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1.
Front Psychol ; 15: 1292175, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38500646

RESUMO

Objective: This multi-center cross-sectional study aimed to delineate latent profiles of benefit finding (BF) in individuals undergoing maintenance hemodialysis (MHD) in Shanghai and examine associations between these BF profiles, social support, and coping style. Methods: A total of 384 individuals undergoing MHD (mean age = 57.90, SD = 13.36) were assessed using the Benefit Finding Scale, Simplified Coping Style Questionnaire, and Perceived Social Support Scale. Latent profile analysis (LPA) identified distinct BF categories. Analysis of variance (ANOVA) evaluated the correlation between BF groups and demographic variables, while the relationship between BF, social support, and coping style was tested through correlation and multiple regression analyses. Results: LPA identified three BF groups: rich BF (54.17%), moderate BF (41.14%), and poor BF (4.69%). Regression analyses indicated that positive coping and social support are protective factors for BF. Additionally, older age and heightened understanding of MHD correlated with higher BF levels. Conclusion: The findings highlighted the importance of recognizing different BF profiles in individuals on MHD and working toward promoting BF levels in the rich BF and moderate BF groups, while helping the poor BF group to identify and address their challenges. Medical professionals should consider interventions tailored to individual psychological profiles to improve mental health and quality of life outcomes in this population.

2.
Artigo em Inglês | MEDLINE | ID: mdl-38501173

RESUMO

We have reported previously that during hypoxia exposure, the expression of mature miR-17~92 was first upregulated and then downregulated in pulmonary artery smooth muscle cells (PASMC) and in mouse lungs in vitro and in vivo. Here we investigated the mechanisms regulating this bi-phasic expression of miR-17~92 in PASMC in hypoxia. We measured the level of primary miR-17~92 in PASMC during hypoxia exposure and found that short-term hypoxia exposure (3%O2, 6 hours) induced the level of primary miR-17~92, while long-term hypoxia exposure (3%O2, 24 hours) decreased its level, suggesting a bi-phasic regulation of miR-17~92 expression at the transcriptional level. We found that short-term hypoxia-induced upregulation of miR-17~92 was HIF1α and E2F1 dependent. Two HIF1α binding sites on miR-17~92 promoter were identified. We also found that long-term hypoxia-induced suppression of miR-17~92 expression could be restored by silencing of p53. Mutation of the p53-binding sites in the miR-17~92 promoter increased miR-17~92 promoter activity in both normoxia and hypoxia. Our findings suggest that the bi-phasic transcriptional regulation of miR-17~92 during hypoxia is controlled by HIF1/E2F1 and p53 in PASMC: during short-term hypoxia exposure, stabilization of HIF1 and induction of E2F1 induces the transcription of miR-17~92; while during long-term hypoxia exposure, hyperphosphorylation of p53 suppresses the expression of miR-17~92.

3.
BMC Nephrol ; 25(1): 46, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38302918

RESUMO

BACKGROUND AND OBJECTIVES: The psychological problems of hemodialysis (HD) patients are prominent, and benefit finding (BF) have been proven beneficial to physical and mental health, fewer researchers explored BF in HD patients. The aim of this study was to investigate the current status of BF in patients with chronic kidney disease and to analyze the factors influencing it in order to provide a reference for subsequent interventions. METHODS: A cross-sectional study was done on 246 HD patients by convenience sampling in the hemodialysis center of a 3 A hospital in Shanghai from March to September 2019. The measures include General Information Questionnaire, Benefit Finding Scale, Perceived Social Support Scale, General Self-efficacy Scale, and Simplified Coping Style scale. RESULTS: The median (interquartile range, IQR) score of BF was 66 (IQR = 19) and it was lower compared with other chronic diseases. Significant differences in BF scores were found between different age groups, HD duration categories, and understanding degrees of HD. Taking BF as the dependent variable, the results of multiple linear regression analysis showed that age, duration of HD, family support, other support, positive coping, and self-efficacy entered the regression equation to explain 43.8% of the total variation. Social support played an indirect effect in the relationship between positive coping and BF, accounting for 54.1% of the total effect. CONCLUSION: The BF of HD patients is worrisome and affected by many factors. Medical staff could pay attention to the positive psychology of HD patients, and construct individualized interventions according to the influencing factors to improve their BF level and achieve physical and mental health.


Assuntos
Adaptação Psicológica , Insuficiência Renal Crônica , Humanos , Estudos Transversais , China/epidemiologia , Diálise Renal/psicologia , Insuficiência Renal Crônica/terapia
4.
Front Microbiol ; 14: 1228693, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37822739

