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  • Frontiers Media SA  (33)
  • 1
    Online Resource
    Online Resource
    Frontiers Media SA ; 2023
    In:  Frontiers in Oncology Vol. 12 ( 2023-1-4)
    In: Frontiers in Oncology, Frontiers Media SA, Vol. 12 ( 2023-1-4)
    Abstract: Tumor mutation burden (TMB) is a promising biomarker positively associated with the benefit of immunotherapy and that might predict the outcome of chemotherapy. We described the prognostic value of TMB in advanced gastric cancer and explored the underlying mechanism. Methods We enrolled 155 TMB-evaluated advanced gastric cancer patients and analyzed the relationship between clinicopathological characteristics and both overall survival (OS) and progression-free survival (PFS) among 40 patients treated with first-line chemotherapy. We further verified the distribution of TMB and analyzed the potential mechanism underlying the prognosis based on The Cancer Genome Atlas (TCGA) database. Results Among the 155 patients, 29 (18.7%) were TMB-high (TMB ≥ 10), roughly the same as the proportion in the TCGA data. Of the 40 patients receiving first-line chemotherapy, the median OS (7.9 vs . 12.1 months; HR 3.18; p = 0.0056) and PFS (4.4 vs . 6.2 months; HR 2.94; p = 0.0099) of the tissue-tested TMB (tTMB)-high patients were inferior to those of the tTMB-low patients. Similarly, unfavorable median OS (9.9 vs . 12.1 months; HR 2.11; p = 0.028) and PFS (5.3 vs . 6.5 months; HR 2.49; p = 0.0054) were shown in the blood-tested TMB (bTMB)-high than in the bTMB-low patients. The Cox analysis demonstrated that both tTMB-high and bTMB-high were significant independent predictors of dreadful OS and PFS. The differentially expressed genes (DEGs) according to TMB status were most significantly enriched in the downregulated metabolic pathway among the TMB-high patients. Conclusions TMB-high advanced gastric cancer patients accounted for around one-sixth and had a poorer prognosis than TMB-low patients when treated with first-line chemotherapy. The potential mechanism might be the downregulated metabolic activity in TMB-high patients.
    Type of Medium: Online Resource
    ISSN: 2234-943X
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2023
    detail.hit.zdb_id: 2649216-7
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  • 2
    In: Frontiers in Pharmacology, Frontiers Media SA, Vol. 13 ( 2022-3-24)
    Abstract: Extracellular vesicles (EVs) are lipid bilayer-delimited particles released by cells, which play an essential role in intercellular communication by delivering cellular components including DNA, RNA, lipids, metabolites, cytoplasm, and cell surface proteins into recipient cells. EVs play a vital role in the pathogenesis of depression by transporting miRNA and effector molecules such as BDNF, IL34. Considering that some herbal therapies exhibit antidepressant effects, EVs might be a practical delivery approach for herbal medicine. Since EVs can cross the blood-brain barrier (BBB), one of the advantages of EV-mediated herbal drug delivery for treating depression with Chinese herbal medicine (CHM) is that EVs can transfer herbal medicine into the brain cells. This review focuses on discussing the roles of EVs in the pathophysiology of depression and outlines the emerging application of EVs in delivering CHM for the treatment of depression.
