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  • 1
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    Online Resource
    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-
    Abstract: 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.
    Type of Medium: Online Resource
    ISSN: 1999-4915
    URL: Article
    DOI: 10.3390/v14020333
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2516098-9
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  • 2
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    A Functional Polymorphism Downstream of Vitamin A Regulator Gene CYP26B1 Is Associated with Hand Osteoarthritis
    MDPI AG ; 2023
    In:  International Journal of Molecular Sciences Vol. 24, No. 3 ( 2023-02-03), p. 3021-
    Details
    In: International Journal of Molecular Sciences, MDPI AG, Vol. 24, No. 3 ( 2023-02-03), p. 3021-
    Abstract: While genetic analyses have revealed ~100 risk loci associated with osteoarthritis (OA), only eight have been linked to hand OA. Besides, these studies were performed in predominantly European and Caucasian ancestries. Here, we conducted a genome-wide association study in the Han Chinese population to identify genetic variations associated with the disease. We recruited a total of 1136 individuals (n = 420 hand OA-affected; n = 716 unaffected control subjects) of Han Chinese ancestry. We carried out genotyping using Axiom Asia Precisi on Medicine Research Array, and we employed the RegulomeDB database and RoadMap DNase I Hypersensitivity Sites annotations to further narrow down our potential candidate variants. Genetic variants identified were tested in the Geisinger’s hand OA cohort selected from the Geisinger MyCode community health initiative (MyCode®). We also performed a luciferase reporter assay to confirm the potential impact of top candidate single-nucleotide polymorphisms (SNPs) on hand OA. We identified six associated SNPs (p-value = 6.76 × 10−7–7.31 × 10−6) clustered at 2p13.2 downstream of the CYP26B1 gene. The strongest association signal identified was rs883313 (p-value = 6.76 × 10−7, odds ratio (OR) = 1.76), followed by rs12713768 (p-value = 1.36 × 10−6, OR = 1.74), near or within the enhancer region closest to the CYP26B1 gene. Our findings showed that the major risk-conferring CC haplotype of SNPs rs12713768 and rs10208040 [strong linkage disequilibrium (LD); D’ = 1, r2 = 0.651] drives 18.9% of enhancer expression activity. Our findings highlight that the SNP rs12713768 is associated with susceptibility to and severity of hand OA in the Han Chinese population and that the suggested retinoic acid signaling pathway may play an important role in its pathogenesis.
    Type of Medium: Online Resource
    ISSN: 1422-0067
    URL: Article
    DOI: 10.3390/ijms24033021
    Language: English
    Publisher: MDPI AG
    Publication Date: 2023
    detail.hit.zdb_id: 2019364-6
    SSG: 12
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  • 3
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    High-Grade B-Cell Lymphoma (HGBL) with MYC and BCL2 and/or BCL6 Rearrangements Is Predominantly BCL6-Rearranged and BCL6-Expressing in Taiwan
    MDPI AG ; 2021
    In:  Cancers Vol. 13, No. 7 ( 2021-03-31), p. 1620-
    Details
    In: Cancers, MDPI AG, Vol. 13, No. 7 ( 2021-03-31), p. 1620-
    Abstract: This study investigated the epidemiological and clinical peculiarities of BCL2 and BCL6 rearrangement in patients with high grade B-cell lymphoma (HGBL) from Taiwan, compared with data from Western countries. Two hundred and eighty-two DLBCL cases from Taipei Medical University-affiliated hospitals (n = 179) and Tri-Service General Hospital (n = 103) were enrolled for this study. From the 282, 47 (16.7%) had MYC translocation; 24 of these harbored concurrent BCL2 and/or BCL6 translocation (double-hit, DH or triple-hit, TH). Twelve DH-HGBL cases had simultaneous MYC and BCL6 translocations, 8 harbored MYC and BCL2 rearrangement, while the remaining 4 patients exhibited TH. Together, 66.7% of DH/TH-HGBL patients were BCL6 rearrangement positive. Among these BCL6-rearranged DH/TH-HGBL patients, only 6 (37.5%) overexpressed MYC and BCL6 proteins simultaneously, indicating that MYC-BCL6 co-overexpression may not be plausible surrogate biomarker for screening BCL6-rearranged DH-HGBL. By the end of year 5, all patients with TH-HGBL, BCL2 DH-HGBL and all but one BCL6 DH-HGBL cases had expired or were lost to follow-up. Progression-free survival (PFS) was longer for the non-DH/TH-HGBL group compared with the DH/TH-HGBL group. While the patients with BCL2 DH-HGBL were lost to follow-up by day 800, their remaining TH-HGBL and BCL6 DH-HGBL peers exhibited very poor PFS, regardless of age strata. More so, patients with BCL6 rearrangement were 5.5-fold more likely associated with extranodal involvement compared with their BCL2-rearranged peers. Moreover, ~60.0% of the BCL6-rearranged DH-HGBL cases were non-GCB, suggesting that including screening for BCL6 rearrangement in patients with the non-GCB phenotype may aid medical decision-making and therapeutic strategy. Contrary to contemporary data from western countries, 2 in every 3 patients with DH/TH-HGBL in Taiwan harbor BCL6 rearrangement. Consistent with present findings, we recommend mandatory screening for BCL6 rearrangement in patients with aggressive HGBL in Taiwan.
