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2.
J Pharmacol Exp Ther ; 2021 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-34215702

RESUMO

Phosphorylation of the eukaryotic translation initiation factor 2 α-subunit (eIF2ɑ),which subsequently upregulates activating transcription factor 4 (ATF4), is the core event in the integrated stress response (ISR) pathway. Previous studies indicate phosphorylation of eIF2ɑ in atrial tissue in response to atrial fibrillation (AF). This study investigated the role of ISR pathway in experimental AF by using a small-molecule ISR inhibitor (ISRIB). Accordingly, rats were subjected to coronary artery occlusion to induce myocardial infarction (MI), or sham operation, and received either trans-ISRIB (2 mg/kg/day, i.p.) or vehicle for seven days. Thereafter, animals were subjected to the AF inducibility test by transesophageal rapid burst pacing followed by procurement of left atrium (LA) for assessment of atrial fibrosis, inflammatory indices, autophagy-related proteins, ISR activation, ion channel, and connexin43 expression. Results showed a significant increase in the AF vulnerability and the activation of ISR in LA as evidenced by enhanced eIF2α phosphorylation. ISRIB treatment suppressed upregulation of ATF4, fibrosis as indexed by determination of α-smooth muscle actin and collagen levels, inflammatory macrophage infiltration (i.e., CD68 and iNOS/CD68-positive macrophage) and autophagy as determined by expression of LC3. Further, ISRIB treatment reversed the expression of relevant ion channel (i.e., Nav1.5, Cav1.2, and Kv4.3) and Cx43 remodeling. Collectively, the results suggest that the ISR is a key pathway in pathogenesis of AF, post-MI, and represents a novel target for treatment of AF. Significance Statement Activation of integrated stress response (ISR) pathway as evidenced by enhanced eIF2α phosphorylation in left atrium plays a key role in atrial fibrillation (AF). A small-molecule ISR inhibitor (ISRIB) reduces AF and atrial arrhythmogenic substrate. The mechanism of ISRIB may be mediated by suppressing ISR pathway-related cardiac fibrosis, inflammatory macrophage infiltration, autophagy, and restoring the expression of ion channel and Cx43. This study suggests a key dysfunctional role for ISR in pathogenesis of AF with implications for novel treatment.

3.
Clin Liver Dis ; 25(3): 483-492, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34229835

RESUMO

Alcohol-associated liver disease (ALD) is a consequence of excessive alcohol use. It comprises a spectrum of histopathologic changes ranging from simple steatosis, steatohepatitis, and cirrhosis to hepatocellular carcinoma. The public health impact of ALD is growing because of an increase in the prevalence and incidence of ALD in parallel with liver transplant and mortalities. There are multiple factors involved in the pathogenesis and progression of ALD. Reducing alcohol consumption is the cornerstone of ALD management. The efforts to reduce excessive alcohol use at the individual and population levels are urgently needed to prevent adverse outcomes from ALD.

4.
NPJ Biofilms Microbiomes ; 7(1): 58, 2021 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-34244520

RESUMO

The low viability during gastrointestinal transit and poor mucoadhesion considerably limits the effectiveness of Ligilactobacillus salivarius Li01 (Li01) in regulating gut microbiota and alleviating inflammatory bowel disease (IBD). In this study, a delivery system was designed through layer-by-layer (LbL) encapsulating a single Li01cell with chitosan and alginate. The layers were strengthened by cross-linking to form a firm and mucoadhesive shell (~10 nm thickness) covering the bacterial cell. The LbL Li01 displayed improved viability under simulated gastrointestinal conditions and mucoadhesive function. Almost no cells could be detected among the free Li01 after 2 h incubation in digestive fluids, while for LbL Li01, the total reduction was around 3 log CFU/mL and the viable number of cells remained above 6 log CFU/mL. Besides, a 5-fold increase in the value of rupture length and a two-fold increase in the number of peaks were found in the (bacteria-mucin) adhesion curves of LbL Li01, compared to those of free Li01. Oral administration with LbL Li01 on colitis mice facilitated intestinal barrier recovery and restoration of the gut microbiota. The improved functionality of Li01 by LbL encapsulation could increase the potential for the probiotic to be used in clinical applications to treat IBD; this should be explored in future studies.