    Type of Medium: Online Resource
    ISSN: 1663-9812
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2587355-6
    SSG: 15,3
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  • 3
    In: Frontiers in Bioengineering and Biotechnology, Frontiers Media SA, Vol. 11 ( 2023-5-2)
    Abstract: Background: Vogt-Koyanagi-Harada (VKH) disease is a common and easily blinded uveitis entity, with choroid being the main involved site. Classification of VKH disease and its different stages is crucial because they differ in clinical manifestations and therapeutic interventions. Wide-field swept-source optical coherence tomography angiography (WSS-OCTA) provides the advantages of non-invasiveness, large-field-of-view, high resolution, and ease of measuring and calculating choroid, offering the potential feasibility of simplified VKH classification assessment based on WSS-OCTA. Methods: 15 healthy controls (HC), 13 acute-phase and 17 convalescent-phase VKH patients were included, undertaken WSS-OCTA examination with a scanning field of 15 × 9 mm 2 . 20 WSS-OCTA parameters were then extracted from WSS-OCTA images. To classify HC and VKH patients in acute and convalescent phases, two 2-class VKH datasets (HC and VKH) and two 3-class VKH datasets (HC, acute-phase VKH, and convalescent-phase VKH) were established by the WSS-OCTA parameters alone or in combination with best-corrected visual acuity (logMAR BCVA) and intraocular pressure (IOP), respectively. A new feature selection and classification method that combines an equilibrium optimizer and a support vector machine (called SVM-EO) was adopted to select classification-sensitive parameters among the massive datasets and to achieve outstanding classification performance. The interpretability of the VKH classification models was demonstrated based on SHapley Additive exPlanations (SHAP). Results: Based on pure WSS-OCTA parameters, we achieved classification accuracies of 91.61% ± 12.17% and 86.69% ± 8.30% for 2- and 3-class VKH classification tasks. By combining the WSS-OCTA parameters and logMAR BCVA, we achieved better classification performance of 98.82% ± 2.63% and 96.16% ± 5.88%, respectively. Through SHAP analysis, we found that logMAR BCVA and vascular perfusion density (VPD) calculated from the whole field of view region in the choriocapillaris (whole FOV CC-VPD) were the most important features for VKH classification in our models. Conclusion: We achieved excellent VKH classification performance based on a non-invasive WSS-OCTA examination, which provides the possibility for future clinical VKH classification with high sensitivity and specificity.
    Type of Medium: Online Resource
    ISSN: 2296-4185
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2023
    detail.hit.zdb_id: 2719493-0
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  • 4
    In: Frontiers in Neurology, Frontiers Media SA, Vol. 14 ( 2023-6-1)
    Abstract: The aim of this large, prospective, double-blind randomized controlled trial is to investigate the effect of atorvastatin on the formation of collateral blood vessels in patients after encephaloduroarteriosynangiosis (EDAS) and to provide a theoretical basis for clinical drug intervention. Specifically, we will determine whether atorvastatin has an effect on the development of collateral vascularization and on cerebral blood perfusion after revasculoplasty in patients with moyamoya disease (MMD). Methods and analysis Overall, 180 patients with moyamoya disease will be recruited and randomly assigned to the atorvastatin treatment group or the placebo control group in a 1:1 ratio. Before revascularization surgery, magnetic resonance imaging (MRI) scanning and digital subangiography (DSA) examination will be routinely performed on the enrolled patients. All patients will receive intervention via EDAS. According to the randomization results, patients in the experimental group will be treated with atorvastatin (20 mg/day, once a day, for 8 weeks) and patients in the control group will be treated with placebo (20 mg/day, once a day, for 8 weeks). All participants will return to the hospital for MRI scan and DSA examination 6 months after EDAS surgery. The primary outcome of this trial will be the difference in the formation of collateral blood vessels revealed by DSA examination at 6 months after EDAS surgery between the two groups. The secondary outcome will be an improvement in the dynamic susceptibility contrast sequence cerebral perfusion on MRI at 6 months after EDAS, compared to the preoperative baseline. Ethics and dissemination This study was approved by the Ethics Committee of the First Medical Center of the PLA General Hospital. All participates will voluntary provide written informed consent before participating in the trial. Clinical trial registration ClinicalTrials.gov , ChiCTR2200064976.
