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The Critical Role of Galectin-12 in Modulating Lipid Metabolism in Sebaceous Glands

The Journal of investigative dermatology 2023年第6期143卷 913-924.e4页

作者： Ching-Han Tsao Wei-Chen Hsieh Feng-Jen Lin Ri-Yao Yang Meng-Ting Chang Maria Karmella Apaya Lie-Fen Shyur Liang-Yin Ke Christos C Zouboulis Fu-Tong Liu Institute of Biomedical Sciences Academia Sinica Taipei Taiwan Ph.D. Program in Translational Medicine Kaohsiung Medical University and Academia Sinica Taipei Taiwan. Institute of Biomedical Sciences Academia Sinica Taipei Taiwan. Graduate Institute of Immunology College of Medicine National Taiwan University Taipei Taiwan. Department of Molecular & Cellular Oncology The University of Texas MD Anderson Cancer Center Houston Texas USA. Agricultural Biotechnology Research Center Academia Sinica Taipei Taiwan. Ph.D. Program in Translational Medicine Kaohsiung Medical University and Academia Sinica Taipei Taiwan Department of Medical Laboratory Science and Biotechnology College of Health Sciences Kaohsiung Medical University Kaohsiung Taiwan. Departments of Dermatology Venereology Allergology and Immunology Dessau Medical Center Brandenburg Medical School Theodor Fontane and Faculty of Health Sciences Brandenburg Dessau Germany. Department of Dermatology School of Medicine University of California-Davis Sacramento California USA. Electronic address: ftliu@ibms.sinica.edu.tw.

Sebaceous glands play an important role in maintaining the skin barrier function by producing lipids. dysregulated lipid production in these glands may contribute to the pathogenesis of human skin diseases. Galectin-12, a member of the β-galactoside‒binding lectin family, is preferentially expressed in adipocytes, where it regulates adipogenesis and functions as an intrinsic negative regulator of lipolysis. It is also expressed by sebocytes and contributes to the proliferation of this cell type. In this study, we show the association between galectin-12 expression and sebocyte differentiation. Galectin-12 knockdown in a human sebocyte cell line reduced lipogenesis and decreased the production of cholesteryl esters, triglycerides, free fatty acids, and cholesterol. Metabolomic analysis of skin surface lipids showed that the levels of the lipids mentioned earlier decreased in sebaceous gland‒specific galectin-12‒knockout mice compared with that in wild-type mice. In addition, galectin-12 positively regulated peroxisome proliferator‒activated receptor-γ transcriptional activity in sebocytes stimulated with fatty acids. downregulating galectin-12 suppressed the expression of peroxisome proliferator‒activated receptor-γ target genes-acetyl-coenzyme A synthetase 2 gene ACS2 and diacylglycerol O-acyltransferase 1 gene dGAT1-that are required for fatty acid activation and cholesterol and triglyceride biosynthesis. In conclusion, galectin-12 is a positive regulator of sebaceous lipid metabolism with a potential role in the maintenance of skin homeostasis.

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Transformative lactera-polypyrrole@carrageenan microparticles leveraging NIR for skin regeneration and stress relief

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International journal of biological macromolecules 2025年 316卷 144436页

