effectiveness. This research establishes a versatile platform for protein-based nanosized materials accommodating various therapeutic agents in biotechnological applications.


Assuntos
Nanopartículas , Polifenóis , Polifenóis/química , Nanopartículas/química , Animais , Camundongos , Ibuprofeno/química , Portadores de Fármacos/química , Humanos , Albuminas/química , Soroalbumina Bovina/química
3.
Carcinogenesis ; 45(6): 378-386, 2024 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-38375679

RESUMO

Estrogen plays a crucial role in ovarian tumorigenesis. Phytoestrogens (PEs) are a type of daily dietary nutrient for humans and possess a mild estrogenic characteristic. This study aimed to assess the correlation of the consumption of dietary PEs with ovarian cancer risk using data in the prostate, lung, colorectal and ovarian (PLCO) cancer screening trial. Participants were enrolled in PLCO from 1993 to 2001. Hazard ratios (HR) and 95% confidence intervals (CI) were utilized to determine the association between the intake of PEs and ovarian cancer occurrence, which were calculated by the Cox proportional hazards regression analysis. In total, 24 875 participants were identified upon completion of the initial dietary questionnaire (DQX). Furthermore, the analysis also included a total of 45 472 women who filled out the diet history questionnaire (DHQ). Overall, after adjustment for confounders, the dietary intake of total PEs was significantly associated with the risk of ovarian cancer in the DHQ group (HRQ4vsQ1 = 0.69, 95% CI: 0.50-0.95; P for trend = 0.066). Especially, individuals who consumed the highest quartile of isoflavones were found to have a decreased risk of ovarian cancer in the DHQ group (HRQ4vsQ1 = 0.68, 95% CI: 0.50-0.94; P for trend = 0.032). However, no such significant associations were observed for the DQX group. In summary, this study suggests that increased dietary intake of total PEs especially isoflavones was linked with a lower risk for developing ovarian cancer. More research is necessary to validate the findings and explore the potential mechanisms.


Assuntos
Dieta , Neoplasias Ovarianas , Fitoestrógenos , Humanos , Feminino , Fitoestrógenos/administração & dosagem , Neoplasias Ovarianas/epidemiologia , Neoplasias Ovarianas/prevenção & controle , Neoplasias Ovarianas/etiologia , Estudos Prospectivos , Pessoa de Meia-Idade , Fatores de Risco , Masculino , Idoso , Neoplasias Pulmonares/epidemiologia , Neoplasias Pulmonares/etiologia , Neoplasias Pulmonares/prevenção & controle , Inquéritos e Questionários , Isoflavonas/administração & dosagem , Neoplasias Colorretais/epidemiologia , Neoplasias Colorretais/etiologia , Neoplasias Colorretais/prevenção & controle , Neoplasias da Próstata/epidemiologia , Neoplasias da Próstata/etiologia
4.
Immun Inflamm Dis ; 12(2): e1202, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38411294

RESUMO

BACKGROUND: Histiocytic necrotizing lymphadenitis (HNL) is a self-limited inflammatory disease of unknown pathogenesis. A very small fraction of patients with HNL could develop hemophagocytic lymphohistiocytosis (HLH), a hyperinflammatory disorder. These patients are diagnosed as HNL with HLH (HNL-HLH). HNL-HLH in the pediatric population has been systemically studied, however, the clinical, laboratory, and radiological features and outcomes of adult patients with HNL-HLH remain to be explored. We aimed to explore the clinical, laboratory, and radiological features and outcomes of adult patients with HNL-HLH. METHODS: We collected the clinical data of patients with HNL-HLH admitted to the First Affiliated Hospital of Nanjing Medical University from October 2010 to June 2015. All the patients underwent lymph node biopsy and have a pathological diagnosis of HNL. The age, gender, clinical presentation, lymph node signs, laboratory findings and imaging data, and pathological findings of the patients were collected. RESULTS: In this study, we reported five adult patients with HNL-HLH. All five patients showed enlarged lymph nodes and prolonged fever. Laboratory findings were consistent with the diagnosis of HLH. 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) showed enlarged lymph nodes with increased FDG uptake and splenic hypermetabolism could be present. All the patients responded well to corticosteroids and had a good prognosis. Two of the five patients were diagnosed with systemic lupus erythematosus during the follow-up. CONCLUSIONS: Our study demonstrated that adult patients with HNL-HLH showed distinct clinical, laboratory, and radiological features. And the prognosis is good and patients could be managed with steroids and supportive care.


