Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 15.773
Filtrar
1.
J Sep Sci ; 2021 Apr 09.
Artículo en Inglés | MEDLINE | ID: mdl-33835702

RESUMEN

Molecularly imprinted polymers developed fifty years ago have garnered enormous attention as receptor-like materials. Lately, molecularly imprinted polymers have been employed as a specific target tool in favor of cancer diagnosis and therapy by the selective recognition of tumor cells. Although the molecular imprinting technology has been well-innovated recently, cell still remain the most challenging target for imprinting. In this review, we summarize the advances in the synthesis of molecularly imprinted polymers suitable for the selective recognition of tumor cells. Through a sustained effort, three strategies have been developed including peptide-imprinting, polysaccharide-imprinting, and whole-cell imprinting, which have resulted in inspiring applications in effective cancer diagnosis and therapy. The major challenges and perspectives on the further directions related to the synthesis of molecularly imprinted polymers was also outlined. This article is protected by copyright. All rights reserved.

2.
Transpl Infect Dis ; : e13611, 2021 Apr 07.
Artículo en Inglés | MEDLINE | ID: mdl-33825274

RESUMEN

BACKGROUND AND OBJECTIVE: Invasive fungal disease (IFD) is associated with a high mortality for patients with hematological malignancies undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT). This study aimed not only to develop a proven/probable IFD risk-scoring model but to identify high-risk populations that would benefit from anti-fungal prophylaxis. METHODS: Data from the China Assessment of Antifungal Therapy in Hematological Diseases (CAESAR) study were retrieved, and all patients (n=1053) undergoing allo-HSCT were randomly divided into the training set (n=685) for model development and the validation set (n=368) for model verification. A weighted risk score for proven or probable IFD was established through multivariate logistic regression analysis. RESULTS: The study population had a mean age of 28.95 years and the majority underwent myeloablative transplantation in complete remission 1 (53.4%). Five risk factors of IFD were identified, namely neutropenia lasting longer than 14 days, corticosteroid use, diabetes, haploidentical donor, and unrelated donor. Based on the risk score for IFD, the patients were categorized into three groups: low risk (score 0-4, 1.5%-4.0%), intermediate risk (score 5-8, 9.8%), and high risk (score>8, 24.7%-14.0%). Anti-fungal prophylaxis may provide benefits for patients with intermediate (8.5% vs. 18.5%, P=0.0085) or high risk (19.4% vs. 30.8%, P=0.4651) but not low risk (2.1% vs. 3.8%, P=0.6136) of IFD. CONCLUSION: A practical weighted risk score for IFD in patients receiving allo-HSCT was established, which can aid decision-making regarding administration of anti-fungal prophylaxis.

3.
Neurogenetics ; 2021 Apr 03.
Artículo en Inglés | MEDLINE | ID: mdl-33811585

RESUMEN

We report a multiplex family with extended multisystem neurological phenotype associated with a CRYAB variant. Two affected siblings were evaluated with whole exome sequencing, muscle biopsy, laser microdissection, and mass spectrometry-based proteomic analysis. Both patients and their mother manifested a combination of early-onset cataracts, cardiomyopathy, cerebellar ataxia, optic atrophy, cognitive impairment, and myopathy. Whole exome sequencing identified a heterozygous c.458C>T variant mapped to the C-terminal extension domain of the Alpha-crystallin B chain, disrupting its function as a molecular chaperone and its ability to suppress protein aggregation. In accordance with the molecular findings, muscle biopsies revealed subsarcolemmal deposits that appeared dark with H&E and trichrome staining were negative for the other routine histochemical staining and for amyloid with the Congo-red stain. Electron microscopy demonstrated that the deposits were composed of numerous parallel fibrils. Laser microdissection and mass spectrometry-based proteomic analysis revealed that the inclusions are almost exclusively composed of crystallized chaperones/heat shock proteins. Moreover,  a structural model suggests that Ser153 could be involved in monomer stabilization, dimer association, and possible binding of partner proteins. We propose that our report potentially expands the complex phenotypic spectrum of alpha B-crystallinopathies with possible effect of a CRYAB variant on the central nervous system.

