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1.
Sci Rep ; 10(1): 16478, 2020 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-33020536

RESUMO

Phospholamban (PLN) is an important regulator for sarcoendoplasmic reticulum (SR) calcium transport ATPase (SERCA), which uptakes Ca2+ to SR during the diastolic phase of cardiomyocytes to maintain intracellular calcium homeostasis. Mutations on PLN result in intracellular calcium disorder, myocardial contraction defect, and eventually heart failure and/or malignant ventricular arrhythmia. Since 2003, several kinds of PLN mutations have been identified in familial dilated cardiomyopathy (DCM) patients, illustrating a few clinical characteristics that differs from classical DCM patients. Herein, we report a large PLN-R14del family with typical clinical characteristics reported including relatively late-onset clinical symptoms, low-voltage in ECG, as well as frequent ventricular arrythmias. Moreover, members underwent cardiac magnetic resonance (CMR) examination showed a strikingly similar pattern of late gadolinium enhancement (LGE)-Sub-epicardial involvement in the left ventricular (LV) lateral wall with or without linear mid-wall enhancement in the interventricular septum. The former one can also present in younger PLN-R14del carriers despite completely normal LV structure and function. Meanwhile, T1 mapping also found significantly increased extracellular volume (ECV) in PLN-R14del carriers. These findings highlight the special role of CMR to phenotyping PLN-induced cardiomyopathy patients and distinguish them from other types of cardiomyopathy.

2.
J Hum Genet ; 2020 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-33040084

RESUMO

Long continuous stretches of homozygosity (LCSH) are associated with risk of recessive disorders. Though LCSH can be detected by SNP microarrays, additional testing is necessary to clarify the clinical significance. This study is to assess the yield of additional exome sequencing (ES) after LCSH detection and inform the likelihood of eventual diagnosis. In 2226 patients referred to SNP microarrays, 35 patients met the criteria of indicative LCSH. These patients were recruited and went through additional ES. The diagnostic yield was analyzed, and the LCSH pattern was compared between eventually diagnosed cases and those undiagnosed. The results showed additional ES attained a diagnostic yield of 31.4% (11/35), but only one-third of the yield (11.4%, 4/35) was relevant to LCSH. In contrast, two-thirds of the diagnostic variants (20%, 7/35) were de novo or dominantly inherited, irrelevant to the original LCSH finding. No particular LCSH pattern, including the chromosomal coverage or LCSH size, was found to associate with the diagnostic outcome. We concluded that additional ES after LCSH detection could reveal diagnostic variants, but it is strongly recommended to consider all possible inheritance mode, as the diagnostic variants may be irrelevant to the original LCSH finding.

3.
J Magn Reson Imaging ; 2020 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-33043991

RESUMO

BACKGROUND: Liver fibrosis is a common process resulting from various etiologies. Sustained progression of liver fibrosis leads to cirrhosis, even hepatocellular carcinoma. Thus, noninvasive staging of liver fibrosis is of clinical importance. Radiomics is an emerging approach for staging liver fibrosis. However, the feature selection methods and classifier models are complicated, and may result in a discrepancy of diagnostic performance owing to different radiomics models. PURPOSE: To identify the optimal feature selection and classifier methods for predicting liver fibrosis by using nonenhanced T1 -weighted imaging. STUDY TYPE: Prospective. ANIMAL MODEL: Wistar rats, total 97. FIELD STRENGTH/SEQUENCE: 3T, 3D T1 -weighted images with fast-spoiled gradient echo (FSPGR). ASSESSMENT: Liver fibrosis rats were induced via subcutaneous injection of a mixture of carbon tetrachloride. Rats in the control group were injected with saline. Segmentation and feature extraction were performed by 3D slicer and the image biomarker explorer (IBEX) software package. Data preprocessing, feature selection, model building, and model comparative evaluation were conducted with Python. The liver fibrosis stage was determined by pathological examination. STATISTICAL TESTS: Receiver operating characteristic curve, fuzzy comprehensive evaluation. RESULTS: For discriminating between F0 and F1-2, F0 and F3-4, F0 and F1-4, F0-1 and F2-4, F0-2 and F3-4, and F0-3 and F4, the accuracies of 12 radiomics models were 77.27-90.91%, 73.33-86.67%, 80.56-91.67%, 74.07-88.89%, 76.47-88.24%, and 79.49-92.31%, respectively. The AUCs of the radiomics models were 0.86-0.97, 0.85-0.95, 0.89-0.97, 0.81-0.96, 0.82-0.93, and 0.85-0.96, respectively. The least absolute shrinkage and selection operator / support vector machine (LASSO-SVM) model had high AUCs of 0.93-0.97. For discriminating between F0 and F1-2, F0 and F3-4, F0 and F1-4, F0-1 and F2-4, and F0-2 and F3-4, the fuzzy comprehensive evaluation showed that the LASSO-SVM model had a high fuzzy score/order of 0.087-0.091/1. DATA CONCLUSION: LASSO-SVM appears to be the optimal model for predicting liver fibrosis by using nonenhanced T1 -weighted imaging in a rodent model of liver fibrosis. LEVEL OF EVIDENCE: 2. TECHNICAL EFFICACY STAGE: 2.