RESUMO

Background: In recent decades, the decline of male sperm quality has become a worldwide phenomenon, with sperm quality of critical importance for the ability to conceive naturally. Recent studies suggest that male fertility function is closely linked to the gut microbiota, however, the cause-and-effect association between the gut microbiota and male infertility risk is currently unclear. Methods: We performed one two-sample Mendelian randomization (MR) study, which uses summary data on human gut microbiota from the MiBioGen consortium as factors of exposure. FinnGen Consortium R8 data was used to obtain GWAS data for male infertility. To evaluate cause-and-effect associations linking gut microbiota and male infertility risk with multiple Mendelian randomization methods, we included inverse variance weighted (IVW), MR-Egger, and Maximum Likelihood (ML) Ratio. The heterogeneity of instrumental variables was evaluated through Cochran's Q, Rucker's Q, and leave-one-out analysis methods. Results: We found a positive association between Allisonella, Anaerotruncus, Barnesiella, Intestinibacter, and Lactococcus with male infertility risk according to the MR analysis results. Bacteroides Romboutsia, Ruminococcaceae (NK4A2140group), and Ruminococcaceae (UCG011) play a protective function in male infertility pathogenesis. Conclusion: It was found that gut microbiota and infertility are causally related in this study. In subsequent studies, there is a need to build a larger and more comprehensive GWAS database on male infertility, which will reveal the underlying mechanisms for gut microbiota and male infertility. There is a need for randomized controlled trials for validating the protective effect of the associated gut microbiota against male infertility risk, and for exploring the associated mechanisms.

6.
Front Public Health ; 11: 1103022, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36817910

RESUMO

Background: Excessive doses of electromagnetic radiation pose a negative impact on the central nervous system and lead to mental disorders. Molecular hydrogen can scavenge intracellular hydroxyl radicals, acting as an antioxidant, anti-apoptotic and anti-inflammatory agent. We seek to assess the capability of molecular hydrogen to ameliorate brain damage induced by electromagnetic radiation. Methods: NEMP (nuclear electromagnetic pulse), a subset of electromagnetic pulse with high voltage value that could cause severe brain injury, was applied to this study. Male wild-type rats were divided into four groups: the control group, the H2 (Molecular hydrogen) group, the NEMP group and the NEMP+H2 group. Rats in the H2 group and the NEMP+H2 group were fed with saturated hydrogen-rich water from 3 days before NEMP exposure (electromagnetic field intensity 400 kV/m, rising edge 20 ns and pulse width 200 ns) to the day of sacrifice. One day after exposure, animal behavior experiments were performed, and samples for transcriptomics and metabolomics analysis were collected. Seven days after exposure, histopathological experiments were conducted. Results: The data from the elevated plus maze and the open field test showed that NEMP exposure elicited anxiety-like behavior in rats, which could be alleviated by H2 treatment. Histopathological results manifested that NEMP exposure-induced injuries of the neurons in the hippocampus and amygdala could be attenuated by H2 treatment. Transcriptomic results revealed that NEMP exposure had a profound effect on microtubule structure in the brain. And the combined analysis of transcriptomics and metabolomics showed that H2 has a significant impact on the neuroactive ligand-receptor interaction, synaptic vesicle cycle and synapse etc. Moreover, it was indicated that the glutathione metabolic pathway played a vital role in the NEMP exposure-induced damage and the protective activity of H2. Conclusions: H2 is identified as a potent agent against NEMP exposure-induced brain damage and has the potential to be a promising electromagnetic radiation protectant.


Assuntos
Lesões Encefálicas , Transcriptoma , Ratos , Masculino , Animais , Estresse Oxidativo , Fenômenos Eletromagnéticos , Hidrogênio/química , Hidrogênio/farmacologia , Encéfalo
7.
Chinese Journal of Pediatrics ; (12): 1011-1017, 2023.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-1013215

RESUMO

Objective: The kidney disease: improving global outcome (KDIGO) and pediatric reference change value optimized for acute kidney injury (pROCK) criteria were used to evaluate the incidence, stages and mortality of acute kidney injury (AKI). The differences between the 2 criteria were compared for exploring the value of pROCK criteria in diagnosing pediatric AKI and predicting adverse outcomes. Methods: In the multicenter prospective clinical cohort study, we collected general data and clinical data such as serum creatinine values from 1 120 children admitted to 4 PICUs of Children's Hospital of Soochow University, Children's Hospital of Fudan University, Anhui Provincial Children's Hospital, and Xuzhou Children's Hospital from September 2019 to February 2021. AKI was defined and staged according to the KDIGO and pROCK criteria. The incidence of AKI, the consistency of AKI definite diagnosis and stages, and the mortality in PICU were compared between the 2 groups. The chi-square test or Fisher's exact test was applied for comparison between 2 groups. The Cohen's Kappa and Weighted Kappa analyses were used for evaluating diagnostic consistency. The Cox regression analysis was used to evaluate the correlation between AKI and mortality. Results: A total of 1 120 critically ill children were included, with an age of 33 (10, 84) months. There are 668 boys and 452 girls. The incidence of AKI defined by the KDIGO guideline was higher than that defined by pROCK criteria (27.2%(305/1 120), 14.7%(165/1 120), χ2=52.78, P<0.001). The concordance rates of the 2 criteria for the diagnosis of AKI and AKI staging were 87.0% (κ=0.62) and 79.7% (κ=0.58), respectively. Totally 63 infants with AKI stage 1 defined by the KDIGO guideline were redefined as non-AKI by following the pROCK criteria. The PICU mortality rate of these infants was similar to patients without AKI defined by KDIGO guideline(P=0.761). After adjusting for confounders, AKI defined by KDIGO or pROCK criteria was an independent risk factor of death in PICU (AHR=2.04, 2.73,95%CI 1.27-3.29, 1.74-4.28, both P<0.01), and the risk of death was higher when using the pROCK compared with the KDIGO criteria. As for the KDIGO criteria, mild AKI was not associated with the mortality in PICU (P=0.702), while severe AKI was associated with increased mortality (P<0.001). As for the pROCK criteria, both mild and severe AKI were risk factors of PICU death in children (HR=3.51, 6.70, 95%CI 1.94-6.34, 4.30-10.44, both P<0.001). In addition, The AKI severity was positively associated with the mortality. Conclusions: The AKI incidence and staging varied depending on the used diagnostic criteria. The KDIGO definition is more sensitive, while the pROCK-defined AKI is more strongly associated with high mortality rate.


