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1.
JCI Insight ; 5(19)2020 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-33004687

RESUMO

Depression and anxiety are frequently observed in patients suffering from neuropathic pain. The underlying mechanisms remained unclear. The ventrolateral orbital cortex (VLO) has attracted considerable interest in its role in antidepressive effect in rodents. In the present study, we further investigated the role of the VLO in the anxiodepressive consequences of neuropathic pain in a chronic constriction injury of infraorbital nerve-induced trigeminal neuralgia (TN) mouse model. Elevated plus maze, open field, forced swimming, tail suspension, and sucrose preference tests were used to evaluate anxiodepressive-like behaviors. The results show that chemogenetic activation of bilateral VLO neurons, especially CaMK2A+ pyramidal neurons, blocked the TN-induced anxiodepressive-like behaviors. Chemogenetic and optogenetic activation of VGLUT2+ or inhibition of VGAT+ VLO neurons was sufficient to produce an antianxiodepressive effect in TN mice. Pharmacological activation of D1-like receptors (D1Rs) but not D2Rs in the VLO significantly alleviated TN-induced depressive-like behaviors. Electrophysiological recordings revealed a decreased excitability of VLO excitatory neurons following neuropathic pain. Furthermore, activation of submedius thalamic nucleus-VLO (Sm-VLO) projection mimicked the antianxiodepressive effect of VLO excitation. Conversely, activation of VLO-periaqueductal gray matter (PAG) projection had no effect on TN-induced anxiodepressive behaviors. This study provides a potentially novel mechanism-based therapeutic strategy for the anxiodepressive consequences of neuropathic pain.

2.
Artigo em Inglês | MEDLINE | ID: mdl-33026617

RESUMO

Panzhihua City, a typical eco-fragile region for agro-sylvo-pastoral industry in China, is located in the dry-hot valley of the Jinsha River, characterized by its big landform undulation, great elevation difference, uneven hydrothermal conditions, and complex geological structure. As a crucial ecological barrier in upper reaches of the Yangtze River, this area is abundant in water resources and mineral resources, such as vanadium and titanium. However, due to its over-development for nonnatural urban economy in the mining industry, agriculture, and animal husbandry, ecological problems are getting worse. Such problems as soil erosion and groundwater pollution have led obvious ecological degeneration in Panzhihua city. Therefore, for protecting the eco-environment and planning construction, it is significant to scientifically recognize that how eco-environment changes based on spatial-temporal, and how the driving mechanism affects Panzhihua city. Nowadays, there are some theories and methods that study eco-environmental protection and city construction in Panzhihua, but they are not comprehensive enough to study its spatial-temporal evolution and driving-force system. This study takes Panzhihua City as the research area of which evaluation factors, for example, topography, soil, vegetation, and meteorological factors, are chosen to construct an evaluation system suitable for the ecological environment vulnerability of Panzhihua City. These factors are selected in three aspects, which are ecological sensitivity, ecological recovery, and ecological pressure from 2005 to 2015 in this area. Then, spatial principal component analysis method, CA-Markov model, and dynamic degree model are applied to analyze the spatial-temporal evolution for ecological vulnerability based on three periods from 2005 to 2015 in Panzhihua City. Besides, GeoDetector is used to quantitatively analyze how spatial-temporal disparities change and what drives them to change. The results show that (1) during these 10 years, the overall ecological fragility of Panzhihua City is steadily increasing from northwest to southeast. The overall ecological quality is moderate, and regional differences are obvious. Places of moderate vulnerability or above are distributed in central and eastern regions of frequent human activities; places of mild vulnerability or below are distributed in the regions of Yanbian County and Miyi County. (2) The comparison of the changing rates based on vulnerability levels is severe > potential > moderate > mild > slight. The overall vulnerability changes within a small trend, showing a balanced two-way transition state between adjacent vulnerability levels. The comprehensive index for overall ecological vulnerability decreases period by period. (3) The interactions between each two factors toward spatial differentiation and explanatory power by ecological vulnerability show a two-factor-enhanced relation, indicating that multiple factors form the ecological vulnerability of Panzhihua City.

