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1.
Proc Natl Acad Sci U S A ; 120(23): e2302858120, 2023 06 06.
Artigo em Inglês | MEDLINE | ID: mdl-37252995

RESUMO

Arabinogalactan (AG) is an essential cell wall component in mycobacterial species, including the deadly human pathogen Mycobacterium tuberculosis. It plays a pivotal role in forming the rigid mycolyl-AG-peptidoglycan core for in vitro growth. AftA is a membrane-bound arabinosyltransferase and a key enzyme involved in AG biosynthesis which bridges the assembly of the arabinan chain to the galactan chain. It is known that AftA catalyzes the transfer of the first arabinofuranosyl residue from the donor decaprenyl-monophosphoryl-arabinose to the mature galactan chain (i.e., priming); however, the priming mechanism remains elusive. Herein, we report the cryo-EM structure of Mtb AftA. The detergent-embedded AftA assembles as a dimer with an interface maintained by both the transmembrane domain (TMD) and the soluble C-terminal domain (CTD) in the periplasm. The structure shows a conserved glycosyltransferase-C fold and two cavities converging at the active site. A metal ion participates in the interaction of TMD and CTD of each AftA molecule. Structural analyses combined with functional mutagenesis suggests a priming mechanism catalyzed by AftA in Mtb AG biosynthesis. Our data further provide a unique perspective into anti-TB drug discovery.


Assuntos
Mycobacterium tuberculosis , Humanos , Galactanos , Pentosiltransferases/genética
2.
Plant Physiol ; 191(1): 96-109, 2023 01 02.
Artigo em Inglês | MEDLINE | ID: mdl-36282529

RESUMO

Degradation of starch accumulated in pollen provides energy and cellular materials for pollen germination and pollen tube elongation. Little is known about the function of cytosolic disproportionating enzyme2 (DPE2) in rice (Oryza sativa). Here, we obtained several DPE2 knockout mutant (dpe2) lines via genomic editing and found that the mutants grew and developed normally but with greatly reduced seed-setting rates. Reciprocal crosses between dpe2 and wild-type plants demonstrated that the mutant was male sterile. In vitro and in vivo examinations revealed that the pollen of the dpe2 mutant developed and matured normally but was defective in germination and elongation. DPE2 deficiency increased maltose content in pollen, whereas it reduced the levels of starch, glucose, fructose, and adenosine triphosphate (ATP). Exogenous supply of glucose or ATP to the germination medium partially rescued the pollen germination defects of dpe2. The expression of cytosolic phosphorylase2 (Pho2) increased significantly in dpe2 pollen. Knockout of Pho2 resulted in a semi-sterile phenotype. We failed to obtain homozygous dpe2 pho2 double mutant lines. Our results demonstrate that maltose catalyzed by DPE2 to glucose is the main energy source for pollen germination and pollen tube elongation, while Pho2 might partially compensate for deficiency of DPE2.


Assuntos
Arabidopsis , Oryza , Tubo Polínico/genética , Tubo Polínico/metabolismo , Oryza/genética , Oryza/metabolismo , Arabidopsis/genética , Maltose/metabolismo , Pólen/genética , Pólen/metabolismo , Glucose/metabolismo , Amido/metabolismo , Germinação/genética
3.
Ecotoxicol Environ Saf ; 274: 116218, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38492481

RESUMO

Cyfluthrin (Cy) is a widely used pyrethroid insecticide. There is growing evidence that Cy can cause damage to the nervous, reproductive, and immune systems, but there is limited evidence on the potential effects of maternal Cy exposure on offspring. A model of maternal Cy exposure was used to assess its neurobehavioral effects on young-adult offspring. We found that gestational Cy exposure affected pregnancy outcomes and fetal development, and that offspring showed impairments in anxiety as well as learning and memory, accompanied by impairments in hippocampal synaptic ultrastructure and synaptic plasticity. In addition, the IP3R-GRP75-VDAC1 apoptogenic pathway was also upregulated, and in vitro models showed that inhibition of this pathway alleviated neuronal apoptosis as well as synaptic plasticity damage. In conclusion, maternal Cy exposure during pregnancy can cause neurobehavioral abnormalities and synaptic damage in offspring, which may be related to neuronal apoptosis induced by activation of the IP3R-GRP75-VDAC1 pathway in the hippocampus of offspring. Our findings provide clues to understand the neurotoxicity mechanism of maternal Cy exposure to offspring during pregnancy.


