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OBJECTIVE: To examine the association between pre-pregnancy BMI and severe maternal morbidity (SMM), perinatal death and severe neonatal morbidity in twin pregnancies. METHODS: All twin births at ≥ 20 weeks gestation in British Columbia, Canada, from 2000 to 2017 were included. We estimated rates of SMM, a perinatal composite of death and severe morbidity, and its components per 10,000 pregnancies. Confounder-adjusted rate ratios (aRR) between pre-pregnancy BMI and outcomes were estimated using robust Poisson regression. RESULTS: Overall, 7770 (368 underweight, 1704 overweight, and 1016 obese) women with twin pregnancy were included. The rates of SMM were: 271.1, 320.4, 270.0, and 225.9 in underweight, normal BMI, overweight and obese women, respectively. There was little association between obesity and any of the primary outcomes (e.g., aRR = 1.09, 95% CI = 0.85, 1.38 for composite perinatal outcome). Underweight women had higher rates of the composite perinatal adverse outcome (aRR = 1.79, 95% CI = 1.32-2.43), driven by increased rates of severe respiratory distress syndrome, and neonatal death. CONCLUSIONS: There was no evidence of elevated risk of adverse outcomes among twin pregnancies of women who were overweight or obese. Risk was higher in underweight women, who may require specific care when carrying twins.
Assuntos
Sobrepeso , Complicações na Gravidez , Gravidez , Recém-Nascido , Feminino , Humanos , Índice de Massa Corporal , Magreza/complicações , Magreza/epidemiologia , Estudos Retrospectivos , Complicações na Gravidez/epidemiologia , Obesidade/complicações , Obesidade/epidemiologia , Resultado da Gravidez/epidemiologia , Fatores de RiscoRESUMO
OBJECTIVES: Targeted inhibition of inflammatory response can reduce diabetic cerebral ischemia-reperfusion (I/R) injure. Pyroptosis is characterized by caspase-1 dependence and the release of a large number of pro-inflammatory factors. LncRNA-Fendrr is associated with a variety of diseases, but Fendrr has not been studied in diabetic cerebral I/R. NLR-family CARD-containing protein 4 (NLRC4) regulate the pyroptosis of microglia cells. This study was designed to investigate whether Fendrr is involved in the effects of diabetic cerebral I/R injury. METHODS: The diabetic brain I/R model in mice was constructed. Mouse microglia cell line BV-2 cells were exposed to high glucose followed by hypoxia/reoxygenation (H/R). Fendrr and some pyroptosis-associated proteins were detected by qRT-PCR, western blot or ELISA. HE staining was used to detect pathological changes. Microglia pyroptosis was detected by TUNEL staining. RNA pull-down and RNA Immunoprecipitation were used to detect binding of Fendrr to HERC2 (E3 ubiquitin ligase), and CO-IP detected binding of HERC2 to NLRC4. The ubiquitination of NLRC4 was detected by ubiquitination experiments. RESULTS: Fendrr was significantly increased in the diabetic cerebral I/R model, and NLRC4 inflammatory complex and pyroptosis mediated inflammatory factors were increased. NLRC4 and inflammatory cytokines associated with pyroptosis were decreased in the high glucose-treated hypoxia/reoxygenation (H/R)-induced microglia after Fendrr knockdown. Fendrr bound to HERC2 protein, and HERC2 bound to NLRC4. Meanwhile, Fendrr could inhibit the ubiquitination of NLRC4, HERC2 promoted the ubiquitination of NLRC4 protein. Moreover, the effect of Fendrr overexpression in the diabetic cerebral I/R model of microglia can be reversed by HERC2 overexpression. CONCLUSION: Fendrr can protect against the ubiquitination and degradation of NLRC4 protein through E3 ubiquitin ligase HERC2, thereby accelerating the pyroptosis of microglia.
