Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 311
Filtrar
1.
World J Clin Cases ; 9(30): 9070-9076, 2021 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-34786389

RESUMO

BACKGROUND: Hemorrhagic transformation (HT) is a common complication in patients with cerebral infarction. However, its pathogenesis is poorly understood. The knowledge of factors that may increase risk for HT may help in improving the safety of thrombolytic therapy. AIM: To investigate the predictive value of serum calcium, albumin, globulin and matrix metalloproteinase-9 (MMP-9) levels for HT after intravenous thrombolysis (IVT) in patients with acute cerebral infarction. METHODS: Five hundred patients with acute cerebral infarction who received IVT with alteplase within 4.5 h after the onset of disease between January 2018 and January 2021 at our hospital were selected as the study subjects. They were divided into groups based on computed tomography scan results of the brain made within 36 h after thrombolysis. Forty patients with HT were enrolled in an observation group and 460 patients without HT were enrolled in a control group. Serum calcium, albumin, globulin and MMP-9 levels were compared between the two groups. Regression analysis was used to discuss the relationship between these indices and HT. RESULTS: The previous history of hypertension, diabetes, atrial fibrillation, cerebrovascular diseases, smoking and alcohol intake were not associated with HT after IVT in patients with acute cerebral infarction (all P > 0.05). The National Institutes of Health stroke scale (NHISS) score was associated with HT after IVT in patients with acute cerebral infarction (P < 0.05). The serum calcium and albumin levels were lower in the observation group than in the control group (all P < 0.05). The levels of globulin and MMP-9 were significantly higher in the observation group than in the control group (all P < 0.05). Logistic regression analysis showed that NHISS score, serum calcium, albumin, globulins and MMP-9 were independent factors influencing the occurrence of HT following IVT in patients with cerebral infarction (P < 0.05). CONCLUSION: Serum calcium, albumin, globulin and MMP-9 levels are risk factors for HT after IVT in patients with acute cerebral infarction. Moreover, NHISS score can be used as a predictor of post-thrombolytic HT.

2.
Front Immunol ; 12: 741371, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34650564

RESUMO

Delivery by cesarean section (CS) is linked to an increased incidence of food allergies in children and affects early gut microbiota colonization. Furthermore, emerging evidence has connected disordered intestinal microbiota to food allergies. Here, we investigated the impact of CS on a rat model for food allergy to ovalbumin (OVA). Rats delivered by CS were found to be more responsive to OVA sensitization than vaginally born ones, displaying a greater reduction in rectal temperature upon challenge, worse diarrhea, and higher levels of OVA-specific antibodies and histamine. 16S rRNA sequencing of feces revealed reduced levels of Lactobacillus and Bifidobacterium in the CS rats. Preventative supplementation with a probiotic combination containing Lactobacillus and Bifidobacterium could protect CS rats against an allergic response to OVA, indicating that the microbiota dysbiosis contributes to CS-related response. Additionally, probiotic intervention early in life might help to rebuild aberrant Th2 responses and tight junction proteins, both of which have been linked to CS-related high allergic reactions. Taken together, this study shows that disordered intestinal microbiota plays an essential role in the pathogenesis of food allergy mediated by CS. More importantly, interventions that modulate the microbiota composition in early life are therapeutically relevant for CS-related food allergies.

3.
J Appl Toxicol ; 2021 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-34561900

RESUMO

Aflatoxin is a secondary metabolite secreted by Aspergillus flavus, parasitic Aspergillus, and other fungi through the polyketone pathway, and it can be detected in many foods. Aflatoxin has strong toxicity and carcinogenicity, and many studies have shown that aflatoxin is highly associated with liver cancer. In the present study, malignant transformation of L02 cells was induced by aflatoxin B1 (AFB1), and the gene expression, miRNA expression, and methylation level were detected by high-throughput sequencing. The gene and miRNA expression results showed that 2547 genes and 315 miRNAs were changed in the AFB1-treated group compared with the DMSO group. Among them, RSAD2 and SCIN were significantly upregulated, whereas TRAPPC3L and UBE2L6 were significantly downregulated. Has-miR-33b-3p was significantly upregulated, whereas Has-miR-3613-5p was significantly downregulated. The methylation results showed that 2832 CpG sites were methylated on the promoter or coding DNA sequence (CDS) of the gene, whereas the expression of DNMT3a and DNMT3b was significantly upregulated. Moreover, hypermethylation occurred in TRAPPC3L, CDH13, and SPINK13. The results of GO and KEGG pathway analyses showed that significantly changed genes and miRNAs were mainly involved in tumor formation, proliferation, invasion, and migration. The results of network map analysis showed that Hsa-miR-3613-5p, Hsa-miR-615-5p, Hsa-miR-615-3p, and Hsa-miR-3158-3p were the key miRNAs for malignant transformation of L02 cells induced by AFB1. In addition, the expression of ONECUT2, RAP1GAP2, and FSTL4 was regulated by DNA methylation and miRNAs. These results suggested that the gene expression network regulated by DNA methylation and miRNAs may play a vital role in AFB1-induced hepatocellular carcinoma.