作者： Sih-Chi Chuang Shih-An Yu Pei-Chia Hung Andrew E-Y Chuang Jia-Wei Liang Lekshmi Rethi Chih-Kuang Chen Hsu-Wei Fang Hieu Trung Nguyen Hsien-Tsung Lu Department of Chemical Engineering and Biotechnology National Taipei University of Technology Taipei 10608 Taiwan Doctoral Program of Biochemical and Biomedical Engineering National Taipei University of Technology Taipei 10608 Taiwan. Hsuan Chen Technology CO. LTD. New Taipei City 22055 Taiwan. Graduate Institute of Biomedical Materials and Tissue Engineering College of Biomedical Engineering Taipei Medical University New Taipei City Taiwan International Ph.D. Program in Biomedical Engineering College of Biomedical Engineering Taipei Medical University New Taipei City Taiwan Cell Physiology and Molecular Image Research Center Taipei Medical University-Wan Fang Hospital Taipei 11696 Taiwan. Hsuan Chen Technology CO. LTD. New Taipei City 22055 Taiwan Graduate Institute of Biomedical Materials and Tissue Engineering College of Biomedical Engineering Taipei Medical University New Taipei City Taiwan. International Ph.D. Program in Biomedical Engineering College of Biomedical Engineering Taipei Medical University New Taipei City Taiwan. Department of Physical Medicine and Rehabilitation Chang Gung Memorial Hospital Taoyuan Taiwan. School of Medicine Chang Gung University Taoyuan Taiwan. Graduate Institute of Clinical Medicine College of Medicine Taipei Medical University Taipei Taiwan. Department of Chemical Engineering and Biotechnology National Taipei University of Technology Taipei 10608 Taiwan. Department of Orthopedics and Trauma Faculty of Medicine University of Medicine and Pharmacy at Ho Chi Minh City Ho Chi Minh City 700000 Viet Nam. Department of Orthopedic Taipei Medical University Hospital Taipei City 11031 Taiwan Department of Orthopedics School of Medicine College of Medicine Taipei Medical University Taipei 11031 Taiwan International Ph.D. Program in Cell Therapy and Regenerative Medicine College of Medicine Taipei Medical University Taipei 11031 Taiwan. Electronic address: lu7788@tmu.edu.tw.

Effective wound healing remains a significant challenge in regenerative medicine, particularly in minimizing inflammation and promoting scarless recovery. This study introduces a bioengineered LAC-PPy@Car MF composite, designed to leverage near-infrared (NIR)-induced ph.tothermal therapy alongside biotherapeutics to accelerate tissue regeneration. The composite integrates the ph.tothermal properties of polypyrrole (PPy) with the anti-inflammatory and regenerative potential of Lactera (LAC) and Carrageenan (Car). Upon NIR activation, the composite generates localized mild-hyperthermia, reducing oxidative stress, enhancing Aryl Hydrocarbon Receptor (AhR) activity, and upregulating heat shock proteins (HSP). These effects synergistically create a bioactive environment conducive to cellular proliferation and tissue repair. Biochemical evaluations demonstrate that LAC-PPy@Car MF effectively reduces oxidative stress, stimulates fibroblast migration, and promotes the proliferation of skin cells. Immunofluorescence staining reveals significant activation of AhR and HSP in treated tissues, correlating with accelerated cellular proliferation and improved skin architecture. The NIR-triggered ph.tothermal effect enhances the therapeutic potential of the composite, ensuring precise and minimally invasive treatment for burn injuries. These findings position ph.totherapeutic LAC-PPy@Car MF as a promising candidate for advanced wound healing applications. Its dual functionality, combining ph.tothermal therapy with bioactive healing properties, offers a transformative approach to regenerative medicine, paving the way for improved clinical outcomes in wound care.

关键词： Tissue regeneration

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Toxoplasma gondii infection in small ruminants from Khyber Pakhtunkhwa, Pakistan: Seroprevalence, spatial distribution and associated risk factors

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Veterinary Parasitology: Regional Studies and Reports 2024年 47卷 100979页