Assuntos
Proteínas de Membrana , Nitrilas , Piretrinas , Feminino , Humanos , Gravidez , Hipocampo/metabolismo , Proteínas de Choque Térmico HSP70/metabolismo , Proteínas de Membrana/efeitos dos fármacos , Proteínas de Membrana/metabolismo , Nitrilas/toxicidade , Piretrinas/toxicidade , Canal de Ânion 1 Dependente de Voltagem/efeitos dos fármacos , Canal de Ânion 1 Dependente de Voltagem/metabolismo , Ratos , Receptores de Inositol 1,4,5-Trifosfato/efeitos dos fármacos , Receptores de Inositol 1,4,5-Trifosfato/metabolismo
4.
Ecotoxicol Environ Saf ; 270: 115828, 2024 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-38118331

RESUMO

BACKGROUND: Anemia seriously affects the health and quality of life of the older adult population and may be influenced by various types of environmental metal exposure. Current studies on metals and anemia are mainly limited to single metals, and the association between polymetals and their mixtures and anemia remains unclear. METHODS: We determined 11 urinary metal concentrations and hemoglobin levels in 3781 participants. Binary logistic regression and restricted cubic spline (RCS) model were used to estimate the association of individual metals with anemia. We used Bayesian kernel machine regression (BKMR) and Quantile g-computation (Q-g) regression to assess the overall association between metal mixtures and anemia and identify the major contributing elements. Stratified analyses were used to explore the association of different metals with anemia in different populations. RESULTS: In a single-metal model, nine urinary metals significantly associated with anemia. RCS analysis further showed that the association of arsenic (As) and copper (Cu) with anemia was linear, while cobalt, molybdenum, thallium, and zinc were non-linear. The BKMR model revealed a significant positive association between the concentration of metal mixtures and anemia. Combined Q-g regression analysis suggested that metals such as Cu, As, and tellurium (Te) were positively associated with anemia, with Te as the most significant contributor. Stratified analyses showed that the association of different metals with anemia varied among people of different sexes, obesity levels, lifestyle habits, and blood pressure levels. CONCLUSIONS: Multiple metals are associated with anemia in the older adult population. A significant positive association was observed between metal mixture concentrations and anemia, with Te being the most important factor. The association between urinary metal concentrations and anemia is more sensitive in the non-hypertensive populations.


Assuntos
Anemia , Arsênio , Humanos , Idoso , Estudos Transversais , Teorema de Bayes , Vida Independente , Qualidade de Vida , Metais/urina , Arsênio/urina , Anemia/epidemiologia , China/epidemiologia
5.
BMC Oral Health ; 24(1): 467, 2024 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-38632555

RESUMO

BACKGROUND: The temporomandibular joint (TMJ) is closely related to the dynamic balance and stability of mandibular function and orthodontic treatment. Skeletal class II female patients are thought to be at high risk for TMJ disease. The relationship between the TMJ and craniofacial structures is still controversial. This study compared the morphology and position of the TMJ in skeletal class II adolescents and adults with various vertical facial types using cone-beam computed tomography (CBCT). MATERIALS AND METHODS: A total of 117 skeletal class II patients were divided into three groups according to the FH-GoGn angle (hypodivergent, normodivergent and hyperdivergent), with 40 class I normodivergent patients serving as controls. Each group contained two age subgroups (adolescents: 11-14 years old, adults: 18-35 years old). The size (condylar length, height, long and short axis diameter, glenoid fossa width and depth) and shape (condylar neck inclination, condylar head angle and long axis angle, articular eminence inclination) of the condyle and fossa, joint space (anterior, superior, posterior, mesial and lateral), and position of the fossa (vertical, transverse, and anteroposterior distance) and condyle were measured and compared using CBCT. RESULTS: Class II hypodivergent patients exhibited the greatest condylar length, height, and long- and short-axis diameter; steepest articular eminence; deepest fossa depth; largest superior, mesial and lateral joint spaces; and highest fossa position in both age groups. The manifestations of class II hyperdivergent patients were mostly the opposite. In adults, except for the condylar long axis angle, the measurements of the condyle increased differently among skeletal patterns, while the measurements of the fossa decreased, as the joint spaces and fossa position remained approximately stable compared with those in adolescents. CONCLUSION: The vertical skeletal pattern, rather than the class II sagittal skeletal pattern, may be the main factor affecting the morphology and position of the TMJ. Attention should be given to the TMJ area in hyperdivergent patients with a relatively poor-fit condyle-fossa relationship. The changes in the TMJ with age were mainly morphological rather than positional and varied with skeletal pattern.


