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  • 1
    In: Cancers, MDPI AG, Vol. 11, No. 6 ( 2019-05-28), p. 739-
    Abstract: Hepatocellular carcinoma (HCC) ranks as the fourth leading cause of cancer-related deaths worldwide. Sorafenib was the only U.S. Food and Drug Administration (FDA) approved drug for treating advanced HCC until recently, so development of new target therapy is urgently needed. In this study, we established a zebrafish drug screening platform and compared the therapeutic effects of two multiple tyrosine kinase inhibitors, 419S1 and 420S1, with Sorafenib. All three compounds exhibited anti-angiogenesis abilities in immersed fli1:EGFP transgenic embryos and the half inhibition concentration (IC50) was determined. 419S1 exhibited lower hepatoxicity and embryonic toxicity than 420S1 and Sorafenib, and the half lethal concentration (LC50) was determined. The therapeutic index (LC50/IC50) for 419S1 was much higher than for Sorafenib and 420S1. The compounds were either injected retro-orbitally or by oral gavage to adult transgenic zebrafish with HCC. The compounds not only rescued the pathological feature, but also reversed the expression levels of cell-cycle-related genes and protein levels of a proliferation marker. Using a patient-derived-xenograft assay, we found that the effectiveness of 419S1 and 420S1 in preventing liver cancer proliferation is better than that of Sorafenib. With integrated efforts and the advantage of the zebrafish platform, we can find more effective and safe drugs for HCC treatment and screen for personalized medicine.
    Type of Medium: Online Resource
    ISSN: 2072-6694
    Language: English
    Publisher: MDPI AG
    Publication Date: 2019
    detail.hit.zdb_id: 2527080-1
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  • 2
    In: Journal of Clinical Medicine, MDPI AG, Vol. 11, No. 4 ( 2022-02-21), p. 1131-
    Abstract: Background: We investigated the superiority of arthroscopy-assisted reduction and internal fixation (ARIF) to open reduction and internal fixation (ORIF) for treating glenoid fracture with scapular involvement. Methods: We retrospectively enrolled patients with glenoid fracture who underwent ARIF or ORIF from 2010–2020. Radiographic outcomes were assessed, and clinical outcomes (active range of motion [ROM], visual analog scale [VAS] , Constant, and Disabilities of the Arm, Shoulder and Hand [DASH]) were evaluated 12 months postoperatively. Results: Forty-four patients with Ideberg type II–VI glenoid fractures (ARIF: 20; ORIF: 24; follow-up 12–22 months) were included. Union was achieved in all patients. Active ROM values were comparable between the approaches. Constant and DASH scores were non-significantly better with ARIF (90.9 ± 9.2 vs. 86.6 ± 18.1 [p = 0.341] and 6.8 ± 9.4 vs. 9.3 ± 21.3 [p = 0.626], respectively). However, VAS scores were significantly lower with ARIF (1.5 ± 0.6 vs. 2.7 ± 1.4, p = 0.001). Associated intra-articular lesions (articular depressions [80%] , superior labral anterior-posterior tear [20%], labral tears [30%] ) were found in most ARIF cases and were repaired during ARIF. Conclusions: For glenoid fracture with scapular involvement, ARIF allows accurate diagnosis of fracture pattern and the management of associated intra-articular lesions, with better pain control outcomes than ORIF. Thus, arthroscopy-assistant surgery should be considered in patient with glenoid fracture.
    Type of Medium: Online Resource
    ISSN: 2077-0383
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2662592-1
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  • 3
    In: Medicina, MDPI AG, Vol. 56, No. 12 ( 2020-11-28), p. 655-
    Abstract: Background and Objectives: The proximity of the popliteal vessels in the distal femur may increase the risk of iatrogenic vascular injury during cerclage wiring. In this study, the closest location and distance of the popliteal vessels to the femur was examined using magnetic resonance imaging (MRI). The associations between anthropometric factors and the distance that would guide the placement of wires safely during surgery were also identified. Materials and Methods: We reviewed adult knee magnetic resonance images and recorded: (1) the relation and the shortest horizontal distance (d-H) from the femoral cortex to the popliteal vessels in axial images and (2) the vertical distance (d-V) from the adductor tubercle to the axial level of the d-H values in coronal images. The effects of anthropometric factors (sex, age, body height, body weight, body mass index, thigh circumference, femoral length and femoral width) on these distances were analysed. Results: Analysis of 206 knee magnetic resonance images revealed that the closet locations of popliteal vessels were at the posteromedial aspect of the femur. The d-H and d-V were 7.38 ± 3.22 mm and 57.01 ± 11.14 mm, respectively, and were both shorter in women than in men (p 〈 0.001). Multivariate analysis identified thigh circumference and femoral length as the most influential factors for the d-H and d-V, respectively (p 〈 0.001). Linear regression demonstrated a strong positive linear correlation between the thigh circumference and the d-H and between the femoral length and the d-V (Pearson’s r = 0.891 and 0.806, respectively (p 〈 0.001)). Conclusions: The closet location and distance of the popliteal vessels to the femur provide useful information for wire placement during distal femoral fracture surgery while minimising the risk of vascular injury. Given that patients with a smaller thigh circumference and a shorter femoral length are more likely to have a smaller d-H and a shorter d-V, respectively, cautious measures should be taken in such cases.