    Type of Medium: Online Resource
    ISSN: 2072-6694
    URL: Article
    DOI: 10.3390/cancers13071620
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2527080-1
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  • 4
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    Radiotherapy Is Associated with an Accelerated Risk of Carotid Atherosclerosis in Patients with Nasopharyngeal Carcinoma: A Nine-Year Prospective Follow-Up Study
    MDPI AG ; 2022
    In:  Cancers Vol. 14, No. 5 ( 2022-02-27), p. 1234-
    Details
    In: Cancers, MDPI AG, Vol. 14, No. 5 ( 2022-02-27), p. 1234-
    Abstract: Radiation-related extracranial vasculopathy is a common late effect after radiation in patients with nasopharyngeal carcinoma (NPC). We proposed the hypothesis that radiation-related extracranial vasculopathy is a progressive process that can begin immediately after radiotherapy and persist for a longer period, and inflammation and oxidative stress may play a pivotal role in this process. Thirty-six newly diagnosed NPC patients were assessed with B-mode ultrasound for the common carotid artery (CCA) intima media thickness (IMT) measurement as well as surrogate markers at three different stages (baseline, immediately after concurrent chemoradiation therapy (CCRT), and 9 years after enrollment). A healthy control group was also recruited for comparison. Surrogate markers including a lipid profile, HbA1c, inflammation, oxidative stress, and platelet activation markers were assessed. The mean CCA IMT in the NPC group were increased immediately after CCRT (p = 0.043). The mean CCA IMT value after a 9-year follow-up also showed a significant increase in NPC and control group, respectively (p 〈 0.0001 and p 〈 0.0001, paired t test). The annual increase mean CCA IMT (mm) was 0.053 ± 0.025 and 0.014 ± 0.013 in NPC and control group, respectively (p 〈 0.0001). The baseline high sensitivity CRP (hs-CRP), thiol, TBARS, and CD63 level were significantly higher in the NPC group (hs-CRP, p = 0.001, thiol, p 〈 0.0001, TBARS, p = 0.05, and CD63 level, p = 0.04). The thiol and TBARS levels were significantly lower in NPC patients immediately after CCRT (thiol, p 〈 0.0001, and TBARS, p = 0.043). The CD62P level was significantly higher while the thiol level was significantly lower in the NPC group after a 9-year follow-up (CD62P level, p = 0.007; and thiol level, p = 0.004). Radiation-related extracranial vasculopathy is a progressive process that begins immediately after radiotherapy with significantly increased carotid IMT compared to the control group during the 9-year follow-up. Chronic inflammation and oxidative stress might serve to drive the process and also contribute to increased platelet activation.
    Type of Medium: Online Resource
    ISSN: 2072-6694
    URL: Article
    DOI: 10.3390/cancers14051234
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2527080-1
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  • 5
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    The Impact on the Clinical Prognosis of Low Serum Selenium Level in Patients with Severe Trauma: Systematic Review and Meta-Analysis
    MDPI AG ; 2022
    In:  Nutrients Vol. 14, No. 6 ( 2022-03-18), p. 1295-
    Details
    In: Nutrients, MDPI AG, Vol. 14, No. 6 ( 2022-03-18), p. 1295-
    Abstract: This study was designed to examine the most up-to-date evidence about how low plasma selenium (Se) concentration affects clinical outcomes, such as mortality, infectious complications, and length of ICU or hospital stay, in patients with major trauma. We searched three databases (MEDLINE, EMBASE, and Web of Science) with the following keywords: “injury”, “trauma”, “selenium”, and “trace element”. Only records written in English published between 1990 and 2021 were included for analysis. Four studies were eligible for meta-analyses. The results of the meta-analysis showed that a low serum selenium level did not exert a negative effect on the mortality rate (OR 1.07, 95% CI: 0.32, 3.61, p = 0.91, heterogeneity, I2 = 44%). Regarding the incidence of infectious complications, there was no statistically significant deficit after analyses of the four studies (OR 1.61, 95% CI: 0.64, 4.07, p = 0.31, heterogeneity, I2 = 70%). There were no differences in the days spent in the ICU (difference in means (MD) 1.53, 95% CI: −2.15, 5.22, p = 0.41, heterogeneity, I2 = 67%) or the hospital length of stay (MD 6.49, 95% CI: −4.05, 17.02, p = 0.23, heterogeneity, I2 = 58%) in patients with low serum Se concentration. A low serum selenium level after trauma is not uncommon. However, it does not negatively affect mortality and infection rate. It also does not increase the overall length of ICU and hospital stays.