Assuntos
Côndilo Mandibular , Articulação Temporomandibular , Adulto , Adolescente , Humanos , Feminino , Criança , Adulto Jovem , Estudos Transversais , Mandíbula , Face , Tomografia Computadorizada de Feixe Cônico/métodos
6.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 55(3): 662-670, 2024 May 20.
Artigo em Zh | MEDLINE | ID: mdl-38948267

RESUMO

Objective: To establish a universally applicable logistic risk prediction model for diabetes mellitus type 2 (T2DM) in the middle-aged and elderly populations based on the results of a Meta-analysis, and to validate and confirm the efficacy of the model using the follow-up data of medical check-ups of National Basic Public Health Service. Methods: Cohort studies evaluating T2DM risks were identified in Chinese and English databases. The logistic model utilized Meta-combined effect values such as the odds ratio (OR) to derive ß, the partial regression coefficient, of the logistic model. The Meta-combined incidence rate of T2DM was used to obtain the parameter α of the logistic model. Validation of the predictive performance of the model was conducted with the follow-up data of medical checkups of National Basic Public Health Service. The follow-up data came from a community health center in Chengdu and were collected between 2017 and 2022 from 7602 individuals who did not have T2DM at their baseline medical checkups done at the community health center. This community health center was located in an urban-rural fringe area with a large population of middle-aged and elderly people. Results: A total of 40 cohort studies were included and 10 items covered in the medical checkups of National Basic Public Health Service were identified in the Meta-analysis as statistically significant risk factors for T2DM, including age, central obesity, smoking, physical inactivity, impaired fasting glucose, a reduced level of high-density lipoprotein cholesterol (HDL-C), hypertension, body mass index (BMI), triglyceride glucose (TYG) index, and a family history of diabetes, with the OR values and 95% confidence interval (CI) being 1.04 (1.03, 1.05), 1.55 (1.29, 1.88), 1.36 (1.11, 1.66), 1.26 (1.07, 1.49), 3.93 (2.94, 5.24), 1.14 (1.06, 1.23), 1.47 (1.34, 1.61), 1.11 (1.05, 1.18), 2.15 (1.75, 2.62), and 1.66 (1.55, 1.78), respectively, and the combined ß values being 0.039, 0.438, 0.307, 0.231, 1.369, 0.131, 0.385, 0.104, 0.765, and 0.507, respectively. A total of 37 studies reported the incidence rate, with the combined incidence being 0.08 (0.07, 0.09) and the parameter α being -2.442 for the logistic model. The logistic risk prediction model constructed based on Meta-analysis was externally validated with the data of 7602 individuals who had medical checkups and were followed up for at least once. External validation results showed that the predictive model had an area under curve (AUC) of 0.794 (0.771, 0.816), accuracy of 74.5%, sensitivity of 71.0%, and specificity of 74.7% in the 7602 individuals. Conclusion: The T2DM risk prediction model based on Meta-analysis has good predictive performance and can be used as a practical tool for T2DM risk prediction in middle-aged and elderly populations.


Assuntos
Diabetes Mellitus Tipo 2 , Humanos , Diabetes Mellitus Tipo 2/epidemiologia , Pessoa de Meia-Idade , Idoso , Fatores de Risco , Modelos Logísticos , Feminino , Masculino , China/epidemiologia , Estudos de Coortes , Saúde Pública , Incidência
7.
J Cell Mol Med ; 27(10): 1384-1397, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-37005492

RESUMO

Human placental mesenchymal stem cells (PMSCs) can prevent liver ischaemia-reperfusion injury (LIRI). However, their therapeutic effects are limited. Therefore, additional research is required to elucidate the mechanisms of PMSC-mediated LIRI prevention and enhance the related therapeutic effects. This study aimed to examine the role of the Lin28 protein in the regulation of glucose metabolism in PMSCs. Further, it explored whether Lin28 could enhance the protective effects of PMSCs against LIRI and investigated the underlying mechanisms. Western blotting was performed to examine Lin28 expression in PMSCs under hypoxic conditions. A Lin28 overexpression construct was introduced into PMSCs, and the effect on glucose metabolism was examined using a glucose metabolism kit. Further, the expression of some proteins involved in glucose metabolism and the PI3K-AKT pathway and the levels of microRNA Let-7a-g were examined using western blots and real-time quantitative PCR, respectively. To examine the relationship between Lin28 and the PI3K-Akt pathway, the effects of AKT inhibitor treatment on the changes induced by Lin28 overexpression were examined. Subsequently, AML12 cells were co-cultured with PMSCs to elucidate the mechanisms via which PMSCs prevent hypoxic injury in liver cells in vitro. Finally, C57BL/6J mice were used to establish a partial warm ischaemia-reperfusion model. The mice received intravenous injections containing PMSCs (control and Lin28-overexpressing PMSCs). Finally, their serum transaminase levels and degree of liver injury were assessed using biochemical and histopathological methods, respectively. Lin28 was upregulated under hypoxic conditions in PMSCs. Lin28 exerted protective effects against hypoxia-induced cell proliferation. Moreover, it increased the glycolytic capacity of PMSCs, allowing PMSCs to produce more energy under hypoxic conditions. Lin28 also activated the PI3K-Akt signalling pathway under hypoxic conditions, and its effects were attenuated by AKT inhibition. Lin28 overexpression could protect cells against LIRI-induced liver damage, inflammation and apoptosis and could also attenuate hypoxia-induced hepatocyte injury. Lin28 enhances glucose metabolism under hypoxic conditions in PMSCs, thereby exerting protective effects against LIRI by activating the PI3K-Akt signalling pathway. Our study is the first to report the potential of genetically modified PMSCs for LIRI treatment.