5.
J Transl Med ; 19(1): 314, 2021 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-34284793

RESUMO

BACKGROUND: Circular RNA (circRNA) has been demonstrated to participate in cervical cancer development. In this study, we analyzed the role of hsa_circ_0000520 in cervical cancer. METHODS: Fifty-two pairs of cervical cancer and adjacent normal tissue samples were collected, and five human cervical cancer cell lines were obtained followed by the detection of hsa_circ_0000520 expression. Nuclear-cytoplasmic isolation and fluorescence in situ hybridization were performed to analyze the subcellular localization of hsa_circ_0000520 while linear RNA was digested by RNase R. Gain- or loss-of function experiments on hsa_circ_0000520 were performed, followed by detection of cell proliferation and cell cycle by EdU, Cell Counting Kit-8, colony formation assay, and flow cytometry respectively. RESULTS: Hsa_circ_0000520 and cyclin-dependent kinase 2 (CDK2) were highly expressed in cervical cancer tissues. Binding sites between microRNA-1296 (miR-1296) and hsa_circ_0000520 or CDK2 were verified. Antibody to Argonaute 2 (Ago2) could precipitate hsa_circ_0000520, indicating that hsa_circ_0000520 could competitively bind to miR-1296 via Ago2. Silencing hsa_circ_0000520 inhibited cervical cancer cell proliferation and promoted the inhibitory effects of miR-1296 on CDK2, thereby blocking cell cycle progression and promoting apoptosis. CONCLUSION: These results support the premise that targeting hsa_circ_0000520 can be a potential approach to combat cervical cancer.

6.
Cell Death Dis ; 12(8): 721, 2021 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-34285192

RESUMO

Brain metastases remain a major problem in patients with advanced non-small cell lung cancer (NSCLC). The permeability of the blood-brain barrier (BBB) is highly increased during lung cancer brain metastasis; however, the underlying mechanism remains largely unknown. We previously found that lnc-MMP2-2 is highly enriched in tumor growth factor (TGF)-ß1-mediated exosomes and regulates the migration of lung cancer cells. This study aimed to explore the role of exosomal lnc-MMP2-2 in the regulation of BBB and NSCLC brain metastasis. Here, using endothelial monolayers and mouse models, we found that TGF-ß1-mediated NSCLC-derived exosomes efficiently destroyed tight junctions and the integrity of these natural barriers. Overexpression of lnc-MMP2-2 in human brain microvascular endothelial cells increased vascular permeability in endothelial monolayers, whereas inhibition of lnc-MMP2-2 alleviated these effects. Furthermore, lnc-MMP2-2 knockdown markedly reduced NSCLC brain metastasis in vivo. Mechanistically, through luciferase reporter assays, RNA pull-down assay, and Ago2 RNA immunoprecipitation assay, we showed that lnc-MMP2-2 served as a microRNA sponge or a competing endogenous RNA for miR-1207-5p and consequently modulated the derepression of EPB41L5. In conclusion, TGF-ß1-mediated exosomal lnc-MMP2-2 increases BBB permeability to promote NSCLC brain metastasis. Thus, exosomal lnc-MMP2-2 may be a potential biomarker and therapeutic target against lung cancer brain metastasis.

7.
Artigo em Inglês | MEDLINE | ID: mdl-34297526

RESUMO

Developing nonprecious electrocatalysts operating in acidic and alkaline media for an oxygen reduction reaction (ORR) is essential for sustainable energy technologies. Increasing the metal active site density is an effective strategy to enhance the activity, but it remains challenging because of metal sintering during pyrolysis. Here, we report a novel strategy of enriching atomically dispersed cobalt species in nitrogen-doped carbon for improving the electrocatalytic performance. A hollow carbon nanosphere with reduced shell thickness was obtained by taking advantage of the carbothermic reaction between carbon and ZnO template, and the resulting cobalt enrichment in the ultrathin carbon shell leads to an increase of the density of Co atoms. Together with advantageous microstructure features such as high surface area and multiscale porosity, the corresponding catalyst demonstrated promising oxygen reduction reaction performance in strong acidic and alkaline electrolytes and has two times higher kinetic current density than the nonenriched one. The present work provides an attractive and facile route to engineer active site in electrocatalysts.