Assuntos
Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Injúria Renal Aguda/epidemiologia , Estudos de Coortes , Estado Terminal , Estudos Prospectivos , Fatores de Risco
8.
Chinese Journal of Pediatrics ; (12): 922-927, 2023.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-1013198

RESUMO

Objective: To investigate the clinical characteristics of hospitalized children infected with the Omicron variant in Kunming after the withdrawal of non-pharmaceutical interventions (NPI) and analyze the risk factors of severe cases. Methods: Clinical data was retrospectively collected from 1 145 children with SARS-CoV-2 Omicron infection who were hospitalized in six tertiary grade A hospitals in Kunming from December 10th, 2022 to January 9th, 2023. According to clinical severity, these patients were divided into the general and severe SARS-CoV-2 groups, and their clinical and laboratory data were compared. Between-group comparison was performed using t-test, chi-square test and Mann-Whitney U test. Spearman correlation test and multivariate Logistic regression analysis were used to determine the risk factors of severe illness. Results: A total of 1 145 hospitalized patients were included, of whom 677 were male and 468 female. The age of these patients at visit was 1.7 (0.5, 4.1) years. Specifically, there were 758 patients (66.2%) aged ≤3 years at visit and 387 patients (33.8%) aged >3 years. Of these children, 89 cases (7.8%) had underline diseases and the remaining 1 056 cases (92.2%) had no combined diseases. Additionally, of all the patients, 319 cases (27.9%) were vaccinated with one or two doses of SARS-CoV-2 vaccine, 748 cases (65.3%) had acute upper respiratory tract infection (AURTI), and six cases died (0.5%). A total of 1 051 cases (91.8%) were grouped into general SARS-CoV-2 group and 94 cases (8.2%) were grouped into severe SARS-CoV-2 group. Compared with the general cases, the severe cases showed a lower rate of SARS-CoV-2 vaccination and younger median age, lower lymphocyte count, as well as proportions of CD8+T lymphocyte (36 cases (38.3%) vs. 283 cases (26.9%), 0.5 (2.6, 8.0) vs. 1.6 (0.5, 3.9) years, 1.3 (1.0, 2.7) ×109 vs. 2.7 (1.3,4.4)×109/L, 0.17 (0.12, 0.24) vs. 0.21 (0.15, 0.16), respectively, χ2=4.88, Z=-2.21,-5.03,-2.53, all P<0.05). On the other hand, the length of hospital stay, proportion of underline diseases, ALT, AST, creatine kinase isoenzyme, and troponin T were higher in the severe group compared to those in the general group ((11.6±5.9) vs. (5.3±1.8) d, 41 cases (43.6%) vs. 48 cases (4.6%), 67 (26,120) vs. 20 (15, 32) U/L, 51 (33, 123) vs. 44 (34, 58) U/L、56.9 (23.0, 219.3) vs. 3.6 (1.9, 17.9) U/L, 12.0 (4.9, 56.5) vs. 3.0 (3.0, 7.0) ×10-3 pg/L,respectively, t=-20.43, χ2=183.52, Z=-9.14,-3.12,-6.38,-3.81, all P<0.05). Multivariate regression analysis indicated that increased leukocyte count (OR=1.88, 95%CI 1.18-2.97, P<0.01), CRP (OR=1.18, 95%CI 1.06-1.31, P<0.01), ferritin (OR=1.01, 95%CI 1.00-1.00, P<0.01), interleukin (IL)-6 (OR=1.05, 95%CI 1.01-1.08, P=0.012), D-dimer (OR=2.56, 95%CI 1.44-4.56, P<0.01) and decreased CD4+T lymphocyte (OR=0.84, 95%CI 0.73-0.98, P=0.030) were independently associated with the risk of severe SARS-CoV-2 in hospitalized children with Omicron infection. Conclusions: After the withdrawal of NPI, the pediatric inpatients with Omicron infection in Kunming were predominantly children younger than 3 years of age, and mainly manifested as AURTI with relatively low rate of severe SARS-CoV-2 infection and mortality. Elevated leukocyte counts, CRP, ferritin, IL-6, D-dimer, and decreased CD4+T lymphocytes are significant risk factors for developing severe SARS-CoV-2 infection.