    Type of Medium: Online Resource
    ISSN: 1664-2295
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2023
    detail.hit.zdb_id: 2564214-5
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  • 5
    In: Frontiers in Neurology, Frontiers Media SA, Vol. 13 ( 2022-4-26)
    Abstract: To explore the genetic basis and molecular mechanism of native arteriogenesis and therapeutic synangiosis in moyamoya disease (MMD). Methods An angiography-based study using patients from a prospective trial of encephaloduroarteriosynangiosis (EDAS) surgery was performed. The spontaneous collaterals grades were evaluated according to the system described by a new grading system. Blood samples were collected from all the recruited patients before EDAS and during the second hospitalization 3 months post-EDAS. We performed Boolean analysis using a combination of specific cell surface markers of CD34 bri CD133 + CD45 dim KDR + . Genotyping of p.R4810K was also performed. The correlation of age, sex, initial symptoms at diagnosis, collateral grade, Suzuki stages, the RNF213 genotype, time to peak (TTP), and endothelial progenitor cell (EPC) count with good collateral circulation was evaluated. Results Eighty-five patients with MMD were included in this study. The mutation rate of RNF213 p.R4810K in our study was 25.9% (22/85). The heterozygous mutations were occurred significantly more frequently in the cases that were presented with infarction, worse neurological status, severe posterior cerebral artery (PCA) stenosis, and longer TTP delay. Further, the heterozygous mutations occurred significantly more frequently in the poor collateral stage group. Lower grades were significantly correlated with severe ischemia symptoms, worse neurological status, and a longer TTP delay. The post-operative angiographic findings showed that a good Matsushima grade was correlated with heterozygous mutations, a lower collateral stage, and a longer TTP delay. The CD34 bri CD133 + CD45 dim KDR + cell count in patients 3 months post-EDAS was significantly higher as compared to the count before EDAS in the good Matsushima grade group. However, this change was not observed in the poor Matsushima grade group. Conclusions These data imply that mutations of RNF213 p.R4810K affect the establishment of spontaneous collateral circulation, and EPCs are involved in the process of formation of new EDAS collaterals.
    Type of Medium: Online Resource
    ISSN: 1664-2295
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2564214-5
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  • 6
    In: Frontiers in Neurology, Frontiers Media SA, Vol. 13 ( 2022-5-6)
    Abstract: To explore the long-term progression of neoangiogenesis after indirect revascularization for moyamoya disease (MMD). Methods We enrolled patients who were diagnosed with MMD and treated by encephaloduroarteriosynangiosis (EDAS) surgery at our center from December 2002 through September 2009. A comparative study between short-term (6–12 months) and long-term (duration ≥ 8 years) follow-up angiographies was performed. The development of collateral circulation through EDAS was graded according to the system described by the Matsushima grade system. Results A total of 78 patients who received indirect EDAS were enrolled in the study. The mean age at the first operation was 26.9 ± 15.0 years. The Matsushima grades of the same hemisphere were higher at the long-term follow-up compared with the short-term follow-up. Importantly, no attenuation was observed in any hemisphere during the long-term follow-up. In total, 51 hemispheres (32.7%) and 26 hemispheres (16.6%) had progression during the short-term and the long-term follow-up, respectively. The ipsilateral Suzuki stage showed a significant negative correlation with progression pace. Furthermore, higher Suzuki stages were significantly correlated with the postsurgical Matsushima grade at both time points. A total of nine strokes (11.5%) occurred in 78 patients was reported at the long-term follow-up. The annual incidence rate of recurrent strokes was higher for the stage progression group than for the stable group. Conclusion For patients with MMD, postsurgical neoangiogenesis after indirect bypass continuously improved with time. The short-term progression of the internal carotid artery (ICA) might be attributed to cerebral revascularization, while the long-term progression should be attributed to the natural progression of the disease.
