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1.
Exp Brain Res ; 242(6): 1507-1515, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38719948

RESUMEN

Alzheimer's disease is a progressive neurodegenerative disorder characterized by impairments in synaptic plasticity and cognitive performance. Current treatments are unable to achieve satisfactory therapeutic effects or reverse the progression of the disease. Calcineurin has been implicated as part of a critical signaling pathway for learning and memory, and neuronal calcineurin may be hyperactivated in AD. To investigate the effects and underlying mechanisms of FK506, a calcineurin inhibitor, on Alzheimer-like behavior and synaptic dysfunction in the 3 × Tg-AD transgenic mouse model of Alzheimer's disease, we investigated the effect of FK506 on cognitive function and synaptic plasticity in the 3 × Tg-AD transgenic mouse model of Alzheimer's disease. The results showed that FK506 treatment ameliorated cognitive deficits, as indicated by the decreased latency in the water maze, and attenuated tau hyperphosphorylation in 3 × Tg-AD mice. Treatment with FK506 also reduced the levels of certain markers of postsynaptic deficits, including PSD-95 and NR2B, and reversed the long-term potentiation deficiency and dendritic spine impairments in 3 × Tg-AD mice. These findings suggest that treatment with calcineurin inhibitors such as FK506 can be an effective therapeutic strategy to rescue synaptic deficit and cognitive impairment in familial Alzheimer's disease and related tauopathies.


Asunto(s)
Enfermedad de Alzheimer , Inhibidores de la Calcineurina , Modelos Animales de Enfermedad , Ratones Transgénicos , Tacrolimus , Animales , Enfermedad de Alzheimer/tratamiento farmacológico , Enfermedad de Alzheimer/metabolismo , Enfermedad de Alzheimer/fisiopatología , Tacrolimus/farmacología , Inhibidores de la Calcineurina/farmacología , Ratones , Aprendizaje por Laberinto/efectos de los fármacos , Aprendizaje por Laberinto/fisiología , Calcineurina/metabolismo , Plasticidad Neuronal/efectos de los fármacos , Plasticidad Neuronal/fisiología , Proteínas tau/metabolismo , Receptores de N-Metil-D-Aspartato/metabolismo , Receptores de N-Metil-D-Aspartato/antagonistas & inhibidores , Masculino , Sinapsis/efectos de los fármacos , Sinapsis/metabolismo , Homólogo 4 de la Proteína Discs Large/metabolismo
2.
BMC Musculoskelet Disord ; 25(1): 245, 2024 Mar 28.
Artículo en Inglés | MEDLINE | ID: mdl-38539146

RESUMEN

BACKGROUND: Sarco-osteoporosis is a skeletal muscle disease associated with aging and complex pathological factors. At present, there are few studies on the analysis of its related factors, and a nomogram to estimate the risk of sarco-osteoporosis in middle-aged and elderly patients is not available. METHODS: A total of 386 patients admitted to our hospital from October 2021 to October 2022 were collected, and the general demographic data and clinical data of the patients were collected.386 subjects were enrolled in the study and randomly divided into training set and validation set at a ratio of 7:3. In the training set, the Least absolute shrinkage and selection operator(LASSO)regression technique was used to select the optimal predictive features, and multivariate logistic regression was used to screen the factors associated with sarco-osteoporosis, and a nomogram was constructed using meaningful variables from multivariate analysis. The performance of the nomograms was assessed and validated by Area Under Curve (AUC) and calibration curves. RESULTS: There were no significant differences in baseline characteristic of individuals in training set and validation set, six variables with non-zero coefficients were screened based on LASSO regression in the training set. Multivariate logistic regression analysis showed that the related factors for sarco-osteoporosis in middle-aged and elderly inpatients included age (OR = 1.08, 95%CI 1.03 ∼ 1.14), regular exercise (OR = 0.29, 95%CI 0.15 ∼ 0.56), albumin (OR = 0.9, 95%CI 0.82 ∼ 0.98), height (OR = 0.93, 95%CI 0.88 ∼ 0.99) and lean mass index (OR = 0.66, 95%CI 0.52 ∼ 0.85), and a nomogram was constructed based on the above factors. AUC of nomogram were 0.868(95%CI 0.825 ∼ 0.912) in the training set and 0.737(95%CI 0.646 ∼ 0.828) in the validation set. Calibration curve analysis showed that the predicted probability of sarco-osteoporosis had high consistency with the actual probability, and the absolute error of the training set and verification set was 0.018 and 0.03, respectively. CONCLUSIONS: Our research showed that the occurrence of sarco-osteoporosis was associated with age, regular exercise, albumin, height and lean mass index, and we have developed a nomogram that can be effectively used in the preliminary and in-depth risk prediction of sarco-osteoporosis in middle-aged and elderly hospitalized patients.


