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1.
Front Cardiovasc Med ; 9: 837142, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35498024

RESUMO

Intrauterine hypoxia is a common complication during pregnancy and could increase the risk of cardiovascular disease in offspring. However, the underlying mechanism is controversial. Memantine, an NMDA receptor antagonist, is reported to be a potential cardio-protective agent. We hypothesized that antenatal memantine treatment could prevent heart injury in neonatal offspring exposed to intrauterine hypoxia. Pregnant rats were exposed to gestational hypoxia or antenatal memantine treatment during late pregnancy. Newborns were then sacrificed to assess multiple parameters. The results revealed that Intrauterine hypoxia resulted in declining birth weight, heart weight, and an abnormally high heart weight/birth weight ratio. Furthermore, intrauterine hypoxia caused mitochondrial structural, functional abnormalities and decreased expression of DRP1, and upregulation of NMDAR1 in vivo. Antenatal memantine treatment,an NMDARs antagonist, improved these changes. In vitro, hypoxia increased the glutamate concentration and expression of NMDAR1. NMDAR activation may lead to similar changes in mitochondrial function, structure, and downregulation of DRP1 in vitro. Pharmacological blockade of NMDARs by the non-competitive NMDA antagonist MK-801 or knockdown of the glutamate receptor NR1 significantly attenuated the increased mitochondrial reactive oxygen species and calcium overload-induced by hypoxia exposure. These facts suggest that memantine could provide a novel and promising treatment for clinical use in intrauterine hypoxia during pregnancy to protect the cardiac mitochondrial function in the offspring. To our best knowledge, our research is the first study that shows intrauterine hypoxia can excessively activate cardiac NMDARs and thus cause mitochondrial dysfunction.

2.
Ital J Pediatr ; 48(1): 64, 2022 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-35505407

RESUMO

BACKGROUND: In recent years, reports of refractory Mycoplasma pneumoniae pneumonia (RMPP) have gradually increased, including reports on how these conditions threaten the lives of children. However, the specific mechanism of Mycoplasma pneumoniae pneumonia (MPP) remains unclear. This study aimed to investigate the relationship between community-acquired respiratory distress syndrome toxin (CARDS TX) and High-mobility group box protein 1-Toll-like receptors-Myeloid differentiation factor 88 (HMGB1-TLRs-MyD88) in MPP and to examine the immune pathogenesis of Mycoplasma pneumoniae infection. METHODS: Children who were diagnosed with MPP and examined by bronchoscopy were included in the MPP group. Additionally, children who underwent bronchoscopy because of bronchial foreign bodies in the same period were included in the control group. Gene expression of CARDS TX, HMGB1, Toll-like receptor 2 (TLR2), Toll-like receptor 4 (TLR4), MyD88, and cluster of differentiation 14 (CD14) in bronchoalveolar lavage fluid (BALF) were detected using real-time reverse transcription-polymerase chain reaction. Correlations between CARDS TX and HMGB1-TLRs-MyD88 were analyzed. RESULTS: CARDS TX, HMGB1, TLR2, MyD88, and CD14 mRNA expression in BALF in the MPP group was significantly higher than that in the control group (all P < 0.05). CARDS TX mRNA expression was positively correlated with HMGB1, TLR2, MyD88, and CD14 mRNA expression (all P < 0.05). Furthermore, HMGB1 mRNA expression was positively correlated with TLR2, MyD88, and CD14 mRNA expression (all P < 0.05). CONCLUSIONS: CARDS TX may participate in the immune pathogenesis of MPP through the HMGB1-TLRs/CD14-MyD88 pathway.


Assuntos
Proteína HMGB1 , Pneumonia por Mycoplasma , Síndrome do Desconforto Respiratório , Criança , Proteína HMGB1/genética , Proteína HMGB1/metabolismo , Humanos , Mycoplasma pneumoniae , Fator 88 de Diferenciação Mieloide/genética , Fator 88 de Diferenciação Mieloide/metabolismo , Pneumonia por Mycoplasma/diagnóstico , RNA Mensageiro/metabolismo , Transdução de Sinais , Receptor 2 Toll-Like/genética , Receptor 2 Toll-Like/metabolismo , Receptores Toll-Like/genética , Receptores Toll-Like/metabolismo
3.
Am J Nucl Med Mol Imaging ; 12(2): 54-62, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35535119