Assuntos
Proteínas Reguladoras de Apoptose/metabolismo , Proteínas de Ligação ao Cálcio/metabolismo , Diabetes Mellitus/genética , Fatores de Troca do Nucleotídeo Guanina/metabolismo , Infarto da Artéria Cerebral Média/genética , Microglia/metabolismo , RNA Longo não Codificante , Traumatismo por Reperfusão/genética , Animais , Encéfalo/metabolismo , Linhagem Celular , Diabetes Mellitus/metabolismo , Infarto da Artéria Cerebral Média/metabolismo , Inflamação/genética , Masculino , Camundongos Endogâmicos C57BL , Piroptose , RNA Longo não Codificante/genética , Traumatismo por Reperfusão/metabolismo , UbiquitinaçãoRESUMO
BACKGROUND: The majority of previous studies on severe preeclampsia, eclampsia, and hemolysis, elevated liver enzymes, and low platelet count syndrome were hospital-based or included a relatively small number of women. Large, population-based studies examining gestational age-specific incidence patterns and risk factors for these severe pregnancy complications are lacking. OBJECTIVE: This study aimed to assess the gestational age-specific incidence rates and risk factors for severe preeclampsia, hemolysis, elevated liver enzymes, and low platelet count syndrome, and eclampsia. STUDY DESIGN: We carried out a retrospective, population-based cohort study that included all women with a singleton hospital birth in Canada (excluding Quebec) from 2012 to 2016 (N=1,078,323). Data on the primary outcomes (ie, severe preeclampsia, hemolysis, elevated liver enzymes, and low platelet count syndrome, and eclampsia) were obtained from delivery hospitalization records abstracted by the Canadian Institute for Health Information. A Cox regression was used to assess independent risk factors (eg, maternal age and chronic comorbidity) for each primary outcome and to assess differences in the effects at preterm vs term gestation (<37 vs ≥37 weeks). RESULTS: The rates of severe preeclampsia (n=2533), hemolysis, elevated liver enzymes, and low platelet count syndrome (n=2663), and eclampsia (n=465) were 2.35, 2.47, and 0.43 per 1000 singleton pregnancies, respectively. The cumulative incidence of term-onset severe preeclampsia was lower than that of preterm-onset severe preeclampsia (0.87 vs 1.54 per 1000; rate ratio, 0.57; 95% confidence intervals, 0.53-0.62), the rates of hemolysis, elevated liver enzymes, and low platelet count syndrome were similar (1.32 vs 1.23 per 1000; rate ratio, 0.93; 95% confidence interval, 0.86-1.00), and the preterm-onset eclampsia rate was lower than the term-onset rate (0.12 vs 0.33 per 1000; rate ratio, 2.64; 95% confidence interval, 2.16-3.23). For each primary outcome, chronic comorbidity and congenital anomalies were stronger risk factors for preterm- vs term-onset disease. Younger mothers (aged <25 years) were at higher risk for severe preeclampsia at term and for eclampsia at all gestational ages, whereas older mothers (aged ≥35 years) had elevated risks for severe preeclampsia and hemolysis, elevated liver enzymes, and low platelet count syndrome. Regardless of gestational age, nulliparity was a risk factor for all outcomes, whereas socioeconomic status was inversely associated with severe preeclampsia. CONCLUSION: The risk for severe preeclampsia declined at term, eclampsia risk increased at term, and hemolysis, elevated liver enzymes, and low platelet count syndrome risk was similar for preterm and term gestation. Young maternal age was associated with an increased risk for eclampsia and term-onset severe preeclampsia. Prepregnancy comorbidity and fetal congenital anomalies were more strongly associated with severe preeclampsia, hemolysis, elevated liver enzymes, and low platelet count syndrome, and eclampsia at preterm gestation.
Assuntos
Eclampsia/epidemiologia , Hemólise , Testes de Função Hepática , Pré-Eclâmpsia/epidemiologia , Nascimento Prematuro/epidemiologia , Nascimento a Termo , Trombocitopenia/epidemiologia , Adolescente , Adulto , Canadá/epidemiologia , Estudos de Coortes , Feminino , Humanos , Incidência , Paridade , Gravidez , Complicações Hematológicas na Gravidez , Estudos Retrospectivos , Fatores de Risco , Classe Social , Adulto JovemRESUMO
OBJECTIVE: The aim of this study was to analyze the pharmacokinetics/pharmacodynamics (PK/PD) of higher-dose tigecycline (100 mg q12h) in severely infected intensive care unit (ICU) patients receiving continuous renal replacement therapy (CRRT). MATERIALS AND METHODS: In this prospective single-center observational study, severely infected patients receiving intravenous tigecycline were enrolled. They were divided into a CRRT group (7 cases) and a non-CRRT group (9 cases). The blood samples and CRRT ultrafiltrate were collected. The drug concentration in each sample was determined by a HPLC-UV method. The pharmacokinetic parameters were simulated and calculated with DAS 2.0. The PK/PD parameters were evaluated according to published data. The registration number of this study is NCT02931526 in ClinicalTrials.gov. RESULTS: In the non-CRRT group, Cmax, Cmin, and AUC0-24 were 1.00 ± 0.66 µg×mL-1, 0.20 ± 0.12 µg×mL-1, and 22.12 ± 14.46 µg×h×mL-1, respectively. The clinical efficiency was 55.6%, and the bacterial clearance rate was 77.8%. In the CRRT group, Cmax, Cmin, and AUC0-24 were 0.96 ± 0.31 µg×mL-1, 0.22 ± 0.12 µg×mL-1, and 19.90 ± 8.14 µg×h×mL-1, respectively. The clinical efficiency was 28.6%, and the bacterial clearance rate was 28.6%. The individual differences of tigecycline plasma concentrations in our study were widely variable, and the differences of the two groups' PK/PD parameters had no statistical significance (p < 0.05). CONCLUSION: CRRT may have had little influence in tigecycline metabolism in our study, and therapeutic drug monitoring needs to be introduced for critically ill patients because of various pharmacokinetic parameters.
