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1.
Sci Rep ; 11(1): 21830, 2021 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-34750414

RESUMO

Atopic dermatitis (AD) is a common and complex skin disorder, and the 5q22.1 region had been reported to be associated with AD. To confirm the susceptibility gene for AD in the 5q22.1 region by haplotype and targeted capture sequencing. The haplotypes were reconstructed with the genotyping data of four SNPs and six deletions from 3624 Chinese Hans AD patients and 5076 controls. The targeted capture sequencing spanning 5q22.1 region was performed in the selected samples. The gene level enrichment analysis was done using loss of function variants. A total of 62 haplotypes were found, and the H15 haplotype had the strongest association with AD (P = 3.92 × 10-10, OR 0.17, 95% CI 0.09-0.32). However, no co-segregation mutation sites were found in the sequencing analysis within the 16 selected samples, while the enrichment analysis indicated that TMEM232 was significantly associated with AD (P = 7.33 × 10-5, OR 0.33, 95% CI 0.19-0.58). This study confirms previous findings that the TMEM232 gene is associated with AD by haplotype analysis and targeted capture sequencing.

2.
Genet Test Mol Biomarkers ; 25(10): 638-645, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34609929

RESUMO

Background: Genome-wide association studies (GWASs) have identified many genetic variants that are risk factors for numerous immune-mediated diseases. In particular, different immune-mediated diseases have been found to share the same susceptibility loci. Therefore, exploring the genetic overlap between atopic dermatitis (AD) and other immune-mediated diseases in more detail may help identify additional shared susceptibility loci among common immune-mediated diseases. Recent evidence suggests that the 11q23.3 locus is a susceptibility locus shared among multiple immune-mediated diseases. Objective: This study was designed to investigated whether SNPs at the chromosome 11q23.3 locus are associated with AD in the Han Chinese population. Methods: In total, 16 SNPs within the 11q23.3 locus were genotyped using TaqMan assays for 1,012 AD cases and 1,362 controls. From these SNPs, we selected rs638893 with an association values of p < 5 × 10-2 for AD for further analysis in an independent replication study using the Sequenom MassARRAY system to genotype an additional (consisting of 1,288 cases and 1,380 controls). The combined analyses were performed in two stages using a meta-analytical method. Results: We identified a common variant at 11q23.3 (rs638893), that was significantly associated (p = 1.58 × 10-3, OR = 1.22) with AD. The genotype-based association analysis revealed that the recessive model provided the best fit for rs638893. Conclusion: Our study identified a variant on chromosome 11q23.3 that likely confers susceptibility to AD, thereby advancing our understanding of the genetic basis of this disease.

3.
Immunol Lett ; 240: 98-105, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34710506

RESUMO

Psoriasis is an immune-mediated genetic disease involving innate and the adaptive immune system. Aurora kinase A (AURKA) belongs to a seine/threonine kinases family and is elevated in lesional psoriatic tissues. This research aimed to investigate the effects of AURKA on psoriasis progression and whether it worked by regulating autophagy or inflammasome activation. The results showed that the expression of AURKA was higher in psoriasis tissue than that in the psoriasis skin. IFN-γ (100 ng/mL) plus poly (dA:dT) (2 mg/mL) induced the increased AURKA, secretion of IL-1ß, IL-18 and the active form of caspase-1 (p20). AURKA knockdown inhibited the inflammatory responses of keratinocytes and the activation of AIM2 inflammasome, and enhanced autophagy. 3MA (autophagy inhibitor) attenuated the effects of AURKA on AIM2 inflammasome. In addition, AURKA promoted the activation of the AKT/mTOR pathway. Akt inhibitor (PI-103) attenuated AIM2 inflammasome activation induced by Aurka overexpression. In conclusion, this research demonstrated that AURKA promoted the psoriasis-related inflammation by blocking autophagy-mediated AIM2 inflammasome suppression. AURKA has the potential to be explored as a new promising target for the treatment for psoriasis.