作者： Khattak, Irfan Usman, Tahir Swelum, Ayman A. Nasreen, Nasreen Khan, Adil Haider, Jamila Muhammad, Javed Chen, Chien-Chin Ben Said, Mourad College of Veterinary and Animal Husbandry Abdul Wali Khan University Mardan Khyber Pakhtunkhwa Pakistan Department of Animal Production College of Food and Agriculture Sciences King Saud University Riyadh 11451 Saudi Arabia Department of Zoology Khyber Pakhtunkhwa Abdul Wali Khan University Mardan 2320 Pakistan Department of Zoology Khyber Pakhtunkhwa Bacha Khan University Charsadda Pakistan Department of Biology Mount Allison University Sackville E4L1E4 NB Canada Department of Microbiology Shaheed Benazir Women University Peshawar Khyber Pakhtunkhwa Pakistan Department of Microbiology University of Haripur Khyber Pakhtunkhwa Pakistan Department of Pathology Ditmanson Medical Foundation Chia-Yi Christian Hospital Chiayi 600 Taiwan Department of Cosmetic Science Chia Nan University of Pharmacy and Science Tainan 717 Taiwan Ph.D. Program in Translational Medicine Rong Hsing Research Center for Translational Medicine National Chung Hsing University Taichung 402 Taiwan Department of Biotechnology and Bioindustry Sciences College of Bioscience and Biotechnology National Cheng Kung University Tainan 701 Taiwan Laboratory of Microbiology National School of Veterinary Medicine of Sidi Thabet University of Manouba Manouba 2010 Tunisia Department of Basic Sciences Higher Institute of Biotechnology of Sidi Thabet University of Manouba Manouba 2010 Tunisia

The primary aim of this investigation was to assess the occurrence of Toxoplasma gondii infection among sheep and goats in five districts within the southern region of Khyber Pakhtunkhwa province, Pakistan. Additionally, the study aimed to pinpoint potential factors associated with the spread of this infection. Serum samples were gathered from a total of 3505 small ruminants, comprising 1810 sheep and 1695 goats. These samples were then subjected to testing for anti-Toxoplasma antibodies using the Toxo-Latex slide Agglutination test. Concurrently, a predetermined questionnaire was employed to gather data on possible risk factors. The collected data underwent bivariate frequency analysis and multivariable logistic regression analyses. The findings revealed that 20.08% of the examined animals had positive results for anti-Toxoplasma antibodies. Notably, the prevalence of T. gondii was notably higher among sheep, with 21.8% of the sheep testing positive, as opposed to the 18% of tested goats (P = 0.007). The seroprevalence percentages were comparable across the five districts for both types of animals. For goats, the prevalence ranged from 16.8% to 20.1%, while for sheep, it ranged from 20.2% to 24%. Among the younger population (≤1 year), the seroprevalence was statistically lower at 17.7% compared to the older population (>1 year) at 23.1% (P < 0.001). Female animals demonstrated a higher prevalence (21.9%) in contrast to their male counterparts (17.8%) (P = 0.002). Animals reared for breeding and milking purposes displayed a greater seroprevalence (23.9%) compared to those intended for sale (17.7%) (P < 0.001). Furthermore, animals kept under a transhumant production system displayed the lowest prevalence (18.9%), followed by sedentary (21.7%) and nomadic (31.2%) herds (P < 0.001). The outcomes of this study highlight the importance of implementing management interventions to curtail T. gondii infection among animals within the Khyber Pakhtunkhwa province of Pakista

关键词： Epidemiological investigation Pakistan Risk factors Seroprevalence Small ruminants Toxoplasma gondii

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Meta-analysis study of the therapeutic impact of Mesenchymal stem cells derived exosomes for chronic kidney diseases

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Biochemistry and Bioph.sics Reports 2025年 43卷

作者： Himanshu Gunjan Ramendera Pati Pandey Riya Mukherjee Chung-Ming Chang Graduate Institute of Biomedical Sciences Chang Gung University No. 259 Wenhua 1st Road Guishan District Taoyuan City 33302 Taiwan ROC School of Health Sciences and Technology (SoHST) UPES Bidholi Dehradun 248007 Uttarakhand India Department of Biotechnology and Microbiology SRM University Delhi-NCR Sonepat Haryana India Master & Ph.D. Program in Biotechnology Industry Chang Gung University No. 259 Wenhua 1st Road Guishan District Taoyuan City 33302 Taiwan ROC Department of Medical Biotechnology and Laboratory Science Chang Gung University No. 259 Wenhua 1st Road Guishan District Taoyuan City 33302 Taiwan ROC

