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  • 1
    Online Resource
    Online Resource
    Minor Glomerular Abnormalities are Associated with Deterioration of Long-Term Kidney Function and Mitochondrial Injury
    MDPI AG ; 2019
    In:  Journal of Clinical Medicine Vol. 9, No. 1 ( 2019-12-22), p. 33-
    Details
    In: Journal of Clinical Medicine, MDPI AG, Vol. 9, No. 1 ( 2019-12-22), p. 33-
    Abstract: Minor glomerular abnormalities (MGAs) are unclassified glomerular lesions indicated by the presence of minor structural abnormalities that are insufficient for a specific pathological diagnosis. The long-term clinical outcomes and pathogenesis have not been examined. We hypothesized that MGAs would be associated with the deterioration of long-term kidney function and increased urinary mitochondrial DNA (mtDNA) copy numbers. We retrospectively enrolled patients with MGAs, age-/sex-/estimated glomerular filtration rate (eGFR)-matched patients with immunoglobulin A nephropathy (IgAN), and similarly matched healthy controls (MHCs; n = 49 each). We analyzed the time × group interaction effects of the eGFR and compared mean annual eGFR decline rates between the groups. We prospectively enrolled patients with MGAs, age- and sex-matched patients with IgAN, and MHCs (n = 15 each) and compared their urinary mtDNA copy numbers. Compared to the MHC group, the MGA and IgAN groups displayed differences in the time × group effects of eGFR, higher mean annual rates of eGFR decline, and higher urinary mtDNA copy numbers; however, these groups did not significantly differ from each other. The results indicate that MGAs are associated with deteriorating long-term kidney function, and mitochondrial injury, despite few additional pathological changes. We suggest that clinicians conduct close long-term follow-up of patients with MGAs.
    Type of Medium: Online Resource
    ISSN: 2077-0383
    URL: Article
    DOI: 10.3390/jcm9010033
    Language: English
    Publisher: MDPI AG
    Publication Date: 2019
    detail.hit.zdb_id: 2662592-1
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  • 2
    Online Resource
    Online Resource
    Aquilariae Lignum Methylene Chloride Fraction Attenuates IL-1β-Driven Neuroinflammation in BV2 Microglial Cells
    MDPI AG ; 2020
    In:  International Journal of Molecular Sciences Vol. 21, No. 15 ( 2020-07-30), p. 5465-
    Details
    In: International Journal of Molecular Sciences, MDPI AG, Vol. 21, No. 15 ( 2020-07-30), p. 5465-
    Abstract: Microglial hyperactivation and neuroinflammation are known to induce neuronal death, which is one of the main causes of neurodegenerative disorders. We previously found that Aquilariae Lignum extract attenuated both neuronal excitotoxicity and neuroinflammation in vivo and in vitro. For further analysis, we extracted the methylene chloride fraction of Aquilariae Lignum to determine the bioactive compounds. In this study, we investigated the anti-neuroinflammatory effects and underlying mechanisms of the Aquilariae Lignum fraction (ALF) using lipopolysaccharide (LPS)-stimulated BV2 microglial cells. BV2 cells were pretreated with ALF (0.5, 1, and 2.5 μg/mL) before treatment with LPS (1 μg/mL). Pretreatment with ALF significantly attenuated the LPS-induced overproductions of nitric oxide (NO), cyclooxygenase-2 (COX-2), prostaglandin E2 (PGE2), and interleukin (IL)-1β. These anti-inflammatory effects were supported by ALF-mediated modulation of the nuclear factor-kappa B (NF-κB) pathway. Furthermore, ALF exerted strong anti-inflammasome effects, as shown by IL-1β-specific inhibitory activity, but not activity against tumor necrosis factor (TNF)-α, along with inhibition of caspase-1 activity and NACHT, LRR, and PYD domain-containing protein 3 (NLRP3)-related molecules. These results indicate the potent anti-neuroinflammatory activity of ALF and that its underlying mechanism may involve the regulation of NLRP3 inflammasome-derived neuroinflammation in microglial cells.