Assuntos
Terapia de Substituição Renal Contínua , Antibacterianos , Estado Terminal , Humanos , Estudos Prospectivos , TigeciclinaRESUMO
The literature on malignant cardiac tumors is relatively limited because they are rare, especially among the Chinese population. We analyzed 14 patients diagnosed with malignant cardiac tumors in Fuwai Hospital and present the results of surgical treatments on the tumors. The mean age at tumor diagnosis was 47 years in a male-dominated cohort. There was a high frequency of pericardial effusion and coronary artery involvement in our group. We compared the survival times of patients who received different treatments and found that surgery improved prognosis of tumors, especially for patients who underwent orthotopic heart transplantation.
Assuntos
Procedimentos Cirúrgicos Cardíacos/métodos , Ecocardiografia/métodos , Neoplasias Cardíacas/diagnóstico , Imagem Cinética por Ressonância Magnética/métodos , Tomografia Computadorizada por Raios X/métodos , Biomarcadores Tumorais/análise , China/epidemiologia , Feminino , Neoplasias Cardíacas/mortalidade , Neoplasias Cardíacas/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Taxa de Sobrevida/tendênciasRESUMO
Long noncoding RNA (lncRNA) metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) was widely recognized to be implicated in human cancer, vascular diseases, and neurological disorders. This study was to explore the role and underlying mechanism of MALAT1 in acute spinal cord injury (ASCI). ASCI models in adult rats were established and demonstrated by a numerical decrease in BBB scores. Expression profile of MALAT1 and miR-199b following ASCI in rats and in vitro was determined using quantitative real-time PCR. RNA pull-down assays combined with RIP assays were performed to explore the interaction between MALAT1 and miR-199b. In the present study, MALAT1 expression was significantly increased (2.4-fold that of control) in the spinal cord of the rat contusion epicenter accompanied by activation of IKKß/NF-κB signaling pathway and an increase in the level of proinflammatory cytokines TNF-α and IL-1ß. Upon treatment with LPS, MALAT1 expression dramatically increased in the microglia in vitro, but knockdown of MALAT1 attenuated LPS-induced activation of MGs and TNF-α and IL-1ß production. Next, we confirmed that LPS-induced MALAT1 activated IKKß/NF-κB signaling pathway and promoted the production of proinflammatory cytokines TNF-α and IL-1ß through downregulating miR-199b. More importantly, MALAT1 knockdown gradually improved the hindlimb locomotor activity of ASCI rats as well as inhibited TNF-α, IL-1ß levels, and Iba-1 protein, the marker of activated microglia in injured spinal cords. Our study demonstrated that MALAT1 was dysregulated in ASCI rats and in LPS-activated MGs, and MALAT1 knockdown was expected to attenuate ASCI through repressing inflammatory response of MGs.
Assuntos
Quinase I-kappa B/genética , Inflamação/genética , MicroRNAs/genética , Microglia/fisiologia , NF-kappa B/genética , RNA Longo não Codificante/genética , Traumatismos da Medula Espinal/genética , Animais , Células Cultivadas , Citocinas/genética , Regulação para Baixo/genética , Interleucina-1beta/genética , Locomoção/genética , Camundongos , Ratos , Ratos Sprague-Dawley , Transdução de Sinais/genética , Traumatismos da Medula Espinal/patologia , Fator de Necrose Tumoral alfa/genéticaRESUMO
This study aimed to investigate the toxicity mechanism of beta-cypermethrin (beta-CYP) on fertility in female mice. Eighty female mice were randomly assigned to four groups of 20 mice each: one control group and three beta-CYP-treated groups. The control group was administered corn oil only, while the three beta-CYP-treated groups were given corn oil containing 1.38, 2.76, and 5.52â¯mg/kg bw.d beta-CYP for 180 days through intragastric administration. The results found that the 2.76 and 5.52â¯mg/kg bw.d beta-CYP significantly decreased the rate of successful pregnancy (pâ¯<â¯0.05). The concentrations of biomarkers related to oxidative stress were significantly elevated, while the concentrations of the endogenic enzymatic antioxidants were significantly decreased by the beta-CYP exposure (all pâ¯<â¯0.05). The expression levels of inflammatory-related molecules and the DNA-protein crosslink coefficient in mice uteri were significantly increased after beta-CYP exposure (all pâ¯<â¯0.05). The concentration of 8-hydroxy-2-deoxyguanosine was significantly increased in the 5.52â¯mg/kg bw.d beta-CYP group (pâ¯<â¯0.05). These results suggested that beta-CYP exposure significantly decreased female reproduction by enhancing oxidative stress in uterine tissue, which led to the increased inflammatory response and oxidative DNA damage in uterine tissue.
