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  • Frontiers Media SA  (14)
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  • 2020-2024  (14)
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  • Frontiers Media SA  (14)
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  • Unknown  (14)
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  • 2020-2024  (14)
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  • 1
    Online Resource
    Online Resource
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    Frontiers Media SA ; 2023
    In:  Frontiers in Molecular Neuroscience Vol. 16 ( 2023-7-27)
    Details
    In: Frontiers in Molecular Neuroscience, Frontiers Media SA, Vol. 16 ( 2023-7-27)
    Abstract: The pathogenic gene CDH23 plays a pivotal role in tip links, which is indispensable for mechanoelectrical transduction in the hair cells. However, the underlying molecular mechanism and signal regulatory networks that influence deafness is still largely unknown. Methods In this study, a congenital deafness family, whole exome sequencing revealed a new mutation in the pathogenic gene CDH23 , subsequently; the mutation has been validated using Sanger sequencing method. Then CRISPR/Cas9 technology was employed to knockout zebrafish cdh23 gene. Startle response experiment was used to compare with wide-type, the response to sound stimulation between wide-type and cdh23 −/− . To further illustrate the molecular mechanisms underlying congenital deafness, comparative transcriptomic profiling and multiple bioinformatics analyses were performed. Results The YO-PRO-1 assay result showed that in cdh23 deficient embryos, the YO-PRO-1 signal in inner ear and lateral line neuromast hair cells were completely lost. Startle response experiment showed that compared with wide-type, the response to sound stimulation decreased significantly in cdh23 mutant larvae. Comparative transcriptomic showed that the candidate genes such as atp1b2b and myof could affect hearing by regulating ATP production and purine metabolism in a synergetic way with cdh23 . RT-qPCR results further confirmed the transcriptomics results. Further compensatory experiment showed that ATP treated cdh23 −/− embryos can partially recover the mutant phenotype. Conclusion In conclusion, our study may shed light on deciphering the principal mechanism and provide a potential therapeutic method for congenital hearing loss under the condition of CDH23 mutation.
    Type of Medium: Online Resource
    ISSN: 1662-5099
    URL: Article
    URL: Article
    URL: Article
    DOI: 10.3389/fnmol.2023.1079529
    DOI: 10.3389/fnmol.2023.1079529.s001
    DOI: 10.3389/fnmol.2023.1079529.s002
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2023
    detail.hit.zdb_id: 2452967-9
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  • 2
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    7,8-Dihydroxyflavone Attenuates Alcohol-Related Behavior in Rat Models of Alcohol Consumption via TrkB in the Ventral Tegmental Area
    Frontiers Media SA ; 2020
    In:  Frontiers in Neuroscience Vol. 14 ( 2020-5-19)
    Details
    In: Frontiers in Neuroscience, Frontiers Media SA, Vol. 14 ( 2020-5-19)
    Type of Medium: Online Resource
    ISSN: 1662-453X
    URL: Article
    DOI: 10.3389/fnins.2020.00467
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2020
    detail.hit.zdb_id: 2411902-7
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  • 3
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    Risk factors in the development of gastric adenocarcinoma in the general population: A cross-sectional study of the Wuwei Cohort
    Frontiers Media SA ; 2023
    In:  Frontiers in Microbiology Vol. 13 ( 2023-1-12)
    Details
    In: Frontiers in Microbiology, Frontiers Media SA, Vol. 13 ( 2023-1-12)
    Abstract: Several risk factors have been identified for the development of gastric adenocarcinoma (GAC), where the control group was usually a healthy population. However, it is unclear at what stage known risk factor exert their influence toward the progression to cancer. Based on the Wuwei Cohort, we enrolled 1,739 patients with chronic non-atrophic gastritis (no-CAG), 3,409 patients with chronic atrophic gastritis (CAG), 1,757 patients with intestinal metaplasia (IM), 2,239 patients with low-grade dysplasia (LGD), and 182 patients with high-grade dysplasia (HGD) or GAC to assess the risk factors between each two consecutive stages from no-CAG to GAC/HGD using adjusted logistic regression. We found that different groups of risk factors were associated with different stages. Age, occupation of farmer, low annual family income, Helicobacter pylori ( H. pylori ) infection, drinking, eating hot food, histories of gastritis and peptic ulcer were associated with the development of CAG. Age, illiteracy, H. pylori infection, smoking, eating hot food, eating quickly, and histories of gastritis and gallbladder diseases were associated with the progression to IM from CAG. Male, occupation of farmer and history of peptic ulcer were associated with the development of LGD from IM. Age, male and polyp history appeared to be risk factors associated with the development of GAC/HGD from LGD. In conclusion, it seems that most risk factors function more as a set of switches that initiated the GAC carcinogenesis. H. Pylori eradication and control of other risk factors should be conducted before IM to decrease the incidence of GAC.
