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1.
Cell ; 185(10): 1777-1792.e21, 2022 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-35512705

RESUMO

Spatially resolved transcriptomic technologies are promising tools to study complex biological processes such as mammalian embryogenesis. However, the imbalance between resolution, gene capture, and field of view of current methodologies precludes their systematic application to analyze relatively large and three-dimensional mid- and late-gestation embryos. Here, we combined DNA nanoball (DNB)-patterned arrays and in situ RNA capture to create spatial enhanced resolution omics-sequencing (Stereo-seq). We applied Stereo-seq to generate the mouse organogenesis spatiotemporal transcriptomic atlas (MOSTA), which maps with single-cell resolution and high sensitivity the kinetics and directionality of transcriptional variation during mouse organogenesis. We used this information to gain insight into the molecular basis of spatial cell heterogeneity and cell fate specification in developing tissues such as the dorsal midbrain. Our panoramic atlas will facilitate in-depth investigation of longstanding questions concerning normal and abnormal mammalian development.

2.
Int J Biol Macromol ; 209(Pt B): 1914-1921, 2022 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-35500772

RESUMO

The complexation of carboxymethyl short-chain amylose (CSA) and hydroxypropyl trimethyl ammonium chloride chitosan (HACC) and the stability of CSA/HACC nanocomplex were investigated. Resonance light scattering (RLS), turbidity, nanoparticle size and zeta potential analyses revealed that the complex coacervation occurred between CSA and HACC. The mass ratio and pH markedly influenced the complexation behavior; CSA with a higher degree of substitution (DS0.2) altered the complexation at a lower mass ratio and pH, increasing the turbidity and RLS intensity. The results of particle size and zeta potential analyses indicated that CSA/HACC complexes possessed the good pH and ionic strength stability. In addition to electrostatic interactions, hydrogen bonding and hydrophobic effects were also determined to be involved in the complexation process using thermal titration calorimetry (ITC). Additionally, the process was spontaneous, and CSA with a higher DS showed stronger complexation ability. These results may enable the understanding of polysaccharide complex behaviors.

3.
Cell Death Discov ; 8(1): 254, 2022 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-35523787

RESUMO

Age-related osteoporosis is characterized by the accumulation of senescent osteoblastic cells in bone microenvironment and significantly reduced osteogenic differentiation. Clearing of the senescent cells is helpful to improve bone formation in aged mice. Bone morphogenetic protein 9 (BMP9), a multifunctional protein produced and secreted by liver, was reported to improve osteoporosis caused by estrogen withdrawal. However, the mechanism of BMP9 has not been fully elucidated, and its effect on senile osteoporosis has not been reported. This study reveals that BMP9 significantly increases bone mass and improves bone biomechanical properties in aged mice. Furthermore, BMP9 reduces expression of senescent genes in bone microenvironment, accompanied by decreased senescence-associated secretory phenotypes (SASPs) such as Ccl5, Mmp9, Hmgb1, Nfkb1, and Vcam1. In vitro, Bmp9 treatment inhibits osteoblast senescence through activating Smad1, which suppresses the transcriptional activity of Stat1, thereby inhibits P21 expression and SASPs production. Furthermore, inhibiting the Smad1 signal in vivo can reverse the inhibitory effect of BMP9 on Stat1 and downstream senescent genes, which eliminates the protection of BMP9 on age-related osteoporosis. These findings highlight the critical role of BMP9 on reducing age-related bone loss by inhibiting osteoblast senescence through Smad1-Stat1-P21 axis.

4.
J Hazard Mater ; 435: 128981, 2022 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-35523090

RESUMO

Environmental risk of multi-year polythene film mulching (PM) was evaluated and investigated. The location observation following 19-year (2000-2018) PM in irrigated region indicated that the cumulative accumulation of soil microplastics was as high as 2900 ± 19.5 n kg-1. Microplastic accumulation was tightly associated with soil plasticizer concentration (Pearson's r = 0.728, p <0.05), and the concentration of dominant phthalic acid esters (PAEs) was up to 117.5-705 µg kg-1. As such, we conducted organic mulching substitute experiment (2019-2020) with non-mulching (CK), maize straw mulching (SM), living clover mulching (CM), PM, PM+SM and PM+CM respectively. The data showed that organic mulching (SM, CM) achieved similar productivity benefit as PM-involved treatments (p > 0.05). Critically, total concentration of PAEs decreased by 6.43% in SM relative to CK, and by 9.61% in PM+SM relative to PM respectively. High throughput sequencing indicated that the proportions of predominant bacteria and fungi were totally lower in PM than those of organic mulching, particularly Sphingomonadaceae and Stachybotryaceae. KEGG analyses indicated that organic mulching promoted the metabolisms of polycyclic aromatic hydrocarbons, benzoic acid (probability>75%) and heterologous organism metabolism (p<0.001), due to improved microbial community assembly. Therefore, organic mulching efficiently accelerated microbial mineralization of PM pollutants, and may act as a green solution to displace PM.