Assuntos
Inseticidas/toxicidade , Piretrinas/toxicidade , Útero/efeitos dos fármacos , Animais , Dano ao DNA , Feminino , Fertilidade/efeitos dos fármacos , Masculino , Camundongos , Estresse Oxidativo/efeitos dos fármacos , Gravidez , Útero/metabolismoRESUMO
This study aimed to investigate the effects of beta-cypermethrin (ß-CYP) on female reproductive function and examine the morphology of the uterine endometrium and follicular development. The results found that the rate of successful pregnancy in the ß-CYP-treated groups significantly decreased. The levels of serum E2 and FSH were significantly increased in the ß-CYP-treated groups. The concentrations of serum P and LH were significantly decreased in the ß-CYP-treated groups. The uterine endometrium was damaged and the endometrial pinopode was markedly inhibited. In addition, the total number of follicles of all types was significantly lower in the medium- and high-dose ß-CYP-treated groups. These results suggest that ß-CYP significantly affected the reproductive function of female mice. ß-CYP may have significantly decreased the fertility of female mice by disturbing the reproductive hormone concentrations and inhibiting the development of the endometrium and the endometrial pinopode.
Assuntos
Inseticidas/toxicidade , Piretrinas/toxicidade , Fenômenos Reprodutivos Fisiológicos/efeitos dos fármacos , Animais , Endométrio/efeitos dos fármacos , Endométrio/patologia , Estrogênios/sangue , Feminino , Hormônio Foliculoestimulante/sangue , Hormônio Luteinizante/sangue , Masculino , Camundongos , Gravidez , Progesterona/sangueRESUMO
MicroRNAs (miRNAs) are 18-24 nucleotides non-coding RNAs that regulate gene expression by post-transcriptional suppression of mRNA. The Chinese giant salamander (CGS, Andrias davidianus), which is an endangered species, has become one of the important models of animal evolution; however, no miRNA studies on this species have been conducted. In this study, two small RNA libraries of CGS ovary and testis were constructed using deep sequencing technology. A bioinformatics pipeline was developed to distinguish miRNA sequences from other classes of small RNAs represented in the sequencing data. We found that many miRNAs and other small RNAs such as piRNA and tsRNA were abundant in CGS tissue. A total of 757 and 756 unique miRNAs were annotated as miRNA candidates in the ovary and testis respectively. We identified 145 miRNAs in CGS ovary and 155 miRNAs in CGS testis that were homologous to those in Xenopus laevis ovary and testis respectively. Forty-five miRNAs were more highly expressed in ovary than in testis and 21 miRNAs were more highly expressed in testis than in ovary. The expression profiles of the selected miRNAs (miR-451, miR-10c, miR-101, miR-202, miR-7a and miR-499) had their own different roles in other eight tissues and different development stages of testis and ovary, suggesting that these miRNAs play vital regulatory roles in sexual differentiation, gametogenesis and development in CGS. To our knowledge, this is the first study to reveal miRNA profiles that are related to male and female CGS gonads and provide insights into sex differences in miRNA expression in CGS.
Assuntos
Perfilação da Expressão Gênica , Sequenciamento de Nucleotídeos em Larga Escala/métodos , MicroRNAs/genética , Ovário/metabolismo , Testículo/metabolismo , Urodelos/genética , Animais , Biologia Computacional , Feminino , Masculino , Ovário/citologia , Testículo/citologia , Urodelos/classificaçãoRESUMO
Inflammatory response played an important role in the progression of spinal cord injury (SCI). Several miRNAs were associated with the pathology of SCI. However, the molecular mechanism of miRNA involving in inflammatory response in acute SCI (ASCI) was poorly understood. Sprague-Dawley (SD) rats were divided into 2 groups: control group (n=6) and acute SCI (ASCI) group (n=6). The expression of miR-199b and IκB kinase ß-nuclear factor-kappa B (IKKß-NF-κB) signaling pathway were evaluated by quantitative reverse transcription-PCR (qRT-PCR) in rats with ASCI and in primary microglia activated by lipopolysaccharide (LPS). We found that downregulation of miR-199b and activation of IKKß/NF-κB were observed in rats after ASCI and in activated microglia. miR-199b negatively regulated IKKß by targeting its 3'- untranslated regions (UTR) through using luciferase reporter assay. Overexpression of miR-199b reversed the up-regulation of IKKß, p-p65, tumor necrosis factor-α (TNF-α) and interleukin-1ß (IL-1ß) in LPS-treated BV2 cells assessed by western blotting analysis. In addition, BMS-345541 reversed the up-regulation effects of miR-199b inhibitor on the expression of TNF-α and IL-1ß. In the SCI rats, overexpression of miR-199b attenuated ASCI and decreased the expression of IKKß-NF-κB signaling pathway and TNF-α and IL-1ß. These results indicated that miR-199b attenuated ASCI at least partly through IKKß-NF-κB signaling pathway and affecting the function of microglia. Our findings suggest that miR-199b may be employed as therapeutic for spinal cord injury.