4.
Lancet Infect Dis ; 2020 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-33031750

RESUMO

BACKGROUND: Since 1997, epidemics of hand, foot, and mouth disease associated with enterovirus A71 (EV-A71) have affected children younger than 5 years in the Asia-Pacific region, including mainland China. EV-A71 vaccines have been licensed for use in children aged 6-71 months in China, but not for infants younger than 6 months. We aimed to assess the dynamics of maternal EV-A71 antibodies to inform choice of potential vaccination strategies to protect infants younger than 6 months, because they have a substantial burden of disease. METHODS: We did a longitudinal cohort study with mother-neonate pairs in local hospitals in southern China during 2013-18. We collected cord blood from neonates and venous blood from mothers at delivery. We followed up and collected blood samples from the children at ages 2, 4, 6, 12, 24, and 36 months and tested for the presence of neutralising antibodies against EV-A71 with virus neutralisation assays. Seropositivity, or protective titre, was defined as a neutralisation antibody titre of 16 or higher. We estimated the seroprevalence, geometric mean titre (GMT), and transfer ratio of maternal antibodies. We used a binomial distribution to derive the 95% CIs of seroprevalence. Seropositivity between mothers and neonates was compared by use of an agreement (κ), while GMTs were compared by use of paired Student's t tests. FINDINGS: Between Sept 20, 2013, and Oct 14, 2015, 1054 mothers with 1066 neonates were enrolled. The EV-A71 GMT was similar among pairs of neonates (22·7, 95% CI 20·8-24·9) and mothers (22·1, 95% CI 20·2-24·1; p=0·20). The mean transfer ratio of maternal antibodies was 1·03 (95% CI 0·98-1·08). Although 705 (66%) of 1066 neonates acquired protective concentrations of EV-A71 antibodies from mothers, these declined rapidly, with a half-life of 42 days (95% CI 40-44). The time to loss of protective immunity was extended to 5 months in neonates with mothers who had titres of 128 or higher. By age 30 months, 28% of children had become seropositive because of natural infection. INTERPRETATION: EV-A71 maternal antibodies were efficiently transferred to neonates, but declined quickly to below the protective threshold, particularly among those whose mothers had low antibody titres. Our findings suggest that maternal vaccination could be explored to provide neonatal protection against EV-A71 through maternal antibodies. Catch-up vaccination between ages 6 months to 5 years could provide protection to the approximately 30-90% of children that have not had natural EV-A71 infection by that age. FUNDING: National Science Fund for Distinguished Young Scholars, National Natural Science Foundation of China.

5.
Mini Rev Med Chem ; 2020 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-32912124

RESUMO

Many plants in the genus Zanthoxylum, belonging to the Rutaceae family, are recorded as folk medicines for the treatment of various diseases, which attracts much attention for their phytochemical and pharmacological activity investigations. Alkaloids are the largest secondary metabolites with structurally diverse types found in this genus and they demonstrate a wide range of biological activities. The aim of this review is to provide a summary on the isolation, classification, and biological properties of the alkaloids from Zanthoxylum species, which also will bring more attention to other researchers for further biological study on alkaloids for the new drug development.