5.
Environ Pollut ; 306: 119381, 2022 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-35500711

RESUMO

In China, PM2.5 pollution has caused extensive death and economic loss. Thus, an accurate assessment of the spatial distribution of these losses is crucial for delineating priority areas for air pollution control in China. In this study, we assessed the PM2.5 exposure-related health effects according to the integrated exposure risk function and non-linear power law (NLP) function in 338 prefecture-level cities in China by utilizing online monitoring data and the PM2.5 Hindcast Database (PHD). Our results revealed no significant difference between the monitoring data and PHD (p value = 0.66 > 0.05). The number of deaths caused by PM2.5-related Stroke (cerebrovascular disease), ischemic heart disease, chronic obstructive pulmonary disease, and lung cancer at the national level estimated through the NLP function was 0.27 million (95% CI: 0.06-0.50), 0.23 million (95% CI: 0.08-0.38), 0.31 million (95% CI: 0.04-0.57), and 0.31 million (95% CI: 0.16-0.40), respectively. The total economic cost at the national level in 2016 was approximately US$80.25 billion (95% CI: 24.46-132.25). Based on a comparison of Z statistics, we propose that the evaluation results obtained using the NLP function and monitoring data are accurate. Additionally, according to scenario simulations, Beijing, Chongqing, Tianjin, and other cities should be priority areas for PM2.5 pollution control to achieve considerable health benefits. Our statistics can help improve the accuracy of PM2.5-related health effect assessments in China.

6.
Neurologist ; 2022 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-35533999

RESUMO

BACKGROUND: Medullary infarction (MI) often leads to severe dysphagia and sudden death. We investigated whether dysphagia was associated with sudden death. METHODS: Patients with MI were divided into sudden death group and nonsudden death group. Dysphagia was evaluated in 2 ways: the water-swallowing test (WST) points and the degree of dysphagia. Random undersampling (RUS), random oversampling (ROS), and synthetic minority oversampling technique (SMOTE) techniques were used to process the original data and solve the imbalance problem between 2 classes. Univariate and multivariate logistic regressions were used to analyze the association between the independent variables (WST and degree of dysphagia) and the dependent variable (sudden death or not), while the National Institutes of Health Stroke Scale (NIHSS) score was used as a control. RESULTS: Univariate logistic regression analysis showed that for all resampling methods, both the WST and NIHSS were risk factors for sudden death after MI. For multivariable logistic regression, the fitting effect of RUS logistic regression was satisfactory, which showed the same results. The results of the univariate logistic regression analysis of dysphagia degree showed that for all resampling methods, compared with no dysphagia, both mild to moderate dysphagia degree and severe dysphagia degree were risk factors for sudden death. For multivariable logistic regressions, the logistic regressions of the original data and the RUS resampling method were satisfactory which showed the same results. CONCLUSIONS: Dysphagia is closely related to sudden death after MI. The more severe the dysphagia, the higher is the incidence of sudden death.

7.
Foods ; 11(9)2022 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-35563929

RESUMO

Maltooligosaccharides are a novel type of functional oligosaccharides with potential applications in food processing and can be produced by glycosyl hydrolases hydrolyzing starch. However, the main obstacle in industrial applications is the balance between the high temperature of the process and the stability of enzymes. In this study, based on the structural information and in silico tools (DSDBASE-MODIP, Disulfide by Design2 and FoldX), two disulfide bond mutants (A211C-S214C and S409C-Q412C) of maltotetraose-forming amylase from Pseudomonas saccharophila STB07 (MFAps) were generated to improve its thermostability. The mutation A211C-S214C was closer to the catalytic center and showed significantly improved thermostability with a 2.6-fold improved half-life at 60 °C and the thermal transition mid-point increased by 1.6 °C, compared to the wild-type. However, the thermostability of mutant S409C-Q412C, whose mutation sites are closely to CBM20, did not change observably. Molecular dynamics simulations revealed that both disulfide bonds A211C-S214C and S409C-Q412C rigidified the overall structure of MFAps, however, the impact on thermostability depends on the position and distance from the catalytic center.