    Type of Medium: Online Resource
    ISSN: 1422-0067
    URL: Article
    DOI: 10.3390/ijms21155465
    Language: English
    Publisher: MDPI AG
    Publication Date: 2020
    detail.hit.zdb_id: 2019364-6
    SSG: 12
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  • 3
    Online Resource
    Online Resource
    An Adrenalectomy Mouse Model Reflecting Clinical Features for Chronic Fatigue Syndrome
    MDPI AG ; 2020
    In:  Biomolecules Vol. 10, No. 1 ( 2020-01-01), p. 71-
    Details
    In: Biomolecules, MDPI AG, Vol. 10, No. 1 ( 2020-01-01), p. 71-
    Abstract: Chronic fatigue syndrome (CFS) is one of the most intractable diseases and is characterized by severe central fatigue that impairs even daily activity. To date, the pathophysiological mechanisms are uncertain and no therapies exist. Therefore, a proper animal model reflecting the clinical features of CFS is urgently required. We compared two CFS animal models most commonly used, by injection with lipopolysaccharide (LPS from Escherichia coli O111:B4) or polyinosinic: polycytidylic acid (poly I:C), along with bilateral adrenalectomy (ADX) as another possible model. Both LPS- and poly I:C-injected mice dominantly showed depressive behaviors, while ADX led to fatigue-like performances with high pain sensitivity. In brain tissues, LPS injection notably activated microglia and the 5-hydroxytryptamine (HT)1A receptor in the prefrontal cortex and hippocampus. Poly I:C-injection also remarkably activated the 5-HT transporter and 5-HT1A receptor with a reduction in serotonin levels in the brain. ADX particularly activated astrocytes and transforming growth factor beta (TGF-β) 1 in all brain regions. Our results revealed that LPS and poly I:C animal models approximate depressive disorder more closely than CFS. We suggest that ADX is a possible method for establishing a mouse model of CFS reflecting clinical features, especially in neuroendocrine system.
    Type of Medium: Online Resource
    ISSN: 2218-273X
    URL: Article
    DOI: 10.3390/biom10010071
    Language: English
    Publisher: MDPI AG
    Publication Date: 2020
    detail.hit.zdb_id: 2701262-1
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  • 4
    Online Resource
    Online Resource
    Survival Benefit after Shifting from Upfront Surgery to Neoadjuvant Treatment in Borderline Resectable Pancreatic Cancer
    MDPI AG ; 2023
    In:  Biomedicines Vol. 11, No. 8 ( 2023-08-18), p. 2302-
    Details
    In: Biomedicines, MDPI AG, Vol. 11, No. 8 ( 2023-08-18), p. 2302-
    Abstract: According to the 2016 National Comprehensive Cancer Network (NCCN) guidelines, patients with borderline resectable pancreatic cancer (BRPC) should receive chemotherapy as the first-line treatment. This study examined the real-world survival benefits of modifying BRPC treatment guidelines. Patients treated for BRPC at a single institution from 2013 to 2015 (pre-guideline group) and 2017 to 2019 (post-guideline group) were retrospectively reviewed. According to the treatment method used, patients were classified into upfront surgery (US), surgery after neoadjuvant treatment (NAT), and chemotherapy only (CO) groups. Overall survival (OS) was compared according to period and treatment type. Factors associated with OS were analyzed using a Cox regression model. Among the 165 patients, 63 were in the pre-guideline group and 102 patients were in the post-guideline group. The median OS was significantly improved in the post-guideline group compared to the pre-guideline group (29 vs. 13 months, p 〈 0.001). According to the treatment method, the median OS of the NAT group was significantly longer than that of the US and CO groups (40 vs. 16 vs. 15 months, respectively, p 〈 0.001). In multivariate analysis, tumor size, differentiation, NAT, and perineural invasion were significant prognostic factors. NAT is an important treatment option for BRPC and increased patient survival in the real world.
    Type of Medium: Online Resource
    ISSN: 2227-9059
    URL: Article
    DOI: 10.3390/biomedicines11082302
    Language: English
    Publisher: MDPI AG
    Publication Date: 2023
    detail.hit.zdb_id: 2720867-9
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  • 5
    Online Resource
    Online Resource
    Clinical Outcome of Resected Non-Ampullary Duodenal Adenocarcinoma: A Single Center Experience
    MDPI AG ; 2022
    In:  Journal of Clinical Medicine Vol. 12, No. 1 ( 2022-12-27), p. 210-
    Details
    In: Journal of Clinical Medicine, MDPI AG, Vol. 12, No. 1 ( 2022-12-27), p. 210-
    Abstract: (1) Background: This study identified the clinical outcome and prognostic factors of resected non-ampullary duodenal adenocarcinoma (NADA) in a single tertiary cancer center. (2) Methods: The medical records of 109 patients with NADA who underwent curative surgery between 2000 and 2018 were reviewed retrospectively. (3) Results: The mean age was 62.4 years with a male predominance (70.6%). The majority of tumors were located at the 2nd portion (58.7%). Fifty-seven patients (52.3%) had symptoms at diagnosis. CA19-9 was elevated in 32 patients (29.4%). Of this cohort, most patients were diagnosed as stage III (64.2%). The median overall survival was 92.9 months, and the 1-, 3-, and 5-year survival rates were 84.4%, 71.6%, and 53.7%, respectively. In univariate and multivariate analysis, age, symptoms, CA19-9, and margin status were associated with overall survival and symptoms, CA19-9 and margin status were also associated with recurrence. When correlating symptoms with stages, patients with symptoms at diagnosis had more advanced stages (all p 〈 0.001). (4) Conclusion: Old age, elevated CA19-9, symptoms, and margin status were independent prognostic factors of NADA, and the patients with symptoms at diagnosis tend to have more advanced stages and a poor prognosis.