RESUMO

Positron emission tomography (PET) can accurately locate and quantify radioactivity over traditional single photon emission computed tomography (SPECT), encouraging its application in kidney function evaluation and glomerular filtration rate (GFR) measurement. 68Ga-ethylenediamine-tetraacetic acid (68Ga-EDTA) is a novel PET tracer for renal scan but a mature GFR calculation method still pending establishment. Herein, we aim to investigate the imaging performance of 68Ga-EDTA dynamic PET in healthy C57BL/6 mice, establish quantitative methods to calculate GFR, and evaluate its feasibility in mice with kidney dysfunction. Dynamic PET of 68Ga-EDTA successfully visualized the whole process of tracer elimination. GFR values were measured by the integral method (253.80±40.11 µL/min) and the Patlak Plot method (22.69±9.75 µL/min), while blood clearance rate of the tracer was found at 787.46±70.86 µL/min. The PET-based GFR values correlate well with the GFRblood (R2=0.7468, R2=0.8793). The Integral method provides better accuracy than Patlak Plot method. Further application of GFR measurement in kidney-diseased mice proves better performance of the Integral method for defining split renal function.

4.
Front Immunol ; 13: 884373, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35572560

RESUMO

Background: Gastric cancer (GC) is the third leading cause of cancer-associated deaths worldwide. Stromal cells, especially mesenchymal stem cells (MSCs), play significant roles in the development of therapy resistance depending on their paracrine function. The PD-1/PD-L1 crosstalk between cancer and immune cells has been well studied. Emerging evidence suggests that PD-L1 also contributes to tumor resistance to therapy. Methods: Cell survival and apoptosis were assessed using CCK-8, colony formation, and flow cytometry assays. Protein alterations were analyzed via Western blot. Gene knockdown and overexpression were achieved with siRNA/shRNA and lentiviral infection, respectively. Drug effects on tumors in vivo were assessed with xenografts in nude mice. In addition, GC patient samples after chemotherapy treatment were collected to observe the relationship between chemotherapy effect and CTCF or PD-L1. Results: In response to 5-fluorouracil or paclitaxel treatment, GCMSC-CM enhanced the cell viability and decreased the apoptosis rate. Furthermore, blocking PD-L1 or CTCF in GC cells prevented GCMSC-induced drug resistance accompanied by a decline in cell stemness. Consistent with these in vitro observations, mice treated with GCMSC-CM showed a lower sensitivity to 5-fluorouracil. In addition, high expression of CTCF and PD-L1 was associated with poor chemotherapy progression in the clinic. Conclusion: Study results demonstrate a mechanism where GCMSC-CM promotes GC chemoresistance by upregulating CTCF-PD-L1 and provide strong evidence in support of targeting CTCF-PD-L1 signaling as a strategy to prevent resistance in the clinic.

5.
J Informetr ; 16(2): 101295, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35529705

RESUMO

Based on publication data on coronavirus-related fields, this study applies a difference in differences approach to explore the evolution of gender inequalities before and during the COVID-19 pandemic by comparing the differences in the numbers and shares of authorships, leadership in publications, gender composition of collaboration, and scientific impacts. We find that, during the pandemic: (1) females' leadership in publications as the first author was negatively affected; (2) although both females and males published more papers relative to the pre-pandemic period, the gender gaps in the share of authorships have been strengthened due to the larger increase in males' authorships; (3) the share of publications by mixed-gender collaboration declined; (4) papers by teams in which females play a key role were less cited in the pre-pandemic period, and this citation disadvantage was exacerbated during the pandemic; and (5) gender inequalities regarding authorships and collaboration were enhanced in the initial stage of COVID-19, widened with the increasing severity of COVID-19, and returned to the pre-pandemic level in September 2020. This study shows that females' lower participation in teams as major contributors and less collaboration with their male colleagues also reflect their underrepresentation in science in the pandemic period. This investigation significantly deepens our understanding of how the pandemic influenced academia, based on which science policies and gender policy changes are proposed to mitigate the gender gaps.