8.
Animals (Basel) ; 12(9)2022 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-35565570

RESUMO

Pathogenic infection of fishes is an important constraining factor affecting marine aquaculture. Insufficient understanding of the molecular mechanisms has affected the diagnosis and corresponding treatment. Here, we reported the dynamic changes of gene expression patterns in the Chinese tongue sole kidney at 16 h, 48 h, 72 h and 96 h after Vibrio harveyi infection. In total, 366, 214, 115 and 238 differentially expressed genes were obtained from the 16 h-vs. -C, 48 h-vs. -C, 72 h-vs. -C and 96 h-vs. -C group comparisons, respectively. KEGG enrichment analysis revealed rapid up-regulation of several immune-related pathways, including IL-17, TNF and TLR signaling pathway. More importantly, time-series analyses of transcriptome showed that immune genes were specifically up-regulated in a short period of time and then decreased. The expression levels of chemokines increased after infection and reached a peak at 16 h. Specifically, Jak-STAT signaling pathway played a crucial role in the regulation during Vibrio harveyi infection. In the later stages of infection, genes in the neuroendocrine pathway, such as glucocorticoid-related genes, were activated in the kidney, indicating a close connection between the immune system and neuroendocrine system. Our dynamic transcriptome analyses provided profound insight into the gene expression profile and investigation of immunogenetic mechanisms of Chinese tongue sole.

9.
Trials ; 23(1): 404, 2022 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-35568917

RESUMO

BACKGROUND: Common and frequent as acute pain is, it is often underestimated and undertreated in older people with dementia in nursing homes and inadequate pain management remains an issue. METHODS: The study is designed to be a randomized, sham-controlled trial and is underway in nursing homes located in China. A total of 206 dementia patients are being recruited from nursing homes in Yinchuan, China. They are randomly allocated to an intervention or a controlled group in a 1:1 ratio. The intervention group will be treated with true APP therapy, while the other group will receive APP at sham point stimulation therapy. The patients will be assessed at baseline (T0), at 5 min during performing the intervention (T1), and at 5 min after completion of the intervention (T2). The primary outcome is the level of pain relief at T1 and T2. Physiological parameters, side effects and additional use of analgesics during the procedure, satisfaction from caregivers, and acceptance of patients are evaluated as secondary outcomes. DISCUSSION: The results of this study are expected to verify the analgesic effect of APP for acute pain in patients with mild dementia in nursing homes. It has the potential to prompt APP therapy to be implemented widely in dementia patients with acute pain in nursing homes. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2100047932 . Registered on 27 June 2021. Currently, patient recruitment is ongoing. Recruitment is expected to take place from December 2020 to December 2021.

10.
Int J Biol Macromol ; 209(Pt A): 144-152, 2022 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-35381284

RESUMO

The effect of four kinds of potato flour with different gelatinization degrees on the quality of steam bread was investigated in the present study. Results showed that medium-well flour (MWF) and potato flakes (PF) steamed bread, particularly MWF steamed bread, possessed the desired product properties liked by consumers. The MWF steamed bread had the highest appearance score (42.78) and total sensory evaluation score (81.60), and the PF steamed bread exhibited the highest specific volume (1.84 mL/g) and taste score (43.05). An increase in the degree of potato flour gelatinization led to an increase in dough gas retention coefficient from 80.20 mL/100 mL to 85.17 mL/100 mL and a more uniform and dense dough microstructure. During dough preparation, the increased gelatinization degree of potato flours enhanced the hydroscopicity competition between potato starch and gluten, resulting in a flocculent gluten network and increased potato starch volume during steaming. During steaming, steamed bread with higher gelatinization degree of potato flour formed a homogenous and dense starch gel-gluten double network, making them softer with more uniform gas cells and larger specific volume. Thus, this study provides a perspective of the effect of starch gelatinization on steamed bread quality.

