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1.
Int J Cancer ; 2021 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-34664266

RESUMO

Colonization of specific bacteria in the human mouth were reported to be associated with gastric cancer risk. However, previous studies were limited by retrospective study designs and low taxonomic resolutions. We performed a prospective case-control study nested within three cohorts to investigate the relationship between oral microbiome and gastric cancer risk. Shotgun metagenomic sequencing was employed to characterize the microbiome in pre-diagnostic buccal samples from 165 cases and 323 matched controls. Associations of overall microbial richness and abundance of microbial taxa, gene families, and metabolic pathways with gastric cancer risk were evaluated via conditional logistic regression. Analyses were performed within each cohort and results were combined by meta-analyses. We found that overall microbial richness was associated with decreased gastric cancer risk, with an odds ratio (OR) per standard deviation (SD) increase in Simpson's reciprocal index of 0.77 (95% confidence interval [CI]=0.61-0.99). Nine taxa, 38 gene families, and six pathways also showed associations with gastric cancer risk at P<0.05. Neisseria mucosa and Prevotella pleuritidis were enriched, while Mycoplasma orale and Eubacterium yurii were depleted among cases with ORs and 95% CIs per SD increase in centered log-ratio transformed taxa abundance of 1.31 (1.03-1.67), 1.26 (1.00-1.57), 0.74 (0.59-0.94) and 0.80 (0.65-0.98), respectively. The top two gene families (P = 3.75×10-4 and 3.91×10-4 ) and pathways (P = 1.75×10-3 and 1.53×10-3 ) associated with gastric cancer were related to the decreased risk and are involved in hexitol metabolism. Our study supports the hypothesis that oral microbiota may play a role in gastric cancer etiology. This article is protected by copyright. All rights reserved.

2.
Front Microbiol ; 12: 710678, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34603237

RESUMO

The apicomplexan Babesia microti is a main pathogenic parasite causing human babesiosis, which is one of the most widely distributed tick-borne diseases in humans. Pyruvate kinase (PYK) plays a central metabolic regulatory role in most living organisms and catalyzes the essentially irreversible step in glycolysis that converts phosphoenolpyruvate (PEP) to pyruvate. Hence, PYK is recognized as an attractive therapeutic target in cancer and human pathogens such as apicomplexans. In this study, we cloned, expressed, and purified B. microti PYK I (BmPYKI). Western blotting illustrated that anti-rBmPYKI antibody could specifically recognize the native BmPYKI protein in the lysate of B. microti with a 54-kDa band, which is consistent with the predicted size. In addition, the enzymatic activity of the purified recombinant PYKI (rPYKI) was tested under a range of pH values. The results showed that the maximum catalytic activity could be achieved at pH 7.0. The saturation curves for substrates demonstrated that the K m value for PEP was 0.655 ± 0.117 mM and that for ADP was 0.388 ± 0.087 mM. We further investigated the effect of 13 compounds on rBmPYKI. Kinetic analysis indicated that six inhibitors (tannic acid, shikonin, apigenin, PKM2 inhibitor, rosiglitazone, and pioglitazone) could significantly inhibit the catalytic activity of PYKI, among which tannic acid is the most efficient inhibitor with an IC50 value 0.49 µM. Besides, four inhibitors (tannic acid, apigenin, shikonin, and PKM2 inhibitor) could significantly decrease the growth of in vitro-cultured B. microti with IC50 values of 0.77, 2.10, 1.73, and 1.15 µM. Overall, the present study provides a theoretical basis for the design and development of new anti-Babesia drugs.

3.
Food Sci Biotechnol ; 30(9): 1233-1241, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34603822

RESUMO

Sufu is a common solid-state traditional fermented food made from soybean. Huase sufu is a typical type found in several provinces of China, especially in Hubei. However, little is known about the bacterial community. High-throughput sequencing technology revealed that the dominant taxa at phylum level were: Firmicutes, Proteobacteria and Bacteroides, and at the genus level were: Pseudomonas, Lactococcus, Acinetobacter, etc. Additionally, LEfSe revealed that compared with the bacterial community of red sufu and white sufu, the biomarker genera for both huase sufu were Enterococcus, and Myroides. Moreover, there were twenty-eight hubs for the huase sufu samples, and four of them were dominant genera: Citrobacter, Myroides, Vagococcus, and Enterococcus. These results provide a new insight into our understanding of the bacterial diversity of huase sufu, and will facilitate the isolation, screening, and development potential bacterial strains for production of huase sufu. Supplementary Information: The online version contains supplementary material available at 10.1007/s10068-021-00963-3.

