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1.
Heart Surg Forum ; 24(2): E278-E281, 2021 03 25.
Artigo em Inglês | MEDLINE | ID: mdl-33798043

RESUMO

Pulmonary artery sling (PAS) is a rare congenital vascular anomaly. Ninety percent of patients with PAS have respiratory distress and need surgical correction. Asymptomatic adult presentation of PAS is rare. We report the case of a 56-year-old female with an asymptomatic left pulmonary artery sling.

2.
Langmuir ; 2021 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-33826349

RESUMO

Poly(ethylene-co-vinyl acetate) (PEVAc) nanocomposites containing exfoliated α-zirconium phosphate (ZrP) have been prepared using a simple solution mixing method to improve their barrier and mechanical properties. ZrP was pre-exfoliated with a surfactant, followed by additional targeted surface functionalization and surfactant exchange to allow for hydrogen bonding of ZrP with the acetate functionality on PEVAc and to improve ZrP surface hydrophobicity. The solvent is found to play an important role in stabilizing ZrP exfoliation in the presence of PEVAc to retain full exfoliation and homogeneous dispersion upon the removal of the solvent. The PEVAc/ZrP nanocomposite exhibits greatly improved oxygen barrier, melt strength, and mechanical properties. The usefulness of the present study for the preparation of olefinic polymer nanocomposites is discussed.

3.
Heart Surg Forum ; 24(2): E249-E255, 2021 03 05.
Artigo em Inglês | MEDLINE | ID: mdl-33798054

RESUMO

OBJECTIVE: This study aimed to evaluate the application of synchronized nasal intermittent positive pressure ventilation (SNIPPV) in the respiratory weaning of infants after congenital heart surgery. METHODS: We retrospectively analyzed the clinical data of 63 infants who were extubated from mechanical ventilation after congenital heart surgery between January 2020 and September 2020. The data, including demographics, anatomic diagnosis, radiology and laboratory test results, and perioperative variables were recorded. RESULTS: The extubation failure rate within 48 h after extubation was significantly lower in the SNIPPV group than in the nasal continuous positive airway pressure (NCPAP) group. The PaO2 level and PaO2/FiO2 ratio within 48 h after extubation were higher in the SNIPPV group than in the NCPAP group (P < .05). Meanwhile, the PaCO2 level within 48 h was significantly lower in the SNIPPV group (P < .05). Compared with the NCPAP group, the median duration of postoperative noninvasive support and the duration from extubation to hospital discharge were shorter in the SNIPPV group; the total hospital cost was lower in the SNIPPV group. No significant differences were observed between the two groups concerning VAP, pneumothorax, feeding intolerance, sepsis, mortality, and other complications (P > .05). CONCLUSION: SNIPPV was shown to be superior to NCPAP in avoiding reintubation after congenital heart surgery in infants and significantly improved oxygenation and reduced PaCO2 retention after extubation. Further studies are needed to confirm the efficacy and safety of SNIPPV as a routine weaning strategy.

4.
Food Chem ; 355: 129608, 2021 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-33799260

RESUMO

Effects of enzymatic hydrolysis on the structural, rheological, and functional properties of mulberry leaf polysaccharide (MLP) were characterized in this study. The enzymatic hydrolysis of MLP raised the carbonyl, carboxyl, and hydroxyl groups from 7.21 ± 0.86 to 10.08 ± 0.28 CO/100 Glu, 9.40 ± 0.13 to 17.55 ± 0.34 COOH/100 Glu, and 5.71 ± 0.33 to 8.14 ± 0.24 OH/100 Glu, respectively. Meanwhile, an increase in thixotropic performance and structure-recovery capacities were observed in hydrolyzed MLP, while the molecular weight, surface tension, apparent viscosity, and thermal stability were decreased. An improved antioxidant activity of MLP was also achieved after the enzymatic degradation. Moreover, the hydrolyzed MLP showed greater ability to promote the growths of Bifidobacterium bifidum, Bifidobacterium adolescentis, Lactobacillus rhamnosus, and Lactobacillus acidophilus and the production of acetic acid, butyric acid, and lactic acid. The results demonstrate that enzymatic modification is a useful approach for polysaccharide processing.