    Type of Medium: Online Resource
    ISSN: 1648-9144
    Language: English
    Publisher: MDPI AG
    Publication Date: 2020
    detail.hit.zdb_id: 2088820-X
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  • 4
    In: Molecules, MDPI AG, Vol. 23, No. 12 ( 2018-12-05), p. 3217-
    Abstract: Demethoxycurcumin (DMC), through a self-assembled amphiphilic carbomethyl-hexanoyl chitosan (CHC) nanomatrix has been successfully developed and used as a therapeutic approach to inhibit cisplatin-induced drug resistance by suppressing excision repair cross-complementary 1 (ERCC1) in non-small cell lung carcinoma cells (NSCLC). Previously, DMC significantly inhibited on-target cisplatin resistance protein, ERCC1, via PI3K-Akt-snail pathways in NSCLC. However, low water solubility and bioavailability of DMC causes systemic elimination and prevents its clinical application. To increase its bioavailability and targeting capacity toward cancer cells, a DMC-polyvinylpyrrolidone core phase was prepared, followed by encapsulating in a CHC shell to form a DMC-loaded core-shell hydrogel nanoparticles (DMC-CHC NPs). We aimed to understand whether DMC-CHC NPs efficiently potentiate cisplatin-induced apoptosis through downregulation of ERCC1 in NSCLC. DMC-CHC NPs displayed good cellular uptake efficiency. Dissolved in water, DMC-CHC NPs showed comparable cytotoxic potency with free DMC (dissolved in DMSO). A sulforhodamine B (SRB) assay indicated that DMC-CHC NPs significantly increased cisplatin-induced cytotoxicity by highly efficient intracellular delivery of the encapsulated DMC. A combination of DMC-CHC NPs and cisplatin significantly inhibited on-target cisplatin resistance protein, ERCC1, via the PI3K-Akt pathway. Also, this combination treatment markedly increased the post-target cisplatin resistance pathway including bax, and cytochrome c expressions. Thymidine phosphorylase (TP), a main role of the pyrimidine salvage pathway, was also highly inhibited by the combination treatment. The results suggested that enhancement of the cytotoxicity to cisplatin via administration of DMC-CHC NPs was mediated by down-regulation of the expression of TP, and ERCC1, regulated via the PI3K-Akt pathway.
    Type of Medium: Online Resource
    ISSN: 1420-3049
    Language: English
    Publisher: MDPI AG
    Publication Date: 2018
    detail.hit.zdb_id: 2008644-1
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  • 5
    In: Cells, MDPI AG, Vol. 12, No. 16 ( 2023-08-21), p. 2111-
    Abstract: MicroRNA (miRNA) 107 expression is downregulated but Wnt3a protein and β-catenin are upregulated in degenerated intervertebral disc (IVD). We investigated mir-107/Wnt3a-β-catenin signaling in vitro and in vivo following hyperbaric oxygen (HBO) intervention. Our results showed 96 miRNAs were upregulated and 66 downregulated in degenerated nucleus pulposus cells (NPCs) following HBO treatment. The 3′ untranslated region (UTR) of the Wnt3a mRNA contained the “seed-matched-sequence” for miR-107. MiR-107 was upregulated and a marked suppression of Wnt3a was observed simultaneously in degenerated NPCs following HBO intervention. Knockdown of miR-107 upregulated Wnt3a expression in hyperoxic cells. HBO downregulated the protein expression of Wnt3a, phosphorylated LRP6, and cyclin D1. There was decreased TOP flash activity following HBO intervention, whereas the FOP flash activity was not affected. HBO decreased the nuclear translocation of β-catenin and decreased the secretion of MMP-3 and -9 in degenerated NPCs. Moreover, rabbit serum KS levels and the stained area for Wnt3a and β-catenin in repaired cartilage tended to be lower in the HBO group. We observed that HBO inhibits Wnt3a/β-catenin signaling-related pathways by upregulating miR-107 expression in degenerated NPCs. HBO may play a protective role against IVD degeneration and could be used as a future therapeutic treatment.