3.
Nat Prod Res ; : 1-7, 2020 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-33016123

RESUMO

One new piperazinedione derivative, nigerpiperazine A (1), along with six known compounds (2-7) were isolated from the fungus Aspergillus niger JX-5 from mangrove Ceriops tagal. Nigerpiperazine A (1) was elucidated by spectroscopic analyses and 13C NMR chemical shift calculations, compounds 4 and 5 were determined by X-ray and the CD spectra. The absolute configuration of 4 was identified by X-ray for the first time. Compounds 1 and 4 showed inhibitory activities against Helicoverpa armigera Hubner with the IC50 values of 200 and 100 µg/mL, respectively.

4.
BMC Microbiol ; 20(1): 311, 2020 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-33054730

RESUMO

BACKGROUND: The symbiotic bacteria associated with edible fungi are valuable microbial resources worthy of in-depth exploration. It is important to analyze the community structure and succession of symbiotic bacteria in mushrooms. This can assist in the isolation of growth-promoting strains that have an essential relationship with the cultivation cycle as well as the agronomic traits and yields of fruiting bodies. RESULTS: In all of the samples from cultivation bags of Hypsizygus marmoreus, 34 bacterial phyla were detected. Firmicutes was the most abundant bacterial phylum (78.85%). The genus Serratia showed an exponential increase in abundance in samples collected from the cultivation bags in the mature period, reaching a peak abundance of 55.74% and the dominant symbiotic flora. The most predominant strain was Serratia odorifera HZSO-1, and its abundance increased with the amount of hyphae of H. marmoreus. Serratia odorifera HZSO-1 could reside in the hyphae of H. marmoreus, promote growth and development, shorten the fruiting cycle by 3-4 days, and further increase the fruiting body yield by 12%. CONCLUSIONS: This study is a pioneering demonstration of the community structure of the symbiotic microbiota and bacteria-mushroom interaction in the growth and development of edible fungi. This work lays a theoretical foundation to improve the industrial production of mushrooms with symbiotic bacteria as assisting agents.

5.
J Agric Food Chem ; 2020 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-33059450

RESUMO

Three novel dimeric bithiophenes, echinbithiophenedimers A-C (1-3), along with two known thiophenes, 4 and 5, were obtained from Echinops latifolius, and their structures were identified through extensive spectroscopic analysis and electronic circular dichroism calculations. Compounds 1-3 possessed new carbon skeletons; they are dimeric bithiophenes with 1 and 2 featuring an unprecedented 1,3-dioxolane ring system and 3 featuring an unusual 1,4-dioxane ring. These compounds are the first examples of bithiophene dimers furnished by different cyclic diethers. Dimeric bithiophenes 1-3 had good antifungal activities against five phytopathogenic fungi, and compound 3 showed excellent activity against Alternaria alternate and Pyricularia oryzae, with a minimal inhibitory concentration value of 8 µg/mL, which was close to or higher than that of carbendazim. Moreover, its effect on the mycelial morphology was observed by scanning electron microscopy. Compounds 1-3, which were demonstrated to be nonphototoxic thiophenes, exhibited better nematicidal activity than the commercial nematicide ethoprophos against Meloidogyne incognita. This study revealed that dimeric bithiophenes containing 1,3-dioxolane or 1,4-dioxane rings could be used as novel antifungal and nematicidal agents for controlling plant fungal and nematode pathogens.

6.
BMC Med Genomics ; 13(1): 146, 2020 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-33023580

RESUMO

BACKGROUND: Phelan-McDermid syndrome (PMS, OMIM#606232), or 22q13 deletion syndrome, is a rare genetic disorder caused by deletion of the distal long arm of chromosome 22 with a variety of clinical features that display considerably heterogeneous degrees of severity. The SHANK3 gene is understood to be the critical gene for the neurological features of this syndrome. CASE PRESENTATION: We describe one pair of boy-girl twins with a 22q13 deletion not involving the SHANK3 gene. Interestingly, the clinical and molecular findings of the two patients were identical, likely resulting from germline mosaicism in a parent. The boy-girl twins showed intellectual disability, speech absence, facial dysmorphism, cyanosis, large fleshy hands and feet, dysplastic fingernails and abnormal behaviors, and third-generation sequencing showed an identical de novo interstitial deletion of 6.0 Mb in the 22q13.31-q13.33 region. CONCLUSIONS: Our case suggests that prenatal diagnosis is essential for normal parents with affected children due to the theoretical possibility of parental germline mosaicism. Our results also indicated that other genes located in the 22q13 region may have a role in explaining symptoms in individuals with PMS. In particular, we propose that four candidate genes, CELSR1, ATXN10, FBLN1 and WNT7B, may also be involved in the etiology of the clinical features of PMS. However, more studies of smaller interstitial deletions with 22q13 are needed to corroborate our hypothesis and better define the genotype-phenotype correlation. Our findings contribute to a more comprehensive understanding of PMS.

