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  • 2020-2024  (451)
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  • 2020-2024  (451)
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  • 2023  (451)
  • 1
    In: JAMA Network Open, American Medical Association (AMA), Vol. 6, No. 8 ( 2023-08-14), p. e2328828-
    Abstract: Ginkgo diterpene lactone meglumine (GDLM) has attracted much attention because of its potential neuroprotective properties in ischemic stroke. The efficacy of GDLM in patients with acute ischemic stroke (AIS) needs to be verified by well-designed randomized clinical trials. Objective To assess the efficacy and safety of GDLM in patients with AIS. Design, Setting, and Participants This multicenter, randomized, double-blind, placebo-controlled, parallel-group trial involved 3448 patients who had AIS, were aged 18 to 80 years, had a clinically diagnosed AIS symptom within 48 hours of onset, had a modified Rankin Scale (mRS) score of 0 or 1 prior to onset, and had a National Institutes of Health Stroke Scale score ranging from 4 to 24. The trial took place at 100 centers in China from February 1, 2016, to May 1, 2018. The mRS is a global stroke disability scale with scores ranging from 0 (no symptoms or completely recovered) to 6 (death). The National Institutes of Health Stroke Scale is a tool used by clinicians to quantify impairment caused by stroke (range, 0-42, with higher scores indicating greater severity). Data were analyzed from January 2019 to December 2022. Interventions Patients were randomized to receive GDLM or placebo once daily via intravenous infusion in a 1:1 ratio. The treatment was dispensed within 48 hours after symptoms and continued for 14 days. Interventions of thrombolysis and thrombectomy were not permitted during the treatment. Main Outcomes and Measures The primary outcome was the proportion of patients with an mRS of 0 or 1 on day 90 after randomization. Safety outcomes included adverse events and serious adverse events. Results A total of 3448 patients were randomized, with 1725 patients assigned to the GDLM group and 1723 patients assigned to the placebo group. The median (IQR) age of the patients was 63 (55-71) years, and 1232 (35.7%) were women. The primary outcome on day 90 occurred in 877 patients (50.8%) in the GDLM group, and 759 patients (44.1%) in the placebo group (risk difference, 6.79%; 95% CI, 3.46%-10.10%; odds ratio, 1.31; 95% CI, 1.15-1.50; relative risk, 1.15; 95% CI, 1.08-1.24; P   & amp;lt; .001). Adverse events occurred relatively equally between the 2 groups (303 [17.6%] vs 298 [17.3%] ; risk difference, 0.27%; 95% CI, −2.26% to 2.80%; odds ratio, 1.02; 95% CI, 0.85-1.21; relative risk, 1.02; 95% CI, 0.88-1.17; P  = .83). Conclusions and Relevance Among patients with AIS in this randomized clinical trial, GDLM improved the proportion of patients achieving favorable clinical outcomes at 90 days compared with placebo. Trial Registration ClinicalTrials.gov Identifier: NCT02526225
    Type of Medium: Online Resource
    ISSN: 2574-3805
    Language: English
    Publisher: American Medical Association (AMA)
    Publication Date: 2023
    detail.hit.zdb_id: 2931249-8
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  • 2
    Online Resource
    Online Resource
    Springer Science and Business Media LLC ; 2023
    In:  Journal of Translational Medicine Vol. 21, No. 1 ( 2023-12-04)
    In: Journal of Translational Medicine, Springer Science and Business Media LLC, Vol. 21, No. 1 ( 2023-12-04)
    Abstract: ND630 is believed to be a new therapy pharmacologic molecule in targeting the expression of ACACA and regulating the lipid metabolism. However, the function of ND630 in prostate cancer remains unknown. KIF18B, as an oncogene, plays a vital role in prostate cancer progression. circKIF18B_003 was derived from oncogene KIF18B and was markedly overexpressed in prostate cancer tissues. We speculated that oncoprotein KIF18B-derived circRNA circKIF18B_003 might have roles in prostate cancer promotion. The aim of this study was to validate whether ND630 could control ACACA and lipid reprogramming in prostate cancer by regulating the expression of circKIF18B_003. Methods RT-qPCR was used to analyze the expression of circKIF18B_003 in prostate cancer cell lines and prostate cancer samples. circKIF18B_003 expression was modulated in prostate cancer cells using circKIF18B_003 interference or overexpression plasmid. We examined the function and effects of circKIF18B_003 in prostate cancer cells using CCK-8, colony formation, wound healing, and Transwell invasion assays and xenograft models. Fluorescence in situ hybridization (FISH) was performed to evaluate the localization of circKIF18B_003. RNA immunoprecipitation (RIP), RNA pull down, and luciferase reporter assay were performed to explore the potential mechanism of circKIF18B_003. Results The function of ND630 was determined in this study. circKIF18B_003 was overexpressed in prostate cancer tissues, and overexpression of circKIF18B_003 was associated with poor survival outcome of prostate cancer patients. The proliferation, migration, and invasion of prostate cancer cells were enhanced after up-regulation of circKIF18B_003. circKIF18B_003 is mainly located in the cytoplasm of prostate cancer cells, and the RIP and RNA pull down assays confirmed that circKIF18B_003 could act as a sponge for miR-370-3p. Further study demonstrated that up-regulation of circKIF18B_003 increased the expression of ACACA by sponging miR-370-3p. The malignant ability of prostate cancer cells enhanced by overexpression of circKIF18B_003 was reversed by the down-regulation of ACACA. We found that overexpression of circKIF18B_003 was associated with lipid metabolism, and a combination of ND-630 and docetaxel markedly attenuated tumor growth. Conclusion ND630 could control ACACA and lipid reprogramming in prostate cancer by regulating the expression of circKIF18B_003. ND630 and circKIF18B_003 may represent a novel target for prostate cancer.