4.
Zhongguo Dang Dai Er Ke Za Zhi ; 23(8): 828-834, 2021 Aug 15.
Artigo em Inglês, Chinês | MEDLINE | ID: mdl-34511173

RESUMO

OBJECTIVES: To study the expression of adipokines in children with primary nephrotic syndrome (PNS) before and after treatment and its correlation with blood lipids, as well as the role of adipokines in PNS children with hyperlipidemia. METHODS: A total of 90 children who were diagnosed with incipient PNS or recurrence of PNS after corticosteroid withdrawal for more than 6 months were enrolled as subjects. Thirty children who underwent physical examination were enrolled as the control group. Venous blood samples were collected from the children in the control group and the children with PNS before corticosteroid therapy (active stage) and after urinary protein clearance following 4 weeks of corticosteroid therapy (remission stage). ELISA was used to measure the levels of adipokines. An automatic biochemical analyzer was used to measure blood lipid levels. RESULTS: Compared with the control group, the children with PNS had a significantly lower level of omentin-1 in both active and remission stages, and their level of omentin-1 in the active stage was significantly lower than that in the remission stage (P<0.001). For the children with PNS, the level of chemerin in the active stage was significantly higher than that in the remission stage, and the children with PNS in the active stage had a significantly higher level of chemerin than the control group (P<0.001). For the children with PNS, atherogenic index of plasma, atherogenic coefficient (AC), castelli risk index-1 (CRI-1), castelli risk index-2 (CRI-2), and non-high-density lipoprotein in the active stage were significantly higher than those in the remission stage (P<0.001), and these indices in the children with PNS in the active stage were significantly higher than those in the control group (P<0.001). The children with PNS in the remission stage had significantly higher atherogenic index of plasma, AC, CRI-1, and non-high-density lipoprotein than the control group (P<0.001). Compared with the control group, the children with PNS in the remission stage had significantly higher serum levels of total cholesterol, triglyceride, high-density lipoprotein, low-density lipoprotein, apolipoprotein B, and apolipoprotein A (P<0.01). In the children with PNS, the ratio of omentin-1 before and after corticosteroid therapy was positively correlated with that of high-density lipoprotein, 24-hour urinary protein excretion, and high-density lipoprotein/apolipoprotein A before and after treatment, and it was negatively correlated with the ratio of AC and CRI-1 before and after treatment (P<0.05). The PNS children with low omentin-1 levels in the active stage had significantly higher levels of CRI-1, CRI-2, AC, and apolipoprotein B/apolipoprotein A ratio than those with high omentin-1 levels (P<0.05). CONCLUSIONS: Omentin-1 may be associated with disease activity, dyslipidemia, and proteinuria in children with PNS. Blood lipid ratios may be more effective than traditional blood lipid parameters in monitoring early cardiovascular risk in children with PNS.


Assuntos
Citocinas/metabolismo , Hiperlipidemias , Lectinas/metabolismo , Síndrome Nefrótica , Adipocinas , Quimiocinas , Criança , Citocinas/genética , Proteínas Ligadas por GPI/genética , Proteínas Ligadas por GPI/metabolismo , Humanos , Lectinas/genética , Lipídeos , Síndrome Nefrótica/tratamento farmacológico , Proteinúria
5.
Artigo em Inglês | MEDLINE | ID: mdl-34497089

RESUMO

BACKGROUND: The role of methylation in pancreatic cancer risk remains unclear. We integrated genome and methylome data to identify CpG sites (CpG) with the genetically predicted methylation to be associated with pancreatic cancer risk. We also studied gene expression to understand the identified associations. METHODS: Using genetic data and white blood cell methylation data from 1,595 subjects of European descent, we built genetic models to predict DNA methylation levels. After internal and external validation, we applied prediction models with satisfactory performance to the genetic data of 8,280 pancreatic cancer cases and 6,728 controls of European ancestry to investigate the associations of predicted methylation with pancreatic cancer risk. For associated CpGs, we compared their measured levels in pancreatic tumor versus benign tissue. RESULTS: We identified 45 CpGs at nine loci showing an association with pancreatic cancer risk, including 15 CpGs showing an association independent from identified risk variants. We observed significant correlations between predicted methylation of 16 of the 45 CpGs and predicted expression of eight adjacent genes, of which six genes showed associations with pancreatic cancer risk. Of the 45 CpGs, we were able to compare measured methylation of 16 in pancreatic tumor versus benign pancreatic tissue. Of them, six showed differentiated methylation. CONCLUSIONS: We identified methylation biomarker candidates associated with pancreatic cancer using genetic instruments and added additional insights into the role of methylation in regulating gene expression in pancreatic cancer development. IMPACT: A comprehensive study using genetic instruments identifies 45 CpG sites at nine genomic loci for pancreatic cancer risk.