Assuntos
Humanos , Criança , Feminino , Masculino , COVID-19 , Vacinas contra COVID-19 , Estudos Retrospectivos , SARS-CoV-2 , Ferritinas , Interleucina-6
9.
International Eye Science ; (12): 1589-1593, 2023.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-980560

RESUMO

AIM: To investigate the bacterial flora and antibiotic susceptibility testing of conjunctival sac in adolescents after wearing orthokeratology(OK)lens.METHODS:A total of 101 adolescents aged 8 to 14 who admitted to outpatient department of Xi'an No.1 Hospital from September 2021 to August 2022 were recruited in this cross-sectional observational study. There were 51 cases wearing OK Lens(wearing group)and 50 patients not wearing contact lens(non-lens group), the right eye of all patients was selected into the group. The culture of bacterial flora in conjunctival sac between the two groups were compared, the species were identified by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry, and the antibiotic susceptibility testing was carried out for the positive strains cultured in the wearing group.RESULTS:The positive rate of conjunctival sac bacterial cultured in the wearing group and the non-lens group was 68.6%(35/51)and 60.0%(30/50), respectively(P&#x003E;0.05). In both groups, the bacteria with the highest detection rate were staphylococcus epidermidis and staphylococcus aureus. The sensitivity rates of the strains detected in the wearing group to drugs are as follows: Levofloxacin(98%), Moxifloxacin(98%), Gatifloxacin(98%), Cefuroxime(98%), Cefathiamidine(98%), Rifampicin(98%), Chloramphenicol(96%), Cefoxitin(95%), Clindamycin(80%), Gentamicin(74%), Fusidic acid(72%), Tobramycin(64%), Compound sulfamethoxazole(26%), Mezlocillin(10%), Azithromycin(6%), of which the sensitivity rate of Gram-positive cocci was 100% sensitive to Vancomycin.CONCLUSION:Gram-positive cocci are the main bacteria isolated from conjunctival sac of adolescents after wearing OK Lens. Wearing OK Lens will not significantly increase the positive rate of conjunctival sac bacterial flora. Results of antibiotic susceptibility testing may provide guidance for empirical medication in patients wearing OK lens after eye infection.

10.
Oxid Med Cell Longev ; 2022: 3469474, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36199428

RESUMO

Infertility has got to be a broadly concerned social issue these days, in which the malefactor cannot be overlooked. Numerous studies have shown that electromagnetic pulse (EMP) radiation may have seriously damaging effects on reproductive health, through nonthermal effects and oxidative stress. Molecular hydrogen, a selective hydroxyl radical scavenger, explains the protective effects against many diseases closely associated with oxidative damage, such as ionizing radiation (IR). We sought to characterize the beneficial effects of molecular hydrogen on the male reproductive system in a rodent EMP exposure model. The 8-week-old male Sprague-Dawley rats were exposed to EMP (peak intensity 1000 kV/m, pulse edge 20 ns, pulse width 200 ns, 1 Hz, and 200 pulses), with or without hydrogen-rich water. The pathological structure of the testis, the rate of apoptosis of the testis, the serum testosterone level, the sperm parameters, and the activity of the antioxidant enzymes of the testis were measured. Then, transcriptomic and untargeted metabolomic analyses were applied to uncover the underlying mechanism. Exposure to EMP increased testicular apoptosis rate and apoptosis protein level, decreased sperm viability and motility, decreased serum testosterone levels, and diminished testicular antioxidant capacity. Molecular hydrogen-alleviated damage decreased the testicular apoptosis rate and apoptosis protein level, increased sperm motility, increased serum testosterone levels, and improved antioxidative capacity. Omics results showed that molecular hydrogen has a strong influence on metabolic pathways, and EMP affects mainly oxidative phosphorylation, TNF signaling pathways, and cytokine-receptor interactions. The mechanism of molecular hydrogen's effect may be related to the reversal of some metabolite levels. These observations warrant molecular hydrogen as an innovative approach for potential protection against EMP.


Assuntos
Antioxidantes , Roedores , Animais , Antioxidantes/farmacologia , Citocinas/metabolismo , Fenômenos Eletromagnéticos , Hidrogênio/metabolismo , Hidrogênio/farmacologia , Radical Hidroxila/metabolismo , Masculino , Estresse Oxidativo , Ratos , Ratos Sprague-Dawley , Roedores/metabolismo , Sêmen/metabolismo , Motilidade dos Espermatozoides , Testículo/metabolismo , Testosterona , Água/farmacologia
12.
BMC Med Genomics ; 15(1): 136, 2022 06 18.
Artigo em Inglês | MEDLINE | ID: mdl-35717189