    Type of Medium: Online Resource
    ISSN: 1479-5876
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2023
    detail.hit.zdb_id: 2118570-0
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  • 3
    Online Resource
    Online Resource
    Frontiers Media SA ; 2023
    In:  Frontiers in Oncology Vol. 13 ( 2023-6-6)
    In: Frontiers in Oncology, Frontiers Media SA, Vol. 13 ( 2023-6-6)
    Abstract: Immunogenic cell death (ICD) plays a vital role in tumor progression and immune response. However, the integrative role of ICD-related genes and subtypes in the tumor microenvironment (TME) in prostate cancer (PCa) remains unknown. Materials and methods The sample data were obtained from The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), and Memorial Sloan Kettering Cancer Center (MSKCC) prostate cancer-related databases. We first divided the subtypes based on ICD genes from 901 PCa patients and then identified the prognosis- related genes (PRGs) between different ICD subtypes. Subsequently, all the patients were randomly split into the training and test groups. We developed a risk signature in the training set by least absolute shrinkage and selection operator (LASSO)–Cox regression. Following this, we verified this prognostic signature in both the training test and external test sets. The relationships between the different subgroups and clinical pathological characteristics, immune infiltration characteristics, and mutation status of the TME were examined. Finally, the artificial neural network (ANN) and fundamental experiment study were constructed to verify the accuracy of the prognostic signature. Results We identified two ICD clusters with immunological features and three gene clusters composed of PRGs. Additionally, we demonstrated that the risk signature can be used to evaluate tumor immune cell infiltration, prognostic status, and an immune checkpoint inhibitor. The low-risk group, which has a high overlap with group C of the gene cluster, is characterized by high ICD levels, immunocompetence, and favorable survival probability. Furthermore, the tumor progression genes selected by the ANN also exhibit potential associations with risk signature genes. Conclusion This study identified individuals with high ICD levels in prostate cancer who may have more abundant immune infiltration and revealed the potential effects of risk signature on the TME, immune checkpoint inhibitor, and prognosis of PCa.
    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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  • 4
    In: Separation and Purification Technology, Elsevier BV, Vol. 315 ( 2023-06), p. 123701-
    Type of Medium: Online Resource
    ISSN: 1383-5866
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2023
    detail.hit.zdb_id: 2022535-0
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  • 5
    In: Frontiers in Immunology, Frontiers Media SA, Vol. 14 ( 2023-9-11)
    Abstract: Hepatocellular carcinoma (HCC), the most common primary malignancy of the liver, is one of the leading causes of cancer-related death and is associated with a poor prognosis. The tumor microenvironment (TME) of HCC comprises immune, immunosuppressive, and interstitial cells with hypoxic, angiogenic, metabolic reprogramming, inflammatory, and immunosuppressive features. Exosomes are nanoscale extracellular vesicles that secrete biologically active signaling molecules such as deoxyribonucleic acid (DNA), messenger ribonucleic acid (mRNA), microribonucleic acid (miRNA), proteins, and lipids. These signaling molecules act as messengers in the tumor microenvironment, especially the tumor immunosuppressive microenvironment. Exosomal circRNAs reshape the tumor microenvironment by prompting hypoxic stress response, stimulating angiogenesis, contributing to metabolic reprogramming, facilitating inflammatory changes in the HCC cells and inducing tumor immunosuppression. The exosomes secreted by HCC cells carry circRNA into immune cells, which intervene in the activation of immune cells and promote the overexpression of immune checkpoints to regulate immune response, leading tumor cells to acquire immunosuppressive properties. Furthermore, immunosuppression is the final result of a combination of TME-related factors, including hypoxia, angiogenesis, metabolic reprogramming, and inflammation changes. In conclusion, exosomal circRNA accelerates the tumor progression by adjusting the phenotype of the tumor microenvironment and ultimately forming an immunosuppressive microenvironment. HCC-derived exosomal circRNA can affect HCC cell proliferation, invasion, metastasis, and induction of chemoresistance. Therefore, this review aimed to summarize the composition and function of these exosomes, the role that HCC-derived exosomal circRNAs play in microenvironment formation, and the interactions between exosomes and immune cells. This review outlines the role of exosomal circRNAs in the malignant phenotype of HCC and provides a preliminary exploration of the clinical utility of exosomal circRNAs.
