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Ovarian cancer is a common, highly lethal tumor. Herein, we reported that S-phase kinase-associated protein 2 (Skp2) is essential for the growth and aerobic glycolysis of ovarian cancer cells. Skp2 was upregulated in ovarian cancer tissues and associated with poor clinical outcomes. Using a customized natural product library screening, we found that xanthohumol inhibited aerobic glycolysis and cell viability of ovarian cancer cells. Xanthohumol facilitated the interaction between E3 ligase Cdh1 and Skp2 and promoted the Ub-K48-linked polyubiquitination of Skp2 and degradation. Cdh1 depletion reversed xanthohumol-induced Skp2 downregulation, enhancing HK2 expression and glycolysis in ovarian cancer cells. Finally, a xenograft tumor model was employed to examine the antitumor efficacy of xanthohumol in vivo. Collectively, we discovered that xanthohumol promotes the binding between Skp2 and Cdh1 to suppress the Skp2/AKT/HK2 signal pathway and exhibits potential antitumor activity for ovarian cancer cells.
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Flavonoides , Glucólisis , Neoplasias Ováricas , Propiofenonas , Proteínas Quinasas Asociadas a Fase-S , Ubiquitinación , Propiofenonas/farmacología , Proteínas Quinasas Asociadas a Fase-S/metabolismo , Proteínas Quinasas Asociadas a Fase-S/genética , Flavonoides/farmacología , Femenino , Humanos , Neoplasias Ováricas/tratamiento farmacológico , Neoplasias Ováricas/metabolismo , Glucólisis/efectos de los fármacos , Animales , Transducción de Señal/efectos de los fármacos , Cadherinas/metabolismo , Carcinogénesis/efectos de los fármacos , Antígenos CD/metabolismo , Hexoquinasa/metabolismo , Línea Celular Tumoral , Proteínas Proto-Oncogénicas c-akt/metabolismo , Ratones , Fitoterapia , Ratones Desnudos , Antineoplásicos Fitogénicos/farmacologíaRESUMEN
Three-dimensional (3D) graphene oxide (GO)-based aerogels, GO and 4-methyl-5-thiazoleethanol (MTZE) composites, were prepared by a facile hydrothermal method. Due to the hydrogen bonding and π-π stacking interactions, the produced 3D GO-MTZE composites possessed large cylindrical structures. The morphologies, composition, and chemical states of 3D GO-MTZE3:1 composite were characterized by Fourier transform infrared (FT-IR) spectroscopy, X-ray photoelectron spectroscopy (XPS), scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDS), and N2 adsorption-desorption isotherms based on the Brunauer-Emmett-Teller (BET) method. The existence of nitrogen (N)-containing heterocyclic system and oxygen (O)-containing branched chain of MTZE contributed to the formation of 3D structures, while the complexation effect of heterocyclic sulfur (S)- and N-containing functional groups of MTZE for metal cations dominated the adsorption performance of 3D GO-MTZE3:1 composite, which could selectively adsorb copper ions (Cu2+). In addition, the better hydrophobic property of 3D GO-MTZE3:1 composite facilitates its facile recycling from aqueous solution after adsorption. The adsorption data of 3D GO-MTZE3:1 composite toward Cu2+ fitted well (R2 = 0.9996) with the linear pseudo-second-order kinetic model, giving an equilibrium rate constant (k2) of 0.0187 g mg-1 min-1. The linear Langmuir isothermal model could more accurately describe the experimental data, indicating the adsorption process is mainly dominated by the complexation interactions between MTZE and Cu2+. The thermodynamic parameters of ΔG° (< 0), ΔH° (> 0), and ΔS° (> 0) further indicate that the adsorption is a spontaneous and endothermic, confirming that the complexation between Cu2+ and 3D GO-MTZE3:1 composite occurs. Due to its high selectivity for Cu2+, good hydrophobicity, and excellent stability, the developed 3D GO-MTZE3:1 composite possesses might be promisingly used in the aqueous selective enrichment/removal of Cu2+.
