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  • 1
    Online Resource
    Online Resource
    Translational Medicine in Uremic Vascular Calcification: Scavenging ROS Attenuates p-Cresyl Sulfate-Activated Caspase-1, NLRP3 Inflammasome and Eicosanoid Inflammation in Human Arterial Smooth Muscle Cells
    MDPI AG ; 2022
    In:  Life Vol. 12, No. 5 ( 2022-05-23), p. 769-
    Details
    In: Life, MDPI AG, Vol. 12, No. 5 ( 2022-05-23), p. 769-
    Abstract: We formerly proved that uremic vascular calcification (UVC) correlates tightly with oxidative elastic lamina (EL) injury and two cell fates (apoptosis and osteocytic conversion) in smooth muscle cells (SMC) of chronic kidney disease (CKD) patients and eliminating p-cresyl sulfate (PCS)-activated intracellular ROS ameliorates the MAPK signaling pathway in a human arterial SMC (HASMC) model. Nonetheless, whether ROS scavenger attenuates PCS-triggered inflammasome activation and eicosanoid inflammation in the UVC process remains unknown. Patients with lower extremity amputation were categorized into CKD and normal control group according to renal function. We used immunohistochemistry stain to analyze UVC in arterial specimens, including oxidative injury (8-hydroxy-2′-deoxyguanosine (8-OHdG) and internal EL disruption), cytosolic phospholipase A2 (cPLA2), cyclooxygenase 2 (COX2), interleukin-1 beta (IL-1β), caspase-1 and NLRP3. To simulate the patho-mechanism of human UVC, the therapeutic effects of ROS scavenger on PCS-triggered inflammatory pathways was explored in a HASMC model. We found CKD patients had higher circulating levels of PCS and an increase in medial arterial calcification than the control group. In CKD arteries, the severity of UVC corresponded with expressions of oxidative EL disruption and 8-OHdG. Furthermore, coupling expressions of cPLA2 and COX2 were accentuated in CKD arteries, indicative of eicosanoid inflammation. Notably, tissue expressions of IL-1β, caspase-1 and NLRP3 were enhanced in parallel with UVC severity, indicative of inflammasome activation. From bedside to bench, ROS scavenger attenuates PCS-activated expressions of cPLA2/COX2, pro-caspase-1 and NLRP3 in the HASMC model. UVC as an inevitable outcome is predictive of death in CKD patients. Nonetheless, UVC remain pharmacoresistant despite the evolution of treatment for mineral-parathyroid hormone-vitamin D axis. Beyond the mineral dysregulation, the stimulation of pro-oxidant PCS alone results in eicosanoid inflammation and inflammasome activation. Concerning the key role of Caspase-1 in pyroptosis, cell fates of HASMC in uremic milieu are not limited to apoptosis and osteogenesis. In view of this, reducing ROS and PCS may act as a therapeutic strategy for UVC-related cardiovascular events in CKD patients.