Assuntos
Hepatopatias , Traumatismo por Reperfusão , Animais , Feminino , Humanos , Camundongos , Gravidez , Apoptose/genética , Glucose/farmacologia , Hipóxia , Camundongos Endogâmicos C57BL , Fosfatidilinositol 3-Quinases/genética , Fosfatidilinositol 3-Quinases/metabolismo , Placenta/metabolismo , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Traumatismo por Reperfusão/genética , Traumatismo por Reperfusão/prevenção & controle , Traumatismo por Reperfusão/metabolismo
8.
Theor Appl Genet ; 136(3): 47, 2023 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-36912930

RESUMO

KEY MESSAGE: Plastidial α-glucan phosphorylase is a key factor that cooperates with plastidial disproportionating enzyme to control short maltooligosaccharide mobilization during the initiation process of starch molecule synthesis in developing rice endosperm. Storage starch synthesis is essential for grain filling. However, little is known about how cereal endosperm controls starch synthesis initiation. One of core events for starch synthesis initiation is short maltooligosaccharide (MOS) mobilization consisting of long MOS primer production and excess MOS breakdown. By mutant analyses and biochemical investigations, we present here functional identifications of plastidial α-glucan phosphorylase (Pho1) and disproportionating enzyme (DPE1) during starch synthesis initiation in rice (Oryza sativa) endosperm. Pho1 deficiency impaired MOS mobilization, triggering short MOS accumulation and starch synthesis reduction during early seed development. The mutant seeds differed significantly in MOS level and starch content at 15 days after flowering and exhibited diverse endosperm phenotypes during mid-late seed development: ranging from pseudonormal to shrunken (Shr), severely or excessively Shr. The level of DPE1 was almost normal in the PN seeds but significantly reduced in the Shr seeds. Overexpression of DPE1 in pho1 resulted in plump seeds only. DPE1 deficiency had no obvious effects on MOS mobilization. Knockout of DPE1 in pho1 completely blocked MOS mobilization, resulting in severely and excessively Shr seeds only. These findings show that Pho1 cooperates with DPE1 to control short MOS mobilization during starch synthesis initiation in rice endosperm.


Assuntos
Endosperma , Oryza , Endosperma/genética , Endosperma/metabolismo , Oryza/metabolismo , Fosforilases/genética , Fosforilases/metabolismo , Amido/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Regulação da Expressão Gênica de Plantas
9.
Ecotoxicol Environ Saf ; 259: 114966, 2023 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-37182299

RESUMO

BACKGROUND: Environmental metal exposure is associated with elevated triglycerides (TG) and the development of chronic kidney disease (CKD). However, the relationship between metal exposure and glomerular filtration rate (GFR) remains uncertain, and the mediating effect of TG between the two is unclear. METHODS: This study measured the concentrations of 14 metals in urine samples from 3752 elderly people in the community. The most relevant metals were screened by least absolute shrinkage and selection operator (LASSO) regression. The relationship between combined exposure to multiple metals and abnormal estimated glomerular filtration rate (eGFR) was explored using multivariate logistic regression analysis and Bayesian kernel machine regression (BKMR) analysis. Generalized linear regression models and the Karlson-Holm-Breen (KHB) method were used to assess the mediating effects of TG. RESULTS: In the single-metal model, calcium (Ca), iron (Fe), selenium (Se), strontium (Sr), and thallium (Tl) showed significant negative correlations with the prevalence of abnormal eGFR (all P < 0.05). In the multi-metals model, Ca, Se, and Tl continued to show significant negative correlations, while vanadium (V) and zinc (Zn) showed significant positive correlations with abnormal eGFR (all P < 0.05). The BKMR model showed a negative joint effect of the mixture of Ca, V, Zn, Se, and Tl on the prevalence of abnormal eGFR. The generalized linear regression model showed a significant positive correlation between the concentrations of Ca (ß = 0.07), Zn (ß = 0.07), Se (ß = 0.09), and TG levels (all P < 0.05). In the mediation analysis, TG masked a 4.30% and 5.21% correlation between Ca and Se and the prevalence of eGFR abnormalities, respectively. CONCLUSIONS: Urinary concentration of multiple metals is significantly associated with eGFR abnormalities, and Ca, and Se may be among the potential protective factors. TG masked some of the protective effects of Ca and Se.