4.
Plant J ; 2021 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-34695268

RESUMO

Dwarfing rootstocks and dwarf cultivars are urgently needed for modern pear cultivation. However, germplasm resources for dwarfing pear are limited, and the underlying mechanisms remain unclear. We previously showed that dwarfism in pear is controlled by the single dominant gene PcDw (Dwarf). We report here that the expression of PcAGP7-1 (ARABINOGALACTAN PROTEIN 7-1), a key candidate gene for PcDw, is significantly higher in dwarf-type pear plants because of a mutation in an E-box in the promoter. Electrophoretic mobility shift assays and transient infiltration showed that the transcription factors PcBZR1 and PcBZR2 could directly bind to the E-box of the PcAGP7-1 promoter and repress transcription. Moreover, transgenic pear lines overexpressing PcAGP7-1 exhibited obvious dwarf phenotypes, whereas RNA interference pear lines for PcAGP7-1 were taller than controls. PcAGP7-1 overexpression also enhanced cell wall thickness, affected cell morphogenesis, and reduced brassinolide (BL) content, which inhibited BR signaling via a negative feedback loop, resulting in further dwarfing. Overall, we identified a dwarfing mechanism in perennial woody plants involving the BL-BZR/BES-AGP-BL regulatory module. Our findings provide insight into the molecular mechanism of plant dwarfism and suggest strategies for the molecular breeding of dwarf pear cultivars.

5.
Food Funct ; 12(22): 11387-11398, 2021 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-34672304

RESUMO

Cancer is a major threat to human health worldwide, yet the clinical therapies remain unsatisfactory. In this study, we found that a Tetrastigma hemsleyanum leaves flavone (TLF) intervention could achieve tumor inhibition. Besides, neochlorogenic acid (NA), which had the highest absorbance peak in the HPLC profile of TLF, showed superior anti-proliferation ability over TLF, and could effectively trigger apoptosis, restrain migration, and facilitate cytoskeleton collapse, suggesting its key role in TLF's anticancer property. Molecular docking analysis suggested that NA was capable of binding with mitochondrial Ca2+ uniporter (MCU), and further experiments confirmed that NA upregulated the MCU level to permit excess calcium ion influx, leading to mitochondrial calcium imbalance, dysfunction, structure alteration, and ROS elevation. Moreover, tumor-bearing mice were applied to further confirm the excellent tumor inhibition ability of NA under Ca2+-abundant conditions. Therefore, this study uncovered that NA could effectively trigger robust MCU-mediated calcium overload cancer therapy, which could be utilized in novel strategies for future cancer treatment.

6.
Food Funct ; 12(22): 11599-11610, 2021 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-34713882

RESUMO

Type 2 diabetes mellitus is a disease associated with an oxidative milieu that often leads to adverse health outcomes. Multiple anthocyanins have been reported to possess outstanding antioxidant activity, however, their effects on hyperglycemia-related oxidative stress remain elusive. In the present study, cyanidin-3-O-glucoside (C3G), a typical anthocyanin with various widely accepted health benefits, was applied to alleviate oxidative stress in pancreas islets under the conditions of hyperglycemia. Firstly, significantly decreased mitochondrial membrane potential (MMP) and antioxidant enzymes, as well as increased reactive oxygen species (ROS) and O2- levels, were detected after exposure to a series of concentrations of high glucose (HG) and palmitic acid (PA), which manifested oxidative stress triggered by mitochondrial damage. To evaluate the antioxidant effect of C3G in vitro, the islet cell line NIT-1 was used, and results proved that C3G could effectively relieve cellular oxidative stress induced by HG and PA. Furthermore, we found that the antioxidant effect of C3G was achieved by activating mitophagy via the PINK1-PARKIN signaling pathway. More importantly, an autophagy inhibitor chloroquine (CQ) was added to verify our findings at the protein level, and we observed the co-localization of mitochondria and lysosomes, which may form autophagolysosomes to clean damaged mitochondria. Immediately afterwards, more studies were conducted on pancreatic islets of diabetic db/db mice to verify the antioxidant effect of C3G discovered in islet cells. Along with the decline in fasting blood glucose, the oxidative stress in pancreas islets was successfully alleviated in diabetic db/db mice after supplementation with C3G. This was demonstrated by increased levels of ROS, and the impaired activities of anti-oxidative enzymes superoxide dismutase (SOD) and catalase (CAT) were partly reversed by C3G intervention. Our study has provided evidence for the alleviation effect of C3G against oxidative stress in pancreas islets, which may provide enlightenment for improving the health situation of diabetic patients in the future.