    Type of Medium: Online Resource
    ISSN: 2075-1729
    URL: Article
    DOI: 10.3390/life12050769
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2662250-6
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  • 2
    Online Resource
    Online Resource
    Synergistic Chemopreventive Effects of a Novel Combined Plant Extract Comprising Gallic Acid and Hesperidin on Colorectal Cancer
    MDPI AG ; 2023
    In:  Current Issues in Molecular Biology Vol. 45, No. 6 ( 2023-06-05), p. 4908-4922
    Details
    In: Current Issues in Molecular Biology, MDPI AG, Vol. 45, No. 6 ( 2023-06-05), p. 4908-4922
    Abstract: Background/Aim: Colorectal cancer (CRC) is the third most common cancer with a high mortality rate worldwide. Although gallic acid and hesperidin exert anticancer activity, synergistic effects of gallic acid and hesperidin against CRC remain elusive. This study aims to investigate the therapeutic mechanism of a novel combination of gallic acid and hesperidin against CRC cell growth, including cell viability, cell-cycle-associated proteins, spheroid formation, and stemness. Methods: Gallic acid and hesperidin derived from Hakka pomelo tea (HPT) were detected by colorimetric methods and high-performance liquid chromatography using ethyl acetate as an extraction medium. CRC cell lines (HT-29 and HCT-116) treated with the combined extract were investigated in our study for cell viability (trypan blue or soft agar colony formation assay), cell cycle (propidium iodide staining), cell-cycle-associated proteins (immunoblotting), and stem cell markers (immunohistochemistry staining). Results: Compared with other extraction methods, HPT extraction using an ethyl acetate medium exerts the most potent effect on inhibiting HT-29 cell growth in a dose-dependent manner. Furthermore, the treatment with combined extract had a higher inhibitory effect on CRC cell viability than gallic acid or hesperidin alone. The underlying mechanism was involved in G1-phase arrest and Cip1/p21 upregulation that could attenuate HCT-116 cell proliferation (Ki-67), stemness (CD-133), and spheroid growth in a 3D formation assay mimicking in vivo tumorigenesis. Conclusion: Gallic acid and hesperidin exert synergistic effects on cell growth, spheroids, and stemness of CRC and may serve as a potential chemopreventive agent. Further testing for the safety and effectiveness of the combined extract in large-scale randomized trials is required.
    Type of Medium: Online Resource
    ISSN: 1467-3045
    URL: Article
    DOI: 10.3390/cimb45060312
    Language: English
    Publisher: MDPI AG
    Publication Date: 2023
    detail.hit.zdb_id: 2090836-2
    SSG: 12
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  • 3
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    Increased Diagnostic Yield of Array Comparative Genomic Hybridization for Autism Spectrum Disorder in One Institution in Taiwan
    MDPI AG ; 2021
    In:  Medicina Vol. 58, No. 1 ( 2021-12-22), p. 15-
    Details
    In: Medicina, MDPI AG, Vol. 58, No. 1 ( 2021-12-22), p. 15-
    Abstract: Background and Objectives: Chromosomal microarray offers superior sensitivity for identification of submicroscopic copy number variants (CNVs) and is recommended for the initial genetic testing of patients with autism spectrum disorder (ASD). This study aims to determine the diagnostic yield of array comparative genomic hybridization (array-CGH) in ASD patients from a cohort of Chinese patients in Taiwan. Materials and Methods: Enrolled in this study were 80 ASD children (49 males and 31 females; 2–16 years old) followed up at Taipei MacKay Memorial Hospital between January 2010 and December 2020. The genomic DNA extracted from blood samples was analyzed by array-CGH via the Affymetrix GeneChip Genome-Wide Human single nucleotide polymorphism (SNP) and NimbleGen International Standards for Cytogenomic Arrays (ISCA) Plus Cytogenetic Arrays. The CNVs were classified into five groups: pathogenic (pathologic variant), likely pathogenic (potential pathologic variant), likely benign (potential normal genomic variant), benign (normal genomic variant), and uncertain clinical significance (variance of uncertain significance), according to the American College of Medical Genetics (ACMG) guidelines. Results: We identified 47 CNVs, 31 of which in 27 patients were clinically significant. The overall diagnostic yield was 33.8%. The most frequently clinically significant CNV was 15q11.2 deletion, which was present in 4 (5.0%) patients. Conclusions: In this study, a satisfactory diagnostic yield of array-CGH was demonstrated in a Taiwanese ASD patient cohort, supporting the clinical usefulness of array-CGH as the first-line testing of ASD in Taiwan.