Assuntos
Taxa de Filtração Glomerular , Metais , Triglicerídeos , Idoso , Humanos , Teorema de Bayes , Cálcio , População do Leste Asiático , Vida Independente , Selênio , Zinco , Metais/urina
10.
Environ Toxicol ; 38(4): 727-742, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36515635

RESUMO

Cyfluthrin is widely used in the field of sanitary pest control by its wide insecticidal spectrum, high efficiency and low toxicity, low residue, and good biodegradability. But, as a double-edged sword, a large amount of cyfluthrin remains are still in the environment. The residual cyfluthrin is absorbed into the food chain through vegetation and then poses a risk to soil organisms and human health. Several studies have suggested that cyfluthrin is one of the main factors causing testicular damage, but the mechanism remains unclear. In this study, we established in vivo and in vitro models of testicular injury in rats and GC-2 cells exposed to cyfluthrin to explore whether stimulator of interferon genes (STING) gene mediates the regulation of AMPK/mTOR/p70S6K autophagy pathway, which lays a foundation for further study of the mechanism of testicular injury induced by cyfluthrin. The results showed that the activity of super oxide dismutase in testis decreased and the activity of malonic dialdehyde increased with the increase of concentration in vivo and in vitro. At the same time, the levels of mitochondrial damage and inflammation in the testis also increased, which further activated autophagy. In this process, the increased level of inflammation is related to the increased expression of STING gene, and AMPK/mTOR/p70S6K autophagy pathway is also involved. To sum up, cyfluthrin has certain reproductive toxicity, and long-term exposure can induce testicular cell damage. STING gene can participate in cyfluthrin-induced testicular injury through AMPK/mTOR/P70S6K autophagy pathway.


Assuntos
Proteínas Quinases Ativadas por AMP , Transdução de Sinais , Masculino , Ratos , Humanos , Animais , Proteínas Quinases Ativadas por AMP/metabolismo , Proteínas Quinases S6 Ribossômicas 70-kDa/metabolismo , Serina-Treonina Quinases TOR/metabolismo , Autofagia , Interferons
11.
J Sports Sci ; 41(10): 937-946, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37598352

RESUMO

While a higher level of physical activity (PA) is inversely associated with a higher breast cancer (BC) risk, the health benefits of daily steps on obesity-related BC biomarkers remain unclear. We aimed to understand the associations of changes in step counts with levels of five obesity-related BC biomarkers during a two-year follow-up. In total, 144 non-cancer women (47.96 ± 5.72) were observed on both 2019 and 2021. A structured questionnaire, daily steps and fasting blood samples were collected before (t0, 2019) and after (t1, 2021). Levels of biomarkers (IGF-binding proteins 3, adiponectin, soluble leptin receptor, C-reactive protein, and resistin) were assayed by ELISA. Participants were divided into persistent low steps, decreasing steps, increasing steps, and persistent high steps. Associations of categories on proposed biomarkers were estimated using linear regression models, with persistent low steps as reference. Associations between time-varying step counts with biomarkers were quantified using mixed linear models. Compared with persistent low steps, increasing steps is associated with a reduction in C-reactive protein level (ß=-0.74, 95%CI=-1.23--0.26, P-value = 2.98 × 10-3). An inverse association between time-varying step counts with C-reactive protein level was identified, consistent across different obesity types and baseline step level categories. No association with daily step counts was observed for other proteins.


Assuntos
Biomarcadores Tumorais , Neoplasias da Mama , Humanos , Feminino , Actigrafia , Smartphone , Proteína C-Reativa , Obesidade , Biomarcadores
12.
BMC Oral Health ; 23(1): 508, 2023 07 21.
Artigo em Inglês | MEDLINE | ID: mdl-37479973

RESUMO

BACKGROUND: Whether slim the face or not after removed third molars is the concern of some orthodontic treatment candidates. The aim of this article is to explore the volume changes of facial soft and hard tissues after third molars extraction, as well as develop a reproducible clinical protocol to precisely assess facial soft tissue volume change. METHODS: A non-randomized, non-blind, self-controlled pilot study was conducted. 24 adults aged 18-30 had ipsilateral third molars extracted. The body weight change was controlled within 2 kg. Structured light scans were taken under a standardized procedure pre-extraction (T0), three (T1), and six (T2) months post-extraction; CBCTs were taken at T0 and T2. The projection method was proposed to measure the soft tissue volume (STV) and the soft tissue volume change (STVC) by the Geomagic software. The hard tissue volume change (HTVC) was measured in the Dragonfly software. RESULTS: The final sample size is 23, including 5 males (age 26.6 ± 2.5 years) and 18 females (age 27.3 ± 2.5 years). The HTVC was - 2.33 ± 0.46ml on the extraction side. On the extraction side, the STV decreased by 1.396 (95% CI: 0.323-2.470) ml (P < 0.05) at T1, and increased by 1.753 (95% CI: -0.01-3.507) ml (P = 0.05) at T2. T2 and T0 had no difference (P > 0.05). The inter and intra-raters ICC of the projection method was 0.959 and 0.974. There was no correlation between the STVC and HTVC (P > 0.05). CONCLUSIONS: After ipsilateral wisdom teeth extraction, the volume of hard tissue on the extraction side reduces, and the volume of facial soft tissue does not change evidently. However, further research with large sample size is still needed. The STV measurement has excellent repeatability. It can be extended to other interested areas, including forehead, nose, paranasal, upper lip, lower lip and chin, which is meaningful in the field of orthodontics and orthopedics. TRIAL REGISTRATION: ChiCTR, ChiCTR1800018305 (11/09/2018), http://www.chictr.org.cn/showproj.aspx?proj=28868 .


