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  • 1
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    Circulating Growth Differentiation Factor 15 Is Associated with Diabetic Neuropathy
    MDPI AG ; 2022
    In:  Journal of Clinical Medicine Vol. 11, No. 11 ( 2022-05-27), p. 3033-
    Details
    In: Journal of Clinical Medicine, MDPI AG, Vol. 11, No. 11 ( 2022-05-27), p. 3033-
    Abstract: Background: Growth differentiation factor (GDF15) is a superfamily of transforming growth factor-beta which has been suggested to be correlated with various pathological conditions. The current study aimed to investigate the predicted role of circulating GDF15 in diabetic metabolism characteristics and diabetic neuropathy. Methods: 241 diabetic patients and 42 non-diabetic subjects were included to participate in the study. The plasma GDF15 levels were measured using ELISA. Chronic kidney disease and albuminuria were defined according to the Kidney Disease: Improving Global Outcomes (KDIGO) guideline. The nerve conductive study (NCS) was performed with measurement of distal latency, amplitude, nerve conduction velocity (NCV), H-reflex, and F-wave studies. Results: The diabetic group had a significantly higher prevalence of chronic kidney disease and higher plasma GDF15 level. After adjusting for age and BMI, GDF15 was significantly positively correlated with waist circumference (r = 0.332, p = 〈 0.001), hip circumference (r = 0.339, p 〈 0.001), HbA1c (r = 0.302, p 〈 0.001), serum creatine (r = 0.146, p = 0.017), urine albumin/creatinine ratio (r = 0.126, p = 0.040), and HOMA-IR (r = 0.166, p = 0.007). As to NCS, GDF15 was significantly correlated with all latency and amplitude of sensory and motor nerves, as well as F-wave and H-reflex latencies. The area under the curve (AUC) in predicting tibial motor nerve neuropathy (MNCV) in all subjects and in the diabetic group for GDF15 was 0.646 (p = 0.001) and 0.610 (p = 0.012), respectively; for HbA1c was 0.639 (p = 0.001) and 0.604 (p = 0.018), respectively. Predicting ulnar sensory nerve neuropathy for GDF15 was 0.639 (p = 0.001) and 0.658 (p = 0.001), respectively; for HbA1c was 0.545 (p = 0.307) and 0.545 (p = 0.335), respectively. Predicting median sensory nerve neuropathy for GDF15 was 0.633 (p = 0.007) and 0.611 (p = 0.032), respectively; for HbA1c was 0.631 (p = 0.008) and 0.607 (p = 0.038), respectively. Predicting CKD for GDF15 was 0.709 (95% CI, 0.648–0.771), p 〈 0.001) and 0.676 (95% CI, 0.605–0.746), p 〈 0.001), respectively; for HbA1c was 0.560 (95% CI, 0.493–0.627); p = 0.080) and 0.515 (95% CI, 0.441–0.588); p = 0.697), respectively. Conclusions: We suggest that there is a significant association between the increased serum GDF-15 level and metabolic parameters and diabetic neuropathy. Plasma GDF15 may be an independent predictor of diabetic neuropathy.
    Type of Medium: Online Resource
    ISSN: 2077-0383
    URL: Article
    DOI: 10.3390/jcm11113033
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
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  • 2
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    Coexistence of Multiple Myositis-Specific Antibodies in Patients with Idiopathic Inflammatory Myopathies
    MDPI AG ; 2022
    In:  Journal of Clinical Medicine Vol. 11, No. 23 ( 2022-11-25), p. 6972-
    Details
    In: Journal of Clinical Medicine, MDPI AG, Vol. 11, No. 23 ( 2022-11-25), p. 6972-
    Abstract: The mutual exclusivity of myositis-specific antibodies (MSAs) has been reported before, but the coexistence of 2 or more MSAs was still found in a few case reports. This study aims to confirm the existence and prevalence of double MSAs in patients with idiopathic inflammatory myopathy (IIM) and to clarify the clinical features of these patients. One hundred fifty-one patients with IIM diagnosed from 1 July 2018 to 31 July 2022, at National Cheng Kung University Hospital, Taiwan, were enrolled and divided into two groups, patients with ≤1 MSA (n = 128, 84.8%) and those with ≥2 MSAs (n = 23, 15.2%) according to the initial serology results. After being re-examined by ANA-IIF assay, 8 out of 23 patients were confirmed to have ≥2 MSAs. The demographic data and clinical features were presented. The prevalence of double-positive MSAs among IIM was 5.3% in this cohort. The coexistence of two MSAs in an IIM patient does exist but is rare. Patients with two MSAs belonging to two distinct IIM subtypes presented clinical features skewed to one subtype instead of “mixed phenotypes”. No apparent difference in clinical severity was found between patients with ≥2 MSAs and ≤1 MSA. Longer follow-ups and more studies are required to characterize the patients of IIM with ≥2 MSAs.
