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  • 1
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    A Weakly Supervised Deep Learning Method for Guiding Ovarian Cancer Treatment and Identifying an Effective Biomarker
    MDPI AG ; 2022
    In:  Cancers Vol. 14, No. 7 ( 2022-03-24), p. 1651-
    Details
    In: Cancers, MDPI AG, Vol. 14, No. 7 ( 2022-03-24), p. 1651-
    Kurzfassung: Ovarian cancer is a common malignant gynecological disease. Molecular target therapy, i.e., antiangiogenesis with bevacizumab, was found to be effective in some patients of epithelial ovarian cancer (EOC). Although careful patient selection is essential, there are currently no biomarkers available for routine therapeutic usage. To the authors’ best knowledge, this is the first automated precision oncology framework to effectively identify and select EOC and peritoneal serous papillary carcinoma (PSPC) patients with positive therapeutic effect. From March 2013 to January 2021, we have a database, containing four kinds of immunohistochemical tissue samples, including AIM2, c3, C5 and NLRP3, from patients diagnosed with EOC and PSPC and treated with bevacizumab in a hospital-based retrospective study. We developed a hybrid deep learning framework and weakly supervised deep learning models for each potential biomarker, and the experimental results show that the proposed model in combination with AIM2 achieves high accuracy 0.92, recall 0.97, F-measure 0.93 and AUC 0.97 for the first experiment (66% training and 34%testing) and high accuracy 0.86 ± 0.07, precision 0.9 ± 0.07, recall 0.85 ± 0.06, F-measure 0.87 ± 0.06 and AUC 0.91 ± 0.05 for the second experiment using five-fold cross validation, respectively. Both Kaplan-Meier PFS analysis and Cox proportional hazards model analysis further confirmed that the proposed AIM2-DL model is able to distinguish patients gaining positive therapeutic effects with low cancer recurrence from patients with disease progression after treatment (p 〈 0.005).
    Materialart: Online-Ressource
    ISSN: 2072-6694
    URL: Article
    DOI: 10.3390/cancers14071651
    Sprache: Englisch
    Verlag: MDPI AG
    Publikationsdatum: 2022
    ZDB Id: 2527080-1
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  • 2
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    Strategy and Evaluation of Vehicle Collision Avoidance Control via Hardware-in-the-Loop Platform
    MDPI AG ; 2016
    In:  Applied Sciences Vol. 6, No. 11 ( 2016-11-01), p. 327-
    Details
    In: Applied Sciences, MDPI AG, Vol. 6, No. 11 ( 2016-11-01), p. 327-
    Materialart: Online-Ressource
    ISSN: 2076-3417
    URL: Article
    DOI: 10.3390/app6110327
    Sprache: Englisch
    Verlag: MDPI AG
    Publikationsdatum: 2016
    ZDB Id: 2704225-X
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  • 3
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    Hyperuricemia and Its Association with Osteoporosis in a Large Asian Cohort
    MDPI AG ; 2022
    In:  Nutrients Vol. 14, No. 11 ( 2022-05-26), p. 2206-
    Details
    In: Nutrients, MDPI AG, Vol. 14, No. 11 ( 2022-05-26), p. 2206-
    Kurzfassung: In this paper, we aimed to examine the protective role of hyperuricemia in the prevalence of osteoporosis in a large Asian cohort. A total of 119,037 participants from 29 recruitment centers in Taiwan were enrolled onto our study. Participants with serum uric acid greater than 7.0 mg/dL in men and 6.0 mg/dL in women were classified as the hyperuricemia group whereas the others were the control group. The mean age of all participants was 50; there were 23,114 subjects (19%) with hyperuricemia. Osteoporosis was observed in 8243 (9%) and 1871 (8%) participants in the control and hyperuricemia groups, respectively. After adjusting for confounders, a lower risk of osteoporosis was found in the hyperuricemia group compared with the control group (odds ratio, 0.916; 95% confidence interval, 0.864 to 0.970). A subgroup analysis showed that hyperuricemia was associated with a lower risk of osteoporosis in females, but not in males. Women with serum uric acid greater than 8.0 mg/dL were not associated with a greater risk of osteoporosis. Our study suggests that hyperuricemia decreases the risk of osteoporosis in females, but not in males. The protective role was no longer apparent when the serum uric acid level was greater than 8 mg/dL.
