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  • 1
    In: Progress in Natural Science, Elsevier BV, Vol. 19, No. 10 ( 2009-10), p. 1261-1269
    Type of Medium: Online Resource
    ISSN: 1002-0071
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2009
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    detail.hit.zdb_id: 2094449-4
    SSG: 11
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  • 2
    In: Antioxidants, MDPI AG, Vol. 11, No. 1 ( 2021-12-28), p. 66-
    Abstract: Denervated muscle atrophy is a common clinical disease that has no effective treatments. Our previous studies have found that oxidative stress and inflammation play an important role in the process of denervated muscle atrophy. Extracellular vesicles derived from skin precursor-derived Schwann cells (SKP-SC-EVs) contain a large amount of antioxidants and anti-inflammatory factors. This study explored whether SKP-SC-EVs alleviate denervated muscle atrophy by inhibiting oxidative stress and inflammation. In vitro studies have found that SKP-SC-EVs can be internalized and caught by myoblasts to promote the proliferation and differentiation of myoblasts. Nutrient deprivation can cause myotube atrophy, accompanied by oxidative stress and inflammation. However, SKP-SC-EVs can inhibit oxidative stress and inflammation caused by nutritional deprivation and subsequently relieve myotube atrophy. Moreover, there is a remarkable dose-effect relationship. In vivo studies have found that SKP-SC-EVs can significantly inhibit a denervation-induced decrease in the wet weight ratio and myofiber cross-sectional area of target muscles. Furthermore, SKP-SC-EVs can dramatically inhibit highly expressed Muscle RING Finger 1 and Muscle Atrophy F-box in target muscles under denervation and reduce the degradation of the myotube heavy chain. SKP-SC-EVs may reduce mitochondrial vacuolar degeneration and autophagy in denervated muscles by inhibiting autophagy-related proteins (i.e., PINK1, BNIP3, LC3B, and ATG7). Moreover, SKP-SC-EVs may improve microvessels and blood perfusion in denervated skeletal muscles by enhancing the proliferation of vascular endothelial cells. SKP-SC-EVs can also significantly inhibit the production of reactive oxygen species (ROS) in target muscles after denervation, which indicates that SKP-SC-EVs elicit their role by upregulating Nrf2 and downregulating ROS production-related factors (Nox2 and Nox4). In addition, SKP-SC-EVs can significantly reduce the levels of interleukin 1β, interleukin-6, and tumor necrosis factor α in target muscles. To conclude, SKP-SC-EVs may alleviate the decrease of target muscle blood perfusion and passivate the activities of ubiquitin-proteasome and autophagy-lysosome systems by inhibiting oxidative stress and inflammatory response, then reduce skeletal muscle atrophy caused by denervation. This study not only enriches the molecular regulation mechanism of denervated muscle atrophy, but also provides a scientific basis for SKP-SC-EVs as a protective drug to prevent and treat muscle atrophy.
    Type of Medium: Online Resource
    ISSN: 2076-3921
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
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    SSG: 15,3
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  • 3
    In: Molecular Cancer Research, American Association for Cancer Research (AACR), Vol. 11, No. 10 ( 2013-10-01), p. 1269-1278
    Abstract: Everolimus, an mTOR inhibitor, showed great clinical efficacy in combination with tamoxifen, letrozole, or exemestane for the treatment of estrogen receptor-positive (ER+) breast cancer. However, its antitumor activity was shown to be compromised by a compensatory process involving AKT activation. Here, it was determined whether combining an additional PI3K inhibitor can reverse this phenomenon and improve treatment efficacy. In breast cancer cells (MCF-7 and BT474), everolimus inhibited the mTOR downstream activity by limiting phosphorylation of p70S6K and 4EBP1, which resulted in p-Ser473-AKT activation. However, addition of a LY294002, a PI3K inhibitor, to tamoxifen and everolimus treatment improved the antitumor effect compared with tamoxifen alone or the other two agents in combination. Moreover, LY294002 suppressed the activity of the PI3K/AKT/mTOR axis and mitigated the p-Ser473-AKT activation feedback loop in both cell lines. Critically, this combination scheme also significantly inhibited the expression of HIF-1a, an angiogenesis marker, under hypoxic conditions and reduced blood vessel sprout formation in vitro. Finally, it was shown that the three-agent cocktail had the greatest efficacy in inhibiting MCF-7 xenograft tumor growth and angiogenesis. Taken together, these results suggest that inhibition of PI3K and mTOR may further improve therapy in ER+ breast cancer cells. Implications: Combinatorial inhibition of the PI3K/AKT/mTOR signaling axis may enhance endocrine-based therapy in breast cancer. Mol Cancer Res; 11(10); 1269–78. ©2013 AACR.