11.
Fish Shellfish Immunol ; 124: 462-471, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35483595

RESUMO

Exocyst complex component 3 Sec6 of mammals, one of the components of the exocyst complex, participates in numerous cellular functions, such as promoting cell migration and inhibiting apoptosis. In this study, the Sec6 was obtained from Epinephelus coioides, an economically important cultured fish. The full length of E. coioides Sec6 was 2655 bp including a 245 bp 5' UTR, a 154 bp 3' UTR, and a 2256 bp open reading frame (ORF) encoding 751 amino acids, with a molecular mass of 86.76 kDa and a theoretical pI of 5.57. Sec6 mRNA was detected in all the tissues examined, but the expression level is different in these tissues. Using fluorescence microscopy, Sec6 were distributed in both the nucleus and the cytoplasm. After SGIV infection, the expression of E. coioides Sec6 was significantly up-regulated in both trunk kidney and spleen response to Singapore grouper iridovirus (SGIV), an important pathogens of E. coioides. Sec6 could increase the SGIV-induced cytopathic effects (CPE), the expression of the SGIV genes VP19, LITAF, MCP, ICP18 and MCP, and the viral titers. Besides, E. coioides Sec6 significantly downregulated the promoter of NF-κB and AP-1, and inhibited the SGIV-induced apoptosis. The results demonstrated that E. coioides Sec6 might play important roles in SGIV infection.

12.
J Pharm Pharmacol ; 2022 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-35429380

RESUMO

OBJECTIVES: To explore gingerol's potential mechanism for treating liver cancer using network pharmacology and molecular docking technology and to conduct in-vitro experiments of human liver cancer cell HepG2 to verify important signalling pathways. METHODS: We obtained potential targets of gingerol derivatives (6-gingerol, 8-gingerol and 10-gingerol) from PubChem and SwissTargetPrediction websites and collected related targets for liver cancer with the help of GeneCards. We performed Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis on key targets using the DAVID data platform and combined with Cytoscape 3.7.1 software to construct a component-target-signal pathway interaction map to study its mechanism of action. Subsequently, the components and key proteins were molecularly docked through Autodock Vina software. Finally, the important signal pathways were verified by HepG2 cell in-vitro experiments. KEY FINDINGS: A total of 318 drug targets were screened for gingerol derivatives, and 2509 gene targets related to liver cancer were collected. The Venn diagram showed that there were 104 intersection targets between gingerol derivatives and liver cancer. Module analysis results show that these intersection targets can be divided into 5 modules and 49 nodes. Bioinformatics analysis found that GO obtained 20 important functional items including cancer cell proliferation, protein kinase activity, phosphotransferase activity and kinase activity; KEGG enrichment analysis yielded a total of 20 key signal pathways including the PI3K-Akt signalling pathway. The results of molecular docking show that the binding energy of gingerol derivatives has good binding activity with PI3K and Akt. In-vitro experimental results show that gingerol derivatives and compound gingerol (compound gingerol is composed of 6-gingerol, 8-gingerol and 10-gingerol in a ratio of 7:1.5:1.5) can produce HepG2 cell proliferation inhibition, and each administration group can significantly increase the apoptosis rate of HepG2 cells and the fluorescence intensity of the nucleus and block the cell cycle in the S phase; the results of Western Blot and real-time quantitative PCR show that gingerol derivatives and compound gingerol can down-regulate the expression of Akt and p-Akt and up-regulate the expression of Bax/Bcl-2. And the effect of compound gingerol is more obvious than that of gingerol derivatives. CONCLUSIONS: The results of network pharmacology and experimental validation suggest that gingerol derivatives and compound gingerol can act against liver cancer by acting on the PI3K-Akt signalling pathway.

13.
Cluster Comput ; : 1-26, 2022 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-35431616

RESUMO

Surgical case scheduling is a key issue in the field of medician, which is a challenging work because of the difficulty in assigning resources to patients. This study regards the surgical case scheduling problem as a flexible job shop scheduling problem (FJSP). Considering the switching and preparation time of patients in different stage, an improved multi-objective imperialist competitive algorithm (IMOICA), which adopts the non-dominant sorting method, is proposed to optimize the whole scheduling. First, the social hierarchy strategy is developed to initialize the empire. Then, to enhance the global search ability of the algorithm, the concept of attraction and repulsion (AR) is introduced into the assimilation strategy. Moreover, to increase the diversity of the population, the revolution strategy is utilized. Finally, the variable neighborhood search (VNS) strategy is embedded to improve its exploitation capacity further. Experiments show that scheduling in advance saves time and cost, and IMOICA can solve the surgical case scheduling problem studied efficiently.

