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  • Frontiers Media SA  (107)
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  • Frontiers Media SA  (107)
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  • 1
    In: Frontiers in Immunology, Frontiers Media SA, Vol. 12 ( 2021-5-5)
    Abstract: Hyperforin is a major active constituent of Hypericum perforatum  L. extract, which is widely used for the treatment of depressive disorders. Recent studies have reported that hyperforin reduced inflammation in stroke and suppressed proliferation and differentiation in keratinocytes. Psoriasis is a chronic immune-mediated inflammatory skin disease in which the IL-23/IL-17 axis plays an important role. To investigate the underlying inflammatory mechanisms and response of hyperforin in psoriasis, we use imiquimod (IMQ)-induced mice model, in vitro cultured murine splenic γδ T cells, and HaCaT cells in this study. Data showed that hyperforin reduced epidermal thickness and decreased IMQ-induced pathological scores of cutaneous skin lesions in mice. Meanwhile we proved that hyperforin suppressed infiltration of CD3 + T cells and downregulated expression of Il1 , Il6 , Il23 , Il17a , Il22 , antimicrobial peptides (AMPs) in the skin lesion. Hyperforin significantly inhibited imiquimod-induced splenomegaly, reduced serum levels of TNF-α and IL-6, and IL-17A in splenocytes and draining lymph nodes. Our study also suggested that hyperforin lessened the infiltration of γδ T cell and CCR6 + γδ T cells in spleen and lymph nodes. Hyperforin also suppressed the typical psoriasis-like inflammatory responses and the infiltration of IL-17A + cells in dermal γδ T cells of IMQ treated Tcrd −/− mice transferred with γδ T cells. In vitro studies, hyperforin reduced the expression and secretion of IL-17A in γδ T cells, and suppressed the activation of MAPK/STAT3 pathways in human keratinocyte HaCaT cells and γδ T cells. In conclusion, hyperforin alleviates IMQ-induced inflammation in psoriasis through suppressing the immune responses exerted by IL-17 A-producing γδ T cells and related cytokines by modulating MAPK/STAT3 pathways. Our study provided a novel therapeutic tragedy for psoriasis by which hyperforin attenuates psoriasis-related inflammatory responses.
    Type of Medium: Online Resource
    ISSN: 1664-3224
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2021
    detail.hit.zdb_id: 2606827-8
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  • 2
    Online Resource
    Online Resource
    Frontiers Media SA ; 2022
    In:  Pathology and Oncology Research Vol. 28 ( 2022-6-27)
    In: Pathology and Oncology Research, Frontiers Media SA, Vol. 28 ( 2022-6-27)
    Abstract: Acute myeloid leukemia (AML) represents an aggressive hematopoietic malignancy with a prognosis inferior to that of other leukemias. Recent targeted therapies offer new opportunities to achieve better treatment outcomes. However, due to the complex heterogeneity of AML, its prognosis remains dismal. In this study, we first identified the correlation between high expression of BRD4 and overall survival of patients with AML. Targeted degradation of BRD2, BRD3, and BRD4 proteins by dBET1, a proteolysis-targeting chimera (PROTAC) against the bromodomain and extra-terminal domain (BET) family members, showed cytotoxic effects on Kasumi (AML1-ETO), NB4 (PML-RARa), THP-1 (MLL-AF9), and MV4-11 (MLL-AF4) AML cell lines representing different molecular subtypes of AML. Furthermore, we determined that dBET1 treatment arrested cell cycling and enhanced apoptosis and c-MYC was identified as the downstream target. Collectively, our results indicated that dBET1 had broad anti-cancer effects on AML cell lines with different molecular lesions and provided more benefits to patients with AML.
