Publications by authors named "W H Linda Kao"

1,018 Publications

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Novel serotonin-boosting effect of incense smoke from Kynam agarwood in mice: The involvement of multiple neuroactive pathways.

J Ethnopharmacol 2021 Mar 29;275:114069. Epub 2021 Mar 29.

Department of Biochemical Science and Technology, National Taiwan University, Taipei, 10617, Taiwan. Electronic address:

Ethnopharmacological Relevance: Stress is a state of feeling that inhibits one from responding properly in the face of a threat. Agarwood smoke has been used in traditional medicine as a sedative anti-anxious, and anti-restless therapy. Its scent emitted from heat induces people to enter a stable state; however, the underlying molecular effect is still unclear.

Aim Of The Study: This study analyzed novel biological events and gene expression signatures induced by agarwood incense smoke in mice.

Materials And Methods: Incense smoke was produced by heating at 150 °C for 30 min in a headspace autosampler oven. We treated mice with exposure to incense smoke from Kynam agarwood for 45 min/day for 7 consecutive days. After a 7-day inhalation period, the potent agarwood smoke affected-indicators in serum were measured, and the RNA profiles of the mouse brains were analyzed by microarray to elucidate the biological events induced by agarwood incense smoke.

Results: Chemical profile analysis showed that the major component in the incense smoke of Kynam was 2-(2-phenylethyl) chromone (26.82%). Incense smoke from Kynam induced mice to enter a stable state and increased the levels of serotonin in sera. The emotion-related pathways, including dopaminergic synapse, serotonergic synapse, GABAergic synapse, long-term depression and neuroactive ligand-receptor interaction, were significantly affected by incense smoke. Moreover, the expression of Crhr2 and Chrnd genes, involved with neuroactive ligand-receptor interaction pathway, was upregulated by incense smoke.

Conclusions: By a newly-established incense smoke exposure system, we first identified that anti-anxious and anti-depressant effects of agarwood incense smoke were likely associated with the increase of serotonin levels and multiple neuroactive pathways in mice.
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http://dx.doi.org/10.1016/j.jep.2021.114069DOI Listing
March 2021

Cyproterone acetate acts as a disruptor of the aryl hydrocarbon receptor.

Sci Rep 2021 Mar 9;11(1):5457. Epub 2021 Mar 9.

Department of Biochemical Science and Technology, National Chiayi University, Chiayi, 60004, Taiwan, ROC.

Prostate cancer is a major cause of death in males. Cyproterone acetate (CPA), the steroidal anti-androgen for part of androgen deprivation therapy, may block the androgen-receptor interaction and then reduce serum testosterone through its weak anti-gonadotropic action. In addition to CPA inducing hepatitis, CPA is known to cause liver tumors in rats also. Aryl hydrocarbon receptor (AhR) is a cytoplasmic receptor and regulates multiple physiological functions. CYP1A1 is an AhR-targeted gene. We found that CPA induced CYP1A1 expression, transcriptional activity of the aryl hydrocarbon response element (AHRE), and the nuclear localization of AhR in mouse Hepa-1c1c7 cells. However, CPA suppressed CYP1A1 mRNA expression and the transcriptional activity of AHRE in human HepG2 and MCF7 cells, and also decreased AhR ligand-induced CYP1A1 protein expression and transcriptional activity of AHRE in HepG2 cells. In summary, CPA is an AhR agonist in mouse cells, but an AhR antagonist in human cells. Accordingly, CPA potentially plays a role as an endocrine disruptor of the AhR. This study helps us to understand why CPA induces acute hepatitis, gene mutation, and many other side effects. In addition, it may trigger further studies investigating the relationships between CPA, glucocorticoid receptor and castration-resistant prostate cancer in the future.
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http://dx.doi.org/10.1038/s41598-021-84769-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7943802PMC
March 2021

Electrical Cardiometry and Cardiac Biomarkers in 24-h and 48-h Ultramarathoners.

Int J Sports Med 2021 Mar 9. Epub 2021 Mar 9.

Department of Emergency Medicine, Mackay Memorial Hospital, Taipei, Taiwan.