6.
Medicine (Baltimore) ; 99(33): e21387, 2020 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-32871988

RESUMO

To investigate the estimated glomerular filtration rates of chronic hepatitis B (CHB) patients with or without liver cirrhosis, and to explore the related risk factors.A total of 559 CHB patients were enrolled. Liver cirrhosis was diagnosed with ultrasound. The Child-Pugh scoring system was used to stage patients with liver cirrhosis. The Modification of Diet in Renal Disease (MDRD) formula was used to calculate the estimated glomerular filtration rate (eGFR).A total of 296 patients were involved. The results showed that the incidence of renal impairment in patients with liver cirrhosis was 8.45% (25/296). The incidence of renal impairment in Child-Pugh C patients was significantly higher than that in Child-Pugh B and Child-Pugh Grade A patients (i.e., 17.2% [17/99] vs 6.67% [7/105] vs 1.09% [1/92], respectively, P < .001); age, hyperuricemia, and Child-Pugh score are all risk factors for impaired renal function.With the deterioration of liver function in patients with cirrhosis, the incidence of impaired renal function has increased significantly, and renal function should be closely monitored to guide patients in clinical medication.


Assuntos
Taxa de Filtração Glomerular , Hepatite B Crônica/complicações , Cirrose Hepática/complicações , Insuficiência Renal/etiologia , Adulto , Feminino , Humanos , Cirrose Hepática/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Fatores de Risco
7.
Talanta ; 220: 121422, 2020 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-32928432

RESUMO

Abnormal DNA glycosylases are concerned with the aging process as well as numerous pathologies in humans. Herein, a sensitive fluorescence method utilizing target-induced ligation-dependent tricyclic cascade amplification reaction was developed for the detecting DNA glycosylase activity. The presence of DNA glycosylase triggered the cleavage of damaged base in hairpin substrate, successively activating ligation-dependent strand displacement amplification (SDA) and exponential amplification reaction (EXPAR) for the generation of large amount of reporter probes. The resultant reporter probes bound with the signal probes to form stable dsDNA duplexes. And then the signal probes could be digested circularly in the dsDNA duplexes by T7 exonuclease, leading to the generation of an enhanced fluorescence signal. Due to the high efficiency of tricyclic cascade amplification and the low background signal deriving from the inhibition of nonspecific amplification, this method exhibited a detection limit of 0.14 U/mL and a dynamic range from 0.16 to 8.0 U/mL. Moreover, it could be applied for detecting DNA glycosylase activity in human serum with good selectivity and high sensitivity, and even quantifying other types of enzyme with 5'-PO4 residue cleavage product by rationally designing the corresponding substrate. Importantly, this method could be performed in homogenous solution without any complicated separation steps, providing a new strategy for DNA glycosylase-related biomedical research.

8.
Cell Biochem Funct ; 2020 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-32869878

RESUMO

It is reported that long intergenic non-coding RNA 00662 (LINC00662) plays an oncogenic role in tumours. However, the mechanism of LINC00662 in regulating the progression and radiosensitivity of cervical cancer (CC) is not clear. In this study, quantitative real-time polymerase chain reaction (qRT-PCR) was adopted to detect LINC00662 and miR-497-5p expressions in CC tissues and cells. The expression of cell division cycle 25 A (CDC25A) in CC cells was examined by Western blot. CC cell proliferation was determined by cell counting kit-8 (CCK-8) and BrdU assays. The survival rate of CC cells was evaluated by colony formation assay under different doses of X-ray irradiation. CC cell migration and invasion were probed by Transwell assay. Besides, the interactions between miR-497-5p and LINC00662, and miR-497-5p and the 3'UTR of CDC25A were verified by dual-luciferase reporter assay, RIP assay, and RNA pull-down experiments. We demonstrated that, LINC00662 expression was remarkably raised in CC tissues and cell lines. LINC00662 overexpression promoted proliferation, migration, invasion and radioresistance of CC cells, and LINC00662 knockdown inhibited the above malignant phenotypes of CC cells. In terms of mechanism, LINC00662 facilitated CC progression and radioresistance by adsorbing miR-497-5p and indirectly up-regulating CDC25A expression. In a word, the LINC00662/miR-497-5p/CDC25A axis boosts proliferation and metastasis of CC cells and enhances the radioresistance of cancer cells. SIGNIFICANCE OF THE STUDY: CC poses a threat to the health of women all over the world. In this study, we demonstrated for the first time that LINC00662 expression was remarkably raised in CC tissues and cells. Cellular experiments confirmed that LINC00662 facilitated cell proliferation, migration, invasion and radiation resistance through the miR-497-5p/CDC25A axis, which might be a promising target for CC treatments.