RESUMO

BACKGROUND: Uniparental disomy (UPD) is a condition in which both chromosomes are inherited from the same parent, except for imprinting disorders. Uniparental isodisomy (UPiD) may result in a homozygous variant contributing to an autosomal recessive disorder in the offspring of a heterozygous carrier. Junctional epidermolysis bullosa intermediate (JEB intermediate) is an autosomal recessive inherited disease that is associated with a series of gene variants, including those of COL17A1. CASE PRESENTATION: We report the first case of complete paternal UPiD of chromosome 10 harbouring a novel homozygous variant in COL17A1: c.1880(exon23)delG (p.G627Afs*56). This variant led to the clinical phenotype of junctional epidermolysis bullosa intermediate in a 5-year-old child. Trio-whole exome sequencing (Trio-WES) and in silico data analysis were used for variant identification, Sanger sequencing was performed for variant validation, and pathological examination was performed as the gold standard for phenotype confirmation. CONCLUSIONS: We recommend the use of WES as a first-tier test for the diagnosis of epidermolysis bullosa, especially for paediatric patients. Moreover, UPD events should be detected and analysed routinely through WES data in the future.


Assuntos
Epidermólise Bolhosa Juncional , Criança , Pré-Escolar , Cromossomos Humanos Par 10 , Epidermólise Bolhosa Juncional/genética , Epidermólise Bolhosa Juncional/patologia , Heterozigoto , Homozigoto , Humanos , Dissomia Uniparental
13.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-928761

RESUMO

OBJECTIVE@#To investigate the regulatory effect and mechanism of DNA methyltransferase 3A (DNMT3a) in hydroquinone-induced hematopoietic stem cell toxicity.@*METHODS@#Cells (HSPC-1) were divided into 4 groups, that is A: normal HSPC-1; B: HQ-intervented HSPC-1; C: group B + pcDNA3 empty vector; D: group B + pcDNA3- DNMT3a. RT-qPCR and Western blot were used to detect the expression levels of DNMT3a and PARP-1 mRNA and protein, respectively. Cell morphology was observe; Cell viability and apoptosis rate of HSPC-1 were detected by MTT and flow cytometry, respectively.@*RESULTS@#Compared with group A, the expression levels of DNMT3a mRNA and protein in HSPC-1 of group B were decreased, while PARP-1 mRNA and protein were increased (P<0.05); there was no significant difference in the above indexes between group C and group B; compared with group B, the expression levels of DNMT3a mRNA and protein showed increased, while PARP-1 mRNA and protein were decreased significantly in cells of group D transfected with DNMT3a (P<0.05). Cells in each group were transfected with DNMT3a and cultured for 24 h, HSPC-1 in group A showed high density growth and mononuclear fusion growth, while the number of HSPC-1 in group B and C decreased and grew slowly. Compared with group B and C, the cell growth rate of group D was accelerated. The MTT analysis showed that cell viability of HSPC-1 in group B were lower than that of group A at 24 h, 48 h and 72 h (P<0.05); after transfected with DNMT3a, the cell viability of HSPC-1 in group D were higher than that of group B at 24 h, 48 h and 72 h (P<0.05). The apoptosis rate of cells in group B was significantly higher than that of group A (P<0.001), while the apoptosis rate in group D was lower than that of group B (P<0.001).@*CONCLUSION@#DNMT3a may be involved in the damage of hematopoietic stem cells induced by hydroquinone, which may be related to the regulation of PARP-1 activity by hydroquinone-inhibited DNMT3a.


Assuntos
Humanos , Apoptose , Proliferação de Células , DNA Metiltransferase 3A , Células-Tronco Hematopoéticas/efeitos dos fármacos , Hidroquinonas/toxicidade , Poli(ADP-Ribose) Polimerase-1 , RNA Mensageiro/metabolismo
14.
J Pharm Pharmacol ; 73(6): 796-807, 2021 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-33734400

RESUMO

OBJECTIVES: Glucolipid metabolic disorders (GLMD) promote a series of major chronic diseases. Polygoni Multilori Radix Preparata (PMRP) has been widely acknowledged in the prevention and treatment of GLMD. We previously reported that water extract (WE) of PMRP and its major bioactive constituents such as polysaccharides (POL) and 2,3,5,4´-tetrahydroxy-stilbene-2-O-ß-D-glucoside (TSG) could alleviate GLMD. The mitochondrial dysfunction is an important mechanism of GLMD, but the underlying mechanisms behind the regulation of mitochondria to alleviate GLMD by WE, POL from PMRP and TSG are still unknown. METHODS: In this study, we elucidated the effects of WE, POL, and TSG towards regulating the mitochondrial dysfunction and alleviating GLMD using mitochondrial metabonomics. A rat model of GLMD was established by high-sugar and high-fat (HS-HF) diet. Rats were intragastrically given WE, POL, and TSG for 12 weeks. The liver mitochondrial metabolites were analyzed by ultra-high-performance liquid chromatography/mass spectrometry followed by multivariate statistical analysis to identify the differential metabolites and metabolic pathways. KEY FINDINGS: The WE, POL, and TSG could significantly restore the level of endogenous metabolites in liver mitochondria toward normal status. In total, sixteen, seven, and fourteen differential metabolites were identified in the liver mitochondrial samples obtained from the WE, GOL, and TSG groups, respectively. These metabolites were found to be mainly involved in glycerol phospholipid, histidine, alanine, aspartic acid, glutamate metabolism, and arginine biosynthesis. CONCLUSIONS: PMRP could improve the liver mitochondrial function by regulating the mitochondrial metabolic pathways to alleviate GLMD. Therefore, the application of PMRP might be a promising mitochondrial regulator/nutrient for alleviating GLMD-associated diseases and the mitochondrial metabonomics might provide insights into the evaluation of the efficacies and mechanisms of action of drugs.


