Publications by authors named "P M Shih"

462 Publications

Can I Take a Break? Facilitating In-Home Respite Care for Family Caregivers of Older Adults.

AMIA Annu Symp Proc 2020 25;2020:850-859. Epub 2021 Jan 25.

Indiana University Bloomington, Bloomington, IN, USA.

Respite care can provide a chance for family caregivers to take a temporary and flexible break from their long-term caregiving work. Despite its beneficial aspects and value, there is little research on how technology might mitigate barriers to using respite care. The purpose of this paper is to understand the current practices and challenges that people face within the ecosystem of respite care work in the context of in-home care. Based on an in-depth interview study of 18 primary family caregivers, respite family caregivers, and respite professional caregivers, we identified different relationships, phases, and needs of each stakeholder and issues of trust and information sharing that need improvement. We discuss design considerations on how future information and communication technologies (ICTs) could mitigate the barriers identified in this work.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8075491PMC
January 2021

Sinularin, an Anti-Cancer Agent Causing Mitochondria-Modulated Apoptosis and Cytoskeleton Disruption in Human Hepatocellular Carcinoma.

Int J Mol Sci 2021 Apr 11;22(8). Epub 2021 Apr 11.

Department of Marine Biotechnology and Resources, National Sun Yat-sen University, Kaohsiung 80424, Taiwan.

Liver cancer remains a leading cause of death, despite advances in anti-cancer therapies. To develop novel drugs, natural products are being considered as a good source for exploration. In this study, a natural product isolated from a soft coral was applied to evaluate its anti-cancer activities in hepatocellular carcinoma SK-HEP-1 cells. Sinularin was determined to have half-maximal inhibitory concentration (IC) values of ~10 μM after 24, 48, and 72 h. The TUNEL assay and annexin V/PI staining results showed that sinularin induced DNA fragmentation and apoptosis, respectively. An investigation at the molecular level demonstrated that the expression levels of cleaved caspases 3/9 were significantly elevated at 10 μM sinularin. Mitochondrial and intracellular reactive oxygen species (ROS) levels were significantly increased following sinularin treatment, which also affected the mitochondrial membrane potential. In addition, it significantly lowered the mitochondrial respiration parameters and extracellular acidification rates at 10 μM. Further investigation showed that sinularin significantly attenuated wound healing, cell migration, and potential colony formation at 10 μM. Fluorescence microscopic observations showed that the distribution of F-actin filaments was significantly altered at 10 μM sinularin. Supported by Western blot analyses, the expression levels of AKT, p-ERK (extracellular-signal-related kinase), vimentin and VEGF were significantly down-regulated, whereas p-p38, pJNK and E-cadherin were significantly increased. Overall, at the IC concentration, sinularin was able to significantly affect SK-HEP-1 cells.
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http://dx.doi.org/10.3390/ijms22083946DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8069418PMC
April 2021

In-planta production of the biodegradable polyester precursor 2-pyrone-4,6-dicarboxylic acid (PDC): Stacking reduced biomass recalcitrance with value-added co-product.

Metab Eng 2021 Apr 22;66:148-156. Epub 2021 Apr 22.

Joint BioEnergy Institute, EmeryStation East, 5885 Hollis St, 4th Floor, Emeryville, CA, 94608, USA; Environmental Genomics and Systems Biology Division, Lawrence Berkeley National Laboratory, 1 Cyclotron Road, Berkeley, CA, 94720, USA. Electronic address:

2-Pyrone-4,6-dicarboxylic acid (PDC), a chemically stable intermediate that naturally occurs during microbial degradation of lignin by bacteria, represents a promising building block for diverse biomaterials and polyesters such as biodegradable plastics. The lack of a chemical synthesis method has hindered large-scale utilization of PDC and metabolic engineering approaches for its biosynthesis have recently emerged. In this study, we demonstrate a strategy for the production of PDC via manipulation of the shikimate pathway using plants as green factories. In tobacco leaves, we first showed that transient expression of bacterial feedback-resistant 3-deoxy-D-arabinoheptulosonate 7-phosphate synthase (AroG) and 3-dehydroshikimate dehydratase (QsuB) produced high titers of protocatechuate (PCA), which was in turn efficiently converted into PDC upon co-expression of PCA 4,5-dioxygenase (PmdAB) and 4-carboxy-2-hydroxymuconate-6-semialdehyde dehydrogenase (PmdC) derived from Comamonas testosteroni. We validated that stable expression of AroG in Arabidopsis in a genetic background containing the QsuB gene enhanced PCA content in plant biomass, presumably via an increase of the carbon flux through the shikimate pathway. Further, introducing AroG and the PDC biosynthetic genes (PmdA, PmdB, and PmdC) into the Arabidopsis QsuB background, or introducing the five genes (AroG, QsuB, PmdA, PmdB, and PmdC) stacked on a single construct into wild-type plants, resulted in PDC titers of ~1% and ~3% dry weight in plant biomass, respectively. Consistent with previous studies of plants expressing QsuB, all PDC producing lines showed strong reduction in lignin content in stems. This low lignin trait was accompanied with improvements of biomass saccharification efficiency due to reduced cell wall recalcitrance to enzymatic degradation. Importantly, most transgenic lines showed no reduction in biomass yields. Therefore, we conclude that engineering plants with the proposed de-novo PDC pathway provides an avenue to enrich biomass with a value-added co-product while simultaneously improving biomass quality for the supply of fermentable sugars. Implementing this strategy into bioenergy crops has the potential to support existing microbial fermentation approaches that exploit lignocellulosic biomass feedstocks for PDC production.
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http://dx.doi.org/10.1016/j.ymben.2021.04.011DOI Listing
April 2021