7.
Plant Sci ; 312: 111026, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34620431

RESUMO

Brassinosteroids (BRs) play numerous important roles in plant growth and development. Previous studies reported that BRs could promote stem growth by regulating the expression of xyloglucan endotransglucosylase/hydrolases (XTHs). However, the mechanism of XTHs involved in stem growth remains unclear. In this study, PcBRU1, which belonged to the XTH family, was upregulated by exogenous BL treatment in Pyrus communis. The expression of PcBRU1 was highest in stems and lowest in leaves. Subcellular localization analysis indicated that PcBRU1 was located in the plasma membrane. Furthermore, overexpressing PcBRU1 in tobaccos promoted the plant height and internode length. Electron microscopy and anatomical structure analysis showed that the cell wall was significantly thinner and the cells were slenderer in transgenic tobacco lines overexpressing PcBRU1 than in wild-type tobaccos. PcBRU1 promoted stem growth as it loosened the cell wall, leading to the change in cell morphology. In addition, overexpressing PcBRU1 altered the root development and leaf shape of transgenic tobaccos. Taken together, the results could provide a theoretical basis for the XTH family in regulating cell-wall elongation and stem growth.


Assuntos
Crescimento Celular , Glicosiltransferases/metabolismo , Folhas de Planta/metabolismo , Caules de Planta/metabolismo , Pyrus/crescimento & desenvolvimento , Pyrus/genética , Pyrus/metabolismo , Parede Celular/metabolismo , Produtos Agrícolas/genética , Produtos Agrícolas/crescimento & desenvolvimento , Produtos Agrícolas/metabolismo , Regulação da Expressão Gênica de Plantas , Genes de Plantas , Variação Genética , Genótipo , Glicosiltransferases/genética , Fenótipo , Folhas de Planta/genética , Folhas de Planta/crescimento & desenvolvimento , Caules de Planta/crescimento & desenvolvimento , Tabaco/genética , Tabaco/crescimento & desenvolvimento , Tabaco/metabolismo
8.
BMC Plant Biol ; 21(1): 433, 2021 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-34556040

RESUMO

BACKGROUND: Resveratrol (Res), a phytoalexin, has been widely reported to participate in plant resistance to fungal infections. However, little information is available on its role in abiotic stress, especially in iron deficiency stress. Malus baccata is widely used as apple rootstock in China, but it is sensitive to iron deficiency. RESULTS: In this study, we investigated the role of exogenous Res in M. baccata seedings under iron deficiency stress. Results showed that applying 100 µM exogenous Res could alleviate iron deficiency stress. The seedlings treated with Res had a lower etiolation rate and higher chlorophyll content and photosynthetic rate compared with the apple seedlings without Res treatment. Exogenous Res increased the iron content in the roots and leaves by inducing the expression of MbAHA genes and improving the H+-ATPase activity. As a result, the rhizosphere pH decreased, iron solubility increased, the expression of MbFRO2 and MbIRT1 was induced, and the ferric-chelated reductase activity was enhanced to absorb large amounts of Fe2+ into the root cells under iron deficiency conditions. Moreover, exogenous Res application increased the contents of IAA, ABA, and GA3 and decreased the contents of DHZR and BL for responding to iron deficiency stress indirectly. In addition, Res functioned as an antioxidant that strengthened the activities of antioxidant enzymes and thus eliminated reactive oxygen species production induced by iron deficiency stress. CONCLUSION: Resveratrol improves the iron deficiency adaptation of M. baccata seedlings mainly by regulating iron absorption.