8.
Genes (Basel) ; 12(7)2021 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-34199009

RESUMO

Familial exudative vitreoretinopathy (FEVR) is an inherited disorder characterized by abnormalities in the retinal vasculature. The FZD4 gene is associated with FEVR, but the prevalence and impact of FZD4 copy number variation (CNV) on FEVR patients are unknown. The aim of this study was to better understand the genetic features and clinical manifestations of patients with FZD4 CNVs. A total of 651 FEVR families were recruited. Families negative for mutations in FEVR-associated genes were selected for CNV analysis using SeqCNV. Semiquantitative multiplex polymerase chain reaction and multiplex ligation-dependent probe amplification were conducted to verify the CNVs. Four probands were found to carry whole-gene deletions of FZD4, accounting for 5% (4/80) of probands with FZD4 mutations and 0.6% (4/651) of all FEVR probands. The four probands exhibited similar phenotypes of unilateral retinal folds. FEVR in probands with CNVs was not more severe than in probands with FZD4 missense mutations (p = 1.000). Although this is the first report of FZD4 CNVs and the associated phenotypes, the interpretation of FZD4 CNVs should be emphasized when analyzing the next-generation sequencing data of FEVR patients because of their high prevalence.

9.
Neuropsychologia ; : 107968, 2021 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-34310972

RESUMO

Racial categorization of faces has a notable impact on human behavior, but its neural underpinnings remain unresolved. Previous electroencephalography (EEG) research focused on contributions of phase-locked neural activities to racial categorization of faces. We investigated functional roles of non-phase-locked neural oscillations in spontaneous racial categorization of faces by recording EEG from Chinese adults who performed an individuation task on Asian/White faces in Experiment 1 and on Asian/Black faces in Experiment 2. We quantified neural processes involved in spontaneous racial categorization of faces by examining repetition suppression of non-phase-locked neural oscillations when participants viewed faces of one race presented repeatedly in the same block of trials (repetition condition), or faces of two races presented alternately in the same block of trials (alternating condition). We found decreased power of alpha (9-13 Hz) oscillations in the repetition than alternating conditions at 80-240 ms over frontal-central electrodes induced by White/Black (but not Asian) faces. Moreover, larger repetition suppression of alpha oscillations in response to White/Black (vs. Asian) faces predicted greater implicit negative attitudes toward White/Black faces across individuals. Our findings suggest that non-phase-locked alpha oscillations are engaged in spontaneous racial categorization of faces and are associated with implicit negative attitudes toward other-race faces.

10.
Artigo em Inglês | MEDLINE | ID: mdl-34312713

RESUMO

Akkermansia muciniphila is a next-generation probiotic with significant application prospects. The role of A. muciniphila in metabolic diseases and tumor immunotherapy has been widely recognized. Recent clinical trials further confirmed its safety and therapeutic value in human metabolic diseases. A. muciniphila also shows potential in the treatment of intestinal inflammatory diseases, especially for inflammatory bowel disease (IBD). The improvement in the efficacy of washed microbiota transplantation (WMT) in treating IBD is closely related to the increase in the abundance of A. muciniphila in patients' gut. However, there is still controversy regarding the pro-inflammatory or anti-inflammatory effect of A. muciniphila on IBD. Currently, several studies targeting the correlation between A. muciniphila and IBD have demonstrated opposite conclusions. Similarly, the interventional studies exploring causality between them also come to conflicting results. This article therefore aims to review the relationship between A. muciniphila and IBD, the effect of intervention of A. muciniphila on IBD, and the possible reasons for the contradictory role of A. muciniphila in the treatment of IBD. KEY POINTS: The effect of A. muciniphila on inflammatory bowel disease is controversy. A. muciniphila shows anti-inflammatory potential in IBD. The colitogenicity of A. muciniphila is context dependent.

11.
Protein Expr Purif ; : 105948, 2021 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-34303809

RESUMO

A certain impurity may bind weaker or tighter to a particular type of chromatography column (e.g., ion exchange, hydrophobic interaction or mixed-mode) than the target protein, and this forms the basis for separation. For impurities that bind weaker, they can be removed by an appropriate pre-elution wash. However, we previously showed that wash-enabled impurity clearance is usually sensitive to loading density, causing poor robustness of the process. In this work, with a bispecific antibody case study, we compared the relative robustness of anion exchange and the corresponding mixed-mode chromatography, which mediates both anion exchange and hydrophobic interactions, on removing a weakly-bound byproduct by wash. It was learned that under a fixed appropriate wash condition, the latter achieves consistent byproduct clearance and good yield over a much wider range of loading density than the former. As wide loading density range is highly desirable for large-scale manufacturing, the above finding suggests that for a chromatography step that employs stepwise elution and relies on pre-elution wash for removing weakly-bound impurities, mixed-mode chromatography could be a better choice than the corresponding monomode ion exchange chromatography.