Assuntos
Regulação para Baixo , Quinase I-kappa B/metabolismo , MicroRNAs/metabolismo , Microglia/metabolismo , NF-kappa B/metabolismo , Transdução de Sinais , Traumatismos da Medula Espinal/genética , Traumatismos da Medula Espinal/patologia , Doença Aguda , Animais , Feminino , Inflamação/patologia , Lipopolissacarídeos , Camundongos , MicroRNAs/genética , Microglia/patologia , Ratos Sprague-Dawley , Fator de Transcrição RelA/metabolismo , Regulação para Cima/genéticaRESUMO
Glycidyl fatty acid esters (GEs), one of the main contaminants in processed oils, are mainly formed during the deodorization step in the refining process of edible oils and therefore occur in almost all refined edible oils. GEs are potential carcinogens, due to the fact that they readily hydrolyze into the free form glycidol in the gastrointestinal tract, which has been found to induce tumors in various rat tissues. Furthermore, glycidol has already been identified as a "possible human carcinogen'' (group 2A) by the Intl. Agency for Research on Cancer (IARC). Therefore, significant effort has been devoted to inhibit and eliminate the formation of GEs. The aim of this review is to provide a comprehensive summary on the following topics: (i) GE occurrence data for different edible oils and oil-based food products, (ii) precursors of GEs, (iii) factors influencing the formation of GEs, (iv) potential reaction mechanisms involving the leaving group and reaction intermediates, and (v) analytical methods, including the indirect and direct methods. More importantly, the various elimination methods for GEs in refined edible oils are being reviewed with focus on 3 aspects: (i) inhibition and removal of reactants, (ii) modification of reactive conditions, and (iii) elimination of GE products.
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Four new farnesyl phenolic compounds, ganosinensols A-D (1-4) were isolated from the 95% EtOH extract of the fruiting bodies of Ganoderma sinense. Two pairs of enantiomers, 1/2, and 3/4 were isolated by HPLC using a Daicel Chiralpak IE column. Their structures were elucidated from extensive spectroscopic analyses and comparison with literature data. The absolute configurations of 1-4 were assigned by ECD spectra. All of these isolated compounds showed potent inhibitory activity against LPS-induced nitric oxide production in RAW 264.7 macrophages, with IC50 values from 1.15 to 2.26µM.
Assuntos
Ganoderma/química , Óxido Nítrico/antagonistas & inibidores , Fenóis/farmacologia , Animais , Relação Dose-Resposta a Droga , Lipopolissacarídeos/antagonistas & inibidores , Lipopolissacarídeos/farmacologia , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Camundongos , Estrutura Molecular , Óxido Nítrico/biossíntese , Fenóis/química , Fenóis/isolamento & purificação , Células RAW 264.7 , Relação Estrutura-AtividadeRESUMO
BACKGROUND: Obesity increases risk of pre-eclampsia, but the association with haemolysis, elevated liver enzymes and low platelets (HELLP) syndrome is understudied. OBJECTIVE: To examine the association between prepregnancy body mass index (BMI) and HELLP syndrome, including early-onset versus late-onset disease. STUDY DESIGN: A retrospective cohort study using population-based data. SETTING: British Columbia, Canada, 2008/2009-2019/2020. POPULATION: All pregnancies resulting in live births or stillbirths at ≥20 weeks' gestation. METHODS: BMI categories (kg/m2) included underweight (<18.5), normal (18.5-24.9), overweight (25.0-29.9) and obese (≥30.0). Rates of early-onset and late-onset HELLP syndrome (<34 vs ≥34 weeks, respectively) were calculated per 1000 ongoing pregnancies at 20 and 34 weeks' gestation, respectively. Cox regression was used to assess the associations between risk factors (eg, BMI, maternal age and parity) and early-onset versus late-onset HELLP syndrome. MAIN OUTCOME MEASURES: Early-onset and late-onset HELLP syndrome. RESULTS: The rates of HELLP syndrome per 1000 women were 2.8 overall (1116 cases among 391 941 women), and 1.9, 2.5, 3.2 and 4.0 in underweight, normal BMI, overweight and obese categories, respectively. Overall, gestational age-specific rates of HELLP syndrome increased with prepregnancy BMI. Obesity (compared with normal BMI) was more strongly associated with early-onset HELLP syndrome (adjusted HR (AHR) 2.24 (95% CI 1.65 to 3.04) than with late-onset HELLP syndrome (AHR 1.48, 95% CI 1.23 to 1.80) (p value for interaction 0.025). Chronic hypertension, multiple gestation, bleeding (<20 weeks' gestation and antepartum) also showed differing AHRs between early-onset versus late-onset HELLP syndrome. CONCLUSIONS: Prepregnancy BMI is positively associated with HELLP syndrome and the association is stronger with early-onset HELLP syndrome. Associations with early-onset and late-onset HELLP syndrome differed for some risk factors, suggesting possible differences in aetiological mechanisms.