4.
Angew Chem Int Ed Engl ; 60(45): 24214-24219, 2021 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-34476881

RESUMO

The scarcity of reliable methods for synthesizing chiral gem-diarylmethine borons limits their applications. Herein, we report a method for highly enantioselective dirhodium-catalyzed B-H bond insertion reactions with diaryl diazomethanes as carbene precursors. These reactions afforded chiral gem-diarylmethine borane compounds in high yield (up to 99 % yield), high activity (turnover numbers up to 14 300), high enantioselectivity (up to 99 % ee) and showed unprecedented broad functional group tolerance. The borane compounds synthesized by this method could be efficiently transformed into diaryl methanol, diaryl methyl amine, and triaryl methane derivatives with good stereospecificity. Mechanistic studies suggested that the borane adduct coordinated to the rhodium catalyst and thus interfered with decomposition of the diazomethane, and that insertion of a rhodium carbene (generated from the diaryl diazomethane) into the B-H bond was most likely the rate-determining step.

5.
World J Clin Cases ; 9(21): 5909-5920, 2021 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-34368309

RESUMO

BACKGROUND: Experimental evidence has indicated the benefits of statins for the treatment of postoperative delirium. Previously, clinical trials did not reach definite conclusions on the effects of statins on delirium. Some clinical trials have indicated that statins reduce postoperative delirium and improve outcomes, while some studies have reported negative results. AIM: To evaluate whether perioperative rosuvastatin treatment reduces the incidence of delirium and improves clinical outcomes. METHODS: This randomized, double-blind, and placebo-controlled trial was conducted in a single center in Jiangsu, China. This study enrolled patients aged greater than 60 years who received general anesthesia during elective operations and provided informed consent. A computer-generated randomization sequence (in a 1:1 ratio) was used to randomly assign patients to receive either rosuvastatin (40 mg/d) or placebo. Participants, care providers, and investigators were all masked to group assignments. The primary endpoint was the incidence of delirium, which was assessed twice daily with the Confusion Assessment Method during the first 7 postoperative days. Analyses were performed on intention-to-treat and safety populations. RESULTS: Between January 1, 2017 and January 1, 2020, 3512 patients were assessed. A total of 821 patients were randomly assigned to receive either placebo (n = 411) or rosuvastatin (n = 410). The incidence of postoperative delirium was significantly lower in the rosuvastatin group [23 (5.6%) of 410 patients] than in the placebo group {42 (13.5%) of 411 patients [odds ratios (OR) = 0.522, 95% confidence interval (CI): 0.308-0.885; P < 0.05]}. No significant difference in 30-d all-cause mortality (6.1% vs 8.7%, OR = 0.67, 95%CI: 0.39-1.2, P = 0.147) was observed between the two groups. Rosuvastatin decreased the hospitalization time (13.8 ± 2.5 vs 14.2 ± 2.8, P = 0.03) and hospitalization expenses (9.3 ± 2.5 vs 9.8 ± 2.9, P = 0.007). No significant differences in abnormal liver enzymes (9.0% vs 7.1%, OR = 1.307, 95%CI: 0.787-2.169, P = 0.30) or rhabdomyolysis (0.73% vs 0.24%, OR = 3.020, 95%CI: 0.31-29.2, P = 0.37) were observed between the two groups. CONCLUSION: The current study suggests that perioperative rosuvastatin treatment reduces the incidence of delirium after an elective operation under general anesthesia. However, the evidence does not reveal that rosuvastatin improves clinical outcomes. The therapy is safe. Further investigation is necessary to fully understand the potential usefulness of rosuvastatin in elderly patients.