    Type of Medium: Online Resource
    ISSN: 2077-0383
    URL: Article
    DOI: 10.3390/jcm11236972
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
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  • 3
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    High-Sensitivity Dual-Probe Detection of Urinary miR-141 in Cancer Patients via a Modified Screen-Printed Carbon Electrode-Based Electrochemical Biosensor
    MDPI AG ; 2021
    In:  Sensors Vol. 21, No. 9 ( 2021-05-03), p. 3183-
    Details
    In: Sensors, MDPI AG, Vol. 21, No. 9 ( 2021-05-03), p. 3183-
    Abstract: The screening and diagnosis of cancer are hallmarks of medicine in the aging population. Recently, microRNAs have shown potential for use as biomarkers, which could advance the field of diagnostics. The presence of miRNA-141 in the serum has been well described in several malignancies. However, the invasive approach used for sampling represents the major limitation for its practical application and, hence, its notable absence as a method for screening the general population. In light of this, we aimed to develop a high-sensitivity microRNA (miR) biosensor for application in the diagnosis of all miR-141-associated cancers, such as colorectal cancer (CRC) and breast cancer (BC). The novelty lies in our dual-probe design, which is reliant on the hybridization of the fluorescein isothiocyanate (FITC) targeting probe onto an existing sample of urinary miR-141 in the first step, followed by complementary binding with a biotinylated probe that has been coated on a modified screen-printed carbon electrode (SPCE). The hybridization of the probe and sensor produces signals via the catalytic reduction of H2O2 at HRP-modified SPCEs in the presence of H2O, which was measured by either cyclic voltammetry or chronoamperometry (CA) currents. In our study, the detection and expression of miR-141 in a cohort of colorectal cancer (n = 6) and breast cancer (n = 4) samples showed that its levels were significantly higher than in a healthy cohort (n = 9) (p 〈 0.004). Moreover, our miR sensor demonstrated high stability, reliability, and sensitivity (p 〈 0.0001). This work hopefully provides new information for the detection and monitoring of de novo and existing cancers.
    Type of Medium: Online Resource
    ISSN: 1424-8220
    URL: Article
    DOI: 10.3390/s21093183
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2052857-7
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  • 4
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    Hepatic Steatosis Assessment as a New Strategy for the Metabolic and Nutritional Management of Duchenne Muscular Dystrophy
    MDPI AG ; 2022
    In:  Nutrients Vol. 14, No. 4 ( 2022-02-09), p. 727-
    Details
    In: Nutrients, MDPI AG, Vol. 14, No. 4 ( 2022-02-09), p. 727-
    Abstract: Growing evidence suggests that patients with Duchenne muscular dystrophy (DMD) have an increased risk of obesity and metabolic syndrome (MetS). The aim of this study was to investigate the potential risk factors for MetS and hepatic steatosis in patients with different stages of DMD. A total of 48 patients with DMD were enrolled and classified into three stages according to ambulatory status. Body mass index (BMI), serum fasting glucose, insulin, and lipid profiles including triglycerides (TG) and high-density lipoprotein were measured, and the homeostatic model assessment for insulin resistance (HOMA-IR) index was evaluated. Ultrasound examinations of the liver were performed to assess hepatic steatosis using the Nakagami parameter index (NPI). The results showed that BMI, TG, HOMA-IR, and ultrasound NPI differed significantly among DMD stages (p 〈 0.05). In contrast to the low rates of conventional MetS indices, including disturbed glucose metabolism (0%), dyslipidemia (14.28%), and insulin resistance (4.76%), a high proportion (40.48%) of the patients had significant hepatic steatosis. The ultrasound NPI increased with DMD progression, and two thirds of the non-ambulatory patients had moderate to severe hepatic steatosis. Steroid treatment was a risk factor for hepatic steatosis in ambulatory patients (p 〈 0.05). We recommend that DMD patients should undergo ultrasound evaluations for hepatic steatosis for better metabolic and nutritional management.
