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OBJECTIVES: This study investigated the potential effects of perfluoroalkyl substance (PFAS) in serum on MAFLD, NAFLD, and liver fibrosis. METHODS: Our sample included 696 participants (≥ 18 years) from the 2017-2018 NHANES study with available serum PFASs, covariates, and outcomes. Using the first quartile of PFAS as the reference group, we used weighted binary logistic regression and multiple ordered logistic regression used to analyze the relationship between PFAS and MAFLD, NAFLD, and liver fibrosis and multiple ordinal logistic regression to investigate the relationship between PFAS and MAFLD, NAFLD, and liver fibrosis and calculated the odds ratio (OR) and 95% confidence interval for each chemical. Finally, stratified analysis and sensitivity analysis were performed according to gender, age, BMI, and serum cotinine concentration. RESULTS: A total of 696 study subjects were included, including 212 NAFLD patients (weighted 27.03%) and 253 MAFLD patients (weighted 32.65%). The quartile 2 of serum PFOA was positively correlated with MAFLD and NAFLD (MAFLD, OR 2.29, 95% CI 1.05-4.98; NAFLD, OR 2.37, 95% CI 1.03-5.47). PFAS were not significantly associated with liver fibrosis after adjusting for potential confounders in MAFLD and NAFLD. Stratified analysis showed that PFOA was strongly associated with MAFLD, NAFLD, and liver fibrosis in males and obese subjects. In women over 60 years old, PFHxS was also correlated with MAFLD, NAFLD, and liver fibrosis. CONCLUSION: The serum PFOA was positively associated with MAFLD and NAFLD in US adults. After stratified analysis, the serum PFHxS was correlated with MFALD, NAFLD, and liver fibrosis.
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BACKGROUND: This study aimed to explore the potential associations between trans fatty acid (TFA) and α-klotho levels. METHODS: Datasets from the 2009-2010 National Health and Nutrition Examination Survey (NHANES) were analysed for this study. Multivariable linear regression and restricted cubic spline (RCS) analyses were performed to examine the relationships between plasma TFA and serum α-klotho levels. RESULTS: A total of 1,205 participants were included, with a geometric mean (GM) of 803.60 (95% CI: 787.45, 820.00) pg/mL for serum α-klotho levels. RCS analysis revealed L-shaped relationships between TFA and α-klotho levels. The inflection points for palmitelaidic acid (PA), vaccinic acid (VA), elaidic acid (EA), and total TFA levels were 4.55, 20.50, 18.70, and 46.40 µmol/L, respectively. Before reaching the inflection point, serum α-klotho levels were negatively correlated with plasma PA, VA, EA and total TFA levels, with ß values (95% CI) of -0.15 (-0.24, -0.06), -0.16 (-0.23, -0.09), -0.14 (-0.22, -0.05) and - 0.19 (-0.27, -0.11), respectively. Linolelaidic acid (LA) levels exhibited an inverse and linear association with α-klotho levels ( Pnonlinearity=0.167, Poverall<0.001). L-shaped relationships between TFA and α-klotho levels were also observed in the subgroups of participants who were aged < 65 years, were male, did not exercise, were ex-smokers, and were overweight/obese. CONCLUSIONS: L-shaped correlations between plasma PA, VA, EA, and total TFA levels and serum α-klotho levels were observed among adults in the United States.
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Proteínas Klotho , Inquéritos Nutricionais , Ácidos Graxos trans , Humanos , Masculino , Feminino , Estados Unidos/epidemiologia , Pessoa de Meia-Idade , Adulto , Ácidos Graxos trans/sangue , Glucuronidase/sangue , Idoso , Ácidos Oleicos/sangue , Ácido Oleico/sangue , Modelos LinearesRESUMO
Malaria is a severe disease that presents a significant threat to human health. As resistance to current drugs continues to increase, there is an urgent need for new antimalarial medications. Aminoacyl-tRNA synthetases (aaRSs) represent promising targets for drug development. In this study, we identified Plasmodium falciparum tyrosyl-tRNA synthetase (PfTyrRS) as a potential target for antimalarial drug development through a comparative analysis of the amino acid sequences and three-dimensional structures of human and plasmodium TyrRS, with particular emphasis on differences in key amino acids at the aminoacylation site. A total of 2141 bioactive compounds were screened using a high-throughput thermal shift assay (TSA). Okanin, known as an inhibitor of LPS-induced TLR4 expression, exhibited potent inhibitory activity against PfTyrRS, while showing limited inhibition of human TyrRS. Furthermore, bio-layer interferometry (BLI) confirmed the high affinity of okanin for PfTyrRS. Molecular dynamics (MD) simulations highlighted the stable conformation of okanin within PfTyrRS and its sustained binding to the enzyme. A molecular docking analysis revealed that okanin binds to both the tyrosine and partial ATP binding sites of the enzyme, preventing substrate binding. In addition, the compound inhibited the production of Plasmodium falciparum in the blood stage and had little cytotoxicity. Thus, okanin is a promising lead compound for the treatment of malaria caused by P. falciparum.