Assuntos
Adaptação Fisiológica/efeitos dos fármacos , Transporte de Íons/efeitos dos fármacos , Ferro/deficiência , Ferro/metabolismo , Malus/metabolismo , Doenças das Plantas/induzido quimicamente , Resveratrol/metabolismo , Estresse Fisiológico/efeitos dos fármacos , China , Produtos Agrícolas/metabolismo , Plântula/metabolismo
9.
Food Funct ; 12(20): 10160-10170, 2021 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-34528983

RESUMO

Hyperlipidemia, liver steatosis and insulin resistance are common metabolic diseases associated with obesity. The present study was designed to investigate the in vivo protective value of black rice anthocyanins (BRAN) on hyperlipidemia, liver steatosis and insulin resistance in mice with high-fat-diet (HFD)-induced obesity and elucidate the underlying mechanism. Specific pathogen-free male C57BL/6J mice (four weeks old, weighing 17.6-20.9 g) were randomly divided into three groups and fed with low-fat diet (LFD, 10% fat energy), HFD (45% fat energy), or HFD supplemented with BRAN by intragastric administration for 14 weeks. The obesity-related biochemical indices and hepatic gene expression levels were determined. 16S rRNA sequencing was used to determine the gut microbial changes induced by BRAN treatment. The results showed that the body weight gain, triglycerides, total cholesterol, steatosis scores and insulin resistance index in the BRAN group decreased by 24.69%, 29.83%, 28.08%, 46.67% and 40.42%, respectively, compared to the HFD group. Gene expression analysis indicated that BRAN treatment improved the gene expression profiles involved in lipid metabolism compared with the mice fed HFD alone. Moreover, BRAN treatment significantly altered the composition of the gut microbiota, which was closely correlated with the obesity-related biomarkers. In conclusion, this study demonstrated that dietary supplementation of BRAN protected from obesity-associated hyperlipidemia, hepatic steatosis and insulin resistance by influencing the gut microbiota and lipid metabolism.

10.
J Sci Food Agric ; 2021 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-34514612

RESUMO

BACKGROUND: Pomegranate is a rich source of polyphenols and has been used as a dietary supplement and pharmaceutical ingredient. This study aimed to investigate the pomegranate fruit pulp polyphenols (PFP) with regard to their anti-obesity activity and gut microbiota-modulating effect in mice. Thirty-six 4-week-old specific pathogen-free C57BL/6J mice (weight: 17.7-20.8 g) were randomly divided into three groups and fed with low-fat diet (10% fat energy), high-fat diet (HFD) (45% fat energy), or HFD supplemented with PFP by intragastric administration for 14 weeks. The obesity-related clinical indicators were investigated, and the composition of fecal microbiota was analyzed by 16S rRNA sequencing. RESULTS: Our results showed that PFP treatment reduced HFD-induced body weight gain by 35.23% (P < 0.05), steatosis scores by 50% (P < 0.05) and insulin resistance by 56.84% (P < 0.05), compared with the mice fed HFD alone. Moreover, compared with the mice in the HFD group, PFP supplement changed the composition of the gut microbiota, and enriched Akkermansia muciniphila, Parabacteroides distasonis, Bacteroides acidifaciens, Mucispirillum schaedleri and Lachnospiraceae bacterium 28-4, which were negatively correlated with physical biomarkers, including body weight, glucose, triglycerides and total cholesterol. CONCLUSION: PFP alleviated HFD-induced obesity, insulin resistance and hepatic steatosis in mice, and the changes in the gut microbiota might be one of the potential mechanisms through which PFP improved obesity and obesity-related disorders, eventually benefiting the recipient. © 2021 Society of Chemical Industry.