9.
Signal Transduct Target Ther ; 5(1): 212, 2020 09 22.
Artigo em Inglês | MEDLINE | ID: mdl-32963228

RESUMO

The outbreaks of severe acute respiratory syndrome (SARS) and Coronavirus Disease 2019 (COVID-19) caused by SARS-CoV and SARS-CoV-2, respectively, have posed severe threats to global public health and the economy. Treatment and prevention of these viral diseases call for the research and development of human neutralizing monoclonal antibodies (NMAbs). Scientists have screened neutralizing antibodies using the virus receptor-binding domain (RBD) as an antigen, indicating that RBD contains multiple conformational neutralizing epitopes, which are the main structural domains for inducing neutralizing antibodies and T-cell immune responses. This review summarizes the structure and function of RBD and RBD-specific NMAbs against SARS-CoV and SARS-CoV-2 currently under development.


Assuntos
Anticorpos Monoclonais/química , Anticorpos Neutralizantes/química , Anticorpos Antivirais/química , Infecções por Coronavirus/prevenção & controle , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , Síndrome Respiratória Aguda Grave/prevenção & controle , Glicoproteína da Espícula de Coronavírus/química , Anticorpos Monoclonais/biossíntese , Anticorpos Neutralizantes/biossíntese , Anticorpos Antivirais/biossíntese , Betacoronavirus/efeitos dos fármacos , Betacoronavirus/imunologia , Betacoronavirus/patogenicidade , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/virologia , Reações Cruzadas , Epitopos/química , Epitopos/imunologia , Epitopos/metabolismo , Humanos , Modelos Moleculares , Peptidil Dipeptidase A/química , Peptidil Dipeptidase A/imunologia , Peptidil Dipeptidase A/metabolismo , Pneumonia Viral/imunologia , Pneumonia Viral/virologia , Ligação Proteica , Estrutura Secundária de Proteína , Receptores Virais/química , Receptores Virais/imunologia , Receptores Virais/metabolismo , Vírus da SARS/efeitos dos fármacos , Vírus da SARS/imunologia , Vírus da SARS/patogenicidade , Síndrome Respiratória Aguda Grave/imunologia , Síndrome Respiratória Aguda Grave/virologia , Glicoproteína da Espícula de Coronavírus/imunologia , Glicoproteína da Espícula de Coronavírus/metabolismo , Vírion/imunologia , Vírion/ultraestrutura
10.
Brain Res ; : 147121, 2020 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-32919982

RESUMO

Epilepsy is a common neurological disease and its most common type is temporal lobe epilepsy (TLE). Novel therapeutics is needed as many TLE patients are resistant to treatments like anticonvulsants or temporal lobectomy. Stem cell therapy has great promise in regeneration medicine. In the current study, we tried to investigate the potential protective effects of adipose-derived stem cell (ADSC) transplantation in epileptic rats. Epilepsy model was established by intra-hippocampal injection of kainic acid (KA) in rats. ADSCs were isolated, differentiated and transplanted into hippocampus of KA rats. There were three groups of rats: normal control group receiving saline injection and no transplantation, KA+sham group receiving KA injection and sham transplantation surgery and KA+transplantation group receiving KA injection and ADSC transplantation. We found that ADSCs were highly positive for CD44, CD90, CD29 and CD105, and neural differentiation induced the expression of neuronal markers like Tuj1, MAP2, NeuN and PSD-95. EEG recording showed that KA induced seizure activity while ADSC transplantation inhibited seizure activity. In training session of Morris water maze task, KA injection impaired the learning capacity of rats while ADSC transplantation restored the learning capacity at 2-week or 2-month post transplantation. In probe session of Morris water maze task, KA injection impaired the memory of rats while ADSC transplantation restored the memory at 2-week or 2-month post transplantation. Transplanted ADSCs released BDNF, NT3 and NT4. Pro-apoptotic BAX was reduced while anti-apoptotic BCL-2 and BCL-xL were increased in hippocampus post ADSC transplantation. Our study suggests that ADSC transplantation inhibits KA-induced seizures and improves the learning and memory function of epileptic rats.