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Antimaláricos , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , Plasmodium falciparum , Tirosina-tRNA Ligase , Plasmodium falciparum/efeitos dos fármacos , Plasmodium falciparum/enzimologia , Tirosina-tRNA Ligase/antagonistas & inibidores , Tirosina-tRNA Ligase/metabolismo , Humanos , Antimaláricos/farmacologia , Antimaláricos/química , Inibidores Enzimáticos/farmacologia , Inibidores Enzimáticos/química , Sítios de Ligação , Ligação Proteica , Animais , Malária Falciparum/tratamento farmacológico , Malária Falciparum/parasitologiaRESUMO
Arabidopsis (Arabidopsis thaliana) PROTEIN ARGININE METHYLTRANSFERASE5 (PRMT5), a highly conserved arginine (Arg) methyltransferase protein, regulates multiple aspects of the growth, development, and environmental stress responses by methylating Arg in histones and some mRNA splicing-related proteins in plants. Hydrogen sulfide (H2S) is a recently characterized gasotransmitter that also regulates various important physiological processes. l-cysteine desulfhydrase (LCD) is a key enzyme of endogenous H2S production. However, our understanding of the upstream regulatory mechanisms of endogenous H2S production is limited in plant cells. Here, we confirmed that AtPRMT5 increases the enzymatic activity of AtLCD through methylation modifications during stress responses. Both atprmt5 and atlcd mutants were sensitive to cadmium (Cd2+), whereas the overexpression (OE) of AtPRMT5 or AtLCD enhanced the Cd2+ tolerance of plants. AtPRMT5 methylated AtLCD at Arg-83, leading to a significant increase in AtLCD enzymatic activity. The Cd2+ sensitivity of atprmt5-2 atlcd double mutants was consistent with that of atlcd plants. When AtPRMT5 was overexpressed in the atlcd mutant, the Cd2+ tolerance of plants was significantly lower than that of AtPRMT5-OE plants in the wild-type background. These results were confirmed in pharmacological experiments. Thus, AtPRMT5 methylation of AtLCD increases its enzymatic activity, thereby strengthening the endogenous H2S signal and ultimately improving plant tolerance to Cd2+ stress. These findings provide further insights into the substrates of AtPRMT5 and increase our understanding of the regulatory mechanism upstream of H2S signals.
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Proteínas de Arabidopsis , Arabidopsis , Sulfeto de Hidrogênio , Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Metilação , Cistationina gama-Liase/genética , Sulfeto de Hidrogênio/farmacologia , Sulfeto de Hidrogênio/metabolismo , Arginina/metabolismoRESUMO
OBJECTIVES: To investigate the sleep patterns and characteristics of infants and young children and the association between sleep patterns and breastfeeding. METHODS: A general information questionnaire, Brief Infant Sleep Questionnaire (BISQ), and a questionnaire on feeding were used to investigate the sleep quality and feeding patterns of 1 148 infants and young children aged 7-35 months. The K-means clustering method was used to identify sleep patterns and characteristics. A multivariate logistic regression analysis was used to investigate the association between sleep patterns and breastfeeding. RESULTS: Three typical sleep patterns were identified for the 1 148 infants and young children aged 7-35 months: early bedtime and long sleep time; short sleep latency and moderate sleep time; late bedtime, prolonged sleep latency, and insufficient sleep time. The third pattern showed sleep disorders. The multivariate logistic regression analysis showed that compared with formula feeding, exclusive breastfeeding within 6 months after birth reduced the risk of sleep disorder patterns by 69% (OR=0.31, 95%CI: 0.11-0.81). The risk of sleep disorder patterns was reduced by 40% (OR=0.60, 95%CI: 0.38-0.96) in the infants receiving breastfeeding for 4-6 months compared with those receiving breastfeeding for 1-3 months. CONCLUSIONS: There are different sleep patterns in infants and young children, and breastfeeding can reduce the development of sleep disorder patterns.