Our study aimed to (i) utilize novel electrical cardiometry and observe acute changes in cardiac biomarkers among 24-h and 48-h ultra-marathoners, and (ii) examine whether alterations in cardiac responses were associated with the average running speed of these participants. Twenty-four 24-h and sixteen 48-h ultra-marathoners were recruited. Electrical cardiometry in the 2 groups showed significant post-race drops in systolic pressure (24-h: p=0.001; 48-h: p=0.016) and rapid increases in heart rate (24-h, p=0.004; 48-h, p=0.001). Cardiac output increased in 48-h runners (p=0.012) and stroke volume decreased in 24-h runners (p=0.009) at post-test. Six of 20 (30%) 24-h and 4 of 16 (25%) 48-h runners had high-sensitivity troponin T values above the reference interval after the races. N-terminal proB-type natriuretic peptide levels showed a 15-fold increase in 24-h runners and a 10-fold increase in 48-h runners at post-race. There was a positive correlation between delta N-terminal proB-type natriuretic peptide and running mileage (0.629, p=0.003) in 24-h ultra-marathoners. In conclusion, stroke volume and cardiac output showed inconsistent changes between the 2 groups. Average running speed has a significant effect on post-exercise elevation in cardiac biomarkers.
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http://dx.doi.org/10.1055/a-1380-4219DOI Listing
March 2021

Development of cisplatin-loaded hydrogels for trans-portal vein chemoembolization in an orthotopic liver cancer mouse model.

Drug Deliv 2021 Dec;28(1):520-529

Department of Surgery, HKU-SZH and Faculty of Medicine, The University of Hong Kong, Hong Kong, China.

Transarterial chemoembolization is a standard treatment for intermediate-stage hepatocellular carcinoma (HCC). This study evaluated the anti-tumor effect of the semi-interpenetrating network (IPN) hydrogel as a novel embolic material for trans-portal vein chemoembolization (TPVE) . A nude mice orthotopic HCC model was established, followed by TPVE using IPN hydrogel loaded with or without cisplatin. Portal vein blockade was visualized by MRI and the development of tumor was monitored by IVIS Spectrum Imaging. Tumor proliferation and angiogenesis were evaluated by Ki67 and CD34 staining respectively. Intra-tumor caspase 3, Akt, ERK1/2, and VEGF activation were detected by Western Blot. F-FMISO uptake was evaluated by microPET-MRI scanning. IPN hydrogel first embolized the left branch of portal vein within 24 hours and further integrated into the intra-tumor vessels during 2 weeks after the treatment. Mice treated with cisplatin-loaded hydrogels exhibited a significant decrease in tumor growth, along with lower plasma AFP levels as compared to hydrogel-treated and untreated tumor-bearing mice. By Ki67 and CD34 staining, the TPVE with IPN hydrogel suppressed tumor proliferation and angiogenesis. In addition, increased tumor apoptosis shown by up-regulation of caspase 3 with decreased expressions of tumor cell survival indicators Akt and ERK1/2 were observed in the treatment groups. Consistent with the decreased expression of VEGF after TPVE, hypoxia level in the tumor was also reduced as indicated by F-FMISO uptake level. IPN hydrogel-based TPVE significantly suppressed the tumor development by regulating intra-tumor angiogenesis and cell survival in an orthotopic HCC mouse model, suggesting a viable embolic agent for transarterial chemoembolization.
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http://dx.doi.org/10.1080/10717544.2021.1895908DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7946021PMC
December 2021

Sofosbuvir/velpatasvir for patients with chronic hepatitis C virus infection and compensated liver disease: real-world data in Taiwan.

Hepatol Int 2021 Mar 6. Epub 2021 Mar 6.

Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.

Background: Data regarding the real-world effectiveness and safety of sofosbuvir/velpatasvir (SOF/VEL) for East Asian patients with chronic hepatitis C virus (HCV) infection and compensated liver disease are limited. We evaluated the performance of SOF/VEL for 12 weeks for HCV-infected patients with compensated liver disease in a large real-world cohort in Taiwan.

Methods: Between July 2019 and March 2020, 1880 HCV-infected patients with compensated liver disease who received SOF/VEL 400/100 mg once daily for 12 weeks were included at 15 academic centers in Taiwan. The sustained virologic response at off-treatment week 12 (SVR) was assessed for evaluable (EP) and per-protocol populations (PP). The tolerance was also reported.

Results: The SVR rates by EP and PP analyses were 95.6% [1798 of 1880 patients; 95% confidence interval (CI) 94.6-96.5%] and 99.3% (1798 of 1811 patients; 95% CI 98.8-99.6%), respectively. Among 82 patients who failed to achieve SVR, 13 (15.9%) were attributed to virologic failures. The SVR rates were comparable regardless of baseline characteristics. A total of 1859 (98.9%) patients completed 12-week SOF/VEL treatment. Four (0.2%) patients discontinued treatment due to adverse events (AEs). All patients with serious AEs or deaths were judged not related to SOF/VEL. The AEs occurring in ≥ 10% included headache (16.8%), fatigue (16.2%), nausea (11.8%), and insomnia (11.1%). Nine (0.5%) and 2 (0.1%) patients had grade 3 total bilirubin and alanine aminotransferase elevations.

Conclusions: SOF/VEL for 12 weeks is efficacious and well-tolerated by chronic HCV-infected patients with compensated liver disease in Taiwan.
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http://dx.doi.org/10.1007/s12072-021-10158-xDOI Listing
March 2021