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  • 1
    Online Resource
    Online Resource
    Therapeutic Opportunities of Targeting Histone Deacetylase Isoforms to Eradicate Cancer Stem Cells
    MDPI AG ; 2018
    In:  International Journal of Molecular Sciences Vol. 19, No. 7 ( 2018-07-02), p. 1939-
    Details
    In: International Journal of Molecular Sciences, MDPI AG, Vol. 19, No. 7 ( 2018-07-02), p. 1939-
    Type of Medium: Online Resource
    ISSN: 1422-0067
    URL: Article
    DOI: 10.3390/ijms19071939
    Language: English
    Publisher: MDPI AG
    Publication Date: 2018
    detail.hit.zdb_id: 2019364-6
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  • 2
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    Calycosin, a Common Dietary Isoflavonoid, Suppresses Melanogenesis through the Downregulation of PKA/CREB and p38 MAPK Signaling Pathways
    MDPI AG ; 2022
    In:  International Journal of Molecular Sciences Vol. 23, No. 3 ( 2022-01-25), p. 1358-
    Details
    In: International Journal of Molecular Sciences, MDPI AG, Vol. 23, No. 3 ( 2022-01-25), p. 1358-
    Abstract: Calycosin, a bioactive isoflavonoid isolated from root extracts of Astragalus membranaceus, has been reported to inhibit melanogenesis, the mechanism of which remains undefined. In this study, we interrogated the mechanistic basis by which calycosin inhibits melanin production in two model systems, i.e., B16F10 melanoma cells and zebrafish embryos. Calycosin was effective in protecting B16F10 cells from α-melanocyte-stimulating hormone (α-MSH)-induced melanogenesis and tyrosinase activity. This anti-melanogenic effect was accompanied by decreased expression levels of microphthalmia-associated transcription factor (MITF), a key protein controlling melanin synthesis, and its target genes tyrosinase and tyrosinase-related protein-2 (TRP-2) in calycosin-treated cells. Mechanistically, we obtained the first evidence that calycosin-mediated MITF downregulation was attributable to its ability to block signaling pathways mediated by cAMP response element-binding protein (CREB) and p38 MAP kinase. The protein kinase A (PKA) inhibitor H-89 and p38 inhibitor SB203580 validated the premise that calycosin inhibits melanin synthesis and tyrosinase activity by regulating the PKA/CREB and p38 MAPK signaling pathways. Moreover, the in vivo anti-melanogenic efficacy of calycosin was manifested by its ability to suppress body pigmentation and tyrosinase activity in zebrafish embryos. Together, these data suggested the translational potential of calycosin to be developed as skin-lightening cosmeceuticals.
    Type of Medium: Online Resource
    ISSN: 1422-0067
    URL: Article
    DOI: 10.3390/ijms23031358
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2019364-6
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  • 3
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    Synthesis and Structure–Activity Relationship of Salvinal Derivatives as Potent Microtubule Inhibitors
    MDPI AG ; 2023
    In:  International Journal of Molecular Sciences Vol. 24, No. 7 ( 2023-03-28), p. 6386-
    Details
    In: International Journal of Molecular Sciences, MDPI AG, Vol. 24, No. 7 ( 2023-03-28), p. 6386-
    Abstract: Salvinal is a natural lignan isolated from the roots of Salvia mitorrhiza Bunge (Danshen). Previous studies have demonstrated its anti-proliferative activity in both drug-sensitive and -resistant cancer cell lines, with IC50 values ranging from 4–17 µM. In this study, a series of salvinal derivatives was synthesized and evaluated for the structure–activity relationship. Among the twenty-four salvinal derivatives, six compounds showed better anticancer activity than salvinal. Compound 25 displayed excellent anticancer activity, with IC50 values of 0.13–0.14 µM against KB, KB-Vin10 (overexpress MDR/Pgp), and KB-7D (overexpress MRP) human carcinoma cell lines. Based on our in vitro microtubule depolymerization assay, compound 25 showed depolymerization activity in a dose-dependent manner. Our findings indicate that compound 25 is a promising anticancer agent with depolymerization activity that has potential for the management of malignance.