14.
World J Clin Cases ; 10(9): 2700-2709, 2022 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-35434115

RESUMO

BACKGROUND: Pulmonary embolism (PE) is a fatal clinical syndrome that is generally caused by an embolus from unstable deep venous thrombosis (DVT). However, clinical and biochemical factors that are related to the stability of DVT are not fully understood. AIM: To evaluate the relationships between plasma antigen levels of factor XII (FXII:Ag) and factor XI (FXI:Ag) with the stability of DVT. METHODS: Patients with DVT and no PE, DVT and PE, and controls with no DVT or PE that matched for age, gender, and comorbidities were included in this study. FXII:Ag and FXI:Ag in peripheral venous blood were measured using enzyme-linked immunosorbent assays. RESULTS: Using the 95th percentile of FXI:Ag in patients with DVT and PE as the cut-off, a higher FXI:Ag was associated with a higher risk of unstable DVT (odds ratio: 3.15, 95% confidence interval: 1.18-8.43, P = 0.019). Stratified analyses showed consistent results in patients ≤ 60 years (P = 0.020), but not in those > 60 years (P = 0.346). CONCLUSION: Higher plasma FXI:Ag might be a marker for unstable DVT, which might be associated with PE in these patients.

15.
Phys Chem Chem Phys ; 24(16): 9256-9262, 2022 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-35388845

RESUMO

In recent years, three-dimensional (3D) high-temperature superconductors at ultrahigh pressure have been reported, typical examples are the polyhydrides H3S, LaH10, YH9, etc. To find high-temperature two-dimensional (2D) superconductors at atmospheric pressure is another research hotspot. Here, we investigated the possible superconductivity in a hydrogenated monolayer phosphorus carbide based on first-principles calculations. The results reveal that monolayer PC3 transforms from a semiconductor to a metal after hydrogenation. Interestingly, the C-π-bonding band contributes most to the states at the Fermi level. Based on the electron-phonon coupling mechanism, it is found that the electron-phonon coupling constant of HPC3 is 0.95, which mainly originates from the coupling of C-π electrons with the in-plane vibration modes of C and H. The calculated critical temperature Tc is 31.0 K, which is higher than those in most 2D superconductors. By further applying a biaxial tensile strain of 3%, the Tc can be boosted to 57.3 K, exceeding the McMillan limit. Thus, hydrogenation and strain are effective ways for increasing the superconducting Tc of 2D materials.

16.
BMC Med ; 20(1): 140, 2022 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-35473809

RESUMO

BACKGROUND: Poor graft function (PGF) or prolonged isolated thrombocytopenia (PT), which are characterized by pancytopenia or thrombocytopenia, have become serious complications after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Our previous single-arm trial suggests that N-acetyl-L-cysteine (NAC) prophylaxis reduced PGF or PT after allo-HSCT. Therefore, an open-label, randomized, phase 3 trial was performed to investigate the efficacy and tolerability of NAC prophylaxis to reduce PGF or PT after allo-HSCT. METHODS: A phase 3, open-label randomized trial was performed. Based on the percentage of CD34+VEGFR2 (CD309)+ endothelial cells (ECs) in bone marrow (BM) detected by flow cytometry at 14 days before conditioning, patients aged 15 to 60 years with acute leukemia undergoing haploidentical HSCT were categorized as low-risk (EC ≥ 0.1%) or high-risk (EC < 0.1%); patients at high risk were randomly assigned (2:1) to receive NAC prophylaxis or nonprophylaxis. The primary endpoint was PGF and PT incidence at +60 days post-HSCT. RESULTS: Between April 18, 2019, and June 24, 2021, 120 patients with BM EC <0.1% were randomly assigned for NAC (group A, N = 80) or nonprophylaxis (group B, N = 40), and 105 patients with EC≥0.1% (group C) were also analyzed. The +60 days incidence of PGF and PT was 7.5% (95% CI, 1.7 to 13.3%) and 22.5% (95% CI, 9.1 to 35.9%) in group A and group B (hazard ratio, 0.317; 95% CI, 0.113 to 0.890; P = 0.021) and 11.4% (95% CI, 5.2 to 17.6%) in group C (hazard ratio, 0.643; 95% CI, 0.242 to 1.715; P = 0.373). Consistently, NAC prophylaxis gradually improved BM ECs and CD34+ cells in group A, whereas reduced their reactive oxygen species (ROS) levels post-HSCT. Within 60 days post-HSCT, the most common grade 3 to 5 adverse events for the NAC and control groups were infections (19/80 [24%] vs. 10/40 [25%]) and gastrointestinal adverse events (16/80 [20%] vs. 7/40 [18%]). There were no treatment-related deaths. CONCLUSIONS: N-Acetyl-L-cysteine prophylaxis can prevent the occurrence of poor hematopoietic function and is well tolerated in haploidentical HSCT. It may offer a potential pathogenesis-oriented therapeutic approach for patients with poor hematopoietic function. TRIAL REGISTRATION: This trial was registered at ClinicalTrials.gov as #NCT03967665.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Trombocitopenia , Acetilcisteína/uso terapêutico , Células Endoteliais , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Prostaglandinas F , Trombocitopenia/etiologia
17.
Front Pharmacol ; 13: 811017, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35479307