11.
Materials (Basel) ; 13(18)2020 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-32947933

RESUMO

The National Institute of Standards and Technology (NIST), the National Institutes of Health (NIH) and other industry stakeholders have been working together to enable fluorescence intensities of flow cytometer calibration beads to be assigned quantitative equivalent reference fluorophore (ERF) values with high accuracy and precision. The ultimate goal of this effort is to accurately quantify the number of antibodies bound to individual living cells. The expansion of this effort to assign ERF values to more than 50 fluorescence channels and particles with diameters ranging from 10 µm down to 80 nm is reported here.

12.
FASEB J ; 2020 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-32949431

RESUMO

As a reversible scar repair reaction, liver fibrosis can be blocked or even reversed by proper intervention during its formation. Our work suggests that acid-sensitive ion channel 1a (ASIC1a) participates in liver fibrosis and presents a novel mechanism involving m6 A modification and miR-350/SPRY2. We demonstrated that the expression of ASIC1a was significantly increased in liver tissue of patients with liver fibrosis and animal models of liver fibrosis, as well as PDGF-BB-induced activated HSC-T6. After downregulating the expression of ASIC1a, the degree of liver fibrosis is reduced and HSC activation was inhibited, the level of m6 A modification and miR-350 expression were also reduced. The results of dual luciferase reporter assay showed that miR-350 can bind to the target gene SPRY2 and inhibit its expression. We also found that METTL3 can regulate the extent of m6 A modification of pri-miR-350 by binding to DGCR8. In addition, silencing or blocking the expression of ASIC1a can reduce the expression of PI3K/AKT and ERK signaling pathway-related proteins in activated HSCs. Taken together, we demonstrated that ASIC1a regulates the processing of miR-350 through METTL3-dependent m6 A modification, and mature miR-350 targets SPRY2 and further promotes liver fibrosis through the PI3K/KT and ERK pathways.

13.
J Int Med Res ; 48(9): 300060520946871, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32962499

RESUMO

Cases of extrahepatic bile duct carcinoma are mostly adenocarcinomas and extrahepatic bile duct squamous cell carcinomas are rare. We report here a case of choledochal squamous cell carcinoma in a young woman who underwent surgery and chemotherapy. The woman presented with abdominal discomfort. A physical examination showed tenderness in the upper abdomen. Laboratory tests showed elevated direct bilirubin, total bilirubin, and C-reactive protein levels. Abdominal computed tomography and magnetic resonance imaging showed a cystic-solid mixed soft tissue mass in the common bile duct. Pain symptoms in the patient were not relieved and surgical treatment was performed. Postoperative pathological results showed a choledochal cyst complicated by squamous cell carcinoma. The patient was treated by biliary intestinal anastomosis followed by chemotherapy. However, the patient developed liver metastasis and recurrence at a 6-month follow-up. Primary congenital bile duct cysts with squamous cell carcinoma are extremely rare. Surgical resection is the main treatment option for choledochal squamous cell carcinoma. Postoperative chemoradiotherapy can be used, but the efficacy is poor and chemotherapy does not significantly prolong the patient's survival.

14.
Environ Technol ; : 1-12, 2020 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-32876536

RESUMO

Cr(VI)-imprinting thiosemicarbazide-functionalized sodium alginate (IIPTSC@SA) microspheres were fabricated to achieve the good selective adsorption for Cr(VI) removal from aqueous solution containing multiple ions. The selective adsorption and reusability of IIPTSC@SA microsphere were intensively investigated. The results showed that the grafting conditions of thiosemicarbazide were optimized at 0.2 g of TSC at 60 °C for 5 h and the ion-imprinting conditions at 100 mL of 2 wt % glutaraldehyde at 60 °C for 6 h. IIPTSC@SA microspheres exhibited the maximum adsorption capacity of 252.5 mg/g and good selectivity to remove Cr(VI) from multi-ion coexisting water. The adsorption process complied with a monolayer adsorption by virtue of chemical interactions together with endothermic spontaneously. After eight adsorption-desorption, the adsorption capacity and selectivity of IIPTSC@SA microspheres remained relatively stable.