6.
Zhong Nan Da Xue Xue Bao Yi Xue Ban ; 47(3): 396-400, 2022 Mar 28.
Artigo em Inglês, Chinês | MEDLINE | ID: mdl-35545334

RESUMO

Brain-lung-thyroid syndrome is a rare autosomal dominant disorder. More than 100 cases have been reported worldwide, but few cases have been reported in China. In December 2018, a boy with brain-lung-thyroid syndrome, aged 3 years and 10 months, was admitted to Xiangya Hospital of Central South University due to repeated cough for more than 3 years. In infancy of the boy, psychomotor retardation, repeated cough, and hypothyroidism were found. Gene detection showed that there was c.927delc heterozygous variation in NKX2-1 gene (NM-001079668: exon3: c.927delC). The variation of this gene locus has not been reported in relevant literature so far, which indicates a new mutation. According to the above clinical manifestations and examination results, the boy was diagnosed as brain-lung-thyroid syndrome, which mainly characterized by nervous system disorders, accompanied by respiratory manifestations and hypothyroidism. The boy was treated with oral dopasehydrazine to relieve tremor and levothyroxine sodium tablets to relieve hypothyroidism. Anti-infection, atomization, rehabilitation training and other symptomatic supporting treatment were also administered. The boy's language and movement have improved, the thyroid hormone level is normal, and there are still repeated respiratory tract infections.


Assuntos
Hipotireoidismo Congênito , Tosse , Atetose/genética , Coreia , Hipotireoidismo Congênito/diagnóstico , Hipotireoidismo Congênito/genética , Humanos , Masculino , Síndrome do Desconforto Respiratório do Recém-Nascido , Fator Nuclear 1 de Tireoide/genética
7.
Artigo em Inglês | MEDLINE | ID: mdl-35432560

RESUMO

Objective: To systematically assess the clinical efficacy of the Jie Yu Wan (JYW) formula in treating generalized anxiety disorder (GAD). Methods: A multicenter, prospective, double-blind, double-dummy, randomized controlled trial (RCT) was conducted at four hospitals in China. A total of one hundred thirty-three patients with GAD were enrolled from 2017 to 2019. This study aimed to evaluate the effects of a Traditional Chinese Medicine (TCM) JYW formula on GAD at eight weeks, with the use of Buspirone as the comparator. A stepwise dosing protocol was used (JYW: high dose 24 g/day, low dose 12 g/day; Buspirone: high dose 30 mg/day, low dose 15 mg/day) and the dose was adjusted depending on whether the treatment response of Hamilton Anxiety Scale (HAMA) score was less than or equal to 25% after one week. The primary outcome was a change in total score on the HAMA. The secondary outcomes included the Hamilton Depression Scale (HAMD), Clinical Global Impression (CGI) scale, and TCM Syndrome Scale. Adverse events were recorded using the Treatment Emergent Symptom Scale (TESS). Assessments were conducted at the baseline and 1, 2, 4, and 8 weeks. Results: A total of one hundred thirty-three participants were randomly assigned to the JYW group (n = 66) and the Buspirone group (n = 67). One hundred twenty-one patients (91%) completed at least one follow-up session. There were no significant differences between the two groups in terms of gender, age, disease course, HAMA, HAMD, CGI, and TCM Syndrome Scale scores at baseline (all P > 0.05). Repeated-measures analysis of variance revealed statistically significant time effects for the HAMA (P=0.002), HAMD (P = 0.018), and CGI (P=0.001) in both groups. Sensitivity analyses supported the credibility of the main results (P > 0.05). The group effect was not significant for the HAMA (P=0.43), HAMD (P=0.27), CGI (P=0.37), and TCM Syndrome Scale (P=0.86). Furthermore, there were no significant interaction effects between time and group in terms of the HAMA (P=0.47), HAMD (P=0.79), CGI (P=0.67), and TCM Syndrome Scale (P=0.69). After one week, 53 patients (80%) of the JYW group and 52 patients (78%) of the Buspirone group were adjusted to high doses. The interaction effect between time, group, and the dose was determined by repeated measures ANOVA test, and the HAMA score served as the outcome measure. The interaction effect between time and dose was statistically significant (P=0.04), which shows that high-dose JYW (24 g/day) was more effective in decreasing patients' HAMA scores than low-dose JYW (12 g/day), and Buspirone had the same effect, which means that high-dose Buspirone (30 mg/day) was more effective than low dose. (15 mg/day). Conclusions: The conclusion of this study supports that JYW and Buspirone can effectively alleviate the anxiety symptoms of GAD patients, which are both effective and safe for treatment of mild to moderate GAD. Besides, high-dose JYW or Buspirone are more effective than low-dose, which is of great importance in assisting clinical medication choice.