6.
Medicine (Baltimore) ; 100(30): e26701, 2021 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-34397698

RESUMO

BACKGROUND: Advanced cancer (AC) patients experience serious physical and psychological problems with the disease progression. When approaching the end of life, these patients have to cope with not only the bodily illness, but also the spiritual crisis. Conventional psychological treatments reduce distress to a certain extent, but for patients with AC, especially when they face progressive illness and are approaching death, their psychological problems are complex, and no simple solutions are in sight. Therefore, we designed this study to evaluate the efficacy of the combined Naikan therapy (NT) and Morita therapy (MT) on psychological distress and posttraumatic growth in patients with AC. METHOD: One hundred thirty patients newly diagnosed with AC were allocated randomly into treatment (n = 65) and control (n = 65) groups. Patients in the treatment group received combined NT and MT for 7 consecutive weeks, while the control group received normal medical treatments without NT and MT. Patients were assessed before and after the therapies. The primary outcome measures include distress thermometer (DT) and posttraumatic growth, and the secondary outcome measure contains the list of distress problems. RESULTS: At the post-treatment stage, the treatment group displayed a decreased score of psychological distress as compared to that in the control group, which accompanied by a higher post-traumatic growth total score and subscale scores in relationship to others, new possibilities, personal strength, spiritual changes, and appreciation of life. A significant decrease in fear, sleeping difficulty/insomnia, nervousness/anxiety, and loss of appetite was also observed in the treatment group. CONCLUSION: The results proved that the combined Naikan and Morita therapies decreased the psychological distress and improved the posttraumatic growth of the patients with AC. TRIAL REGISTRATION: ChiCTR1900026691.


Assuntos
Adaptação Psicológica , Humanismo , Neoplasias/terapia , Angústia Psicológica , China , Humanos , Neoplasias/psicologia , Crescimento Psicológico Pós-Traumático
7.
Parasitol Res ; 120(8): 2863-2872, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34219188

RESUMO

Babesia orientalis, belonging to the phylum Apicomplexa, is mainly accountable for water buffalo babesiosis, which adversely affected the livestock industry in China. Variant erythrocyte surface antigen-1 (VESA1), an antigen that helps infected erythrocytes to escape from host immune responses, was first reported in Babesia bovis. Various VESA1 proteins have also been characterized in other Babesia species. Nevertheless, there is no research on the identification and characterization of VESA1 proteins in Babesia orientalis. In this study, the BoVESA1 gene was amplified from both gDNA and cDNA. The results revealed that it is an intronless gene with a full length of 753 bp, encoding a protein of 250 amino acids with a predicted molecular weight of 28 kDa. The coding sequence (CDS) was cloned into the pGEX-6p-1 vector using a homologous recombination kit and expressed as a glutathione-S-transferase (GST)-fusion protein with a molecular weight of 53 kDa. The tertiary structure of BoVESA1 was predicted using the I-TASSER software. The recombinant protein was subjected to western blotting; the immunogenicity of recombinant BoVESA1 (rBoVESA1) was identified by incubating it with B. orientalis-positive serum. The native BoVESA1 was identified using the lysates of B. orientalis-infected water buffalo erythrocytes incubated with the anti-rBoVESA1 mouse serum. The results showed a band of ~ 28 kDa, which is similar to the predicted size. Immunofluorescence assay (IFA) using anti-rBoVESA1 serum probed indicated a strong signal in the infected RBCs, while the negative control showed no signal. In conclusion, the VESA1 protein was first identified in B. orientalis. This study facilitated further investigation of B. orientalis, and the results indicated that BoVESA1 may serve as a potential candidate antigen for diagnosis and detection of B. orientalis infection.