Assuntos
Linfadenite Histiocítica Necrosante , Linfo-Histiocitose Hemofagocítica , Adulto , Humanos , Criança , Linfadenite Histiocítica Necrosante/complicações , Linfadenite Histiocítica Necrosante/diagnóstico , Linfadenite Histiocítica Necrosante/tratamento farmacológico , Linfo-Histiocitose Hemofagocítica/complicações , Linfo-Histiocitose Hemofagocítica/diagnóstico , Linfo-Histiocitose Hemofagocítica/tratamento farmacológico , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/efeitos adversos , Linfonodos , Biópsia/efeitos adversos
6.
Blood Sci ; 5(4): 258-268, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37941916

RESUMO

Ruxolitinib is a cornerstone of management for some subsets of myeloproliferative neoplasms (MPNs); however, a considerable number of patients respond suboptimally. Here, we evaluated the efficacy of micheliolide (MCL), a natural guaianolide sesquiterpene lactone, alone or in combination with ruxolitinib in samples from patients with MPNs, JAK2V617F-mutated MPN cell lines, and a Jak2V617F knock-in mouse model. MCL effectively suppressed colony formation of hematopoietic progenitors in samples from patients with MPNs and inhibited cell growth and survival of MPN cell lines in vitro. Co-treatment with MCL and ruxolitinib resulted in greater inhibitory effects compared with treatment with ruxolitinib alone. Moreover, dimethylaminomicheliolide (DMAMCL), an orally available derivative of MCL, significantly increased the efficacy of ruxolitinib in reducing splenomegaly and cytokine production in Jak2V617F knock-in mice without evident effects on normal hematopoiesis. Importantly, MCL could target the Jak2V617F clone and reduce mutant allele burden in vivo. Mechanistically, MCL can form a stable covalent bond with cysteine residues of STAT3/5 to suppress their phosphorylation, thus inhibiting JAK/STAT signaling. Overall, these findings suggest that MCL is a promising drug in combination with ruxolitinib in the setting of suboptimal response to ruxolitinib.

7.
Environ Res ; 219: 115097, 2023 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-36566965

RESUMO

As one of the key stable crops to feed half of the world's population, how rice cropping system affects honey bee health regarding pesticide exposure and forage availability is under investigated. We predicted honey bees were stressed by high pesticide exposure and forage dearth in monoculture rice systems. Providing access to natural habitats is a typical approach to mitigate the negative impact of intensive agriculture on honey bees. We aimed to determine if bee colonies located in landscapes with more cover of forest habitat would collect more forage and be exposed to less pesticides. We selected beekeeping locations in rice dominated landscapes (as control), mosaic landscapes of rice and medium woodland (MW) cover, and landscapes of high woodland (HW) cover, respectively, in July when rice starts bloom and pesticides are commonly used. Colonies were inspected at a biweekly frequency from July to October with population growth and forage (nectar and pollen) availability estimated. Pollen and bees were collected in middle August for pesticide exposure analysis. We did not observe enhancement in forage availability and reduction in pesticide exposure in landscapes with increased forest habitat (i.e., MW or HW cover), and all colonies failed in the end. Other natural habitats that can supplement flower shortage periods in forest can be considered for supporting bee health. Our results suggest that forest should be carefully assessed for being incorporated into beekeeping management or pollinator conservation when forest phenology can be a factor to affect its impact as a natural habitat.