8.
Artigo em Inglês | MEDLINE | ID: mdl-35429285

RESUMO

BACKGROUND AND OBJECTIVE: 101BHG-D01 nasal spray is the first novel long-acting cholinergic M receptor antagonist under development to treat rhinorrhea in rhinitis. This first-in-human study aimed to evaluate the safety, tolerability, and pharmacokinetics of 101BHG-D01 nasal spray following single intranasal doses in healthy Chinese subjects. METHODS: A randomized, double-blind, placebo-controlled, single-dose escalation study was conducted in healthy Chinese volunteers after intranasal doses of 101BHG-D01 nasal spray or placebo ranging from 40 µg to 960 µg (total of six doses). Blood samples were collected at scheduled time points, and plasma concentrations were determined using a validated high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method. A non-compartmental method was used to calculate the main pharmacokinetic parameters, including the area under the plasma concentration-time curve from time zero to the time of the last measurable concentration (AUC0-t), the area under the plasma concentration-time curve from time zero to infinity (AUC0-∞), the maximum plasma concentration (Cmax), the time to maximum plasma concentration (Tmax), and the elimination half-life (t1/2). Safety was evaluated by monitoring adverse events, laboratory assays, vital signs, physical examinations, 12-lead electrocardiograms (ECGs), anterior rhinoscopy, ophthalmic examination, and ambulatory ECG monitoring. RESULTS: Following single intranasal dosing, 101BHG-D01 was rapidly absorbed with a median Tmax of 0.34-0.50 h and eliminated slowly with a mean t1/2 ranging from 4.29 to 46.76 h for different dose groups. The Cmax and AUC of 101BHG-D01 increased linearly across the examined dose range of 40-960 µg. 101BHG-D01 nasal spray was well tolerated, all AEs were mild, and no serious adverse events occurred during the study. CONCLUSIONS: 101BHG-D01 nasal spray was safe and well tolerated in healthy Chinese subjects when administered intranasally in single escalating doses. The mean Cmax and AUC increased proportionally to the studied dose. The pharmacokinetic, safety, and tolerability profiles of 101BHG-D01 nasal spray indicate that it is a good candidate for further development as a treatment for rhinorrhea in rhinitis.

9.
Gland Surg ; 11(3): 535-544, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35402212

RESUMO

Background: Hürthle cell carcinoma is a rare subtype of thyroid cancer, and its clinical behavior and biological characteristics remain unclear. This study aimed to establish nomogram models for the prognostic evaluation of Hürthle cell thyroid carcinoma (HCTC) in terms of both cancer-specific survival (CSS) and overall survival (OS). Methods: Data for a total of 3,264 patients with HCTC (2004 to 2018) were extracted from the Surveillance, Epidemiology, and End Results (SEER) database. Univariate and multivariate Cox regression analysis was performed to identify significant predictors of prognosis and develop a prognostic nomogram. The performance of the model was assessed based on the area under the receiver operating characteristic curve (AUC), concordance index (c-index), and calibration curves. Results: Multivariate Cox regression analysis showed that age, sex, summary stage, tumor size, N stage, M stage, and treatment with thyroidectomy were independent predictors of OS. Moreover, age, summary stage, tumor size, N stage, M stage, AJCC stage, and treatment with thyroidectomy were significantly correlated with CSS. The c-index of the OS and CSS nomograms developed based on these factors was 0.822 (95% CI: 0.803-0.841) and 0.893 (95% CI: 0.866-0.920), respectively. The AUC was 0.888, 0.841, and 0.834 for 1-, 3-, and 5-year OS and 0.970, 0.949, and 0.933 for 1-, 3-, and 5-year CSS, respectively. The calibration curves showed good agreement between observed and predicted values. Moreover, decision curve analysis revealed that the nomogram had a better clinical utility than individual clinicopathological markers. Conclusions: A prognostic nomogram that allows the individualized assessment of OS and CSS in HCTC was developed. This nomogram could be used to guide treatment decisions in patients with HCTC.