    Type of Medium: Online Resource
    ISSN: 2072-6643
    URL: Article
    DOI: 10.3390/nu14040727
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2518386-2
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  • 5
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    Multiple Single Nucleotide Polymorphism Testing Improves the Prediction of Diabetic Retinopathy Risk with Type 2 Diabetes Mellitus
    MDPI AG ; 2021
    In:  Journal of Personalized Medicine Vol. 11, No. 8 ( 2021-07-21), p. 689-
    Details
    In: Journal of Personalized Medicine, MDPI AG, Vol. 11, No. 8 ( 2021-07-21), p. 689-
    Abstract: Diabetic retinopathy (DR) is one of the most frequent causes of irreversible blindness, thus prevention and early detection of DR is crucial. The purpose of this study is to identify genetic determinants of DR in individuals with type 2 diabetic mellitus (T2DM). A total of 551 T2DM patients (254 with DR, 297 without DR) were included in this cross-sectional research. Thirteen T2DM-related single nucleotide polymorphisms (SNPs) were utilized for constructing genetic risk prediction model. With logistic regression analysis, genetic variations of the FTO (rs8050136) and PSMD6 (rs831571) polymorphisms were independently associated with a higher risk of DR. The area under the curve (AUC) calculated on known nongenetic risk variables was 0.704. Based on the five SNPs with the highest odds ratio (OR), the combined nongenetic and genetic prediction model improved the AUC to 0.722. The discriminative accuracy of our 5-SNP combined risk prediction model increased in patients who had more severe microalbuminuria (AUC = 0.731) or poor glycemic control (AUC = 0.746). In conclusion, we found a novel association for increased risk of DR at two T2DM-associated genetic loci, FTO (rs8050136) and PSMD6 (rs831571). Our predictive risk model presents new insights in DR development, which may assist in enabling timely intervention in reducing blindness in diabetic patients.
    Type of Medium: Online Resource
    ISSN: 2075-4426
    URL: Article
    DOI: 10.3390/jpm11080689
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2662248-8
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  • 6
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    Clinical Efficacy of Adjuvant Chemotherapy in Advanced Upper Tract Urothelial Carcinoma (pT3-T4): Real-World Data from the Taiwan Upper Tract Urothelial Carcinoma Collaboration Group
    MDPI AG ; 2022
    In:  Journal of Personalized Medicine Vol. 12, No. 2 ( 2022-02-06), p. 226-
    Details
    In: Journal of Personalized Medicine, MDPI AG, Vol. 12, No. 2 ( 2022-02-06), p. 226-
    Abstract: The clinical efficacy of adjuvant chemotherapy in upper tract urothelial carcinoma (UTUC) is unclear. We aimed to assess the therapeutic outcomes of adjuvant chemotherapy in patients with advanced UTUC (pT3-T4) after radical nephroureterectomy (RNU). We retrospectively reviewed the data of 2108 patients from the Taiwan UTUC Collaboration Group between 1988 and 2018. Comprehensive clinical features, pathological characteristics, and survival outcomes were recorded. Univariate and multivariate Cox proportional hazards models were used to evaluate overall survival (OS), cancer-specific survival (CSS), and disease-free survival (DFS). Of the 533 patients with advanced UTUC included, 161 (30.2%) received adjuvant chemotherapy. In the multivariate analysis, adjuvant chemotherapy was significantly associated with a reduced risk of overall death (hazard ratio (HR), 0.599; 95% confidence interval (CI), 0.419–0.857; p = 0.005), cancer-specific mortality (HR, 0.598; 95% CI, 0.391–0.914; p = 0.018), and cancer recurrence (HR, 0.456; 95% CI, 0.310–0.673; p 〈 0.001). The Kaplan–Meier survival analysis revealed that patients receiving adjuvant chemotherapy had significantly better five-year OS (64% vs. 50%, p = 0.002), CSS (70% vs. 62%, p = 0.043), and DFS (60% vs. 48%, p = 0.002) rates compared to those who did not receive adjuvant chemotherapy. In conclusion, adjuvant chemotherapy after RNU had significant therapeutic benefits on OS, CSS, and DFS in advanced UTUC.