5.
Antioxidants (Basel) ; 10(4)2021 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-33805536

RESUMO

Selenium (Se) is an essential micro-mineral and plays important roles in antioxidant responses, and also influences lipid metabolism and selenoprotein expression in vertebrates, but the effects and mechanism remain unknown. The study was undertaken to decipher the insights into dietary Se influencing lipid metabolism and selenoprotein expression in the anterior and middle intestine (AI and MI) of yellow catfish Pelteobagrus fulvidraco. Yellow catfish (weight: 8.27 ± 0.03 g) were fed a 0.03- (M-Se), 0.25- (A-Se), or 6.39- (E-Se) mg Se/kg diet for 12 wk. AI and MI were analyzed for triglycerides (TGs) and Se concentrations, histochemistry and immunofluorescence, enzyme activities, and gene and protein levelsassociated with antioxidant responses, lipid metabolism, endoplasmic reticulum (ER) stress, and selenoproteome. Compared to the A-Se group, M-Se and E-Se diets significantly decreased weight gain (WG) and increased TGs concentration in the AI and MI. In the AI, compared with A-Se group, M-Se and E-Se diets significantly increased activities of fatty acid synthase, expression of lipogenic genes, and suppressed lipolysis. In the MI, compared to the A-Se group, M-Se and E-Se diets significantly increased activities of lipogenesis and expression of lipogenic genes. Compared with A-Se group, E-Se diet significantly increased glutathione peroxidase (GPX) activities in the AI and MI, and M-Se diet did not significantly reduce GPX activities in the AI and MI. Compared with the A- Se group, E-Se diet significantly increased glutathione peroxidase (GPX) activities in the plasma and liver, and M-Se diet significantly reduced GPX activities in the plasma and liver. Compared with the A-Se group, M-Se and E-Se groups also increased glucose-regulated protein 78 (GRP78, ER stress marker) protein expression of the intestine. Dietary Se supplementation also differentially influenced the expression of the 28 selenoproteins in the AI and MI, many of which possessed antioxidant characteristics. Compared with the A-Se group, the M-Se group significantly decreased mRNA levels of txnrd2 and txnrd3, but made no difference on mRNA levels of these seven GPX proteins in the MI. Moreover, we characterized sterol regulatory element binding protein 1c (SREBP1c) binding sites of three ER-resident proteins (selenom, selenon, and selenos) promoters, and found that Se positively controlled selenom, selenon, and selenos expression via SREBP1c binding to the selenom, selenon, and selenos promoter. Thus, dietary marginal and excess Se increased TGs deposition of yellow catfish P. fulvidraco, which might be mediated by ER-resident selenoproteins expression and ER stress.

6.
Hemoglobin ; : 1-4, 2021 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-33792470

RESUMO

In this study, we report two novel thalassemia variants detected in Chinese individuals using targeted NGS technology. We detected a novel frameshift variant, HBB: c.181delG, in a 32-year-old Chinese individual. This novel variant [a single nucleotide deletion at nucleotide 181 of codon 60 (-G)], was detected by targeted next generation sequencing (NGS), resulting in a stop codon at codon 60 in exon 2 of the HBB gene. The impact of this novel variant was further analyzed by an in vitro model. We also identified a novel in-frame variant, HBA1: c.121_126delAAGACC [codons 40/41 (-AAGACC)], in another Chinese individual in this study. We named these two novel variants, HBB: c.181delG and HBA1: c.121_126delAAGACC according to the Human Genome Variation Society (HGVS), which were detected by the first author. These two novel variants have expanded the mutation spectrum of thalassemia and it would be beneficial for carrier screening, genetic counseling and prenatal diagnosis (PND) of thalassemia.