7.
Int J Med Sci ; 17(16): 2427-2439, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33029085

RESUMO

Background and aim: Competing endogenous RNA (ceRNA) is believed to play vital roles in tumorigenesis. The goal of this study was to screen prognostic biomarkers in lung adenocarcinoma (LUAD). Methods: Common differentially expressed genes (DEGs) were collected from Gene Expression Omnibus (GEO) databases and The Cancer Genome Atlas databases (TCGA) using GEO2R and "limma" package in R, respectively. Overlapping DEGs were conducted using enrichment of functions and protein-protein interaction (PPI) network to discover significant candidate genes. By using a comprehensive analysis, we constructed an mRNA mediated ceRNA network. Survival rates were used Kaplan-Meier analysis. Statistical analysis was used to further identify the prognosis of studied genes. Results: Integrated analysis of GSE32863 and TCGA databases, a total of 886 overlapping DEGs, including 279 up-regulated and 607 down-regulated genes were identified. Considering the highest term of candidate genes in PPI, we identified TPX2, which was enriched in cell division signaling pathway. Besides, 35 differentially expressed miRNAs (DEmiRNAs) were predicted to target TPX2 and only 7 DEmiRNAs were identified to be prognostic biomarkers in LUAD. Then, 30 differentially expressed lncRNAs (DElncRNAs) were predicted to bind these 7 DEmiRNAs. Finally, we found that 7 DElncRNAs were correlated with the overall survival (all p <0.05). Furthermore, we identified elevated TPX2 was strongly correlated with the worse survival rate among 458 samples. Univariate and multivariate cox analysis showed TPX2 may act as an independent factor for prognosis in LUAD (p <0.05). Then pathway enrichment results suggested that TPX2 may facilitate tumorigenesis by participating in several cancer-related signaling pathways in LUAD, especially in Notch signal pathway. Conclusions: TPX2-related lncRNAs and miRNAs are related to the survival of LUAD. 7 lncRNAs, 7 miRNAs and TPX2 may serve as prognostic biomarkers in LUAD.

8.
Aging Clin Exp Res ; 2020 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-33052590

RESUMO

OBJECTIVE: To evaluate the effect of nutrition combined physical exercise interventions on age-related cognitive decline by a systematic review and meta-analysis. METHODS: We searched 9 databases, including PubMed, EMbase, The Cochrane Library, Web of Science, Science Direct, China National Knowledge Infrastructure (CNKI), VIP Information, China Biological Medical Database (CBM) and Wanfang for studies published until the end of December 2019. The selected trials should meet the following criteria, study objects: healthy adults aged 65 and over with cognitive dysfunction or diagnosed as MCI, but not meet the diagnostic criteria for dementia as well as no restriction on follow-up time, race or gender. Study interventions: multiple interventions including nutrition and exercise. EXCLUSION CRITERIA: (1) studies included elderly people with any type of dementia or patients with cognitive impairment induced by secondary causes, including drug, alcohol, severe organic brain diseases, mental disorders. (2) Republished literature. (3) Studies with significant differences in baseline data between groups. (4) The data in the study cannot be converted into the required data format. We reviewed and extracted information and assessed the risk of bias of recruited studies independently. Meta-analysis was performed using STATA v.15.1 software. The bias of publication was estimated by Egger test. RESULTS: A total of six RCTs representing 1039 participates were included in our meta-analysis. In terms of global cognitive function that has been assessed by neuropsychological test in different combinations, the result showed that the beneficial effect of nutrition combined exercise interventions was statistically significant [SMD = 0.23, 95% CI (0.1, 0.36), P = 0.0004]. There were no statistical differences from assays on MMSE scores, Memory, Executive Function, Attention, and Information Processing Speed across groups. CONCLUSIONS: The current study shows that nutrition combined exercise interventions can improve global cognitive function in the aged with cognitive decline. Further researches emphasizing on longer follow-up time, experimental randomness, credibility and scale would better elucidate the effect of nutrition combined exercise interventions on cognitive function, particularly in older adults. (registration number: CRD42020159291, date of registration: 28/04/2020).