    Type of Medium: Online Resource
    ISSN: 2073-4409
    Language: English
    Publisher: MDPI AG
    Publication Date: 2023
    detail.hit.zdb_id: 2661518-6
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  • 6
    Online Resource
    Online Resource
    MDPI AG ; 2017
    In:  International Journal of Molecular Sciences Vol. 18, No. 2 ( 2017-02-07), p. 347-
    In: International Journal of Molecular Sciences, MDPI AG, Vol. 18, No. 2 ( 2017-02-07), p. 347-
    Type of Medium: Online Resource
    ISSN: 1422-0067
    Language: English
    Publisher: MDPI AG
    Publication Date: 2017
    detail.hit.zdb_id: 2019364-6
    SSG: 12
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  • 7
    In: Antioxidants, MDPI AG, Vol. 10, No. 6 ( 2021-06-02), p. 897-
    Abstract: Liver damage induced by paracetamol overdose is the main cause of acute liver failure worldwide. In order to study the hepatoprotective effect of Sanghuangporus sanghuang mycelium (SS) on paracetamol-induced liver injury, SS was administered orally every day for 6 days in mice before paracetamol treatment. SS decreased serum aminotransferase activities and the lipid profiles, protecting against paracetamol hepatotoxicity in mice. Furthermore, SS inhibited the lipid peroxidation marker malondialdehyde (MDA), hepatic cytochrome P450 2E1 (CYP2E1), and the histopathological changes in the liver and decreased inflammatory activity by inhibiting the production of proinflammatory cytokines in paracetamol-induced acute liver failure. Moreover, SS improved the levels of glutathione (GSH), superoxide dismutase (SOD), glutathione peroxidase (GPx), and catalase in the liver. Significantly, SS diminished mitogen-activated protein kinase (MAPK), Toll-like receptor 4 (TLR4), phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt), and the nuclear factor-kappa B (NF-κB) axis, as well as upregulated the Kelch-like ECH-associated protein 1 (Keap1)/erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) pathway, in paracetamol-induced mice. SS mainly inhibited the phosphorylation of the liver kinase B1 (LKB1), Ca2+/calmodulin-dependent kinase kinase β (CaMKKβ), and AMP-activated protein kinase (AMPK) protein expression. Furthermore, the protective effects of SS on paracetamol-induced hepatotoxicity were abolished by compound C, an AMPK inhibitor. In summary, we provide novel molecular evidence that SS protects liver cells from paracetamol-induced hepatotoxicity by inhibiting oxidative stress and inflammation.
    Type of Medium: Online Resource
    ISSN: 2076-3921
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2704216-9
    SSG: 15,3
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  • 8
    Online Resource
    Online Resource
    MDPI AG ; 2023
    In:  International Journal of Molecular Sciences Vol. 24, No. 15 ( 2023-07-29), p. 12190-
    In: International Journal of Molecular Sciences, MDPI AG, Vol. 24, No. 15 ( 2023-07-29), p. 12190-
    Abstract: Drug combination therapy is a key approach in cancer treatments, aiming to improve therapeutic efficacy and overcome drug resistance. Evaluation of intracellular response in cancer cells to drug treatment may disclose the underlying mechanism of drug resistance. In this study, we aimed to investigate the effect of osimertinib, a tyrosine kinase inhibitor (TKI), and a curcumin derivative, 35d, on HCC827 cells and tumors by analyzing alterations in metabolome and related regulations. HCC827 tumor-bearing SCID mice and cultured HCC827 cells were separately examined. The treatment comprised four conditions: vehicle-only, 35d-only, osimertinib-only, and a combination of 35d and osimertinib. The treated tumors/cells were subsequently subjected to metabolomics profiling, fatty acyl analysis, mitochondrial potential measurement, and cell viability assay. Osimertinib induced changes in the ratio of short-chain (SC) to long-chain (LC) fatty acyls, particularly acylcarnitines (ACs), in both tumors and cells. Furthermore, 35d enhanced this effect by further lowering the SC/LC ratio of most ACs. Osimertinib and 35d also exerted detrimental effects on mitochondria through distinct mechanisms. Osimertinib upregulated the expression of carnitine palmitoyltransferase I (CPTI), while 35d induced the expression of heat shock protein 60 (HSP60). The alterations in ACs and CPTI were correlated with mitochondrial dysfunction and inhibited cell growth. Our results suggest that osimertinib and 35d disrupted the fatty acyl metabolism and induced mitochondrial stress in cancer cells. This study provides insights into the potential application of fatty acyl metabolism inhibitors, such as osimertinib or other TKIs, and mitochondrial stress inducers, such as curcumin derivatives, as combination therapy for cancer.