7.
Mol Phylogenet Evol ; 161: 107171, 2021 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-33798674

RESUMO

With some 7300 species of small nonvascular spore-producing plants, liverworts represent one of the major lineages of land plants. Although multi-locus molecular phylogenetic studies have elucidated relationships of liverworts at different taxonomic categories, the backbone phylogeny of liverworts is still to be fully resolved, especially for the placement of Ptilidiales and the relationships within Jungermanniales and Marchantiales. Here, we provided phylogenomic inferences of liverworts based on 42 newly sequenced and 24 published liverwort plastid genomes representing all but two orders of liverworts, and characterized the evolution of the plastome in liverworts. The structure of the plastid genome is overall conserved across the phylogeny of liverworts, with only two structural variants detected from simple thalloids, besides 18 out of 43 liverwort genera showing intron variations in their plastomes. Complex thalloid liverworts maintain the most plastid genes, and seem to undergo fewer gene deletions and pseudogenization events than other liverworts. Plastid phylogenetic inferences yielded mostly robustly supported relationships, and consistently resolved Ptilidiales as the sister to Porellales. The relative ratio of silent substitutions across the three genetic compartments (i.e., 1:15:10, for mitochondrial:plastid:nuclear) suggests that liverwort plastid genes have the potential to evolve faster than their nuclear counterparts, unlike in any other major land plant lineages where the mutation rate of nuclear genes overwhelm those of their plastid and mitochondrial counterparts.

8.
Hepatology ; 2021 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-33713358

RESUMO

Characterized by hepatocyte steatosis, inflammation, and fibrosis, nonalcoholic steatohepatitis (NASH) is a complicated process that contributes to end-stage liver disease and, eventually, hepatocellular carcinoma (HCC). Tumor necrosis factor alpha (TNF-α)-induced protein 8-like 1 (TIPE1), a new member of the TNF-α-induced protein 8 family, has been explored in immunology and oncology research, but little is known about its role in metabolic diseases. Here, we revealed that hepatocyte-specific deletion of TIPE1 exacerbated diet-induced hepatic steatosis, inflammation, and fibrosis as well as systemic metabolic disorders during NASH pathogenesis. Conversely, hepatocyte-specific overexpression of TIPE1 dramatically prevented the progression of these abnormalities. Mechanically, TIPE1 directly interacted with apoptosis signal-regulating kinase 1 (ASK1) to suppress its TNF receptor-associated factor 6 (TRAF6)-catalyzed polyubiquitination activation upon metabolic challenges, thereby inhibiting downstream c-Jun N-terminal kinase (JNK) and p38 signaling pathway. Importantly, dramatically reduced TIPE1 expression was observed in the livers of nonalcoholic fatty liver disease (NAFLD) patients, suggesting that TIPE1 might be a promising therapeutic target for NAFLD and related metabolic diseases. Conclusion: TIPE1 protects against hepatic steatosis, inflammation, and fibrosis through directly binding ASK1 and restraining its TRAF6-catalyzed polyubiquitination during the development of NASH. Therefore, targeting TIPE1 could be a promising therapeutic approach for NAFLD treatment.