6.
Food Funct ; 12(17): 7954-7963, 2021 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-34251375

RESUMO

In this study, the immunomodulatory effect of sea buckthorn (SBT) pulp oil was elucidated in immunosuppressed Balb/c mice induced by cyclophosphamide (CTX). The results showed that SBT pulp oil could reverse the decreasing trend of body weight, thymus/spleen index and hematological parameters induced by CTX. Compared with immunosuppressive mice induced by CTX, SBT pulp oil could enhance NK cytotoxicity, macrophage phagocytosis, and T lymphocyte proliferation, and regulate the proportion of T cell subsets in mesenteric lymph nodes (MLN), and promote the production of secretory immunoglobulin A (sIgA), IFN-γ, IL-2, IL-4, IL-12 and TNF-α in the intestines. In addition, SBT pulp oil can promote the production of short fatty acids (SCFAs), increase the diversity of gut microbiota, improve the composition of intestinal flora, increase the abundance of Alistipes, Bacteroides, Anaerotruncus, Lactobacillus, ASF356, and Roseburia, while decreasing the abundance of Mucispirillum, Anaeroplasma, Pelagibacterium, Brevundimonas, Ochrobactrum, Acinetobacter, Ruminiclostridium, Blautia, Ruminiclostridium, Oscillibacter, and Faecalibaculum. This study shows that SBT pulp oil can regulate the diversity and composition of intestinal microflora in CTX-induced immunosuppressive Balb/c mice, thus enhancing the intestinal mucosa and systemic immune response. The results can provide a basis for understanding the function of SBT pulp oil and its application as a new probiotic and immunomodulator.

7.
Magn Reson Chem ; 2021 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-34212405

RESUMO

The local structural, electronic, optical, and electron paramagnetic resonance (EPR) properties are uniformly studied for Cu2+ -doped rutile (TiO2 ) crystals by using the density functional theory (DFT) calculations. The local cation-oxygen bond lengths and planar bond angle, band gap, Mulliken charge and overlapping population, density of state (DOS), and UV-Vis absorption spectra are calculated for pure and copper-doped rutile. The smaller overlapping population of Cu-O bonds in the doped system than Ti-O bonds in pure rutile reflects weaker orbital admixtures or covalency of the former. Compared with pure rutile, Cu2+ doping leads to significant redshift of the UV-Vis absorption band and the narrow impurity band in visible and near-infrared regions arising from the Cu2+ d-d transitions and narrowing of the band gap by about 0.636 eV, possibly suggesting enhancement of visible light activity. The Cu dopant induces a spin magnetic moment of 0.74 µB for the doped rutile. The calculated UV-Vis absorption spectra and spin Hamiltonian parameters for copper-doped rutile show reasonable agreement with the experimental data and some improvement related to the previous perturbation formula calculations. Present systematic studies would be helpful to understand the mechanisms of the enhancement in the optical and magnetic properties of this material with transition-metal (especially Cu2+ ) dopants.

8.
Yi Chuan ; 43(6): 571-579, 2021 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-34284988

RESUMO

Long interspersed element-1 (LINE-1), which is the only autonomous retrotransposon in human genome, makes up about 17% of the human genome. For LINE-1 retrotransposition may result in genome instability, it was strictly restricted by organisms, and its expression was therefore barely detected in normal somatic cells. However, the expression of LINE-1 is a common phenomenon in most tumor or cancer tissues, suggesting a close relationship between LINE-1 expression and cancer development. Differentially expressed LINE-1 in cancer tissues can be used as a biomarker for tumor diagnosis and an important indicator of prognosis after cancer therapeutics. Meanwhile, the feasibility of LINE-1 as a potential drug target for tumor treatment has also been evaluating and verifying in clinicals. In this review, we introduce the application of LINE-1 as a biomarker in tumor diagnosis and prognostic, as well as the research progress in LINE-1 as potential drug target for tumor treatment, in order to provide some references for clinical application in cancer treatment.


Assuntos
Elementos Nucleotídeos Longos e Dispersos , Neoplasias , Carcinogênese/genética , Transformação Celular Neoplásica , Genoma Humano , Humanos , Elementos Nucleotídeos Longos e Dispersos/genética , Neoplasias/diagnóstico , Neoplasias/genética , Neoplasias/terapia
9.
Front Immunol ; 12: 687296, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34177939