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Cobre , Grafito , Adsorción , Cobre/química , Grafito/química , Contaminantes Químicos del Agua/química , Espectroscopía Infrarroja por Transformada de FourierRESUMEN
BACKGROUND: To predict the microvascular invasion (MVI) in patients with cHCC-ICC. METHODS: A retrospective analysis was conducted on 119 patients who underwent CT enhancement scanning (from September 2006 to August 2022). They were divided into MVI-positive and MVI-negative groups. RESULTS: The proportion of patients with CEA elevation was higher in the MVI-positive group than in the MVI-negative group, with a statistically significant difference (P = 0.02). The MVI-positive group had a higher rate of peritumoral enhancement in the arterial phase (P = 0.01) whereas the MVI-negative group had more oval and lobulated masses (P = 0.04). According to the multivariate analysis, the increase in CEA (OR = 10.15, 95% CI: 1.11, 92.48, p = 0.04), hepatic capsular withdrawal (OR = 4.55, 95% CI: 1.44, 14.34, p = 0.01) and peritumoral enhancement (OR = 6.34, 95% CI: 2.18, 18.40, p < 0.01) are independent risk factors for predicting MVI. When these three imaging signs are combined, the specificity of MVI prediction was 70.59% (series connection), and the sensitivity was 100% (parallel connection). CONCLUSIONS: Our multivariate analysis found that CEA elevation, liver capsule depression, and arterial phase peritumoral enhancement were independent risk factors for predicting MVI in cHCC-ICC.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/diagnóstico por imagen , Carcinoma Hepatocelular/irrigación sanguínea , Neoplasias Hepáticas/diagnóstico por imagen , Neoplasias Hepáticas/irrigación sanguínea , Estudios Retrospectivos , Microvasos/diagnóstico por imagen , Invasividad Neoplásica , Tomografía Computarizada por Rayos XRESUMEN
Type 2 diabetes mellitus (T2DM) has become a major health problem, threatening the quality of life of nearly 500 million patients worldwide. As a typical multifactorial metabolic disease, T2DM involves the changes and interactions of various metabolic pathways such as carbohydrates, amino acid, and lipids. It has been suggested that metabolites are not only the endpoints of upstream biochemical processes, but also play a critical role as regulators of disease progression. For example, excess free fatty acids can lead to reduced glucose utilization in skeletal muscle and induce insulin resistance; metabolism disorder of branched-chain amino acids contributes to the accumulation of toxic metabolic intermediates, and promotes the dysfunction of ß-cell mitochondria, stress signal transduction, and apoptosis. In this paper, we discuss the role of metabolites in the pathogenesis of T2DM and their potential as biomarkers. Finally, we list the effects of anti-hyperglycemic drugs on serum/plasma metabolic profiles.
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Diabetes Mellitus Tipo 2 , Resistencia a la Insulina , Humanos , Diabetes Mellitus Tipo 2/metabolismo , Calidad de Vida , Resistencia a la Insulina/fisiología , Aminoácidos de Cadena Ramificada/metabolismo , Hipoglucemiantes/uso terapéuticoRESUMEN
Objectives: Augmented renal clearance (ARC) is a state of enhanced renal function commonly observed in 30%-65% of critically ill patients despite normal serum creatinine levels. Using unadjusted standard dosing regimens of renally eliminated drugs in ARC patients often leads to subtherapeutic concentrations, poor clinical outcomes, and the emergence of multidrug-resistant bacteria. We summarized pharmaceutical, pharmacokinetic, and pharmacodynamic research on the definition, underlying mechanisms, and risk factors of ARC to guide individualized dosing of antibiotics and various strategies for optimizing outcomes. Methods: We searched for articles between 2010 and 2022 in the MEDLINE database about ARC patients and antibiotics and further provided individualized antibiotic dosage regimens for patients with ARC. Results: 25 antibiotic dosage regimens for patients with ARC and various strategies for optimization of outcomes, such as extended infusion time, continuous infusion, increased dosage, and combination regimens, were summarized according to previous research. Conclusion: ARC patients, especially critically ill patients, need to make individualized adjustments to antibiotics, including dose, frequency, and method of administration. Further comprehensive research is required to determine ARC staging, expand the range of recommended antibiotics, and establish individualized dosing guidelines for ARC patients.
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Objective: To evaluate the efficacy of applying mecapegfilgrastim for peripheral blood hematopoietic stem cell (PBSC) mobilization in patients with hematologic neoplasms, and to investigate the influencing factors of PBSC collection. Methods: Patients who underwent PBSC mobilization in the Department of Hematology, Mianyang Central Hospital between April 2016 and May 2022 were retrospectively analyzed. The CD34 + cell collection results of two groups, the mecapegfilgrastim group ( n=28), or the PEG group, and the recombinant human granulocyte colony-stimulating factor (rhG-CSF) group ( n=30), were compared, and the influencing factors of collection failure were analyzed. Results: The success rates of CD34 + cells collection in the PEG group and the rhG-CSF group were 75.0% and 63.3%, respectively ( P>0.05). The median CD34 + cell counts were 3.37×10 6/kg and 2.68×10 6/kg, respectively, showing no significant difference. After combined mobilization with plerixafor, the median counts of CD34 + cells collected in the PEG group and rhG-CSF group were 4.23×10 6/kg and 3.26×10 6/kg, respectively, showing no significant difference ( P>0.05). There was no significant difference in hematopoietic system reconstruction and infections between the two groups ( P>0.05). Multivariate analysis found non-plasma cell disease (odds ratio [ OR]=19.697, 95% confidence interval [ CI] : 1.501-258.537, P=0.023), anemia before collection ( OR=18.571, 95% CI: 1.354-254.775, P=0.029) and white blood cell count before collection under 32×10 9 L -1 ( OR=85.903, 95% CI: 4.947-1491.807, P=0.002) to be independent risk factors for PBSC collection failure. Conclusion: The effect of PBSC mobilization with mecapegfilgrastim was comparable to that of rhG-CSF in patients with hematologic neoplasms. Furthermore, combined mobilization with plerixafor was feasible and effective. Patients with leukemia or lymphoma, anemia, and WBC<32×10 9 L -1 before stem cell collection have a high probability of PBSC collection failure.