Mesenchymal stem cell-derived exosomes (EXOs) represent a promising avenue for treating chronic kidney diseases (CKd), though their precise impact remains somewhat elusive. To address this gap, we conducted a systematic analysis, scouring databases and clinical trial repositories for relevant studies from 2019 to 2023. Seventeen papers were meticulously selected for their focus on mesenchymal stem cell-derived exosomes (MSC-EXOs) and their potential in CKd treatment. Our comprehensive meta-analysis, incorporating 15 preclinical and 6 clinical studies, underscores the efficacy of MSC-EXOs in improving renal function while attenuating tubular injury, inflammation, apoptosis, collagen deposition, and renal fibrosis. Notably, post-treatment with MSC-EXOs exhibited significant associations with various CKd markers, with pooled proportions indicating a considerable impact on blood urea nitrogen (BUN) and serum creatinine (SCR) levels. Subgroup analyses based on animal models further elucidated heterogeneity within the studies. In conclusion, MSC-EXOs demonstrate promise in enhancing renal function and reducing CKd risk, as evidenced by both preclinical and clinical data. Their efficacy in lowering SCR and BUN levels while enhancing filtration rate suggests MSC-EXOs as a viable and secure alternative to cell-based therapies, thereby providing valuable insights for personalized CKd treatments despite inherent limitations.

关键词： Mesenchymal stem cells Exosome Chronic kidney diseases Renal fibrosis Meta-analysis

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Transdermal nanolipoplex simultaneously inhibits subcutaneous melanoma growth and suppresses systemically metastatic melanoma by activating host immunity

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Nanomedicine: Nanotechnology, Biology, and Medicine 2023年 47卷 102628-102628页

作者： Chen, Chia-Hung Weng, Tzu-Han Chuang, Cheng-Hsun Huang, Kai-Yao Huang, Sih-Cheng Chen, Pin-Rong Huang, Hsiao-Hsuan Huang, Ling-Ya Shen, Pei-Chun Chuang, Po-Ya Huang, Hsiao-Yen Wu, Yi-Syuan Chang, Hao-Chiun Weng, Shun-Long Liao, Kuang-Wen Department of Medical Research Hsinchu MacKay Memorial Hospital Hsinchu City30071 Taiwan Dependent of Medical Education MacKay Memorial Hospital Taipei10449 Taiwan Institute of Molecular Medicine and Bioengineering National Yang Ming Chiao Tung University Hsinchu City30068 Taiwan Department of Biological Science and Technology National Yang Ming Chiao Tung University Hsinchu City30068 Taiwan Industrial Development Graduate Program of College of Biological Science and Technology National Yang Ming Chiao Tung University Hsinchu City30068 Taiwan Institute of Bioinformatics and Systems Biology National Yang Ming Chiao Tung University Hsinchu City30068 Taiwan Department of Medicine MacKay Medical College New Taipei City25245 Taiwan Department of Obstetrics and Gynecology Hsinchu MacKay Memorial Hospital Hsinchu City30071 Taiwan MacKay Junior College of Medicine Nursing and Management Taipei City11260 Taiwan Drug Development and Value Creation Research Center College of Dental Medicine Kaohsiung Medical University School of Dentistry Graduate Institute of Medicine College of Medicine Center for Cancer Research Kaohsiung Medical University Kaohsiung City80708 Taiwan Center for Intelligent Drug Systems and Smart Bio-devices National Yang Ming Chiao Tung University Hsinchu City30068 Taiwan Department of Biotechnology and Bioindustry Sciences National Cheng Kung University Tainan City70101 Taiwan Ph.D. Degree Program of Biomedical Science and Engineering National Yang Ming Chiao Tung University Hsinchu City30068 Taiwan