Asunto(s)
Pacientes Internos , Osteoporosis , Anciano , Humanos , Persona de Mediana Edad , Envejecimiento , Albúminas , Nomogramas , Osteoporosis/diagnóstico , Osteoporosis/epidemiología , Estudios Retrospectivos , Zonisamida
3.
Neurosci Lett ; 825: 137700, 2024 Mar 10.
Artículo en Inglés | MEDLINE | ID: mdl-38401642

RESUMEN

Multiple biological functions of MTMR14 including regulation of autophagy, inflammation and Ca2+ homeostasis have been reported. However, its functional contribution to learning and memory remains unclear. In this study, we investigated whether upregulation of MTMR14 induced cognitive impairment and the underlying mechanisms. MTMR14 level was significantly increased in cells or brain tissues that overexpressed P301S-tau. The fusion of autophagosome and lysosome was significantly inhibited by overexpression of MTMR14 or P301S-tau. Upregulation of MTMR14 led to cognitive impairments in 2-month-old mice by inhibiting synaptic protein expression. These findings suggest that MTMR14 may be a key risk factor for cognitive ability.


Asunto(s)
Enfermedad de Alzheimer , Proteínas tau , Ratones , Animales , Regulación hacia Arriba , Aprendizaje por Laberinto/fisiología , Ratones Transgénicos , Proteínas tau/metabolismo , Modelos Animales de Enfermedad , Enfermedad de Alzheimer/metabolismo , Monoéster Fosfórico Hidrolasas/genética
4.
Diabetes Obes Metab ; 26(1): 311-318, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37871985

RESUMEN

AIMS: To investigate the efficacy and safety of ultra-rapid lispro (URLi) versus insulin lispro in predominantly Chinese patients with type 1 diabetes (T1D) in a prospective, randomized, double-blind, treat-to-target, phase 3 study. MATERIALS AND METHODS: Following a lead-in period, during which insulin glargine U-100 or insulin degludec U-100 was optimized, patients were randomly assigned (1:1) to URLi (n = 176) or insulin lispro (n = 178). The primary objective was to test the noninferiority of URLi to insulin lispro in glycaemic control (noninferiority margin = 0.4% for glycated haemoglobin [HbA1c] change from baseline to week 26), with testing for the superiority of URLi to insulin lispro with regard to 1- and 2-hour postprandial glucose (PPG) excursions during a mixed-meal tolerance test and HbA1c change at week 26 as the multiplicity-adjusted objectives. RESULTS: From baseline to week 26, HbA1c decreased by 0.21% and 0.28% with URLi and insulin lispro, respectively, with a least squares mean treatment difference of 0.07% (95% confidence interval -0.11 to 0.24; P = 0.467). URLi demonstrated smaller 1- and 2-hour PPG excursions at week 26 with least squares mean treatment differences of -1.0 mmol/L (-17.8 mg/dL) and -1.4 mmol/L (-25.5 mg/dL), respectively (p < 0.005 for both) versus insulin lispro. The safety profiles of URLi and insulin lispro were similar. CONCLUSIONS: In this study, URLi administered in a basal-bolus regimen demonstrated superiority to insulin lispro in controlling PPG excursions, with noninferiority of HbA1c control in predominantly Chinese patients with T1D.


Asunto(s)
Diabetes Mellitus Tipo 1 , Diabetes Mellitus Tipo 2 , Humanos , Insulina Lispro/uso terapéutico , Diabetes Mellitus Tipo 1/tratamiento farmacológico , Glucemia , Hipoglucemiantes/uso terapéutico , Hemoglobina Glucada , Estudios Prospectivos , Insulina Glargina , China , Insulina
5.
Ecotoxicol Environ Saf ; 268: 115732, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-38000301

RESUMEN

Glutathione plays a critical role in plant growth, development and response to stress. It is a major cellular antioxidant and is involved in the detoxification of xenobiotics in many organisms, including plants. However, the role of glutathione-dependent redox homeostasis and associated molecular mechanisms regulating the antioxidant system and pesticide metabolism remains unclear. In this study, endogenous glutathione levels were manipulated by pharmacological treatments with glutathione synthesis inhibitors and oxidized glutathione. The application of oxidized glutathione enriched the cellular oxidation state, reduced the activity and transcript levels of antioxidant enzymes, upregulated the expression level of nitric oxide and Ca2+ related genes and the content, and increased the residue of chlorothalonil in tomato leaves. Further experiments confirmed that glutathione-induced redox homeostasis is critical for the reduction of pesticide residues. RNA sequencing analysis revealed that miRNA156 and miRNA169 that target transcription factor SQUAMOSA-Promoter Binding Proteins (SBP) and NUCLEAR FACTOR Y (NFY) potentially participate in glutathione-mediated pesticide degradation in tomato plants. Our study provides important clues for further dissection of pesticide degradation mechanisms via miRNAs in plants.