12.
Zhongguo Zhen Jiu ; 41(7): 711-5, 2021 Jul 12.
Artigo em Chinês | MEDLINE | ID: mdl-34259399

RESUMO

OBJECTIVE: To compare the clinical effect between yin-yang penetrating acupuncture with elongated needle and routine acupuncture for spastic limb dysfunction after stroke. METHODS: A total of 60 patients were randomized into an observation group and a control group, 30 cases in each group. Both groups received basic treatment, yin-yang penetrating acupuncture with elongated needle was applied from Yanglingquan (GB 34) to Xuanzhong (GB 39), Quchi (LI 11) to Wenliu (LI 7), Huantiao (GB 30) to Fengshi (GB 31), Jianyu (LI 15) to Quchi (LI 11), etc. on the affected side in the observation group; routine acupuncture was applied at Neiguan (PC 6), Shuigou (GV 26), Sanyinjiao (SP 6), Jiquan (HT 1), Chize (LU 5), Weizhong (BL 40), Jianyu (LI 15), etc. on the affected side in the control group. Once a day, 5 times a week, 2 weeks as a course, 2 courses were required in the two groups. Before and after treatment,the modified Ashworth scale (MAS) grade, Fugl-Meyer assessment scale (FMA) score, activity of daily living scale (ADL) (Barthel index) score were observed, and the clinical effect was evaluated in the two groups. RESULTS: Compared before treatment, the MAS grade after treatment was improved in the two groups (P<0.05), that in the observation group was superior to the control group (P<0.05). Compared before treatment, the FMA and ADL scores after treatment were increased in the two groups (P<0.05), the changes in the observation group were larger than the control group (P<0.05). The total effective rate in the observation group was 80.0% (24/30), which was superior to 70.0% (21/30) in the control group (P<0.05). CONCLUSION: Yin-yang penetrating acupuncture with elongated needle could improve muscle tension, spasm grade and motor function in patients with spastic limb dysfunction after stroke, enhance the activity of daily living, its clinical effect is superior to routine acupuncture.


Assuntos
Terapia por Acupuntura , Acidente Vascular Cerebral , Pontos de Acupuntura , Humanos , Espasticidade Muscular/etiologia , Espasticidade Muscular/terapia , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/terapia , Resultado do Tratamento , Yin-Yang
13.
Cancer Med ; 2021 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-34227248

RESUMO

It was previously reported that PRR34-AS1 was overexpressed in some solid tumors. PRR34-AS1 promoter was shown to have a differential methylation region (DMR), and was hypomethylated in acute myeloid leukemia (AML). Therefore, the present study used real-time quantitative PCR (RQ-PCR) to explore the expression characteristics of PRR34-AS1 in AML. In addition, the correlation between the expression of PRR34-AS1 and clinical prognosis of AML was determined. The findings of this study indicated that high PRR34-AS1 expression was bound up with shorter overall survival (OS) in AML patients (p = 0.002). Moreover, patients with high expression of PRR34-AS1 had significantly lower complete remission (CR) rate compared with those with low expression of PRR34-AS1 after induction chemotherapy. Furthermore, multivariate analysis confirmed that PRR34-AS1 expression was an independent factor affecting CR in whole-AML, non-APL-AML, and CN-AML patients (p = 0.032, 0.039, and 0.036, respectively). Methylation-specific PCR (MSP) and bisulfite sequencing PCR (BSP) were used to explore the methylation status of PRR34-AS1. PRR34-AS1 promoter showed a pattern of hypomethylation in AML patients compared with normal controls (p = 0.122). Notably, of whole-AML and non-APL-AML patients, PRR34-AS1 hypomethylated patients presented a significantly shorter OS than those with a hypermethylated PRR34-AS1 (p = 0.010 and 0.037, respectively). Multivariate analysis confirmed that the hypomethylation of PRR34-AS1 served as an independent prognostic indicator in both whole-cohort AML and non-APL-AML categories (p = 0.057 and 0.018, respectively). In summary, the findings of this study showed that abnormalities in PRR34-AS1 are associated with poor prognosis in AML. Therefore, monitoring this index may be important in the prognosis of AML and can provide information on effective chemotherapy against the disease.