    Materialart: Online-Ressource
    ISSN: 2072-6643
    URL: Article
    DOI: 10.3390/nu14112206
    Sprache: Englisch
    Verlag: MDPI AG
    Publikationsdatum: 2022
    ZDB Id: 2518386-2
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  • 4
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    Distribution of Dermacentor silvarum and Associated Pathogens: Meta-Analysis of Global Published Data and a Field Survey in China
    MDPI AG ; 2021
    In:  International Journal of Environmental Research and Public Health Vol. 18, No. 9 ( 2021-04-22), p. 4430-
    Details
    In: International Journal of Environmental Research and Public Health, MDPI AG, Vol. 18, No. 9 ( 2021-04-22), p. 4430-
    Kurzfassung: Dermacentor silvarum is an obligate blood sucking arthropod and transmits various pathogens to humans and domestic animals. Recently several new viruses were detected in D. silvarum as an emerging disease threat. In this study, we aimed to analyze its geographical distribution and associated pathogens. Data were collected from multiple sources, including a field survey, reference book, and literature review. We searched various electronic databases with the terms “Dermacentor silvarum” OR “D. silvarum” for studies published since 1963 and the positive rates for Dermacentor silvarum-associated pathogens were estimated by meta-analysis. D. silvarum was found only in four countries in Eurasia, ranging from 22° N to 57° N latitude. At least 20 human pathogens were associated with D. silvarum, including five species of spotted fever group rickettsiae, three species in the family of Anaplasmataceae, three genospecies in the complex Borrelia burgdorferi sensu lato, Francisella tularensis, Babesia venatorum, Coxiella buenetii, Borrelia miyamotoi, and five species of virus. Among them, Rickettsia raoultii was widely detected in D. silvarum, showing the highest pooled positive rate (25.15%; 95% CI 13.31–39.27). Our work presents the most comprehensive data and analysis (to our knowledge) for the geographical distribution of D. silvarum and associated pathogens, revealing an emerging threat to public health and stocking farming. Continued surveillance and further investigations should be enhanced.
    Materialart: Online-Ressource
    ISSN: 1660-4601
    URL: Article
    DOI: 10.3390/ijerph18094430
    Sprache: Englisch
    Verlag: MDPI AG
    Publikationsdatum: 2021
    ZDB Id: 2175195-X
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  • 5
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    Scavenging Intracellular ROS Attenuates p-Cresyl Sulfate-Triggered Osteogenesis through MAPK Signaling Pathway and NF-κB Activation in Human Arterial Smooth Muscle Cells
    MDPI AG ; 2020
    In:  Toxins Vol. 12, No. 8 ( 2020-07-24), p. 472-
    Details
    In: Toxins, MDPI AG, Vol. 12, No. 8 ( 2020-07-24), p. 472-
    Kurzfassung: Osteogenesis in human arterial smooth muscle cell (HASMC) is a key feature of uremic vascular calcification (UVC). Concerning pro-oxidant properties of p-cresyl sulfate (PCS), the therapeutic effect of reactive oxygen species (ROS) scavenger on PCS triggered inflammatory signaling transduction in osteogenesis was investigated in this translational research. Based on severity level of chronic kidney disease (CKD), arterial specimens with immunohistochemistry stain were quantitatively analyzed for UVC, oxidative injury and osteogenesis along with PCS concentrations. To mimic human UVC, HASMC model was used to explore whether PCS-induced ROS could trigger mitogen-activated protein kinase (MAPK) pathways with nuclear factor-κB (NF-κB) translocation that drive context-specific gene/protein expression, including Runt-related transcription factor 2 (Runx2) and alkaline phosphatase (ALP). In parallel with PCS accumulation, CKD arteries corresponded with UVC severity, oxidative DNA damage (8-hydroxy-2′-deoxyguanosine), Runx2 and ALP. PCS directly phosphorylated extracellular signal-regulated kinase (ERK)/c-Jun N-terminal kinase (JNK)/P38 (pERK/pJNK/pP38) and modulated NF-κB translocation to promote expressions of Runx2 and ALP in HASMC. Notably, intracellular ROS scavenger attenuated pERK signaling cascade and downstream osteogenic differentiation. Collectively, our data demonstrate PCS induces osteogenesis through triggering intracellular ROS, pERK/pJNK/pP38 MAPK pathways and NF-κB translocation to drive Runx2 and ALP expressions, culminating in UVC. Beyond mineral dysregulation, osteocytic conversion in HASMC could be the stimulation of PCS. Thus PCS may act as a pro-osteogenic and pro-calcific toxin. From the perspective of translational medicine, PCS and intracellular ROS could serve as potential therapeutic targets for UVC in CKD patients.