RESUMO

Background: Targeting immune checkpoints for HIV treatment potentially provides a double benefit resulting from the ability to restore viral-specific CD8+ T-cell functions and enhance HIV production from reservoir cells. Despite promising pre-clinical data, PD-1 blockade alone in HIV-1-infected patients with advanced cancer has shown limited benefits in controlling HIV, suggesting the need for additional targets beyond PD-1. CD39 and PD-1 are highly co-expressed on CD8+ T cells in HIV-1 infection. However, the characteristics of CD39 and PD-1 dual-positive CD8+ T-cell subsets in chronic HIV-1 infection remain poorly understood. Methods: This study enrolled 72 HIV-1-infected patients, including 40 treatment naïve and 32 ART patients. A total of 11 healthy individuals were included as controls. Different subsets of CD8+ T cells defined by CD39 and/or PD-1 expression were studied by flow cytometry. The relationships between the frequencies of the different subsets and parameters indicating HIV-1 disease progression were analyzed. Functional (i.e., cytokine secretion, viral inhibition) assays were performed to evaluate the impact of the blockade of adenosine and/or PD-1 signaling on CD8+ T cells. Results: The proportions of PD-1+, CD39+, and PD-1+CD39+ CD8+ T cells were significantly increased in treatment naïve patients but were partially lowered in patients on antiretroviral therapy. In treatment naïve patients, the proportions of PD-1+CD39+ CD8+ T cells were negatively correlated with CD4+ T-cell counts and the CD4/CD8 ratio, and were positively correlated with viral load. CD39+CD8+ T cells expressed high levels of the A2A adenosine receptor and were more sensitive to 2-chloroadenosine-mediated functional inhibition than their CD39- counterparts. In vitro, a combination of blocking CD39/adenosine and PD-1 signaling showed a synergic effect in restoring CD8+ T-cell function, as evidenced by enhanced abilities to secrete functional cytokines and to kill autologous reservoir cells. Conclusion: In patients with chronic HIV-1 infection there are increased frequencies of PD-1+, CD39+, and PD-1+CD39+ CD8+ T cells. In treatment naïve patients, the frequencies of PD-1+CD39+ CD8+ T cells are negatively correlated with CD4+ T-cell counts and the CD4/CD8 ratio and positively correlated with viral load. Combined blockade of CD39/adenosine and PD-1 signaling in vitro may exert a synergistic effect in restoring CD8+ T-cell function in HIV-1-infected patients.


Assuntos
Adenosina/metabolismo , Fármacos Anti-HIV/farmacologia , Apirase/antagonistas & inibidores , Linfócitos T CD8-Positivos/efeitos dos fármacos , Inibidores Enzimáticos/farmacologia , Infecções por HIV/tratamento farmacológico , HIV-1/efeitos dos fármacos , Inibidores de Checkpoint Imunológico/farmacologia , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Adulto , Apirase/metabolismo , Linfócitos T CD8-Positivos/imunologia , Linfócitos T CD8-Positivos/metabolismo , Linfócitos T CD8-Positivos/virologia , Estudos de Casos e Controles , Células Cultivadas , Sinergismo Farmacológico , Quimioterapia Combinada , Feminino , Infecções por HIV/imunologia , Infecções por HIV/metabolismo , Infecções por HIV/virologia , HIV-1/imunologia , HIV-1/patogenicidade , Humanos , Masculino , Pessoa de Meia-Idade , Receptor de Morte Celular Programada 1/metabolismo , Carga Viral , Adulto Jovem
10.
Chin J Nat Med ; 19(5): 351-363, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33941340

RESUMO

Digestive system cancers, including liver, gastric, colon, esophageal and pancreatic cancers, are the leading cause of cancers with high morbidity and mortality, and the question of their clinical treatment is still open. Previous studies have indicated that Ziyuglycoside II (ZYG II), the major bioactive ingredient extract from Sanguisorba officinalis L., significantly inhibits the growth of various cancer cells. However, the selective anti-tumor effects of ZYG II against digestive system cancers are not systemically investigated. In this study, we reported the anti-cancer effect of ZYG II on esophageal cancer cells (OE21), cholangiocarcinoma cells (HuCCT1), gastric cancer cells (BGC-823), liver cancer cells (HepG2), human colonic cancer cells (HCT116), and pancreatic cancer cells (PANC-1). We also found that ZYG II induced cell cycle arrest, oxidative stress and mitochondrial apoptosis. Network pharmacology analysis suggested that UBC, EGFR and IKBKG are predicted targets of ZYG II. EGFR signaling was suggested as the critical pathway underlying the anti-cancer effects of ZYG II and both docking simulation and western blot analysis demonstrated that ZYG II was a potential EGFR inhibitor. Furthermore, our results showed synergistic inhibitory effects of ZYG II and chemotherapy 5-FU on the growth of cancer cells. In summary, ZYG II are effective anti-tumor agents against digestive cancers. Further systemic evaluation of the anti-cancer activities in vitro and in vivo and characterization of underlying mechanism will promote the development of novel supplementary therapeutic strategies based on ZYG II for the treatment of digestive system cancers.