Assuntos
Antígenos de Protozoários/imunologia , Antígenos de Superfície/imunologia , Babesia , Animais , Antígenos de Protozoários/genética , Antígenos de Superfície/genética , Babesia/genética , Babesia/imunologia , Babesiose , Búfalos , Clonagem Molecular , Eritrócitos , Camundongos , Filogenia , Proteínas de Protozoários/genética , Proteínas de Protozoários/imunologia
8.
Front Immunol ; 12: 623492, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34079537

RESUMO

Babesia orientalis, a major infectious agent of water buffalo hemolytic babesiosis, is transmitted by Rhipicephalus haemaphysaloides. However, no effective vaccine is available. Essential antigens that are involved in parasite invasion of host red blood cells (RBCs) are potential vaccine candidates. Therefore, the identification and the conduction of functional studies of essential antigens are highly desirable. Here, we evaluated the function of B. orientalis merozoite surface antigen 2c1 (BoMSA-2c1), which belongs to the variable merozoite surface antigen (VMSA) family in B. orientalis. We developed a polyclonal antiserum against the purified recombinant (r)BoMSA-2c1 protein. Immunofluorescence staining results showed that BoMSA-2c1 was expressed only on extracellular merozoites, whereas the antigen was undetectable in intracellular parasites. RBC binding assays suggested that BoMSA-2c1 specifically bound to buffalo erythrocytes. Cytoadherence assays using a eukaryotic expression system in vitro further verified the binding and inhibitory ability of BoMSA-2c1. We found that BoMSA-2c1 with a GPI domain was expressed on the surface of HEK293T cells that bound to water buffalo RBCs, and that the anti-rBoMSA2c1 antibody inhibited this binding. These results indicated that BoMSA-2c1 was involved in mediating initial binding to host erythrocytes of B. orientalis. Identification of the occurrence of binding early in the invasion process may facilitate understanding of the growth characteristics, and may help in formulating strategies for the prevention and control of this parasite.


Assuntos
Antígenos de Protozoários/metabolismo , Antígenos de Superfície/metabolismo , Babesia/metabolismo , Babesiose/parasitologia , Adesão Celular , Eritrócitos/parasitologia , Merozoítos/metabolismo , Proteínas de Protozoários/metabolismo , Animais , Antígenos de Protozoários/genética , Antígenos de Superfície/genética , Babesia/genética , Babesia/patogenicidade , Babesiose/sangue , Búfalos , Eritrócitos/metabolismo , Células HEK293 , Humanos , Merozoítos/genética , Merozoítos/patogenicidade , Proteínas de Protozoários/genética
9.
J Nurs Manag ; 29(7): 2225-2233, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34021661

RESUMO

AIM: This study aimed to explore the effect of organisational innovation climate on nurse innovation behaviour and the mediating role of psychological empowerment. BACKGROUND: Encouraging nurses to generate more innovative behaviours has become an important development direction for improving the quality of nursing services. METHOD: We employed a self-report questionnaire to collect data in Jinan City, China. A total of 2018 valid surveys were obtained. Hierarchical multiple regression model analysis was conducted to test the study hypothesis. RESULT: The mean values of innovation behaviour and organisational innovation climate were 35.29 and 83.30, respectively. Psychological empowerment was found to have partially mediating effect on the relationship between organisational innovation climate and innovation behaviour. CONCLUSION: Organisational innovation climate has significant impact on innovation behaviour, and it can indirectly affect innovation behaviour via the mediating role of psychological empowerment. IMPLICATIONS FOR NURSING MANAGEMENT: Nursing managers should enhance innovation climate through formal rules, procedures and training activities. They can establish resource guarantee system and information sharing platform, and strengthen work autonomy for nurses to improve their psychological empowerment.


Assuntos
Enfermeiras Administradoras , Enfermeiras e Enfermeiros , China , Estudos Transversais , Humanos , Inovação Organizacional , Inquéritos e Questionários
10.
Parasitol Int ; 83: 102351, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33872796

RESUMO

Babesia microti is one of the most important pathogens causing humans and rodents babesiosis-an emerging tick-borne disease that occurs worldwide. At present, the gold standard for the detection of Babesia is the microscopic examination of blood smears, but this diagnostic test has several limitations. The recombinase polymerase amplification with lateral flow (LF-RPA) assay targeting the mitochondrial cytochrome oxidase subunit I (cox I) gene of B. microti was developed in this study. The LF-RPA can be performed within 10-30 min, at a wide range of temperatures between 25 and 45 °C, which is much faster and easier to perform than conventional PCR. The results showed that the LF-RAP can detect 0.25 parasites/µl blood, which is 40 times more sensitive than the conventional PCR based on the V4 variable region of 18S rRNA. Specificity assay showed no cross-reactions with DNAs of related apicomplexan parasites and their host. The applicability of the LF-RPA method was further evaluated using two clinical human samples and six experimental mice samples, with seven samples were positively detected, while only three of them were defined as positive by conventional PCR. These results present the developed LF-RPA as a new simple, specific, sensitive, rapid and convenient method for diagnosing infection with B. microti. This novel assay was the potential to be used in field applications and large-scale sample screening.