9.
Neuropharmacology ; : 108356, 2020 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-33069757

RESUMO

Endothelin-1 (ET-1), an endogenous vasoconstrictor, has been known as a pro-nociceptive agent involved in multitude of pain. ET-1 acts on endothelin receptors on vascular endothelial cells, sensitizes release of ATP, which then acts on P2X3 receptors on nociceptors and results in mechanical hyperalgesia. Both endothelin receptors and P2X3 receptors are present in primary sensory neuron, where it remains unclear whether there is an interaction between them. Herein, we reported that ET-1 potentiated the electrophysiological activity of P2X3 receptors in rat dorsal root ganglia (DRG) neurons. ET-1 concentration-dependently increased α,ß-methylene-ATP (α,ß-meATP)-evoked inward currents, which were mediated by P2X3 receptors. ET-1 shifted the α,ß-meATP concentration-response curve upwards, with an increase of 34.38 ±â€¯4.72% in the maximal current response to α,ß-meATP in the presence of ET-1. ET-1 potentiation of α,ß-meATP-evoked currents was voltage-independent. ET-1 potentiated P2X3 receptor-mediated currents through endothelin-A receptors (ETAR), but not endothelin-B receptors (ETBR). ET-1 potentiation was supressed by blockade of intracellular G-protein or protein kinase C (PKC) signaling. Moreover, there is a synergistic effect on mechanical allodynia induced by intraplantar injection of ET-1 and α,ß-meATP in rats. Pharmacological blockade of P2X3 receptors also alleviated ET-1-induced mechanical allodynia. These results suggested that ET-1 sensitized P2X3 receptors in primary sensory neurons via an ETAR and PKC signaling pathway. Our data provide evidence that cutaneous ET-1 induced mechanical allodynia not only by increasing the release of ATP from vascular endothelial cells, but also by sensitizing P2X3 receptors on nociceptive DRG neurons.

10.
Plant Physiol ; 2020 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-32878973

RESUMO

Mammalian histone deacetylases (HDACs) undergo phosphorylation to regulate their localization, activity and function. However, little is known about the regulation of plant HDAC function and activity by phosphorylation. Here, we report the crystal structure of the Reduced Potassium Dependency3/Histone Deacetylase1 (RPD3/HDA1) type class II histone deacetylase HDA15 in Arabidopsis (Arabidopsis thaliana). The histone deacetylase domain of HDA15 (HDA15HD) assembles as tetrameric forms with each monomer composed of 12 α-helices and 9 ß-sheets. The L1 loop and ß2 sheet of HDA15HD are the essential interfaces for the tetramer formation. The N-terminal zinc finger domain enhances HDA15HD dimerization and increases its enzymatic activity. Furthermore, HDA15 can also be phosphorylated at Ser448 and Ser452 in etiolated seedlings. The HDA15 phosphorylation status determines its sub-nuclear localization and oligomerization. Phosphomimetics of HDA15 partially disrupt its oligomerization and cause loss of enzymatic activity and translocation from the nucleolus into nucleoplasm. Together, these data indicate that phosphorylation plays a critical role in regulating the structure and function of HDA15.

11.
Respir Res ; 21(1): 227, 2020 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-32873299

RESUMO

BACKGROUND: AKT2 is highly expressed in many human cancers, including non-small cell lung cancer (NSCLC). Accumulating evidence has also revealed that AKT2 can promote NSCLC cell proliferation and metastasis. However, the involved mechanism remains unclear. Herein, our study mainly explored the function of AKT2 during cancer progression and uncovered a new post-transcriptional mechanism of AKT2 expression in lung adenocarcinoma (LUAD). METHODS: Quantitative real-time (qRT-PCR), western blot and immunohistochemistry (IHC) assays were performed to detect the expression of AKT2 and other proteins. Cell counting kit-8 (CCK-8), colony formation and EdU assays were performed to assess cell proliferation. Flow cytometry analysis was used to detect changes in the cell cycle and apoptosis. Transwell assays were used to evaluate cell migration and invasion. Additionally, a luciferase reporter assay and western blotting were employed to assess miR-124 targeting of AKT2. Xenograft mouse model was used to observe the role of miR-124/AKT2 axis on the occurrence and development of LUAD. RESULTS: We showed that AKT2 was highly expressed in NSCLC tissues and closely related to the poor prognosis of LUAD patients. Moreover, AKT2 affected LUAD cell proliferation, migration and invasion by regulating the cell cycle and promoting the occurrence of epithelial-mesenchymal transition (EMT) and the expression of matrix metalloproteinases (MMPs). In addition, we demonstrated that miR-124 overexpression downregulated AKT2 expression by binding to the 3'-untranslated region (3'- UTR) of AKT2 and thus inhibited the occurrence and development of LUAD in vivo and in vitro. CONCLUSIONS: Our results suggest that miR-124 overexpression can negatively regulate AKT2 and thus inhibit the progression of LUAD. Therefore, the miR-124/AKT2 axis may serve as a potential target for novel therapies for LUAD.

