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  • 11
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    Online Resource
    Revisiting Genetic Epidemiology with a Refined Targeted Gene Panel for Hereditary Hearing Impairment in the Taiwanese Population
    MDPI AG ; 2023
    In:  Genes Vol. 14, No. 4 ( 2023-04-07), p. 880-
    Details
    In: Genes, MDPI AG, Vol. 14, No. 4 ( 2023-04-07), p. 880-
    Abstract: Hearing impairment is one of the most common sensory disorders in children, and targeted next-generation sequencing (NGS)-based genetic examinations can assist in its prognostication and management. In 2020, we developed a simplified 30-gene NGS panel from the original 214-gene NGS version based on Taiwanese genetic epidemiology data to increase the accessibility of NGS-based examinations. In this study, we evaluated the diagnostic performance of the 30-gene NGS panel and compared it with that of the original 214-gene NGS panel in patient subgroups with different clinical features. Data on the clinical features, genetic etiologies, audiological profiles, and outcomes were collected from 350 patients who underwent NGS-based genetic examinations for idiopathic bilateral sensorineural hearing impairment between 2020 and 2022. The overall diagnostic yield was 52%, with slight differences in genetic etiology between patients with different degrees of hearing impairment and ages of onset. No significant difference was found in the diagnostic yields between the two panels, regardless of clinical features, except for a lower detection rate of the 30-gene panel in the late-onset group. For patients with negative genetic results, where the causative variant is undetectable on current NGS-based methods, part of the negative results may be due to genes not covered by the panel or yet to be identified. In such cases, the hearing prognosis varies and may decline over time, necessitating appropriate follow-up and consultation. In conclusion, genetic etiologies can serve as references for refining targeted NGS panels with satisfactory diagnostic performance.
    Type of Medium: Online Resource
    ISSN: 2073-4425
    URL: Article
    DOI: 10.3390/genes14040880
    Language: English
    Publisher: MDPI AG
    Publication Date: 2023
    detail.hit.zdb_id: 2527218-4
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  • 12
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    The Bioactive Core and Corona Synergism of Quantized Gold Enables Slowed Inflammation and Increased Tissue Regeneration in Wound Hypoxia
    MDPI AG ; 2020
    In:  International Journal of Molecular Sciences Vol. 21, No. 5 ( 2020-03-02), p. 1699-
    Details
    In: International Journal of Molecular Sciences, MDPI AG, Vol. 21, No. 5 ( 2020-03-02), p. 1699-
    Abstract: The progress of wound regeneration relies on inflammation management, while neovascular angiogenesis is a critical aspect of wound healing. In this study, the bioactive core and corona synergism of quantized gold (QG) were developed to simultaneously address these complicated issues, combining the abilities to eliminate endotoxins and provide oxygen. The QG was constructed from ultrasmall nanogold and a loosely packed amine-based corona via a simple process, but it could nonetheless eliminate endotoxins (a vital factor in inflammation also called lipopolysaccharides) and provide oxygen in situ for the remodeling of wound sites. Even while capturing endotoxins through electrostatic interactions, the catalytic active sites inside the nanogold could maintain its surface accessibility to automatically transform the overexpressed hydrogen peroxide in hypoxic wound regions into oxygen. Since the inflammatory stage is an essential stage of wound healing, the provision of endotoxin clearance by the outer organic corona of the QG could slow inflammation in a way that subsequently promoted two other important stages of wound bed healing, namely proliferation and remodeling. Relatedly, the efficacy of two forms of the QG, a liquid form and a dressing form, was demonstrated at wound sites in this study, with both forms promoting the development of granulation, including angiogenesis and collagen deposition. Thus, the simply fabricated dual function nanocomposite presented herein not only offers reduced batch-to-batch variation but also increased options for homecare treatments.