    Type of Medium: Online Resource
    ISSN: 1422-0067
    Language: English
    Publisher: MDPI AG
    Publication Date: 2023
    detail.hit.zdb_id: 2019364-6
    SSG: 12
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  • 9
    In: Nutrients, MDPI AG, Vol. 15, No. 15 ( 2023-07-25), p. 3291-
    Abstract: Body mass index (BMI) as well as sugar-sweetened beverages (SSB) has been suggested to independently decrease 25-hydroxyvitamin D (25(OH)D). However, the relationship between SSB, BMI, and 25(OH)D is uncertain. This study aimed to investigate the potential mediating role of BMI in the association between SSB intake and 25(OH)D. A total of 4505 representative U.S. adults aged above 20 years and without liver conditions were selected from the 2013–2014 NHANES. All analyses were performed under survey modules with appropriate sampling weights. The prevalence of 25(OH)D insufficiency and deficiency was 37.8% and 24.1% in U.S. adults, respectively. Compared with non-SSB consumers, an increased risk of vitamin D deficiency was found in either heavy SSB consumers or soda consumers, respectively (aOR = 2.10, 95% CI = 1.25–3.54 in heavy SSB consumers; aOR = 1.61, 95% CI = 1.06–2.44 in soda consumers). Around 21.3% of the total effect of sugar intake from SSB on decreased 25(OH)D was explained by BMI. In conclusion, high total sugar intake from SSB and BMI independently contribute to lower 25(OH)D, and BMI mediates the inverse association between total sugar intake from SSB intake and 25(OH)D. Furthermore, an increased risk of having vitamin D deficiency was found in the population who consumed higher levels of sugar from SSB or soda drinks.
    Type of Medium: Online Resource
    ISSN: 2072-6643
    Language: English
    Publisher: MDPI AG
    Publication Date: 2023
    detail.hit.zdb_id: 2518386-2
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  • 10
    In: International Journal of Environmental Research and Public Health, MDPI AG, Vol. 20, No. 1 ( 2022-12-30), p. 681-
    Abstract: Excessive sugar-sweetened beverages (SSB) consumption and abdominal obesity have been independently linked to numerous disorders, including diabetes and elevated C-reactive protein (CRP). This study aimed to explore the association between SSB intake, abdominal obesity, and inflammation in normal and prediabetic adults. Sugar intake from SSBs was calculated from 24-h dietary recalls and further classified into non-, medium-, and high-intake. The status of non- and prediabetes was identified based on hemoglobin A1c level. All analyses were performed under a survey module with appropriate sampling weights to control for the complex survey design. A total of 5250 eligible adults without diabetes were selected from the 2007–2010 NHANES. A 1.31-fold increased risk of developing prediabetes was observed in people who consumed high sugar from SSBs when compared to non-SSB consumers. Among individuals with prediabetes, adults who consumed a high amount of sugar from SSB had a 1.57-fold higher risk to increase CRP when compared to non-SSB consumers, even after adjusting for abdominal obesity. Furthermore, the association between the high amount of sugar intake from SSBs and elevated CRP was strengthened by abdominal obesity in prediabetes (p for interaction term = 0.030). Our findings highlight that a positive association between sugar intake from SSBs and CRP levels was only observed in US adults with prediabetes. Abdominal obesity may strengthen this effect in prediabetic adults with a high amount of sugar intake from SSBs.
    Type of Medium: Online Resource
    ISSN: 1660-4601
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2175195-X
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