10.
J Clin Pharm Ther ; 2022 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-35362180

RESUMO

WHAT IS KNOWN AND OBJECTIVE: Henagliflozin is a novel selective sodium-glucose co-transporter 2 (SGLT2) inhibitor with similar inhibitory effect to ertugliflozin. Glimepiride is widely used to treat type 2 diabetes mellitus (T2DM) with few cardiovascular side effects. In the present study, we aimed at evaluating the pharmacokinetic (PK) interactions between henagliflozin and glimepiride. METHODS: An open-label, single-centre, single-arm, 3-period, 3-treatment, self-control study was conducted in twelve healthy Chinese male subjects. During each study period, subjects received a single oral dose of glimepiride 2 mg, multiple oral doses of henagliflozin 10 mg or a combination of the two drugs. Serial blood samples were collected 24 h post-dosing for PK analyses. Finger-tip blood glucose was also tested for safety evaluation. RESULTS AND DISCUSSION: Co-administration of henagliflozin with glimepiride did not affect their plasma PK profiles. For henagliflozin, the 90% confidence intervals for the geometric mean ratio (GMR) for the maximum plasma concentrations at steady-state (Cmax ss ) and the area under the plasma concentration-time curve during a dosing interval at steady-state (AUCτ, ss ) of combination therapy to henagliflozin alone were 1.00 (0.93-1.08) and 1.00 (0.98-1.02), respectively. For glimepiride, the corresponding values of combination therapy to glimepiride alone were 1.00 (0.88-1.13) for maximum plasma concentrations (Cmax ), 0.91 (0.84-0.99) for the area under the plasma concentration-time curve from 0-24 h (AUC0-24h ) and 0.91 (0.83-1.00) for the plasma concentration-time curve from 0 h to infinite (AUC0-inf ), respectively. All values fell within the equivalence range of 0.8-1.25. All monotherapies and combination therapy led to no serious adverse events and were well tolerated. WHAT IS NEW AND CONCLUSION: Multiple doses of henagliflozin did not exert a significant change on glimepiride PK profiles and a single dose of glimepiride had little effect on henagliflozin blood concentration. Thus, henagliflozin can be co-administered with glimepiride without dose adjustment of either drug.

11.
PNAS Nexus ; 1(1): pgab003, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35360552

RESUMO

Age-related macular degeneration (AMD) is the principal cause of blindness in developed countries, and its prevalence will increase to 288 million people in 2040. Therefore, automated grading and prediction methods can be highly beneficial for recognizing susceptible subjects to late-AMD and enabling clinicians to start preventive actions for them. Clinically, AMD severity is quantified by Color Fundus Photographs (CFP) of the retina, and many machine-learning-based methods are proposed for grading AMD severity. However, few models were developed to predict the longitudinal progression status, i.e. predicting future late-AMD risk based on the current CFP, which is more clinically interesting. In this paper, we propose a new deep-learning-based classification model (LONGL-Net) that can simultaneously grade the current CFP and predict the longitudinal outcome, i.e. whether the subject will be in late-AMD in the future time-point. We design a new temporal-correlation-structure-guided Generative Adversarial Network model that learns the interrelations of temporal changes in CFPs in consecutive time-points and provides interpretability for the classifier's decisions by forecasting AMD symptoms in the future CFPs. We used about 30,000 CFP images from 4,628 participants in the Age-Related Eye Disease Study. Our classifier showed average 0.905 (95% CI: 0.886-0.922) AUC and 0.762 (95% CI: 0.733-0.792) accuracy on the 3-class classification problem of simultaneously grading current time-point's AMD condition and predicting late AMD progression of subjects in the future time-point. We further validated our model on the UK Biobank dataset, where our model showed average 0.905 accuracy and 0.797 sensitivity in grading 300 CFP images.

12.
ACS Omega ; 7(13): 11166-11176, 2022 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-35415320

RESUMO

Sho-saiko-to is a well-known traditional Chinese medicine compound and is considered to have therapeutic effects against many diseases, including thyroid cancer (TC). However, the mechanisms and therapeutic targets of Sho-saiko-to against TC remain unclear. In this study, network pharmacology, molecular docking, and cell experiments were combined to predict and verify the targets and mechanisms of the active ingredients of Sho-saiko-to against TC. The results demonstrated that the main chemical ingredients of Sho-saiko-to could suppress the viability and proliferation of TC cells, promote apoptosis through the caspase3 pathway, and induce autophagy through the PI3K-AKT pathway. In addition, Sho-saiko-to could also induce the redifferentiation of anaplastic thyroid cancer. Our study provides a novel approach for treating differentiated thyroid cancer (DTC) or radioactive iodine refractory differentiated thyroid cancer (RAIR-DTC).