    Type of Medium: Online Resource
    ISSN: 1532-2807
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2002501-4
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  • 3
    Online Resource
    Online Resource
    Frontiers Media SA ; 2022
    In:  Frontiers in Plant Science Vol. 13 ( 2022-9-6)
    In: Frontiers in Plant Science, Frontiers Media SA, Vol. 13 ( 2022-9-6)
    Abstract: Thinopyrum intermedium (JJJ s J s StSt, 2 n = 6 x = 42), a member of tertiary gene pool of hexaploid wheat ( Triticum aestivum L., AABBDD, 2 n = 6 x = 42), provides several beneficial genes for wheat improvement. In this study, line CH51 was developed from the BC 1 F 8 progeny of a partial wheat- Th. intermedium amphiploid TAI8335 (2 n = 56) and wheat cultivar (cv.) Jintai 170. Somatic metaphase chromosome counting showed that CH51 had stable 42 chromosomes. Genomic in situ hybridization (GISH) analysis showed that CH51 had 40 wheat chromosomes and two Th. intermedium chromosomes involving translocation between J s - and St-genome chromosomes. Non-denaturing fluorescence in situ hybridization (ND-FISH) analysis revealed that CH51 lacked a pair of wheat chromosome 6B. Wheat 55K SNP array analysis verified that chromosome 6B had the highest percentage of missing SNP loci in both CH51 and Chinese Spring (CS) nullisomic 6B-tetrasomic 6D (CS-N6BT6D) and had the highest percentage of polymorphic SNP loci between CH51 and cv. Jintai 170. We identified that CH51 was a wheat- Th. intermedium T6StS.6J s L (6B) disomic substitution line. Disease resistance assessment showed that CH51 exhibited high levels of resistance to the prevalent Chinese leaf rust and stripe rust races in the field. Therefore, the newly developed line CH51 can be utilized as a potential germplasm in wheat disease resistance breeding.
    Type of Medium: Online Resource
    ISSN: 1664-462X
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2687947-5
    detail.hit.zdb_id: 2613694-6
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  • 4
    In: Frontiers in Oncology, Frontiers Media SA, Vol. 13 ( 2023-9-22)
    Abstract: In early-stage epithelial ovarian cancer (EOC), how to perform lymphadenectomy to avoid stage migration and achieve reliable targeted excision has not been explored in depth. This study comprehensively considered the stage migration and survival to determine appropriate numbers of examined lymph node (ELN) for early-stage EOC and high-grade serous ovarian cancer (HGSOC). Methods From the Surveillance, Epidemiology, and End Results database, we obtained 10372 EOC cases with stage T1M0 and ELN ≥ 2, including 2849 HGSOC cases. Generalized linear models with multivariable adjustment were used to analyze associations between ELN numbers and lymph node stage migration, survival and positive lymph node (PLN). LOESS regression characterized dynamic trends of above associations followed by Chow test to determine structural breakpoints of ELN numbers. Survival curves were plotted using Kaplan-Meier method. Results More ELNs were associated with more node-positive diseases, more PLNs and better prognosis. ELN structural breakpoints were different in subgroups of early-stage EOC, which for node stage migration or PLN were more than those for improving outcomes. The meaning of ELN structural breakpoint varied with its location and the morphology of LOESS curve. To avoid stage migration, the optimal ELN for early-stage EOC was 29 and the minimal ELN for HGSOC was 24. For better survival, appropriate ELN number were 13 and 8 respectively. More ELNs explained better prognosis only at a certain range. Discussion Neither too many nor too few numbers of ELN were ideal for early-stage EOC and HGSOC. Excision with appropriate numbers of lymph node draining the affected ovary may be more reasonable than traditional sentinel lymph node resection and systematic lymphadenectomy.