Asunto(s)
Plaguicidas , Solanum lycopersicum , Antioxidantes/metabolismo , Solanum lycopersicum/genética , Disulfuro de Glutatión/metabolismo , Glutatión/metabolismo , Oxidación-Reducción , Plaguicidas/metabolismo , Plantas/metabolismo , Homeostasis , Estrés Oxidativo
6.
Materials (Basel) ; 16(9)2023 Apr 25.
Artículo en Inglés | MEDLINE | ID: mdl-37176254

RESUMEN

To obtain the magnesium oxychloride cement concrete (MOCC) ratio with excellent water resistance quickly and accurately, a BP neural network (BPNN) model with a topology structure of 4-10-2 was designed, and the PSO (particle swarm optimization), GWO (gray wolf optimization), and WOA (whale optimization algorithm) algorithms were used to optimize the model. The input layer parameters of the model above were n(MgO/MgCl2), Grade I fly ash, phosphoric acid (PA), and phosphate fertilizer (PF) content, and the output layer was the MOCC's compressive strength and softening coefficient. The model had a dataset of 144 groups, including 100 training set data, 22 verification set data, and 22 test set data. The results showed that the PSO-BPNN model had the highest predictive accuracy among the four models, with a mean R2 of 0.99, mean absolute error(MAE) of 0.52, mean absolute percentage error(MAPE) of 0.01, and root mean square error (RMSE) of 0.73 in predicting compressive strength, and a mean R2 of 0.99, MAE of 0.44, MAPE of 0.01, and RMSE of 0.62 in predicting the softening coefficient. The results showed that using the PSO-BPNN to predict the compressive strength and softening coefficient of MOCC is feasible and can provide theoretical guidance for designing the MOCC mix.

7.
BMC Womens Health ; 23(1): 111, 2023 03 18.
Artículo en Inglés | MEDLINE | ID: mdl-36934254

RESUMEN

BACKGROUND: Pituitrin injection solution is an indispensable hemostatic utilized in clinical practice and is widely used in myomectomy. However, there have been reports of adverse reactions leading to gastrointestinal injury, hyponatremia and hypokalemia, anaphylaxis, cardiac arrest, etc. Thus, the safety of pituitrin should be taken seriously. CASE PRESENTATION: In the present study, three cases of cardiac arrest caused by pituitrin injection during laparoscopic myomectomy, who were successfully resuscitated in our hospital, are reported. CONCLUSION: The clinical data and surgical procedures in the patient should be analyzed to find the causes of cardiac arrest. Medication and resuscitation should be summarized to ensure the safety of the patient.


Asunto(s)
Paro Cardíaco , Laparoscopía , Hormonas Neurohipofisarias , Miomectomía Uterina , Neoplasias Uterinas , Femenino , Humanos , Miomectomía Uterina/efectos adversos , Miomectomía Uterina/métodos , Paro Cardíaco/inducido químicamente , Inyecciones , Laparoscopía/efectos adversos , Laparoscopía/métodos , Neoplasias Uterinas/cirugía , Neoplasias Uterinas/etiología
8.
Medicine (Baltimore) ; 102(3): e32624, 2023 Jan 20.
Artículo en Inglés | MEDLINE | ID: mdl-36701737

RESUMEN

To analyze the clinical effect of standardized nursing for lymphoma patients and the influencing factors of nosocomial infection, a total of 360 diffuse large B-cell lymphoma patients with disease recurrence or progression after first-line treatment were retrospectively selected from our hospital from January 2021 to July 2022. After standardized nursing, the overall infection rate of lymphoma patients was 2.50% (9/360), which was significantly lower than the overall infection rate of our hospital in 2021 (7.44%, 844/11342) (P < .05). The proportion of 3 kinds of pathogenic bacteria detected were G+ bacteria (33.5%), G- bacteria (53.3%), and fungi (13.2%). The pathogenic bacteria genus with the most G+ bacteria is Enterococcus, the pathogenic bacteria genus with the most G+ bacteria is Enterobacteriaceae, and the pathogenic bacteria with the most fungi is Candida albicans. Female infection rate was significantly higher than male (P < .05). There was no significant difference in nosocomial infection among different marital status/fertility status (P > .05). The nosocomial infection of patients with different hospitalization times was statistically significant (P < .05). The duration of hospitalization in the infected group was significantly higher than that in the non-infected group (P < .05). The clinical effect of standardized nursing for lymphoma patients is significant, and the influencing factors of nosocomial infection include patient gender, hospitalization frequency, and hospitalization duration.