12.
J Comp Eff Res ; 9(12): 839-848, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32885988

RESUMO

Background: The aim of the present study was to systematically review the exiting literature and to proceed a meta-analysis to determine the impact of chronic obstructive pulmonary disease (COPD) on mortality in patients with community acquired pneumonia. Materials & methods: Eligible studies were searched from PubMed, Cochrane Library and EMBASE. Odds ratios (ORs) with 95% CIs were used as effect estimates. Results: Twenty cohort studies were included. Analysis of unadjusted data revealed nonsignificant short- and long-term mortality associated with COPD. Analysis of adjusted 30-days mortality showed similarly no association between COPD and increased 30-days mortality (OR: 1.06, [0.68, 1.44]) but a positive association when COPD was confirmed spirometrically (OR: 1.84, [1.06, 2.62]). Conclusion: There is still no evidence to clear the impact of COPD on mortality in patients with community acquired pneumonia. More prospective studies with spirometrically-defined COPD and adequate adjustment for confounders are needed.

13.
Photodiagnosis Photodyn Ther ; : 102014, 2020 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-32950730

RESUMO

Glucose is main energy substance to drive the physiological events of the cell while resource mainly depends on uptake of glucose. Malignant cells exhibited a much higher rate of glycolysis than healthy cells to relieve the increased needs of energy. It will induce the overexpressive of Glucose Transporter (GLUT) to transport more glucose into malignant cells. Our research regarded overexpressive GLUT as a target of nanoparticles. Substrate of GLUT galactose conjugated Polyethylene glycol-Distearyl phosphatidyl ethanolamine (PEG-DSPE) as a kind of ligand was selected to modified liposome. Thermally activated delayed fluorescence (TADF) was encapsulated as fluorescent probe to evaluate its abilities of targeting malignant cells, and the results of confocal microscopy and flow cytometry demonstrated that Galactose-PEG-DSPE modified liposome had the stronger efficiency of cellular uptake by HepG2 cells compared with Blank-PEG-DSPE modified liposome. The effect of GLUT1 inhibitor on cellular uptake of Galactose-PEG-DSPE modified liposomes showed that the mechanism might be relative to Warburg effect causing GLUT overexpression.

14.
Expert Opin Drug Metab Toxicol ; : 1-5, 2020 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-32915093

RESUMO

BACKGROUND: This study aims to investigate the incidence of aspartate aminotransferase (AST), alanine aminotransferase (ALT) and triglyceride (TG) elevation, and the relationship with the phase I unit effect, and the moderate activity in healthy subjects enrolled in Phase I clinical trials. METHODS: The demographic, AST, ALT, TG and activity data were collected from the placebo (146 subjects) groups and tested drug (885 subjects) groups in 20 phase I trials. RESULTS: Elevated AST, ALT and TG levels above the upper limit of normal were detected in 1.37%, 4.79% and 34.7% of subjects in the placebo group, respectively, 3.73%, 6.67% and 39.2% of subjects in the tested drug group, respectively. The incidence of elevated AST, ALT and TG increased with the extended hospital stay. However, the incidence of elevated AST and ALT, but not the elevated TG, was reduced in subjects with moderate exercise during their hospital stay. The logistic regression analysis revealed that the baseline AST and ALT level, female gender, moderate exercise and duration of hospital stay were independent risk factors for ALT elevation. CONCLUSION: Moderate exercise during hospital stay may reduce the elevation rate of transaminases, but not TG, in subjects at phase I trials.

