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  • 1
    Online Resource
    Online Resource
    Role of Integrin αvβ3 in Doxycycline-Induced Anti-Proliferation in Breast Cancer Cells
    Frontiers Media SA ; 2022
    In:  Frontiers in Cell and Developmental Biology Vol. 10 ( 2022-2-14)
    Details
    In: Frontiers in Cell and Developmental Biology, Frontiers Media SA, Vol. 10 ( 2022-2-14)
    Abstract: Doxycycline, an antibiotic, displays the inhibition of different signal transduction pathways, such as anti-inflammation and anti-proliferation, in different types of cancers. However, the anti-cancer mechanisms of doxycycline via integrin αvβ3 are incompletely understood. Integrin αvβ3 is a cell-surface anchor protein. It is the target for estrogen, androgen, and thyroid hormone and plays a pivotal role in the proliferation, migration, and angiogenic process in cancer cells. In our previous study, thyroxine hormones can interact with integrin αvβ3 to activate the extracellular signal-regulated kinase 1/2 (ERK1/2), and upregulate programmed death-ligand 1 ( PD-L1 ) expression. In the current study, we investigated the inhibitory effects of doxycycline on proliferation in two breast cancer cell lines, MCF-7 and MDA-MB-231 cells. Doxycycline induces concentration-dependent anti-proliferation in both breast cancer cell lines. It regulates gene expressions involved in proliferation, pro-apoptosis, and angiogenesis. Doxycycline suppresses cell cyclin D1 ( CCND1 ) and c-Myc which play crucial roles in proliferation. It also inhibits PD-L1 gene expression. Our findings show that modulation on integrin αvβ3 binding activities changed both thyroxine- and doxycycline-induced signal transductions by an integrin αvβ3 inhibitor (HSDVHK-NH 2 ). Doxycycline activates phosphorylation of focal adhesion kinase (FAK), a downstream of integrin, but inhibits the ERK1/2 phosphorylation. Regardless, doxycycline-induced FAK phosphorylation is blocked by HSDVHK-NH 2 . In addition, the specific mechanism of action associated with pERK1/2 inhibition via integrin αvβ3 is unknown for doxycycline treatment. On the other hand, our findings indicated that inhibiting ERK1/2 activation leads to suppression of PD-L1 expression by doxycycline treatment. Furthermore, doxycycline-induced gene expressions are disturbed by a specific integrin αvβ3 inhibitor (HSDVHK-NH 2 ) or a mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinases (ERK) kinase (MAPK/ERK, MEK) inhibitor (PD98059). The results imply that doxycycline may interact with integrin αvβ3 and inhibits ERK1/2 activation, thereby regulating cell proliferation and downregulating PD-L1 gene expression in estrogen receptor (ER)-negative breast cancer MDA-MB-231 cells.