4.
J Geriatr Psychiatry Neurol ; : 8919887211006467, 2021 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-33792435

RESUMEN

Sensory impairments, such as visual and hearing impairments, and cognitive decline are prevalent among mid-age and older adults in China. With 4-year longitudinal data from the China Health and Retirement Longitudinal Study, we assessed the association between self-reported sensory impairments and episodic memory. Multivariate linear mixed-effects models were used to estimate the association of baseline sensory impairment in 2011-2012 with cognitive decline at 2- and 4-year follow-up visits. Among the 13,097 participants, longitudinal associations were identified between having hearing loss (ß = -0.14, 95% CI: -0.22, -0.05), having both poor hearing and vision (ß = -0.14, 95% CI: -0.23, -0.04) and decline in immediate word recall over 4 years, compared to those without self-reported sensory impairment. In addition, these associations were more significant among those aged 60 and older and among women. Further research is needed to investigate these associations in the longer term, providing evidence to support interventions that can prevent or delay sensory impairments and preserve cognitive functions in older adults.

5.
Front Cell Infect Microbiol ; 11: 638990, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33816342

RESUMEN

Purpose: Recurrent tuberculosis (TB) is defined by more than one TB episode per patient and is caused by re-infection with a new Mycobacterium tuberculosis (Mtb) strain or relapse with the previous strain. Recurrence of TB is one important obstacle for End TB strategy in the world and elucidating the triggers of recurrence is important for the current TB control strategy in China. This study aimed to analyze the sources of recurrent TB by the molecular genotyping method. Method: A population-based surveillance was undertaking on all culture-positive TB cases in Jiangsu province, China from 2013 to 2019. Phenotypic drug susceptibility test (DST) by proportion method and mycobacterial interspersed repetitive units-variable number of tandem repeat (MIRU-VNTR) were adopted for drug resistance and genotype detection. Results: A total of 1451 culture-positive TB patients were collected and 30 (2.06%, 30/1451) TB cases had recurrent TB episodes. Except 7 isolates were failed during subculture, 23 paired isolates were assessed. After genotyping by MIRU-VNTR, 12 (52.17%, 12/23) paired recurrence TB were demonstrated as relapse and 11 (47.83%,11/23) paired cases were identified as re-infection. The average interval time for recurrence was 24.04 (95%CI: 19.37-28.71) months, and there was no significant difference between relapse and re-infection. For the relapsed cases, two paired isolates exhibited drug resistance shifting, while four paired isolates revealed inconsistent drug resistance among the re-infection group including two multidrug-resistant tuberculosis (MDR-TB) at the second episode. Conclusion: Relapse and re-infection contributed equally to the current situation of recurrence TB in Jiangsu, China. Besides, more efficient treatment assessment, specific and vigorous interventions are urgently needed for MDR-TB patients, considering obvious performance among re-infection cases.

6.
J Vis Exp ; (169)2021 Mar 20.
Artículo en Inglés | MEDLINE | ID: mdl-33818573

RESUMEN

In an injured neonatal myocardium, macrophages facilitate cardiomyocyte proliferation and angiogenesis and promote heart regeneration. The present study reveals that transplantation of neonatal cardiac macrophages recruited by injury promotes adult heart regeneration after myocardial infarction with improvement of cardiac function and cardiomyocyte proliferation. The results indicate that neonatal cardiac macrophage transplantation could be a promising strategy for cardiac injury treatment. Here, we provide the technical details, including the isolation of neonatal cardiac macrophages from apical resection-injured neonatal mouse hearts, the transplantation of macrophages into myocardial-infarcted adult mice, and the estimation of heart regeneration after a macrophage graft.