Assuntos
Neoplasias do Sistema Digestório , Sanguisorba , Saponinas , Apoptose , Linhagem Celular Tumoral , Proliferação de Células , Neoplasias do Sistema Digestório/tratamento farmacológico , Células HCT116 , Células Hep G2 , Humanos , Quinase I-kappa B , Sanguisorba/química , Saponinas/farmacologia
11.
Mar Pollut Bull ; 168: 112439, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33993042

RESUMO

The Yellow Sea (YS) has been subjected to harmful algal blooms (HABs) for several decades. In this study, we compiled and analyzed a dataset of 165 red tides from 1972 to 2017 and a dataset of green tides from 2008 to 2017 in the YS. The most notable feature of red tides in the YS is the increasing dominance of dinoflagellate red tides in terms of frequency, scale, seasonal distribution, spatial coverage, and red tide causative species. The increasing dominance of dinoflagellate red tides is closely related to eutrophication and the development of the mariculture industry in the YS. However, the dinoflagellate red tides in the northern Yellow Sea (NYS) and the southern Yellow Sea (SYS) have different features. The apparent changes in red tides in the SYS in terms of frequency and seasonal patterns might have been caused by recurrent large-scale green tides in the last decade.


Assuntos
Dinoflagelados , Proliferação Nociva de Algas , China , Eutrofização
12.
Bioorg Med Chem ; 39: 116166, 2021 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-33910157

RESUMO

Constitutive activation of Hedgehog (Hh) pathway is intimately related with the occurrence and development of several malignancies, such as medulloblastoma (MB) and other tumors. Therefore, small molecular inhibitors of Hh pathway are urgently needed. In this study, three new steroidal alkaloids, ⊿5 (20R, 24R) 23-oxo-24-methylsolacongetidine, ⊿5 (20S, 24R) 23-oxo-24-methylsolacongetidine and veralinine 3-O-α-l-rhamnopyranosyl-(1 â†’ 2)-ß-D-glucopyranoside, together with six known alkaloids, 20-epi-verazine, verazine, protoverine 15-(l)-2'-methylbutyrate, jervine, veramarine and ß1-chaconine, were isolated and determined from Veratrum grandiflorum Loes. The dual-luciferase bioassay indicated that all compounds exhibited significant inhibitions of Hh pathway with IC50 values of 0.72-14.31 µM against Shh-LIGHT 2 cells. To determine whether these Hh pathway inhibitors act with the Smoothened (Smo) protein, which is an important oncoprotein and target for this pathway, BODIPY-cyclopamine (BC) competitive binding assay was preferentially performed. Compared with BC alone, all compounds obviously reduced the fluorescence intensities of BC binding with Smo in Smo-overexpression HEK293T cells through fluorescence microscope and flow cytometer. By directly interacting with Smo, it revealed that they were actually novel natural Smo inhibitors. Then, their anti-tumor effects were investigated against the human MB cell line DAOY, which is a typical pediatric brain tumor cells line with highly expressed Hh pathway. Interestingly, most of compounds had slight proliferation inhibitions on DAOY cells after treatment for 24 h same as vismodegib, while ß1-chaconine showed the strongest inhibitory effect on the growth of DAOY with IC50 value of 5.35 µM. In conclusion, our studies valuably provide several novel natural Smo inhibitors for potential targeting treatment of Hh-dependent tumors.


Assuntos
Alcaloides/isolamento & purificação , Alcaloides/farmacologia , Proliferação de Células/efeitos dos fármacos , Meduloblastoma/patologia , Receptor Smoothened/antagonistas & inibidores , Esteroides/química , Veratrum/química , Alcaloides/química , Linhagem Celular Tumoral , Células HEK293 , Humanos , Estrutura Molecular , Análise Espectral/métodos
13.
Zhongguo Zhen Jiu ; 41(4): 451-7, 2021 Apr 12.
Artigo em Chinês | MEDLINE | ID: mdl-33909370

RESUMO

OBJECTIVE: To systematically evaluate the efficacy and safety of conventional therapy combined with moxibustion in the treatment of chronic obstructive pulmonary disease (COPD) in stable phase based on Meta-analysis medicine. METHODS: The randomized controlled trials (RCTs) of moxibustion as adjuvant therapy for COPD were retrieved from the databases of CNKI, Wanfang, SinoMed, PubMed, Web of Science, Cochrane Library and Ebsco. RevMan5.3 software was used for Meta analysis, and the quality of evidence was evaluated according to GRADE standards. RESULTS: A total of 16 RCTs were included, involving 1425 patients. The results of Meta-analysis showed that: compared with the conventional treatment, ①the adjuvant therapy with moxibustion had advantages in reducing the number of acute exacerbations [MD=-0.31, 95%CI:-0.49--0.13, P=0.0006]; ②the adjuvant therapy with moxibustion improved lung function significantly [FEV1% (MD=4.00, 95%CI:2.63-5.37, P<0.000 01) and FEV1/FVC (MD=3.56, 95%CI:1.69-5.43, P=0.000 2)]; ③the adjuvant therapy with moxibustion could extend the 6 min walking distance (6WMD) (MD=35.00, 95%CI:18.02-51.99, P<0.000 1); ④the adjuvant therapy with moxibustion could improve the modified British Medical Research Council breathing questionnaire (mMRC) classification significantly (MD=-0.62, 95%CI:-1.18--0.05, P=0.03); ⑤no adverse reaction was reported in the included literature. CONCLUSION: The efficacy of moxibustion as adjuvant therapy for COPD in stable phase is better than that of simple conventional therapy. Due to insufficient clinical evidence and the limitations of this study, clinical safety is unclear and further evidence is needed to support the results.