    Type of Medium: Online Resource
    ISSN: 1422-0067
    URL: Article
    DOI: 10.3390/ijms24076386
    Language: English
    Publisher: MDPI AG
    Publication Date: 2023
    detail.hit.zdb_id: 2019364-6
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  • 4
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    Targeting Triple Negative Breast Cancer Stem Cells by Heat Shock Protein 70 Inhibitors
    MDPI AG ; 2022
    In:  Cancers Vol. 14, No. 19 ( 2022-10-07), p. 4898-
    Details
    In: Cancers, MDPI AG, Vol. 14, No. 19 ( 2022-10-07), p. 4898-
    Abstract: Triple negative breast cancer (TNBC) is considered the most aggressive breast cancer with high relapse rates and poor prognosis. Although great advances in the development of cancer therapy have been witnessed over the past decade, the treatment options for TNBC remain limited. In this study, we investigated the effect and potential underlying mechanism of the Hsp70 inhibitors, compound 1 and compound 6, on breast cancer stem cells (BCSCs) in TNBC cells. Our results showed that compound 1 and 6 exhibited potent tumor suppressive effects on cell viability and proliferation, and effectively inhibited BCSC expansion in TNBC cells. Reminiscent with the effect of Hsp70 inhibitors, Hsp70 knockdown effectively suppressed mammosphere formation and the expressions of BCSCs surface markers. Mechanistically, evidence showed that the Hsp70 inhibitors inhibited BCSCs by down-regulating β-catenin in TNBC cells. Moreover, we used the Hsp70 inhibitors treated TNBC cells and a stable Hsp70 knockdown clone of MDA-MB-231 cells to demonstrate the in vivo efficacy of Hsp70 inhibition in suppressing tumorigenesis and xenograft tumor growth. Together, these findings suggest the potential role of Hsp70 as a target for TNBC therapy and foster new therapeutic strategies to eliminate BCSCs by targeting Hsp70.
    Type of Medium: Online Resource
    ISSN: 2072-6694
    URL: Article
    DOI: 10.3390/cancers14194898
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2527080-1
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  • 5
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    A Meta-Analysis of Comparing Intermittent Epidural Boluses and Continuous Epidural Infusion for Labor Analgesia
    MDPI AG ; 2020
    In:  International Journal of Environmental Research and Public Health Vol. 17, No. 19 ( 2020-09-27), p. 7082-
    Details
    In: International Journal of Environmental Research and Public Health, MDPI AG, Vol. 17, No. 19 ( 2020-09-27), p. 7082-
    Abstract: With the development of medical equipment and techniques in labor anesthesia, it is a major issue to investigate the risks and treatment effects among techniques such as continuous epidural infusion (CEI) and intermittent epidural bolus (IEB). However, there is a controversial result regarding two techniques. This study was conducted through meta-analysis of randomized controlled trials (RCTs) for labor analgesia between the CEI and IEB techniques. The pooled results were presented as weighted mean differences (WMDs) together with 95% confidence intervals (CIs) and odds ratios (ORs) together with 95% CIs, respectively. Eleven RCTs were included in this meta-analysis. Four hundred sixty-five parturients accepted CEI, whereas 473 parturients accepted IEB labor analgesia. Elven identified low- risk bias studies were recruited for meta-analysis. The results presented no statistical difference in cesarean delivery rate between IEB and CEI (OR, 0.96; 95% CI, 0.67–1.37) and duration of second stage of labor (WMD, −3.82 min; 95% CI, −8.28 to 0.64). IEB had statistically significant lessened risk of instrumental delivery (OR, 0.59; 95% CI, 0.39–0.90) and for the use in local anesthetic (WMD, −1.71 mg bupivacaine equivalents per hour; 95% CI, −1.88 and −1.55). Accepted IEB had a higher score of maternal satisfaction (WMD, −6.95 mm; 95% CI, −7.77 to −6.13). Based on evidence, IEB showed a greater benefit for slightly reducing the use in local anesthetic, reduced risk of instrumental delivery, and improved maternal satisfaction for the requirement of labor epidural analgesia for healthy women. In the future, more studies need to be conducted to practice the IEB regimen and explore its influence on labor analgesia.