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Aleitamento Materno , Transtornos do Sono-Vigília , Lactente , Criança , Feminino , Humanos , Pré-Escolar , Inquéritos e Questionários , Sono , Análise por ConglomeradosRESUMO
OBJECTIVE: Ertugliflozin is approved in the US and European Union as a stand-alone product for adults with type 2 diabetes mellitus as once daily (QD) dosing. The approved fixed-dose combination (FDC) of ertugliflozin and immediate-release metformin is dosed twice daily (BID). This study assessed steady-state pharmacokinetics (PK; area under the concentration-time curve over 24 hours (AUC24)) and pharmacodynamics (PD; urinary glucose excretion over 24 hours (UGE24)) for ertugliflozin 5 and 15 mg total daily doses administered BID or QD. MATERIALS AND METHODS: In this open-label, two-cohort, randomized, multiple-dose, crossover study, healthy subjects received ertugliflozin 2.5 mg BID and 5 mg QD (n = 28) or ertugliflozin 7.5 mg BID and 15 mg QD (n = 22) for 6 days. Plasma and urine samples were collected for 24 hour post morning dose on day 6 in each period. RESULTS: The geometric mean ratio (GMR) (90% CI) of ertugliflozin AUC24 was 100.8% (98.8%, 102.8%) for 2.5 mg BID vs. 5 mg QD, and 99.7% (97.1%, 102.5%) for 7.5 mg BID vs. 15 mg QD. GMR (90% CI) of UGE24 for BID vs. QD administration was 110.2% (103.0%, 117.9%) at a total daily dose of 5 mg, and 102.8% (97.7%, 108.1%) at 15 mg. The 90% CIs of the GMR of AUC24 and UGE24 for BID vs. QD dosing were within the acceptance range for equivalence (80 - 125%) and the prespecified criterion for similarity (70 - 143%), respectively. All treatments were well tolerated. CONCLUSION: There are no clinically meaningful differences in steady-state PK or PD between ertugliflozin BID and QD regimens at total daily doses of 5 and 15 mg, supporting BID administration of ertugliflozin as a component of the ertugliflozin/metformin (immediate-release) FDC.
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Compostos Bicíclicos Heterocíclicos com Pontes/administração & dosagem , Compostos Bicíclicos Heterocíclicos com Pontes/farmacocinética , Diabetes Mellitus Tipo 2/tratamento farmacológico , Inibidores do Transportador 2 de Sódio-Glicose/administração & dosagem , Inibidores do Transportador 2 de Sódio-Glicose/farmacocinética , Adolescente , Adulto , Estudos Cross-Over , Feminino , Voluntários Saudáveis , Humanos , Masculino , Metformina , Pessoa de Meia-Idade , Adulto JovemRESUMO
Heavy metal (HM) contamination on agricultural land not only reduces crop yield but also causes human health concerns. As a plant gasotransmitter, hydrogen sulfide (H2 S) can trigger various defense responses and help reduce accumulation of HMs in plants; however, little is known about the regulatory mechanisms of H2 S signaling. Here, we provide evidence to answer the long-standing question about how H2 S production is elevated in the defense of plants against HM stress. During the response of Arabidopsis to chromium (Cr6+ ) stress, the transcription of L-cysteine desulfhydrase (LCD), the key enzyme for H2 S production, was enhanced through a calcium (Ca2+ )/calmodulin2 (CaM2)-mediated pathway. Biochemistry and molecular biology studies demonstrated that Ca2+ /CaM2 physically interacts with the bZIP transcription factor TGA3, a member of the 'TGACG'-binding factor family, to enhance binding of TGA3 to the LCD promoter and increase LCD transcription, which then promotes the generation of H2 S. Consistent with the roles of TGA3 and CaM2 in activating LCD expression, both cam2 and tga3 loss-of-function mutants have reduced LCD abundance and exhibit increased sensitivity to Cr6+ stress. Accordingly, this study proposes a regulatory pathway for endogenous H2 S generation, indicating that plants respond to Cr6+ stress by adjusting the binding affinity of TGA3 to the LCD promoter, which increases LCD expression and promotes H2 S production. This suggests that manipulation of the endogenous H2 S level through genetic engineering could improve the tolerance of grains to HM stress and increase agricultural production on soil contaminated with HMs.