Assuntos
Assistência Odontológica , Feminino , Humanos , Masculino , Queixo , Lábio , Projetos Piloto , Adulto
13.
J Appl Toxicol ; 42(3): 475-489, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-34561900

RESUMO

Aflatoxin is a secondary metabolite secreted by Aspergillus flavus, parasitic Aspergillus, and other fungi through the polyketone pathway, and it can be detected in many foods. Aflatoxin has strong toxicity and carcinogenicity, and many studies have shown that aflatoxin is highly associated with liver cancer. In the present study, malignant transformation of L02 cells was induced by aflatoxin B1 (AFB1), and the gene expression, miRNA expression, and methylation level were detected by high-throughput sequencing. The gene and miRNA expression results showed that 2547 genes and 315 miRNAs were changed in the AFB1-treated group compared with the DMSO group. Among them, RSAD2 and SCIN were significantly upregulated, whereas TRAPPC3L and UBE2L6 were significantly downregulated. Has-miR-33b-3p was significantly upregulated, whereas Has-miR-3613-5p was significantly downregulated. The methylation results showed that 2832 CpG sites were methylated on the promoter or coding DNA sequence (CDS) of the gene, whereas the expression of DNMT3a and DNMT3b was significantly upregulated. Moreover, hypermethylation occurred in TRAPPC3L, CDH13, and SPINK13. The results of GO and KEGG pathway analyses showed that significantly changed genes and miRNAs were mainly involved in tumor formation, proliferation, invasion, and migration. The results of network map analysis showed that Hsa-miR-3613-5p, Hsa-miR-615-5p, Hsa-miR-615-3p, and Hsa-miR-3158-3p were the key miRNAs for malignant transformation of L02 cells induced by AFB1. In addition, the expression of ONECUT2, RAP1GAP2, and FSTL4 was regulated by DNA methylation and miRNAs. These results suggested that the gene expression network regulated by DNA methylation and miRNAs may play a vital role in AFB1-induced hepatocellular carcinoma.


Assuntos
Aflatoxina B1/toxicidade , Metilação de DNA , Redes Reguladoras de Genes/efeitos dos fármacos , MicroRNAs/genética , Linhagem Celular , Metilação de DNA/efeitos dos fármacos , Humanos , Fígado/efeitos dos fármacos , Fígado/fisiologia
14.
Environ Toxicol ; 37(5): 1136-1151, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35099110

RESUMO

The pesticide 2,4-dichlorophenoxyacetic acid (2,4-D) exerts neurotoxic effects; however, its action mechanism remains unclear. Here, we used BV2 cells as a model and divided them into six groups: control group (serum-free medium), lipopolysaccharide (LPS) (1 µg/mL), 2,4-D (1.2 µmol/mL), Lycium barbarum polysaccharide (LBP; 300 µg/mL LBP), LPS (1 µg/mL) + LBP (300 µg/mL), and 2,4-D (1.2 µmol/mL) + LBP (300 µg/mL) with dimethyl sulfoxide as the solvent. Our results showed that 2,4-D treatment decreased superoxide dismutase and glutathione peroxidase activities and increased malondialdehyde content. The percentage of microglial activation (co-expression of ionized calcium-binding adaptor protein-1 + CD68) in the LPS and 2,4-D groups and the levels of tumor necrosis factor alpha, interleukin (IL) 1 beta, IL-6, and IL-18 in the cell supernatant were increased. The protein and mRNA levels of Nod-like receptor protein 3 (NLRP3), apoptosis-associated speck-like protein, caspase-1, IL-1ß, IL-18, and p62 increased, whereas those of LC3II/I and Beclin-1 decreased in the 2,4-D group. The protein expression and mRNA levels of NLRP3, cleaved caspase-1, IL-1ß, IL-18, and p62 decreased significantly, whereas the protein expression and mRNA levels of LC3II/I and Beclin-1 increased in small interfering RNA of NLRP3-treated BV2 cells stimulated with 2,4-D and LPS. In conclusion, 2,4-D enhanced cell migration, promoted oxidative stress, induced excessive release of mitochondrial reactive oxygen species, promoted microglial cell activation, released inflammatory factors, activated NLRP3 inflammasomes, and inhibited autophagy. Meanwhile, LBP reduced inflammation and the release of mitochondrial reactive oxygen species, inhibited NLRP3 inflammasome activation, and regulated autophagy, thereby playing a neuroprotective role.