    Type of Medium: Online Resource
    ISSN: 2296-634X
    URL: Article
    DOI: 10.3389/fcell.2022.829788
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2737824-X
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  • 2
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    Inhibitory Effect of Anoectochilus formosanus Extract on Hyperglycemia-Related PD-L1 Expression and Cancer Proliferation
    Frontiers Media SA ; 2018
    In:  Frontiers in Pharmacology Vol. 9 ( 2018-8-2)
    Details
    In: Frontiers in Pharmacology, Frontiers Media SA, Vol. 9 ( 2018-8-2)
    Type of Medium: Online Resource
    ISSN: 1663-9812
    URL: Article
    DOI: 10.3389/fphar.2018.00807
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2018
    detail.hit.zdb_id: 2587355-6
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  • 3
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    Image1.pdf
    Frontiers Media SA ; 2021
    In:  Frontiers in Pharmacology Vol. 12 ( 2021-6-28)
    Details
    In: Frontiers in Pharmacology, Frontiers Media SA, Vol. 12 ( 2021-6-28)
    Abstract: The application of ultrasound microbubbles (USMBs) enhances the permeability of the round window membrane (RWM) and improves drug delivery to the inner ear. In this study, we investigated the efficiency of USMB-aided delivery of chitosan-coated gold nanoparticles (CS-AuNPs) and the mechanism of USMB-mediated enhancement of RMW permeability. We exposed mouse inner ears to USMBs at an intensity of 2 W/cm 2 and then filled the tympanic bulla with CS-AuNPs or fluorescein isothiocyanate-decorated CS-AuNPs (FITC-CS-AuNPs). The membrane uptake of FITC-CS-AuNPs and their depth of permeation into the three-layer structure of the RWM, with or without prior USMB treatment, were visualized by z-stack confocal laser scanning microscopy. Ultrastructural changes in the RWM due to USMB-mediated cavitation appeared as sunburn-like peeling and various degrees of depression in the RWM surface, with pore-like openings forming in the outer epithelium. This disruption of the outer epithelium was paralleled by a transient reduction in tight junction (TJ)-associated protein levels in the RWM and an enhanced delivery of FITC-CS-AuNPs into the RWM. Without prior USMB exposure, the treatment with CS-AuNPs also caused a noticeable reduction in TJ proteins of the RWM. Our findings indicated that the combined treatment with USMBs and CS-AuNPs represents a promising and efficient drug and gene delivery vehicle for a trans -RWM approach for inner ear therapy. The outer epithelial layer of the RWM plays a decisive role in controlling the transmembrane transport of substances such as CS-AuNPs following the administration of USMBs. Most importantly, the enhanced permeation of AuNPs involved the transient disruption of the TJ-created paracellular barrier in the outer epithelium of the RWM.
    Type of Medium: Online Resource
    ISSN: 1663-9812
    URL: Article
    URL: Article
    DOI: 10.3389/fphar.2021.689032
    DOI: 10.3389/fphar.2021.689032.s001
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2021
    detail.hit.zdb_id: 2587355-6
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  • 4
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    DataSheet_1.docx
    Frontiers Media SA ; 2021
    In:  Frontiers in Oncology Vol. 11 ( 2021-7-7)
    Details
    In: Frontiers in Oncology, Frontiers Media SA, Vol. 11 ( 2021-7-7)
    Abstract: Immune checkpoint inhibitors (ICIs) have been approved to treat patients with various cancer types, including lung cancer, in many countries. This study aims to investigate the effectiveness and safety of ICIs under different treatment conditions of non-small cell lung cancer patients. A population-based retrospective cohort study was conducted using the electronic health records of three medical centers in Taiwan. From January 01, 2016, to November 30, 2018, a total of 91 ICIs and 300 traditional chemotherapy users who had undergone stage III and IV lung cancer treatment were included in the study. We performed the randomized matched pair design by selecting a Chemotherapy subject for each ICI patient in the sample population. All subjects were monitored from the date of taking ICIs or chemotherapy drugs until the event of death, loss to follow-up, or were occurred with any defined adverse events. Kaplan-Meier estimators and cox proportional hazard regression models were used to compute the overall survival, efficacy, and safety of the ICIs group. The median overall survival (OS) in the ICI and Chemo groups after matching was 11.2 months and 10.5 months, respectively. However, the results showed no significant OS differences between ICIs and chemo groups for both before and after matching (HR,1.30; 95%CI, 0.68-2.46; p=0.428 before matching and HR,0.96; 95CI%, 0.64-1.44; p=0.838 after matching). We observed that with the higher amount of PD-L1, the length of the patients’ overall survival was (positive vs. negative PD-L1, HR,0.21; 95%CI, 0.05-0.80; p=0.022). The incidences of serious adverse drug events above grade 3 in the ICIs and traditional chemo groups were 12.7% and 21.5%, respectively. We also found that the number of AEs was less in ICIs than in the Chemo group, and the AEs that occurred after treatments were observed earlier in the ICIs compared to the Chemo group. ICIs drugs were observed to be safer than traditional chemotherapy as they had a lower risk of serious adverse drug events. It is necessary to pay attention to immune-related side effects and provide appropriate treatment. Furthermore, the patient’s physical status and PD-L1 test can be used to evaluate the clinical effectiveness of ICIs.