    Type of Medium: Online Resource
    ISSN: 1664-2295
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2564214-5
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  • 7
    In: Frontiers in Physiology, Frontiers Media SA, Vol. 13 ( 2022-11-9)
    Abstract: Basolateral potassium channels in the distal convoluted tubule (DCT) are composed of inwardly-rectifying potassium channel 4.1 (Kir4.1) and Kir5.1. Kir4.1 interacts with Kir5.1 to form a 40 pS K + channel which is the only type K + channel expressed in the basolateral membrane of the DCT. Moreover, Kir4.1/Kir5.1 heterotetramer plays a key role in determining the expression and activity of thiazide-sensitive Na-Cl cotransport (NCC). In addition to Kir4.1/Kir5.1, Kir1.1 (ROMK) is expressed in the apical membrane of the late DCT (DCT2) and plays a key role in mediating epithelial Na + channel (ENaC)-dependent K + excretion. High dietary-K + -intake (HK) stimulates ROMK and inhibits Kir4.1/Kir5.1 in the DCT. Inhibition of Kir4.1/Kir5.1 is essential for HK-induced suppression of NCC whereas the stimulation of ROMK is important for increasing ENaC-dependent K + excretion during HK. We have now used the patch-clamp-technique to examine whether gender and Cl − content of K + -diet affect HK-induced inhibition of basolateral Kir4.1/Kir5.1 and HK-induced stimulation of ROMK. Single-channel-recording shows that basolateral 40 pS K + channel (Kir4.1/Kir5.1) activity of the DCT defined by NP o was 1.34 (1% KCl, normal K, NK), 0.95 (5% KCl) and 1.03 (5% K + -citrate) in male mice while it was 1.47, 1.02 and 1.05 in female mice. The whole-cell recording shows that Kir4.1/Kir5.1-mediated-K + current of the early-DCT (DCT1) was 1,170 pA (NK), 725 pA (5% KCl) and 700 pA (5% K + -citrate) in male mice whereas it was 1,125 pA, 674 pA and 700 pA in female mice. Moreover, K + -currents (I K ) reversal potential of DCT (an index of membrane potential) was -63 mV (NK), −49 mV (5% KCl) and −49 mV (5% K-citrate) in the male mice whereas it was -63 mV, −50 mV and −50 mV in female mice. Finally, TPNQ-sensitive whole-cell ROMK-currents in the DCT2 /initial-connecting tubule (CNT) were 910 pA (NK), 1,520 pA (5% KCl) and 1,540 pA (5% K + −citrate) in male mice whereas the ROMK-mediated K + currents were 1,005 pA, 1,590 pA and 1,570 pA in female mice. We conclude that the effect of HK intake on Kir4.1/Kir5.1 of the DCT and ROMK of DCT2/CNT is similar between male and female mice. Also, Cl − content in HK diets has no effect on HK-induced inhibition of Kir4.1/Kir5.1 of the DCT and HK-induced stimulation of ROMK in DCT2/CNT.
    Type of Medium: Online Resource
    ISSN: 1664-042X
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2564217-0
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  • 8
    Online Resource
    Online Resource
    Frontiers Media SA ; 2019
    In:  Frontiers in Pharmacology Vol. 9 ( 2019-1-14)
    In: Frontiers in Pharmacology, Frontiers Media SA, Vol. 9 ( 2019-1-14)
    Type of Medium: Online Resource
    ISSN: 1663-9812
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2019
    detail.hit.zdb_id: 2587355-6
    SSG: 15,3
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  • 9
    Online Resource
    Online Resource
    Frontiers Media SA ; 2019
    In:  Frontiers in Oncology Vol. 9 ( 2019-11-11)
    In: Frontiers in Oncology, Frontiers Media SA, Vol. 9 ( 2019-11-11)
    Type of Medium: Online Resource
    ISSN: 2234-943X
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2019
    detail.hit.zdb_id: 2649216-7
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  • 10
    Online Resource
    Online Resource
    Frontiers Media SA ; 2022
    In:  Frontiers in Genetics Vol. 13 ( 2022-5-20)
    In: Frontiers in Genetics, Frontiers Media SA, Vol. 13 ( 2022-5-20)
    Abstract: Non-obstructive azoospermia (NOA) is one of the most important causes of male infertility. Although many congenital factors have been identified, the aetiology in the majority of idiopathic NOA (iNOA) cases remains unknown. Herein, using single-cell RNA-Seq data sets (GSE149512) from the Gene Expression Omnibus (GEO) database, we constructed transcriptional regulatory networks (TRNs) to explain the mutual regulatory relationship and the causal relationship between transcription factors (TFs). We defined 10 testicular cell types by their marker genes and found that the proportion of Leydig cells (LCs) and macrophages (tMΦ) was significantly increased in iNOA testis. We identified specific TFs including LHX9, KLF8, KLF4, ARID5B and RXRG in iNOA LCs. In addition, we found specific TFs in iNOA tMΦ such as POU2F2, SPIB IRF5, CEBPA, ELK4 and KLF6. All these identified TFs are strongly engaged in cellular fate, function and homeostasis of the microenvironment. Changes in the activity of the above-mentioned TFs might affect the function of LCs and tMΦ and ultimately cause spermatogenesis failure. This study illustrate that these TFs play important regulatory roles in the occurrence and development of NOA.
    Type of Medium: Online Resource
    ISSN: 1664-8021
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2606823-0
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