RESUMO

Purpose: A novel once-daily divalproex-extended release (ER) dose formulation has been developed; this formulation prolongs the therapeutic serum levels of the drug, compared with the twice-daily conventional divalproex-delayed release (DR) formulation. This study aimed to systematically examine and compare the efficacy, safety, and retention rates of the ER divalproex (VPA-ER) and conventional DR divalproex (VPA-DR) formulations. Methods: Randomized control trials (RCTs) reporting the efficacy, adverse events (AEs), and medication compliance of ER and DR divalproex were searched in online databases, including PubMed, Embase, and Cochrane Library databases, by searching MeSH words and term words. Observational studies with potential biases were excluded. The meta-analysis was performed using Stata 16.0 software. Findings: Thirteen RCTs, involving 1,028 participants, were included in this meta-analysis. Efficacy, AEs, and drug retention rates were the main study outcomes. According to our study, VPA-ER presented clinically significant benefits compared with the placebo in the population with bipolar disorder (BD) (39.5% versus 27.2%, p < 0.001). A similar efficacy of VPA-ER and VPA-DR in controlling seizures was observed in epilepsy patients (87.4% versus 86.5%, p = 0.769). A significantly lower incidence of AEs was reported in the VPA-ER group than in the placebo group (26.8% versus 34.8%, p = 0.003). By contrast, there was no evidence of difference in safety between VPA-ER and VPA-DR (29.4% versus 30.5%, p = 0.750). In addition, the drug retention rate was significantly lower in the VPA-ER group than in the placebo group (76.0% versus 82.7%, p = 0.020), especially in migraine patients (p = 0.022) and in patients who were treated for fewer than 4 weeks (p = 0.018). Implications: The efficacy of VPA-ER was significantly superior to that of the placebo treatment, which provided efficacy similar to that of conventional VPA-DR. VPA-ER is well tolerated with a low rate of AEs compared to the placebo. In addition, the acceptable medicine compliance of VPA-ER was conducive to the long-term maintenance treatment of chronic diseases. Although we analyzed open labels and crossover design RCTs, large-scale multicenter studies on the efficacy and medicine compliance of new ER formulations with less AEs are required to validate our conclusion.

18.
Front Oncol ; 12: 829230, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35480120

RESUMO

Background: Early detection of colorectal cancer (CRC) is crucial to the treatment and prognosis of patients. Traditional screening methods have disadvantages. Methods: 231 blood samples were collected from 86 CRC, 56 colorectal adenoma (CRA), and 89 healthy individuals, from which extracellular vesicle long RNAs (exLRs) were isolated and sequenced. An CRC diagnostic signature (d-signature) was established, and prognosis-associated cell components were evaluated. Results: The exLR d-signature for CRC was established based on 17 of the differentially expressed exLRs. The d-signature showed high diagnostic efficiency of CRC and control (CRA and healthy) samples with an area under the curve (AUC) of 0.938 in the training cohort, 0.943 in the validation cohort, and 0.947 in an independent cohort. The d-signature could effectively differentiate early-stage (stage I-II) CRC from healthy individuals (AUC 0.990), as well as differentiating CEA-negative CRC from healthy individuals (AUC 0.988). A CRA d-signature was also generated and could differentiate CRA from healthy individuals both in the training (AUC 0.993) and validation (AUC 0.978) cohorts. The enrichment of class-switched memory B-cells, B-cells, naive B-cells, and mast cells showed increasing trends between CRC, CRA, and healthy cohorts. Class-switched memory B-cells, mast cells, and basophils were positively associated with CRC prognosis while natural killer T-cells, naive B-cells, immature dendritic cells, and lymphatic endothelial cells were negatively associated with prognosis. Conclusions: Our study identified that the exLR d-signature could differentiate CRC from CRA and healthy individuals with high efficiency and exLR profiling also has potential in CRA screening and CRC prognosis prediction.