    Type of Medium: Online Resource
    ISSN: 1422-0067
    URL: Article
    DOI: 10.3390/ijms21051699
    Language: English
    Publisher: MDPI AG
    Publication Date: 2020
    detail.hit.zdb_id: 2019364-6
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  • 13
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    Non-Hepatic Alkaline Phosphatase, hs-CRP and Progression of Vertebral Fracture in Patients with Rheumatoid Arthritis: A Population-Based Longitudinal Study
    MDPI AG ; 2018
    In:  Journal of Clinical Medicine Vol. 7, No. 11 ( 2018-11-13), p. 439-
    Details
    In: Journal of Clinical Medicine, MDPI AG, Vol. 7, No. 11 ( 2018-11-13), p. 439-
    Abstract: Background: Interactions and early warning effects of non-hepatic alkaline phosphatase (NHALP) and high-sensitivity C-reactive protein (hs-CRP) on the progression of vertebral fractures (VFs) in patients with rheumatoid arthritis (RA) remain unclear. We aim to explore whether serum concentrations of NHALP and hs-CRP could serve as a promising dual biomarker for prognostic assessment of VF progression. Methods: Unadjusted and adjusted hazard ratios (aHRs) of VF progression were calculated for different categories of serum NHALP and hs-CRP using the Cox regression model in RA patients. The modification effect between serum NHALP and hs-CRP on VF progression was determined using an interaction product term. Results: During 4489 person-years of follow-up, higher NHALP ( 〉 125 U/L) and hs-CRP ( 〉 3.0 mg/L) were robustly associated with incremental risks of VF progression in RA patients (aHR: 2.2 (95% confidence intervals (CIs): 1.2–3.9) and 2.0 (95% CI: 1.3–3.3) compared to the lowest HR category, respectively). The interaction between NHALP and hs-CRP on VF progression was statistically significant (p 〈 0.05). In the stratified analysis, patients with combined highest NHALP and hs-CRP had the greatest risk of VF progression (aHR: 4.9 (95% CI: 2.5–9.6)) compared to the lowest HR group (NHALP 〈 90 U/L and hs-CRP 〈 1 mg/L). Conclusions: In light of underdiagnoses of VFs and misleading diagnosis by single test, NHALP and hs-CRP could serve as compensatory biomarkers to predict subclinical VF progression in RA patients.
    Type of Medium: Online Resource
    ISSN: 2077-0383
    URL: Article
    DOI: 10.3390/jcm7110439
    Language: English
    Publisher: MDPI AG
    Publication Date: 2018
    detail.hit.zdb_id: 2662592-1
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  • 14
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    Protective Effect of Piplartine against LPS-Induced Sepsis through Attenuating the MAPKs/NF-κB Signaling Pathway and NLRP3 Inflammasome Activation
    MDPI AG ; 2021
    In:  Pharmaceuticals Vol. 14, No. 6 ( 2021-06-18), p. 588-
    Details
    In: Pharmaceuticals, MDPI AG, Vol. 14, No. 6 ( 2021-06-18), p. 588-
    Abstract: Piplartine (or Piperlongumine) is a natural alkaloid isolated from Piper longum L., which has been proposed to exhibit various biological properties such as anti-inflammatory effects; however, the effect of piplartine on sepsis has not been examined. This study was performed to examine the anti-inflammatory activities of piplartine in vitro, ex vivo and in vivo using murine J774A.1 macrophage cell line, peritoneal macrophages, bone marrow-derived macrophages and an animal sepsis model. The results demonstrated that piplartine suppresses iNOS and COX-2 expression, reduces PGE2, TNF-α and IL-6 production, decreases the phosphorylation of MAPKs and NF-κB and attenuates NF-κB activity by LPS-activated macrophages. Piplartine also inhibits IL-1β production and suppresses NLRP3 inflammasome activation by LPS/ATP- and LPS/nigericin-activated macrophages. Moreover, piplartine reduces the production of nitric oxide (NO) and TNF-α, IL-6 and IL-1β, decreases LPS-induced tissue damage, attenuates infiltration of inflammatory cells and enhances the survival rate. Collectively, these results demonstrate piplartine exhibits anti-inflammatory activities in LPS-induced inflammation and sepsis and suggest that piplartine might have benefits for sepsis treatment.