    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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  • 5
    Online Resource
    Online Resource
    Frontiers Media SA ; 2022
    In:  Frontiers in Plant Science Vol. 13 ( 2022-9-9)
    In: Frontiers in Plant Science, Frontiers Media SA, Vol. 13 ( 2022-9-9)
    Abstract: Leaf color is one of the most important features for plants used for landscape and ornamental purposes. However, the regulatory mechanism of yellow leaf coloration still remains elusive in many plant species. To understand the complex genetic mechanism of yellow-leaf Forsythia , we first compared the pigment content and leaf anatomical structure of yellow-leaf and green-leaf accessions derived from a hybrid population. The physiological and cytological analyses demonstrated that yellow-leaf progenies were chlorophyll deficient with defected chloroplast structure. With comparative transcriptome analysis, we identified a number of candidate genes differentially expressed between yellow-leaf and green-leaf Forsythia plants. Among these genes, we further screened out two candidates, ChlH (magnesium chelatase Subunit H) and POLGAMMA2 (POLYMERASE GAMMA 2), with consistent relative-expression pattern between different colored plants. To verify the gene function, we performed virus-induced gene silencing assays and observed yellow-leaf phenotype with total chlorophyll content reduced by approximately 66 and 83% in ChlH -silenced and POLGAMMA2- silenced plants, respectively. We also observed defected chloroplast structure in both ChlH -silenced and POLGAMMA2- silenced Forsythia . Transient over-expression of ChlH and POLGAMMA2 led to increased chlorophyll content and restored thylakoid architecture in yellow-leaf Forsythia . With transcriptome sequencing, we detected a number of genes related to chlorophyll biosynthesis and chloroplast development that were responsive to the silencing of ChlH and POLGAMMA2 . To summarize, ChlH and POLGAMMA2 are two key genes that possibly related to yellow-leaf coloration in Forsythia through modulating chlorophyll synthesis and chloroplast ultrastructure. Our study provided insights into the molecular aspects of yellow-leaf Forsythia and expanded the knowledge of foliage color regulation in woody ornamental plants.
    Type of Medium: Online Resource
    ISSN: 1664-462X
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2687947-5
    detail.hit.zdb_id: 2613694-6
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  • 6
    Online Resource
    Online Resource
    Frontiers Media SA ; 2015
    In:  Frontiers in Human Neuroscience Vol. 9 ( 2015-04-16)
    In: Frontiers in Human Neuroscience, Frontiers Media SA, Vol. 9 ( 2015-04-16)
    Type of Medium: Online Resource
    ISSN: 1662-5161
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2015
    detail.hit.zdb_id: 2425477-0
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  • 7
    Online Resource
    Online Resource
    Frontiers Media SA ; 2022
    In:  Frontiers in Physiology Vol. 13 ( 2022-3-14)
    In: Frontiers in Physiology, Frontiers Media SA, Vol. 13 ( 2022-3-14)
    Abstract: In amyotrophic lateral sclerosis (ALS), progressive weakness significantly limits the ability to exercise. However, measurements of the impaired exercise function and their practical value to assess disease progression in ALS are scarce. Cardiopulmonary exercise testing (CPET) is a non-invasive accurate method used to comprehensively quantify exercise physiology in a variety of diseases. This study aimed to evaluate the clinical value of CPET and to explore its association with disease severity and prognosis prediction in ALS. Methods A total of 319 participants were enrolled in this 3-year prospective study. After strict quality control, 109 patients with ALS and 150 age- and sex-matched healthy controls were included with comprehensive clinical assessment and follow-ups. The incremental ramp protocol for symptom-limited CPET was applied in both groups. The exercise physiology during peak effort exercise was systematically measured, including the overall aerobic capacity of exercise (VO 2 peak) and the respective capacity of the exercise-involved organs [cardiac response (heart rate peak—HR peak), ventilatory efficiency (VE/VCO 2 slope), breathing economy (VE/VO 2 peak), and other relevant parameters]. Disease severity and progression were evaluated using recognized scales. Survival was monitored with regular follow-ups every 6 months. Results Decreased exercise capacity (VO 2 peak & lt; 16 ml/kg/min) occurred more frequently in patients with ALS than in controls (44.95% vs. 9.33%, p & lt; 0.01). In patients with ALS, the average VO 2 peak (16.16 ± 5.43 ml/kg/min) and HR peak [135 (112–153) bpm] were significantly lower ( p & lt; 0.01) than in controls [22.26 ± 7.09 ml/kg/min; 148 (135–164) bpm], but the VE/VCO 2 slope was significantly higher [28.05 (25.03–32.16) vs. 26.72 (24.37–29.58); p = 0.03]. In patients with ALS, the VO 2 peak and HR peak were significantly correlated with disease severity and progression scores ( p & lt; 0.05). Survival analyses revealed the VO 2 peak and HR peak as protective indicators while the VE/VO 2 peak as a detrimental indicator for the prognostic prediction in ALS (HR = 0.839, p = 0.001; HR = 0.967, p & lt; 0.001; HR = 1.137, p = 0.028, respectively). Conclusion Our prospective study quantified the significantly decreased exercise capacity in ALS through non-invasive CPET. The impaired VO 2 peak and HR peak closely correlated with disease severity and independently predicted a worse prognosis. Our findings identified the clinical value of CPET as an objective indicator of disease progression in ALS.