Assuntos
Doenças Metabólicas/tratamento farmacológico , Metabolômica , Extratos Vegetais/farmacologia , Polygonum/química , Animais , Cromatografia Líquida de Alta Pressão , Dieta Hiperlipídica , Modelos Animais de Doenças , Glicolipídeos/metabolismo , Masculino , Espectrometria de Massas , Doenças Metabólicas/metabolismo , Mitocôndrias Hepáticas/efeitos dos fármacos , Mitocôndrias Hepáticas/metabolismo , Raízes de Plantas , Ratos , Ratos Sprague-Dawley
15.
Acta Anatomica Sinica ; (6): 628-634, 2021.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-1015440

RESUMO

Objective To explore the effect and mechanism of ginsenoside Re on the intestinal mucosa of severe acute pancreatitis (SAP) mice by regulating the Janus kinase 2/signal transducer and activator of transcription 3 (JAK2/ STAT3) pathway. Methods Totally 48 mice were divided into : control group, SAP group, SAP + ginsenoside Re group and SAP + ginsenoside Re + LY2784544 group (n = 12). The mice were intraperitoneally injected with caerulein solution (after fasting for 12 hours, 100 μg/kg, 6 times, injection interval 60 minutes) to establish SAP models. Mice in the SAP+ ginsenoside Re group were intraperitoneally injected with ginsenoside Re (4 mg/kg, 1 time a day for 7 consecutive days). Intraperitoneal injection of 12.7 mg/kg LY2784544 was used to inhibit the JAK2/STAT3 pathway. Pancreatic and intestinal mucosal injury were detected in each group. The wet to dry weight ratio of pancreas, serum amylase and inflammatory factor levels were detected in each group. The intestinal mucosal barrier function was analyzed by detecting the levels of D-lactic acid and fluorescein isothiocyanate dextran (FITC-D). The damage of pancreatic tissue and intestinal mucosa tissue was observed by HE staining. Western blotting was used to detect the levels of apoptotic proteins Bax and Bcl-2 in the intestinal mucosa. The JAK2/STAT3 pathway expression levels in pancreatic tissue and intestinal mucosa tissue were detected by Realtime PCR and Western blotting. Results The pancreatic index, serum amylase, interieukin 6 (IL-6) and tumor necrosis factor a (TNF-a), FITC-D, D-lactic acid, Bax protein levels, JAK2 and STAT3 mRNA and protein levels in the SAP group were significantly higher than those in the control group, while Bcl-2 protein was significantly lower than that in the control group (P<0.05). The Bcl-2 protein of SAP+ginsenoside Re group was significantly higher than that of SAP group, and other indexes were significantly lower than those in SAP group (P<0.05). The Bcl-2 protein of SAP+ginsenoside Re+ LY2784544 group was significantly higher than that of SAP + ginsenoside Re group, and other indexes were significantly lower than those in the SAP+ginsenoside Re group (P<0.05). Conclusion Ginsenoside Re may reduce the pancreatic injury in SAP model mice by inhibiting the JAK/STAT pathway to alleviate the inflammatory response, and may protect the small intestinal mucosal barrier by alleviating pancreatitis and inhibiting the intestinal mucosal JAK/STAT pathway to inhibit cell apoptosis.

16.
Journal of Experimental Hematology ; (6): 1768-1774, 2021.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-922332

RESUMO

OBJECTIVE@#To investigate the effect of silencing DNA methyltransferase 1(DNMT1) to the methylation of the promoter of the tumor suppressor gene wnt-1 (WIF-1) in human chronic myeloid leukemia (CML) cells.@*METHODS@#DNMT1 siRNAi plasmid was constructed and DNMT1 siRNAi was transfected into CML K562 cells. RT-PCR and Western blot were used to detect the expression of DNMT1 gene and related protein, and methylation PCR was used to detect WIF-1 gene promoter methylation level. The trypan blue exclusion and MTT assay were used to detect the cell proliferation, flow cytometry were used to detect the cell apoptosis rate, colony formation assay was used to detect cell colony formation ability. Expression of Wnt/β- catenin and its downstream signaling pathway proteins were detected by Western blot after DNMT1 gene was silenced.@*RESULTS@#The expression level of DNMT1 mRNA and its related protein in the experimental group were significantly lower than those in the control group and negative control group (P<0.05). After 72 hours of successful transfection, the WIF-1 gene in the control group and negative control group were completely methylated, while in the experimental group, the methylation level significantly decreased. The results of MSP showed that the PCR product amplified by the unmethylated WIF-1 primer in the experimental group increased significantly,while by the methylated WIF-1 primer decreased significantly. After 48 h of transfection, the OD value, viable cell number and colony formation of the cells in experimental group were significantly lower than those in the negative control group and the control group (P<0.05). The apoptosis rate of the cells in experimental group was significantly higher than those in the negative control group and control group (P<0.05). The expression levels of β- actin, myc, cyclin D1 and TCF-1 in K562 cells in the experimental group were significantly lower than those in the negative control group and control group (P<0.05).@*CONCLUSION@#Silencing DNMT1 gene can inhibit the proliferation and promote the apoptosis of K562 cells. The mechanism may be related to reverse the hypermethylation level of the WIF-1 gene promoter, thereby inhibit the activity of the Wnt/β- catenin signaling pathway.