    Type of Medium: Online Resource
    ISSN: 2077-0383
    URL: Article
    DOI: 10.3390/jcm12010210
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2662592-1
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  • 6
    Online Resource
    Online Resource
    An Unambiguous Delay-And-Multiply Acquisition Scheme for GPS L1C Signals
    MDPI AG ; 2018
    In:  Sensors Vol. 18, No. 6 ( 2018-05-28), p. 1739-
    Details
    In: Sensors, MDPI AG, Vol. 18, No. 6 ( 2018-05-28), p. 1739-
    Type of Medium: Online Resource
    ISSN: 1424-8220
    URL: Article
    DOI: 10.3390/s18061739
    Language: English
    Publisher: MDPI AG
    Publication Date: 2018
    detail.hit.zdb_id: 2052857-7
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  • 7
    Online Resource
    Online Resource
    Pathological Response Predicts Survival after Pancreatectomy following Neoadjuvant FOLFIRINOX for Pancreatic Cancer
    MDPI AG ; 2022
    In:  Cancers Vol. 15, No. 1 ( 2022-12-31), p. 294-
    Details
    In: Cancers, MDPI AG, Vol. 15, No. 1 ( 2022-12-31), p. 294-
    Abstract: Background: The clinical course of complete pathologic response (cPR) in pancreatic cancer after neoadjuvant chemotherapy is not well known. The aim of this study was to investigate the clinical course of patients according to pathological response, including cPR, who received only FOLIFIRNOX in advanced pancreatic cancer. Methods: Patients who underwent pancreatectomy after FOLFIRINOX for pancreatic ductal adenocarcinoma (PDAC) from 2017 to 2019 were retrospectively reviewed. cPR was defined as an absence of residual tumor on pathologic report. A nearly complete pathologic response (ncPR) was defined as a tumor confined to pancreas parenchyma, less than 1 cm without lymph-node metastasis. cPR and ncPR were assigned into a favorable pathologic response group (fPR). Kaplan–Meier method and Cox proportional hazard models were used for analysis. Results: Of a total 64 patients, 8 (12.5%) had a cPR and 8 (12.5%) had a ncPR. In the fPR group, median OS and DFS were superior to those of non-pathologic response group (more than 60 months vs. 38 months, p 〈 0.001; more than 42 months vs. 10 months, p 〈 0.001). On multivariable analyses, fPR and adjuvant therapy were independent prognostic factors for OS (HR: 0.12; 95% CI: 0.02–0.96, p = 0.05; HR: 0.26; 95% CI: 0.09–0.74, p = 0.01) and DFS (HR: 0.31; 95% CI: 0.12–0.86, p = 0.02; HR:0.31; 95% CI: 0.13–0.72, p = 0.01). Conclusions: pathologic response predicts survival after pancreatectomy following neoadjuvant FOLFIRINOX for pancreatic cancer, and adjuvant chemotherapy following neoadjuvant treatment might be beneficial for OS and DFS.
    Type of Medium: Online Resource
    ISSN: 2072-6694
    URL: Article
    DOI: 10.3390/cancers15010294
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2527080-1
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  • 8
    Online Resource
    Online Resource
    microRNA in Extracellular Vesicles Released by Damaged Podocytes Promote Apoptosis of Renal Tubular Epithelial Cells
    MDPI AG ; 2020
    In:  Cells Vol. 9, No. 6 ( 2020-06-05), p. 1409-
    Details
    In: Cells, MDPI AG, Vol. 9, No. 6 ( 2020-06-05), p. 1409-
    Abstract: Tubular injury and fibrosis are associated with progressive kidney dysfunction in advanced glomerular disease. Glomerulotubular crosstalk is thought to contribute to tubular injury. microRNAs (miRNAs) in extracellular vesicles (EVs) can modulate distant cells. We hypothesized that miRNAs in EVs derived from injured podocytes lead to tubular epithelial cell damage. As proof of this concept, tubular epithelial (HK2) cells were cultured with exosomes from puromycin-treated or healthy human podocytes, and damage was assessed. Sequencing analysis revealed the miRNA repertoire of podocyte EVs. RNA sequencing identified 63 upregulated miRNAs in EVs from puromycin-treated podocytes. Among them, five miRNAs (miR-149, -424, -542, -582, and -874) were selected as candidates for inducing tubular apoptosis according to a literature-based search. To validate the effect of the miRNAs, HK2 cells were treated with miRNA mimics. EVs from injured podocytes induced apoptosis and p38 phosphorylation of HK2 cells. The miRNA-424 and 149 mimics led to apoptosis of HK2 cells. These results show that miRNAs in EVs from injured podocytes lead to damage to tubular epithelial cells, which may contribute to the development of tubular injury in glomerular disease.