11.
Biomaterials ; 277: 121080, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34488120

RESUMO

Calcium overload therapy has attracted widespread attention in oncological field, whereas its efficacy has been limited due to insufficient calcium ions in tumor site and poor efficiency of calcium entering tumor, resulting in dissatisfied therapeutic effect. Kaempferol-3-O-rutinoside (KAE), a biosafe flavone with excellent anti-cancer ability, can effectively disrupt calcium homeostasis regulation and facilitate calcium influx, while calcium carbonate (CaCO3) serves as an ideal calcium ions supplier. Inspired by these concepts, KAE loaded into CaCO3 nanoparticles and incorporated with the cancer cell membrane (M) for synergistic tumor therapy. In this therapeutic platform (M@CaCO3@KAE), membrane coating ensures targeted delivery of CaCO3@KAE. Upon reaching tumor, CaCO3@KAE specifically responds to tumor microenvironment, consequently releases KAE and calcium ions. KAE effectively breaks the calcium balance, while calcium ions remarkably aggravate and magnify KAE-mediated calcium overload. Accordingly, mitochondrial structure and functions are destructed, causing cytoskeleton collapse and oxidative stress, leading to cancerous cellular apoptosis. With the combined and cascaded efficacy, considerable in vitro and in vivo tumor inhibition was achieved by M@CaCO3@KAE. This study provides an alternative nano-system, acting as a biomimetic calcium bomb, to ensure targeted, synergistic, efficient and biosafe calcium overload tumor therapy.


Assuntos
Nanopartículas , Neoplasias , Apoptose , Cálcio , Carbonato de Cálcio , Estresse Oxidativo
12.
Plant J ; 108(3): 814-828, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34469599

RESUMO

Drought stress severely limits plant growth and production in apple (Malus domestica Borkh.). To breed water-deficit-tolerant apple cultivars that maintain high yields under slight or moderate drought stress, it is important to uncover the mechanisms underlying the transcriptional regulation of chlorophyll metabolism in apple. To explore this mechanism, we generated transgenic 'Gala3' apple plants with overexpression or knockdown of MdWRKY17, which encodes a transcription factor whose expression is significantly induced by water deficit. Under moderate drought stress, we observed significantly higher chlorophyll contents and photosynthesis rates in overexpression transgenic plants than in controls, whereas these were dramatically lower in the knockdown lines. MdWRKY17 directly regulates MdSUFB expression, as demonstrated by in vitro and in vivo experiments. MdSUFB, a key component of the sulfur mobilization (SUF) system that assembles Fe-S clusters, is essential for inhibiting chlorophyll degradation and stabilizing electron transport during photosynthesis, leading to higher chlorophyll levels in transgenic apple plants overexpressing MdWRKY17. The activated MdMEK2-MdMPK6 cascade by water-deficit stress fine-tunes the MdWRKY17-MdSUFB pathway by phosphorylating MdWRKY17 under water-deficit stress. This fine-tuning of the MdWRKY17-MdSUFB regulatory pathway is important for balancing plant survival and yield losses (chlorophyll degradation and reduced photosynthesis) under slight or moderate drought stress. The phosphorylation by MdMEK2-MdMPK6 activates the MdWRKY17-MdSUFB pathway at S66 (identified by LC-MS), as demonstrated by in vitro and in vivo experiments. Our findings reveal that the MdMEK2-MdMPK6-MdWRKY17-MdSUFB pathway stabilizes chlorophyll levels under moderate drought stress, which could facilitate the breeding of apple varieties that maintain high yields under drought stress.

13.
J Dairy Sci ; 104(11): 11457-11465, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34419274

RESUMO

Freeze drying is one of the most convenient ways to preserve microorganisms, but in the freeze-drying process, strains will inevitably suffer varying degrees of damage under different conditions. The deterioration of cell membrane integrity is one of the main forms of damage. The type and ratio of fatty acids in the cell membrane affect its characteristics. Therefore, it is worth investigating whether certain fatty acids can increase freeze-drying resistance. In this study, we found that adding a low concentration of oleic acid to a cryoprotectant could increase survival rate of strains of Lactiplantibacillus plantarum following freeze drying, and the optimal concentration of oleic acid was determined to be 0.001%. When 0.001% oleic acid was added to phosphate-buffered saline, the freeze-drying survival rate of L. plantarum increased by up to 6.63 times. Adding 0.001% oleic acid to sorbitol, the survival rate of L. plantarum increased by as much as 3.65 times. The 0.001% oleic acid-sucrose cryoprotectant resulted in a freeze-drying survival rate of L. plantarum of about 90%, a 2.26-fold improvement compared with sucrose alone. Although the effect of oleic acid depends on the cryoprotectants used and the strain treated, addition of oleic acid showed significant improvement overall. Further experiments showed that adding a low concentration of oleic acid to the cryoprotectants improved the freeze-drying survival rate of L. plantarum by maintaining cell membrane integrity and lactate dehydrogenase activity. Our findings provide a new strategy for safeguarding bacterial viability in commonly used cryoprotectants by the addition of a common food ingredient, which may be extensively applied in the food industry.