Assuntos
Babesia microti/isolamento & purificação , Babesiose/diagnóstico , Técnicas de Amplificação de Ácido Nucleico/métodos , Animais , Babesia microti/enzimologia , Babesiose/parasitologia , DNA de Protozoário/análise , Camundongos , Camundongos Endogâmicos BALB C , Parasitemia/parasitologia , Proteínas de Protozoários/análise , Recombinases/análise
11.
Cancers (Basel) ; 13(9)2021 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-33922500

RESUMO

We previously identified a locus at 21q22.3, tagged by the single nucleotide polymorphism (SNP) rs35418111, being associated with breast cancer risk at a genome-wide significance level; however, the underlying causal functional variants and gene(s) responsible for this association are unknown. We performed functional genomic analyses to identify potential functional variants and target genes that may mediate this association. Functional annotation for SNPs in high linkage disequilibrium (LD, r2 > 0.8) with rs35418111 in Asians showed evidence of promoter and/or enhancer activities, including rs35418111, rs2078203, rs8134832, rs57385578, and rs8126917. These five variants were assessed for interactions with nuclear proteins by electrophoretic mobility shift assays. Our results showed that the risk alleles for rs2078203 and rs35418111 altered DNA-protein interaction patterns. Cis-expression quantitative loci (cis-eQTL) analysis, using data from the Genotype-Tissue Expression database (GTEx) European-ancestry female normal breast tissue, indicated that the risk allele of rs35418111 was associated with a decreased expression of the YBEY gene, a relatively uncharacterized endoribonuclease in humans. We investigated the biological effects of YBEY on breast cancer cell lines by transient knock-down of YBEY expression in MCF-7, T47D, and MDA-MB-231 cell lines. Knockdown of YBEY mRNA in breast cancer cell lines consistently decreased cell proliferation, colony formation, and migration/invasion, regardless of estrogen receptor status. We performed RNA sequencing in MDA-MB-231 cells transfected with siRNA targeting YBEY and subsequent gene set enrichment analysis to identify gene networks associated with YBEY knockdown. These data indicated YBEY was involved in networks associated with inflammation and metabolism. Finally, we showed trends in YBEY expression patterns in breast tissues from The Cancer Genome Atlas (TCGA); early-stage breast cancers had elevated YBEY expression compared with normal tissue, but significantly decreased expression in late-stage disease. Our study provides evidence of a significant role for the human YBEY gene in breast cancer pathogenesis and the association between the rs35418111/21q22.3 locus and breast cancer risk, which may be mediated through functional SNPs, rs35418111 and rs2078203, that regulate expression of YBEY.

12.
Cancer Epidemiol Biomarkers Prev ; 30(9): 1634-1642, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33795214

RESUMO

BACKGROUND: Metabolomics is widely used to identify potential novel biomarkers for cancer risk. No investigation, however, has been conducted to prospectively evaluate the role of perturbation of metabolome in gastric cancer development. METHODS: 250 incident cases diagnosed with primary gastric cancer were selected from the Shanghai Women's Health and the Shanghai Men's Health Study, and each was individually matched to one control by incidence density sampling. An untargeted global profiling platform was used to measure approximately 1,000 metabolites in prediagnostic plasma. Conditional logistic regression was utilized to generate ORs and P values. RESULTS: Eighteen metabolites were associated with gastric cancer risk at P < 0.01. Among them, 11 metabolites were lysophospholipids or lipids of other classes; for example, 1-(1-enyl-palmitoyl)-GPE (P-16:0) (OR = 1.56; P = 1.89 × 10-4). Levels of methylmalonate, a suggested biomarker of vitamin B12 deficiency, was correlated with increased gastric cancer risk (OR = 1.42; P = 0.004). Inverse associations were found for three biomarkers for coffee/tea consumption (3-hydroxypyridine sulfate, quinate and N-(2-furoyl) glycine), although the associations were only significant when comparing cases that were diagnosed within 5 years after the blood collection to matched controls. Most of the identified associations were more profound in women and never smokers than their male or ever smoking counterparts and some with notable significant interactions. CONCLUSIONS: Our study identified multiple potential risk biomarkers for gastric cancer independent of Helicobacter pylori infection and other major risk factors. IMPACT: New risk-assessment tools to identify high-risk population could be developed to improve prevention of gastric cancer.See related commentary by Drew et al., p. 1601.