Asunto(s)
Infección Hospitalaria , Linfoma , Humanos , Masculino , Femenino , Infección Hospitalaria/epidemiología , Infección Hospitalaria/microbiología , Estudios Retrospectivos , Recurrencia Local de Neoplasia , Enterobacteriaceae , Bacterias
9.
Altern Ther Health Med ; 29(1): 124-129, 2023 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-35986739

RESUMEN

Context: Chronic obstructive pulmonary disease (COPD) is a common, chronic inflammatory disease of the airway, and acute exacerbation of COPD (AE-COPD) refers to the manifestations of inflammation in the lungs that appear within a short period of time. Some patients contract pneumonia, and they can be prone to recurrent attacks of AE-COPD combined with pneumonia. The efficacy of conventional treatments isn't generally satisfactory. Objective: The study intended to investigate the effectiveness and safety of piperacillin tazobactam in combination with the use of high-frequency chest-wall oscillation (HFCWO) to produce expectoration for the treatment of pneumonia in patients with AE-COPD and to provide a reference for clinical treatment. Design: The research team designed a prospective, randomized controlled trial. Setting: The study took place at the Sixth Hospital of Wuhan of the Affiliated Hospital of Jianghan University in Wuhan, China. Participants: Participants were 92 patients who had been admitted to the hospital between January 2020 and November 2021 with AE-COPD combined with pneumonia. Intervention: Using the random number table method, the research team randomly assigned participants to one of two groups, an intervention group or a control group, each with 46 participants. The control group received conventional treatment with oxygen, antibiotics, antispasmodics, antiasthmatic drugs, and phlegmolytic drugs as well as HFCWO for sputum removal. In addition to those treatments, the intervention group received piperacillin tazobactam. Outcome measures: The research team measured the treatment's efficacy at one day postintervention. At baseline and at one day postintervention, the study also measured pulmonary function, laboratory indexes, and blood-gas-analysis indexes. In addition, the research team identified the time of disappearance of clinical symptoms, including the disappearance of cough, sputum, dyspnea, and pulmonary rales; calculated the length of hospital stay, and evaluated the treatment's safety. Results: Postintervention, the intervention group's clinical efficacy was significantly higher than that of the control group (P < .05), and the group's cough, coughing of sputum, dyspnea, disappearance time of pulmonary rales, and hospitalization times were all significantly lower than those in the control group (P < .05). The FEV1, FVC, FEV1% and FEV1/FVC levels were higher in both groups postintervention than at baseline and were significantly higher in the intervention group than in the control group (P < .05). Postintervention, the levels of IL-2, IL-10, TNF-α, CRP and PCT were lower in both groups than at baseline, and the intervention group's levels were significantly lower than those in the control group (P < .05). Postintervention, the PaCO2 level decreased and PaO2 and SaO2 levels increased in both groups compared to baseline; the intervention group's PaCO2 level was lower and PaO2 and SaO2 levels were higher than those in the control group. During the treatment, no adverse reactions occurred in the control group, and one participant had a decreased appetite in the intervention group; the incidence of adverse reactions in that group was 2.17% (1/46). That participant received no special treatment, and the condition improved after stopping the drug. Conclusion: Piperacillin tazobactam combined with HFCWO for sputum evacuation can effectively treat patients with pneumonia in acute exacerbation of COPD, with high safety. The treatment is worthy of clinical application.


Asunto(s)
Oscilación de la Pared Torácica , Neumonía , Enfermedad Pulmonar Obstructiva Crónica , Humanos , Combinación Piperacilina y Tazobactam/uso terapéutico , Tos , Ruidos Respiratorios , Estudios Prospectivos , Enfermedad Pulmonar Obstructiva Crónica/tratamiento farmacológico , Disnea/terapia , Oxígeno/uso terapéutico
10.
Microbiol Spectr ; 10(4): e0022522, 2022 08 31.
Artículo en Inglés | MEDLINE | ID: mdl-35863021