7.
Dev Comp Immunol ; : 104092, 2021 Apr 02.
Artículo en Inglés | MEDLINE | ID: mdl-33819545

RESUMEN

DNA methyltransferase, a key enzyme mediating DNA methylation, is involved in numerous processes including genomic imprinting, X chromosome inactivation, transposable element suppression, and immune defense in vertebrates. In the present study, a DNA cytosine-5-methyltransferase 3 was identified from oyster Crassostrea gigas (designed as CgDNMT3). There were a PWWP domain, a PHD domain and a DNA-methylase domain in the deduced amino acid sequences of CgDNMT3, and the conserved motifs I, IV, VI, Ⅷ, IX and X were identified in its C-terminal catalytic DNA-methylase domain. The mRNA transcripts of CgDNMT3 were detected in haemocytes, mantle, gill, adductor muscle, digestive gland and labial palp, with higher expression level in haemocytes (6.54 folds of those in gill, p < 0.01). The expression level of CgDNMT3 mRNA in haemocytes increased significantly after LPS primed (2.87 folds of that in control group, p < 0.05) in vitro or Vibrio splendidus challenging (1.94 folds of that in control group, p < 0.05) in vivo. Immunocytochemical analysis revealed that CgDNMT3 protein was distributed mainly in cytoplasm and partial in nucleus of oyster haemocytes. After CgDNMT3 was transfected and expressed in HEK293T cells, the DNA 5-methylcytosine (5-mc) level in the transfected group was significantly increased, which was 1.22 folds (p < 0.05) of the pcDNA-3.1 group (p < 0.05). The expressions of oyster CgIL17-1, CgIL17-2 and CgIL17-5 in haemocytes increased (13.05 folds, 4.78 folds and 9.41 folds of that in control group, respectively) at 12 h after V. splendidus challenging, but the increase were significantly inhibited when the oysters were pre-treated with DNA methyltransferase inhibitor 5-Azacytidine, which were 9 folds, 1.93 folds and 3.22 folds of that in control group, respectively. These results collectively suggested that CgDNMT3 was a conserved member of DNA methyltransferase 3 family in oysters, and participated in regulating the expression of cytokines during immune response.

8.
Aesthetic Plast Surg ; 2021 Apr 05.
Artículo en Inglés | MEDLINE | ID: mdl-33821308

RESUMEN

BACKGROUND: Facial thread-lifting (FTL) has gained more popularity, but the incidences of complications following FTL remain controversial. We aimed to perform a meta-analysis and systematic review to estimate the incidences of complications and to compare the short- and long-term satisfaction rates following FTL. METHODS: We searched PubMed, Web of Science, Embase and Cochrane library for eligible studies. The primary outcome was the incidences of complications following FTL. The secondary outcome was the satisfaction rate immediately and 6-month after FTL. The pooled incidences of complications and 95% confidence intervals were estimated using random-effects models. RESULTS: A total of 26 studies were included in this meta-analysis. Swelling was the most commonly reported complication with a pooled incidence of 35%, followed by skin dimpling (10%), paresthesia (6%), thread visibility/palpability (4%), infection (2%), and thread extrusion (2%). Absorbable threads were associated with a significantly lower risk of paresthesia (3.1% vs. 11.7%) and thread extrusion (1.6% vs. 7.6%) than non-absorbable threads. Patients older than 50 years had a significantly higher risk of dimpling (16% vs. 5.6%) and infection (5.9% vs. 0.7%) than their younger counterparts. In addition, the pooled long-term satisfaction rate was significantly decreased compared to it immediately after FTL (88% vs. 98%). CONCLUSION: Non-absorbable threads and older age of patients are associated with higher risks of complications. Therefore, we recommend a judicious use of non-absorbable threads and FLT in older patients. Furthermore, it should be discussed with patients preoperatively that the rejuvenation effect of FTL may not maintain in the long-term. LEVEL OF EVIDENCE III: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

9.
Microb Drug Resist ; 2021 Mar 31.
Artículo en Inglés | MEDLINE | ID: mdl-33794134

RESUMEN

Objective: Shaanxi is the most highly populated province with high burdens of tuberculosis in northwestern China. The aim of this study was to investigate the molecular characteristics and drug resistance of Mycobacterium tuberculosis isolates from Shaanxi province of China in 2018. Methods: Phenotypic drug susceptibility testing and spoligotyping methods were performed on 518 M. tuberculosis isolates; drug-resistant isolates were sequenced in 11 drug loci, including katG, inhA, oxyR-ahpC, rpoB, embB, rpsL, rrs1 (nucleotides 388-1084), gyrA, gyrB, rrs2 (nucleotides 1158-1674), and eis. Results: The prevalences of isoniazid, rifampicin, ethambutol, streptomycin, ofloxacin, and kanamycin resistance were 22.0%, 19.3%, 7.9%, 23.8%, 10.4%, and 3.3%, respectively. The Beijing family (82.8%) was the predominant genotype, followed by the T (9.3%), H (0.6%), CAS (0.4%), LAM (0.4%), and U (0.4%) families. The percentage of Beijing genotype in a central area (88.1%) was higher than in the south (77.3%) and the north area (80.1%) (p < 0.05), while the sex, age, and treatment history between Beijing and non-Beijing family were not statistically different. Mutation analysis found that the most prevalent mutations were katG315, rpoB531, embB306, rpsL43, gyrA94, and rrs1401; the Beijing family exhibited a high rate of isoniazid-resistant isolates carrying katG315 mutations (p < 0.05). Furthermore, compared with the phenotypic data, the sensitivities of isoniazid, rifampicin, ethambutol, streptomycin, ofloxacin, and kanamycin resistance by sequencing base on 11 loci were 85.1%, 94.0%, 53.7%, 74.8%, 77.8%, and 64.7%, respectively. Conclusions: Shaanxi has a serious epidemic of drug-resistant tuberculosis, Beijing family is the predominant genotype, and the distribution showed geographic diversity. The prevalence of Beijing genotypes has a tendency to promote the transmission of high-level isoniazid-resistant M. tuberculosis. Besides, the hot spot regions localized in the embB, rrs2, and eis gene appear not to serve as excellent biomarkers for predicting ethambutol and kanamycin resistance in Shaanxi.