    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 ; 2022
    In:  Frontiers in Cardiovascular Medicine Vol. 9 ( 2022-7-7)
    In: Frontiers in Cardiovascular Medicine, Frontiers Media SA, Vol. 9 ( 2022-7-7)
    Abstract: Arterial stiffness forms the basis of cardiovascular diseases (CVD) and is also an independent predictor of CVD risk. Early detection and intervention of arterial stiffness are important for improving the global burden of CVD. Pulse wave velocity (PWV) is the gold standard for assessing arterial stiffness and the molecular mechanism of arterial stiffness remains to be studied. Extracellular matrix (ECM) remodeling is one of the major mechanisms of arterial stiffness. Partial quantitative changes of ECM proteins can be detected in plasma. Therefore, we examined the hypothesis that a discovery proteomic comparison of plasma proteins between high arterial stiffness (baPWV ≥ 1,400 cm/s) and normal arterial stiffness (baPWV & lt; 1,400 cm/s) populations might identify relevant changed ECM proteins for arterial stiffness. Plasma samples were randomly selected from normal arterial stiffness ( n = 6) and high arterial stiffness ( n = 6) people. Isobaric tags for relative and absolute quantitation (iTRAQ) based quantitative proteomics technique was performed to find a total of 169 differentially expressed proteins (DEPs). Nine ECM proteins were included in all DEPs and were all up-regulated proteins. Fibulin-1 had the highest statistically fold-change (FC = 3.7, p & lt; 0.0001) in the high arterial stiffness population compared with the control group during the nine ECM proteins. The expression of plasma fibulin-1 in normal arterial stiffness ( n = 112) and high arterial stiffness ( n = 72) populations was confirmed through enzyme-linked immunosorbent assay (ELISA). Similarly, ELISA results showed that plasma concentrations of fibulin-1 in the high arterial stiffness group were higher than those in the normal arterial stiffness group (12.69 ± 0.89 vs. 9.84 ± 0.71 μg/ml, p & lt; 0.05). Univariate analysis of fibulin-1 with brachial-ankle pulse wave velocity (baPWV) indicated that fibulin-1 was positively correlated with baPWV in all participants ( r = 0.32, p & lt; 0.01) and a stronger positive correlation between baPWV and fibulin-1 in high arterial stiffness group ( r = 0.64, p & lt; 0.0001) was found. Multiple regression analysis of factors affecting baPWV showed that fibulin-1 was also a significant determinant of the increased ba-PWV ( R 2 = 0.635, p = 0.001). Partial correlation analysis showed that baPWV increased with the growth of plasma fibulin-1( r = 0.267, p & lt; 0.001). In conclusion, our results demonstrated that fibulin-1 is positively correlated with ba-PWV and an independent risk factor for arterial stiffness.