13.
Toxicol Lett ; 346: 7-15, 2021 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-33811973

RESUMO

Our previous studies found that M10, a myricetin-3-O-ß-d-lactose sodium salt, possessed higher effects of ameliorating ulcerative colitis (UC) than Myricetin in mice. Here, we aim to investigate whether the inhibition of UC is the consequence of the effects of M10 that leads to the changed microbiota. Mice model of UC was induced by dextran sulfate sodium (DSS) treatment. M10 and Myricetin were orally administrated for 12 weeks. We performed 16S rDNA sequencing assay to analyze the composition of gut microbiota isolated from ileocecum. Both M10 and Myricetin normalized the composition of Firmicutes and Actinobacteria as healthy mice had. At genus level, the effects of M10 and Myricetin on colitis were associated to the increase of probiotics, such as Akkermansia, and the inhibition of pathogenic microorganisms, such as Ruminococcus and Parabacteroides. M10 had stronger activity than Myricetin in the improvement of biosynthesis and degradation activities, resulting to increasing metabolism of sulfur, pyruvate, steroid biosynthesis and unsaturated fatty acid biosynthesis in gut. Furthermore, M10 normalized the proportion of Firmicutes and Actinobacteria in gut microbiota. It suggests that the improvements in UC are the consequence of the effect of M10 that leads to the changed intestinal microbiota. Conclusion: M10 contributed the pharmacological effects on UC by modification of the intestinal microbiota.


Assuntos
Alanina/análogos & derivados , Bactérias/efeitos dos fármacos , Flavonoides/farmacologia , Microbioma Gastrointestinal/efeitos dos fármacos , Hidroxiquinolinas/farmacologia , Alanina/farmacologia , Animais , Anti-Inflamatórios não Esteroides/uso terapêutico , Bactérias/genética , Colite Ulcerativa , Sulfato de Dextrana , Masculino , Mesalamina/uso terapêutico , Camundongos , Camundongos Endogâmicos C57BL , RNA Bacteriano/genética
14.
Br J Pharmacol ; 178(11): 2351-2369, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33645631

RESUMO

BACKGROUND AND PURPOSE: It is well known that microsatellite instability-high (MSI-H) is associated with 5-fluorouracil (5-FU) resistance in colorectal cancer. MSI-H is the phenotype of DNA mismatch repair deficiency (MMR-D), mainly occurring due to hypermethylation of MLH1 promoter CpG island. However, the mechanisms of MMR-D/MSI-H are unclear. We aim to investigate the pathway of MMR-D/MSI-H involved in 5-FU resistance. EXPERIMENTAL APPROACH: Human colorectal cancer specimens were diagnosed for MSI-H by immunohistochemistry and western blotting. Proteome microarray interactome assay was performed to screen nuclear proteins interacting with ATG5. Nuclear ATG5 and ATG5-Mis18α overexpression were analysed in ATG5high colorectal cancer bearing mice. The methylation assay determined the hypermethylation of hMLH1 promoter CpG island in freshly isolated human colorectal cancer tissue samples and HT29atg5 and SW480atg5 cancer cells. KEY RESULTS: In ATG5high colorectal cancer patients, 5-FU-based therapy resulted in nuclear translocation of ATG5, leading to MSI-H. Colorectal cancer in Atg5 Tg mice demonstrated 5-FU resistance, compared to Atg5+/- and WT mice. Proteome microarray assay identified Mis18α, a protein localized on the centromere and a source for methylation of the underlying chromatin, which responded to the translocated nuclear ATG5 leading to ATG5-Mis18α conjugate overexpression. This resulted in MLH1 deficiency due to hypermethylation of hMLH1 promoter CpG island, while the deletion of nuclear Mis18α failed to induce ATG5-Mis18α complex and MMR-D/MSI-H. CONCLUSIONS AND IMPLICATIONS: Nuclear ATG5 resulted in MMR-D/MSI-H through its interaction with Mis18α in ATG5high colorectal cancer cells. We suggest that ATG5-Mis18α or Mis18α may be a therapeutic target for treating colorectal cancer.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal , Proteína 5 Relacionada à Autofagia , Neoplasias Colorretais , Instabilidade de Microssatélites , Proteínas Adaptadoras de Transdução de Sinal/genética , Animais , Neoplasias Encefálicas , Proteínas Cromossômicas não Histona , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/genética , DNA , Metilação de DNA , Humanos , Camundongos , Proteína 1 Homóloga a MutL/genética , Síndromes Neoplásicas Hereditárias
15.
Sheng Li Xue Bao ; 73(1): 42-50, 2021 Feb 25.
Artigo em Chinês | MEDLINE | ID: mdl-33665659