13.
Artigo em Inglês | MEDLINE | ID: mdl-35419986

RESUMO

This study aimed to compare the pharmacokinetics, safety, and immunogenicity of the prefilled syringe (PFS) with lyophilized (LYO) recombinant human tumor necrosis factor-α receptor II:lgG Fc fusion protein (rhTNFR:Fc) in healthy Chinese male subjects. A single-center, randomized, open-label, 2-period, crossover study was performed in healthy Chinese male subjects. Subjects were randomly assigned into 2 sequences and received a subcutaneous injection of 25 mg rhTNFR:Fc PFS or rhTNFR:Fc LYO (Anbainuo), with a 35-day washout between the 2 periods. Blood samples were collected at specified time intervals, and then serum concentrations of rhTNFR:Fc were analyzed by enzyme-linked immunosorbent assay. The maximum serum concentration, area under the concentration-time curve (AUC) from time 0 to the last quantifiable concentration, and AUC from time 0 to infinity were all calculated and evaluated. Meanwhile, safety and immunogenicity were also assessed. A total of 82 subjects completed the study, and six subjects withdrew for various reasons. The 90%CIs for geometric mean ratios of maximum serum concentration, AUC from time 0 to the last quantifiable concentration, and AUC from time 0 to infinity were all within the equivalence range of 80% to 125%. Safety was comparable between the 2 formulations with low immunogenicity. rhTNFR:Fc PFS exhibited similar pharmacokinetic and safety profiles of rhTNFR:Fc LYO (Anbainuo) in healthy Chinese male subjects.

14.
Lupus ; 31(7): 837-847, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35446734

RESUMO

Renal injury in lupus nephritis (LN) does not manifest as one uniform entity. The clinical presentation, management, and prognosis of membranous LN (MLN) differ from that of the proliferative LN (PLN). Differentiating the molecular mechanisms involved in MLN and PLN and discovering the reliable biomarkers for early diagnosis and target therapy are important. We compared the kidney protein expression patterns of 11 pure MLN and 12 pure PLN patients on formalin-fixed paraffin-embedded (FFPE) kidney tissues using label-free liquid chromatography-mass spectrometry (LC-MS) for quantitative proteomics analysis. FunRich software was used to identify proteins in differentially expressed pathways. Quantitative comparisons of differentially expressed proteins in each patient were further analyzed based on protein intensity levels determined by LC-MS. The protein-protein interaction (PPI) network of the differentially expressed genes (DEGs) was established through Search Tool for the Retrieval of Interacting Genes database (STRING) website, visualized by Cytoscape. A total of 5112 proteins were identified. In total, 12 significantly upregulated (fold change ≥2, p < 0.05) proteins were identified in the MLN group and 220 proteins (fold change ≥2, p < 0.05) were upregulated in the PLN group. Further analysis showed that the most significant upregulated pathway involved in MLN was histone deacetylase (HDAC) class I pathway, and the three most significant upregulated pathways in PLN were interferon signaling, interferon gamma signaling, and the immune system. Next, we selected sirtuin-2 (SIRT2) in MLN, and vascular cell adhesion protein 1 (VCAM1) and Bcl-xl in PLN for further mass spectrometry (MS) intensity and PPI analysis. SIRT2 expression was significantly increased in the MLN group compared with the PLN group, and VCAM1, Bcl-xl expression was significantly increased in the PLN group compared with the MLN group, based on MS intensity. These results may help to improve our understanding of the underlying molecular mechanisms of MLN and PLN and provide potential targets for the diagnosis and treatment of different subclasses of LN.

15.
Clin Transl Sci ; 2022 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-35235711

RESUMO

The aim of this study was to evaluate the relationship between polymorphisms in CYP2C19 and the single-dose pharmacokinetics (PKs) of omeprazole in healthy Chinese volunteers. A 20 mg single dose of omeprazole (Losec) enteric-coated capsules or tablets was orally administered to 656 healthy subjects from eight subcenters. The polymorphic alleles of CYP2C19*2, *3, and *17 were determined by Sanger sequencing and Agena mass array. Plasma concentrations of omeprazole were determined by high-performance liquid-chromatography tandem mass spectrometry. PK parameters of area under the concentration versus time curve (AUC)0-t , AUC from zero to infinity (AUC0-∞ ), maximum plasma concentration (Cmax ), and terminal half-life (t1/2 ) were significantly influenced by CYP2C19 phenotype (all p < 0.001) and diplotype (all p < 0.001), and the same results were obtained in the subgroup analysis of the effects of diet and dosage form. The polymorphisms of CYP2C19*2(rs4244285; all PK parameters p < 0.001) and *3(rs4986893; pCmax  = 0.020, and the p values of other PK parameters were less than 0.001) were significantly associated with the PKs of omeprazole. For CYP2C19*17 (rs12248560), only t1/2 showed a significant correlation (p = 0.032), whereas other PK parameters did not. The present study demonstrated that the Pks of omeprazole is greatly influenced by CYP2C19.