Assuntos
Oryza , Praguicidas , Abelhas , Animais , Agricultura , Criação de Abelhas , Néctar de Plantas
8.
Clin Endocrinol (Oxf) ; 98(6): 813-822, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-36536522

RESUMO

OBJECTIVE: The impact of selenium (Se) on human thyroid function remains unclear, with inconsistent results from recent epidemiological studies. Moreover, the observed associations are prone to bias due to potential confounding and reverse causation. Mendelian randomization (MR) analysis facilitates the large minimization of biases produced by environmental and lifestyle influences, providing unconfounded estimates of causal effects using instrumental variables. We aim to examine the association between Se concentrations and human thyroid function using a two-sample MR analysis. DESIGN AND METHODS: Genetic instruments for Se concentrations, including toenail and blood (TAB) and blood Se concentrations, were identified from a genome-wide association study (GWAS) of blood Se (n = 5477) and toenail Se levels (n = 4162). GWAS summary statistics on thyroid phenotypes were downloaded from the ThyroidOmics consortium, including thyroid-stimulating hormone (TSH) (n = 54,288), free thyroxin (FT4) (n = 49,269), hypo (n = 53,423), and hyperthyroidism (n = 51,823). The MR study was conducted using the inverse-variance weighted (IVW) method, supplemented with the weighted median and the mode-based method. RESULTS: Genetically determined TAB Se was negatively associated with FT4 (ß = -.067; 95% confidence interval [CI] = -0.106, -0.028; p = 0.001) using the IVW analyses, as well in the additional analyses using the weighted median and weighted-mode methods. No evidence in heterogeneity, pleiotropy or outlier single-nucleotide polymorphisms was detected (all p > 0.05). Suggestive casual association between increased genetically determined TAB Se concentrations and decreased hypothyroidism risk was found by the IVW method (odds ratio [OR] = 0.847; 95% CI = 0.728, 0.985; p = 0.031). The causal effect of TAB Se on FT4 was observed in women (ß = -.076; 95% CI = -0.129, -0.024; p = 0.004). However, the influence of genetically determined higher Se concentrations on TSH levels and hyperthyroidism revealed insignificance in the primary and sensitivity analyses. CONCLUSIONS: The present MR study indicated that high Se concentration enable the decreasing of FT4 levels, and the effects of Se concentrations on FT4 remain sex-specific.


Assuntos
Hipertireoidismo , Selênio , Masculino , Humanos , Feminino , Análise da Randomização Mendeliana/métodos , Estudo de Associação Genômica Ampla , Tireotropina , Polimorfismo de Nucleotídeo Único/genética
9.
Haematologica ; 108(5): 1359-1373, 2023 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-36005555

RESUMO

Apart from the central role of the activated JAK/STAT signaling pathway, ASXL1 mutations are the most recurrent additional mutations in myeloproliferative neoplasms and occur much more commonly in myelofibrosis than in essential thrombocythemia and polycythemia vera. However, the mechanism of the association with ASXL1 mutations and bone marrow fibrosis remains unknown. Here, integrating our own data from patients with myeloproliferative neoplasms and a hematopoietic-specific Asxl1 deletion/Jak2V617F mouse model, we show that ASXL1 mutations are associated with advanced myeloproliferative neoplasm phenotypes and onset of myelofibrosis. ASXL1 mutations induce skewed monocyte/macrophage and neoplastic monocyte-derived fibrocyte differentiation, consequently they enhance inflammation and bone marrow fibrosis. Consistently, the loss of ASXL1 and JAK2V617F mutations in hematopoietic stem and progenitor cells leads to enhanced activation of polycomb group target genes, such as EGR1. The upregulation of EGR1, in turn, accounts for increased hematopoietic stem and progenitor cell commitment to the monocyte/macrophage lineage. Moreover, EGR1 induces the activation of TNFA and thereby further drives the differentiation of monocytes to fibrocytes. Accordingly, combined treatment with a TNFR antagonist and ruxolitinib significantly reduces fibrocyte production in vitro. Altogether, these findings demonstrate that ASXL1 mutations accelerate fibrocyte production and inflammation in myeloproliferative neoplasms via the EGR1-TNFA axis, explaining the cellular and molecular basis for bone marrow fibrosis and the proof-ofconcept for anti-fibrosis treatment.