Benefit for clinical melanoma treatments, the transdermal neoadjuvant therapy could reduce surgery region and increase immunotherapy efficacy. Using lipoplex (Lipo-PEG-PEI-complex, LPPC) encapsulated doxorubicin (dOX) and carrying CpG oligodeoxynucleotide;the transdermally administered nano-liposomal drug complex (LPPC-dOX-CpG) would have high cytotoxicity and immunostimulatory activity to suppress systemic metastasis of melanoma. LPPC-dOX-CpG dramatically suppressed subcutaneous melanoma growth by inducing tumor cell apoptosis and recruiting immune cells into the tumor area. Animal studies further showed that the colonization and growth of spontaneously metastatic melanoma cells in the liver and lung were suppressed by transdermal LPPC-dOX-CpG. Furthermore, NGS analysis revealed IFN-γ and NF-κB pathways were triggered to recruit and activate the antigen-presenting-cells and effecter cells, which could activate the anti-tumor responses as the major mechanism responsible for the therapeutic effect of LPPC-dOX-CpG. Finally, we have successfully proved transdermal LPPC-dOX-CpG as a promising penetrative carrier to activate systemic anti-tumor immunity against subcutaneous and metastatic tumor. © 2022

关键词： Tumors

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Enhancing miso production with optimized puffed-rice koji and its biological function evaluation

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Food Bioscience 2024年 60卷

作者： Lin, Shin-Ping Chou, Yu-Chieh Chen, Chiao-En Lai, Yen-Tso Hsieh, Chen-Che Tsai, Tsung-Yu Lin, Yun-Hsin Santoso, Shella Permatasari Lin, Hui-Wen Cheng, Kuan-Chen School of Food Safety Taipei Medical University 250 Wu-Hsing Street Taipei 11031 Taiwan Research Center of Biomedical Device Taipei Medical University 250 Wu-Hsing Street Taipei 11031 Taiwan TMU Research Center for Digestive Medicine Taipei Medical University 250 Wu-Hsing Street Taipei 11031 Taiwan Ph.D. Program in Drug Discovery and Development Industry College of Pharmacy Taipei Medical University 250 Wu-Hsing Street Taipei 11031 Taiwan Institute of Food Science and Technology National Taiwan University 1 Roosevelt Rd. Sec. 4 Taipei 10617 Taiwan Department of Food and Nutrition Providence University 200 Sec. 7 Taiwan Boulevard Shalu Dist. Taichung 43301 Taiwan Institute of Biotechnology National Taiwan University 1 Roosevelt Rd. Sec. 4 Taipei 10617 Taiwan Department of Food Science Fu Jen Catholic University 510 Zhongzheng Rd. Xinzhuang Dist. New Taipei City 242062 Taiwan Department of Chemical Engineering Widya Mandala Surabaya Catholic University 37 Jl. Kalijudan 37 East Java Surabaya 60114 Indonesia Collaborative Research Center for Zero Waste and Sustainability 37 Jl. Kalijudan East Java Surabaya 60114 Indonesia Department of Optometry Asia University 500 Lioufeng Rd. Wufeng Taichung 41354 Taiwan Department of Medical Research China Medical University Hospital China Medical University 91 Hsueh-Shih Road Taichung 40402 Taiwan

In order to enhance enzyme activities of koji and further improve the health benefits and nutritional value of miso, puffed rice was used to prepare koji with optimization of fermentation utilizing response surface methodology (RSM), and the optimized puffed rice koji was used to produce miso and low-salt miso. Results showed that β-glucosidase activity increased by 1.98-fold after RSM optimization. The optimized puffed rice koji also showed the highest β-amylase and protease activities (237.1 and 968.8 units/g, respectively) compared to rice koji (108.7 and 637.4 units/g, respectively). Moreover, miso made from puffed-rice koji presented a much higher polyph.nol content, antioxidant activity, and aglycone conversion. These findings clarified the relationship between changes in enzyme activities in koji and the important components of miso, and also advance solid-state fermentation research and development of functional miso. © 2024