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Neoplasias Hematológicas , Trasplante de Células Madre Hematopoyéticas , Compuestos Heterocíclicos , Humanos , Movilización de Célula Madre Hematopoyética/métodos , Estudios Retrospectivos , Factor Estimulante de Colonias de Granulocitos/uso terapéutico , Neoplasias Hematológicas/terapia , Antígenos CD34RESUMEN
Highly sensitive gas sensors with remarkably low detection limits are attractive for diverse practical application fields including real-time environmental monitoring, exhaled breath diagnosis, and food freshness analysis. Among various chemiresistive sensing materials, noble metal-decorated semiconducting metal oxides (SMOs) have currently aroused extensive attention by virtue of the unique electronic and catalytic properties of noble metals. This review highlights the research progress on the designs and applications of different noble metal-decorated SMOs with diverse nanostructures (e.g., nanoparticles, nanowires, nanorods, nanosheets, nanoflowers, and microspheres) for high-performance gas sensors with higher response, faster response/recovery speed, lower operating temperature, and ultra-low detection limits. The key topics include Pt, Pd, Au, other noble metals (e.g., Ag, Ru, and Rh.), and bimetals-decorated SMOs containing ZnO, SnO2, WO3, other SMOs (e.g., In2O3, Fe2O3, and CuO), and heterostructured SMOs. In addition to conventional devices, the innovative applications like photo-assisted room temperature gas sensors and mechanically flexible smart wearable devices are also discussed. Moreover, the relevant mechanisms for the sensing performance improvement caused by noble metal decoration, including the electronic sensitization effect and the chemical sensitization effect, have also been summarized in detail. Finally, major challenges and future perspectives towards noble metal-decorated SMOs-based chemiresistive gas sensors are proposed.
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OBJECTIVES: Limited data on clinical and microbiological efficacy, patient mortality, and other associated factors are available for ceftazidime/avibactam (CAZ/AVI)-based regimens for carbapenem-resistant Gram-negative bacteria (CR-GNB). This study aimed to assess these issues retrospectively using multicenter data. METHODS: This multicenter study included CR-GNB infected patients treated with CAZ/AVI-based regimens for more than three days. Patient characteristics, bacterial culture reports, drug-sensitivity test results, and antibiotic use, including CAZ/AVI use, were extracted from the patient's clinical records. The clinical and microbiological efficacy of the combined drug regimen and patient mortality were evaluated according to corresponding definitions. Univariate and multivariate logistic regressions were performed to explore the efficacy and mortality-related factors. RESULTS: A total of 183 patients with CR-GNB infection were considered for the analysis according to the inclusion and exclusion criteria. After the treatment of CAZ/AVI-based regimens, the clinical efficacy was 75.4 %. The 7-day microbial efficacy and clearance rate after treatment were 43.7 % and 66.0 %, respectively. Moreover, 30-day all-cause and in-hospital mortality were 11.5 % and 14.2 %, respectively. Harboring renal dysfunction (creatinine clearance rate (CCR) of<20 mL/min), cardiovascular diseases, and digestive system diseases were independent risk factors for poor clinical efficacy of CAZ/AVI-based regimens. Bloodstream infection (BSI), patients with the adjusted doses of CAZ/AVI, and CAZ/AVI co-administration with carbapenem were independently associated factors of bacterial clearance by CAZ/AVI-based regimens. Age, total hospital stays, use of mechanical ventilation, and cumulative CAZ/AVI dose were independent factors associated with all-cause mortality. CONCLUSION: CAZ/AVI was an effective drug in treating CR-GNB infection. CAZ/AVI that is mostly excreted by the kidney and is accumulated in renal impairment should be renally adjusted. Renal dysfunction and the adjusted dose of CAZ/AVI were associated with efficacy. Clinicians should individualize CAZ/AVI regimen and dose by the level of renal function to achieve optimal efficacy and survival. The efficacy of CAZ/AVI in the treatment of CR-GNB infection, as well as the implementation of individualized precision drug administration of CAZ/AVI according to patients' different infection sites, renal function, bacterial types, bacterial resistance mechanisms, blood concentration monitoring and other conditions need to be further studied in multicenter.