9.
BMC Pediatr ; 21(1): 121, 2021 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-33706747

RESUMO

BACKGROUND: Malignant melanoma (MM) arises predominantly after adolescence and is uncommon in children. Congenital MM in newborns is even rarer with a dearth of published literature; as a consequence, there is no uniform standard for the pathogenesis and treatment for neonatal malignant melanoma. Herein we report a case of giant congenital nodular MM in a newborn, including its clinical, imaging, pathological and molecular pathological features. This case is the largest giant congenital primary nodular malignant melanoma in utero in neonates currently reported in China. CASE PRESENTATION: A female neonatal patient was found to have a 2.97 cm× 1.82 cm×1.50 cm mass with a clear boundary at the right acromion in color Doppler ultrasound examination at 24 weeks of gestation. The mass increased to 3.0 cm×5.0 cm×9.0 cm at birth, and local ulceration was seen. MRI demonstrated that the mass was located on the right shoulder and underarm in a lobulated appearance, and surrounded the right scapula which was deformed. Clinical stage:IV(AJCC 8th Edition (2017)). α-Fetoprofein (AFP) by hematological examination: 1210ng/ml, NSE: 21.28ng/ml, LDH: 842U/L. The patient underwent surgical resection of the tumor, and was pathologically diagnosed as neonatal congenital malignant melanoma; immunohistochemistry (IHC): S-100 (+), HMB45 (+), Melan A (+), and Tyrosinase (+). Molecular pathological examination for BRAF V600E showed no mutations (Quantitative Real-time PCR, qPCR); And so were NRAS, C-kit (exons 9,11,13,14,17,18), and TERT (promoter locus, C228T and C250T) (Sanger sequencing). Non-surgical therapies were not carried out after the surgical resection of the tumor. After 6 months of follow-up, the child developed normally, and color Doppler ultrasound showed no obvious tumor growth or abnormality in the original tumor site. CONCLUSIONS: It is extremely rare to see giant congenital primary nodular MM in utero in neonates. The pathogenesis, treatment and prognosis of congenital MM need further research. The diagnosis mainly depends on histopathology and immunohistochemistry, and it needs to be differentiated from malignant lymphoma and primitive neuroectodermal tumor. The current treatment strategy for MM relies on the surgical excision of the mass. Research directed at molecular detection for genetic mutations would contribute to targeted therapy and better prognosis.

10.
Stem Cell Res ; 53: 102255, 2021 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-33647874

RESUMO

Peripheral blood was extracted from a 45-year old female patient clinically diagnosed with Stickler syndrome harboring a heterozygous splicing mutation in COL2A1 (NM_033150, IVS22-1C>T). Induced pluripotent stem cells (iPSC) were reprogrammed by sendai virus encoding Klf-4, c-Myc, Oct-4, and Sox-2. The iPSC line showed pluripotency, which was verified by immunofluorescence staining. The iPSC line showed normal karyotype, and could form embryoid bodies in vitro and differentiate into the 3 germ layers in vivo. This in vitro cellular model can be used to study the pathogenesis underlying Stickler syndrome.

11.
Stem Cell Res ; 53: 102221, 2021 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-33677395

RESUMO

Peripheral blood was extracted from a 48-year old healthy male donor. Induced pluripotent stem cells (iPSC) were reprogrammed by sendai virus encoding Klf-4, c-Myc, Oct-4, and Sox-2. The iPSC line showed pluripotency, which was verified by immunofluorescence staining. The iPSC line showed normal karyotype, and could form embryoid bodies in vitro and differentiate into the 3 germ layers in vivo. This cell line can be served as healthy control for studying inherited disease.

12.
Gene ; 783: 145564, 2021 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-33711408

RESUMO

The family Mycetophilidae (Diptera: Sciaroidea) consists of more than 4,500 described species distributed worldwide. Among them, dozens of species have been reported to be economically important to cultivated mushrooms and crops. Relationships among subfamilies in Mycetophilidae have been controversial by using morphological characters or gene markers. In this study, five mycetophilid mitogenomes representing four subfamilies were sequenced and analyzed with 15 published sciaroid mitogenomes as ingroup, while another two species representing two closely related families were chosen as outgroup. All of the sequenced mitogenomes contain 37 genes arranged in the ancestral order, including 13 protein-coding genes (PCGs), 22 transfer RNAs (tRNA) genes, two ribosomal RNA (rRNA) genes and a control region (CR). Among mycetophilid mitogenomes, Leu, Ile, Phe, and Met are the most frequently encoded amino acids (AA), with TTA (Leu), ATT (Ile), TTT (Phe) and ATA (Met) being the most frequent codons. Meanwhile, the phylogenetic results reconstructed based on PCGs, PCGs + rRNAs and AA sequences respectively show that the clade of Sciaroidea was well separated from outgroup, further confirming its monophyly. The phylogenetic relationships within Mycetophilidae were recovered as (Manotinae + Sciophilinae) + (Mycomyinae + Mycetophilinae). Mapped to the phylogram, the gene rearrangements occur frequently in the crown group, implying extremely rapid evolutionary rates in Sciaridae and Cecidomyiidae, which might be the reason why the two families have such high species diversity.