Assuntos
Crioprotetores , Ácido Oleico , Animais , Liofilização/veterinária , Viabilidade Microbiana , Sacarose
14.
Food Funct ; 12(18): 8351-8365, 2021 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-34338262

RESUMO

Lung cancer has been threatening human health worldwide for a long time. However, the clinic therapies remain unsatisfactory. In this study, the anti-adenocarcinoma lung cancer A549 cell line abilities of Tetrastigma hemsleyanum tuber flavonoids (THTF) were evaluated in vivo, and isobaric tags for relative and absolute quantification (iTRAQ)-based proteomic analysis was conducted to detect the protein alterations in THTF-treated solid tumors. The differentially expressed proteins were related to the cytoskeleton and mostly accumulated in the calcium signaling pathway. The in vitro study illustrated that 80 µg mL-1 THTF significantly suppressed cellular viability to approximately 75% of the control. Further results suggested that kaempferol-3-O-rutinoside (K3R), the major component of THTF, effectively triggered cytoskeleton collapse, mitochondrial dysfunction and consequent calcium overload to achieve apoptosis, which remained consistent with proteomic results. This study uncovers a new mechanism for THTF anti-tumor ability, and suggests THTF and K3R as promising anti-cancer agents, providing new ideas and possible strategies for future anti-lung cancer prevention and therapy.

15.
Mol Biol Rep ; 48(8): 5955-5964, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34350550

RESUMO

BACKGROUND: Vitiligo is a complex disease in which patchy depigmentation is the result of an autoimmune-induced loss of melanocytes in affected regions. On the basis of a genome-wide linkage analysis of vitiligo in the Chinese Han population, we previously showed significant evidence of a linkage between 22q12 and vitiligo. Our aim in the current study was to identify vitiligo susceptibility variants within an expanded region of the 22q12 locus. METHODS AND RESULTS: An in-depth analysis of the expanded region of the 22q12 locus was performed by imputation using a large GWAS dataset consisting of 1117 cases and 1701 controls. Eight nominal SNPs were selected and genotyped in an independent cohort of Chinese Han individuals (2069 patients and 1370 control individuals) by using the Sequenom MassArray iPLEX1 system. The data were analyzed with PLINK 1.07 software. The C allele of rs730669 located in ZDHHC8/RTN4R showed a strong association with vitiligo (P = 3.25 × 10-8, OR = 0.81). The C allele of rs4820338 located in VPREB1 and the A allele of rs2051582 (a SNP reported in our previous study) located in IL2RB showed a suggestive association with vitiligo (P = 1.04 × 10-5, OR = 0.86; P = 1.78 × 10-6, OR = 1.27). The three identified SNPs showed independent associations with vitiligo in a conditional logistic regression analysis (all P < 1.0 × 10-5; all D' < 0.05 and r2 < 1.0 × 10-4). CONCLUSIONS: The study reveals that two novel variants rs730669 (ZDHHC8/RTN4R) and rs4820338 (VPREB1) on 22q11.2 might confer susceptibility to vitiligo and affect disease subphenotypes. The presence of multiple independent variants emphasizes their important roles in the genetic pathogenesis of disease.