15.
J Int Med Res ; 48(9): 300060520949409, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32938270

RESUMO

OBJECTIVE: Several recent studies have shown that the aldosterone synthase gene (CYP11B2) -344C/T polymorphism is related to cardiovascular diseases. However, whether the -344C allele influences the incidence of cardiovascular diseases in Chinese patients with hypertension is unclear. METHODS: Chinese patients with essential hypertension were genotyped for the -344C/T polymorphism in CYP11B2 (n = 755; CC, n = 112; CT, n = 361; TT, n = 282) and followed for 11 years for major adverse cardiovascular events (MACEs), including stroke, onset of coronary artery disease (CAD), and CAD-related death. Established cardiovascular risk factors were used to adjust the multivariate Cox analysis. RESULTS: After a mean follow-up period of 7.60 ± 1.12 years, a significantly higher incidence of MACEs was seen in patients with the CC genotype than in those with the CT and TT genotypes. The CC variant was significantly and independently predictive of MACEs (hazard ratio = 2.049), CAD (hazard ratio = 1.754), and stroke (hazard ratio = 2.588), but not CAD-related stroke or death. CONCLUSION: The CYP11B2 -344 CC genotype is a risk factor for CAD and stroke, independent of other established cardiovascular risk factors in Chinese patients with hypertension.

16.
Int J Biol Macromol ; 165(Pt A): 675-682, 2020 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-32979450

RESUMO

Roasting may be beneficial to extend the shelf life by inactivating the lipases and peroxidases in highland barley, but it may lead to the deterioration of starch quality. In this study, the pre-treatment techniques of pearling and tempering were tried to improve the efficiency of inactivation, and different roasting treatment parameters were compared to obtain the optimum treatment conditions, under which thermally degraded starch may be less. Pearling had been proved to be an effective means in reducing enzyme content, and tempering could improve the sensitivity of enzymes to heat. Synergism of the two pre-treatment methods increased the inactivation of lipase and peroxidase in highland barley to 80% and 100%, respectively, and the optimal pre-treatment and roasting condition was P20M16T16 (20% pearling rate, 16% moisture, and 16 min treatment time) at 180 °C. Under this condition, the starch quality was basically consistent with those of control starch. For roasting treatment starch, the birefringence intensity, swelling power, and solubility slightly decreased and the polarized cross also still existed, while the relative crystallinity slightly increased and the crystal type unchanged. Roasting treatment starch showed higher pasting temperature and lower paste viscosity, and the increasing To, Tp, and the decreasing enthalpy.

17.
Cancer Med ; 2020 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-32970934

RESUMO

To explore the characteristics and prognostic significance of genetic mutations in acute myeloid leukemia (AML), we screened the gene mutation profile of 171 previously untreated AML patients using a next-generation sequencing technique targeting 127 genes with potential prognostic significance. A total of 390 genetic alterations were identified in 149 patients with a frequency of 87.1%. Younger age and high sensitivity to induction chemotherapy were associated with a lower number of mutations. NPM1 mutation was closely related to DNMT3A and FLT3-internal tandem duplication (FLT3-ITD) mutations, but mutually exclusive with ASXL1 mutation and CEBPAdouble mutation . In univariate analysis, ASXL1 or TET2 mutation predicted shorter overall survival (OS) or relapse-free survival (RFS), DNMT3A, FLT3-ITD, or RUNX1 mutation predicted a higher likelihood of remission-induction failure, whereas NRAS mutation or CEBPAdouble mutation predicted longer OS. Concurrent DNMT3A, FLT3-ITD, and NPM1 mutations predicted shorter OS. Hypomethylation agents could improve the OS in patients with DNA methylation-related mutations. According to multivariate analysis, TET2 mutation was recognized as an independent prognostic factors for RFS. In summary, our study provided a detailed pattern of gene mutations and their prognostic relevance in Chinese AML patients based on targeted next-generation sequencing screening.