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Infecciones Bacterianas , Infecciones por Bacterias Gramnegativas , Enfermedades Renales , Humanos , Ceftazidima/uso terapéutico , Carbapenémicos/farmacología , Carbapenémicos/uso terapéutico , Estudios Retrospectivos , Antibacterianos/uso terapéutico , Infecciones por Bacterias Gramnegativas/tratamiento farmacológico , Infecciones Bacterianas/tratamiento farmacológico , Bacterias Gramnegativas , Pruebas de Sensibilidad MicrobianaRESUMEN
According to the theory of coordinated reset (CR) stimulation, multifocal bursts of stimuli delivered in a random order with a specific interval may reduce the resonance power of the oscillatory generator in the epicenter. We develop a noninvasive coordinated multifocal burst stimulation (COMBS) with three repetitive transcranial stimulation machines based on CR theory to modulate the target frequency in the primary motor cortex and to assess its effect on motor cortical excitability in separate experiments. Electroencephalography and electromyography were recorded in 16 healthy participants during a finger-tapping task, both before and after the intervention. The resting oscillatory power at the targeted frequency was not changed by COMBS. α-Band power was increased in both preparation and movement stages and the low ß-band power was increased in the movement stage of the finger tapping task. The extent of low ß-band event-related desynchronization was reduced by COMBS. There were no changes in reaction time, but there was a trend for a reduced error rate after COMBS. In another 14 healthy participants, there were no significant changes in cortical excitability before and after COMBS measured by rest motor threshold, short interval intracortical inhibition, short interval intracortical facilitation, and cortical silent period. The result indicates that COMBS may modify the cortical oscillatory power and its perturbation within specific movement stage.NEW & NOTEWORTHY This is the first study, to our knowledge, to apply coordinated reset (CR) neuromodulation to the motor cortex with three repetitive transcranial magnetic stimulation (rTMS) stimulators to assess its effect on cortical oscillation. The results revealed enhancement of α-band power specifically in preparation and movement stages and low ß-band power in the movement stage of a motor task. It postulated that CR stimulation may modify the motor cortical oscillation in the specific movement stages.
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Corteza Motora , Estimulación Magnética Transcraneal , Humanos , Estimulación Magnética Transcraneal/métodos , Corteza Motora/fisiología , Potenciales Evocados Motores/fisiología , Electroencefalografía/métodos , ElectromiografíaRESUMEN
To observe the effect of magnesium ion on vascular function in rats after long-term exhaustive exercise. Forty male SD rats were divided into two groups, the control group (CON group, n = 20) and the exhaustive exercise group (EEE group, n = 20). Exhausted rats performed 1W adaptive swimming exercise (6 times/W, 15min/time), and then followed by 3W formal exhaustive exercise intervention. Hematoxylin and eosin (HE) staining was used to detect the morphological changes of rat thoracic aorta. The contents of interleukin-1 ß (IL-1ß) and tumor necrosis factor-α (TNF-α) in serum of rats were determined by enzyme-linked immunosorbent assay (ELISA), and the contents of malondialdehyde (MDA), reactive oxygen species (ROS), nitric oxide (NO) and endothelin 1 (ET-1) in serum of rats were determined by biochemical kit. Vascular ring test detects vascular function. Compared with the CON group, the smooth muscle layer of the EEE group became thicker, the cell arrangement was disordered, and the integrity of endothelial cells was destroyed; the serum Mg2+ in EEE group was decreased; the serum levels of IL-1ß, TNF-α, MDA and ROS in EEE group were significantly higher than those in the CON group (P are all less than 0.05); the serum NO content in EEE group was significantly decreased, and the ratio of NO/ET-1 was significantly decreased. In the exhaustion group, the vasoconstriction response to KCl was increased, and the relaxation response to Ach was weakened, while 4.8mM Mg2+ could significantly improve this phenomenon (P are all less than 0.01). The damage of vascular morphology and function in rats after exhaustion exercise may be related to the significant increase of serum IL-1ß, TNF-α, ROS, MDA and ET-1/NO ratio in rats after exhaustion exercise, while Mg2+ can significantly improve the vasomotor function of rats after exhaustion exercise.
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Magnesio , Factor de Necrosis Tumoral alfa , Ratas , Masculino , Animales , Ratas Sprague-Dawley , Especies Reactivas de Oxígeno , Células EndotelialesRESUMEN
Emerging chromium (Cr) species have attracted increasing concern. A majority of Cr species, especially hexavalent chromium (Cr(VI)), could lead to lethal effects on human beings, animals, and aquatic lives even at low concentrations. One of the conventional water-treatment methodologies, adsorption, could remove these toxic Cr species efficiently. Additionally, adsorption possesses many advantages, such as being cost-saving, easy to implement, highly efficient and facile to design. Previous research has shown that the application of different adsorbents, such as carbon nanotubes (carbon nanotubes (CNTs) and graphene oxide (GO) and its derivatives), activated carbons (ACs), biochars (BCs), metal-based composites, polymers and others, is being used for Cr species removal from contaminated water and wastewater. The research progress and application of adsorption for Cr removal in recent years are reviewed, the mechanisms of adsorption are also discussed and the development trend of Cr treatment by adsorption is proposed.