19.
J Sci Food Agric ; 2022 Apr 14.
Artigo em Inglês | MEDLINE | ID: mdl-35426124

RESUMO

BACKGROUND: The formation of starch-lipid complexes is of interest to food processing and human nutrition. Fatty acid (FA) structure is important for the formation and structure of starch-FA complexes. However, there is limited research regarding the complexing behavior between amylose and different kinds of FAs, as well as the relationship between fine structures and digestibility of the formed complexes. This study aimed to investigate the behavior, fine structure, and digestibility of complexes formed between high amylose maize starch (HMS) and FA having various chain lengths and unsaturation degrees. RESULTS: Complexes containing different FA structures showed V6III -type crystals. Complexes containing 18-carbon unsaturated FAs displayed significantly higher complexing index (P < 0.05) than other complexes. Complexes containing 12-carbon FAs and 18-carbon FAs with one unsaturation degree showed a higher degree of structural order and resistant starch (RS) content than other complexes. The 12-carbon FAs exhibited a higher binding degree with helical cavity of amylose than other FAs. Additionally, 10-carbon and 18-carbon saturated FAs tended to combine with HMS outside amylose helices more than other FAs. Laser confocal micro-Raman imaging revealed that the physically embedded 10-carbon and 18-carbon saturated FAs showed heterogeneous distribution in complexes, and that the complexed 18-carbon FAs with one unsaturation degree exhibited homogeneous distribution. CONCLUSION: The behavior, structural order and digestibility of complexes could be regulated by FA structure. The 12-carbon FAs and 18-carbon FAs with one unsaturation degree were more suitable for the production of HMS-FA complexes with higher structural order and RS content than other FAs. © 2022 Society of Chemical Industry.

20.
Front Oncol ; 12: 861151, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35387128

RESUMO

Background: To determine whether vascular index (VI; defined as the ratio of Doppler signal pixels to pixels in the total lesion) measured via superb microvascular imaging in breast cancer correlates with immunohistochemically defined subtype and is able to predict molecular subtypes. Methods: This prospective study involved 225 patients with 225 mass-type invasive breast cancers (mean size 2.6 ± 1.4 cm, range 0.4~5.9 cm) who underwent ultrasound and superb microvascular imaging (SMI) at Peking Union Medical College Hospital before breast surgery from December 2016 to June 2018. The correlations between primary tumor VI measured via SMI, clinicopathological findings, and molecular subtype were analyzed. The performance of VI for prediction of molecular subtypes in invasive breast cancer was investigated. Results: The median VI of the 225 tumors was 7.3% (4.2%~11.8%) (range 0%~54.4%). Among the subtypes of the 225 tumors, 41 (18.2%) were luminal A, 91 (40.4%) were luminal B human epidermal growth factor receptor-2 (HER-2)-negative, 26 (11.6%) were luminal B HER-2-positive, 17 (7.6%) were HER-2-positive, and 50 (22.2%) were triple-negative, and the corresponding median VI values were 5.9% (2.6%~11.6%) (range 0%~47.1%), 7.3 (4.4%~10.5%) (range 0%~29.5%), 6.3% (3.9%~11.3%) (range 0.6%~22.2%), 8.2% (4.9%~15.6%) (range 0.9%~54.4%), and 9.2% (5.1%~15.3%) (range 0.7%~32.9%), respectively. Estrogen receptor (ER) negativity, higher tumor grade, and higher Ki-67 index (≥20%) were significantly associated with a higher VI value. Tumor size, ER status, and Ki-67 index were shown to independently influence VI. A cutoff value of 4.1% yielded 79.9% sensitivity and 41.5% specificity with an area under the receiver operating characteristic curve (AUC) of 0.58 for predicting that a tumor was of the luminal A subtype. A cutoff value of 16.4% yielded 30.0% sensitivity and 90.3% specificity with an AUC of 0.60 for predicting a triple-negative subtype. Conclusions: VI, as a quantitative index obtained by SMI examination, could reflect histologic vascular changes in invasive breast cancer and was found to be higher in more biologically aggressive breast tumors. VI shows a certain degree of correlation with the molecular subtype of invasive breast cancer and plays a limited role in predicting the luminal A with high sensitivity and triple-negative subtype with high specificity.

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