16.
Front Neurol ; 13: 778419, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35309563

RESUMO

Alzheimer's disease with psychosis (AD+P) is a heritable phenotypic variant of the disease which is associated with more rapid cognitive deterioration compared to Alzheimer's disease without psychosis (AD-P). Cognitive decline in AD correlates with synapse loss, and our previous studies suggest that those with AD+P have a differentially affected synaptic proteome relative to those with AD-P. In this study, we utilized RNA-sequencing of dorsolateral prefrontal cortex (DLPFC) in a cohort of 80 AD cases to evaluate novel transcriptomic signatures that may confer risk of psychosis in AD. We found that AD+P was associated with a 9% reduction in excitatory neuron proportion compared to AD-P [Mean (SD) AD+P 0.295 (0.061); AD-P 0.324 (0.052), p = 0.026]. mRNA levels contributed only modestly to altered synaptic proteins in AD+P relative to AD-P. Instead, network analysis identified altered expression of gene modules from protein ubiquitination, unfolded protein response, eukaryotic initiation factor 2 (EIF2) signaling and endoplasmic reticulum stress pathways in AD+P. We previously found that neuropathologies account for ~18% of the variance in the occurrence of psychosis in AD. Further inclusion of cell type proportions and differentially expressed modules increased the percent of the variance in psychosis occurrence accounted for in our AD cohort to 67.5%.

17.
Artigo em Inglês | MEDLINE | ID: mdl-35280510

RESUMO

Background: Previous studies have shown that electroacupuncture (EA) has a positive effect on motor and sensory function in patients with spinal cord injury (SCI). This review evaluated the effectiveness of EA for improvement in activities of daily living in patients with SCI. Methods: We searched the Cochrane Library, PubMed, Web of Science, CNKI, WanFang Data, and VIP databases using a search strategy according to the guidelines of the Cochrane Handbook for Systematic Review of Interventions up to 30th September 2020. Only randomized controlled trials (RCTs) of EA in patients with SCI were included. We analyzed the data using RevMan (version 5.3) and graded the quality of evidence using GRADE profiler 3.6.1. Results: This meta-analysis included 10 RCTs with 712 patients. Three studies revealed that the functional independence measure score for SCI patients in the EA group was higher than that in the control group (mean difference [MD] = 13.46, 95% CI: 8.00 to 18.92, P < 0.00001). Five studies showed that the modified Barthel index in the EA group was higher than that in the control group (MD = 6.92, 95% CI: 4.96 to 8.89, P < 0.00001). Five studies showed that the American Spinal Injury Association-motor score (ASIA-motor score) in the EA group was higher than that in the control group (standard MD = 0.96, 95% CI: 0.75 to 1.18, P < 0.00001). Three studies reported the ASIA-tactile and pain scores and also reported that the scores in the EA group were higher than those in the control group, with high homogeneity (tactile I2 = 86%, P = 0.0008; pain I2 = 54%, P = 0.11). The quality of evidence for the use of EA for improvement in motor and sensory function in SCIs was moderate according to the GRADE system. Conclusion: This review suggested that EA improves activities of daily living and motor function in patients with SCI, with a moderate level of evidence.

18.
Zhongguo Zhong Yao Za Zhi ; 47(4): 1085-1094, 2022 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-35285209

RESUMO

This study systematically searched CNKI and Web of Science(WoS) for the research papers on the toxicity of Tripterygium wilfordii included from database inception to August 31, 2021, and visually displayed the authors, research institutions, keywords, and other contents using bibliometrics and CiteSpace 5.8.3. Furthermore, the current situation and research progress on T. wilfordii safety were also analyzed based on information extraction to find the research hotspot, evolution path, and development trend, and to provide references for future research. A total of 1 876 Chinese papers and 243 English papers were included in the study. The analysis of authors showed that WANG Qi and ZHANG Luyong had the most publications in Chinese and English papers, respectively. According to the analysis of research institutions, National Institutes for Food and Drug Control and China Pharmaceutical University possessed the largest number of Chinese and English papers, respectively, but there was less cooperation between them. The analysis of keywords in Chinese and English papers showed that the research contents of the safety of T. wilfordii mainly focused on clinical monitoring, mechanism, dosage form improvement, quality standard, component analysis, monomer research, efficiency and toxicity reduction, etc. Metabonomics, tripterine, and the underlying mechanism of toxicity were the research hotspots in the future. At present, the research on the toxicity of T. wilfordii is still under development. It is necessary to highlight the in-depth research and strengthen the inter-group and inter-region cooperation of authors or institutions to provide references for the research on the toxicity of T. wilfordii.