    Type of Medium: Online Resource
    ISSN: 1664-302X
    URL: Article
    DOI: 10.3389/fmicb.2022.1024155
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2023
    detail.hit.zdb_id: 2587354-4
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  • 4
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    Frontiers Media SA ; 2021
    In:  Frontiers in Pharmacology Vol. 12 ( 2021-5-26)
    Details
    In: Frontiers in Pharmacology, Frontiers Media SA, Vol. 12 ( 2021-5-26)
    Abstract: To characterize human leukocyte antigen (HLA) loci as risk factors in aromatic antiepileptic drug-induced maculopapular exanthema (AED-MPE). A case-control study was performed to investigate HLA loci involved in AED-MPE in a southern Han Chinese population. Between January 2007 and June 2019, 267 patients with carbamazepine (CBZ), oxcarbazepine (OXC), or lamotrigine (LTG) associated MPE and 387 matched drug-tolerant controls from six centers were enrolled. HLA-A/B/C/DRB1 genotypes were determined using sequence-based typing. Potential risk alleles were validated by meta-analysis using data from different populations and in silico analysis of protein-drug interactions. HLA-DRB1*04:06 was significantly associated with OXC-MPE ( p = 0.002, p c = 0.04). HLA-B*38:02 was associated with CBZ-MPE ( p = 0.03). When pooled, HLA-A*24:02, HLA-A*30:01, and HLA-B*35:01 additionally revealed significant association with AED-MPE. Logistic regression analysis showed a multiplicative interaction between HLA-A*24:02 and HLA-B*38:02 in CBZ-MPE. Meta-analysis of data from different populations revealed that HLA-24*:02 and HLA-A*30:01 were associated with AED-MPE ( p = 0.02 and p = 0.04, respectively). In silico analysis of protein-drug interaction demonstrated that HLA-A*24:02 and HLA-A*30:01 had higher affinities with the three aromatic AEDs than the risk-free HLA-A allele. HLA-DRB1*04:06 showed relatively specific high affinity with S-monohydroxy derivative of OXC. HLA-DRB1*04:06 is a specific risk allele for OXC-induced MPE in the Southern Han Chinese. HLA-A*24:02, possibly HLA-A*30:01, are common risk factors for AED-MPE. The multiplicative risk potential between HLA-A*24:02 and HLA-B*38:02 suggests that patients with two risk alleles are at greater risk than those with one risk allele. Inclusion of these HLA alleles in pre-treatment screening would help estimating the risk of AED-MPE.
    Type of Medium: Online Resource
    ISSN: 1663-9812
    URL: Article
    URL: Article
    URL: Article
    URL: Article
    DOI: 10.3389/fphar.2021.671572
    DOI: 10.3389/fphar.2021.671572.s001
    DOI: 10.3389/fphar.2021.671572.s002
    DOI: 10.3389/fphar.2021.671572.s003
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2021
    detail.hit.zdb_id: 2587355-6
    SSG: 15,3
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  • 5
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    Different Perivascular Space Burdens in Idiopathic Rapid Eye Movement Sleep Behavior Disorder and Parkinson’s Disease
    Frontiers Media SA ; 2020
    In:  Frontiers in Aging Neuroscience Vol. 12 ( 2020-11-5)
    Details
    In: Frontiers in Aging Neuroscience, Frontiers Media SA, Vol. 12 ( 2020-11-5)
    Type of Medium: Online Resource
    ISSN: 1663-4365
    URL: Article
    DOI: 10.3389/fnagi.2020.580853
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2020
    detail.hit.zdb_id: 2558898-9
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  • 6
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    Adjuvant Transarterial Chemoembolization for Barcelona Clinic Liver Cancer Stage A Hepatocellular Carcinoma After Hepatectomy
    Frontiers Media SA ; 2020
    In:  Frontiers in Oncology Vol. 10 ( 2020-9-2)
    Details
    In: Frontiers in Oncology, Frontiers Media SA, Vol. 10 ( 2020-9-2)
    Type of Medium: Online Resource
    ISSN: 2234-943X
    URL: Article
    DOI: 10.3389/fonc.2020.01754
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2020
    detail.hit.zdb_id: 2649216-7
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  • 7
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    Frontiers Media SA ; 2022
    In:  Frontiers in Oncology Vol. 12 ( 2022-11-17)
    Details
    In: Frontiers in Oncology, Frontiers Media SA, Vol. 12 ( 2022-11-17)