Assuntos
Neoplasias da Medula Óssea , Transtornos Mieloproliferativos , Policitemia Vera , Mielofibrose Primária , Animais , Camundongos , Proteína 1 de Resposta de Crescimento Precoce/genética , Janus Quinase 2/genética , Mutação , Transtornos Mieloproliferativos/genética , Policitemia Vera/genética , Mielofibrose Primária/genética , Proteínas Repressoras/genética
10.
Int Urol Nephrol ; 55(3): 679-686, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36065044

RESUMO

BACKGROUND: Topical non-steroidal anti-inflammatory drugs (NSAIDs) have lower risks for cardiovascular disease and gastrointestinal adverse effects compared to oral NSAIDs, but there are little data regarding their kidney risks in chronic kidney disease (CKD). We evaluated the risk of adverse acute kidney outcomes in CKD according to route of NSAID administration. METHODS: Retrospective cohort study of adults with CKD (eGFR less than 60 ml/min/1.73 m2) who received prescriptions between 2015 and 2017 from a major healthcare cluster in Singapore. The adverse acute kidney outcomes were acute kidney injury (AKI) and need for nephrology specialist consult within 30 days. RESULTS: Among 6298 adults with CKD (mean age 72.1 ± 13.3 years and eGFR 41.9 ± 12.2 ml/min/1.73 m2), systemic and topical NSAIDs were prescribed in 16.7% and 32.0%, respectively. Incident AKI (any severity), KDIGO Stage 2 or 3 AKI, and need for nephrology specialist consult occurred in 16.7%, 2.6%, and 10.6% of the study cohort, respectively. After adjusting for age, diabetes, recent cardiovascular hospitalization, baseline eGFR, RAAS blocker and diuretic, systemic NSAIDs, and topical NSAIDs, compared with the no-NSAID group, were independently associated with incident AKI [adjusted OR 1.77 (95% CI 1.46-2.15) and 1.38 (1.18-1.63), respectively]. Moderate and severe AKI (adjusted OR 1.68, 95% CI 1.09-2.58, p = 0.02) and need for nephrology consults (adjusted OR 1.41, 95% CI 1.09-1.82, p = 0.008) were also increased in systemic NSAIDs. CONCLUSION: Among adults with CKD, both systemic and topical NSAIDs were independently associated with acute adverse kidney outcomes.


Assuntos
Injúria Renal Aguda , Insuficiência Renal Crônica , Adulto , Humanos , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Estudos Retrospectivos , Anti-Inflamatórios não Esteroides/uso terapêutico , Rim , Insuficiência Renal Crônica/tratamento farmacológico , Injúria Renal Aguda/induzido quimicamente
11.
Front Genet ; 13: 922382, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36437958