    Type of Medium: Online Resource
    ISSN: 1664-3224
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2023
    detail.hit.zdb_id: 2606827-8
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  • 6
    In: JHEP Reports, Elsevier BV, ( 2023-10), p. 100926-
    Type of Medium: Online Resource
    ISSN: 2589-5559
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2023
    detail.hit.zdb_id: 2972660-8
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  • 7
    In: Human Brain Mapping, Wiley, Vol. 44, No. 6 ( 2023-04-15), p. 2365-2379
    Abstract: Functional changes of default mode network (DMN) have been proven to be closely associated with white matter hyperintensity (WMH) related cognitive impairment (CI). However, subsystem mechanisms of DMN underlying WMH‐related CI remain unclear. The present study recruited WMH patients ( n  = 206) with mild CI and normal cognition, as well as healthy controls (HC, n  = 102). Static/dynamic functional connectivity (FC) of the DMN's three subsystems were calculated using resting‐state functional MRI. K‐means clustering analyses were performed to extract distinct dynamic connectivity states. Compared with the WMH‐NC group, the WMH‐MCI group displayed lower static FC within medial temporal lobe (MTL) and core subsystem, between core‐MTL subsystem, as well as between core and dorsal medial prefrontal cortex subsystem. All these static alterations were positively associated with information processing speed (IPS). Regarding dynamic FC, the WMH‐MCI group exhibited higher dynamic FC within MTL subsystem than the HC and WMH‐NC groups. Altered dynamic FC within MTL subsystem mediated the relationship between WMH and memory span (indirect effect: −0.2251, 95% confidence interval [−0.6295, −0.0267]). Additionally, dynamic FCs of DMN subsystems could be clustered into two recurring states. For dynamic FCs within MTL subsystem, WMH‐MCI subjects exhibited longer mean dwell time (MDT) and higher reoccurrence fraction (RF) in a sparsely connected state (State 2). Altered MDT and RF in State 2 were negatively associated with IPS. Taken together, these findings indicated static/dynamic FC of DMN subsystems can provide relevant information on cognitive decline from different aspects, which provides a comprehensive view of subsystem mechanisms of DMN underlying WMH‐related CI.
    Type of Medium: Online Resource
    ISSN: 1065-9471 , 1097-0193
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2023
    detail.hit.zdb_id: 1492703-2
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  • 8
    Online Resource
    Online Resource
    Frontiers Media SA ; 2023
    In:  Frontiers in Microbiology Vol. 14 ( 2023-4-4)
    In: Frontiers in Microbiology, Frontiers Media SA, Vol. 14 ( 2023-4-4)
    Abstract: Anthracnose disease caused by Colletotrichum gloeosporioides is one of the devastating diseases of yams ( Dioscorea sp.) worldwide. In this study, we aimed to isolate endophytic actinobacteria from yam plants and to evaluate their potential for the control of yam anthracnose based on bioassays and genomic analyses. A total of 116 endophytic actinomycete strains were isolated from the surface-sterilized yam tissues from a yam orchard in Hainan Province, China. In total, 23 isolates showed antagonistic activity against C. gloeosporioides . An endophytic actinomycete, designated HNM0140 T , which exhibited strong antifungal activities, multiple biocontrol, and plant growth-promoting (PGP) traits was subsequently selected to colonize in the tissue-cultured seedlings of yam and was tested for its in vivo biocontrol potential on yam anthracnose. The results showed that treatment with strain HNM0140 T markedly reduced the severity and incidence of yam anthracnose under greenhouse conditions. Morphological and chemotaxonomic analyses showed that strain HNM0140 T was assigned to the genus Streptomyces . Phylogenetic analysis based on the 16S rRNA gene sequences indicated that strain HNM0140 T formed a separate cluster together with Streptomyces lydicus ATCC 25470 T (99.45%), Streptomyces chattanoogensis NRRL ISP-5002 T (99.45%), and Streptomyces kronopolitis NEAU-ML8 T (98.97%). The phylogenomic tree also showed that strain HNM0140 T stably clustered with Streptomyces lydicus ATCC 25470 T . The ANI and dDDH between strain HNM0140 T and its closest related-type species were well below the recommended thresholds for species demarcation. Hence, based on the phylogenetic, genomic, and phenotypic analyses, strain HNM0140 T should represent a new streptomycete species named Streptomyces endophytica sp. nov. Genomic analysis revealed that strain HNM0140 T harbored 18 putative BGCs for secondary metabolites, some PGP-related genes, and several genes coding for antifungal enzymes. The presented results indicated that strain HNM0140 T was a promising biocontrol agent for yam anthracnose.