    Type of Medium: Online Resource
    ISSN: 1660-4601
    URL: Article
    DOI: 10.3390/ijerph17197082
    Language: English
    Publisher: MDPI AG
    Publication Date: 2020
    detail.hit.zdb_id: 2175195-X
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  • 6
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    Effects of Different Routes and Forms of Vitamin D Administration on Mesenteric Lymph Node CD4+ T Cell Polarization and Intestinal Injury in Obese Mice Complicated with Polymicrobial Sepsis
    MDPI AG ; 2022
    In:  Nutrients Vol. 14, No. 17 ( 2022-08-29), p. 3557-
    Details
    In: Nutrients, MDPI AG, Vol. 14, No. 17 ( 2022-08-29), p. 3557-
    Abstract: This study compared the efficacies of enteral cholecalciferol and/or intravenous (IV) calcitriol administration on mesenteric lymph node (MLN) cluster-of-differentiation-4-positive (CD4+) T cell distribution and intestinal barrier damage in obese mice complicated with sepsis. Mice were fed a high-fat diet for 16 weeks and then sepsis was induced by cecal ligation and puncture (CLP). Mice were divided into the following sepsis groups: without vitamin D (VD) (S); with oral cholecalciferol 1 day before CLP (G); with IV calcitriol 1 h after CLP (V); and with both cholecalciferol before and IV calcitriol after CLP (GV). All mice were sacrificed at 12 or 24 h after CLP. The findings show that the S group had a higher T helper (Th)17 percentage than the VD-treated groups at 12 h after CLP. The V group exhibited a higher Th1 percentage and Th1/Th2 ratio than the other groups at 24 h, whereas the V and GV groups had a lower Th17/regulatory T (Treg) ratio 12 h post-CLP in MLNs. In ileum tissues, the VD-treated groups had higher tight junction protein and cathelicidin levels, and higher mucin gene expression than the S group at 24 h post-CLP. Also, aryl hydrocarbon receptor (AhR) and its associated cytochrome P450 1A1 and interleukin 22 gene expressions were upregulated. In contrast, levels of lipid peroxides and inflammatory mediators in ileum tissues were lower in the groups with VD treatment after CLP. These results suggest that IV calcitriol seemed to have a more-pronounced effect on modulating the homeostasis of Th/Treg subsets in MLNs. Both oral cholecalciferol before and IV calcitriol after CLP promoted cathelicidin secretion, alleviated intestinal inflammation, and ameliorated the epithelial integrity in obese mice complicated with sepsis possibly via VD receptor and AhR signaling pathways.
    Type of Medium: Online Resource
    ISSN: 2072-6643
    URL: Article
    DOI: 10.3390/nu14173557
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2518386-2
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  • 7
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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
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  • 8
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    Intravenous Glutamine Administration Improves Glucose Tolerance and Attenuates the Inflammatory Response in Diet-Induced Obese Mice after Sleeve Gastrectomy
    MDPI AG ; 2020
    In:  Nutrients Vol. 12, No. 10 ( 2020-10-19), p. 3192-
    Details
    In: Nutrients, MDPI AG, Vol. 12, No. 10 ( 2020-10-19), p. 3192-
    Abstract: Obesity is a health problem associated with many metabolic disorders. Weight reduction can effectively alleviate obesity-associated complications. Sleeve gastrectomy is a commonly used bariatric surgery and is considered safe and effective for improving outcomes. Glutamine (GLN) is an amino acid with anti-oxidative and anti-inflammatory properties. This study used a mouse model of sleeve gastrectomy to investigate the impacts of intravenous GLN administration on glucose tolerance and adipocyte inflammation short-term after surgery. C57BL6 male mice were divided into normal control (NC) and high-fat diet groups. The high-fat diet provided 60% of energy from fat for 10 weeks to induce obesity. Mice fed the high-fat diet were then assigned to a sham (SH) or sleeve gastrectomy with saline (S) or GLN (G) groups. The S group was intravenously injected with saline, while the G group was administered GLN (0.75 g/kg body weight) via a tail vein postoperatively. Mice in the experimental groups were sacrificed on day 1 or 3 after the surgery. Results showed that obesity resulted in fat accumulation, elevated glucose levels, and adipokines production. Sleeve gastrectomy aggravated expressions of inflammatory cytokine and macrophage infiltration markers, cluster of differentiation 68 (CD68), epidermal growth factor-like module-containing mucin-like hormone receptor-like 1 (EMR-1), and macrophage chemoattractant protein-1, in adipose tissues. Treatment of obese mice with GLN downregulated hepatic proteomic profiles associated with the gluconeogenesis pathway and improved glucose tolerance. Moreover, macrophage infiltration and adipose tissue inflammation were attenuated after the sleeve gastrectomy. These findings imply that postoperative intravenous GLN administration may improve glucose tolerance and attenuate inflammation shortly after the bariatric surgery in subjects with obesity.