    Type of Medium: Online Resource
    ISSN: 1648-9144
    URL: Article
    DOI: 10.3390/medicina58010015
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2088820-X
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  • 4
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    Online Resource
    The Circadian Hormone Melatonin Inhibits Morphine-Induced Tolerance and Inflammation via the Activation of Antioxidative Enzymes
    MDPI AG ; 2020
    In:  Antioxidants Vol. 9, No. 9 ( 2020-08-22), p. 780-
    Details
    In: Antioxidants, MDPI AG, Vol. 9, No. 9 ( 2020-08-22), p. 780-
    Abstract: Opioids are commonly prescribed for clinical pain management; however, dose-escalation, tolerance, dependence, and addiction limit their usability for long-term chronic pain. The associated poor sleep pattern alters the circadian neurobiology, and further compromises the pain management. Here, we aim to determine the correlation between constant light exposure and morphine tolerance and explore the potential of melatonin as an adjuvant of morphine for neuropathic pain treatment. Methods: Wistar rats were preconditioned under constant light (LL) or a regular light/dark (LD) cycle before neuropathic pain induction by chronic constriction injury. An intrathecal (i.t.) osmotic pump was used for continued drug delivery to induce morphine tolerance. Pain assessments, including the plantar test, static weight-bearing symmetry, and tail-flick latency, were used to determine the impact of the light disruption or exogenous melatonin on the morphine tolerance progression. Results: constant light exposure significantly aggravates morphine tolerance in neuropathic rats. Continued infusion of low-dose melatonin (3 μg/h) attenuated morphine tolerance in both neuropathic and naïve rats. This protective effect was independent of melatonin receptors, as shown by the neutral effect of melatonin receptors inhibitors. The transcriptional profiling demonstrated a significant enhancement of proinflammatory and pain-related receptor genes in morphine-tolerant rats. In contrast, this transcriptional pattern was abolished by melatonin coinfusion along with the upregulation of the Kcnip3 gene. Moreover, melatonin increased the antioxidative enzymes SOD2, HO-1, and GPx1 in the spinal cord of morphine-tolerant rats. Conclusion: Dysregulated circadian light exposure significantly compromises the efficacy of morphine’s antinociceptive effect, while the cotreatment with melatonin attenuates morphine tolerance/hyperalgesia development. Our results suggest the potential of melatonin as an adjuvant of morphine in clinical pain management, particularly in patients who need long-term opioid treatment.
    Type of Medium: Online Resource
    ISSN: 2076-3921
    URL: Article
    DOI: 10.3390/antiox9090780
    Language: English
    Publisher: MDPI AG
    Publication Date: 2020
    detail.hit.zdb_id: 2704216-9
    SSG: 15,3
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  • 5
    Online Resource
    Online Resource
    Endogenous Expression of G-CSF in Rat Dorsal Root Ganglion Neurons after Nerve Injury
    MDPI AG ; 2021
    In:  Brain Sciences Vol. 11, No. 7 ( 2021-07-20), p. 956-
    Details
    In: Brain Sciences, MDPI AG, Vol. 11, No. 7 ( 2021-07-20), p. 956-
    Abstract: Granulocyte colony-stimulating factor (G-CSF) has been reported to modulate pain function following nerve injury. However, the expression of endogenous G-CSF in the dorsal root ganglion (DRG) and the response to nerve injury remain unclear. In the present study, we demonstrated that G-CSF and G-CSFR are mainly expressed in both small- and medium-diameter DRG neurons in rats and are responsible for transmitting pain responses. G-CSF and G-CSFR were co-expressed in certain nociceptive DRG neurons. In addition, G-CSF was expressed in satellite glial cells around large-diameter DRG neurons. After sciatic nerve injury, the number of G-CSF-positive DRG neurons was increased in both the ipsilateral and contralateral lesion sites in rats. However, G-CSF expression in satellite glial cells was not affected by nerve injury. To clarify the role of G-CSF in pain, exogenous G-CSF was administered to a rat model of neuropathic pain induced by partial sciatic nerve transaction (PST). Our results indicate that treatment with G-CSF did not attenuate but exacerbated neuropathic pain. In summary, G-CSF may directly activate sensory neurons and contribute to nociceptive signaling.