10.
Science ; 2021 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-33795473

RESUMEN

Transcription factor IID (TFIID) recognizes core promoters and supports preinitiation complex (PIC) assembly for RNA polymerase (Pol) II-mediated eukaryotic transcription. Here, we determined the structures of human TFIID-based PIC in three stepwise assembly states and revealed two-track PIC assembly: stepwise promoter deposition to Pol II and extensive modular reorganization on track I (on TATA-DBE promoters) versus direct promoter deposition on track II (on TATA-only and TATA-less promoters). The two tracks converge at ~50-subunit holo-PIC in identical conformation, whereby TFIID stabilizes PIC organization and supports loading (CDK)-activating kinase (CAK) onto Pol II and CAK-mediated phosphorylation of Pol II C-terminal domain. Unexpectedly, TBP of TFIID similarly bends TATA box and TATA-less promoters in PIC. Our study provides structural visualization of stepwise PIC assembly on highly diversified promoters.

11.
Int J Mol Sci ; 22(6)2021 Mar 21.
Artículo en Inglés | MEDLINE | ID: mdl-33801148

RESUMEN

Chemotherapeutics are the mainstay treatment for metastatic breast cancers. However, the chemotherapeutic failure caused by multidrug resistance (MDR) remains a pivotal obstacle to effective chemotherapies of breast cancer. Although in vitro evidence suggests that the overexpression of ATP-Binding Cassette (ABC) transporters confers resistance to cytotoxic and molecularly targeted chemotherapies by reducing the intracellular accumulation of active moieties, the clinical trials that target ABCB1 to reverse drug resistance have been disappointing. Nevertheless, studies indicate that ABC transporters may contribute to breast cancer development and metastasis independent of their efflux function. A broader and more clarified understanding of the functions and roles of ABC transporters in breast cancer biology will potentially contribute to stratifying patients for precision regimens and promote the development of novel therapies. Herein, we summarise the current knowledge relating to the mechanisms, functions and regulations of ABC transporters, with a focus on the roles of ABC transporters in breast cancer chemoresistance, progression and metastasis.

12.
Drug Deliv ; 28(1): 719-732, 2021 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-33825592

RESUMEN

The purpose of this study was to optimize the preparation method of injectable Octreotide microspheres. To explore the correlation between the solvent system and the general properties of microspheres to reduce burst release and enable them to be used for portal hypertension. Octreotide microspheres were prepared by modified double emulsion solution evaporation method after optimizing preparation conditions. The results showed that Octreotide microspheres had a particle size of 57.48 ± 15.24 µm, and the initial release was significantly reduced. In vitro release and in vivo pharmacokinetic data indicated that Octreotide was released stably within 1200 h. The effects on portal vein pressure, liver tissue morphology and other related indexes were observed after administration. As obvious results, injection of Octreotide microspheres could significantly reduce portal vein pressure and reduce the portal vein lumen area in experimental cirrhotic portal hypertensive rats. The optimized Octreotide PLGA microsphere preparation has been proved to have a good effect on PHT in vivo after detecting aminotransferase (AST) and alanine aminotransferase (ALT) activity, liver tissue hydroxyproline (Hyp) content, serum and liver tissue malondialdehyde (MDA) levels, plasma prostacyclin (PGI2) levels, and liver tissue tumor necrosis factor (TNFα) content. In addition, serum and liver tissue superoxide dismutase (SOD) activity and liver tissue glutathione (GSH) content, plasma thromboxane (TXA2), serum nitric oxide (NO), liver tissue nitric oxide synthase (NOS), and plasma and liver tissue endothelin (ET) were significantly increased.