RESUMO

This study was designed to evaluate the role of short-chain fatty acid butyrate acid on intestinal morphology and function, and atherosclerotic plaque formation in apolipoprotein E-knockout (ApoE-/-) mice. ApoE-/- mice on high-fat, high-cholesterol diet were treated with butyrate acid (200 mmol/L) or NaCl (control) in the drinking water for 12 weeks, followed by histological evaluations of atherosclerotic lesion in aorta. Real-time PCR analysis and ELISA were used to measure the expression levels of proinflammatory cytokines. Butyrate acid significantly attenuated high-fat, high-cholesterol diet-induced atherosclerotic plaque formation in ApoE-/- mice. Butyrate acid prevented high-fat, high-cholesterol diet-induced inflammation in both the aorta and the circulation, as evidenced by reduced expression of proinflammatory cytokines. These changes were accompanied by a marked attenuation in metabolic endotoxemia lipopolysaccharide (LPS). Butyrate acid induced intestinal expression of the tight junction proteins (Occludin and zona occuldens protein-1), thereby preventing the gut permeability. Butyrate acid dose-dependently upregulated the expression of the tight junction proteins in Caco-2 cells in GPR41-dependent manner. In conclusion, butyrate acid attenuates atherosclerotic lesions by ameliorating metabolic endotoxemia-induced inflammation through restoration of the gut barrier.


Assuntos
Aterosclerose , Placa Aterosclerótica , Animais , Apolipoproteínas E/genética , Aterosclerose/tratamento farmacológico , Aterosclerose/prevenção & controle , Butiratos/farmacologia , Células CACO-2 , Dieta Hiperlipídica/efeitos adversos , Ácidos Graxos Voláteis , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout
16.
Can J Urol ; 28(1): 10556-10559, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33625347

RESUMO

Non-obstructive, chronic flank pain in urologic patients can be a challenging problem to manage. In this series, we examined the efficacy of celiac plexus blockade in providing pain relief and reducing opiate use in 14 adult urology patients with non-obstructive flank pain for > 1 year. Demographic, clinical, and procedural variables were collected from the medical record for retrospective analysis. Subjective improvement in pain occurred in 11 individuals (79%), and 5 (50%) were able to reduce their daily morphine equivalent dose (MED). Celiac plexus blockade is a viable option for symptomatic relief in urologic patients with non-obstructive chronic flank pain.

17.
World J Clin Cases ; 9(3): 697-706, 2021 Jan 26.
Artigo em Inglês | MEDLINE | ID: mdl-33553411

RESUMO

BACKGROUND: Juvenile-onset primary open-angle glaucoma (JOAG), characterized by severe elevation of intraocular pressure and optic neuropathy prior to the age of 40, is a rare subtype of primary open-angle glaucoma. Several genetic mutations have been associated with JOAG. CASE SUMMARY: The proband patient was a young male, diagnosed with primary open-angle glaucoma at the age of 27. The patient and his unaffected parents who have been excluded from classic genetic mutations for primary open-angle glaucoma were included to explore for other possible genetic variants through whole genome sequencing and bioinformatics analysis. In this trio, we found two heterozygous variants inherited from the parents in the proband: c.281G>A, p.Arg94His in OLFM2 and c.177C>G, p.Ile59Met in SIX6. Both genetic mutations are predicted through bioinformatics analysis to replace evolutionary conserved amino acids, therefore rendering a pathogenic effect on proteins. In contrast, very low frequencies for these genetic mutations were recorded in most common control databases. CONCLUSION: This is the first report on coinherited mutations of OLFM2 and SIX6 in a JOAG family, which shows the complexity of JOAG inheritance. Large-scale clinical screening and molecular functional investigations on these coinherited mutations are imperative to improve our understanding of the development of JOAG.