RESUMEN

Scutellaria tsinyunensis is an endangered species in southwest China, distributed sporadically in mountainous areas at an elevation of approximately 200 to 900 m. Rhizosphere soil properties and fungal communities play critical roles in plant survival and expansion. Nevertheless, understanding of soil properties and fungal communities in the S. tsinyunensis distribution areas is extremely limited. The present study examined soil properties and fungal communities in nearly all extant S. tsinyunensis populations at two altitudinal gradients (low and high groups). Our findings indicated that soil characteristics (i.e., soil pH, water content, and available phosphorus) were affected distinctively by altitudes (P < 0.05). In addition, the low altitude group harbored higher fungal richness and diversity than the high altitude. Co-occurrence network analysis identified six key genera that proved densely connected interactions with many genera. Further analysis represented that the low altitude group harbored three beneficial genera belonging to Ascomycota (Archaeorhizomyces, Dactylella, and Helotiales), whereas the high altitude showed more pathogenic fungi (Apiosporaceae, Colletotrichum, and Fusarium). Correlation analysis found that soil water content was highly correlated with Hydnodontaceae and Lophiostoma. Besides, plants' canopy density was negatively correlated with four pathogenic fungi, indicating that the high abundance of the pathogen at high altitudes probably inhibited the survival of S. tsinyunensis. To sum up, this comprehensive analysis generates novel insights to explore the contrasting responses of S. tsinyunensis rhizosphere fungal communities and provides profound references for S. tsinyunensis habitat restoration and species conservation. IMPORTANCE Our study highlighted the importance of rhizosphere fungal communities in an endangered plant, S. tsinyunensis. Comparative analysis of soil samples in nearly all extant S. tsinyunensis populations identified that soil properties, especially soil water content, might play essential roles in the survival and expansion of S. tsinyunensis. Our findings proved that a series of fungal communities (e.g., Archaeorhizomyces, Dactylella, and Helotiales) could be essential indicators for S. tsinyunensis habitat restoration and protection for the first time. In addition, further functional and correlation analyses revealed that pathogenic fungi might limit the plant expansion into high altitudes. Collectively, our findings displayed a holistic picture of the rhizosphere microbiome and environmental factors associated with S. tsinyunensis.


Asunto(s)
Microbiota , Scutellaria , Biodiversidad , Hongos/fisiología , Plantas , Rizosfera , Suelo/química , Microbiología del Suelo , Agua
11.
Ecotoxicol Environ Saf ; 233: 113296, 2022 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-35158253

RESUMEN

Glutathione (GSH) biosynthesis and regeneration play a significant role in the metabolism of chlorothalonil (CHT) in tomatoes. However, the specific regulatory mechanism of GSH in the degradation of CHT remains uncertain. To address this, we investigate the critical regulatory pathways in the degradation of residual CHT in tomatoes. The results revealed that the detoxification of CHT residue in tomatoes was inhibited by buthionine sulfoximine and oxidized glutathione pretreatment, which increased by 26% and 46.12% compared with control, respectively. Gene silencing of γECS, GS, and GR also compromised the CHT detoxification potential of plants, which could be alleviated by GSH application and decreased the CHT accumulation by 33%, 25%, and 21%, respectively. Notably, it was found that the jasmonic acid (JA) pathway participated in the degradation of CHT regulated by GSH. CHT residues reduced by 28% after application of JA. JA played a role downstream of the glutathione pathway by promoting the degradation of CHT residue in tomatoes via nitric oxide signaling and improving the gene expression of antioxidant and detoxification-related enzymes. This study unveiled a crucial regulatory mechanism of GSH via the JA pathway in CHT degradation in tomatoes and offered new insights for understanding residual pesticide degradation.


Asunto(s)
Solanum lycopersicum , Ciclopentanos , Glutatión/metabolismo , Solanum lycopersicum/genética , Nitrilos , Oxilipinas/metabolismo
12.
Org Lett ; 24(9): 1859-1864, 2022 03 11.
Artículo en Inglés | MEDLINE | ID: mdl-35225627

RESUMEN

With control by N1-substituents, the switchable divergent C-H functionalization reaction of quinoxalin-2(1H)-ones is achieved for the synthesis of (Z)-enaminones and furo[2,3-b]quinoxalines using the combination of a copper catalyst and an oxidant. This new protocol features mild reaction conditions, readily available materials, and a broad substrate scope. Gram-scale and mechanistic studies were also investigated. Furthermore, the desired products exhibited excellent antitumor activity against A549, HepG-2, MCF-7, and HeLa cells, which were tested by MTT assay.


Asunto(s)
Alquinos , Quinoxalinas , Catálisis , Cobre , Células HeLa , Humanos , Estructura Molecular , Quinoxalinas/farmacología
13.
Community Dent Oral Epidemiol ; 50(2): 83-90, 2022 04.
Artículo en Inglés | MEDLINE | ID: mdl-33748987