    Materialart: Online-Ressource
    ISSN: 2072-6651
    URL: Article
    DOI: 10.3390/toxins12080472
    Sprache: Englisch
    Verlag: MDPI AG
    Publikationsdatum: 2020
    ZDB Id: 2518395-3
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  • 6
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    Factors Associated with Significant Platelet Count Improvement in Thrombocytopenic Chronic Hepatitis C Patients Receiving Direct-Acting Antivirals
    MDPI AG ; 2022
    In:  Viruses Vol. 14, No. 2 ( 2022-02-07), p. 333-
    Details
    In: Viruses, MDPI AG, Vol. 14, No. 2 ( 2022-02-07), p. 333-
    Kurzfassung: To clarify the predictive factors of significant platelet count improvement in thrombocytopenic chronic hepatitis C (CHC) patients. CHC patients with baseline platelet counts of 〈 150 × 103/μL receiving direct-acting antiviral (DAA) therapy with at least 12-weeks post-treatment follow-up (PTW12) were enrolled. Significant platelet count improvement was defined as a ≥10% increase in platelet counts at PTW12 from baseline. Platelet count evolution at treatment week 4, end-of-treatment, PTW12, and PTW48 was evaluated. This study included 4922 patients. Sustained virologic response after 12 weeks post-treatment was achieved in 98.7% of patients. Platelet counts from baseline, treatment week 4, and end-of-treatment to PTW12 were 108.8 ± 30.2, 121.9 ± 41.1, 123.1 ± 43.0, and 121.1 ± 40.8 × 103/μL, respectively. Overall, 2230 patients (45.3%) showed significant platelet count improvement. Multivariable analysis revealed that age (odds ratio (OR) = 0.99, 95% confidence interval (CI): 0.99–1.00, p = 0.01), diabetes mellitus (DM) (OR = 1.20, 95% CI: 1.06–1.38, p = 0.007), cirrhosis (OR = 0.66, 95% CI: 0.58–0.75, p 〈 0.0001), baseline platelet counts (OR = 0.99, 95% CI: 0.98–0.99, p 〈 0.0001), and baseline total bilirubin level (OR = 0.80, 95% CI: 0.71–0.91, p = 0.0003) were independent predictive factors of significant platelet count improvement. Subgroup analyses showed that patients with significant platelet count improvement and sustained virologic responses, regardless of advanced fibrosis, had a significant increase in platelet counts from baseline to treatment week 4, end-of-treatment, PTW12, and PTW48. Young age, presence of DM, absence of cirrhosis, reduced baseline platelet counts, and reduced baseline total bilirubin levels were associated with significant platelet count improvement after DAA therapy in thrombocytopenic CHC patients.