Assuntos
Moxibustão , Doença Pulmonar Obstrutiva Crônica , Humanos , Pulmão , Doença Pulmonar Obstrutiva Crônica/terapia , Resultado do Tratamento
14.
Oncologist ; 26(8): 649-e1313, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-33749934

RESUMO

LESSONS LEARNED: MET overexpression is uncommon, and positive MET immunohistochemistry (1+/2+) was an independent positive prognostic factor for response rate and progression-free survival. Whether MET overexpression can be considered a potential predictive biomarker and be used as an inclusion criterion is worth investigating in a future study. BACKGROUND: Metatinib tromethamine tablet (metatinib) is a small molecule receptor kinase inhibitor targeting both c-MET and vascular endothelial growth factor receptor 2. This phase I trial aimed to determine the dose-limiting toxicity (DLT) and maximum tolerated dose (MTD), pharmacokinetics, safety, and efficacy of metatinib in patients with advanced solid tumors. METHODS: Eligible patients received a single dose of metatinib in a 3 + 3 dose-escalation design with dose levels of 25-800 mg/day, after a single dose on day 1, then 2 days off, and then a multidose schedule of once-daily doses for 25 consecutive days (days 4-28). Primary endpoints were MTD and safety; secondary and exploratory endpoints included pharmacokinetics (PK), efficacy, and biomarkers. RESULTS: Eighteen patients (including nine patients with hepatocellular carcinoma [HCC]) received at least one dose of study drug (one patient quit the study without continuous multiple-dose administration after receiving a single dose of metatinib). Hand-foot skin reaction, diarrhea, and liver dysfunction were the DLTs, and 200 mg/day was the MTD. The most common treatment-related adverse events (TRAEs) were skin toxicity (50%), diarrhea (33.3%), and liver dysfunction (27.8%). Three patients (only one of six in the 200 mg/day cohort; the other two in the 300 mg/day cohort) experienced severe TRAEs: one patient with severe liver dysfunction and two patients with severe liver dysfunction and skin toxicity, respectively. Pharmacokinetics assessment indicated that metatinib was rapidly absorbed and metabolized to the formation of reactive metabolite, SCR-1510, after single-dose administration. The mean time taken to achieve maximum concentration and terminal elimination half-life of SCR-1510 was approximately 2.0-3.0 hours and ranged from 8 to 14 hours. Two patients had partial responses. The objective response rate and disease control rate (DCR) were 11.1% and 61.1%, respectively. The median progression-free survival (PFS) was 2.75 months. CONCLUSION: Metatinib administration of 200 mg/day was well tolerated, safe, and effective. The MTD was 200 mg/day, which should be recommended in further investigations.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Comprimidos , Trometamina , Fator A de Crescimento do Endotélio Vascular
15.
J Mol Diagn ; 23(6): 710-718, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33781963

RESUMO

We compared chromosomal mosaicism, detected by next-generation sequencing (NGS), during preimplantation genetic testing (PGT) with that detected by single-nucleotide polymorphism (SNP) array-based PGT to assess the pregnancy outcomes associated with both platforms in a retrospective cohort study of patients undergoing in vitro fertilization in a single university-based assisted reproduction center. In total, 6427 blastocysts biopsied from 1513 patients who underwent 2833 oocyte retrievals from January 2017 to February 2019 were identified. The incidence of mosaicism was significantly higher in the NGS-based PGT group than in the SNP array-based PGT group. Furthermore, some aneuploid specimens were affected by mosaicism. The total mosaicism detection rate with NGS-based PGT (23.3%) was significantly higher than that with SNP array-based PGT (7.7%). Mosaicism rates were similar when stratified by maternal age or PGT type. The SNP array cohort showed a significantly higher spontaneous abortion rate than the NGS cohort (10.07% versus 6.33%; P = 0.0403). The ongoing pregnancy/live birth rate was higher in the NGS cohort (44.1%) than in the SNP array cohort (42.28%). Our results confirm that NGS-based PGT can detect mosaicism more frequently than SNP array-based PGT in trophectoderm specimens. Therefore, clinical application of NGS for PGT may improve pregnancy outcomes compared with that of SNP array-based PGT. More detailed blastocyst detection and classification is necessary to prioritize embryo transfers.