    Type of Medium: Online Resource
    ISSN: 1541-7786 , 1557-3125
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2013
    detail.hit.zdb_id: 2097884-4
    SSG: 12
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  • 4
    In: International Immunopharmacology, Elsevier BV, Vol. 3, No. 13-14 ( 2003-12), p. 1861-1871
    Type of Medium: Online Resource
    ISSN: 1567-5769
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2003
    detail.hit.zdb_id: 2049924-3
    SSG: 15,3
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  • 5
    In: BMC Cancer, Springer Science and Business Media LLC, Vol. 9, No. 1 ( 2009-12)
    Abstract: This study is a retrospective evaluation of the efficacy of neoadjuvant chemotherapy (NC) with a vinorelbine (V) and epirubicin (E) intravenous combination regimen and is aimed at identification of predictive markers for the long-term outcome in noninflammatory locally advanced breast cancer (NLABC). Methods One-hundred-and-nineteen patients with NLABC were identified from September 2001 to May 2006. Analysis was performed in March 2008, with a median follow-up of 63.4 months (range, 9-76 months). All patients were diagnosed with invasive breast cancer using 14 G core needle biopsy and treated with three cycles of VE before surgery. Local-regional radiotherapy was offered to all patients after the completion of chemotherapy followed by hormonal therapy according to hormone receptor status. Tissue sections cut from formalin-fixed paraffin-embedded blocks from biopsy specimens and postoperative tumor tissues were stained for the presence of estrogen receptor (ER), progesterone receptor (PgR), HER-2 (human epidermal growth factor receptor-2), and MIB-1(Ki-67). Results Patients characteristics were median age 52 years (range: 25-70 years); clinical TNM stage, stage IIB (n = 32), stage IIIA (n = 56), stage IIIB (n = 22) and stage IIIC (n = 9). All patients were evaluable for response: clinically complete response was documented in 27 patients (22.7%); 78 (65.6%) obtained partial response; stable disease was observed in 13 (10.9%); 1 patient (0.8%) had progressive disease. Pathological complete response was found in 22 cases (18.5%). Seventy-five patients were alive with no recurrence after a median follow-up of 63.4 months, the 5-year rates for disease-free survival and overall survival were 58.7% and 71.3%, respectively, after the start of NC. On multivariate analysis, the independent variables associated with increased risk of relapse and death were high pre-Ki-67(p = 0.012, p = 0.017, respectively), high post-Ki-67 expression (p = 0.045, p = 0.001, respectively), and non-pCR (p = 0.034, p = 0.027, respectively). A significantly increased risk of death was associated with lack of pre-ER expression (p = 0.002). Among patients with non-pCR, those with a pathological response at the tumor site with special involvement (i.e. skin, vessel and more than one quadrant) were at a higher risk of disease relapse and death (p 〈 0.001, p = 0.001, respectively). Conclusion This study suggests the promising use of a VE regimen as NC for Chinese NLABC after a median follow-up of 63.4 months. Pathological response in the tumor site, pre-Ki-67 and post-Ki-67 expression, and pre-ER expression were the important variables that predicted long-term outcome. Patients with pathological special involvement at the primary site after NC had the lowest survival rates.