13.
JAMA Netw Open ; 4(4): e215262, 2021 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-33844000

RESUMEN

Importance: Time trends and population disparities in nutritional quality of foods from major US sources, including grocery stores, restaurants, schools, worksites, and other sources, are not well established. Objective: To investigate patterns and trends in diet quality by food sources among US children and adults overall and in sociodemographic subgroups. Design, Setting, and Participants: This serial, cross-sectional survey study included respondents from 8 National Health and Nutrition Examination Survey cycles (2003-2018) with valid dietary recalls. Data were analyzed from April 16, 2020, to July 20, 2020. Exposures: Survey cycle, food source, and key sociodemographic subgroups. Main Outcomes and Measures: Mean diet quality of foods (meals, snacks, and beverages) consumed per person, characterized by the American Heart Association diet score (range, 0-80, with higher scores indicating healthier diets), the Healthy Eating Index 2015 (range, 0-100, with higher scores indicating healthier diets), and their components. For the American Heart Association diet score, poor diet was defined as less than 40.0% adherence (score, <32.0), intermediate diet as 40.0% to 79.9% adherence (score, 32.0-63.9), and ideal as 80.0% or greater adherence (score, ≥64.0). Results: The study included 20 905 children 5 to 19 years of age (mean [SD] age, 12.1 [5.24] years; 51.0% male) and 39 757 adults 20 years or older (mean [SD] age, 47.3 [15.1] years; 51.9% female). Diet quality of foods consumed from grocery stores increased modestly in children (53.2% to 45.1% with poor diet quality; P = .006 for trend) and adults (40.1% to 32.9% with poor diet quality; P = .001 for trend), with smaller changes for restaurants among children (84.8% to 79.6% with poor diet quality; P = .003 for trend). Changes for restaurants among adults were not statistically significant (65.4% to 65.2% with poor diet quality; P = .07 with poor diet quality); the same was true of worksites (adults: 55.6% to 50.7% with poor diet quality; P = .25 for trend). Food quality from other sources worsened (children: 40.0% to 51.7% with poor diet quality; adults: 33.8% to 43.8% with poor diet quality; P < .001 for trend each). The largest improvement in diet quality was in schools, with the percentage with poor diet quality decreasing from 55.6% to 24.4% (P < .001 for trend), mostly after 2010, and with equitable improvements across population subgroups. Findings were similar for Healthy Eating Index 2015. Significant disparities in diet quality trends were seen by sex, race/ethnicity, educational level, and household income for food consumed from grocery stores. For example, the proportion of foods consumed from grocery stores that were of poor diet quality decreased among high-income adults (from 36.9% to 26.5%; P = .001 for trend) but not among low-income adults (from 45.8% to 41.3%; P = .09 for trend). Conclusions and Relevance: By 2017-2018, foods consumed at schools improved significantly and provided the best mean diet quality of major US food sources, without population disparities. Additional improvements are needed from all major US food sources, with particular attention on equity.

14.
Artículo en Inglés | MEDLINE | ID: mdl-33846740

RESUMEN

PURPOSE: To evaluate the effectiveness and safety of thermal ablation for primary hyperparathyroidism (pHPT). MATERIALS AND METHODS: From January 2015 to March 2020, data pertaining to patients who received thermal ablation for pHPT at 4 centers were retrospectively analyzed. The median follow-up duration was 18.1months (IQR: 6.5-42.2 months). A cure referred to the reestablishment of normal values of serum calcium and intact parathyroid hormone (iPTH) throughout the entire follow-up period, at least more than 6 months. The technical success, effectiveness, and safety of treatment were analyzed. RESULTS: 119 patients (mean age, 57.2 ± 16.3 years; 81 female) with 134 parathyroid nodules were enrolled. The mean maximum diameter of the parathyroid glands was 1.6 ± 0.9 cm. Ninety-six patients underwent microwave ablation (MWA), and 23 patients underwent radiofrequency ablation (RFA). The technical success rate was 98.3% and the cure rate was 89.9%. Significant differences were found in the maximum diameter between the cured patients and the patients who did not undergo ablation of the target lesions. Except the cases with pHPT nodules<0.6cm in diameter, the cure rate was 95%. There were no difference in cure rates at 6 months between the MWA and RFA (MWA vs. RFA, 90.6% vs. 87.0%; χ2=0.275, p = 0.699). The volume reduction rate of the ablation zone was 94.6% at 12 months. The complication rate was 6.7% (8/119). Except one patient with persistent voice impairment, other symptoms were spontaneously resolved within six months. CONCLUSION: Thermal ablation was effective and safe for pHPT.