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Proteínas de Arabidopsis/metabolismo , Arabidopsis/fisiologia , Fatores de Transcrição de Zíper de Leucina Básica/metabolismo , Sinalização do Cálcio , Cálcio/metabolismo , Cromo/toxicidade , Sulfeto de Hidrogênio/metabolismo , Arabidopsis/genética , Proteínas de Arabidopsis/genética , Fatores de Transcrição de Zíper de Leucina Básica/genética , Calmodulina/genética , Calmodulina/metabolismo , Estresse FisiológicoRESUMO
1. The metabolism, excretion and pharmacokinetics of glasdegib (PF-04449913) were investigated following administration of a single oral dose of 100 mg/100 µCi [14C]glasdegib to six healthy male volunteers (NCT02110342). 2. The peak concentrations of glasdegib (890.3 ng/mL) and total radioactivity (1043 ngEq/mL) occurred in plasma at 0.75 hours post-dose. The AUCinf were 8469 ng.h/mL and 12,230 ngEq.h/mL respectively, for glasdegib and total radioactivity. 3. Mean recovery of [14C]glasdegib-related radioactivity in excreta was 91% of the administered dose (49% in urine and 42% in feces). Glasdegib was the major circulating component accounting for 69% of the total radioactivity in plasma. An N-desmethyl metabolite and an N-glucuronide metabolite of glasdegib represented 8% and 7% of the circulating radioactivity, respectively. Glasdegib was the major excreted component in urine and feces, accounting for 17% and 20% of administered dose in the 0-120 hour pooled samples, respectively. Other metabolites with abundance <3% of the total circulating radioactivity or dose in plasma or excreta were hydroxyl metabolites, a desaturation metabolite, N-oxidation and O-glucuronide metabolites. 4. Elimination of [14C]glasdegib-derived radioactivity was essentially complete, with similar contribution from urinary and fecal routes. Oxidative metabolism appears to play a significant role in the biotransformation of glasdegib.
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Benzimidazóis/farmacocinética , Compostos de Fenilureia/farmacocinética , Administração Oral , Adulto , Biotransformação , Glucuronídeos/metabolismo , Voluntários Saudáveis , Humanos , Masculino , Adulto JovemRESUMO
Our objective was to compare the efficacy of different lengths of rubber tube (6 French) on patients with esophageal stent implantation performed using a silk thread. We measured the effects in terms of pain and foreign body sensation felt in the pharynx and esophageal mucosa of the patients. A retrospective analysis was conducted using records of 65 patients who were divided into 3 groups. Group A had 20 cases with the distal end of the tube toward the nasal cavity, Group B had 21 cases with the distal end of the tube reaching the nasopharynx without exceeding the soft palate, and Group C had 24 cases with the distal end of the tube toward the upper end of the stent. Follow-up was performed on 1 day, 2 days, 1 week, 2 weeks, 4 weeks, 6 weeks, and 8 weeks postoperatively. During each period, the pain scores for Groups B and C were lower than those for Group A (p < .05), whereas no difference was observed when Groups B and C were compared. Although no variations were seen between the 3 groups in terms of the proportion of patients with foreign body sensation on the first day (p > .05), Groups A and B had a lower proportion than Group C (p < .05) at those periods. No difference was observed when Groups A and B were compared. In conclusion, the Group B method was successful in alleviating the side effects caused by the silk thread.
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Doenças do Esôfago/cirurgia , Dor Pós-Operatória/prevenção & controle , Borracha , Seda , Stents , Adulto , Idoso , Desenho de Equipamento , Doenças do Esôfago/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Nasofaringe , Estudos RetrospectivosRESUMO
PURPOSE: Transdermal delivery has the potential to offer improved bioavailability by circumventing first-pass gut and hepatic metabolism. This study evaluated the pharmacokinetics of oral immediate release and transdermal latrepirdine in extensive and poor CYP2D6 metabolizers (EM/PM). METHODS: Latrepirdine transdermal solution was prepared extemporaneously. The solution was applied with occlusive dressing to upper or middle back for 24 h. Each subject received a single dose of 8.14 mg oral, 5 mg transdermal, and 10 mg transdermal (EMs only) latrepirdine free base in a fixed sequence. RESULTS: Twelve EMs and 7 PMs (50-79 years) enrolled and completed the study. Latrepirdine was well tolerated following both routes of administration. Dose-normalized latrepirdine total exposures were approximately 11-fold and 1.5-fold higher in EMs and PMs, respectively following administration of transdermal relative to oral. Differences between EM and PM latrepirdine exposures were decreased, with PMs having 1.9- and 2.7-fold higher peak and total exposures, respectively, following transdermal administration compared to 11- and 20-fold higher exposures, respectively, following oral administration. CONCLUSION: Transdermal delivery can potentially mitigate the large intersubject differences observed with compounds metabolized primarily by CYP2D6. Transdermal delivery was readily accomplished in the clinic using an extemporaneously prepared solution [NCT00990613].