Assuntos
Medicamentos de Ervas Chinesas , Tripterygium , Bibliometria , China , Medicamentos de Ervas Chinesas/toxicidade , Humanos
19.
Mol Ther ; 30(4): 1706-1720, 2022 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-35114391

RESUMO

Endometrial decidualization is a prerequisite for implantation, and impaired decidualization is associated with recurrent implantation failure (RIF). Coding genes of the HOX family have been clarified as critical regulators in endometrial decidualization, but the role of long non-coding RNAs (lncRNAs) in the HOX gene family has yet to be determined. The aim of this study was to clarify the possible roles of lncRNAs in the HOX gene family in decidualization. In this study, we identified that HOXA11-AS was the most reduced lncRNA in the HOX family in the human endometrium during the window of implantation, and it was elevated in RIF patients. Mechanistically, HOXA11-AS negatively regulated decidualization through competitive interaction with PTBP1, an RNA-binding protein. Binding of PTBP1 to HOXA11-AS limited PTBP1 availability to regulate PKM1/2 alternative splicing, resulting in enhanced PKM1 and diminished PKM2 expression, thus attenuating decidualization. The pattern of high HOXA11-AS expression and impaired PKM2 splicing was consistently observed in RIF patients. Collectively, our study indicates that the increase of HOXA11-AS is detrimental to endometrial decidualization, likely contributing to RIF. Our study may shed light on the pathogenesis and treatment of RIF.


Assuntos
Implantação do Embrião , Endométrio , Genes Homeobox , RNA Longo não Codificante , Implantação do Embrião/genética , Endométrio/metabolismo , Feminino , Ribonucleoproteínas Nucleares Heterogêneas/genética , Ribonucleoproteínas Nucleares Heterogêneas/metabolismo , Proteínas de Homeodomínio/genética , Proteínas de Homeodomínio/metabolismo , Humanos , Proteína de Ligação a Regiões Ricas em Polipirimidinas/genética , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Células Estromais/metabolismo , Fatores de Transcrição/genética
20.
CNS Neurosci Ther ; 28(5): 635-647, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35174644

RESUMO

The incidence and disability rate of spinal cord injury (SCI) worldwide are high, imposing a heavy burden on patients. Considerable research efforts have been directed toward identifying new strategies to effectively treat SCI. Governor Vessel electro-acupuncture (GV-EA), used in traditional Chinese medicine, combines acupuncture with modern electrical stimulation. It has been shown to improve the microenvironment of injured spinal cord (SC) by increasing levels of endogenous neurotrophic factors and reducing inflammation, thereby protecting injured neurons and promoting myelination. In addition, axons extending from transplanted stem cell-derived neurons can potentially bridge the two severed ends of tissues in a transected SC to rebuild neuronal circuits and restore motor and sensory functions. However, every single treatment approach to severe SCI has proven unsatisfactory. Combining different treatments-for example, electro-acupuncture (EA) with adult stem cell transplantation-appears to be a more promising strategy. In this review, we have summarized the recent progress over the past two decades by our team especially in the use of GV-EA for the repair of SCI. By this strategy, we have shown that EA can stimulate the nerve endings of the meningeal branch. This would elicit the dorsal root ganglion neurons to secrete excess amounts of calcitonin gene-related peptide centrally in the SC. The neuropeptide then activates the local cells to secrete neurotrophin-3 (NT-3), which mediates the survival and differentiation of donor stem cells overexpressing the NT-3 receptor, at the injury/graft site of the SC. Increased local production of NT-3 facilitates reconstruction of host neural tissue such as nerve fiber regeneration and myelination. All this events in sequence would ultimately strengthen the cortical motor-evoked potentials and restore the motor function of paralyzed limbs. The information presented herein provides a basis for future studies on the clinical application of GV-EA and adult stem cell transplantation for the treatment of SCI.


Assuntos
Terapia por Acupuntura , Eletroacupuntura , Traumatismos da Medula Espinal , Animais , Humanos , Regeneração Nervosa/fisiologia , Ratos , Ratos Sprague-Dawley , Medula Espinal , Traumatismos da Medula Espinal/terapia , Transplante de Células-Tronco
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