13.
Nano Lett ; 2021 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-33764070

RESUMO

Ion selective separators with the capability of conducting lithium ion and blocking polysulfides are critical and highly desired for high-performance lithium-sulfur (Li-S) batteries. Herein, we fabricate an ion selective film of covalent organic framework (denoted as TpPa-SO3Li) onto the commercial Celgard separator. The aligned nanochannels and continuous negatively charged sites in the TpPa-SO3Li layer can effectively facilitate the lithium ion conduction and meanwhile significantly suppress the diffusion of polysulfides via the electrostatic interaction. Consequently, the TpPa-SO3Li layer exhibits excellent ion selectivity with an extremely high lithium ion transference number of 0.88. When using this novel functional layer, the Li-S batteries with a high sulfur loading of 5.4 mg cm-2 can acquire a high initial capacity of 822.9 mA h g-1 and high retention rate of 78% after 100 cycles at 0.2 C. This work provides new insights into developing high-performance Li-S batteries via ion selective separator strategy.

14.
Bull Math Biol ; 83(5): 49, 2021 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-33765224

RESUMO

This paper considers two-species competitive systems with one-species' diffusion between patches. Each species can persist alone in the corresponding patch (a source), while the mobile species cannot survive in the other (a sink). Using the method of monotone dynamical systems, we give a rigorous analysis on persistence of the system, prove local/global stability of the equilibria and show new types of bi-stability. These results demonstrate that diffusion could lead to results reversing those without diffusion, which extend the principle of competitive exclusion: Diffusion could lead to persistence of the mobile competitor in the sink, make it reach total abundance larger than if non-diffusing and even exclude the opponent. The total abundance is shown to be a distorted function (surface) of diffusion rates, which extends both previous theory and experimental observations. A novel strategy of diffusion is deduced in which the mobile competitor could drive the opponent into extinction, and then approach the maximal abundance. Initial population density and diffusive asymmetry play a role in the competition. Our work has potential applications in biodiversity conservation and economic competition.

15.
J Genet Genomics ; 2021 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-33753020

RESUMO

The unusual chromosome 11q23.3 harboring the apolipoprotein (APO) gene cluster has been well documented for its essential roles in plasma lipid-related traits and atherosclerotic cardiovascular diseases. However, its genetic architecture and the potential biological mechanisms underlying complex phenotypes have not been well assessed. We conducted a study for this target region in a Han Chinese population through a stepwise forward framework based on massive parallel sequencing, association analyses, genetic fine mapping, and functional interpretation. The present study identified new meaningful genetic associations that were not simply determined by statistical significance. In addition to the APOA5 gene, we found robust evidence of the genetic commitments of APOC3 and APOA1 to blood lipids. Several variants with high confidence were prioritized along with the potential biological mechanism interpretations in the wake of adaptive fine-mapping analyses. rs2849174 in the APOC3 enhancer was discovered with an unrivaled posterior probability of causality for triglyceride levels and could mediate APOC3 expression through enhancer activity modulated by a combination of histone modifications and transcription factor accessibility. Similarly, multiple lines of evidence converged in favor of rs3741297 as a causal variant influencing high-density lipoprotein cholesterol. Our findings provided novel insights into this genomic locus in the Chinese population.