    Abstract: Characterization of gene mutation profiles can provide new treatment options for patients with diffuse large B-cell lymphoma (DLBCL). However, this method is challenged by the limited source of tissue specimens, especially those of DLBCL patients at advanced stages. Therefore, in the current study, we aimed to describe the gene mutation landscape of DLBCL using circulating tumor DNA (ctDNA) samples obtained from patients’ blood samples, as well as to explore the relationship between ctDNA mutations and the prognosis and treatment response of patients with newly diagnosed DLBCL. Methods A total of 169 newly diagnosed Chinese DLBCL patients were included in this study, among which 85 patients were divided into a training set and 84 were assigned into a validation set. The mutation profile of a 59-gene panel was analyzed by targeted next generation sequencing (NGS) of the patients’ ctDNA samples. Differences in clinical factors between patients with and without ctDNA mutations were analyzed. In addition, we also explored gene mutation frequencies between GCB and non-GCB subtypes, and the relationship between gene mutation status, clinical factors, mean VAF (variant allele frequencies) and the patients’ overall survival (OS) and progression-free survival (PFS). Results ctDNA mutations were detected in 64 (75.3%) patients of the training set and 67 (79.8%) patients of the validation set. The most commonly mutated genes in both sets were PCLO , PIM1 , MYD88 , TP53 , KMT2D , CD79B , HIST1H1E and LRP1B , with mutation frequencies of & gt;10%. Patients with detectable ctDNA mutations trended to present advanced Ann Arbor stages (III-IV), elevated LDH (lactate dehydrogenase) levels, shorter OS and PFS, and a lower complete response (CR) rate to the R-CHOP regimen compared with DLBCL patients without ctDNA mutations. In addition, mean VAF (≥4.94%) and PCLO mutations were associated with poor OS and PFS. Conclusion We investigated the ctDNA mutation landscape in Chinese patients with newly diagnosed DLBCL and found that ctDNA could reflect tumor burden and patients with detectable ctDNA mutations trended to have shorter OS and PFS and a lower CR rate.
    Type of Medium: Online Resource
    ISSN: 2234-943X
    URL: Article
    URL: Article
    URL: Article
    DOI: 10.3389/fonc.2022.1003957
    DOI: 10.3389/fonc.2022.1003957.s001
    DOI: 10.3389/fonc.2022.1003957.s002
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2649216-7
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  • 8
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    Table_1.docx
    Frontiers Media SA ; 2023
    In:  Frontiers in Oncology Vol. 13 ( 2023-3-10)
    Details
    In: Frontiers in Oncology, Frontiers Media SA, Vol. 13 ( 2023-3-10)
    Abstract: Precise risk stratification is increasingly essential in the management of multiple myeloma (MM) as some standard-risk (SR) patients still exhibit similar poor outcomes as genetically high-risk (GHR) patients in the era of novel agents. It has recently been demonstrated that functional high-risk (FHR) patients, those with suboptimal response to first-line induction therapy or early relapse within 12 months, have identifiable molecular characteristics from the SR group in the CoMMpass dataset. However, these findings lack practical validation in the real world. Methods MM cells purified by CD138 microbeads from newly diagnosed MM (NDMM) patients received fluorescence in situ hybridization and sequencing with a 92-gene Panel. Cytogenetic abnormalities defined GHR patients with t(4;14) or t(14;16) or complete loss of functional P53 or 1q21 gain and International Staging System (ISS) stage 3. SR group was patients who did not fulfill any criteria for GHR or FHR. Results There were 145 patients with NDMM, 78 in the SR group, 56 in the GHR group, and 11 in the FHR group. In the FHR group, eight patients were suboptimal responses to induction therapy, and three relapsed within 12 months. We found that male patients, patients with extra-medullary plasmacytoma (EMD), circulating clonal plasma cells (CPC) ≥0.05%, and P53 mono-allelic inactivation were significantly higher in the FHR group compared to the SR group. After a median follow-up of 21.0 months, the median progression-free survival (PFS) and overall survival (OS) were 5.0 months, 19.1 months and 36.6 months in the FHR, GHR, and SR groups, respectively. Compared to the SR group, FHR patients had a higher frequency of mutations in MKI67 , ERN1 , and EML4 . GO analysis showed that mutations in FHR were enriched for oxidative stress, chromosomal segregation, and hypoxia tolerance. Conclusion The FHR found in the SR NDMM patient group has unique clinical features, including being male, with EMD and CPC, and genetic characteristics of mutations affecting oxidative stress, chromosome segregation, and hypoxia tolerance. In contrast to previous reports, our data suggested that patients with P53 mono-allelic inactivation should be classified in the GHR group rather than the FHR group.