RESUMEN

OBJECTIVES: Evidence on serum arsenic and oral cancer risk was limited. We aimed to evaluate the association between serum arsenic and the risk of oral cancer in a southeast China population. METHODS: Serum arsenic was determined for 325 oral cancer patients and 648 controls using inductively coupled plasma-mass spectrometry (ICP-MS). Logistic regression and restricted cubic spline were analysed the association between serum arsenic level and oral cancer risk, and crude and adjusted odds ratios (aOR) with 95% confidence interval (95% CI) were calculated. Factors adjusted for included age, gender, BMI, smoking, drinking, education, residence, marital status and dietary factors. Stratification analysis was further performed according to drinking, smoking and dietary characteristics. RESULTS: Serum arsenic level was lower in the case group (P50  = 19.2µg/L, IQR = 11.6 ~ 26.4µg/L) than in the control group (P50  = 30.2 µg/L, IQR = 25.0 ~ 36.4 µg/L). An inverse but nonlinear association was observed between arsenic level and oral cancer risk by restricted cubic spline. These with moderate serum arsenic levels had a lower risk of oral cancer than those with low levels (OR = 0.11; 95%CI: 0.07-0.18), after adjusting for demographic and dietary intake factors. We also kept serum arsenic as a continuous variable in a regression model, where a similar inverse association between arsenic and oral cancer was observed, with OR = 0.86 (95%CI: 0.84-0.88). Stratification analysis revealed no significant multiplicative interactions between serum arsenic and smoking, drinking or dietary intake. CONCLUSION: Serum arsenic is inversely related to oral cancer risk. Relative to those with low levels of arsenic, people with moderate serum arsenic levels had a lower risk of oral cancer. If confirmed, serum arsenic level may be a useful predictive marker for oral cancer risk.


Asunto(s)
Arsénico , Neoplasias de la Boca , Arsénico/efectos adversos , Arsénico/análisis , Estudios de Casos y Controles , China/epidemiología , Humanos , Neoplasias de la Boca/epidemiología , Neoplasias de la Boca/etiología , Oportunidad Relativa
14.
Front Pharmacol ; 12: 770073, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34744750

RESUMEN

SHR-1222 is a humanized monoclonal antibody targeting sclerostin and has the potential to promote bone formation and reduce bone resorption. This study was aimed to assess the safety, tolerability, pharmacokinetics, pharmacodynamics, and immunogenicity of SHR-1222 in healthy men and postmenopausal women with low bone mass (BMD). It was a randomized, double-blind, placebo-controlled, dose-escalation, phase I study. Subjects received SHR-1222 at 50, 100, 200, 300, and 400 mg sequentially or matching placebo subcutaneously. Totally, 50 subjects with low BMD were enrolled and randomly assigned; 10 received placebo and 40 received SHR-1222 (50 mg, n = 4; 100, 200, 300, or 400 mg, n = 9). The most common adverse events that occurred at least 10% higher in subjects with SHR-1222 treatment than those with placebo were decreased blood calcium, blood urine present, increased blood cholesterol, electrocardiogram T wave abnormal, urinary tract infection, increased blood pressure diastolic, and positive bacterial test. All the above adverse events were mild in severity and well resolved except one of increased blood cholesterol in a subject lost to follow-up. The serum SHR-1222 concentration increased in a dose-dependent manner. Administration of SHR-1222 upregulated the bone-formation markers N-terminal propeptide of type 1 procollagen, osteocalcin, and bone-specific alkaline phosphatase, while downregulated the bone-resorption marker ß-C-telopeptide. The BMD at the lumbar spine notably rose after a single dose of SHR-1222. The largest increase occurred in the 400 mg cohort (3.8, 6.7, and 6.1% on day 29, 57, and 85, respectively; compared with 1.4, 0.8, and 1.0% in the placebo group). Although 10.0% of subjects receiving SHR-1222 tested positive for anti-SHR-1222 antibodies, no obvious effects of antibody formation were found on pharmacokinetics. Overall, SHR-1222 was well tolerated at doses from 50 to 400 mg and is a promising new remedy for osteoporosis. Clinical Trial Registration: http://www.clinicaltrials.gov, NCT03870100.

15.
Exp Ther Med ; 22(5): 1258, 2021 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-34603526

RESUMEN

[This retracts the article DOI: 10.3892/etm.2017.5356.].

16.
Exp Ther Med ; 22(5): 1311, 2021 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-34630665

RESUMEN

The present study was conducted in order to study the detailed molecular mechanism of tumor necrosis factor (TNF)-α in chronic obstructive pulmonary disease (COPD). The rats were treated with cigarette smoke (CS) and lipopolysaccharide (LPS) to establish the COPD model. Next, the changes in lung injury in COPD rats with TNF-α knockdown was tested. Meanwhile, the regulation of TNF-α on MAPK pathway and its downstream molecules (SOCS3/TRAF1) was determined by western blotting. On this basis, the activation of MAPK and inhibition of SOCS3/TRAF1 was also examined. Subsequently, the lung function was tested with the plethysmograph, the cells of bronchoalveolar lavage fluid was counted and classified. Furthermore, lung tissue sections were stained with hematoxylin and eosin to verify whether the treatment of MAPK pathway and downstream molecules affected the effect of TNF-α knockdown on COPD. The present study showed that TNF-α knockdown could alleviate the decrease in the function and inflammatory injury of the lungs of rats with COPD. Western blot analysis verified that TNF-α knockdown could inhibit the activation of MAPK pathway and increase the expression of SOCS3/TRAF1. The following experimental results showed that the relief of lung injury caused by TNF-α knockdown could be deteriorated by activating MAPK pathway. It was also found that the symptom of COPD was decreased following transfection with sh-TNF-α but worsened by SOCS3/TRAF1 knockdown. Overall, TNF-α knockdown inhibited the activation of MAPK pathway and increased the expression of SOCS3/TRAF1, thus delaying the process of COPD.