    Type of Medium: Online Resource
    ISSN: 2072-6643
    URL: Article
    DOI: 10.3390/nu14061295
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2518386-2
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  • 6
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    The Prognosis of Blunt Bowel and Mesenteric Injury—The Pitfall in the Contemporary Image Survey
    MDPI AG ; 2019
    In:  Journal of Clinical Medicine Vol. 8, No. 9 ( 2019-08-24), p. 1300-
    Details
    In: Journal of Clinical Medicine, MDPI AG, Vol. 8, No. 9 ( 2019-08-24), p. 1300-
    Abstract: Delayed diagnosis and intervention of blunt bowel and mesenteric injury (BBMI) is a hazard because of poor prognosis. Computed tomography (CT) is the standard imaging tool to evaluate blunt abdominal trauma (BAT). However, a high missed diagnosis rate for BMMI was reported. In this study, we would like to evaluate the presentation of CT in BBMI. Moreover, we want to evaluate the impact of deferred surgical intervention of BBMI on final prognosis. We performed a retrospective study from 2013–2017, including patients with BAT and BBMI who underwent surgical intervention. We evaluated clinical characteristics, CT images, and surgical timing, as well as analyzed the prognosis of BBMI. There were 6164 BAT patients and 188 BMI patients included. The most common characteristics of CT were free fluid (71.3%), free air (43.6%), and mesenteric infiltration (23.4%). There were no single characteristics of a CT image that can predict BBMI significantly. However, under close monitoring, we find that deferred intervention did not prolong the hospital and intensive care unit stays and did not worsen the prognosis and mortality.
    Type of Medium: Online Resource
    ISSN: 2077-0383
    URL: Article
    DOI: 10.3390/jcm8091300
    Language: English
    Publisher: MDPI AG
    Publication Date: 2019
    detail.hit.zdb_id: 2662592-1
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  • 7
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    The Feasibility and Efficiency of Remote Spirometry System on the Pulmonary Function for Multiple Ribs Fracture Patients
    MDPI AG ; 2021
    In:  Journal of Personalized Medicine Vol. 11, No. 11 ( 2021-10-23), p. 1067-
    Details
    In: Journal of Personalized Medicine, MDPI AG, Vol. 11, No. 11 ( 2021-10-23), p. 1067-
    Abstract: Background: Multiple rib fractures is a common chest trauma with a significant and sustained impact on pulmonary function and quality of life. Continuous monitoring of the pulmonary function parameter was necessary to adjust the therapeutic goals in these patients. We developed an internet-based remote system for lung function monitoring with a remote spirometry and smart device application to follow up these patients consecutively. Method: From Jan 2021 to April 2021, we conducted a prospective study that applied an intelligent spirometry system for patients with multiple rib fractures. With informed consent, we collected clinical data from them and introduced the remote spirometry system. We followed up with these patients for 12 weeks after trauma and compared the recovery of pulmonary function parameters and clinical outcomes. Result: A total of 21 patients were enrolled in our study. We divided them into two groups by the compliance to this remote spirometry system. The improvement of forced vital capacity was better in the good compliance group than the poor compliance group (110% versus 21%, p value 0.049). Moreover, the complication rate was also lower in the good compliance group than the poor compliance group (10% versus 66.7% p value 0.017). Conclusions: Remote spirometry system is a novel system that can help in lung rehabilitation in patients with multiple rib fractures. Patients that cooperate well with this system presented superior lung function improvement and inferior complication rate.