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AIMS: Type 2 diabetes mellitus (T2DM) can remain undiagnosed for many years, during which micro- and macro-vascular complications may develop. This study aimed to assess the worldwide prevalence of diabetic retinopathy (DR) in patients with newly diagnosed T2DM. MATERIALS AND METHODS: We systematically searched electronic databases for relevant studies published from inception to 01 January 2022. Selected studies reported the prevalence of DR among patients with newly diagnosed T2DM, specifying the case definition used. Random-effects meta-analysis was used to derive the pooled prevalence. Subgroup and meta-regression analyses were used to investigate variations in the prevalence estimates in terms of available variables. RESULTS: Data from 77 studies including 99,847 patients with newly diagnosed T2DM were included from 26 countries. The pooled prevalence of DR among patients with newly diagnosed T2DM was 13.1% (95% CI, 11.1%-15.1%; I2 = 97.0%). DR was higher in clinic-based samples compared with community-based samples (15.0%, 95% CI = 12.4%-17.8% vs. 11.5%, 95% CI = 8.9%-14.5%; p = 0.05; I2 = 97.0%) and was higher in countries in the WHO African 19.2% (95% CI, 14.6%-24.3%; I2 = 76.0%), South-East Asia 15.4% (95% CI, 10.0%-21.6%; I2 = 79.1%), and European 15.0% (95% CI, 11.2%-19.2%; I2 = 82.0%) regions. A higher proportion of female patients was significantly associated with a lower prevalence of DR in patients with newly diagnosed T2DM. We observed that the prevalence of DR in patients with newly diagnosed T2DM has remained unchanged over time. CONCLUSIONS: Globally, DR is a prevalent complication among patients with newly diagnosed T2DM indicating the importance of establishing effective strategies to promote regular screening for the early diagnosis of T2DM alongside routine ophthalmic assessment at the time of T2DM diagnosis to reduce the burden of vision-threatening retinopathy.
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Diabetes Mellitus Tipo 2 , Retinopatía Diabética , Humanos , Femenino , Retinopatía Diabética/diagnóstico , Retinopatía Diabética/epidemiología , Retinopatía Diabética/etiología , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/epidemiología , Diabetes Mellitus Tipo 2/diagnóstico , Factores de Riesgo , Prevalencia , OjoRESUMEN
Vascular calcification (VC) is an important hallmark of cardiovascular disease, the osteo-/chondrocyte phenotype differentiation of vascular smooth muscle cells (VSMCs) is the main cause of vascular calcification. Accumulating evidence shows that mitochondrial dysfunction may ultimately be more detrimental in the VSMCs calcification. Mitochondrial participate in essential cellular functions, including energy production, metabolism, redox homeostasis regulation, intracellular calcium homeostasis, apoptosis, and signal transduction. Mitochondrial dysfunction under pathological conditions results in mitochondrial reactive oxygen species (ROS) generation and metabolic disorders, which further lead to abnormal phenotypic differentiation of VSMCs. In this review, we summarize existing studies targeting mitochondria as a treatment for VC, and focus on VSMCs, highlighting recent progress in determining the roles of mitochondrial processes in regulating the phenotype transition of VSMCs, including mitochondrial biogenesis, mitochondrial dynamics, mitophagy, mitochondrial energy metabolism, and mitochondria/ER interactions. Along these lines, the impact of mitochondrial homeostasis on VC is discussed.
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OBJECTIVES: To study the association of maternal methylenetetrahydrofolate dehydrogenase 1 (MTHFD1) and methylenetetrahydrofolate dehydrogenase 2 (MTHFD2) gene polymorphisms with congenital heart disease (CHD) in offspring. METHODS: A hospital-based case-control study was conducted. The mothers of 683 children with CHD alone who attended Hunan Children's Hospital, from November 2017 to March 2020 were enrolled as the case group, and the mothers of 740 healthy children who attended the same hospital during the same period and did not have any deformity were enrolled as the control group. A questionnaire survey was performed to collect related exposure data, and then venous blood samples (5 mL) were collected from the mothers to detect MTHFD1 and MTHFD2 gene polymorphisms. A multivariate logistic regression analysis was used to evaluate the association of MTHFD1 and MTHFD2 gene polymorphisms with CHD. The four-gamete test in Haploview 4.2 software was used to construct haplotypes and evaluate the association between haplotypes and CHD. The generalized multifactor dimensionality reduction method and logistic regression analysis were used to examine gene-gene interaction and its association with CHD. RESULTS: The multivariate logistic regression analysis showed that maternal MTHFD1 gene polymorphisms at rs11849530 (GA vs AA: OR=1.49; GG vs AA: OR=2.04) andat rs1256142 (GA vs GG: OR=2.34; AA vs GG: OR=3.25) significantly increased the risk of CHD in offspring (P<0.05), while maternal MTHFD1 gene polymorphisms at rs1950902 (AA vs GG: OR=0.57) and MTHFD2 gene polymorphisms at rs1095966 (CA vs CC: OR=0.68) significantly reduced the risk of CHD in offspring (P<0.05). The haplotypes of G-G-G (OR=1.86) and G-A-G (OR=1.35) in mothers significantly increased the risk of CHD in offspring (P<0.05). The gene-gene interaction analyses showed that the first-order interaction between MTHFD1 rs1950902 and MTHFD1 rs2236222 and the second-order interaction involving MTHFD1 rs1950902, MTHFD1 rs1256142, and MTHFD2 rs1095966 might be associated with risk of CHD (P<0.05). CONCLUSIONS: Maternal MTHFD1 and MTHFD2 gene polymorphisms and their haplotypes, as well as the interaction between MTHFD1 rs1950902 and MTHFD1 rs2236222 and between MTHFD1 rs1950902, MTHFD1 rs1256142, and MTHFD2 rs1095966, are associated with the risk of CHD in offspring.