Assuntos
Síndrome HELLP , Pré-Eclâmpsia , Gravidez , Feminino , Humanos , Estudos Retrospectivos , Síndrome HELLP/epidemiologia , Sobrepeso/complicações , Sobrepeso/epidemiologia , Índice de Massa Corporal , Colúmbia Britânica/epidemiologia , Magreza/complicações , Hemólise , Fatores de Risco , Obesidade/complicações , Obesidade/epidemiologia , FígadoRESUMO
The aim of the present study was to investigate whether exposure to pesticides beta-cypermethrin (ß-CYP) harms the reproductive capacity of advanced-age female mice. The results evidenced that peri-implantation ß-CYP exposure significantly reduced the number of fetuses per advanced-age female in the first litter, and the number and weight of implantation sites. The levels of decidualization markers were significantly reduced in ß-CYP-administered advanced-age mice. Lower expression of Pcna, Cdk6, Foxo1, Ki67, and p62 protein and mRNA was found in the decidua of ß-CYP-treated advanced-age mice. The levels of Bax, cleaved caspase-3, Lc3a/b, Atg, mTOR, and p-mTOR protein, and the ratio of p-mTOR/mTOR protein expression were clearly downregulated by peri-implantation ß-CYP exposure. These results indicated that peri-implantation ß-CYP exposure may elevate the decline in reproductive capacity of early pregnant mice in advanced age.
Assuntos
Piretrinas , Reprodução , Gravidez , Camundongos , Feminino , Animais , Piretrinas/toxicidade , Serina-Treonina Quinases TOR/genéticaRESUMO
This study aimed to treat diabetic cerebral ischemia-reperfusion injury (CI/RI) by affecting blood brain barrier (BBB) permeability and integrity. The CI/RI model in DM mice and a high glucose (HG) treated oxygen and glucose deprivation/reoxygenation (OGD/R) brain endothelial cell model were established for the study. Evans blue (EB) staining was used to evaluate the permeability of BBB in vivo. TTC staining was used to analyze cerebral infarction. The location and expression of tribbles homolog 3 (TRIB3) in endothelial cells were detected by immunofluorescence. Western blotting was used to detect the protein expressions of TRIB3, tight junction molecules, adhesion molecules, phosphorylated protein kinase B (p-AKT) and AKT. The levels of pro-inflammatory cytokines were detected by qRT-PCR. Trans-epithelial electrical resistance (TEER) and fluorescein isothiocyanate (FITC)-dextran were used to measure vascular permeability in vitro. TRIB3 ubiquitination and acetylation levels were detected. Acetyltransferase bound to TRIB3 were identified by immunoprecipitation. TRIB3 was localized in cerebral endothelial cells and was highly expressed in diabetic CI/R mice. The BBB permeability in diabetic CI/R mice and HG-treated OGD/R cells was increased, while the junction integrity was decreased. Interference with TRIB3 in vitro reduces BBB permeability and increases junction integrity. In vivo interfering with TRIB3 reduced cerebral infarction volume, BBB permeability and inflammation levels, and upregulated p-AKT levels. The phosphatidylinositol 3-kinase (PI3K) inhibitor wortmannin reversed the effects of TRIB3-interfering plasmid. In vitro HG treatment induced TRIB3 acetylation through acetyltransferase p300, which in turn reduced ubiquitination and stabilized TRIB3. Interfering TRIB3 protects BBB by activating PI3K/AKT pathway and alleviates brain injury, which provides a new target for diabetic CI/RI.
Assuntos
Isquemia Encefálica , Diabetes Mellitus , Traumatismo por Reperfusão , Camundongos , Animais , Barreira Hematoencefálica , Proteínas Proto-Oncogênicas c-akt/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Células Endoteliais , Fosfatidilinositol 3-Quinase/metabolismo , Fosfatidilinositol 3-Quinase/farmacologia , Traumatismo por Reperfusão/prevenção & controle , Traumatismo por Reperfusão/metabolismo , Infarto Cerebral/metabolismo , Oxigênio/metabolismo , Glucose/metabolismo , Acetiltransferases/metabolismo , Acetiltransferases/farmacologia , Diabetes Mellitus/metabolismoRESUMO
BACKGROUND: The immunocompetence handicap hypothesis suggests that males with a higher testosterone level should be better at developing male secondary traits, but at a cost of suppressed immune performance. As a result, we should expect that males with an increased testosterone level also possess a higher parasite load. However, previous empirical studies aimed to test this prediction have generated mixed results. Meanwhile, the effect of testosterone level on parasite load in female hosts remains poorly known. METHODS: In this study, we tested this prediction by manipulating testosterone level in Daurian ground squirrels (Spermophilus dauricus), a medium-sized rodent widely distributed in northeast Asia. S. dauricus is an important host of ticks and fleas and often viewed as a considerable reservoir of plague. Live-trapped S. dauricus were injected with either tea oil (control group) or testosterone (treatment group) and then released. A total of 10 days later, the rodents were recaptured and checked for ectoparasites. Fecal samples were also collected to measure testosterone level of each individual. RESULTS: We found that testosterone manipulation and sex of hosts interacted to affect tick load. At the end of the experiment, male squirrels subjected to testosterone implantation had an averagely higher tick load than males from the control group. However, this pattern was not found in females. Moreover, testosterone manipulation did not significantly affect flea load in S. dauricus. CONCLUSIONS: Our results only lent limited support for the immunocompetence handicap hypothesis, suggesting that the role of testosterone on regulating parasite load is relatively complex, and may largely depend on parasite type and gender of hosts.