    Type of Medium: Online Resource
    ISSN: 2234-943X
    URL: Article
    URL: Article
    DOI: 10.3389/fonc.2021.671127
    DOI: 10.3389/fonc.2021.671127.s001
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2021
    detail.hit.zdb_id: 2649216-7
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  • 5
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    DataSheet_1.docx
    Frontiers Media SA ; 2022
    In:  Frontiers in Marine Science Vol. 9 ( 2022-5-13)
    Details
    In: Frontiers in Marine Science, Frontiers Media SA, Vol. 9 ( 2022-5-13)
    Abstract: Marine plastic debris is an environmental problem, and its degradation into microplastics (1-5000 μm) introduces them into the food chain. In this study, small polyoxymethylene (global production ~3000 Tg per year) pellets were exposed in terrestrial and simulated marine environments to heat and light, resulting in cracking during decay with increasing IR absorption (OH-bonds). Furthermore, sunlight over three years reduced pellet mass and diameter (~10% and ~40%), initially yielding 100-300 μm fragments. Changes under UV irradiation were smaller as it could not penetrate into particle interiors. Characteristic spacing of surface striations (100-300 µm) initiated radial cracks to pellet interiors, and breakdown ultimately meant 95% of particles were & lt;300 µm, which are potentially incorporated in marine turbidites.
    Type of Medium: Online Resource
    ISSN: 2296-7745
    URL: Article
    URL: Article
    DOI: 10.3389/fmars.2022.843295
    DOI: 10.3389/fmars.2022.843295.s001
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2757748-X
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  • 6
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    Data_Sheet_1.pdf
    Frontiers Media SA ; 2022
    In:  Frontiers in Surgery Vol. 9 ( 2022-3-24)
    Details
    In: Frontiers in Surgery, Frontiers Media SA, Vol. 9 ( 2022-3-24)
    Abstract: To determine whether treatment with uvulopalatopharyngoplasty (UPPP) or continuous positive airway pressure (CPAP) in patients with obstructive sleep apnea (OSA) prevents hypertension, compared to those not receiving any treatment. Methods A retrospective cohort study was conducted among 413 patients with OSA (age ≥ 35 years) at the Shuang Ho Hospital between 2009 and 2016. The patients were divided into three groups: UPPP, CPAP, and non-treatment groups. Data about the personal characteristics, history of comorbidities, and polysomnography (PSG) reports were collected at baseline. A Cox model with inverse probability of treatment weighting was used to adjust for confounders and baseline diversity. Results After multivariate adjustment and weighting for incident hypertension, patients in both the CPAP and UPPP groups showed a significant preventive effect on hypertension than in the non-treatment group. Moreover, patients in the CPAP group had lower event rates than those in the UPPP group. Conclusion UPPP can prevent the development of new-onset hypertension in patients with OSA. CPAP had a better preventive effect than UPPP. UPPP might be a good alternative for reducing the risk of the onset of hypertension when compliance to CPAP is poor.