    Type of Medium: Online Resource
    ISSN: 2234-943X
    URL: Article
    URL: Article
    URL: Article
    URL: Article
    URL: Article
    DOI: 10.3389/fonc.2023.1110693
    DOI: 10.3389/fonc.2023.1110693.s001
    DOI: 10.3389/fonc.2023.1110693.s002
    DOI: 10.3389/fonc.2023.1110693.s003
    DOI: 10.3389/fonc.2023.1110693.s004
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2023
    detail.hit.zdb_id: 2649216-7
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  • 9
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    Table_1.docx
    Frontiers Media SA ; 2024
    In:  Frontiers in Endocrinology Vol. 15 ( 2024-4-8)
    Details
    In: Frontiers in Endocrinology, Frontiers Media SA, Vol. 15 ( 2024-4-8)
    Abstract: This study aimed to quantify the severity of metabolic syndrome(MetS) and investigate its association with cardiovascular disease(CVD) risk on Chinese adults. Methods 13,500 participants from the Zhejiang Adult Chronic Disease Study were followed up between 2010 and 2021. A continuous MetS severity score derived from the five components of MetS was used to quantify MetS severity, and the association between MetS severity and the risk of incident CVD was assessed using Cox proportional hazard and restricted cubic spline regression. Results Both the presence and severity of MetS were strongly associated with CVD risk. MetS was related to an increased risk of CVD (hazard ratio(HR):1.700, 95% confidence interval(CI): 1.380–2.094). Compared with the hazard ratio for CVD in the lowest quartile of the MetS severity score, that in the second, third, and highest quartiles were 1.812 (1.329–2.470), 1.746 (1.265–2.410), and 2.817 (2.015–3.938), respectively. A linear and positive dose-response relationship was observed between the MetS severity and CVD risk ( P for non-linearity = 0.437). Similar results were found in various sensitivity analyses. Conclusion The MetS severity score was significantly associated with CVD risk. Assessing MetS severity and further ensuring intervention measures according to the different severities of MetS may be more useful in preventing CVD.
    Type of Medium: Online Resource
    ISSN: 1664-2392
    URL: Article
    URL: Article
    DOI: 10.3389/fendo.2024.1341546
    DOI: 10.3389/fendo.2024.1341546.s001
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2024
    detail.hit.zdb_id: 2592084-4
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  • 10
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    Data_Sheet_1.PDF
    Frontiers Media SA ; 2022
    In:  Frontiers in Cardiovascular Medicine Vol. 9 ( 2022-3-8)
    Details
    In: Frontiers in Cardiovascular Medicine, Frontiers Media SA, Vol. 9 ( 2022-3-8)
    Abstract: Endoplasmic Reticulum (ER) stress and oxidative stress have been highly implicated in the pathogenesis of cardiac hypertrophy and heart failure (HF). However, the mechanisms involved in the interplay between these processes in the heart are not fully understood. The present study sought to determine a causative link between Pak2-dependent UPR activation and oxidative stress via Nrf2 regulation under pathological ER stress. We report that sustained ER stress and Pak2 deletion in cardiomyocytes enhance Nrf2 expression. Conversely, AAV9 mediated Pak2 delivery in the heart leads to a significant decrease in Nrf2 levels. Pak2 overexpression enhances the XBP1-Hrd1 UPR axis and ameliorates tunicamycin induced cardiac apoptosis and dysfunction in mice. We found that Pak2 deletion and altered proteostasis render Nrf2 detrimental by switching from its antioxidant role to renin-angiotensin aldosterone system (RAAS) gene regulator. Mechanistically, Pak2 mediated Hrd1 expression targets Nrf2 for ubiquitination and degradation thus preventing its aberrant activation. Moreover, we find a significant increase in Nrf2 with a decrease in Pak2 in human myocardium of dilated heart disease. Using human-induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs), we find that Pak2 is able to ameliorate Nrf2 induced RAAS activation under ER stress. These findings demonstrate that Pak2 is a novel Nrf2 regulator in the stressed heart. Activation of XBP1-Hrd1 is attributed to prevent ER stress-induced Nrf2 RAAS component upregulation. This mechanism explains the functional dichotomy of Nrf2 in the stressed heart. Thus, Pak2 regulation of Nrf2 homeostasis may present as a potential therapeutic route to alleviate detrimental ER stress and heart failure.
    Type of Medium: Online Resource
    ISSN: 2297-055X
    URL: Article
    URL: Article
    DOI: 10.3389/fcvm.2022.851419
    DOI: 10.3389/fcvm.2022.851419.s001
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2781496-8
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