Assuntos
Infestações por Pulgas , Doenças dos Roedores , Sifonápteros , Carrapatos , Animais , Feminino , Masculino , Sciuridae/parasitologia , Infestações por Pulgas/veterinária , Testosterona/fisiologia , Imunocompetência/fisiologiaRESUMO
Importance: The prevalence of overweight and obesity (body mass index [BMI] ≥25) has increased globally, and high BMI has been linked to higher rates of twin birth. However, evidence from large population-based studies is lacking; the issue needs careful study, as women with obesity are also more likely to use assisted reproductive technology (ART), which frequently results in twin pregnancy. Objective: To examine the association between BMI and twin birth and the role of ART as a potential mediator in this association. Design, Setting, and Participants: This retrospective cohort study included all live births and stillbirths with gestational age of 20 weeks or longer in British Columbia, Canada, from 2008 to 2020, using data from the British Columbia Perinatal Database Registry. Data analysis was conducted from November 2022 to June 2023. Exposures: Prepregnancy BMI, calculated as weight in kilograms divided by height in meters squared, and use of ART. Main Outcomes and Measures: The study assessed whether prepregnancy BMI is associated with the rate of twin vs singleton delivery and whether this association is explained by the differential use of ART in women with obesity. Results: A total of 524â¯845 deliveries at 20 weeks' or longer gestation occurred in British Columbia during the study period, and 392â¯046 women had complete data on prepregnancy BMI. The median (IQR) age was 31.4 (27.7-35.0) years, approximately half were nulliparous (243â¯443 [46.4%]) and less than 10% smoked during pregnancy (36â¯894 [7.1%]). Overall, 8295 women had a twin delivery (15.8 per 1000 deliveries), and rates per 1000 deliveries by prepregnancy BMI categories were 11.9 (underweight), 15.1 (normal), 16.0 (overweight), 16.0 (obesity class I), 16.7 (obesity class II), and 18.9 (obesity class III). After adjustment for other covariates, women with underweight had relatively 16% fewer twins compared with women with normal BMI (adjusted risk ratio [aRR], 0.84; 95% CI, 0.74-0.95), while women with overweight, class I obesity, class II obesity, and class III obesity had 14% (aRR, 1.14; 95% CI, 1.07-1.21), 16% (aRR, 1.16; 95% CI, 1.06-1.27), 17% (aRR, 1.17; 95% CI, 1.02-1.34), and 41% higher rates (aRR, 1.41; 95% CI, 1.19-1.66), respectively. The proportion of women who conceived by ART increased with increasing BMI, and ART was associated with nearly a 12-fold higher rate of twin delivery (aRR, 11.80; 95% CI 11.10-12.54). ART explained about a quarter of the association between obesity class I and II and twin delivery (eg, obesity class I, 23% mediated; 95% CI, 7%-39% mediated), but none of this association was mediated by ART in women with class III obesity. Conclusions and relevance: In this cohort study of 524â¯845 births, the rate of twin birth increased with increasing prepregnancy BMI. In women with a BMI between 30 and 40, approximately one-quarter of this association was explained by higher use of ART; however, there was no evidence of such mediation in women with BMI of 40 or greater.
Assuntos
Sobrepeso , Gravidez de Gêmeos , Gravidez , Feminino , Humanos , Lactente , Adulto , Sobrepeso/epidemiologia , Estudos de Coortes , Estudos Retrospectivos , Magreza , Obesidade/epidemiologia , Técnicas de Reprodução Assistida , Colúmbia BritânicaRESUMO
Introduction: To address issues related to shallow soil tillage, low soil nutrient content, and single tillage method in maize production in the Western Inner Mongolia Region, this study implemented various tillage and straw return techniques, including strip cultivation, subsoiling, deep tillage, no-tillage, straw incorporation with strip cultivation, straw incorporation with subsoiling, straw incorporation with deep tillage, and straw incorporation with no tillage, while using conventional shallow spinning by farmers as the control. Methods: We employed Xianyu 696 (XY696) and Ximeng 6 (XM6) as experimental materials to assess maize 100-grains weight, grain filling rate parameters, and grain nutrient quality. This investigation aimed to elucidate how tillage and straw return influence the accumulation of grain material in different maize varieties. Results and discussion: The results indicated that proper implementation of tillage and straw return had a significant impact on the 100-grains weight of both varieties. In comparison to CK (farmer's rotary rotation), the most notable rise in 100-grains weight was observed under the DPR treatment (straw incorporation with deep tillage), with a maximum increase of 4.84% for XY696 and 6.28% for XM6. The proper implementation of tillage and straw return in the field resulted in discernible differences in the stages of improving the grain filling rates of different maize varieties. Specifically, XY696 showed a predominant increase in the filling rate during the early stage (V1), while XM6 exhibited an increase in the filling rates during the middle and late stages (V2 and V3). In comparison to CK, V1 increased by 1.54% to 27.56% in XY696, and V2 and V3 increased by 0.41% to 10.42% in XM6 under various tillage and straw return practices. The proper implementation of tillage and straw return had a significant impact on the nutritional quality of the grains in each variety. In comparison to CK, the DPR treatment resulted in the most pronounced decrease in the soluble sugar content of grains by 25.43% and the greatest increase in the crude fat content of grains by 9.67%. Conclusion: Ultimately, the proper implementation of soil tillage and straw return facilitated an increase in grain crude fat content and significantly boosted grain weight by improving the grouting rate parameters at all stages for various maize varieties. Additionally, the utilization of DPR treatment proved to be more effective. Overall, DPR is the most promising strategy to improve maize yield and the nutritional quality of grain in the long term in the Western Inner Mongolia Region.