Assuntos
Microglia , Proteína 3 que Contém Domínio de Pirina da Família NLR , Ácido 2,4-Diclorofenoxiacético/metabolismo , Ácido 2,4-Diclorofenoxiacético/toxicidade , Animais , Autofagia , Medicamentos de Ervas Chinesas , Inflamassomos/metabolismo , Interleucina-1beta/metabolismo , Lipopolissacarídeos/toxicidade , Camundongos , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Proteínas NLR/metabolismo , Espécies Reativas de Oxigênio/metabolismo
15.
Environ Toxicol ; 37(11): 2764-2779, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36214342

RESUMO

The herbicide 2,4-Dichlorophenoxyacetic acid (2,4-D) is widely used to control broadleaved weeds and has been associated with male infertility. We studied the molecular mechanisms of 2,4-D induced male reproductive system damage and the protective effects of Lycium barbarum polysaccharides (LBP) using Sprague Dawley rats and TM4 cells. Treatment with 2,4-D caused architectural and functional changes in the testis, including collapsed and atrophied seminiferous tubules with reduced number of spermatozoa, scarce sperm in the epididymal duct, low levels of serum testosterone, decreased superoxide dismutase and glutathione peroxidase activity, high malondialdehyde content, and increased apoptosis in the testis and epididymis. The expression of Fas, FasL, FADD, Pro-caspase-8, Cleaved-Caspase-8, Pro-Caspase-3, and Cleaved-Caspase-3 were significantly increased in the testicular tissue of 2,4-D-treated rats. The proliferative activity of TM4 cells decreased with an increase in dose and time of 2,4-D exposure, along with enhanced Fas/Fas ligand expression and a decreased concentration of inhibin B in TM4 cell culture medium. Depletion of Fas by specific shRNA transfection reversed the effects of 2,4-D in TM4 cells, further confirming the involvement of death receptor pathway in 2,4-D-mediated apoptosis of sertoli cells. Treatment with LBP also reversed the effects of 2,4-D in testicular cells, resulting in improved cell architecture along with enhanced proliferative capacity. Moreover, in response to LBP treatment of Sertoli cells, the content of inhibin B increased, the level of reactive oxygen species and malondialdehyde decreased, the activities of superoxide dismutase and glutathione peroxidase increased, and the rate of apoptosis as well as the expression of Fas/Fas ligand signaling pathway proteins decreased.


Assuntos
Herbicidas , Lycium , Ácido 2,4-Diclorofenoxiacético/metabolismo , Ácido 2,4-Diclorofenoxiacético/toxicidade , Animais , Apoptose , Caspase 3/metabolismo , Caspase 8/metabolismo , Proteína Ligante Fas/metabolismo , Glutationa Peroxidase/metabolismo , Herbicidas/toxicidade , Lycium/metabolismo , Masculino , Malondialdeído/metabolismo , Polissacarídeos/farmacologia , RNA Interferente Pequeno/metabolismo , Ratos , Ratos Sprague-Dawley , Espécies Reativas de Oxigênio/metabolismo , Receptores de Morte Celular/metabolismo , Sementes/metabolismo , Superóxido Dismutase/metabolismo , Testículo , Testosterona
16.
BMC Med Educ ; 22(1): 210, 2022 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-35351115

RESUMO

BACKGROUND: Physicians should be equipped with professional competence in health literacy to communicate more effectively with patients with limited health literacy. However, the health literacy curriculum has not yet been refined globally, and is scarce in Taiwan's medical education. We implemented an innovative instructional module to attain professional competence in health literacy among medical students and investigated its effects. METHODS: We adopted a quasi-experimental design and recruited 204 fifth-year Taiwanese medical students between December 2019 and May 2020. Participants who worked as clerks at the Department of Family Medicine of three medical schools in northern Taiwan were assigned to the experimental group through convenience sampling. A total of 98 students received a three-hour innovative instruction, including medical simulation videos, role-playing, and board games. Both the experimental and control groups completed the online pre-test and mail-in post-test. A generalized estimating equation was applied to measure the effects of the intervention. RESULTS: There was a significant difference between the experimental and control groups in terms of professional competence in health literacy in all three aspects. In terms of knowledge, the experimental group improved 12% more than the control group (𝛽=0.12, 95% CI: 0.05 ~ 0.19, p = 0.001). In terms of attitude, the experimental group improved by an average of 0.27 more points per question than the control group (𝛽=0.27, 95% CI: 0.08 ~ 0.46, p = 0.007). As for skill, the experimental group improved by an average of 0.35 more points per question than the control group (𝛽=0.35, 95% CI: 0.14 ~ 0.55, p = 0.001). CONCLUSION: The proposed innovative instructional module significantly improved fifth-year medical students' professional competence in health literacy, which is expected to benefit their future medical practices.