15.
Mol Med Rep ; 23(6)2021 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-33846768

RESUMEN

Diabetic liver injury is a serious complication of type 2 diabetes mellitus (T2DM), which is often irreversible in the later stage, and affects the quality of life. Autophagy serves an important role in the occurrence and development of diabetic liver injury. For example, it can improve insulin resistance (IR), dyslipidaemia, oxidative stress and inflammation. Astragaloside IV (AS­IV) is a natural saponin isolated from the plant Astragalus membranaceus, which has comprehensive pharmacological effects, such as anti­oxidation, anti­inflammation and anti­apoptosis properties, as well as can enhance immunity. However, whether AS­IV can alleviate diabetic liver injury in T2DM and its underlying mechanisms remain unknown. The present study used high­fat diets combined with low­dose streptozotocin to induce a diabetic liver injury model in T2DM rats to investigate whether AS­IV could alleviate diabetic liver injury and to identify its underlying mechanisms. The results demonstrated that AS­IV treatment could restore changes in food intake, water intake, urine volume and body weight, as well as improve liver function and glucose homeostasis in T2DM rats. Moreover, AS­IV treatment promoted suppressed autophagy in the liver of T2DM rats and improved IR, dyslipidaemia, oxidative stress and inflammation. In addition, AS­IV activated adenosine monophosphate­activated protein kinase (AMPK), which inhibited mTOR. Taken together, the present study suggested that AS­IV alleviated diabetic liver injury in T2DM rats, and its mechanism may be associated with the promotion of AMPK/mTOR­mediated autophagy, which further improved IR, dyslipidaemia, oxidative stress and inflammation. Thus, the regulation of autophagy may be an effective strategy to treat diabetic liver injury in T2DM.

16.
Artículo en Inglés | MEDLINE | ID: mdl-33833508

RESUMEN

Background: Penehyclidine hydrochloride is a selective antagonist of M1 and M3 receptors. Clinical studies suggest that it is a potential drug for the treatment of chronic obstructive pulmonary disease (COPD). The purpose of this study was to evaluate the effect of penehyclidine hydrochloride on the inflammatory response of lung tissue during mechanical ventilation in rats with COPD and explore the role of the c-Jun N-terminal kinase/stress-activated protein kinase (JNK/SAPK) signaling pathway. Methods: Eight-week-old male Sprague Dawley rats were exposed to cigarette smoke for 30 minutes every day for two months, and on the first and thirtieth days, 200 ug of lipopolysaccharide was injected into the trachea. Two months later, the rats were randomly divided into the control group (C), model group (M), model + normal saline group (N), and penehyclidine hydrochloride group (H) to undergo anesthesia and mechanical ventilation. In group H, 1 mg/kg of penehyclidine hydrochloride was injected intravenously. Results: The results showed that: ① Compared with group C, the other groups all showed typical chronic obstructive pathological changes in the lung tissue; their wet/dry weight ratio (W/D), TNF-α, JNK, and p-JNK levels increased (P < 0.05), and their interleukin (IL)-10 levels decreased (P < 0.05). ② Compared with group M, there was no significant change in the lung tissue indexes in group N (P > 0.05). ③ Compared with group N, the W/D, TNF-α, JNK, and p-JNK levels in group H decreased (P < 0.05), while the levels of IL-10 increased (P < 0.05). Conclusion: Penehyclidine hydrochloride can alleviate the pulmonary inflammatory response in rats with COPD undergoing mechanical ventilation. The JNK/SAPK signaling pathway may be involved in this process.