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Citocromo P-450 CYP2D6/metabolismo , Indóis/administração & dosagem , Indóis/farmacocinética , Administração Cutânea , Idoso , Disponibilidade Biológica , Estudos Cross-Over , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Projetos PilotoRESUMO
Dacomitinib (PF-00299804) is a small-molecule inhibitor of the tyrosine kinases human epidermal growth factor receptor-1 (HER1; epidermal growth factor receptor, EGFR), HER2, and HER4 currently being developed for the treatment of lung cancer with sensitizing mutations in EGFR or refractory to EGFR-directed treatment. Dacomitinib is largely metabolized by the liver through oxidative and conjugative metabolism; therefore, determination of the impact of varying degrees of hepatic impairment on the pharmacokinetics (PK) of dacomitinib was warranted to ensure patient safety. In this phase I, open-label, parallel-group study, a single dose of dacomitinib was administered to healthy volunteers and to subjects with mild or moderate liver dysfunction, as determined by Child-Pugh classification. The primary goal of this study was to evaluate the effects of mild and moderate hepatic impairment on the single-dose PK profile of dacomitinib, as well as to assess the safety and tolerability in these subjects. Plasma protein binding and impact of hepatic function on the PK of the active metabolite PF-05199265 was also investigated. Twenty-five male subjects received dacomitinib 30 mg, with 8 subjects in the healthy- and mild-impairment cohorts and 9 subjects in the moderate-impairment cohort. Compared with healthy volunteers, there was no significant change in dacomitinib exposure in subjects with mild or moderate liver dysfunction and no observed alteration in plasma protein binding. No serious treatment-related adverse events were reported in any group, and dacomitinib was well tolerated. A dose adjustment does not appear necessary when administering dacomitinib to patients with mild or moderate hepatic impairment.
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Antineoplásicos/farmacocinética , Hepatopatias/metabolismo , Inibidores de Proteínas Quinases/farmacocinética , Quinazolinonas/farmacocinética , Adulto , Idoso , Antineoplásicos/efeitos adversos , Antineoplásicos/sangue , Proteínas Sanguíneas/metabolismo , Citocromo P-450 CYP2D6/genética , Receptores ErbB/antagonistas & inibidores , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Inibidores de Proteínas Quinases/efeitos adversos , Inibidores de Proteínas Quinases/sangue , Quinazolinonas/efeitos adversos , Quinazolinonas/sangueRESUMO
AIMS: The aim of the present study was to evaluate the pharmacokinetics/pharmacodynamics (PK/PD), safety and tolerability of single intravenous (IV) doses of PF-05231023, a long acting fibroblast growth factor 21 (FGF21) analogue being developed for the treatment of type 2 diabetes mellitus (T2DM). METHODS: T2DM subjects (glycosylated haemoglobin: 7.0-10.5%; on stable metformin therapy and/or diet and exercise) were randomized to receive a single dose of placebo or PF-05231023 (0.5-200 mg). Safety evaluations were performed up to 14 days after dosing. PK and PD endpoints were measured and a PK/PD model was developed for triglyceride - an early marker of drug activity. RESULTS: No antidrug antibody or serious adverse events (AEs) were observed. The most frequent AEs were gastrointestinal but were generally mild. Plasma PF-05231023 levels peaked immediately post-IV dosing, with mean terminal half-lives of 6.5-7.7 h and 66.5- 96.6 h for intact C- and N-termini, respectively. Intact C-terminus exposures increased proportionally with increasing dose, whereas N-terminus exposures appeared to trend higher than dose-proportionally. Although no apparent effect on plasma glucose was seen, dose-dependent decreases in triglyceride were observed, with a maximum reduction of 48.5 ± 10.0% (mean ± standard deviation) for the 200 mg dose compared with a reduction of 19.1 ± 26.4% for placebo, demonstrating proof of pharmacology. Moreover, a reduction in total cholesterol and low-density lipoprotein cholesterol and an increase in high-density lipoprotein cholesterol were observed in the high-dose groups. CONCLUSIONS: Single IV doses of PF-05231023 up to 200 mg were generally safe and well tolerated by subjects with T2DM. The observed early sign of pharmacology supports further clinical testing of PF-05231023 upon repeated administration.