    Type of Medium: Online Resource
    ISSN: 2076-3425
    URL: Article
    DOI: 10.3390/brainsci11070956
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2651993-8
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  • 6
    Online Resource
    Online Resource
    A Novel Method for In-Situ Monitoring of Local Voltage, Temperature and Humidity Distributions in Fuel Cells Using Flexible Multi-Functional Micro Sensors
    MDPI AG ; 2011
    In:  Sensors Vol. 11, No. 2 ( 2011-01-26), p. 1418-1432
    Details
    In: Sensors, MDPI AG, Vol. 11, No. 2 ( 2011-01-26), p. 1418-1432
    Type of Medium: Online Resource
    ISSN: 1424-8220
    URL: Article
    DOI: 10.3390/s110201418
    Language: English
    Publisher: MDPI AG
    Publication Date: 2011
    detail.hit.zdb_id: 2052857-7
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  • 7
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    Assessment of Petobo Flowslide Induced by Soil Liquefaction during 2018 Palu–Donggala Indonesian Earthquake
    MDPI AG ; 2023
    In:  Sustainability Vol. 15, No. 6 ( 2023-03-17), p. 5371-
    Details
    In: Sustainability, MDPI AG, Vol. 15, No. 6 ( 2023-03-17), p. 5371-
    Abstract: This paper presents the results of the subsurface investigation and liquefaction assessment of the Petobo flowslide, induced by soil liquefaction during the Mw 7.5 Palu–Donggala earthquake of Indonesia on 28 September 2018. The investigations, including drilling, standard penetration tests, electrical resistivity imaging survey, dynamic probing, groundwater table monitoring, etc., were conducted along the main road that passes through the middle of the flowslide area. Liquefaction assessments and flowslide simulations were carried out with three assumed scenarios. Scenario 1 describes the condition if the flowslide were to be retriggered at the cease of sliding due to the same earthquake striking the site. Scenarios 2 and 3 attempt to examine the influence of locally raised groundwater levels due to the infiltration of the Gumbasa irrigation system and widespread paddy fields of the site as a result of soil liquefaction and the flowslide. Subsurface investigations revealed that, within a 30-m depth of the ground, the sliding area generally consists of sandy deposits of SM/SP/SW, except for the toe portion where thick layers of silt (ML) and clay (CL) were found. The results of field testing and liquefaction assessment identify potentially weak and liquefiable zones which enable the construction of a speculated slip surface for the flowslide. Both liquefaction assessment and flowslide simulations verify that soil liquefaction would be triggered during the earthquake as a result of locally raised groundwater tables, and that a gentle slope (≈3°) that provides static shears would lead to long-distance sliding after shaking. Should the locally raised groundwater tables not exist, the results indicate no soil liquefaction and no flowslide.
    Type of Medium: Online Resource
    ISSN: 2071-1050
    URL: Article
    DOI: 10.3390/su15065371
    Language: English
    Publisher: MDPI AG
    Publication Date: 2023
    detail.hit.zdb_id: 2518383-7
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  • 8
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    Online Resource
    Caffeic Acid Phenethyl Ester Is a Potential Therapeutic Agent for Oral Cancer
    MDPI AG ; 2015
    In:  International Journal of Molecular Sciences Vol. 16, No. 12 ( 2015-05-12), p. 10748-10766
    Details
    In: International Journal of Molecular Sciences, MDPI AG, Vol. 16, No. 12 ( 2015-05-12), p. 10748-10766
    Type of Medium: Online Resource
    ISSN: 1422-0067
    URL: Article
    DOI: 10.3390/ijms160510748
    Language: English
    Publisher: MDPI AG
    Publication Date: 2015
    detail.hit.zdb_id: 2019364-6
    SSG: 12
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  • 9
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    Verification of Saliva Matrix Metalloproteinase-1 as a Strong Diagnostic Marker of Oral Cavity Cancer
    MDPI AG ; 2020
    In:  Cancers Vol. 12, No. 8 ( 2020-08-13), p. 2273-
    Details
    In: Cancers, MDPI AG, Vol. 12, No. 8 ( 2020-08-13), p. 2273-