    Type of Medium: Online Resource
    ISSN: 2075-4426
    URL: Article
    DOI: 10.3390/jpm12020226
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
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  • 7
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    Moscatilin Inhibits Metastatic Behavior of Human Hepatocellular Carcinoma Cells: A Crucial Role of uPA Suppression via Akt/NF-κB-Dependent Pathway
    MDPI AG ; 2021
    In:  International Journal of Molecular Sciences Vol. 22, No. 6 ( 2021-03-13), p. 2930-
    Details
    In: International Journal of Molecular Sciences, MDPI AG, Vol. 22, No. 6 ( 2021-03-13), p. 2930-
    Abstract: Hepatocellular carcinoma (HCC) frequently shows early invasion into blood vessels as well as intrahepatic metastasis. Innovations of novel small-molecule agents to block HCC invasion and subsequent metastasis are urgently needed. Moscatilin is a bibenzyl derivative extracted from the stems of a traditional Chinese medicine, orchid Dendrobium loddigesii. Although moscatilin has been reported to suppress tumor angiogenesis and growth, the anti-metastatic property of moscatilin has not been elucidated. The present results revealed that moscatilin inhibited metastatic behavior of HCC cells without cytotoxic fashion in highly invasive human HCC cell lines. Furthermore, moscatilin significantly suppressed the activity of urokinase plasminogen activator (uPA), but not matrix metalloproteinase (MMP)-2 and MMP-9. Interestingly, moscatilin-suppressed uPA activity was through down-regulation the protein level of uPA, and did not impair the uPA receptor and uPA inhibitory molecule (PAI-1) expressions. Meanwhile, the mRNA expression of uPA was inhibited via moscatilin in a concentration-dependent manner. In addition, the expression of phosphorylated Akt, rather than ERK1/2, was inhibited by moscatilin treatment. The expression of phosphor-IκBα, and -p65, as well as κB-luciferase activity were also repressed after moscatilin treatment. Transfection of constitutively active Akt (Myr-Akt) obviously restored the moscatilin-inhibited the activation of NF-κB and uPA, and cancer invasion in HCC cells. Taken together, these results suggest that moscatilin impedes HCC invasion and uPA expression through the Akt/NF-κB signaling pathway. Moscatilin might serve as a potential anti-metastatic agent against the disease progression of human HCC.
    Type of Medium: Online Resource
    ISSN: 1422-0067
    URL: Article
    DOI: 10.3390/ijms22062930
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2019364-6
    SSG: 12
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  • 8
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    Impacts of the Kuroshio Intrusion through the Luzon Strait on the Local Precipitation Anomaly
    MDPI AG ; 2021
    In:  Remote Sensing Vol. 13, No. 6 ( 2021-03-15), p. 1113-
    Details
    In: Remote Sensing, MDPI AG, Vol. 13, No. 6 ( 2021-03-15), p. 1113-
    Abstract: The Kuroshio Current has its origin in the northwestern Pacific, flowing northward to the east of Taiwan and the northern part of Luzon Island. As the Kuroshio Current flows northward, it quasi-periodically intrudes (hereafter referred to as Kuroshio intrusion (KI)) into the northern South China Sea (SCS) basin through the Luzon Strait. Despite the complex generation mechanisms of KI, the purpose of this study is to improve our understanding of the effects of KI through the Luzon Strait on the regional atmospheric and weather variations. Long-term multiple satellite observations, including absolute dynamic topography, absolute geostrophic currents, sea surface winds by ASCAT, multi-scale ultra-high resolution sea surface temperature (MURSST) level-four analysis, and research-quality three-hourly TRMM multi-satellite precipitation analysis (TMPA), was used to systematically examine the aforementioned scientific problem. Analysis indicates that the KI is interlinked with the consequential anomalous precipitation off southwestern Taiwan. This anomalous precipitation would lead to ~560 million tons of freshwater influx during each KI event. Subsequently, independent moisture budget analysis suggests that moisture, mainly from vertical advection, is the possible source of the precipitation anomaly. Additionally, a bulk formula analysis was applied to understand how KI can trigger the precipitation anomaly through vertical advection of moisture without causing an evident change in the low-level flows. These new research findings might reconcile the divisiveness on why winds are not showing a synchronous response during the KI and consequential anomalous precipitation events.