    Type of Medium: Online Resource
    ISSN: 2072-6643
    URL: Article
    DOI: 10.3390/nu12103192
    Language: English
    Publisher: MDPI AG
    Publication Date: 2020
    detail.hit.zdb_id: 2518386-2
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  • 9
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    Improving Performance and Breakdown Voltage in Normally-Off GaN Recessed Gate MIS-HEMTs Using Atomic Layer Etching and Gate Field Plate for High-Power Device Applications
    MDPI AG ; 2023
    In:  Micromachines Vol. 14, No. 8 ( 2023-08-11), p. 1582-
    Details
    In: Micromachines, MDPI AG, Vol. 14, No. 8 ( 2023-08-11), p. 1582-
    Abstract: A typical method for normally-off operation, the metal–insulator–semiconductor-high electron mobility transistor (MIS-HEMT) has been investigated. Among various approaches, gate recessed MIS-HEMT have demonstrated a high gate voltage sweep and low leakage current characteristics. Despite their high performance, obtaining low-damage techniques in gate recess processing has so far proven too challenging. In this letter, we demonstrate a high current density and high breakdown down voltage of a MIS-HEMT with a recessed gate by the low damage gate recessed etching of atomic layer etching (ALE) technology. After the remaining 3.7 nm of the AlGaN recessed gate was formed, the surface roughness (Ra of 0.40 nm) was almost the same as the surface without ALE (no etching) as measured by atomic force microscopy (AFM). Furthermore, the devices demonstrate state-of-the-art characteristics with a competitive maximum drain current of 608 mA/mm at a VG of 6 V and a threshold voltage of +2.0 V. The devices also show an on/off current ratio of 109 and an off-state hard breakdown voltage of 1190 V. The low damage of ALE technology was introduced into the MIS-HEMT with the recessed gate, which effectively reduced trapping states at the interface to obtain the low on-resistance (Ron) of 6.8 Ω·mm and high breakdown voltage performance.
    Type of Medium: Online Resource
    ISSN: 2072-666X
    URL: Article
    DOI: 10.3390/mi14081582
    Language: English
    Publisher: MDPI AG
    Publication Date: 2023
    detail.hit.zdb_id: 2620864-7
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  • 10
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    Protective Effects of Glutamine and Leucine Supplementation on Sepsis-Induced Skeletal Muscle Injuries
    MDPI AG ; 2021
    In:  International Journal of Molecular Sciences Vol. 22, No. 23 ( 2021-11-30), p. 13003-
    Details
    In: International Journal of Molecular Sciences, MDPI AG, Vol. 22, No. 23 ( 2021-11-30), p. 13003-
    Abstract: This study investigated the effects of l-glutamine (Gln) and/or l-leucine (Leu) administration on sepsis-induced skeletal muscle injuries. C57BL/6J mice were subjected to cecal ligation and puncture to induce polymicrobial sepsis and then given an intraperitoneal injection of Gln, Leu, or Gln plus Leu beginning at 1 h after the operation with re-injections every 24 h. All mice were sacrificed on either day 1 or day 4 after the operation. Blood and muscles were collected for analysis of inflammation and oxidative damage-related biomolecules. Results indicated that both Gln and Leu supplementation alleviated sepsis-induced skeletal muscle damage by reducing monocyte infiltration, calpain activity, and mRNA expression levels of inflammatory cytokines and hypoxia-inducible factor-1α. Furthermore, septic mice treated with Gln had higher percentages of blood anti-inflammatory monocytes and muscle M2 macrophages, whereas Leu treatment enhanced the muscle expressions of mitochondrion-related genes. However, there were no synergistic effects when Gln and Leu were simultaneously administered. These findings suggest that both Gln and Leu had prominent abilities to attenuate inflammation and degradation of skeletal muscles in the early and/or late phases of sepsis. Moreover, Gln promoted the switch of leukocytes toward an anti-inflammatory phenotype, while Leu treatment maintained muscle bioenergetic function.
    Type of Medium: Online Resource
    ISSN: 1422-0067
    URL: Article
    DOI: 10.3390/ijms222313003
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2019364-6
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