    Type of Medium: Online Resource
    ISSN: 2073-4409
    URL: Article
    DOI: 10.3390/cells9061409
    Language: English
    Publisher: MDPI AG
    Publication Date: 2020
    detail.hit.zdb_id: 2661518-6
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  • 9
    Online Resource
    Online Resource
    Time-Varying Risk Factors for Incident Fractures in Kidney Transplant Recipients: A Nationwide Cohort Study in South Korea
    MDPI AG ; 2023
    In:  Journal of Clinical Medicine Vol. 12, No. 6 ( 2023-03-17), p. 2337-
    Details
    In: Journal of Clinical Medicine, MDPI AG, Vol. 12, No. 6 ( 2023-03-17), p. 2337-
    Abstract: Little is known about the time-varying risk factors for fractures in kidney transplant recipients (KTRs). Using the Korea Organ Transplantation Registry, a nationwide cohort study of KTRs, the incidence, locations, and time-varying predictors of fractures were analyzed, including at baseline and post-transplant 6-month variables in KTRs who underwent KT between January 2014 and June 2019. Among 4134 KTRs, with a median follow-up of 2.94 years (12,441.04 person-years), 63 patients developed fractures. The cumulative 5-year incidence was 2.10%. The most frequent locations were leg (25.40%) and foot/ankle (22.22%). In multivariable analysis, older recipient age at baseline (hazard ratio [HR], 1.035; 95% confidence interval [CI] , 1.007–1.064; p = 0.013) and higher tacrolimus trough level (HR, 1.112; 95% CI, 1.029–1.202; p = 0.029) were associated with higher risks for fractures. Pretransplant diabetes mellitus had a time-dependent impact on fractures, with increasing risk as time elapses (HR for diabetes mellitus 1.115; 95% CI, 0.439–2.832; HR for diabetes mellitus × time, 1.049; 95% CI, 1.007–1.094; p = 0.022). In conclusion, KTRs had a high risk of peripheral skeletal fractures in the first 5 years. At baseline recipient age, pretransplant diabetes mellitus and tacrolimus trough level after KT were responsible for the fractures in KTRs.
    Type of Medium: Online Resource
    ISSN: 2077-0383
    URL: Article
    DOI: 10.3390/jcm12062337
    Language: English
    Publisher: MDPI AG
    Publication Date: 2023
    detail.hit.zdb_id: 2662592-1
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  • 10
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    Online Resource
    Design of Self-Healing EPDM/Ionomer Thermoplastic Vulcanizates by Ionic Cross-Links for Automotive Application
    MDPI AG ; 2022
    In:  Polymers Vol. 14, No. 6 ( 2022-03-14), p. 1156-
    Details
    In: Polymers, MDPI AG, Vol. 14, No. 6 ( 2022-03-14), p. 1156-
    Abstract: The development of smart elastomeric materials with inherent self-repairing abilities after mechanical damage has important technological and scientific implications, particularly in regard to the durability and life cycle of rubber products. The interest in self-healing materials for automotive applications is rapidly growing along with the increasing importance of vehicle scratch quality and quantity. The creation of a reversible network by noncovalent ionic cross-linking in elastomer/rubber blends is an effective approach to generate the self-healing phenomenon, with reprocessing and recycling properties. In this work, thermoplastic vulcanizates (TPVs) were prepared using ethylene–propylene–diene (EPDM) polymers and high-acid-containing thermoplastic ionomers. Along with the general EPDM, maleic anhydride grafted EPDM (EPDM-g-MAH) was also used for the preparation of the TPVs. The strategy was based on a simple ionic crosslinking reaction between the carboxyl groups present in the ionomer and zinc oxide (ZnO), where the formation of reversible Zn2+ salt bondings exhibits the self-healing behavior. The heterogeneous blending of EPDM and ionomers was also used to investigate the thermal and mechanical properties of the TPVs. The experimental findings were further supported by the surface morphology of the fracture surfaces viewed using microscopy. The self-healing behavior of the TPVs has been identified by scratch resistance testing, where the EPDM-g-MAH TPVs showed excellent healing efficiency of the scratch surface. Therefore, this work provides an efficient approach to fabricate new ionically cross-linked thermoplastic vulcanizates with excellent mechanical and self-repairing properties for the skins of automotive interior door trims and instrument panel applications.
    Type of Medium: Online Resource
    ISSN: 2073-4360
    URL: Article
    DOI: 10.3390/polym14061156
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2527146-5
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