    Type of Medium: Online Resource
    ISSN: 2296-875X
    URL: Article
    URL: Article
    DOI: 10.3389/fsurg.2022.818591
    DOI: 10.3389/fsurg.2022.818591.s001
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2773823-1
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  • 7
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    Inhibition of SARS-CoV-2 by Highly Potent Broad-Spectrum Anti-Coronaviral Tylophorine-Based Derivatives
    Frontiers Media SA ; 2020
    In:  Frontiers in Pharmacology Vol. 11 ( 2020-12-14)
    Details
    In: Frontiers in Pharmacology, Frontiers Media SA, Vol. 11 ( 2020-12-14)
    Abstract: Tylophorine-based compounds and natural cardiotonic steroids (cardenolides and bufadienolides) are two classes of transmissible gastroenteritis coronavirus inhibitors, targeting viral RNA and host cell factors, respectively. We tested both types of compounds against two types of coronaviruses, to compare and contrast their antiviral properties, and with view to their further therapeutic development. Examples of both types of compounds potently inhibited the replication of both feline infectious peritonitis virus and human coronavirus OC43 with EC 50 values of up to 8 and 16 nM, respectively. Strikingly, the tylophorine-based compounds tested inhibited viral yields of HCoV-OC43 to a much greater extent (7–8 log magnitudes of p.f.u./ml) than the cardiotonic steroids (about 2–3 log magnitudes of p.f.u./ml), as determined by end point assays. Based on these results, three tylophorine-based compounds were further examined for their anti-viral activities on two other human coronaviruses, HCoV-229E and SARS-CoV-2. These three tylophorine-based compounds inhibited HCoV-229E with EC 50 values of up to 6.5 nM, inhibited viral yields of HCoV-229E by 6–7 log magnitudes of p.f.u./ml, and were also found to inhibit SARS-CoV-2 with EC 50 values of up to 2.5–14 nM. In conclusion, tylophorine-based compounds are potent, broad-spectrum inhibitors of coronaviruses including SARS-CoV-2, and could be used for the treatment of COVID-19.
    Type of Medium: Online Resource
    ISSN: 1663-9812
    URL: Article
    DOI: 10.3389/fphar.2020.606097
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2020
    detail.hit.zdb_id: 2587355-6
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  • 8
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    DataSheet1.docx
    Frontiers Media SA ; 2021
    In:  Frontiers in Pharmacology Vol. 12 ( 2021-8-12)
    Details
    In: Frontiers in Pharmacology, Frontiers Media SA, Vol. 12 ( 2021-8-12)
    Abstract: Aspirin was once believed to reduce the mortality of Kawasaki disease (KD) due to its effect on the thrombotic occlusion of coronary arteries. However, conflicting evidence has been found regarding aspirin treatment and its benefit in patients with acute KD. We compared the efficacy of different aspirin doses in acute KD. A literature search of PubMed, EMBASE, and Cochrane databases was conducted to identify studies comparing different doses of aspirin for acute KD. The primary outcome of interest was coronary artery lesions (CAL). We used random-effects network meta-analysis. Six retrospective studies, including 1944 patients receiving aspirin in doses of 0, 3–5, 30–50, or 80–100 mg/kg/day, were selected. The risks of CAL were not significantly different for the various doses of aspirin compared to the placebo: odds ratio (OR) was 1.10 [95% confidence interval (CI): 0.70–1.71] for patients with aspirin 3–5 mg/kg/day; OR = 1.23 (95% CI: 0.67–2.26) for aspirin 30–50 mg/kg/day, and OR = 1.59 (95% CI: 0.74, 3.421) for 80–100 mg/kg/day. The P-score ranged from 0.76 for placebo to 0.19 for aspirin 80–100 mg/kg/day. The different doses of aspirin exhibited no significant difference with regard to the efficacy of CAL or with the secondary outcomes of intravenous immunoglobulin resistance or hospital stays for acute KD. Therefore, we found that treatment without any aspirin is not inferior to other doses of aspirin and can also slightly reduce the risk of CAL.