    Type of Medium: Online Resource
    ISSN: 1471-2407
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2009
    detail.hit.zdb_id: 2041352-X
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  • 6
    In: Scientific Data, Springer Science and Business Media LLC, Vol. 10, No. 1 ( 2023-09-02)
    Abstract: Foundation models, often pre-trained with large-scale data, have achieved paramount success in jump-starting various vision and language applications. Recent advances further enable adapting foundation models in downstream tasks efficiently using only a few training samples, e.g., in-context learning. Yet, the application of such learning paradigms in medical image analysis remains scarce due to the shortage of publicly accessible data and benchmarks. In this paper, we aim at approaches adapting the foundation models for medical image classification and present a novel dataset and benchmark for the evaluation, i.e., examining the overall performance of accommodating the large-scale foundation models downstream on a set of diverse real-world clinical tasks. We collect five sets of medical imaging data from multiple institutes targeting a variety of real-world clinical tasks (22,349 images in total), i.e., thoracic diseases screening in X-rays, pathological lesion tissue screening, lesion detection in endoscopy images, neonatal jaundice evaluation, and diabetic retinopathy grading. Results of multiple baseline methods are demonstrated using the proposed dataset from both accuracy and cost-effective perspectives.
    Type of Medium: Online Resource
    ISSN: 2052-4463
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2023
    detail.hit.zdb_id: 2775191-0
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  • 7
    In: Biochemical Pharmacology, Elsevier BV, Vol. 172 ( 2020-02), p. 113732-
    Type of Medium: Online Resource
    ISSN: 0006-2952
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2020
    detail.hit.zdb_id: 1496199-4
    SSG: 15,3
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  • 8
    In: BMC Cancer, Springer Science and Business Media LLC, Vol. 20, No. 1 ( 2020-12)
    Abstract: Toremifene (TOR) is a selective oestrogen receptor modulator (SERM) and has comparable efficacy to that of tamoxifen (TAM) in breast cancer patients. Herein, we compared the safety of TOR to that of TAM in the adjuvant treatment of premenopausal breast cancer. Methods This was a prospective randomized and open-label clinical study. Premenopausal patients with hormonal receptor (HR)-positive early breast cancer were randomly assigned (1:1) to receive TOR) or TAM treatment. The follow-up period was 1 year. The primary end point was the incidence of ovarian cysts, and secondary end points were the incidence of endometrial thickening, changes in female hormones, the incidence of fatty liver, changes in the modified Kupperman index (mKMI) and changes in quality of life. Results There were 92 patients in the final analysis. The incidences of ovarian cysts were 42.6% in the TOR group and 51.1% in the TAM group ( p  = 0.441). Forty-one patients (87.2%) in the TOR group and 36 patients (80.0%) in the TAM group experienced endometrial thickening ( p  = 0.348). The proportions of patients with fatty liver were 31.9% in the TOR group and 26.7% in the TAM group ( p  = 0.581). No significant differences in the mKMI or quality of life were observed between the two groups. Conclusions TOR and TAM have similar side effects on the female genital system and quality of life in premenopausal early breast cancer patients. Trial registration ClinicalTrials.gov NCT02344940. Registered 26 January 2015 (retrospectively registered).