RESUMO

Background: The association between educational attainment (EA) and offspring birth weight (BW) has been reported by several traditional epidemiological studies. However, evidence for this association tends to be mixed and confounded. This study aimed to investigate the causal association between EA of parents and offspring BW. Methods: Here, we carried out a two-sample bidirectional Mendelian randomization (MR) analysis to examine the causal association between EA of males (n = 131,695) and females (n = 162,028) and offspring BW using genetic instruments. Summary statistics of EA associated single nucleotide polymorphisms (SNPs) were extracted from a GWAS incorporating 293,723 individuals of European descent performed by the Social Science Genetic Association Consortium (SSGAC), and the effects of these SNPs on offspring BW were estimated using a GWAS meta-analysis of 86,577 participants of European descent from 25 studies. Univariable MR analyses were conducted using the inverse-variance weighted (IVW) method and four other methods. Further sensitivity analyses were carried out to test the viability of the results. Multivariable MR was used to examine the confounders between the exposure and outcome. Results: The result shows evidence that the offspring BW is positively causally affected by female EA. Each one standard deviation (SD) increase in female EA was associated with 0.24 SD higher of offspring BW (95% confidence interval [CI], 0.10 to 0.37, p < 0.001 for the IVW method). Similarly, change in offspring BW was 0.21 SD (95% CI: 0.07 to 0.34, p = 2.82 × 10-3) per one SD higher in male EA. No causal effect of BW on EA was found by any of the five methods. The causal association between female EA and offspring BW maintained after adjusting for alcoholic drinks per week and BMI. The effect of male EA on offspring BW was attenuated when we adjusted for BMI and alcoholic drinks per week using multivariable MR analysis. Conclusion: Our study indicated that female EA is positively causally associated with offspring BW. The association between male EA and offspring BW may be confounded by alcoholic drinks per week and BMI.

12.
Front Nutr ; 9: 1012207, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36407512

RESUMO

Tannic acid (TA) has received widespread attention for its beneficial biological function with antioxidant capacity. This study investigated the protective role of TA on the intestinal antioxidant capacity and intestinal barrier in weaned piglets and porcine intestinal epithelial cells (IPEC-J2). A total of 18 weaned piglets were randomly allocated into two groups (n = 9) and fed with a basal diet (control, CON) and a basal diet containing 1,000 mg/kg TA for two weeks. The in vivo results showed that treatment with TA increased both glutathione peroxidase (GSH-PX) activity and the protein expression of ZO-1 in the jejunum of weaned piglets, and reduced the level of malondialdehyde (MDA) in the serum and the mRNA and protein expression of Keap1 in the jejunum of weaned piglets. Furthermore, in vitro results indicated that TA treatment effectively alleviated tert-butyl hydroperoxide (TBH)-induced oxidative stress in IPEC-J2 cells, improved the antioxidant capacity by elevating the cell redox state and activating the Nrf2 pathway, and improved the intestinal barrier by upregulating the mRNA and protein expression of intestinal tight junction proteins and increasing the transepithelial electrical resistance (TEER) value. In conclusion, these results confirmed that TA relieves oxidative injury and improves intestinal barrier function and intestinal antioxidant capacity by activating the Nrf2 signaling pathway. These findings suggest that TA has the potential application in alleviating oxidative stress in the intestine of weaned piglets.

13.
J Oncol ; 2022: 3551167, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36046367

RESUMO

Objective: To evaluate the effects of a trans-theoretical model (TTM) of behavioural change plus motivational interviewing on self-management behavior and quality of life (QoL) in patients with intracranial aneurysm. Methods: A total of 94 patients with intracranial aneurysm treated in the First Affiliated Hospital of Wenzhou Medical University from 2019 to 04/2021-04 were retrospectively analyzed. Among them, 49 patients used TTM + motivational interview as the observation group (Obs group), and 45 patients used the traditional method as the control group (Con group). The Self-Management Behavior Scale for Patients with Intracranial Aneurysm was used for analyzing the changes in the self-management behavior of the two groups of patients, and the MOS 36-item Short Form Health Survey (SF-36) was used to analyze the changes in the QoL of the patients. The incidence of adverse events after 6 months of intervention was counted. In addition, the Barthel Index (BI) and Montreal Cognitive Assessment Scale (MOCA) were used to evaluate the recovery effects of patients. Logistic regression was conducted for analyzing the risk factors of adverse cerebrovascular events. Results: After treatment, the Con group got lower self-management behavior score than the Obs group (P < 0.05), and also got lower SF-36 scores, BI, and MOCA scores than the Obs group (P < 0.05). Age and a history of hypertension were independent risk factors for adverse events. The Hosmer-Lemeshow test was adopted for testing the goodness of fit of the regression equation (P=0.903). With the established model, the area under the receiver operating characteristic curve for predicting adverse events in patients with intracranial aneurysm was determined to be 0.851, indicating that the model performed well as a risk prediction model. Conclusion: TTM + motivational interviewing can help improve the self-management behavior and QoL of patients with intracranial aneurysm without increasing the occurrence of adverse events.