14.
Adv Mater ; : e2008297, 2021 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-34309916

RESUMO

Mass cytometry, also called cytometry by time-of-flight (CyTOF), is an emerging powerful proteomic analysis technique that utilizes metal chelated polymer (MCP) as mass tags for interrogating high-dimensional biomarkers simultaneously on millions of individual cells. However, under the typical polymer-based mass tag system, the sensitivity and multiplexing detection ability has been highly restricted. Herein, a new structure mass tag based on a nanometal organic framework (NMOF) is reported for multiparameter and sensitive single-cell biomarker interrogating in CyTOF. A uniform-sized Zr-NMOF (33 nm) carrying 105 metal ions is synthesized under modulator/reaction time coregulation, which is monodispersed and colloidally stable in water for over one-year storage. On functionalization with an antibody, the Zr mass tag exhibits specific molecular recognition properties and minimal cross-reaction toward nontargeted cells. In addition, the Zr-mass tag is compatible with MCP mass tags in a multiparameter assay for mouse spleen cells staining, which exploits four additional channels, m/z = 90, 91, 92, 94, for single-cell immunoassays in CyTOF. Compared to the MCP mass tag, the Zr-mass tag provides an additional fivefold signal amplification. This work provides the fundamental technical capability for exploiting NMOF-based mass tags for CyTOF application, which opens up possibility of high-dimensional single-cell immune profiling, low abundant antigen detection, and development of new barcoding systems.

15.
Zhongguo Dang Dai Er Ke Za Zhi ; 23(7): 707-712, 2021 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-34266528

RESUMO

OBJECTIVE: To study the drug resistance of Mycoplasma pneumoniae (MP) in the bronchoalveolar lavage fluid (BALF) of children with refractory Mycoplasma pneumoniae pneumonia (RMPP) and the distribution of drug-resistance genes, as well as the association of alleles at 2063 locus of 23SrRNA V region central ring with resistance to antimicrobial drugs. METHODS: BALF specimens were collected from 245 children with RMPP who were admitted to the Children's Hospital Affiliated to Zhengzhou University from March 2016 to December 2020. A rapid cultured drug sensitivity assay was used to detect the resistance of MP isolates to nine commonly used antimicrobial drugs. The real-time PCR was used to measure MP DNA. The direct sequencing was used to detect gene mutations in MP 23SrRNA V region central ring. RESULTS: Among the 245 BALF specimens, 207 tested positive for MP DNA, with a positive rate of 84.5%. The results of drug susceptibility test showed that the children with RMPP had a resistance rate of > 70% to macrolide antimicrobial drugs, with the highest resistance rate to clarithromycin, followed by roxithromycin, clindamycin, acetylspiramycin, erythromycin, and azithromycin, and these children had a resistance rate of < 5% to quinolone antimicrobial drugs. Among the 207 MP DNA-positive specimens, 41 (19.8%) had no drug-resistance gene mutations and 166 (80.2%) had drug-resistance gene mutations, among which 154 (74.4%) had an A→G mutation at 2063 locus of 23SrRNA V region central ring, 7 (3.4%) had an A→G mutation at 2064 locus, and 5 (2.4%) had mutations in both 2063 and 2064 loci. Among the 166 specimens with point mutations of the MP 23SrRNA gene, 159 (95.8%) had point mutations at 2063 locus. The A→G point mutation at 2063 locus of 23SrRNA V region central ring had a great impact on resistance to macrolide antimicrobial drugs. There was a significant difference in the distribution of alleles at 2063 locus between the children with resistance to clarithromycin, roxithromycin, clindamycin, acetylspiramycin, erythromycin, and azithromycin (P < 0.05). CONCLUSIONS: MP in the BALF of children with RMPP has a relatively high resistance rate to macrolide antimicrobial drugs. Resistance to macrolide antimicrobial drugs is closely associated with the A→G point mutation in the 23SrRNA gene, and the point mutation at 2063 locus of 23SrRNA V region central ring may affect the drug-resistance mechanism of MP.


Assuntos
Antibacterianos , Farmacorresistência Bacteriana , Mycoplasma pneumoniae , Pneumonia por Mycoplasma , Antibacterianos/farmacologia , Líquido da Lavagem Broncoalveolar , Criança , Farmacorresistência Bacteriana/genética , Humanos , Mycoplasma pneumoniae/genética , Pneumonia por Mycoplasma/tratamento farmacológico
17.
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.