18.
J Pharm Sci ; 110(6): 2416-2422, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33387598

RESUMO

Sterile filtration is an effective method to remove any microorganisms present during nanoemulsion preparation. However, it lacks effective control parameters. Here, we established a simple and rapid approach for the process control of nanoemulsion sterile filtration by utilizing optical density detection as a process control parameter. During sterile filtration, the optical density or optical density ratio of the filtrate were continuously monitored to explore the correlation between optical density and the emulsion content and the change in the optical density ratio before and after sterile filtration. In the emulsion stability test, the optical density ratio was determined. A good correlation was obtained between the optical density and the nanoemulsion content during sterile filtration, thereby reducing sterile filtration loss. The optical density ratio changed significantly after sterile filtration, indicating that it could be used as a process control parameter to monitor leakage during emulsion sterile filtration. The optical density ratio can be a characterization index for stability monitoring as it is more sensitive than particle size detection and more convenient than large particle detection. These parameters may be used for sterile filtration process control and as an index for nanoemulsion characterization. This approach overcomes the limitations of existing nanoemulsion characterization methods.


Assuntos
Filtração , Emulsões , Tamanho da Partícula
19.
J Obstet Gynaecol Res ; 47(3): 1145-1152, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33462940

RESUMO

AIM: To evaluate the effect of a ketogenic diet (KD) in women with polycystic ovary syndrome (PCOS) and liver dysfunction who were obese. METHODS: Women with PCOS and liver dysfunction who were obese were enrolled in this prospective, open-label, parallel-group, controlled pilot trial, and randomly received KD (KD group) or conventional pharmacological treatment (Essentiale plus Yasmin, control group) in a 1:1 ratio for 12 weeks. The primary endpoint was the liver function markers. Secondary endpoints included the menstrual cycle, anthropometric characteristics, body composition, hormonal levels, and metabolic biomarkers. RESULTS: Of the 20 eligible participants enrolled, 18 participants completed the study. The KD group reported a significant reduction in anthropometric characteristics and body composition from baseline to week 12 (all p < 0.05). In addition, there were significant reductions in menstrual cycle, plasma estradiol, and progesterone levels in two groups (all p < 0.05), but no significant between-group difference was observed. KD significantly reduced the liver function markers compared with control group (p < 0.05). The signs of fatty liver disappeared in six out of seven fatty liver participants in KD group after 12 weeks of intervention, while only one of 10 fatty liver participants in control group disappeared. CONCLUSIONS: In addition to improving the menstrual cycle, KD had the additional benefits of reducing blood glucose and body weight, improving liver function, and treating fatty liver compared to traditional pharmacological treatment in women with PCOS and liver dysfunction who were obese.


Assuntos
Dieta Cetogênica , Hepatopatias , Síndrome do Ovário Policístico , Dieta Redutora , Feminino , Humanos , Obesidade/complicações , Projetos Piloto , Síndrome do Ovário Policístico/complicações , Estudos Prospectivos
20.
World J Clin Cases ; 9(1): 81-90, 2021 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-33511174

RESUMO

BACKGROUND: Computed tomography (CT) has become a routine preoperative examination for tibial plateau fractures (TPFs). Assessing the location of the fragment and intercondylar eminence fracture can provide clinicians with valuable information; however, the evaluation of traumatic meniscal lesion (TML) and arthroscopic management are controversial. AIM: To predict TML by three-dimensional skeletal anatomy changes in unilateral TPF and bilateral TPF on preoperative thin layer CT. METHODS: Acute fracture of tibial plateau patients undergoing arthroscopic surgery between December 2017 and December 2019 were included in this retrospective study. The type, zone, and location of TMLs were diagnosed based on the operation records and/or arthroscopic videos. Measurement of three-dimensional fracture morphology included the following: Frontal fragment width of plateau, sagittal fragment subsiding distance (FSD), sagittal fracture line distance, sagittal posterior tibial slope, and transversal area ratio of fragment area) on preoperative CT three-dimensional plane. The correlation of TML with skeletal values was calculated according to unicondylar TPFs and bicondylar TPFs. RESULTS: A total of 67 patients were enrolled in this study, among which 30 patients had TMLs, lateral/medial (23/7). FSD was a particularly positive factor to predict TML, with odds ratio of 2.31 (1.26-5.63). On sagittal view of CT, FSD degree of 8 mm and posterior tibial slope exceeding 11.74° implied enhanced risk of TML in bicondylar TPFs. On coronal view, once fragment width of plateau surpassed 3 cm, incidence of TML reached 100%. On transverse view, area ratio of fragment as enhanced risk of 5.5% and FSD > 4.3 mm for predicting TML were observed in unicondylar TPFs. CONCLUSION: TML can be predicted by different parameters on preoperative CT views according to unicondylar fractures and bicondylar TPFs.

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