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Anticorpos Monoclonais Humanizados/farmacocinética , Diabetes Mellitus Tipo 2/sangue , Fatores de Crescimento de Fibroblastos/agonistas , Fatores de Crescimento de Fibroblastos/farmacocinética , Administração Intravenosa , Anticorpos Monoclonais Humanizados/administração & dosagem , Anticorpos Monoclonais Humanizados/efeitos adversos , Anticorpos Monoclonais Humanizados/farmacologia , Relação Dose-Resposta a Droga , Feminino , Fatores de Crescimento de Fibroblastos/administração & dosagem , Fatores de Crescimento de Fibroblastos/efeitos adversos , Fatores de Crescimento de Fibroblastos/farmacologia , Humanos , Hipoglicemiantes/administração & dosagem , Hipoglicemiantes/efeitos adversos , Hipoglicemiantes/farmacocinética , Hipoglicemiantes/farmacologia , Masculino , Pessoa de Meia-Idade , Triglicerídeos/sangueRESUMO
BACKGROUND: Potential drugdrug interactions are a concern for patients taking tamoxifen. OBJECTIVE: This study was designed to determine the effect of coadministering desvenlafaxine on tamoxifen pharmacokinetics. MATERIALS AND METHODS: This open-label, 2-period inpatient and outpatient study enrolled healthy, postmenopausal women. Period 1, day 1, subjects were administered tamoxifen 40 mg followed by 23 days of blood sampling for pharmacokinetic analyses. During period 2, subjects received desvenlafaxine 100 mg/d for 28 days; a single dose of tamoxifen 40 mg was administered with desvenlafaxine 100 mg on day 7, followed by 23 days of blood sampling. Pharmacokinetics of tamoxifen and its metabolites (AUC over infinite time (AUC(inf)), AUC to the last measurable concentration (AUC(last)), peak plasma concentration (C(max)) were compared for monotherapy vs. combination therapy using the ratio of adjusted mean differences. A superposition method was used in the statistical analysis of N-desmethyl-tamoxifen and endoxifen to address the carry-over observed for those metabolites. The test for interaction was considered negative if the 90% confidence intervals (CIs) for the ratios were within 80 - 125%. RESULTS: Coadministration of tamoxifen with steady-state desvenlafaxine did not alter tamoxifen AUC(inf), AUC(last), and C(max), as reflected by the ratio of adjusted geometric means (90% CIs) of 100.7% (96.7%, 104.9%), 103.5% (100.2%, 106.9%), and 99.4% (94.0%, 105.2%), respectively. Similarly, coadministration did not alter 4-hydroxy- tamoxifen and N-desmethyl-amoxifen pharmacokinetics. The 11.8% (88.2% (82.6%, 94.2%)) and 8.0% (92.0% (84.7%, 100.0%)) decreases in endoxifen AUC(last) and C(max), respectively, were not significant (90% CIs fell wholly within the prespecified acceptance range). CONCLUSIONS: Steady-state desvenlafaxine 100 mg did not affect tamoxifen pharmacokinetics. For women treated with tamoxifen, desvenlafaxine may represent a safe and effective treatment unlikely to alter tamoxifen efficacy.
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Succinato de Desvenlafaxina/farmacologia , Pós-Menopausa , Tamoxifeno/farmacocinética , Área Sob a Curva , Succinato de Desvenlafaxina/administração & dosagem , Interações Medicamentosas , Feminino , Humanos , Pessoa de Meia-Idade , Tamoxifeno/administração & dosagem , Tamoxifeno/análogos & derivadosRESUMO
BACKGROUND: There have been studies on the relationship between hepatitis B virus (HBV) infection and diet. We hypothesized HBV infection is related to dietary calcium intake, but the evidence is limited. This study aimed to examine whether dietary calcium intake is independently related to HBV infection in the United States population. METHODS: A total of 20,488 participants aged over 20 years from the National Health and Nutrition Examination Survey (NHANES), conducted from 2007 to 2020, were included in this study. Pearson correlation was used to test the association between dietary calcium and serum calcium. The relationships of HBV infection with dietary calcium and serum calcium were assessed by logistic regression models. RESULTS: There was a weak correlation between dietary calcium and serum calcium (r = 0.048). Logistic regression models indicated that HBV infection had a linear negative correlation with dietary calcium (OR 0.37; 95%CI 0.19, 0.76). For each additional 10 mg dietary calcium, the possibility of HBV infection was reduced by 63%. Hepatitis B positive participants had lower serum calcium content than negative participants. Stratified analysis shown the linear relationship between calcium and HBV infection varied among sex, race/ethnicity, and body mass index. CONCLUSION: Our findings demonstrated HBV infection was linearly and inversely correlated with dietary calcium. The current study is expected to offer a fresh perspective on reducing HBV infection.