16.
BMC Microbiol ; 21(1): 68, 2021 02 27.
Artigo em Inglês | MEDLINE | ID: mdl-33639835

RESUMO

BACKGROUND: The genus Lactobacillus is an important component of the gastrointestinal tract of human and animals and commonly considered as probiotic. L. taiwanensis has long been proposed to be a probiotic whereas understanding on this species is still in its infancy. Genomic information of L. taiwanensis is fairly limited. Extensive characterization of its beneficial traits is needed. RESULTS: A new strain CLG01 of L. taiwanensis was isolated from mouse Peyer's patches. We established its probiotic profile through in vitro experiments. Complete genome of this strain was also sequenced and analyzed. L. taiwanensis CLG01 showed robust tolerance to acid and a degree of tolerance to bile salt with a promising antibacterial activity against a broad spectrum of pathogenic bacteria. In vitro treatment of mouse RAW 264.7 macrophage cells with heat-killed bacteria and bacterial supernatant of L. taiwanensis CLG01 resulted in enhancement of immune responses and upregulated expression of TNF-α and IL-6. The strain CLG01 also increased the IL-10 production of macrophages when co-treated with lipopolysaccharide (LPS). Complete genome of L. taiwanensis CLG01 contained a 1.89 Mb chromosome and two plasmids. Further genomic analysis revealed the presence of genes related to its resistance to different stresses and the beneficial effects mentioned above. Moreover, biosynthetic gene clusters (BGCs) encoding antimicrobial peptides, like bacteriocin, linear azol(in)e-containing peptide (LAP) and lanthipeptide, were also identified in the genome of L. taiwanensis CLG01. CONCLUSIONS: L. taiwanensis CLG01, isolated from mouse Peyer's patches, is the first L. taiwanensis strain with both phenotypes and genotypes systematically studied. These preliminary data confirmed the role of L. taiwanensis CLG01 as a potential probiotic candidate with antibacterial and immunomodulatory activity, which provide insight for further investigation to this species.


Assuntos
Antibacterianos , Genoma Bacteriano/genética , Fatores Imunológicos , Lactobacillus/genética , Lactobacillus/metabolismo , Nódulos Linfáticos Agregados/microbiologia , Probióticos , Animais , Antibacterianos/isolamento & purificação , Células Cultivadas , Regulação da Expressão Gênica/imunologia , Fatores Imunológicos/isolamento & purificação , Interleucina-6/genética , Camundongos , Fator de Necrose Tumoral alfa/genética
17.
Aust Crit Care ; 34(4): 388-394, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33097369

RESUMO

BACKGROUND: Numerous studies have demonstrated the benefits and safety of ultrasound guidance in comparison with conventional palpation for radial artery cannulation in adult patients. However, the current evidence for paediatric patients is not fully understood. OBJECTIVE: The objective of this study was to compare the efficiency and safety of ultrasound guidance with those of traditional palpation for radial artery cannulation in paediatric patients and provide convincing evidence for clinical practice. METHODS: PubMed, Cochrane Library, ClinicalTrials.gov (Min et al-2019, NCT02795468, Anantasit et al-2017, NCT02668471), China National Knowledge Infrastructure, and Wanfang Data were systematically searched from their inception until December 31, 2019, to identify relevant randomised controlled trials. Data were extracted from the included studies independently by two investigators. The primary outcome of interest was the first-attempt success rate. Review Manager Version 5.3 and trial sequential analysis (beta = 0.9) were applied to analyse the collected data. RESULTS: A total of eight randomised controlled trials involving 680 paediatric patients were included in this study. The pooled findings showed that ultrasound-guided radial artery cannulation, in comparison with traditional palpation, can significantly improve the first-attempt success rate (relative risk [RR] = 1.65, 95% confidence interval [CI] = 1.36-2.01, P < 0.00001). Trial sequential analysis indicated that this available evidence was conclusive. Moreover, ultrasound guidance was associated with an increased total success rate (RR = 1.38, 95% CI = 1.15-1.66, P = 0.0004), a decreased mean procedural time (standardised mean difference = -0.89, 95% CI = -1.52 to -0.25, P = 0.006), and incidence of haematoma (RR = 0.19, 95% CI = 0.10-0.35, P < 0.00001). CONCLUSION: Ultrasound-guided radial arterial cannulation in paediatric patients is associated with improved first-attempt success rates, total success rates, and mean procedural time and decreased incidence of haematoma. The current evidence suggests that ultrasound guidance should be the standard of care for radial artery cannulation in clinical practice.