    Type of Medium: Online Resource
    ISSN: 1424-8247
    URL: Article
    DOI: 10.3390/ph14060588
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2193542-7
    SSG: 15,3
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  • 15
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    Oleanane-Type Saponins from the Roots of Ligulariopsis shichuana and Their α-Glucosidase Inhibitory Activities
    MDPI AG ; 2017
    In:  Molecules Vol. 22, No. 11 ( 2017-11-17), p. 1981-
    Details
    In: Molecules, MDPI AG, Vol. 22, No. 11 ( 2017-11-17), p. 1981-
    Type of Medium: Online Resource
    ISSN: 1420-3049
    URL: Article
    DOI: 10.3390/molecules22111981
    Language: English
    Publisher: MDPI AG
    Publication Date: 2017
    detail.hit.zdb_id: 2008644-1
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  • 16
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    Factors Related to Family Caregivers’ Readiness for the Hospital Discharge of Advanced Cancer Patients
    MDPI AG ; 2022
    In:  International Journal of Environmental Research and Public Health Vol. 19, No. 13 ( 2022-07-01), p. 8097-
    Details
    In: International Journal of Environmental Research and Public Health, MDPI AG, Vol. 19, No. 13 ( 2022-07-01), p. 8097-
    Abstract: Background: Many family caregivers of advanced cancer patients worry about being unable to provide in-home care and delay the discharge. Little is known about the influencing factors of discharge readiness. Methods: This study aimed to investigate the influencing factors of family caregivers’ readiness, used a cross-sectional survey, and enrolled 123 sets of advanced cancer patients and family caregivers using convenience sampling from four oncology wards in a medical centre in northern Taiwan. A self-developed five-point Likert questionnaire, the “Discharge Care Assessment Scale”, surveyed the family caregivers’ difficulties with providing in-home care. Results: The study showed that the discharge readiness of family caregivers affects whether patients can be discharged home. Moreover, the influencing factors of family caregivers’ discharge readiness were the patient’s physical activity performance status and expressed discharge willingness; the presence of someone to assist family caregivers with in-home care; and the difficulties of in-home care. The best prediction model accuracy was78.0%, and the Nagelkerke R2 was 0.52. Conclusion: Discharge planning should start at the point of admission data collection, with the influencing factors of family caregivers’ discharge readiness. It is essential to help patients increase the likelihood of being discharged home.
    Type of Medium: Online Resource
    ISSN: 1660-4601
    URL: Article
    DOI: 10.3390/ijerph19138097
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2175195-X
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  • 17
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    Immunohistochemistry Staining-Proven Cytomegalovirus Colitis in Living Donor Liver Transplantation
    MDPI AG ; 2022
    In:  Viruses Vol. 15, No. 1 ( 2022-12-30), p. 115-
    Details
    In: Viruses, MDPI AG, Vol. 15, No. 1 ( 2022-12-30), p. 115-
    Abstract: Background and Aims: Cytomegalovirus (CMV) infection is a common occurrence in liver transplantation (LT) even in an era of preventive strategies. However, the diagnosis of CMV colitis remains challenging. This study aimed to focus on the clinical significance of endoscopic biopsy-proven CMV colitis in patients following living donor liver transplantation (LDLT). Methods: From January 2007 to December 2021, a total of 55 CMV colitis cases were retrospectively enrolled and divided into a non-LDLT group in 53 and an LDLT group in 2 cases. Clinical demographics, diagnostic measurement, histopathology, and anti-viral therapy were investigated. Results: There were 1630 cases undergoing LDLT in the period 2007–2021, with only 2 recipients being confirmed to have CMV colitis in 2021 (2/114, 1-year incidence: 1.75%). Comparisons between the 53 non-LDLT cases and 2 LDLT cases are as follows: Serum anti-CMV immunoglobulin M (IgM) was shown to be positive (n = 3, 5.5% vs. n = 0, p = 1.0) and negative (n = 20, 37.7% vs. n = 2, 100%, p = 0.16); anti-CMV immunoglobulin G (IgG) was positive (n = 19, 35.8% vs. n = 2, 100%, p = 0.14) and none were negative; CMV DNAemia was shown to be detectable (n = 14, 26.4% vs. n = 1, 50%, p = 0.47) and undetectable (n = 14, 26.4% vs. n = 1, 50%, p = 0.47). Among the two recipients with CMV colitis, one had CMV DNAemia and the other had no CMV DNAemia upon the development of symptoms; negative anti-CMV-IgM and positive anti-CMV-IgG were observed both pre-transplant and post-transplant; finally, CMV colitis was documented based on the presence of inclusion bodies and positive immunohistochemistry (IHC) staining in histology. Conclusion: Patients with immunocompromised status, in particular organ transplantation, may have positive serum anti-CMV IgM/IgG antibodies both before and after transplantation. This study emphasized the fact that endoscopic biopsy with IHC staining may be a more powerful tool for making an accurate diagnosis of CMV colitis in the setting of living donor liver transplantation.