    Type of Medium: Online Resource
    ISSN: 1663-9812
    URL: Article
    URL: Article
    DOI: 10.3389/fphar.2021.725126
    DOI: 10.3389/fphar.2021.725126.s001
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2021
    detail.hit.zdb_id: 2587355-6
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  • 9
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    Image_5.tif
    Frontiers Media SA ; 2022
    In:  Frontiers in Oncology Vol. 12 ( 2022-8-3)
    Details
    In: Frontiers in Oncology, Frontiers Media SA, Vol. 12 ( 2022-8-3)
    Abstract: The cGAS-STING axis is one of the key mechanisms guarding cells from pathogen invasion in the cytoplasmic compartment. Sensing of foreign DNA in the cytosol by the cGAS-STING axis triggers a stress cascade, culminating at stimulation of the protein kinase TBK1 and subsequently activation of inflammatory response. In cancer cells, aberrant metabolism of the genomic DNA induced by the hostile milieu of tumor microenvironment or stresses brought about by cancer therapeutics are the major causes of the presence of nuclear DNA in the cytosol, which subsequently triggers a stress response. However, how the advanced tumors perceive and tolerate the potentially detrimental effects of cytosolic DNA remains unclear. Here we show that growth limitation by serum starvation activated the cGAS-STING pathway in breast cancer cells, and inhibition of cGAS-STING resulted in cell death through an autophagy-dependent mechanism. These results suggest that, instead of being subject to growth inhibition, tumors exploit the cGAS-STING axis and turn it to a survival advantage in the stressful microenvironment, providing a new therapeutic opportunity against advanced cancer. Concomitant inhibition of the cGAS-STING axis and growth factor signaling mediated by the epidermal growth factor receptor (EGFR) synergistically suppressed the development of tumor organoids derived from primary tumor tissues of triple-negative breast cancer (TNBC). The current study unveils an unexpected function of the cGAS-STING axis in promoting cancer cell survival and the potential of developing the stress-responding pathway as a therapeutic target, meanwhile highlights the substantial concerns of enhancing the pathway’s activity as a means of anti-cancer treatment.
    Type of Medium: Online Resource
    ISSN: 2234-943X
    URL: Article
    URL: Article
    URL: Article
    URL: Article
    URL: Article
    URL: Article
    DOI: 10.3389/fonc.2022.851795
    DOI: 10.3389/fonc.2022.851795.s001
    DOI: 10.3389/fonc.2022.851795.s002
    DOI: 10.3389/fonc.2022.851795.s003
    DOI: 10.3389/fonc.2022.851795.s004
    DOI: 10.3389/fonc.2022.851795.s005
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2649216-7
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  • 10
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    Image_1.pdf
    Frontiers Media SA ; 2022
    In:  Frontiers in Immunology Vol. 13 ( 2022-9-16)
    Details
    In: Frontiers in Immunology, Frontiers Media SA, Vol. 13 ( 2022-9-16)
    Abstract: After kidney transplantation, patients exhibit a poor response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination. However, the efficacy and adverse effects of vaccines based on different platforms in these patients remain unclear. We prospectively analyzed both anti-spike protein antibody and cellular responses 1 month after the first and second doses of SARS-CoV-2 vaccines in 171 kidney transplant patients. Four vaccines, including one viral vector (ChAdOx1 nCov-19, n = 30), two mRNA (mRNA1273, n = 81 and BNT162b2, n = 38), and one protein subunit (MVC-COV1901, n = 22) vaccines were administered. Among the four vaccines, mRNA1273 elicited the strongest humoral response and induced the highest interferon-γ levels in patients with a positive cellular response against the spike protein. Antiproliferative agents were negatively associated with both the antibody and cellular responses. A transient elevation in creatinine levels was noted in approximately half of the patients after the first dose of mRNA1273 or ChadOx1, and only one of them presented with borderline cellular rejection without definite causality to vaccination. In conclusion, mRNA1273 had better immunogenicity than the other vaccines. Further, renal function needs to be carefully monitored after vaccination, and vaccination strategies should be tailored according to the transplant status and vaccine characteristics.
    Type of Medium: Online Resource
    ISSN: 1664-3224
    URL: Article
    URL: Article
    URL: Article
    DOI: 10.3389/fimmu.2022.951576
    DOI: 10.3389/fimmu.2022.951576.s001
    DOI: 10.3389/fimmu.2022.951576.s002
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2606827-8
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