    Abstract: Oral squamous cell carcinoma (OSCC) accounts for 〉 90% of cases of oral cancer, including cancer at the lip and oral cavity and cancer at the oropharynx. Most OSCCs develop from oral potentially malignant disorders (OPMDs), which consist of heterogeneous lesions with different malignant transformation potentials that make early detection of OSCC a challenge. Using a targeted mass spectrometry-based assay to compare multiple candidate proteins, we previously identified matrix metalloproteinase-1 (MMP-1) as one of the most promising salivary OSCC biomarkers. To explore the clinical utility of MMP-1 in OSCC detection, we developed an in-house, sensitive enzyme-linked immunosorbent assay (ELISA) for measuring MMP-1 content, and tested it on saliva samples from 1160 subjects (313 healthy controls, and 578 OPMD and 269 OSCC patients) collected at two medical centers. Salivary MMP-1 levels measured by our in-house ELISA significantly discriminated OSCC patients from non-cancerous groups. A receiver operating characteristic curve analysis showed that MMP-1 was effective in separating non-cancer groups from patients with OSCCs at the oral cavity. Additionally, salivary MMP-1 levels in oral cavity cancer patients were highly correlated with tumor progression (tumor size, lymph node metastasis, and overall stage). Collectively, our results indicate that salivary MMP-1 is an effective biomarker for OSCC that can be sensitively detected using our newly developed ELISA. The newly developed MMP-1 ELISA may be used as a new adjunctive tool to aid in detecting and monitoring OSCC.
    Type of Medium: Online Resource
    ISSN: 2072-6694
    URL: Article
    DOI: 10.3390/cancers12082273
    Language: English
    Publisher: MDPI AG
    Publication Date: 2020
    detail.hit.zdb_id: 2527080-1
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  • 10
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    The Survival of Septic Patients with Compensated Liver Cirrhosis Is Not Inferior to That of Septic Patients without Liver Cirrhosis: A Propensity Score Matching Analysis
    MDPI AG ; 2022
    In:  Journal of Clinical Medicine Vol. 11, No. 6 ( 2022-03-15), p. 1629-
    Details
    In: Journal of Clinical Medicine, MDPI AG, Vol. 11, No. 6 ( 2022-03-15), p. 1629-
    Abstract: Background: We aimed to determine whether septic patients with liver cirrhosis (LC) had worse survival than septic patients without liver cirrhosis (WLC). We also investigated the survival of septic patients with compensated liver cirrhosis (CLC) and decompensated liver cirrhosis (DLC). Methods: This study enrolled 776 consecutive adult patients with sepsis admitted to the medical intensive care units of a tertiary referral hospital. Clinical factors and laboratory data were collected for analysis. Propensity scoring was also used for the control of selection bias. The variables included in the propensity model were age, sex, presence of diabetes mellitus, hypertension, cardiovascular accident, chronic kidney disease, malignancy, APCHE II (Acute Physiology and Chronic Health Evaluation) score, hemoglobin, and platelet data on the day when sepsis was confirmed. Seven-day, ICU, and hospital mortality were analyzed after correcting for these confounding factors. Results: Of the 776 septic patients, 64 (8.2%) septic patients presented with LC. Patients were divided into two groups—LC (n = 64) and WLC (n = 712)—which presented different rates of hospital mortality (LC: 62.5% vs. WLC: 41.0%, p = 0.001). We further separated septic patients with LC into two groups: patients with CLC (n = 24) and those with DLC (n = 40). After propensity score matching, the survival of septic patients with CLC (63.6%) was not inferior to patients WLC (54.5%) (p = 0.411). Patients with DLC had more hospital mortality, even after matching (p 〈 0.05). The Quick SOFA (qSOFA) score, SOFA score, and sub-SOFA score were also comparable between groups. SOFA scores were not significantly different between the CLC and WLC groups after matching. Poor SOFA scores were observed in the DLC group on days 3 and 7 after matching (p 〈 0.05). Conclusions: Septic patients with LC had higher mortality compared to patients WLC before matching. However, after propensity score matching, the survival of septic patients with CLC was non-inferior to patients WLC.
    Type of Medium: Online Resource
    ISSN: 2077-0383
    URL: Article
    DOI: 10.3390/jcm11061629
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2662592-1
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