    Materialart: Online-Ressource
    ISSN: 1999-4915
    URL: Article
    DOI: 10.3390/v14020333
    Sprache: Englisch
    Verlag: MDPI AG
    Publikationsdatum: 2022
    ZDB Id: 2516098-9
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  • 7
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    Effect of Cerenkov Radiation-Induced Photodynamic Therapy with 18F-FDG in an Intraperitoneal Xenograft Mouse Model of Ovarian Cancer
    MDPI AG ; 2021
    In:  International Journal of Molecular Sciences Vol. 22, No. 9 ( 2021-05-06), p. 4934-
    Details
    In: International Journal of Molecular Sciences, MDPI AG, Vol. 22, No. 9 ( 2021-05-06), p. 4934-
    Kurzfassung: Ovarian cancer (OC) metastases frequently occur through peritoneal dissemination, and they contribute to difficulties in treatment. While photodynamic therapy (PDT) has the potential to treat OC, its use is often limited by tissue penetration depth and tumor selectivity. Herein, we combined Cerenkov radiation (CR) emitted by 18F-FDG accumulated in tumors as an internal light source and several photosensitizer (PS) candidates with matched absorption bands, including Verteporfin (VP), Chlorin e6 (Ce6) and 5′-Aminolevulinic acid (5′-ALA), to evaluate the anti-tumor efficacy. The in vitro effect of CR-induced PDT (CR-PDT) was evaluated using a cell viability assay, and the efficiency of PS was assessed by measuring the singlet oxygen production. An intraperitoneal ES2 OC mouse model was used for in vivo evaluation of CR-PDT. Positron emission tomography (PET) imaging and bioluminescence-based imaging were performed to monitor the biologic uptake of 18F-FDG and the therapeutic effect. The in vitro studies demonstrated Ce6 and VP to be more effective PSs for CR-PDT. Moreover, VP was more efficient in the generation of singlet oxygen and continued for a long time when exposed to fluoro-18 (18F). Combining CR emitted by 18F-FDG and VP treatment not only significantly suppressed tumor growth, but also prolonged median survival times compared to either monotherapy.
    Materialart: Online-Ressource
    ISSN: 1422-0067
    URL: Article
    DOI: 10.3390/ijms22094934
    Sprache: Englisch
    Verlag: MDPI AG
    Publikationsdatum: 2021
    ZDB Id: 2019364-6
    SSG: 12
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  • 8
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    PCTAIRE Protein Kinase 1 (PCTK1) Suppresses Proliferation, Stemness, and Chemoresistance in Colorectal Cancer through the BMPR1B-Smad1/5/8 Signaling Pathway
    MDPI AG ; 2023
    In:  International Journal of Molecular Sciences Vol. 24, No. 12 ( 2023-06-11), p. 10008-
    Details
    In: International Journal of Molecular Sciences, MDPI AG, Vol. 24, No. 12 ( 2023-06-11), p. 10008-
    Kurzfassung: Colorectal cancer (CRC) is the third most common cancer and a leading cause of cancer-related mortality worldwide. Even with advances in therapy, CRC mortality remains high. Therefore, there is an urgent need to develop effective therapeutics for CRC. PCTAIRE protein kinase 1 (PCTK1) is an atypical member of the cyclin-dependent kinase (CDK) family, and the function of PCTK1 in CRC is poorly understood. In this study, we found that patients with elevated PCTK1 levels had a better overall survival rate in CRC based on the TCGA dataset. Functional analysis also showed that PCTK1 suppressed cancer stemness and cell proliferation by using PCTK1 knockdown (PCTK1-KD) or knockout (PCTK1-KO) and PCTK1 overexpression (PCTK1-over) CRC cell lines. Furthermore, overexpression of PCTK1 decreased xenograft tumor growth and knockout of PCTK1 significantly increased in vivo tumor growth. Moreover, knockout of PCTK1 was observed to increase the resistance of CRC cells to both irinotecan (CPT-11) alone and in combination with 5-fluorouracil (5-FU). Additionally, the fold change of the anti-apoptotic molecules (Bcl-2 and Bcl-xL) and the proapoptotic molecules (Bax, c-PARP, p53, and c-caspase3) was reflected in the chemoresistance of PCTK1-KO CRC cells. PCTK1 signaling in the regulation of cancer progression and chemoresponse was analyzed using RNA sequencing and gene set enrichment analysis (GSEA). Furthermore, PCTK1 and Bone Morphogenetic Protein Receptor Type 1B (BMPR1B) in CRC tumors were negatively correlated in CRC patients from the Timer2.0 and cBioPortal database. We also found that BMPR1B was negatively correlated with PCTK1 in CRC cells, and BMPR1B expression was upregulated in PCTK1-KO cells and xenograft tumor tissues. Finally, BMPR1B-KD partially reversed cell proliferation, cancer stemness, and chemoresistance in PCTK1-KO cells. Moreover, the nuclear translocation of Smad1/5/8, a downstream molecule of BMPR1B, was increased in PCTK1-KO cells. Pharmacological inhibition of Smad1/5/8 also suppressed the malignant progression of CRC. Taken together, our results indicated that PCTK1 suppresses proliferation and cancer stemness and increases the chemoresponse of CRC through the BMPR1B–Smad1/5/8 signaling pathway.