    Type of Medium: Online Resource
    ISSN: 2297-055X
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2781496-8
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  • 9
    Online Resource
    Online Resource
    Frontiers Media SA ; 2022
    In:  Frontiers in Cardiovascular Medicine Vol. 8 ( 2022-1-21)
    In: Frontiers in Cardiovascular Medicine, Frontiers Media SA, Vol. 8 ( 2022-1-21)
    Abstract: Telomere shortening, an indicator of aging, is associated with age-related diseases. This study aims to investigate the association between leukocyte telomere length (LTL) and thin-capped fibroatheromata (TCFA) and the impact of using LTL cutoff to determine the incidence of major adverse cardiovascular events (MACEs) in patients with angiographically intermediate coronary lesions. Methods This was a signal-center retrospective study focusing on patients who underwent coronary angiography and optical coherence tomography (OCT). The degree of coronary stenosis was assessed by angiography. The presence of TCFA was determined by OCT imaging. A total of 156 patients with angiographically intermediate coronary lesions were enrolled. Results Leukocyte telomere lengths were significantly shorter in the TCFA group compared with non-TCFA group [11.95 (10.56, 15.21) kb vs. 13.81 (12.06, 16.11) kb, p = 0.003]. The short-LTL group and long-LTL group were divided according to the optimal cut-off value which was determined by the receiver operating characteristic (ROC) curve analysis. Logistic regression model revealed that short-LTL was independently associated with TCFA incidence (odds ratio [ OR ] 4.387, 95% CI : 1.902–10.120, p = 0.001) after adjusting for confounding factors. Over a 24-months follow-up, the MACE incidence among patients with short-LTL was significantly higher than those in the long-LTL group (12.5 vs. 2.0%, p = 0.006 by log-rank test). Multivariable cox regression analysis indicated that short-LTL (hazard ratio [ HR ] 9.716, 95% CI : 1.995–47.319, p = 0.005) was an independent prognostic factor of MACE incidence in angiographically intermediate coronary lesions patients. Conclusions Short-LTL was independently associated with the incidence of TCFA and may serve as a prognostic factor for MACE risk on top of conventional risk factors.
    Type of Medium: Online Resource
    ISSN: 2297-055X
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2781496-8
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  • 10
    Online Resource
    Online Resource
    Frontiers Media SA ; 2022
    In:  Frontiers in Cell and Developmental Biology Vol. 10 ( 2022-5-30)
    In: Frontiers in Cell and Developmental Biology, Frontiers Media SA, Vol. 10 ( 2022-5-30)
    Abstract: Tissue expansion is a commonly performed therapy to grow extra skin in vivo for reconstruction. While mechanical stretch-induced epidermal changes have been extensively studied in rodents and cell culture, little is known about the mechanobiology of the human epidermis in vivo . Here, we employed single-cell RNA sequencing to interrogate the changes in the human epidermis during long-term tissue expansion therapy in clinical settings. We also verified the main findings at the protein level by immunofluorescence analysis of independent clinical samples. Our data show that the expanding human skin epidermis maintained a cellular composition and lineage trajectory that are similar to its non-expanding neighbor, suggesting the cellular heterogeneity of long-term expanded samples differs from the early response to the expansion. Also, a decrease in proliferative cells due to the decayed regenerative competency was detected. On the other hand, profound transcriptional changes are detected for epidermal stem cells in the expanding skin versus their non-expanding peers. These include significantly enriched signatures of C-FOS, EMT, and mTOR pathways and upregulation of AREG and SERPINB2 genes. CellChat associated ligand-receptor pairs and signaling pathways were revealed. Together, our data present a single-cell atlas of human epidermal changes in long-term tissue expansion therapy, suggesting that transcriptional change in epidermal stem cells is the major mechanism underlying long-term human skin expansion therapy. We also identified novel therapeutic targets to promote human skin expansion efficiency in the future.
    Type of Medium: Online Resource
    ISSN: 2296-634X
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2737824-X
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