18.
Nanomedicine (Lond) ; 15(22): 2149-2170, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32885720

RESUMO

Extracellular vesicles (EVs), such as exosomes and microvesicles, are nonreplicating lipid bilayer particles shed by most cell types which have the potential to revolutionize the development and efficient delivery of clinical therapeutics. This article provides an introduction to the landscape of EV-based vectors under development for the delivery of protein- and nucleic acid-based therapeutics. We highlight some of the most pressing measurement and standardization challenges that limit the translation of EVs to the clinic. Current challenges limiting development of EVs for drug delivery are the lack of: standardized cell-based platforms for the production of EV-based therapeutics; EV reference materials that allow researchers/manufacturers to validate EV measurements and standardized measurement systems for determining the molecular composition of EVs.

19.
Food Funct ; 11(10): 8743-8756, 2020 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-32955050

RESUMO

Salvianolic acid B (Sal B) exhibits anti-obesity activity, yet the underlying mechanism linking this effect to metabolic endotoxemia remains unexplored. For this purpose, high-fat diet-induced obese mice were orally administered with Sal B for 10 weeks. Hematoxylin/eosin staining, transmission electron microscopy, and immunohistochemical staining were used to evaluate histopathological alterations in the white adipose tissue (WAT) and/or jejunums. The expression levels of genes related to fat and cholesterol synthesis in the WAT were determined by qPCR. The composition of fecal microbiota was profiled by 16S rRNA gene pyrosequencing. Western blotting was employed to evaluate the relative protein expressions involved in lipopolysaccharide (LPS)/toll-like receptor 4 (TLR4) signaling pathway in the WAT. Treatment of obese mice with Sal B improves insulin sensitivity, attenuates body weight gain and alleviates serum levels of LPS and tumor necrosis factor alpha, which is associated with an improvement in intestinal epithelial integrity and probiotic composition as well as a reduction in Gram-negative Proteobacteria and Deferribacteres. In addition, Sal B downregulates the expressions of TLR4 and myeloid differential factor-88, as well as the phosphorylation levels of Jun N-terminal kinase, nuclear factor-kappa B p65, and an insulin receptor substrate in the WAT. In summary, Sal B may attenuate body weight gain and insulin resistance through the regulation of gut microbiota abundances and LPS/TLR4 signaling pathway in obese mice, suggesting Sal B could be a promising drug candidate for protection against obesity.

20.
J Cell Mol Med ; 24(19): 11318-11329, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32889785

RESUMO

Long non-coding RNAs (lncRNAs) have come out as critical molecular regulators of human tumorigenesis. In this study, we sought to identify and functionally characterize lncRNAs as potential mediators of colorectal cancer progression. We screened and identified a novel lncRNA, ADAMTS9-AS1, which was significantly decreased in colorectal cancer tissues and was correlated with clinical outcome of patients according to The Cancer Genome Atlas (TCGA) database. In addition, ADAMTS9-AS1 regulated cell proliferation and migration both in vitro and in vivo. Bioinformatics analysis revealed that overexpression of lncRNA-ADAMTS9-AS1 preferentially affected genes that were linked to proliferation and migration. Mechanistically, we found that ADAMTS9-AS1 obviously suppressed ß-catenin, suggesting that Wnt signalling pathway participates in ADAMTS9-AS1-mediated gene transcriptional regulation in the suppression of colorectal tumorigenesis. Finally, we found that exosomal ADAMTS9-AS1 could serve as a diagnostic biomarker for colorectal cancer with AUC = 0.835 and 95% confidence interval = 0.777-0.911. Our data demonstrated that ADAMTS9-AS1 might play important roles in colorectal cancer by suppressing oncogenesis. Targeting ADAMTS9-AS1 may have potential clinical applications in colorectal cancer prognosis and treatment as an ideal therapeutic target. Finally, exosomal lncRNA-ADAMTS9-AS1 is a promising, novel diagnostic biomarker for colorectal cancer.

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