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Vírus da Hepatite B , Hepatite B , Humanos , Adulto , Cálcio da Dieta , Inquéritos Nutricionais , Cálcio , Hepatite B/epidemiologiaRESUMO
Brassinosteroid (BR)-induced antioxidant defence has been shown to enhance stress tolerance. In this study, the role of the maize 65 kDa microtubule-associated protein (MAP65), ZmMAP65-1a, in BR-induced antioxidant defence was investigated. Treatment with BR increased the expression of ZmMAP65-1a in maize (Zea mays) leaves and mesophyll protoplasts. Transient expression and RNA interference silencing of ZmMAP65-1a in mesophyll protoplasts further revealed that ZmMAP65-1a is required for the BR-induced increase in expression and activity of superoxide dismutase (SOD) and ascorbate peroxidase (APX). Both exogenous and BR-induced endogenous H2O2 increased the expression of ZmMAP65-1a. Conversely, transient expression of ZmMAP65-1a in maize mesophyll protoplasts enhanced BR-induced H2O2 accumulation, while transient silencing of ZmMAP65-1a blocked the BR-induced expression of NADPH oxidase genes and inhibited BR-induced H2O2 accumulation. Inhibiting the activity and gene expression of ZmMPK5 significantly prevented the BR-induced expression of ZmMAP65-1a. Likewise, transient expression of ZmMPK5 enhanced BR-induced activities of the antioxidant defence enzymes SOD and APX in a ZmMAP65- 1a-dependent manner. ZmMPK5 directly interacted with ZmMAP65-1a in vivo and phosphorylated ZmMAP65-1a in vitro. These results suggest that BR-induced antioxidant defence in maize operates through the interaction of ZmMPK5 with ZmMAP65-1a. Furthermore, ZmMAP65-1a functions in H2O2 self-propagation via regulation of the expression of NADPH oxidase genes in BR signalling.
Assuntos
Antioxidantes/metabolismo , Brassinosteroides/metabolismo , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Proteínas de Plantas/genética , Zea mays/genética , Peróxido de Hidrogênio/metabolismo , Proteínas Quinases Ativadas por Mitógeno/genética , Folhas de Planta/enzimologia , Folhas de Planta/genética , Proteínas de Plantas/metabolismo , Reação em Cadeia da Polimerase , Protoplastos/enzimologia , Transdução de Sinais , Zea mays/enzimologiaRESUMO
Background: We evaluated the performance of the Abbott thyroid-stimulating hormone receptor antibody chemiluminescent microparticle immunoassay (CMIA) on the Alinity i. Methods: Verification studies for precision, linearity, analytical measuring range, diagnostic cut offs for Graves' disease were performed. We compared the Abbott CMIA to an established TRAb assay (Roche electrochemiluminescence immunoassay). Method comparison analysis was performed between serum and plasma samples on the Abbott CMIA. Results: Repeatability (CV%) for TRAb were 4.07, 1.56, 0.71 and within-laboratory imprecision (CV%) were 4.07, 1.90, 0.71 at 3.0, 10.0, 30.0 IU/L of TRAb, respectively. Linearity and analytical measuring range were verified from 1.07-47.9 IU/L. The limit of the blank was 0 IU/L, limit of detection was 0.15 IU/L, and limit of quantification was 0.5 IU/L. Passing-Bablok analysis showed agreement between the two assays; Y-intercept = 0.787, slope = 1.04. Passing-Bablok analysis also showed agreement between the plasma and serum samples run on the Abbott CMIA; Y-intercept -0.17, slope = 0.97. Conclusions: The Abbott TRAb CMIA on the Alinity i performs within the manufacturer claims for assay precision, linearity, analytical measuring range, limit of blank, limit of detection, limit of quantitation and diagnostic cut offs for Graves' disease. Thus, the Abbott TRAb CMIA on the Alinity i is fit for clinical use.
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Heavy metal pollution is extraordinary critical, so it is urgent to develop an effective adsorbent to dispose of such pollution. Modified chitosan was combined with polyacrylic acid to form N-carboxymethyl chitosan hydrogel (NCS-hydrogel) adsorbent. The morphology and structure of NCS-hydrogel were analyzed and identified by infrared spectroscopy, scanning electron microscopy, thermogravimetric analysis and other characterization methods. NCS-hydrogel adsorption was used to treat water pollution of Cu, Cd and Pb ions, and the influencing factors of adsorption performance were studied. The intrinsic mechanism of adsorption process was discussed by thermodynamic, kinetic and isotherm models. The results show that the adsorption process of metal ions by NCS-hydrogel meets the spontaneous monolayer chemisorption, and the adsorption process is accompanied by heat release.