Assuntos
Humanos , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Metilação de DNA , Células K562 , Leucemia Mielogênica Crônica BCR-ABL Positiva/genética , Proteínas Repressoras/metabolismo
17.
Surg Oncol ; 34: 113-120, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32891315

RESUMO

MicroRNAs (miRNAs) have been identified as critical modulators of cell migration and invasion, which are the major causes of cancer progression including hepatocellular carcinoma (HCC). However, the accurate role of miR-515-5p in HCC is still uncertain. Here, we report that miR-515-5p expression is down-regulated in HCC tissues and cell lines, and associated with absence of capsule formation (p = 0.015)﹑microvascular invasion(p = 0.003)﹑and advantange TNM stage (II-III) (p = 0.014) in HCC patients. Overexpression of miR-515-5p inhibited migration and invasion of HCC cells in vitro and in vivo, while miR-515-5p knockdown has the inverse effect. Moreover, using miRNA databases and dual-luciferase report assay, we find miR-515-5p directly binds to the 3'-untranslated region (3'-UTR) of interleukin 6 (IL6). In addition, the regulatory association between miR-515-5p and the IL-6/Janus kinase (JNK)/signal transducer and activator of transcription-3 (STAT3) signaling pathway was explored. Furthermore, overexpression of miR-515-5p inhibited the activation of the JAK/STAT3 signaling pathway, which was rescued by overexpression of IL-6. The results of the current study indicate that miR-515-5p overexpression may serve an important role in inhibiting migration and invasion of HCC cells via suppression of IL-6/JAK/STAT3 signaling pathway activation. MiR-515-5p may serve as a potential therapeutic target for HCC.


Assuntos
Carcinoma Hepatocelular/patologia , Regulação Neoplásica da Expressão Gênica , Interleucina-6/metabolismo , Janus Quinase 1/metabolismo , Neoplasias Hepáticas/patologia , MicroRNAs/genética , Fator de Transcrição STAT3/metabolismo , Animais , Apoptose , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Movimento Celular , Proliferação de Células , Feminino , Humanos , Interleucina-6/genética , Janus Quinase 1/genética , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Masculino , Camundongos , Camundongos Nus , Pessoa de Meia-Idade , Prognóstico , Fator de Transcrição STAT3/genética , Taxa de Sobrevida , Células Tumorais Cultivadas , Ensaios Antitumorais Modelo de Xenoenxerto
18.
J Cancer ; 11(17): 5118-5128, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32742459

RESUMO

In patients with hepatocellular carcinoma (HCC), disease progression and associated bone metastasis (BM) can markedly reduce quality of life. While the long non-coding RNA (lncRNA) zinc finger E-box binding homeobox 1 antisense 1 (ZEB1-AS1) has been shown to function as a key regulator of oncogenic processes in HCC and other tumor types, whether it plays a role in controlling HCC BM remains to be established. In the current study, we detected the significant upregulation of lncZEB1-AS1 in HCC tissues, and we found this expression to be associated with BM progression. When we knocked down this lncRNA in HCC cells, we found that this significantly reduced their migratory, invasive, and metastatic activity both in vitro and in vivo. At a mechanistic level, we found that lncZEB1-AS1 was able to target miR-302b and to thereby increase PI3K-AKT pathway activation and EGFR expression, resulting in the enhanced expression of downstream matrix metalloproteinase genes in HCC cells. In summary, our results provide novel evidence that lncZEB1-AS1 can promote HCC BM through a mechanism dependent upon the activation of PI3K-AKT signaling, thus highlighting a potentially novel therapeutic avenue for the treatment of such metastatic progression in HCC patients.