15.
Mol Med Rep ; 22(4): 3316-3326, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32945439

RESUMO

Medullary thyroid carcinoma (MTC) is a relatively rare subtype of thyroid cancer, accounting for 5­10% of all cases of thyroid cancer worldwide. Due to the current lack of knowledge regarding the tumorigenesis of MTC, the clinical treatment of MTC remains a challenge. It has been reported that microRNAs (miRNAs) regulate the progression of MTC; however, the regulatory network of miRNAs and the exact underlying mechanisms are not completely understood. In the present study, an miRNA expression profile (GSE40807), consisting of 80 samples, was downloaded and analyzed using Gene Expression Omnibus­2R to identify differentially expressed miRNAs between MTC and normal samples. miR­592 expression levels were significantly increased in MTC tissues and cell lines compared with normal tissues and cell lines. Patients with high miR­592 expression levels exhibited a less favorable prognosis compared with patients with low miR­592 expression. The results suggested that miR­592 overexpression promoted TT and MZ­CRC­1 cell proliferation in vitro. In addition, miR­592 negatively regulated cyclin­dependent kinase 8 (CDK8) via targeted binding in MTC cells. Moreover, co­transfection of CDK8 overexpression plasmid and miR­592 mimic reversed miR­592­mediated MTC cell proliferation. In conclusion, miR­592 may serve as an oncogene in MTC by decreasing the expression of CDK8, indicating that the miR­592/CDK8 axis might serve as a promising therapeutic target for MTC.

16.
J Int Med Res ; 48(8): 300060520939672, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32865090

RESUMO

OBJECTIVE: We investigated physical deviation and precocious puberty among school-aged children in Leshan City, to provide a theoretical basis for the management of precocious puberty in children. METHODS: We selected 12 primary schools of Leshan City using a cluster random sampling method and conducted physical examinations among healthy students aged 4 12 years. A total of 11,000 students were recruited (5502 boys and 5498 girls). We measured body mass index (BMI), and participants were tested for precocious puberty according to the Tanner stages and standard maps. Nutritional status was also evaluated. RESULTS: Obese and overweight children accounted for a high proportion of participants; the prevalence of underweight was the lowest. The prevalence of obesity among boys was higher than that in girls. Precocious puberty was mainly observed in girls, particularly those age 7 years old. The prevalence of precocious puberty among overweight and obese children was higher than that in children with normal weight. CONCLUSION: We identified a significant sex difference in precocious puberty among children in Leshan City. Overweight and obesity may be associated with precocious puberty.

17.
Ann Hematol ; 99(11): 2619-2628, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32960314

RESUMO

In the era of tyrosine kinase inhibitors (TKIs), allogeneic hematopoietic stem cell transplantation (allo-HSCT) is recommended as a standard approach for Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) achieving complete remission (CR). However, the role of autologous hematopoietic stem cell transplantation (auto-HSCT) in adult patients achieving complete molecular remission (CMR) is an alternative, less toxic treatment options, especially for the patients who lack suitable donors and are unfit for allo-HSCT. Thus, we conducted a systematic review and meta-analysis to compare the efficacy of allo-HSCT and auto-HSCT for the treatment of adult patients with Ph+ ALL. We searched the PubMed, Embase, Scopus, and Cochrane Library for studies published before June 2019 without language restriction. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated for overall survival (OS) and relapse-free survival (RFS) and odds ratios (ORs) and 95% CIs for relapse rate (RR) and treatment-related mortality (TRM). Four prospective studies and one retrospective study were included with a total of 810 patients. We found auto-HSCT was superior to allo-HSCT in OS (HR = 1.42, 95% CI: 1.06-1.91, P = 0.02), and there was no difference between allo-HSCT and auto-HSCT for RFS (HR = 1.10, 95% CI: 0.86-1.40, P = 0.44) and RR (OR = 0.53, 95% CI: 0.22-1.26, P = 0.15). The risk of TRM for patients undergoing allo-HSCT was significantly higher than that of the patients who received auto-HSCT (OR = 5.06, 95% CI: 1.03-24.75, P = 0.05). Our meta-analysis shows that auto-HSCT may be an attractive and alternative treatment option for adult Ph+ ALL patients achieving CMR, with similar or better outcomes than allo-HSCT in the era of TKIs.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Cromossomo Filadélfia , Leucemia-Linfoma Linfoblástico de Células Precursoras/mortalidade , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Adulto , Aloenxertos , Autoenxertos , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Taxa de Sobrevida
18.
Nat Commun ; 11(1): 4810, 2020 09 23.
Artigo em Inglês | MEDLINE | ID: mdl-32968061