Assuntos
Quitosana , Poluentes Químicos da Água , Adsorção , Cádmio , Hidrogéis , Cinética , Chumbo , Águas Residuárias , Poluentes Químicos da Água/análiseRESUMO
Objective: Malnutrition is a common complication of Chronic Kidney Disease (CKD), and it is the risk factor of CKD prognosis. This study aim to evaluate the nutritional status of inpatients with CKD by using the Subjective Global Assessment (SGA), and to analyze the related factors of malnutrition; and to provide effective reference for early detection of malnutrition status in patients with CKD and timely nutrition intervention. Methods: A total of 426 patients (238 male patients, 188 female patients) aged 62.62 ± 14.61 and 61.14 ± 14.82, respectively admitted to the Nephrology Department of Wannan Medical College from February 2020 to December 2020 were selected and included in to this study by convenience sampling. 426 patients with CKD were evaluated by SGA. Human body weight, hemoglobin (Hb), total protein (TP), albumin (ALB), pre-albumin (PA), qualitative analysis of urinary protein and other laboratory indexes were collected and measured. The correlation between malnutrition and age, education, gender, diet, CKD stage and other factors was analyzed by spearman correlation analysis. Results: The incidence of malnutrition was 85.7% among 426 patients with CKD. Gender, age, education level, CKD stage, diabetes mellitus, weight loss and reduced food intake were related to SGA nutritional assessment (P < 0.05). The expression levels of ALB, PA and Hb in the malnutrition group were significantly lower than those in the normal group (P < 0.05). The degree of malnutrition in CKD patients was significant negatively correlated with the expression levels of ALB (r = -0.188), PA (r = -0.262) and Hb (r = -0.176) (P < 0.05). The multivariate Logistic regression analysis model showed that female (OR = 2.155), ≥60 years old (OR = 7.671), weight loss (OR = 10.691), reduced food intake (OR = 28.953), moderate and severe serum ALB expression (OR = 3.391 and 8.326) were risk factors for malnutrition in patients with CKD (P < 0.05). Malnutrition was correlated with the results of qualitative examination of urinary protein (r = 0.268, P < 0.05). Conclusion: Gender, age, weight loss, reduced food intake, serum ALB expression were independently associated with malnutrition in patients with chronic kidney disease, Hence, the medical staff should take timely and effective nutrition intervention for the patients with malnutrition, delay the renal function damage of patients with CKD and improve the quality of life of patients. Inpatients with CKD, especially women, should increase their dietary intake, maintain normal weight and improve their nutritional status.
RESUMO
Introduction: We tested the total spike antibody (S-Ab), IgG/IgM S-Ab, and neutralizing antibody (N-Ab) responses of COVID-19-naïve subjects from before their first BNT162b2 vaccination up to 210 days after boosting. Methods: We studied 136 COVID-19-naïve subjects who received three doses of the Pfizer mRNA vaccine (39 males, 97 females, mean age 43.8 ± 13.5 years) from January 2021 to May 2022. Serum was assessed for total S-Ab (Roche), IgG/M (Abbott), and N-Ab (Snibe). Results: Peak antibody levels were measured 20-30 days after each dose, with booster dosing eliciting significantly higher peak antibodies than the second dose: total S-Ab 2219 vs. 19,551 BAU/mL (difference 16,667 BAU/mL, p < 0.0001); IgG 2270 vs. 2932 BAU/mL (difference 660 BAU/mL, p = 0.04); and N-Ab 3.52 vs. 26.4 µg/mL (difference 21.4 µg/mL, p < 0.0001). Only IgM showed a lower peak post-booster antibody titer (COI 2.11 vs. 0.23, difference 1.63, 95% CI 1.05 to 2.38, p < 0.0001). By 180−210 days after the second or third vaccination, total S-Ab/IgG/N-Ab had decreased by 68.7/93.8/73.6% vs. 82.8/86.3/79.5%. The half-lives of IgG and N-Ab antibodies were longer after the third vaccination (IgG: 65 vs. 34 days, N-Ab: 99 vs. 78 days). Conclusion: Total S-Ab/IgG/N-Ab showed a greater increase post-booster, with IgG/N-Ab having a longer half-life.
RESUMO
An urgent demand for electronic and optoelectronic devices able to work in extreme environments promotes a series of research studies on semiconductor materials. Cubic boron phosphide (BP) as a semiconductor material with excellent characteristics shows great application potential. However, since the synthesis conditions required are difficult to achieve and the growth mechanism of BP is still unclear, there are few reports on the basic properties of BP and pure isotope BP, resulting in a narrow understanding of their special physical properties. Here, we successfully obtained highly pure isotopic 10BP crystals by a vapor-liquid-solid (VLS) method unconventionally designed, which successfully overcomes the thermodynamic conflict between the high melting point of the boron element and low sublimation temperature of the phosphorus element. The 10BP achieved owns an aspect ratio as high as 104 and a hardness up to 41 GPa. Besides, as an indirect bandgap semiconductor, it has ultrawide red emission spectra, a p-type conductivity with extremely low resistivity, and excellent photoelectronic and piezoelectric characteristics. Furthermore, compared with other superhard semiconductors like cubic BN and diamond, 10BP has an obvious advantage of lower growth temperature (1200 °C). All these characteristics confirm the prospects owned by 10BP in its applications to the field of high-conductivity, optoelectronic, strain-sensing, and superhard semiconductors.