    Type of Medium: Online Resource
    ISSN: 1999-4915
    URL: Article
    DOI: 10.3390/v15010115
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2516098-9
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  • 18
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    Association of Common Variants in OLA1 Gene with Preclinical Atherosclerosis
    MDPI AG ; 2022
    In:  International Journal of Molecular Sciences Vol. 23, No. 19 ( 2022-09-29), p. 11511-
    Details
    In: International Journal of Molecular Sciences, MDPI AG, Vol. 23, No. 19 ( 2022-09-29), p. 11511-
    Abstract: Reactive oxygen species impair the blood vessels, leading to the initiation of atherosclerosis, and migration and proliferation of vascular smooth muscle cells and neovascularization by endothelial cells of vasa vasorum are essential for atherosclerosis development. Obg-like ATPase 1 (OLA1), a negative regulator in cellular responses to oxidative stress, binds to breast cancer susceptibility gene 1 (BRCA1), which protects vascular endothelial and smooth muscle cells against reactive oxygen species. However, it is not known whether OLA1 is genetically correlated with atherosclerosis. Here, we conducted two independent population-based case–control studies to explore the effects of variants in OLA1 genes on preclinical atherosclerosis. A total of 564 and 746 subjects who had thicker and normal carotid intima–media thickness (cIMT), respectively, were enrolled. Among 55 screened SNPs, rs35145102, rs201641962, rs12466587, rs4131583, and rs16862482 in OLA1 showed significant associations with cIMT. SNP rs35145102 is a 3′-utr variant and correlates with the differential expression of OLA1 in immune cells. These five genetic markers form a single closely linked block and H1-ATTGT and H2-GCCTC were the top two most prevalent 5-locus haplotypes. The H1 + H1 genotype negatively and H1 + H2 genotype positively correlated with thicker cIMT. The five identified SNPs in the OLA1 gene showed significant correlations with cIMT. Furthermore, we found that OLA1 was required for migration and proliferation of human aortic endothelial and smooth muscle cells and regulated vascular tube formation by human aortic endothelial cells. Therefore, these genetic variants in the OLA1 gene may serve as markers for risk prediction of atherosclerotic diseases.
    Type of Medium: Online Resource
    ISSN: 1422-0067
    URL: Article
    DOI: 10.3390/ijms231911511
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2019364-6
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  • 19
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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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  • 20
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    Genetic Polymorphisms of MnSOD Modify the Impacts of Environmental Melamine on Oxidative Stress and Early Kidney Injury in Calcium Urolithiasis Patients
    MDPI AG ; 2022
    In:  Antioxidants Vol. 11, No. 1 ( 2022-01-13), p. 152-
    Details
    In: Antioxidants, MDPI AG, Vol. 11, No. 1 ( 2022-01-13), p. 152-
    Abstract: Environmental melamine exposure increases the risks of oxidative stress and early kidney injury. Manganese superoxide dismutase (MnSOD), glutathione peroxidase, and catalase can protect the kidneys against oxidative stress and maintain normal function. We evaluated whether their single-nucleotide polymorphisms (SNPs) could modify melamine’s effects. A total of 302 patients diagnosed with calcium urolithiasis were enrolled. All patients provided one-spot overnight urine samples to measure their melamine levels, urinary biomarkers of oxidative stress and renal tubular injury. Median values were used to dichotomize levels into high and low. Subjects carrying the T allele of rs4880 and high melamine levels had 3.60 times greater risk of high malondialdehyde levels than those carrying the C allele of rs4880 and low melamine levels after adjustment. Subjects carrying the G allele of rs5746136 and high melamine levels had 1.73 times greater risk of high N-Acetyl-β-d-glucosaminidase levels than those carrying the A allele of rs5746136 and low melamine levels. In conclusion, the SNPs of MnSOD, rs4880 and rs5746136, influence the risk of oxidative stress and renal tubular injury, respectively, in calcium urolithiasis patients. In the context of high urinary melamine levels, their effects on oxidative stress and renal tubular injury were further increased.
    Type of Medium: Online Resource
    ISSN: 2076-3921
    URL: Article
    DOI: 10.3390/antiox11010152
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2704216-9
    SSG: 15,3
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