17.
Exp Ther Med ; 22(4): 1168, 2021 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-34504613

RESUMEN

[This retracts the article DOI: 10.3892/etm.2017.4435.].

18.
Ultrasonics ; 115: 106460, 2021 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-34029835

RESUMEN

With the development of fifth-generation wireless systems, the Internet of Things, and health services, surface acoustic wave (SAW)-based filters and sensors have attracted considerable interest. This study presents a new structure for high-frequency, large-coupling, and low-cost SAW devices that helps implement high-frequency and wideband filters and enhances the sensitivity of sensors. The structure is based on 15°Y-X LiNbO3, thin SiOx/SiNx bilayer overlay, and Al electrodes. Furthermore, a low-cost fabrication process for SAW devices based on this structure was designed. Simulation and experimental results show that the bilayer substantially weakens the leaky nature of shear-horizontal-type SAWs with a phase velocity higher than that of a slow-shear bulk wave in LiNbO3. Thus, the limitation related to the velocity of 4029 m/s was overcome, and the phase velocity reached approximately 4500 m/s, which means an increase of 50% compared with that of conventional Cu/15°Y-X LiNbO3 devices. Consequently, the frequency dramatically increases, and the quality of the SAW response is ensured. Simultaneously, a large electromechanical coupling factor close to 20% can be achieved, which is still suitable for wideband filters and sensors with high energy transduction coefficients. This new structure is expected to become a major candidate for SAW devices in the future.

19.
Epilepsy Behav ; 117: 107843, 2021 04.
Artículo en Inglés | MEDLINE | ID: mdl-33640565

RESUMEN

PURPOSE: To evaluate the correlation between clinical spectrum and therapeutic outcomes and neuropsychological deficits in children with status epilepticus during sleep (SES). METHODS: The clinical spectrum of patients with SES was defined as follows: status epilepticus of benign childhood epilepsy with centro-temporal spikes (SEBECTs), atypical benign focal epilepsy during childhood (ABFEC), non-idiopathic focal epilepsy (NIFE), and Landau-Kleffner syndrome (LKS). SES cases were divided into 4 groups according to neuropsychological findings before treatment: developmental delay/intellectual disability (DD/ID), cognitive impairment (CI), attention deficit and/or hyperactivity behaviors (AHD), and normal group (NG). The therapeutic outcomes were classified into 3 groups: satisfactory response, recurrence, and seizure control. RESULTS: A total of 39 cases (24 males and 15 females) were recruited, including 3 cases with SEBECTs, 26 with ABFEC, 8 with NIFE [2 with focal cortical dysplasia (FCD)], and 2 with LKS. There were 7 patients in the DD/ID group, 8 in the CI group, 19 in the AHD group, and 5 in the NG group. Neuropsychological outcomes were significantly different among clinical spectrum (P < 0.001), and neuropsychological deficits frequently occurred in the ABFEC group or in the NIFE group. Besides, 18 patients in the satisfactory group had satisfactory response to medicine or surgery (2 out of 18 cases with FCD), whereas recurrence was observed at least one session within one year in 16 cases in the recurrence group, and no improvement in spike-wave index and cognition/behavior was noted in 5 patients in the seizure control group, although seizure could be controlled. There were significant differences in therapeutic outcomes among clinical spectrum (P = 0.041), with the worst outcomes in the NIFE group (only 1 out of 8 with satisfactory good response). CONCLUSIONS: It is important to categorize patients with SES into epilepsy syndromes, including SEBECTs, ABFPEC, NIFE, and LKS; the clinical spectrum may be a significant determinant to influence the outcomes of SES, including neuropsychological deficits and therapeutic outcomes.