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Aminohidrolasas , Cardiopatías Congénitas , Metilenotetrahidrofolato Deshidrogenasa (NADP) , Enzimas Multifuncionales , Aminohidrolasas/genética , Estudios de Casos y Controles , Niño , Femenino , Predisposición Genética a la Enfermedad , Cardiopatías Congénitas/genética , Humanos , Metilenotetrahidrofolato Deshidrogenasa (NADP)/genética , Antígenos de Histocompatibilidad Menor/genética , Madres , Enzimas Multifuncionales/genética , Polimorfismo de Nucleótido Simple , Factores de RiesgoRESUMEN
Methods: Male C57BL/6J mice were randomly divided into six different experimental groups (8 animals/group): (1) normal group (NOR), (2) normal control group (NC), (3) normal + exercise group (NE), (4) IGT group (IGT), (5) IGT control group (IC), and (6) IGT+ exercise group (IE).The exercise group received aerobic exercise for 8 weeks. After the intervention, a blood glucose meter was used to detect the level of glucose tolerance in the mouse's abdominal cavity; a biochemical kit was used to detect serum lipid metabolism indicators, malondialdehyde, and superoxide dismutase levels; the ELISA method was used to detect serum insulin and mouse gastrocnemius homogenate LDH, PDH, SDH, and CCO levels. Western blot method was used to detect the protein expression levels of NOX4, PGC-1α, and Mfn2 in the gastrocnemius muscle of mice. Results: (1) Mice with high-fat diet for 30 weeks showed impaired glucose tolerance, insulin resistance, and lipid metabolism disorders. The level of LDH, PDH, SDH, and CCO in the gastrocnemius homogenate of mice was reduced. The expressions of NOX4 protein were significantly upregulated, while the expressions of PGC-1α and Mfn2 proteins were significantly downregulated. (2) 8-week aerobic exercise improved the disorders of glucose and lipid metabolism in IGT mice and increased homogenized LDH, PDH, SDH, and CCO levels, and the expressions of NOX4, PGC-1α, and Mfn2 proteins in the gastrocnemius muscle of mice were reversed. It is speculated that aerobic exercise can accelerate energy metabolism. Conclusion: (1) C57BL/6 mice were fed high fat for 30 weeks and successfully constructed a mouse model of reduced diabetes; the mice with reduced diabetes have impaired glucose tolerance, insulin resistance, and lipid metabolism disorders; (2) 8 weeks of aerobic exercise improve glucose tolerance, reduce glucose tolerance in mice, reduce insulin resistance, improve lipid metabolism disorders, and reduce oxidative stress; (3) 8-week aerobic exercise reduces skeletal muscle NOX4 expression and increases glucose tolerance; reduces the expression of LDH, PDH, SDH, and CCO in mouse skeletal muscle; increases the expression level of mitochondrial fusion protein 2 and PGC-1α; improves glucose tolerance; reduces energy metabolism of mouse skeletal muscle; reduces oxidative stress; and reduces insulin resistance. It is speculated that aerobic exercise can accelerate energy metabolism. This process may involve two aspects: firstly, increase the expression level of oxidative metabolism enzymes and promote the tricarboxylic acid cycle; secondly, increase the expression of Mfn2 and accelerate mitochondria fission or fusion to regulate energy metabolism, thereby reducing oxidative stress and insulin resistance.
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Intolerancia a la Glucosa , Resistencia a la Insulina , Animales , Glucosa/farmacología , Intolerancia a la Glucosa/metabolismo , Resistencia a la Insulina/fisiología , Masculino , Ratones , Ratones Endogámicos C57BL , Mitocondrias/metabolismo , Mitocondrias Musculares/metabolismo , Músculo Esquelético/metabolismo , Estrés OxidativoRESUMEN
Egg-ceasing is a phenomenon that occurs in most avian species and significantly reduces productivity. Although several factors are reported to regulate the reproduction progress, the underlying molecular mechanism of egg-ceasing remains obscure. Herein, we identified and explored the differentially expressed miRNAs and mRNAs involved in ovarian atrophy via high throughput sequencing. We identified a total of 901 mRNAs and 50 miRNAs that were differentially expressed in egg-laying and atrophic ovaries. Among them, numerous differentially expressed gene (DEG) transcripts and target genes for miRNAs were significantly enriched in Gene Ontology terms such as reproductive processes, cell proliferation, and apoptosis pathways. In addition, an interaction network was constructed by considering target relationships and correlation of the expression levels between ovary development-related genes, miRNAs and pathways. We discovered mRNA and miRNAs transcripts that are candidate regulators of ovary development in egg-ceased geese. Our findings expanded our understanding of the functional of miRNAs in ovarian atrophy and demonstrated that RNA-Seq is a powerful tool for examining the molecular mechanism in regulating egg-ceasing.