Assuntos
Letramento em Saúde , Estudantes de Medicina , Competência Clínica , Currículo , Humanos , Competência Profissional
17.
Clin Otolaryngol ; 47(2): 304-312, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-34821469

RESUMO

OBJECTIVE: The role of ideal cardiovascular health (CVH) metrics in developing hearing loss remains uncertain. Thus, our objective was to analyse the connection between hearing loss and ideal CVH metrics in a 10-year retrospective cohort. STUDY DESIGN: Retrospective cohort study. SETTING: A health management centre in Taiwan. PARTICIPANTS: Participants who underwent the first annual health check-up between 2000 and 2006 and with a follow-up check-up more than ten years later. MAIN OUTCOME MEASURES: Hearing thresholds were measured at 500 Hz, 1000 Hz, 2000 Hz and 4000 Hz. Individuals with a best ear pure-tone audiometry four-frequency average of >25 dB HL were defined as having hearing loss. The ideal CVH metrics were classified into 7 categories based on the American Heart Association's definition. The associations of hearing loss with the sum of the ideal CVH metrics and each ideal CVH metric were examined by multiple logistic regression analysis. RESULTS: The present study consisted of 6974 participants. The 10-year follow-up showed that the odds ratio (OR) of hearing loss was .74 for participants with 5-7 ideal CVH metrics (95% CI, .59-.93, p = .01) compared with those with 0-2 ideal CVH metrics. Among the CVH metrics, participants with an ideal smoking status might have reduced odds of developing hearing loss; the OR was .72 (95% CI, .58-.89, p = .003). CONCLUSIONS: Participants with an increased number of ideal CVH metrics and better performance on the smoking metric had a significantly protective effect regarding hearing loss development.


Assuntos
Perda Auditiva/etiologia , Fatores de Risco de Doenças Cardíacas , Indicadores de Qualidade em Assistência à Saúde , Adulto , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
18.
Water Sci Technol ; 85(3): 799-810, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35166701

RESUMO

ReliefF algorithm was used to analyze the weight of each water quality evaluation factor, and then based on the Relevance Vector Machine (RVM), Particle Swarm Optimization (PSO) was used to optimize the kernel width factor and hyperparameters of RVM to build a water quality evaluation model, and the experimental results of RVM, PSO-RVM, ReliefF-RVM and PSO-ReliefF-RVM were compared. The results show that ReliefF algorithm, combined with threshold value, selects 5 evaluation factors with significant weight from eight evaluation factors, which reduces the amount of data used in the model, CSI index is used to calculate the separability of each evaluation factor combination. The results show that the overall separability of the combination is best when the evaluation factor with significant weight is reserved. When different water quality evaluation factors were included, the evaluation accuracy of PSO-ReliefF-RVM model reached 95.74%, 14.23% higher than that of RVM model, which verified the effectiveness of PSO algorithm and ReliefF algorithm, and had a higher guiding significance for the study of water quality grade evaluation. It has good practical application value.


Assuntos
Algoritmos , Qualidade da Água
19.
Opt Lett ; 46(22): 5639-5642, 2021 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-34780425

RESUMO

In this work, the novel, to the best of our knowledge, blue-cyan Y2Mg0.8Sr0.2Al4SiO12:Eu2+ (YM0.8S0.2AS:Eu2+) phosphors were synthesized by the solid-state method. At 150°C, the emission intensity of Y2Mg0.8Sr0.2Al4SiO12:0.005Eu2+ can retain 96.38% of the relative intensity, which means that this phosphor shows high thermal stability. A white light-emitting diode (LED) device is fabricated by combining a 370 nm near ultraviolet LED chip and commercial phosphors (green, (Ba,Sr)2SiO4:Eu; red, CaSiAlN3:Eu). The white LED has an excellent property with the correlated color temperature CCT=5236K and superhigh color rendering index Ra=96.1, which indicates the potential application in white LED fields.

20.
Inorg Chem ; 60(21): 16593-16603, 2021 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-34672565

RESUMO

Corresponding to the absorption curve of plant photosensitive pigment Pfr, near-infrared light has a broad application prospect in plant lighting. In order to explore this plant growth lamp, the novel near-infrared emitting phosphor LaMg0.5Sn0.5O3:Cr3+ was synthesized, which can be efficiently excited by 467 nm blue light. There are two luminescence centers, which were proven by testing the low-temperature spectrum, the excitation spectrum at different wavelengths, and the lifetime decay curve, and the two cell sequence substitution processes were obtained by Rietveld refinements of XRD. By introducing Ge4+, its luminescence intensity has been increased 1.6 times and the intensity at 150 °C remains at almost 80% that at room temperature. Finally, two different kinds of illumination experiments for plant growth were carried out, and the feasibility of the LaMg0.5(SnGe)0.5O3:Cr3+ phosphor for plant growth was confirmed.


Assuntos
Luminescência
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