16.
Nanotechnology ; 2021 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-33690179

RESUMO

An oral multi-unit delivery system was developed by incorporating the nanoparticle into the nanofiber mat and its efficiency for intestinal-specific delivery and controlled release of a peptide (insulin) was investigated. Initially, the influence of deacetylation degree (DD) of chitosan and ionic gelation methods on the properties of nanoparticles was studied. High DD (95%) chitosan was attributed to higher encapsulation efficiency and stability when crosslinked with polyanion tripolyphosphate. Subsequently, the multi-unit system was fabricated using a pH-sensitive polymer (sodium alginate) as the coating layer to further encapsulate the nanoparticle. Fiber mat with an average diameter of 481±47 nm could significantly decrease the burst release of insulin in acidic condition and release most amount of insulin (>60%) in the simulated intestinal medium. Furthermore, the encapsulated peptide remained in good integrity. This multi-unit carrier provides the better-designed vehicle for intestinal-specific delivery and controlled release of the peptide.

17.
Acta Pharmacol Sin ; 2021 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-33686244

RESUMO

Cardiovascular safety assessment is vital for drug development, yet human cardiovascular cell models are lacking. In vitro mass-generated human pluripotent stem cell (hPSC)-derived cardiovascular cells are a suitable cell model for preclinical cardiovascular safety evaluations. In this study, we established a preclinical toxicology model using same-origin hPSC-differentiated cardiomyocytes (hPSC-CMs) and endothelial cells (hPSC-ECs). For validation of this cell model, alirocumab, a human antibody against proprotein convertase subtilisin kexin type 9 (PCSK9), was selected as an emerging safe lipid-lowering drug; atorvastatin, a common statin (the most effective type of lipid-lowering drug), was used as a drug with reported side effects at high concentrations, while doxorubicin was chosen as a positive cardiotoxic drug. The cytotoxicity of these drugs was assessed using CCK8, ATP, and lactate dehydrogenase release assays at 24, 48, and 72 h. The influences of these drugs on cardiomyocyte electrophysiology were detected using the patch-clamp technique, while their effects on endothelial function were determined by tube formation and Dil-acetylated low-density lipoprotein (Dil-Ac-LDL) uptake assays. We showed that alirocumab did not affect the cell viability or cardiomyocyte electrophysiology in agreement with the clinical results. Atorvastatin (5-50 µM) dose-dependently decreased cardiovascular cell viability over time, and at a high concentration (50 µM, ~100 times the normal peak serum concentration in clinic), it affected the action potentials of hPSC-CMs and damaged tube formation and Dil-Ac-LDL uptake of hPSC-ECs. The results demonstrate that the established same-origin hPSC-derived cardiovascular cell model can be used to evaluate lipid-lowering drug safety in cardiovascular cells and allow highly accurate preclinical assessment of potential drugs.

18.
Chem Soc Rev ; 2021 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-33687389

RESUMO

Molecular separations that enable selective transport of target molecules from gas and liquid molecular mixtures, such as CO2 capture, olefin/paraffin separations, and organic solvent nanofiltration, represent the most energy sensitive and significant demands. Membranes are favored for molecular separations owing to the advantages of energy efficiency, simplicity, scalability, and small environmental footprint. A number of emerging microporous organic materials have displayed great potential as building blocks of molecular separation membranes, which not only integrate the rigid, engineered pore structures and desirable stability of inorganic molecular sieve membranes, but also exhibit a high degree of freedom to create chemically rich combinations/sequences. To gain a deep insight into the intrinsic connections and characteristics of these microporous organic material-based membranes, in this review, for the first time, we propose the concept of organic molecular sieve membranes (OMSMs) with a focus on the precise construction of membrane structures and efficient intensification of membrane processes. The platform chemistries, designing principles, and assembly methods for the precise construction of OMSMs are elaborated. Conventional mass transport mechanisms are analyzed based on the interactions between OMSMs and penetrate(s). Particularly, the 'STEM' guidelines of OMSMs are highlighted to guide the precise construction of OMSM structures and efficient intensification of OMSM processes. Emerging mass transport mechanisms are elucidated inspired by the phenomena and principles of the mass transport processes in the biological realm. The representative applications of OMSMs in gas and liquid molecular mixture separations are highlighted. The major challenges and brief perspectives for the fundamental science and practical applications of OMSMs are tentatively identified.