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Gansos , MicroARNs , Animales , Atrofia/metabolismo , Atrofia/veterinaria , Femenino , Gansos/genética , Gansos/metabolismo , Perfilación de la Expresión Génica/veterinaria , MicroARNs/genética , MicroARNs/metabolismo , Ovario/metabolismo , ARN Mensajero/genética , ARN Mensajero/metabolismo , Estaciones del AñoRESUMEN
BACKGROUND: To date, there has been little focus on research into acupuncture for insomnia after ischemic stroke. Insomnia is one of the most common sequelae after ischemic stroke, and it is the most unrecognized modifiable risk factor. OBJECTIVE: To evaluate the efficacy and safety of acupuncture for insomnia after ischemic stroke. METHODS: In this assessor-participant blinded, randomized, controlled trial, 144 ischemic stroke patients with insomnia meeting Diagnostic and Statistical Manual of Mental Disorders (fifth edition, DSM-5) criteria were assigned to verum or sham acupuncture treatment (n = 72 per group) for three sessions per week over 4 weeks. The outcomes were the Insomnia Severity Index (ISI), Pittsburgh Sleep Quality Index (PSQI), stroke-specific quality of life (SSQoL), and Hospital Anxiety and Depression Scale (HADS) scores. Multiple objective sleep variables were recorded using actigraphy. Assessment was conducted at baseline, and thereafter once biweekly for the 4-week treatment and at 4 weeks of follow-up. RESULTS: The verum acupuncture group had significantly greater improvements than the sham acupuncture group in sleep quality from 2 weeks into treatment throughout the follow-up, indicated by ISI scores and actigraphic variable SE (sleep efficiency). This greater improvement was also observed in the PSQI after 4 weeks of treatment throughout follow-up, as well as actigraphic variable TST (total sleep time), SSQoL and HADS scores at the end of treatment, and SSQoL and depression scores at follow-up. There was no significant difference between groups in the actigraphic variable SA (sleep awakenings). Adverse events were mild in severity, and their incidence was not significantly different between the two groups. CONCLUSION: Acupuncture appears to be efficacious, in terms of improving insomnia, related quality of life, and affective symptoms, for patients with ischemic stroke. TRIAL REGISTRATION NUMBER: ChiCTR-IIC-16008382 (Chinese Clinical Trial Registry).
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Terapia por Acupuntura , Accidente Cerebrovascular Isquémico , Trastornos del Inicio y del Mantenimiento del Sueño , Accidente Cerebrovascular , Humanos , Calidad de Vida , Sueño , Trastornos del Inicio y del Mantenimiento del Sueño/etiología , Trastornos del Inicio y del Mantenimiento del Sueño/terapia , Accidente Cerebrovascular/complicaciones , Accidente Cerebrovascular/terapia , Resultado del TratamientoRESUMEN
PURPOSE: To ascertain if assisted hatching (AH) increases the risk of placenta-associated diseases and perinatal outcomes after frozen-thawed cleavage-stage embryo transfer. METHODS: We retrospectively evaluated 924 women who conceived with frozen-thawed cleavage-stage embryos transfer with (n = 390) or without (n = 534) laser-AH between 2013 and 2015. Data were obtained from the database on in vitro fertilization (IVF) patients in Shanghai First Maternity and Infant Hospital. We assessed neonatal (preterm birth, low birthweight, fetal macrosomia, stillbirth) and obstetric (miscarriage, ectopic pregnancy, post-term pregnancy, gestational diabetes (GDM), preeclampsia, intrahepatic cholestasis (ICP), placenta previa, placental abruption, premature rupture of membranes) outcomes. RESULTS: In twins, the median birthweight was lower in the AH group than that in the control group, and the prevalence of low birthweight (< 2500 g) was significantly higher in the AH group; after adjusting for maternal age, body mass index, mode of fertilization, and parity, no significant difference was found. In twins, no significant difference was detected in the prevalence of stillbirth or preterm pregnancy. In singleton births, there was no significant difference in the prevalence of low birthweight, macrosomia, preterm pregnancy or post-term pregnancy between the two groups. In singletons and twins, there were no significant differences in the prevalence of miscarriage, ectopic pregnancy, preeclampsia, GDM, ICP, or placenta abruption between the two groups. CONCLUSIONS: AH is a relatively safe method and our study provides important information for using this method in carefully selected patients.