18.
Biochem Biophys Res Commun ; 569: 1-9, 2021 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-34216991

RESUMO

Glioblastoma multiforme (GBM) is the most common primary malignant brain tumor without curable therapy. Surgical resection remains the first choice of patients with GBM but tumors relapse rapidly even combined with conventional chemoradiotherapy. The mechanism of GBM rapid recurrence is poorly understood, which is largely due to the lack of an appropriate animal model, thus heavily impedes the improvement of postoperative therapy. Here we established a highly reproducible mouse GBM surgical model by using the syngeneic G422TN-GBM cells, which faithfully recapitulates the features of rapid recurrence of human GBM after surgery. Implanting 2 × 103-5 × 104 of G422TN-GBM cells in mouse cerebral cortex caused death in all animal within 23 days, while surgery was an effective therapy but not curable. After complete removal of visible tumors on day 5-9 of tumor growth, the tumors recurred macroscopically within 5 days accompanied by increasing infiltrative cancer foci. Mechanistically, the rapid recurrence of resected tumors was positively correlated to early Akt activation, which subsequently upregulated PD-L1/Vimentin and promoted proliferation/migration of cancer cells. In addition, environmental astrocytic activation with strong PD-L1 signal was prominent. Taken together, we provided a novel GBM surgical recurrence model for preclinical studies and suggested complicated recurring mechanisms involving in strong oncogenic signaling as well as immune inhibitory signals from both GBM cells and their neighboring astrocytes.

19.
J Trace Elem Med Biol ; 68: 126814, 2021 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-34243025

RESUMO

BACKGROUND: This study tested the hypothesis that abnormal maternal metabolism of both homocysteine and thyroid hormone network in pregnant women is associated with neural tube defects (NTDs) in a part of China with high NTD prevalence. METHODS: A case-control study was performed between 2007 and 2009 in Lüliang Mountains, Shanxi Province. This study included 83 pregnant women who had fetuses with NTDs (cases) and 90 pregnant women with normal fetuses (controls). In addition, a cell model to illustrate the epidemiological findings was established. RESULTS: Fetuses of mother who had both high total homocysteine (tHcy) and inadequate free thyroxine were 3 times more at risk of developing NTDs (adjusted odds ratio = 3.5; 95 % confidence interval = 1.2-10.4; cases vs. controls) using multivariate logistic regression models. Furthermore, biological interaction between metabolisms of Hcy and thyroid hormones was demonstrated in vitro. In homocysteine thiolactone of a metabolite of Hcy-treated mouse embryonic neural stem NE4C cells, genes (Bmp7, Ctnnb1, Notch 1, Gli2, and Rxra) related to both neural tube closure and thyroid hormone network were shown to be regulated by H3K79 homocysteinylation, which increased their expression levels. CONCLUSIONS: The effect of maternal serum high tHcy on risk of developing NTDs is depended on maternal serum level of thyroxine. Meanwhile, a higher level of tHcy might also affect both maternal metabolism of thyroid hormone and neural tube closure in embryogenesis through homocysteinylation of histones.

20.
Int J Biol Macromol ; 186: 145-154, 2021 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-34246667

RESUMO

Herein, three types of silver carp scale gelatins were extracted, and their molecular weight distribution, structural properties, functional properties and emulsifying properties were investigated and discussed. Acetic acid-extracted gelatin (AAG), hot water-extracted gelatin (HWG), and pepsin enzyme-extracted gelatin (PEG) showed similar and four clear bands in sodium dodecyl sulfate-polyacrylamide gel electrophoresis pattern, whereas they showed different ß chain amounts and ß-sheet percentages. The water-holding capacity values (g/g of gelatin) were: AAG (16.8 ± 1.1) > HWG (14.0 ± 0.7) ≈ PEG (13.5 ± 1.6). The fat-binding capacity values (g/g of gelatin) were: AAG (11.8 ± 0.3) > HWG (9.5 ± 1.3) > PEG (5.3 ± 0.4). Emulsion droplet sizes and creaming index values decreased with the increase of gelatin concentrations for all the fish oil-loaded emulsions stabilized by three types of gelatins. Compared with PEG, AAG and HWG show similar and higher emulsion stability at high gelatin concentration (10 mg/mL). The stabilization mechanism of fish oil-loaded silver carp scale gelatin-stabilized emulsions involved an "extraction method-protein molecular weight distribution-protein molecular structure-molecular interaction-emulsibility-droplet structure-emulsion stability" route. This work would be beneficial for the research on the relationship of structure and function of gelatin and to the comprehensive utilization of aquatic products.

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