19.
Aging (Albany NY) ; 132021 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-33744864

RESUMO

AIM: Previous studies have focused on the subpopulations of tumor-infiltrating lymphocytes (TILs) in tumors. This study focuses only on the concentration of TILs in the tumor irrespective of type and elucidates its prognostic value. METHODS: We used 315 HCC patients as the discovery phase and another 343 HCC patients as the validation phase. By following the standardized guideline, density of TILs were categorized into low (TILs < 10%), intermediate (10% ≦ TILs < 50%), and high (TILs ≧ 50%) levels. Associations of TILs with prognostic, immune-related, and genetic variables were examined. RESULTS: We observed a dose-response relation of TILs with overall survival (intermediate: HR, 0.58; 95% confidence interval (CI), 0.36-0.93; high: HR, 0.37; 95% CI, 0.15-0.93) and disease-free survival (intermediate: HR, 0.35; 95% CI, 0.22-0.58; high: HR, 0.23; 95% CI, 0.09-0.58). The prognostic value of TILs was validated in the TCGA set. Mutation burden or the number of neoantigens were not associated with TILs intensity. However, hepatitis B or C virus infection patients had higher TILs intensity in the para-tumor tissue. CONCLUSIONS: The TILs intensity was associated with patients' survival. If confirmed, this would suggest that clinical routine assessment of TILs could provide prognostic information in HCC.

20.
J Ethnopharmacol ; 274: 114067, 2021 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-33771642

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Achyranthes bidentata Blume (AB) is a traditional Chinese medicine (TCM) widely used as a dietary supplement and anti-arthritis drug. Pharmacological studies have shown that Achyranthes bidentata Blume saponins (ABS) are the main bioactive ingredient. However, the metabolic profile and mechanisms of action of ABS against rheumatic arthritis (RA) remain to be established. AIM OF THE STUDY: Our main objective was to investigate the metabolic profile and pharmacological activities of ABS against RA. MATERIALS AND METHODS: In this study, an analytical method based on ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-QTOF/MS) coupled with a metabolism platform was developed for metabolic profiling of ABS in rat liver microsomes and plasma. Then, the in vivo metabolites of ABS and their targets associated with RA were used to construct the network pharmacological analysis. Gene ontology (GO) enrichment, KEGG signaling pathway analyses and pathway network analyses were performed. The therapeutic effect of ABS on RA was further evaluated using an adjuvant arthritis (AA) model and network pharmacology results validated via Western blot. RESULTS: Overall, 26 and 21 metabolites of ABS were tentatively characterized in rat liver microsomes and plasma, respectively. The metabolic pathways of ABS mainly included M+O, M+O-H2, M+O2, and M+O2-H2. Data form network pharmacology analysis suggested that MAPK, apoptosis, PI3K-AKT and p53 signaling pathways contribute significantly to the therapeutic effects of ABS on RA. In pharmacodynamics experiments, ABS ameliorated the symptoms in AA rats in a dose-dependent manner and restored the homeostasis of pro/anti-inflammatory factors. Western blot results further demonstrated a significant ABS-induced decrease in phosphorylation of ERK in the MAPK pathway (P < 0.01). CONCLUSION: Application of an analytical method based on UPLC-QTOF/MS, network pharmacology and validation experiments offers novel insights into the components and mechanisms of ABS that contribute to its therapeutic effects against RA, providing useful directions for further research.

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