14.
N Engl J Med ; 386(21): 1998-2010, 2022 05 26.
Artigo em Inglês | MEDLINE | ID: mdl-35613022

RESUMO

BACKGROUND: Although hypomethylating agents are currently used to treat patients with cancer, whether they can also reactivate and up-regulate oncogenes is not well elucidated. METHODS: We examined the effect of hypomethylating agents on SALL4, a known oncogene that plays an important role in myelodysplastic syndrome and other cancers. Paired bone marrow samples that were obtained from two cohorts of patients with myelodysplastic syndrome before and after treatment with a hypomethylating agent were used to explore the relationships among changes in SALL4 expression, treatment response, and clinical outcome. Leukemic cell lines with low or undetectable SALL4 expression were used to study the relationship between SALL4 methylation and expression. A locus-specific demethylation technology, CRISPR-DNMT1-interacting RNA (CRISPR-DiR), was used to identify the CpG island that is critical for SALL4 expression. RESULTS: SALL4 up-regulation after treatment with hypomethylating agents was observed in 10 of 25 patients (40%) in cohort 1 and in 13 of 43 patients (30%) in cohort 2 and was associated with a worse outcome. Using CRISPR-DiR, we discovered that demethylation of a CpG island within the 5' untranslated region was critical for SALL4 expression. In cell lines and patients, we confirmed that treatment with a hypomethylating agent led to demethylation of the same CpG region and up-regulation of SALL4 expression. CONCLUSIONS: By combining analysis of patient samples with CRISPR-DiR technology, we found that demethylation and up-regulation of an oncogene after treatment with a hypomethylating agent can indeed occur and should be further studied. (Funded by Associazione Italiana per la Ricerca sul Cancro and others.).


Assuntos
Antineoplásicos , Desmetilação , Síndromes Mielodisplásicas , Oncogenes , Regulação para Cima , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Repetições Palindrômicas Curtas Agrupadas e Regularmente Espaçadas , Desmetilação/efeitos dos fármacos , Humanos , Síndromes Mielodisplásicas/tratamento farmacológico , Síndromes Mielodisplásicas/genética , Neoplasias/tratamento farmacológico , Neoplasias/genética , Oncogenes/efeitos dos fármacos , Oncogenes/fisiologia , Fatores de Transcrição/biossíntese , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Regulação para Cima/efeitos dos fármacos
15.
Environ Sci Pollut Res Int ; 29(39): 59903-59914, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35397724

RESUMO

Prenatal exposure to ambient air pollution has been associated with adverse perinatal outcomes in previous studies. However, few studies have examined the interaction between air pollution and the season of conception on term low birth weight (TLBW) or macrosomia. Birth registry data of singleton live births in Wenzhou, China, between January 2015 and December 2016 were accessed from the Wenzhou Maternal and Child Health Information Management platform, and data on the ambient air pollutants in Wenzhou were obtained from the Chinese Air Quality Online Monitoring and Analysis Platform. Single-/two-pollutant binary logistic regression models were used to assess the associations between ambient air pollutants (PM2.5, PM10, NO2, SO2, and O3) and TLBW/macrosomia, further exploring whether the season of conception interacts with air pollution to impact birth weight. Finally, 213,959 term newborns were selected, including 2452 (1.1%) infants with TLBW and 13,173 (6.1%) infants with macrosomia. In the single-/two-pollutant models, we observed an increased risk of TLBW associated with maternal exposure to PM2.5, PM10, SO2, and NO2 during the entire pregnancy, especially in the 2nd trimester. Maternal exposure to O3 during the 1st trimester was associated with increased macrosomia risk, and O3 exposure during the 3rd trimester was associated with increased TLBW risk. Pregnant women who conceive in the warm season may experience a more adverse ambient air environment that is related to the risks of TLBW. These findings add to the evidence suggesting that air pollution and the season of conception may have synergistic effects on adverse perinatal outcomes, especially TLBW. Further prospective cohort studies are needed to validate our results.