16.
Cancer Commun (Lond) ; 41(1): 51-61, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-34236140

RESUMO

BACKGROUND: The interaction between activating receptor NKp30 and its major tumor ligand B7-H6 is important for NK cell-mediated tumor rejection. However, the regulation of B7-H6 by tumor therapeutics remains largely unknown. In this study, we investigated the regulation of B7-H6 by all-trans retinoic acid (atRA), a terminal differentiation inducer of tumor cells that is extensively used for clinical leukemia therapy. METHODS: We investigated the role of NKp30:B7-H6 axis in NK cell-mediated tumor lysis against leukemia cells and the influence of atRA treatment on the cytotoxicity of NK cells using NK cell lines (NK92 and NKG) and leukemia cell lines (U-937 and THP-1). We evaluated the effect of atRA treatment on the expression of B7-H6 using real-time PCR, flow cytometry and western blotting. We used CRISPR/Cas9 to knockdown B7-H6 expression and siRNA to knockdown c-Myc in U-937 cells to evaluate the role of B7-H6 and c-Myc in atRA-induced tumor resistance against NK cells. RESULTS: NK cell-mediated U-937 cell lysis was mainly dependent on NKp30/B7-H6 interaction. Blockade of B7-H6 by monoclonal antibody significantly impaired NK cytotoxicity. atRA treatment induced U-937 resistance to NK cell cytotoxicity by reducing B7-H6 expression, and showed no effect on NK cytotoxicity against B7-H6 knockdown U-937 cells. Epigenetic modifications, such as DNA methylation and histone deacetylase (HDAC), were not responsible for atRA-mediated B7-H6 down-regulation as inhibitors of these pathways could not restore B7-H6 mRNA expression. On the other hand, atRA treatment reduced c-Myc expression, which in turn inhibited the transcription of B7-H6 on leukemia cells. CONCLUSION: atRA treatment promotes tumor cell resistance against NK cell-mediated lysis by down-regulating B7-H6 expression via the c-Myc signaling pathway, suggesting that more attention needs to be paid to the immunological adverse effects in the clinical use of atRA treatment.


Assuntos
Leucemia , Receptor 3 Desencadeador da Citotoxicidade Natural , Humanos , Células Matadoras Naturais , Leucemia/tratamento farmacológico , Leucemia/genética , Transdução de Sinais , Tretinoína/farmacologia
17.
Sci Total Environ ; 795: 148793, 2021 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-34328952

RESUMO

A combination of biochar with exogenous organic material in soils is often used in practical farmland management. The objective of this study was to determine how biochar affects organic matter decomposition by studying the decomposition of 13C-labelled hydrophilic (Hi-) and hydrophobic (Ho-) dissolved organic matter (DOM) in acid and neutral soils during a 60-day incubation experiment. The proportions of carbon (C) mineralization in Hi-DOM with or without biochar addition were 32.6% or 34.5% in acid soil (P > 0.05) and 15.4% or 22.3% in neutral soil (P < 0.05), respectively. In contrast, those proportions of Ho-DOM-C mineralization with or without biochar addition were 20.0% or 21.4% in acid soil and 19.0% or 20.5% in neutral soil (P > 0.05), respectively. These results showed that biochar could protect Hi-DOM against mineralization in neutral soil but exhibited less effect on Ho-DOM mineralization in both acid and neutral soils. Additionally, biochar did not affect microbial incorporation of Hi- or Ho-DOM in acid and neutral soils. However, biochar notably improved the microbial carbon use efficiency (CUE) of Hi-DOM while it significantly reduced the CUE of Ho-DOM in neutral soil (P < 0.05), indicating that the effect of biochar on microbial CUE was related to organic matter type and soil pH. This study suggests that Hi-DOM can outperform Ho-DOM to decrease C loss and improve microbial CUE in neutral soil with biochar addition. This phenomenon could be due mainly to the different chemical compositions of Hi-DOM and Ho-DOM and their distinct microbial preference. These findings can provide references for biochar's ability to regulate the decomposition of organic matter.


Assuntos
Carbono , Carvão Vegetal , Solo
18.
Front Public Health ; 9: 677643, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34268289