    Type of Medium: Online Resource
    ISSN: 2075-4426
    URL: Article
    DOI: 10.3390/jpm11111067
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2662248-8
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  • 8
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    Antrodin C Isolated from Antrodia Cinnamomea Induced Apoptosis through ROS/AKT/ERK/P38 Signaling Pathway and Epigenetic Histone Acetylation of TNFα in Colorectal Cancer Cells
    MDPI AG ; 2023
    In:  Antioxidants Vol. 12, No. 3 ( 2023-03-21), p. 764-
    Details
    In: Antioxidants, MDPI AG, Vol. 12, No. 3 ( 2023-03-21), p. 764-
    Abstract: Background: Antrodin C, a maleimide derivative compound isolated from the ethanol extract of the mycelium of Antrodia cinnamomea, is an endemic fungus of Taiwan and a potential chemoprotective agent. However, the molecular mechanisms underlying the mode of action of antrodin C on cancer cells, especially in human colorectal cancer (CRC), remain unclear. Methods: The cell death and ROS of the antrodin-C-treated HCT-116 cells were measured by annexin V–FITC/propidium iodide staining, DCFDA, and Fluo-3 fluorescence staining assays. Moreover, signaling molecules regulating TNFα cell death pathways and ROS/AKT/ERK/P38 pathways were also detected in cells treated with antrodin C by Western blotting and chromatin immunoprecipitation. The effects of antrodin C were determined in HCT-116 cell xenograft animal models in terms of tumor volumes and histopathological evaluation. Results: Treatment with antrodin C triggered the activation of extrinsic apoptosis pathways (TNFα, Bax, caspase-3, and -9), and also suppressed the expression of anti-apoptotic molecules Bcl-2 in HCT-116 cells in a time-dependent manner. Antrodin C also decreased cell proliferation and growth through the inactivation of cyclin D1/cyclin for the arrest of the cell cycle at the G1 phase. The activation of the ROS/AKT/ERK/P38 pathways was involved in antrodin-C-induced transcriptional activation, which implicates the role of the histone H3K9K14ac (Acetyl Lys9/Lys14) of the TNFα promoters. Immunohistochemical analyses revealed that antrodin C treatment significantly induced TNFα levels, whereas it decreased the levels of PCNA, cyclin D1, cyclin E, and MMP-9 in an in vivo xenograft mouse model. Thus, antrodin C induces cell apoptosis via the activation of the ROS/AKT/ERK/P38 signaling modules, indicating a new mechanism for antrodin C to treat CRC in vitro and in vivo.
    Type of Medium: Online Resource
    ISSN: 2076-3921
    URL: Article
    DOI: 10.3390/antiox12030764
    Language: English
    Publisher: MDPI AG
    Publication Date: 2023
    detail.hit.zdb_id: 2704216-9
    SSG: 15,3
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  • 9
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    ERCC1 Overexpression Increases Radioresistance in Colorectal Cancer Cells
    MDPI AG ; 2022
    In:  Cancers Vol. 14, No. 19 ( 2022-09-30), p. 4798-
    Details
    In: Cancers, MDPI AG, Vol. 14, No. 19 ( 2022-09-30), p. 4798-
    Abstract: Preoperative concurrent chemoradiotherapy (CCRT) is a standard treatment for locally advanced rectal cancer patients, but 20–30% do not benefit from the desired therapeutic effects. Previous reports indicate that high levels of ERCC1 reduce the effectiveness of cisplatin-based CCRT; however, it remains unclear as to whether ERCC1 overexpression increases radiation resistance. To clarify the correlation between ERCC1 levels and radiation (RT) resistance, we established two cell lines (HCT116-Tet-on and COLO205-Tet-on), induced them to overexpress ERCC1, detected cell survival following exposure to radiation, established HCT116-Tet-on and COLO205-Tet-on heterotopic cancer animal models, and detected tumor volume following exposure to radiation. We found that ERCC1 overexpression increased radiation resistance. After regulating ERCC1 levels and radiation exposure to verify the correlation, we noted that increased radiation resistance was dependent on ERCC1 upregulation in both cell lines. For further verification, we exposed HCT116-Tet-on and COLO205-Tet-on heterotopic cancer animal models to radiation and observed that ERCC1 overexpression increased colorectal cancer tumor radioresistance in both. Combined, our results suggest that ERCC1 overexpression may serve as a suitable CCRT prognostic marker for colorectal cancer patients.
    Type of Medium: Online Resource
    ISSN: 2072-6694
    URL: Article
    DOI: 10.3390/cancers14194798
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2527080-1
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  • 10
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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-
    Abstract: 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.
    Type of Medium: Online Resource
    ISSN: 2072-6651
    URL: Article
    DOI: 10.3390/toxins12080472
    Language: English
    Publisher: MDPI AG
    Publication Date: 2020
    detail.hit.zdb_id: 2518395-3
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