Assuntos
Poluentes Atmosféricos , Poluição do Ar , Poluentes Atmosféricos/toxicidade , Criança , China/epidemiologia , Feminino , Macrossomia Fetal/induzido quimicamente , Humanos , Lactente , Recém-Nascido , Exposição Materna , Dióxido de Nitrogênio , Material Particulado , Gravidez , Estudos Retrospectivos , Estações do Ano
18.
Front Microbiol ; 12: 726878, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34539617

RESUMO

BACKGROUND: Resveratrol (RSV) plays a vital role in alleviating various stresses and improving intestinal health. The current study was conducted to explore whether RSV alleviates weaning stress through improving gut health in a weaning mouse model. Forty 21-day-old weaned mice were randomly assigned to a control group without RSV treatment and three treatment groups with 10, 20, and 50 mg/kg RSV for 28 days. RESULTS: The results showed that RSV at a dose of 20 mg/kg improved total body weight, intestinal morphology (villus length and the ratio of villus length to crypt depth), and the levels of intestinal barrier proteins (claudin-1 and occludin), but had little effect on the food intake, crypt depth, and serum free amino acids of mice. Compared with the control group, mice supplemented with RSV had decreased mRNA expression of genes related to inflammatory cytokines (IL-6 and IL-1ß), but increased mRNA expression of genes related to host defense peptides (Defa3, Defa5, Defa20, and Lyz) and short-chain fatty acids (SCFAs) production (propionic acid, isobutyric acid, butyric acid, and isovaleric acid). In addition, 16S rRNA sequencing results showed that RSV supplementation increased the richness indices of intestinal microbiota (Chao, ACE) and shaped the composition of intestinal microbiota (e.g., increased ß-diversity of intestinal microbiota community). Meanwhile, RSV supplementation increased genes of Butyricicoccus, Ruminococcus_1, and Roseburia, which are producers of SCFAs. Furthermore, RSV supplementation significantly influenced the metabolism of intestinal microbiota, namely, amino acids metabolism, lipid metabolism, and defense mechanisms. CONCLUSION: RSV can improve growth performance and intestinal morphology in weaning mice, possibly through improving gut immune response and microbiota function.

20.
Hematol Oncol ; 39(5): 728-732, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34392561

RESUMO

In recent years, genome-based classifications for hematological neoplasms have been proposed successively and proved to be more accurate than histologic classifications. However, some previous studies have reported the racial differences of genetic landscape in persons with hematological neoplasms including myelodysplastic syndromes (MDS), which may cause a genomic classification based on a particular ethnic group does not operate in other races. To determine whether race plays an important role in the genomic-based classification, we validated a newly proposed genomic classification of MDS (J Clin Oncol.2021; JCO2001659), which was based on a large European database, in Chinese patients from our center. Our results showed significant differences between Chinese and European patients including proportion of each group to overall cohort when applying this novel genomic classification. Our data indicate that a genomic classification of hematological neoplasms probably should be revised according to specific genetic features in different races.


Assuntos
Povo Asiático/genética , Biomarcadores Tumorais/genética , Genômica/métodos , Neoplasias Hematológicas/classificação , Sequenciamento de Nucleotídeos em Larga Escala/métodos , População Branca/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Feminino , Seguimentos , Neoplasias Hematológicas/genética , Neoplasias Hematológicas/mortalidade , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Taxa de Sobrevida , Adulto Jovem
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