18.
Magn Reson Chem ; 59(4): 439-446, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33084084

RESUMO

The local structure, d-d transition band, and spin Hamiltonian parameters (SHPs) are theoretically studied for the V4+ probe in Na2 O-PbO-Bi2 O3 -SiO2 (NPBS) glass ceramics containing V2 O5 dopant with various concentration x (0 ≤ x ≤ 5 mol%) by using the perturbation formulas of the SHPs for tetragonally compressed octahedral 3d1 clusters. The first decreasing (or increasing) and then increasing (or decreasing) d-d transition band (= 10 Dq ) and hyperfine structure constants A// and A⊥ (or g factors g// and g⊥ ) with x can be suitably simulated with the similarly varying Fourier type concentration functions of cubic field parameter Dq , covalence factor N, core polarization constant κ, and reduction factor H (or relative tetragonal compression ratio ρ), with the minima (or maxima) at the middle concentration x = 3 mol%, respectively. The above concentration variations of SHPs and the related quantities may originate from the modifications of local crystal field strength, tetragonal compression, and electron cloud distribution near the impurity V4+ with x, corresponding to the highest [V4+ ]/[V5+ ] ratio at 3 mol%. Present studies would be helpful to explore novel sodium lead bismuth silicate glass ceramics by modifying the concentration of V2 O5 dopant.

19.
J Bone Miner Metab ; 39(2): 237-244, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32876727

RESUMO

INTRODUCTION: Bone turnover markers (BTMs) can be used to monitor bone metabolism, while the actual clinical changing in hip fracture had not been certified to evaluate the changes of BTMs during the healing process after surgery of elderly hip fractures; and to get the effects of operation type, gender, serum 25(OH)D level, and age on bone turnover markers. MATERIALS AND METHODS: A total of 100 elderly cases with hip fracture were selected, including 74 females and 26 males, and the patients were followed to 180-230 days after surgery. Serum levels of N-propeptide of type 1 collagen (P1NP), C-terminal crosslinking telopeptides of type 1 collagen (CTX), Osteocalcin (OC), and 25 hydroxy vitamin D (25OHD) were investigated. Bone mineral density (BMD) was measured with dual-energy X-ray absorptiometry (DXA). RESULTS: (1) P1NP and CTX showed peak time at 30-60 days after operation, while OC keep going even at 180-230 days; P1NP showed less than 4 times elevation during healing, CTX and OC only had less than 2 times rise. (2) Female had higher serum CTX and OC than male, intramedullary nailing for intertrochanteric fracture patients had higher P1NP than hip replacement for femoral neck fracture patients, and both the degrees of increase were less than 50%. (3) Serum average 25(OH)D level had no effect on BTMs during the fracture healing; different from the young old (65-84 years), serum OC level of eldest older patients(≥ 85 years) decreased early in the process of fracture healing. CONCLUSIONS: BTMs reached the peak level in 30-60 days after surgery, P1NP showed less than 4 times elevation, and CTX and OC had less than 2 times rise. It was not necessary to take gender into account when observing P1NP, and it was not necessary to take fracture and operation type into account when observing CTX and OC.


Assuntos
Biomarcadores/sangue , Remodelação Óssea , Fraturas do Quadril/sangue , Fraturas do Quadril/cirurgia , Idoso , Idoso de 80 Anos ou mais , Densidade Óssea , Colágeno Tipo I/sangue , Feminino , Seguimentos , Fraturas do Quadril/fisiopatologia , Humanos , Masculino , Osteocalcina/sangue , Fragmentos de Peptídeos/sangue , Peptídeos/sangue , Pró-Colágeno/sangue
20.
Nanoscale ; 13(2): 810-818, 2021 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-33351010

RESUMO

Exploring highly effective and low-cost non-noble metal-based electrocatalysts for oxygen evolution reaction (OER) is critical for renewable energy conversion and metal-air batteries. Herein, a novel and high-efficient OER catalyst was reported with nitrogen-doped oxide/sulfide heterostructures (named N-NiCo2S4/CoO microsphere). The N-NiCo2S4/CoO microsphere was synthesized by annealing NiCo-BTC MOF to a multi-layered hollow structure of NiCo2O4 microspheres, followed by the direct vulcanization in the presence of NH4HCO3, resulting in an oxide/sulfide heterojunction. Benefiting from the nitrogen doping, the abundant multi-layered hollow heterostructure and the interfaces between multiple components, the N-NiCo2S4/CoO microsphere exhibited excellent OER activity with a low overpotential of 227 mV at 10 mA cm-2. The Zn-air battery based on the N-NiCo2S4/CoO + Pt/C catalyst displayed excellent cycling stability after 900 cycles at a large current density of 5 mA cm-2, where the commercial RuO2 + Pt/C-based battery exhibited a big drop after only 30 cycles, suggesting its great application prospects as power source devices.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...