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Background: In vitro fertilization (IVF) as a fertility treatment is associated with adverse perinatal outcomes. Racial/ethnic disparity in severe maternal morbidity (SMM) in women who conceived by IVF is understudied. Objective: To examine differences in the association between race/ethnicity and SMM between women who conceived spontaneously and those who conceived using IVF. Methods: We included all singleton live births and stillbirths in the United States, 2016-2021; data were obtained from the National Center for Health Statistics. Maternal race/ethnicity included non-Hispanic White (NHW), non-Hispanic Black (NHB), American Indian and Alaska Native (AIAN), Asian, Pacific Islander (PI), Hispanic, and mixed-race categories. The SMM composite outcome included eclampsia, uterine rupture, peripartum hysterectomy, blood transfusion, and intensive care unit (ICU) admission. We used logistic regression to adjust for potential confounders (such as age, education, parity, prepregnancy body mass index, smoking during pregnancy, chronic hypertension, and preexisting diabetes) and to assess modification of the association between race/ethnicity and SMM by IVF. Results: The study population included 21,585,015 women: 52% were NHW, 15% NHB, 0.8% AIAN, 6% Asian, 0.2% PI, 24% Hispanic, and 2% were of mixed race. IVF was used by 183,662 (0.85%) women; the rate of the SMM composite outcome was 18.5 per 1000 deliveries and 7.9 per 1000 deliveries in the IVF and spontaneous conception groups, respectively (unadjusted rate ratio 2.34, 95% confidence interval [CI] 2.26-2.43). In women with spontaneous conception, NHB, Asian and mixed-race women had elevated odds of SMM compared with NHW women (adjusted odds ratio [aOR]=1.39, 95% CI 1.37-1.41; aOR=1.04, 95% CI 1.02-1.07; and aOR=1.42, 95% CI 1.38-1.46, respectively). Racial/ethnic disparities in SMM and its components were not different between the IVF and spontaneous conception groups for the mixed-race category. NHB and Hispanic women had significantly higher aORs for uterine rupture/intrapartum hysterectomy compared with NHW women in the IVF group, while Asian women had a higher aOR for ICU admission compared with NHW women in the IVF group. Conclusion: Women who conceived by IVF have a greater than two-fold higher risk of SMM and this higher risk is evident across all racial/ethnic groups. However, NHB and Hispanic women who conceived by IVF had a higher risk of uterine rupture/hysterectomy, and Asian women who conceived by IVF had a higher risk of ICU admission. Our results warrant further investigation examining pregnancy and postpartum care issues among racial/ethnic minority women who conceive using IVF.
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BACKGROUND: Acute kidney injury (AKI) is a common complication after liver transplantation (LT) and associated with a high mortality. The renal resistive index (RI) is used to assess early renal function impairment in critical care patients. However, limited data are available concerning changes of renal RI and the development of AKI early after reperfusion. We approached to investigate the changes of renal RI and AKI after reperfusion in a rat liver transplantation model. METHODS: Rats were randomly divided into sham group or LT group. Ten rats in each group were used for the hemodynamic study and twenty for Doppler measurements during the procedure. Ten rats were sacrificed 30 min or 2 h after the reperfusion. We harvested kidneys, serum and urine for further analysis of the renal function. RESULTS: The intrarenal RI increased significantly in the anhepatic stage and decreased significantly after the reperfusion in the LT group compared with sham group (P < 0.05). AKI was seen after the reperfusion in the LT group. No correlation was noted between the RI and renal function parameters 30 min after reperfusion. CONCLUSIONS: The intrarenal RI increased significantly during the anhepatic stage, and decreased significantly early after the reperfusion. Intrarenal RI was unable to assess renal function in a rat liver transplantation model.