17.
Exp Hematol Oncol ; 10(1): 27, 2021 Apr 09.
Artículo en Inglés | MEDLINE | ID: mdl-33836835

RESUMEN

BACKGROUND: The receptor tyrosine kinase FLT3 with internal tandem duplications within the juxtamembrane domain (FLT3-ITD) is a poor prognostic factor; however, the prognostic significance of missense mutation in the tyrosine kinase domain (FLT3-TKD) is controversial. Furthermore, the accompanying mutations and fusion genes with FLT3 mutations are unclear in acute myeloid leukemia (AML). METHODS: We investigated FLT3 mutations and their correlation with other gene mutations and gene fusions through two RNA-seq based next-generation sequencing (NGS) method and prognostic impact in 207 de novo AML patients. RESULTS: FLT3-ITD mutations were positive in 58 patients (28%), and FLT3-TKD mutations were positive in 20 patients (9.7%). FLT3-ITD was associated with a higher white blood cell count (WBC, mean 72.9 × 109/L vs. 24.2 × 109/L, P = 0.000), higher bone marrow blasts (mean 65.9% vs. 56.0%, P = 0.024), and NK-AML (normal karyotype) (64.8% vs. 48.4%, P = 0.043). NPM1 and DNMT3A mutations were enriched in FLT3-ITD (53.5% vs. 15.3%, P = 0.000; 34.6% vs. 13%, P = 0.003). However, the mutations of CEBPA were excluded in FLT3-AML (3.8% vs. 0% vs. 19.8%, P = 0.005). Mutations of Ras and TP53 were unlikely associated with FLT3-ITD (1.9% vs. 20.6%, P = 0.006; 0% vs. 6.1%, P = 0.04). The common fusion genes (> 10%) in FLT3-ITD had MLL-rearrangement and NUP98-rearrangement, while the common fusion genes in FLT3-TKD had AML1-ETO and MLL-rearrangement. Two novel fusion genes PRDM16-SKI and EFAN2-ZNF238 were identified in FLT3-ITD patients. Gene fusions and NPM1 mutation were mutually excluded in FLT3-ITD and FLT3-TKD patients. Their patterns of mutual exclusivity and cooperation among mutated genes suggest that additional driver genetic alterations are required and reveal two evolutionary patterns of FLT3 pathogenesis. Patients with FLT3-ITD had a lower CR (complete remission) rate, lower 3-year OS (overall survival), DFS (disease-free survival), and EFS (event-free survival) compared to FLT3wtAML. NK-AML with FLT3-ITD had a lower 3-year OS, DFS, and EFS than those without, while FLT3-TKD did not influence the survival in whole cohort and NK-AML. Besides, we found that FLT3-ITD/TET2 bimutation defined a poor prognostic subgroup. CONCLUSIONS: Our study offers deep insights into the molecular pathogenesis and biology of AML with FLT3-ITD and FLT3-TKD by providing the profiles of concurrent molecular alterations and the clinical impact of FLT3-ITD and FLT3-TKD on AML patients.

18.
Br J Pharmacol ; 2021 Apr 10.
Artículo en Inglés | MEDLINE | ID: mdl-33837959

RESUMEN

BACKGROUND AND PURPOSE: Cocamide monoethanolamide (CMEA) is commonly used as a surfactant-foam booster in cosmetic formulations. Upon contact with the eye or other sensitive skin areas, CMEA elicits sting and lasting irritation. We hypothesized a specific molecular interaction with TRPV1 by which CMEA caused eye irritation. EXPERIMENTAL APPROACH: Eye irritancy is evaluated using eye-wiping test in rabbit and mouse. Intracellular Ca2+ concentrations and action potentials are measured using Ca2+ imaging and current clamp, respectively. Voltage clamp, site-direct mutagenesis and molecular modeling identify the binding pocket of CMEA on TRPV1. KEY RESULTS: CMEA-induced eye irritation is ameliorated by selective ablation of TRPV1 and rodents exhibit much stronger responses to CMEA than rabbits. In trigeminal ganglion neurons, CMEA induces Ca2+ influx and neuronal excitability, effects mitigated by TRPV1 inhibitor and absent in TRPV1 knockout neurons. In HEK-293 cell expressing TRPV1, CMEA increases whole-cell currents by increasing channel open probability (EC50 = 10.2 µM) without affecting TRPV2, 3, 4 and TRPA1 activities. Lauric acid monoethanolamide (LAMEA), the most abundant constituent in CMEA, is the most efficacious and potent TRPV1 activator. LAMEA binds to the capsaicin-binding pocket of TRPV1. Both rabbit TRPV1 that possesses the T550I variant and the human TRPV1T550I mutant exhibit much lower sensitivity to LAMEA. CONCLUSIONS AND IMPLICATION: CMEA directly activates TRPV1 to produce eye irritation, and rabbit, the traditional animal model used for eye irritancy test is a poor model for evaluating human eye irritants structurally related to CMEA. Our study identifies potential alternatives to CMEA as non-irritating surfactants.