RESUMO

Purpose: The research objectives of this study are to test the scientific propositions of whether Internet use promotes life satisfaction among the elderly, whether there is variability in the effect of Internet use on the well-being of the elderly, and through what channels Internet use affects the elderly's life satisfaction. Method: Using data from the 2017 Chinese General Social Survey (CGSS), this paper employed linear regression, ordered logit model, and the propensity score matching (PSM) approach to investigate the association of Internet use with life satisfaction among the elderly in China. Results: The results show that Internet use was significantly and negatively associated with the life satisfaction of the Chinese elderly. Further analysis on group heterogeneity demonstrates that the negative association was more prominent among the participants who were males, at a lower age, had lower income and education, non-agricultural registered, and relatively healthy. Finally, the mediating effect indicates that Internet use may affect life satisfaction among the elderly through the channel of reducing their perceptions of social justice. Conclusions: In order to avoid the negative effects of using the Internet, the following policy suggestions are put forward: Improve the elderly's attitudes toward Internet use; pay attention to the sense of fairness of the elderly to improve life satisfaction; guide the elderly to reduce the time of using the Internet.


Assuntos
Uso da Internet , Satisfação Pessoal , Idoso , Atitude , China/epidemiologia , Humanos , Renda , Masculino
19.
Ann Hum Genet ; 85(6): 213-220, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34145571

RESUMO

OBJECTIVE: Systemic lupus erythematosus (SLE) is a complex autoimmune disease with strong genetic predisposition. Genome-wide association studies (GWAS) of SLE have identified more than 50 robust susceptibility loci. However, traditional individual SNP-based GWAS have made it difficult to identify variants with small effects. Moreover, variants revealed by GWAS only explain a limited disease heritability, suggesting that many susceptibility genes remain uncovered. METHODS: We first curated the published SLE GWAS data from 1047 SLE patients and 1205 healthy controls of Chinese ancestry and performed a gene-based association study. Then quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was conducted to verify novel genes identified above. RESULTS: Gene-based association study identified 10 SLE-associated genes, nine of which were reported by previous GWAS, the other one, ILRUN, is a newly identified gene and was further validated by qRT-PCR. Gene expression analysis of Gene Expression Omnibus (GEO) datasets also showed that the expression of ILRUN in patients with SLE was lower than that in normal subjects. CONCLUSION: In this study, gene-based association study and qRT-PCR identified that ILRUN is a novel susceptibility gene of SLE. ILRUN may regulate inflammation and antiviral response through its effect on the transcription of type I interferons )I-IFN, and participate in the pathogenesis of SLE.

20.
Child Abuse Negl ; : 105162, 2021 Jun 16.
Artigo em Inglês | MEDLINE | ID: mdl-34147278

RESUMO

BACKGROUND: Despite substantial evidence in developed countries showing that child maltreatment can lead to serious life-long consequences, relatively few studies so far have examined the associations between childhood maltreatment and adulthood outcomes in developing countries, such as China. It also remains unclear as to the impact of relative poverty on the long-term development of maltreated children. OBJECTIVE: This study aims to investigate the associations between childhood maltreatment and educational, health, and economic outcomes among middle-aged Chinese, as well as explore the moderating effects of relative poverty. PARTICIPANTS AND SETTING: The participants of this study were the middle-aged respondents (aged 45 to 59) in the 2011, 2013, and 2015 China Health and Retirement Longitudinal Studies (CHARLS) and the CHARLS Life History Survey (N = 24,114). METHODS: Physical abuse and emotional neglect were measured to investigate childhood maltreatment. Subjective and objective indicators were used to examine relative poverty. A broad range of midlife outcomes were explored, including educational attainment, physical health, mental health, cognitive functions, labor force participation, wage expenditure, and financial strain. Data analyses were conducted using fixed effects model for panel data and a propensity score matching approach. RESULTS: Childhood physical abuse and emotional neglect were both significantly associated with lower levels of midlife educational attainment, cognitive functions, individual wages, and household expenditures, as well as higher rates of chronic diseases, depressive symptoms, poverty, and welfare involvement. Childhood physical abuse also predicted higher risks of difficulty performing the activities of daily living (ADL), unemployment, and fewer work hours. Early-life exposure to relative poverty was linked to a greater likelihood of childhood maltreatment and mid-life adversities. It further aggravated the negative impacts of childhood maltreatment on middle-age outcomes. CONCLUSION: Child maltreatment had a profound effect on long-term child development and midlife outcomes in Chinese contexts. Relative poverty in early life was a moderator that exacerbated the outcomes associated with childhood maltreatment.

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