    Type of Medium: Online Resource
    ISSN: 1664-302X
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2023
    detail.hit.zdb_id: 2587354-4
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  • 9
    In: Frontiers in Immunology, Frontiers Media SA, Vol. 14 ( 2023-3-27)
    Abstract: Cerebral sparganosis is a rare parasitic infection of the brain tissue. The remission of MRI change and clinical symptom has been used to evaluate the therapeutic effect. However, there is no study to correlate the serum IgG antibody level of sparganum to the prognosis of disease after treatment. Methods 87 patients with cerebral sparganosis were collected from three medical centers. Clinical symptoms and MRI changes were evaluated at 12 months after initial treatment, and serum IgG antibody level of sparganum was evaluated at 2, 6, and 12 months after treatment. The positive cut-off value was based on 2.1 times the optical density (OD) of negative control. The index value was defined as the sample OD divided by the cut-off value. Results Among the 87 patients after treatment, 71 patients had good clinical outcomes, and 16 had poor clinical outcomes. The area under the curve (AUC) showed that the index value measured at 12 months after treatment had the best prediction effect, with a value of 2.014. In the good-outcome group, the index values were less than 2.014 in all 71 patients, and only 8 patients had mildly enhanced residual lesions on MRI. In the poor-outcome group, the index values were more than 2.014 in all 16 patients, and all patients still showed significantly enhanced lesions on MRI. Compared with poor-outcome patients, only 2 patients with good outcomes had disease recurrence after treatment. Discussion This study provided evidence that the serum IgG antibody level of sparganum was a promising biomarker to evaluate the prognosis of patients with cerebral sparganosis after treatment.
    Type of Medium: Online Resource
    ISSN: 1664-3224
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2023
    detail.hit.zdb_id: 2606827-8
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  • 10
    Online Resource
    Online Resource
    Frontiers Media SA ; 2023
    In:  Frontiers in Aging Neuroscience Vol. 15 ( 2023-3-1)
    In: Frontiers in Aging Neuroscience, Frontiers Media SA, Vol. 15 ( 2023-3-1)
    Abstract: The mechanism of gait and balance dysfunction (GBD) in cerebral small vessel disease (CSVD) remains unclear. Evidence supports cognition engages in GBD of CSVD. The cerebellum is important in motor and cognition, while little is known about the influence of the cerebellum on GBD in CSVD. Methods This study is a retrospective cohort study. All participants of this study were enrolled from the CSVD individuals in Nanjing Drum Tower Hospital from 2017 to 2021. The GBD of CSVD patients was defined as Tinetti Test score ≤ 23. Cerebral cortical thickness, cerebellar gray matter volume, the amplitude of low-frequency fluctuation, functional connectivity, and modular interaction were calculated to determine the cortical atrophy and activity patterns of CSVD patients with GBD. The effect of cognitive domains during GBD in CSVD patients was explored by correlation analyses. Results A total of 25 CSVD patients were recruited in CSVD patients with GBD group (Tinetti Test score ≤ 23, mean age ± standard deviation: 70.000 ± 6.976 years), and 34 CSVD patients were recruited in CSVD patients without GBD group (Tinetti Test score & gt; 23, mean age ± standard deviation: 64.029 ± 9.453 years). CSVD patients with GBD displayed worse cognitive performance and cortical atrophy in the right cerebellum VIIIa and bilateral superior temporal gyrus than those without GBD. The right postcentral gyrus, left inferior temporal gyrus, right angular gyrus, right supramarginal gyrus and right middle frontal gyrus were functionally overactivated and showed decreased modular interaction with the right cerebellum. Tinetti Test scores were negatively related to the volume of the right cerebellum VIIIa in CSVD patients with GBD. Notably, memory, especially visuospatial memory, was greatly associated with GBD in CSVD. Conclusion The cortical atrophy and altered functional activity in sensorimotor area and ventral attention network in the cerebellum and cerebrum may underlying the GBD in CSVD. Memory might be critically cognitively responsible for GBD in CSVD.
    Type of Medium: Online Resource
    ISSN: 1663-4365
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2023
    detail.hit.zdb_id: 2558898-9
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