19.
BMC Anesthesiol ; 21(1): 104, 2021 Apr 06.
Artículo en Inglés | MEDLINE | ID: mdl-33823789

RESUMEN

BACKGROUND: Myocardial ischemia-reperfusion injury (MIRI) is the most common cause of death worldwide. The NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3) inflammasome plays an important role in the inflammatory response to MIRI. Dexmedetomidine (DEX), a specific agonist of α2-adrenergic receptor, is commonly used for sedation and analgesia in anesthesia and critically ill patients. Several studies have shown that dexmedetomidine has a strong anti-inflammatory effect in many diseases. Here, we investigated whether dexmedetomidine protects against MIRI by inhibiting the activation of the NLRP3 inflammasome in vitro. METHODS: We established an MIRI model in cardiomyocytes (CMs) alone and in coculture with cardiac fibroblasts (CFs) by hypoxia/reoxygenation (H/R) in vitro. The cells were treated with dexmedetomidine with or without MCC950 (a potent selective NLRP3 inhibitor). The beating rate and cell viability of cardiomyocytes, NLRP3 localization, the expression of inflammatory cytokines and NLRP3 inflammasome-related proteins, and the expression of apoptosis-related proteins, including Bcl2 and BAX, were determined. RESULTS: Dexmedetomidine treatment increased the beating rates and viability of cardiomyocytes cocultured with cardiac fibroblasts. The expression of the NLRP3 protein was significantly upregulated in cardiac fibroblasts but not in cardiomyocytes after H/R and was significantly attenuated by dexmedetomidine treatment. Expression of the inflammatory cytokines IL-1ß, IL-18 and TNF-α was significantly increased in cardiac fibroblasts after H/R and was attenuated by dexmedetomidine treatment. NLRP3 inflammasome activation induced the increased expression of cleaved caspase1, mature IL-1ß and IL-18, while dexmedetomidine suppressed H/R-induced NLRP3 inflammasome activation in cardiac fibroblasts. In addition, dexmedetomidine reduced the expression of Bcl2 and BAX in cocultured cardiomyocytes by suppressing H/R-induced NLRP3 inflammasome activation in cardiac fibroblasts. CONCLUSION: Dexmedetomidine treatment can suppress H/R-induced NLRP3 inflammasome activation in cardiac fibroblasts, thereby alleviating MIRI by inhibiting the inflammatory response.

20.
Pestic Biochem Physiol ; 174: 104803, 2021 May.
Artículo en Inglés | MEDLINE | ID: mdl-33838704

RESUMEN

Deoxymikanolide (DEO) was isolated from Mikania micrantha Bunge and identified as a novel antibacterial compound previously. However, the mode of antimicrobial mechanism of DEO was not clear but hypothesized to affect the morphology and physiology of Ralstonia solanacearum cells. In this study, we confirmed our hypothesis via transmission electron microscopy (TEM) observation and comprehensive physiological analyses, including electric conductivity, glycan and phosphorus metabolism, activities of antioxidant enzymes (catalase, peroxidase, and superoxide dismutase), intrabacterial reactive oxygen species (ROS), and malondialdehyde (MDA) levels. We found that glycan and phosphorus metabolism, electric conductivity, intracellular ROS and MDA levels of R. solanacearum cells were significantly increased, while the activities of three antioxidant enzymes were significantly inhibited by DEO treatment. Moreover, TEM analysis showed that DEO treatment led to an early-stage of cell shrinkage, intermediate-stages of cytoplasmic damage, and a final-stage of cell disruption. Altogether, our data presented here indicate that DEO could adversely affect the physiology and morphology of R. solanacearum cells and be treated as an alternative antibacterial treatment in the future.


Asunto(s)
Ralstonia solanacearum , Catalasa , Lactonas , Sesquiterpenos de Germacrano
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA
...