    Type of Medium: Online Resource
    ISSN: 1471-2407
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2020
    detail.hit.zdb_id: 2041352-X
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  • 9
    In: Atmosphere, MDPI AG, Vol. 14, No. 5 ( 2023-04-28), p. 805-
    Abstract: Mangrove ecosystems can be both significant sources and sinks of greenhouse gases. The restoration of mangrove forests is increasingly used as a natural climate solution tool to mitigate climate change. However, the estimates of carbon exchanges remain unclear, especially from restored mangroves. In this study, we observed the temporal variations in carbon dioxide (CO2) and methane (CH4) fluxes and their biophysical controls for 4 years, based on a closed-path eddy covariance (EC) system. The measurements were conducted in a mangrove wetland park with 14-year-old restored mangroves surrounded by open waters in Guangdong Province, China. The EC measurements showed that the mangrove ecosystem acted as a CO2 source with a net CO2 ecosystem exchange (NEE) of 305 g C m−2 from January 2019 to May 2020 by the 5-m tower measurement. After the tower was adjusted to 10 m, the mangrove showed a CO2 sink with an NEE of −345 g C m−2 from June 2020 to December 2022. The change in tower height influenced the interpretation of interannual trends on NEE. There were no significant interannual trends in the gross primary productivity (GPP) and the ecosystem respiration (Re) values. The change from CO2 source to sink may be attributed to the decrease in land surface proportion by the tower replacement, which reduces the proportion of the mangrove canopy respiration and, therefore, captures lower CO2 fluxes from open waters. The restored mangroves indicated strong CH4 sources of 23.2–26.3 g C m−2 a−1. According to the random forest analysis, the land surface proportion, radiation, and relative humidity were the three most important predictors of NEE, while the CH4 flux was most sensitive to air temperature. Compared to the natural and long-term restored mangroves, this 14-year-old restored mangrove had not yet achieved a maximum carbon sequestration capability. Our study highlights the need for the careful design of long-term observations from restored mangroves and proposes future needs in the context of carbon neutrality.
    Type of Medium: Online Resource
    ISSN: 2073-4433
    Language: English
    Publisher: MDPI AG
    Publication Date: 2023
    detail.hit.zdb_id: 2605928-9
    SSG: 23
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  • 10
    Online Resource
    Online Resource
    Springer Science and Business Media LLC ; 2023
    In:  Cellular & Molecular Biology Letters Vol. 28, No. 1 ( 2023-07-27)
    In: Cellular & Molecular Biology Letters, Springer Science and Business Media LLC, Vol. 28, No. 1 ( 2023-07-27)
    Abstract: Sebaceous glands (SGs) synthesize and secret sebum to protect and moisturize the dermal system via the complicated endocrine modulation. Dysfunction of SG are usually implicated in a number of dermal and inflammatory diseases. However, the molecular mechanism behind the differentiation, development and proliferation of SGs is far away to fully understand. Methods Herein, the rat volar and mammary tissues with abundant SGs from female SD rats with (post-natal day (PND)-35) and without puberty onset (PND-25) were arrested, and conducted RNA sequencing. The protein complex of Neuropeptide Y receptor Y2 (NPY2R)/NPY5R/Nuclear factor of activated T cells 1 (NFATc1) was performed by immunoprecipitation, mass spectrum and gel filtration. Genome-wide occupancy of NFATc1 was measured by chromatin immunoprecipitation sequencing. Target proteins’ expression and localization was detected by western blot and immunofluorescence. Results NPY2R gene was significantly up-regulated in volar and mammary SGs of PND-25. A special protein complex of NPY2R/NPY5R/NFATc1 in PND-25. NFATc1 was dephosphorylated and activated, then localized into nucleus to exert as a transcription factor in volar SGs of PND-35. NFATc1 was especially binding at enhancer regions to facilitate the distal SG and sebum related genes’ transcription. Dual specificity tyrosine phosphorylation regulated kinase 1A (DYRK1A) contributed to NFATc1 phosphorylation in PND-25, and inactivated of DYRK1A resulted in NFATc1 dephosphorylation and nuclear localization in PND-35. Conclusions Our findings unmask the new role of NPY2R/NFATc1/DYRK1A in pubertal SG, and are of benefit to advanced understanding the molecular mechanism of SGs’ function after puberty, and provide some theoretical basis for the treatment of acne vulgaris from the perspective of hormone regulation. Graphical Abstract
    Type of Medium: Online Resource
    ISSN: 1689-1392
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2023
    detail.hit.zdb_id: 2108724-6
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