Asunto(s)
Síndrome de Landau-Kleffner , Estado Epiléptico , Niño , Electroencefalografía , Femenino , Estudios de Seguimiento , Humanos , Masculino , Sueño , Estado Epiléptico/complicaciones
20.
Arch. bronconeumol. (Ed. impr.) ; 56(11): 697-703, nov. 2020. graf, tab
Artículo en Inglés | IBECS | ID: ibc-198925

RESUMEN

INTRODUCTION: Cytochrome P450 (CYP) 2J2 is a major enzyme that controls epoxyeicosatrienoic acids biosynthesis, which may play a role in chronic obstructive pulmonary disease (COPD) development. In this study, we aimed to assess the influence of CYP2J2 polymorphisms with COPD susceptibility. MATERIAL AND METHODS: A case-control study enrolled 313 COPD cases and 508 controls was to investigate the association between CYP2J2 polymorphisms and COPD risk. Agena MassARRAY platform was used to genotype CYP2J2 polymorphisms. Odds ratios (OR) and 95% confidence intervals (CI) were calculated to evaluate the association between CYP2J2 polymorphisms and COPD risk. RESULTS: We observed rs11207535 (homozygote: OR = 0.08, 95%CI = 0.01-0.96, p = 0.047; recessive: OR = 0.08, 95%CI = 0.01-0.94, p = 0.044), rs10889159 (homozygote: OR = 0.08, 95%CI = 0.01-0.92, p = 0.043; recessive: OR = 0.08, 95%CI = 0.01-0.90, p = 0.040) and rs1155002 (heterozygote: OR = 1.63, 95%CI = 1.13-2.36, p = 0.009; dominant: OR = 1.64, 95%CI = 1.15-2.35, p = 0.006; additive: OR = 1.45, 95%CI = 1.09-1.92, p = 0.011) were significantly associated with COPD risk. Allelic tests showed T allele of rs2280274 was related to a decreased risk of COPD and T allele of rs1155002 was associated with an increased COPD risk. Stratified analyses indicated the effects of CYP2J2 polymorphisms and COPD risk were dependent on gender and smoking status (p < 0.05). Additionally, two haplotypes (Ars11207535Crs10889159Trs1155002 and Ars11207535Crs10889159Crs1155002) significantly decreased COPD risk. CONCLUSION: It suggested CYP2J2 polymorphisms were associated with COPD susceptibility in the Chinese Han population


INTRODUCCIÓN: El citocromo P450 (CYP) 2J2 es una enzima importante que controla la biosíntesis de los ácidos epoxieicosatrienoicos, y que podría desempeñar un papel en el desarrollo de la enfermedad pulmonar obstructiva crónica (EPOC). En este estudio, nuestro objetivo fue evaluar la influencia de los polimorfismos de CYP2J2 en la susceptibilidad a la EPOC. MATERIALES Y MÉTODOS: Se realizó un estudio de casos y controles que incluyó 313 casos de EPOC y 508 controles para investigar la asociación entre los polimorfismos de CYP2J2 y el riesgo de desarrollar EPOC. Se utilizó la plataforma Agena MassARRAY para genotipar los polimorfismos de CYP2J2. Se calcularon los odds ratio (OR) con unos intervalos de confianza (IC) del 95% para valorar la asociación entre los polimorfismos de CYP2J2 y el riesgo de la EPOC. RESULTADOS: Observamos que rs11207535 (homocigoto: OR: 0,08, IC 95%: 0,01-0,96; p = 0,047; recesivo: OR: 0,08; IC 95%: 0,01-0,94; p = 0,044), rs10889159 (homocigoto: OR: 0,08, IC 95%: 0,01-0,92; p = 0,043; recesivo: OR: 0,08, IC 95%: 0,01-0,90; p = 0,040) y rs1155002 (heterocigoto: OR: 1,63, IC 95%: 1,13-2,36; p = 0,009; dominante: OR: 1,64, IC 95%: 1,15-2,35; p = 0,006; aditivo: OR: 1,45, IC 95%: 1,09-1,92; p = 0,011) se asociaron significativamente con el riesgo de EPOC. Las pruebas alélicas mostraron que el alelo T de rs2280274 estaba relacionado con una disminución del riesgo de EPOC y el alelo T de rs1155002 se asoció con un mayor riesgo de EPOC. Los análisis estratificados indicaron que los efectos de los polimorfismos de CYP2J2 y el riesgo de EPOC dependían del sexo y del tabaquismo (p < 0,05). Además, 2 haplotipos (Ars11207535Crs10889159Trs1155002 y Ars11207535Crs10889159Crs1155002) reducían significativamente el riesgo de la EPOC. CONCLUSIÓN: El estudio sugirió que los polimorfismos de CYP2J2 se asociaban con la susceptibilidad a la EPOC en la población Han China


Asunto(s)
Humanos , Masculino , Femenino , Persona de Mediana Edad , Anciano , Anciano de 80 o más Años , Enfermedad Pulmonar Obstructiva Crónica/etnología , Enfermedad Pulmonar Obstructiva Crónica/genética , Polimorfismo de Nucleótido Simple , Sistema Enzimático del Citocromo P-450/genética , Estudios de Casos y Controles , Predisposición Genética a la Enfermedad , Factores de Riesgo , Técnicas de Genotipaje , Factores Sexuales , China , Pueblo Asiatico/genética
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