    Type of Medium: Online Resource
    ISSN: 2072-4292
    URL: Article
    DOI: 10.3390/rs13061113
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2513863-7
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  • 9
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    Endometrial Cancer Detection Using a Cervical DNA Methylation Assay (MPap) in Women with Abnormal Uterine Bleeding: A Multicenter Hospital-Based Validation Study
    MDPI AG ; 2022
    In:  Cancers Vol. 14, No. 17 ( 2022-09-05), p. 4343-
    Details
    In: Cancers, MDPI AG, Vol. 14, No. 17 ( 2022-09-05), p. 4343-
    Abstract: Background: We describe a DNA methylation assay, named MPap test, using cervical scraping as an alternative technique for endometrial cancer detection. Methods: A multicenter hospital-based, two-stage validation study was conducted to validate the cancer detection performance of the MPap test. The MPap value was determined from the DNA methylation status of two genes (BHLHE22, CDO1) and combined with two other clinical variables (age, BMI). The cutoff threshold of the MPap value was established in stage 1 and validated in stage 2. A total of 592 women with abnormal uterine bleeding were enrolled from five medical centers throughout Taiwan. Results: In stage 1, the sensitivity, specificity, and positive and negative predictive values of the MPap test for detecting endometrial cancer were 92.9%, 71.5%, 39.8%, and 98.0%, respectively. These values were validated in stage 2, being 92.5%, 73.8%, 40.2%, and 98.1%. Moreover, MPap outperformed transvaginal ultrasound in sensitivity and negative predictive values for detecting endometrial cancer. When we applied the algorithm for triage of endometrial cancer detection by MPap in the Taiwan National Health Insurance dataset, we found that it may reduce invasive procedures by 69~73%. Conclusions: MPap may provide a feasible alternative for endometrial cancer detection and can be considered as a triage test to reduce unnecessary invasive procedures.
    Type of Medium: Online Resource
    ISSN: 2072-6694
    URL: Article
    DOI: 10.3390/cancers14174343
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2527080-1
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  • 10
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    Prognostic Significance of Primary Tumor Location in Upper Tract Urothelial Carcinoma Treated with Nephroureterectomy: A Retrospective, Multi-Center Cohort Study in Taiwan
    MDPI AG ; 2020
    In:  Journal of Clinical Medicine Vol. 9, No. 12 ( 2020-11-27), p. 3866-
    Details
    In: Journal of Clinical Medicine, MDPI AG, Vol. 9, No. 12 ( 2020-11-27), p. 3866-
    Abstract: We sought to examine the effect of tumor location on the prognosis of patients with upper tract urothelial carcinoma (UTUC) treated with radical nephroureterectomy (RNU). This retrospective study came from the Taiwan UTUC Collaboration Group, which consisted of 2658 patients at 15 institutions in Taiwan from 1988 to 2019. Patients with kidney-sparing management, both renal pelvic and ureteral tumors, as well as patients lacking complete data were excluded; the remaining 1436 patients were divided into two groups: renal pelvic tumor (RPT) and ureteral tumor (UT), with 842 and 594 patients, respectively. RPT was associated with more aggressive pathological features, including higher pathological T stage (p 〈 0.001) and the presence of lymphovascular invasion (p = 0.002), whereas patients with UT often had synchronous bladder tumor (p 〈 0.001), and were more likely to bear multiple lesions (p = 0.001). Our multivariate analysis revealed that UT was a worse prognostic factor compared with RPT (overall survival: HR 1.408, 95% CI 1.121–1.767, p = 0.003; cancer-specific survival: HR 1.562, 95% CI 1.169–2.085, p = 0.003; disease-free survival: HR 1.363, 95% CI 1.095–1.697, p = 0.006; bladder-recurrence-free survival: HR 1.411, 95% CI 1.141–1.747, p = 0.002, respectively). Based on our findings, UT appeared to be more malignant and had a worse prognosis than RPT.
    Type of Medium: Online Resource
    ISSN: 2077-0383
    URL: Article
    DOI: 10.3390/jcm9123866
    Language: English
    Publisher: MDPI AG
    Publication Date: 2020
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