Asunto(s)
Nacimiento Prematuro , China/epidemiología , Femenino , Fertilización In Vitro/efectos adversos , Humanos , Recién Nacido , Rayos Láser , Placenta , Embarazo , Resultado del Embarazo/epidemiología , Nacimiento Prematuro/epidemiología , Estudios RetrospectivosRESUMEN
BACKGROUND: Breast cancer remains one of the most dreadful female malignancies globally, in which cancer stem cells (CSCs) play crucial functions. Circular RNAs have drawn great attention in cancer research area and propofol is a widely applied intravenous anesthetic agent. METHODS: In the current study, we explored the function of circular RNA nucleolar and coiled-body phosphoprotein 1 (circNOLC1) in CSCs of breast cancer and the inhibitory impact of propofol on circNOLC1. RESULTS: The expression of circNOLC1 was induced in breast cancer tissues compared with the non-tumor tissues. The silencing of circNOLC1 was able to repress the viability of breast cancer cells. Meanwhile, the numbers of colony formation were suppressed by circNOLC1 knockdown in breast cancer cells. The inhibition of circNOLC1 reduced the invasion and migration ability of breast cancer cells. The mRNA and protein levels of E-cadherin were enhanced but Vimentin levels were reduced by the silencing of circNOLC1. The repression of circNOLC1 decreased the side population (SP) ratio in breast cancer cells. Meanwhile, the sphere formation ability of breast cancer cells was attenuated by the silencing of circNOLC1. The levels of ATP-binding cassette (ABC) superfamily G member 2 (ABCG2), c-Myc, B cell-specific Moloney murine leukemia virus integration site 1 (Bmi1), and SRY-box transcription factor 2 (Sox2) were repressed by the depletion of circNOLC1 in the cells. Regarding to the mechanism, circNOLC1 functioned as a competing endogenous RNAs (ceRNAs) for microRNA-365a-3p (miR-365a-3p) and the inhibition of miR-365a-3p rescued circNOLC1 depletion-repressed proliferation and cancer stem cell activity of breast cancer. MiR-365a-3p targeted signal transducer and activator of transcription 3 (STAT3) in breast cancer cells and circNOLC1 enhanced STAT3 expression by sponging miR-365a-3p. The overexpression of STAT3 could reverse miR-365a-3p or circNOLC1 depletion-inhibited proliferation and cancer stem cell properties of breast cancer. Interestingly, the expression of circNOLC1 and STAT3 was repressed by the treatment of propofol. The enrichment of STAT3 on circNOLC1 promoter was inhibited by propofol. The expression of circNOLC1 was suppressed by the silencing of STAT3 in the cells. The inhibition of circNOLC1 expression by propofol was rescued under the co-treatment of STAT3 overexpression. The overexpression of circNOLC1 rescued propofol-attenuated proliferation and cancer stem cell functions in vitro and in vivo. CONCLUSIONS: Thus, we concluded that circNOLC1 contributes to CSCs properties and progression of breast cancer by targeting miR-365a-3p /STAT3 axis and propofol inhibited circNOLC1 by repressing STAT3 in a feedback mechanism.
Asunto(s)
MicroARNs , Neoplasias , Propofol , Animales , Línea Celular Tumoral , Movimiento Celular/genética , Proliferación Celular , Femenino , Regulación Neoplásica de la Expresión Génica , Ratones , MicroARNs/genética , Células Madre Neoplásicas/metabolismo , Propofol/farmacología , ARN Circular , Factor de Transcripción STAT3/genética , Factor de Transcripción STAT3/metabolismoRESUMEN
Currently, polymyxin B has been widely used in the treatment of multidrug-resistant Gram-negative pathogen infections. Due to the limited pharmacokinetic/pharmacodynamic data, the optimal dosage regimen for the recently proposed therapeutic target of the area under the concentration-time curve over 24 h in steady state divided by the minimum inhibitory concentration 50-100 mgâ h/L has not yet been established. Moreover, most studies have focused on critically ill patients, yet there have been no studies in the field of renal transplantation. To optimize the dosage strategy and reduce the risk of toxicity, a population pharmacokinetics model of polymyxin B with the Phoenix NLME program was developed in our study. A total of 151 plasma samples from 50 patients were collected in the present study. Polymyxin B plasma concentrations were measured by high-performance liquid chromatography-tandem mass spectrometry. A one-compartment model adequately described the data, and the clearance and volume of distribution were 1.18 L/h and 12.09 L, respectively. A larger creatinine clearance was associated with increased clearance of polymyxin B (p < 0.01). Monte Carlo simulation showed that a regimen of a 75 mg loading dose with a 50 mg maintenance dose was a better option to achieve an optimal therapeutic effect (minimum inhibitory concentration ≤1 mg/L) and to reduce the incidence of side effects for patients with renal impairments. The developed model suggested that dosing adjustment should be based on renal function in renal transplant patients.