    Materialart: Online-Ressource
    ISSN: 1422-0067
    URL: Article
    DOI: 10.3390/ijms241210008
    Sprache: Englisch
    Verlag: MDPI AG
    Publikationsdatum: 2023
    ZDB Id: 2019364-6
    SSG: 12
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  • 9
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    Truncated Pneumolysin from Streptococcus pneumoniae as a TLR4-Antagonizing New Drug for Chronic Inflammatory Conditions
    MDPI AG ; 2020
    In:  Cells Vol. 9, No. 5 ( 2020-05-09), p. 1183-
    Details
    In: Cells, MDPI AG, Vol. 9, No. 5 ( 2020-05-09), p. 1183-
    Kurzfassung: Microbial proteins have recently been found to have more benefits in clinical disease treatment because of their better-developed strategy and properties than traditional medicine. In this study, we investigated the effectiveness of a truncated peptide synthesized from the C-terminal sequence of pneumolysin, i.e., C70PLY4, in Streptococcus pneumoniae, in treating chronic inflammatory conditions. It has been shown that C70PLY4 significantly blocks the transendothelial migration of neutrophils and attenuates the formation of atherosclerotic plaque and the secretion of soluble forms of the intercellular adhesion molecule-1 (ICAM-1), the vascular cell adhesion molecule 1 (VCAM-1), and E-selectin in high-fat-diet/streptozotocin-induced inflammatory rats. The mechanism and the docking simulation analysis further indicated that C70PLY4 might serve as a Toll-like receptor 4 (TLR4) antagonist by competing for the binding site of MD2, an indispensable protein for lipopolysaccharide (LPS)–TLR4 interaction signaling, on the TLR4 structure. Moreover, compared to the full-length PLY, C70PLY4 seems to have no cytotoxicity in human vascular endothelial cells. Our study elucidated a possible therapeutic efficacy of C70PLY4 in reducing chronic inflammatory conditions and clarified the underlying mechanism. Thus, our findings identify a new drug candidate that, by blocking TLR4 activity, could be an effective treatment for patients with chronic inflammatory diseases.
    Materialart: Online-Ressource
    ISSN: 2073-4409
    URL: Article
    DOI: 10.3390/cells9051183
    Sprache: Englisch
    Verlag: MDPI AG
    Publikationsdatum: 2020
    ZDB Id: 2661518-6
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  • 10
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    Associations between Water Quality Measures and Chronic Kidney Disease Prevalence in Taiwan
    MDPI AG ; 2018
    In:  International Journal of Environmental Research and Public Health Vol. 15, No. 12 ( 2018-12-03), p. 2726-
    Details
    In: International Journal of Environmental Research and Public Health, MDPI AG, Vol. 15, No. 12 ( 2018-12-03), p. 2726-
    Kurzfassung: To determine the relationships between exposure to environmental contaminants in water and chronic kidney disease (CKD), we investigated the associations of 61 water attributes with the prevalence of CKD and End-Stage Renal Disease (ESRD) using data from 2005 to 2011 from all 22 counties and cities in the main island of Taiwan. We acquired patient information from the Taiwan Longitudinal Health Insurance Database to calculate the age-standardized CKD and ESRD prevalence rates and linked the patients’ residences to the water quality monitoring data, which were sampled periodically for a total of over 45,000 observations obtained from the Taiwan Environmental Water Quality Information Database. The association analysis adjusting for gender, age, and annual effects showed that the zinc (Zn), ammonia, chemical oxygen demand (COD), and dissolved oxygen in rivers were weakly correlated with CKD (τ = 0.268/0.250/0.238/−0.267, p = 6.01×10−6/2.52×10−5/6.05×10−5/3.30×10−5, respectively), but none for ESRD. The importances of Zn and COD in rivers were also demonstrated in a CKD regression model. Moreover, an unusually high CKD prevalence was related to arsenic contamination in groundwater. A further prospective cohort study would improve our understanding of what level of environmental water with risky properties could affect the development of CKD.
    Materialart: Online-Ressource
    ISSN: 1660-4601
    URL: Article
    DOI: 10.3390/ijerph15122726
    Sprache: Englisch
    Verlag: MDPI AG
    Publikationsdatum: 2018
    ZDB Id: 2175195-X
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