19.
J Exp Clin Cancer Res ; 39(1): 114, 2020 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-32552766

RESUMO

BACKGROUND: Circular RNAs (circRNAs) play a critical regulatory role in cancer progression. However, the underlying mechanisms of circRNAs in hepatocellular carcinoma (HCC) metastasis remain mostly unknown. METHODS: Has_circ_0003998 (circ0003998) was identified by RNAs sequencing in HCC patients with /without portal vein tumor thrombus (PVTT) metastasis. The expression level of circ0003998 was further detected by in situ hybridization on tissues microarray (ISH-TMA) and qRT-PCR in 25 HCC patients with PVTT metastasis. Moreover, the 25 HCC patients with PVTT metastasis and 50 HCC patients without PVTT metastasis were recruited together to analyze the correlation between circ0003998 expression and HCC clinical characteristics. Transwell, migration and CCK8 assays, as well as nude mice model of lung or liver metastasis were used to evaluate the role of circ0003998 in epithelial to mesenchymal transition (EMT) in HCC. The regulatory mechanisms of circ0003998 in miR-143-3p and PCBP1 were determined by dual-luciferase reporter assay, nuclear-cytoplasmic fractionation, fluorescent in situ hybridization, RNA pull- down, microRNA sequence, western blot and RNA immunoprecipitation. RESULTS: Compared with adjacent normal liver tissues (ANL), circ0003998 expression was significantly upregulated in PVTT tissues and HCC tissues, and its expression correlates with the aggressive characteristics of HCC patients. Further assays suggested that circ0003998 promoted EMT of HCC both in vitro and in vivo. Mechanistically, our data indicated that circ0003998 may act as a ceRNA (competing endogenous RNA) of microRNA-143-3p to relieve the repressive effect on EMT-related stimulator, FOSL2; meanwhile, circ0003998 could bind with PCBP1-poly(rC) binding protein 1 (PCBP1) to increase the expression level of EMT-related genes, CD44v6. CONCLUSION: Circ0003998 promotes EMT of HCC by circ0003998/miR-143-3p/FOSL2 axis and circ0003998 /PCBP1/CD44v6 axis.


Assuntos
Biomarcadores Tumorais/metabolismo , Carcinoma Hepatocelular/patologia , Proteínas de Ligação a DNA/metabolismo , Transição Epitelial-Mesenquimal , Regulação Neoplásica da Expressão Gênica , Neoplasias Hepáticas/patologia , MicroRNAs/genética , RNA Circular/genética , Proteínas de Ligação a RNA/metabolismo , Animais , Apoptose , Biomarcadores Tumorais/genética , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Movimento Celular , Proliferação de Células , Proteínas de Ligação a DNA/genética , Feminino , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Pessoa de Meia-Idade , Invasividade Neoplásica , Prognóstico , Proteínas de Ligação a RNA/genética , Taxa de Sobrevida , Células Tumorais Cultivadas , Ensaios Antitumorais Modelo de Xenoenxerto
20.
BMC Gastroenterol ; 20(1): 167, 2020 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-32487124

RESUMO

BACKGROUND: Juvenile polyposis syndrome (JPS) is a rare disorder characterized by the presence of multiple juvenile polyps in the gastrointestinal tract, and germline mutations in SMAD4 or BMPR1A. Due to its rarity and complex clinical manifestation, misdiagnosis often occurs in clinical practice. CASE PRESENTATION: A 42-year-old man with multiple pedunculated colorectal polyps and concomitant rectal adenocarcinoma was admitted to our hospital. His mother had died of colon cancer. He was diagnosed with familial adenomatous polyposis (FAP) and underwent total proctocolectomy and ileal pouch anal anastomosis. Two polyps were selected for pathological examination. One polyp had cystically dilated glands with slight dysplasia. The other polyp displayed severe dysplasia and was diagnosed as adenoma. Three years later, his 21-year-old son underwent a colonoscopy that revealed more than 50 pedunculated colorectal juvenile polyps. Both patients harbored a germline pathogenic mutation in BMPR1A. Endoscopic resection of all polyps was attempted but failed. Finally, the son received endoscopic resection of polyps in the rectum and sigmoid colon, and laparoscopic subtotal colectomy. Ten polyps were selected for pathological examination. All were revealed to be typical juvenile polyps, with cystically dilated glands filled with mucus. Thus, the diagnosis of JPS was confirmed in the son. A review of the literatures revealed that patients with JPS can sometimes have adenomatous change. Most polyps in patients with JPS are benign hamartomatous polyps with no dysplasia. A review of 767 colorectal JPS polyps demonstrated that 8.5% of the polyps contained mild to moderate dysplasia, and only 0.3% had severe dysplasia or cancer. It is difficult to differentiate juvenile polyps with dysplasia from adenoma, which could explain why juvenile polyps have been reported to have adenomatous changes in patients with JPS. Therefore, patients with JPS, especially those with concomitant dysplasia and adenocarcinoma, might be easily diagnosed as FAP in clinical practice. CONCLUSIONS: Juvenile polyp with dysplasia is often diagnosed as adenoma, which might lead to the misdiagnosis of JPS as FAP. The differential diagnosis of JPS versus FAP, should be based on comprehensive evaluation of clinical presentation, endoscopic appearance and genetic investigations; not on the presence or absence of adenoma.


Assuntos
Polipose Adenomatosa do Colo/diagnóstico , Receptores de Proteínas Morfogenéticas Ósseas Tipo I/genética , Erros de Diagnóstico , Polipose Intestinal/congênito , Síndromes Neoplásicas Hereditárias/diagnóstico , Proteína Smad4/genética , Polipose Adenomatosa do Colo/genética , Adulto , Mutação em Linhagem Germinativa , Humanos , Polipose Intestinal/diagnóstico , Polipose Intestinal/genética , Masculino , Síndromes Neoplásicas Hereditárias/genética , Adulto Jovem
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