RESUMO

Chimeric antigen receptor (CAR) therapy is a promising immunotherapeutic strategy for treating multiple refractory blood cancers, but further advances are required for solid tumor CAR therapy. One challenge is identifying a safe and effective tumor antigen. Here, we devise a strategy for targeting hepatocellular carcinoma (HCC, one of the deadliest malignancies). We report that T and NK cells transduced with a CAR that recognizes the surface marker, CD147, also known as Basigin, can effectively kill various malignant HCC cell lines in vitro, and HCC tumors in xenograft and patient-derived xenograft mouse models. To minimize any on-target/off-tumor toxicity, we use logic-gated (log) GPC3-synNotch-inducible CD147-CAR to target HCC. LogCD147-CAR selectively kills dual antigen (GPC3+CD147+), but not single antigen (GPC3-CD147+) positive HCC cells and does not cause severe on-target/off-tumor toxicity in a human CD147 transgenic mouse model. In conclusion, these findings support the therapeutic potential of CD147-CAR-modified immune cells for HCC patients.


Assuntos
Basigina/metabolismo , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/metabolismo , Imunoterapia Adotiva/métodos , Neoplasias Hepáticas/tratamento farmacológico , Receptores de Antígenos Quiméricos/efeitos dos fármacos , Animais , Basigina/genética , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , Modelos Animais de Doenças , Feminino , Células Hep G2 , Humanos , Células Matadoras Naturais , Fígado/patologia , Neoplasias Hepáticas/patologia , Masculino , Camundongos , Camundongos Knockout , Camundongos Transgênicos , Ensaios Antitumorais Modelo de Xenoenxerto
19.
Anal Methods ; 12(18): 2398-2406, 2020 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-32930266

RESUMO

Chinese mitten crabs (Eriocheir sinensis) are one of the most popular food items with a high nutritional value. The use of pesticides and environmental pollutants directly influenced improvements in productivity of mitten crabs. However, there is an increasing number of food safety issues raising consumer concerns. It is necessary to determine whether the pollutants that crabs contain are below the maximum residue limits to guarantee food safety. Moreover, there has been very little research on detecting pesticide residues and other pollutants in Chinese mitten crabs due to their complicated matrix effects. In the current study, a Quick, Easy, Cheap, Effective, Rugged and Safe (QuEChERS) method has been modified and validated for the simultaneous analysis of polychlorinated biphenyls (PCBs) and organochlorine pesticides (OCPs) in mitten crabs. By using acetonitrile extraction, low temperature (freezing) precipitation and clean-up by mixed sorbents of C18, PSA and Florisil (magnesium silicate), the method was proved to be valid with linearity, precision, recovery, limit of quantification (LOQ), and limit of detection (LOD) with recoveries ranging from 85.9-119.8% and LOQ within 0.1-3.6 µg kg-1. The method was also applied to detect PCBs and OCPs in 48 crab samples from Jiangxi Province, China. The results showed that most of the crab samples contained PCB 118, beta-HCH and p,p'-DDT, and the content of p,p'-DDD in mitten crabs of Jiangxi Province showed sex-specific differences, which might be connected with sex-differential regulation.

20.
Artigo em Inglês | MEDLINE | ID: mdl-32922362

RESUMO

Melanocortin-4 receptor (MC4R) plays important roles in regulation of multiple physiological processes, and interaction of MC4R and melanocortin receptor accessory protein 2 (MRAP2) is suggested to play pivotal role in energy balance of vertebrates. Topmouth culter (Culter alburnus) is an economically important freshwater fish in China. Herein we cloned culter mc4r, mrap2a, and mrap2b. Culter mc4r consisted of a 981 bp open reading frame encoding a protein of 326 amino acids. qRT-PCR revealed that mc4r, mrap2a, and mrap2b were primarily expressed in the central nervous system. In the periphery, mc4r and mrap2b were expressed more widely in the male, while mrap2a was expressed more widely in the female. Culter MC4R could bind to four peptide agonists and increase intracellular cAMP production dose dependently. Culter MC4R was constitutively active in both cAMP and ERK1/2 pathways, which was differentially regulated by culter MRAP2a and MRAP2b. Culter MRAP2a significantly increased Bmax and decreased agonist-stimulated cAMP, while MRAP2b increased cell surface and total expression but did not affect Bmax and agonist-stimulated cAMP. These results will aid the investigation of the potential physiological processes that MC4R might be involved in topmouth culter.

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