Plasma Linoleate Diols Are Potential Biomarkers for Severe COVID-19 Infections.

Front Physiol 2021 1;12:663869. Epub 2021 Apr 1.

Department of Entomology and Nematology, University of California, Davis, Davis, CA, United States.

Polyunsaturated fatty acids are metabolized into regulatory lipids important for initiating inflammatory responses in the event of disease or injury and for signaling the resolution of inflammation and return to homeostasis. The epoxides of linoleic acid (leukotoxins) regulate skin barrier function, perivascular and alveolar permeability and have been associated with poor outcomes in burn patients and in sepsis. It was later reported that blocking metabolism of leukotoxins into the vicinal diols ameliorated the deleterious effects of leukotoxins, suggesting that the leukotoxin diols are contributing to the toxicity. During quantitative profiling of fatty acid chemical mediators (eicosanoids) in COVID-19 patients, we found increases in the regioisomeric leukotoxin diols in plasma samples of hospitalized patients suffering from severe pulmonary involvement. In rodents these leukotoxin diols cause dramatic vascular permeability and are associated with acute adult respiratory like symptoms. Thus, pathways involved in the biosynthesis and degradation of these regulatory lipids should be investigated in larger biomarker studies to determine their significance in COVID-19 disease. In addition, incorporating diols in plasma multi-omics of patients could illuminate the COVID-19 pathological signature along with other lipid mediators and blood chemistry.
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http://dx.doi.org/10.3389/fphys.2021.663869DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8047414PMC
April 2021

Fucoidan and Fucoxanthin Attenuate Hepatic Steatosis and Inflammation of NAFLD through Modulation of Leptin/Adiponectin Axis.

Mar Drugs 2021 Mar 12;19(3). Epub 2021 Mar 12.

Division of Gastroenterology, Department of Internal Medicine, Wan Fang Hospital, Taipei Medical University, Taipei 116, Taiwan.

Non-alcoholic fatty liver disease (NAFLD) is the emerging cause of chronic liver disease globally and lack of approved therapies. Here, we investigated the feasibility of combinatorial effects of low molecular weight fucoidan and high stability fucoxanthin (LMF-HSFx) as a therapeutic approach against NAFLD. We evaluated the inhibitory effects of LMF-HSFx or placebo in 42 NAFLD patients for 24 weeks and related mechanism in high fat diet (HFD) mice model and HepaRG cell line. We found that LMF-HSFx reduces the relative values of alanine aminotransferase, aspartate aminotransferase, total cholesterol, triglyceride, fasting blood glucose and hemoglobin A1c in NAFLD patients. For lipid metabolism, LMF-HSFx reduces the scores of controlled attenuation parameter (CAP) and increases adiponectin and leptin expression. Interestingly, it reduces liver fibrosis in NAFLD patients, either. The proinflammatory cytokines interleukin (IL)-6 and interferon-γ are reduced in LMF-HSFx group. In HFD mice, LMF-HSFx attenuates hepatic lipotoxicity and modulates adipogenesis. Additionally, LMF-HSFx modulates SIRI-PGC-1 pathway in HepaRG cells under palmitic acid-induced lipotoxicity environment. Here, we describe that LMF-HSFx ameliorated hepatic steatosis, inflammation, fibrosis and insulin resistance in NAFLD patients. LMF-HSFx may modulate leptin-adiponectin axis in adipocytes and hepatocytes, then regulate lipid and glycogen metabolism, decrease insulin resistance and is against NAFLD.
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http://dx.doi.org/10.3390/md19030148DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8001566PMC
March 2021