关键词： Aspergillus oryzae Koji Miso Puffed rice Solid-state fermentation β-glucosidase

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Genome-based characterization of conjugative IncHI1B plasmid carrying carbapenemase genes bla VIM-1 , bla IMP-23 , and truncated bla OXA-256 in Klebsiella pneumoniae NTU107224

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Infection, Genetics and Evolution 2023年 110卷

作者： Li-Li Wen Pei-Yun Kuo Tran Thi dieu Thuy Tran Thi Thuy duong Yu-Tsung Huang Po-Ren Hsueh Yu-Chen Chen Cheng-Yen Kao Graduate Institute of Medical Laboratory Science and Biotechnology Yuanpei University of Medical Technology Hsinchu City Taiwan Institute of Microbiology and Immunology College of Life Sciences National Yang Ming Chiao Tung University Taipei Taiwan Department of Laboratory Medicine and Internal Medicine National Taiwan University Hospital National Taiwan University College of Medicine Taipei Taiwan Ph.D. Program for Aging School of Medicine China Medical University Taichung Taiwan Department of Laboratory Medicine and Internal Medicine China Medical University Hospital School of Medicine China Medical University Taichung Taiwan Genomics Research Center Academia Sinica Taipei Taiwan

The wide dissemination of plasmids carrying antibiotic resistance determinants among bacteria is a severe threat to global public health. Here, we characterized an extensively drug-resistant (XdR) Klebsiella pneumoniae NTU107224 by whole genome sequencing (WGS) in combination with ph.notypic tests. Broth dilution method was used to determine the minimal inhibitory concentrations (MICs) of NTU107224 to 24 antibiotics. The whole genome sequence of NTU107224 was determined by Nanopore/Illumina hybrid genome sequencing. Conjugation assay was performed to determine the transferability of plasmids in NTU107224 to recipient K. pneumoniae 1706. Larvae infection model was used to determine the effect(s) of conjugative plasmid pNTU107224–1 on bacterial virulence. Among the 24 antibiotics tested, XdR K. pneumoniae NTU107224 had low MICs only for amikacin (≤1 μg/mL), polymyxin B (0.25 μg/mL), colistin (0.25 μg/mL), eravacycline (0.25 μg/mL), cefepime/zidebactam (1 μg/mL), omadacycline (4 μg/mL), and tigecycline (0.5 μg/mL). Whole genome sequencing showed that the closed NTU107224 genome comprises a 5,076,795-bp chromosome, a 301,404-bp plasmid named pNTU107224–1, and a 78,479-bp plasmid named pNTU107224–2. IncHI1B plasmid pNTU107224–1 contained three class 1 integrons accumulated various antimicrobial resistance genes (including carbapenemase genes bla VIM-1 , bla IMP-23 , and truncated bla OXA-256 ) and the blast results suggested the dissemination of IncHI1B plasmids in China. By day 7 after infection, larvae infected with K. pneumoniae 1706 and transconjugant had 70% and 15% survival rates, respectively. We found that the conjugative plasmid pNTU107224–1 is closely related to IncHI1B plasmids disseminated in China and contributes to the virulence and antibiotic resistance of pathogens.

关键词： Bacteremia Carbapenemase Conjugative Extensively drug-resistant Whole genome sequencing ARG Antimicrobial resistance gene CFU Colony-forming unit CRKP Carbapenem-resistant Klebsiella pneumoniae ESBL Extended-spectrum β-lactamase MIC Minimal inhibitory concentration MLST Multi-locus sequence typing WGS Whole genome sequencing

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Use of machine learning algorithms to determine the relationship between air pollution and cognitive impairment in Taiwan

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Ecotoxicology and environmental safety 2024年 284卷 116885页

作者： Cheng-Hong Yang Chih-Hsien Wu Kuei-Hau Luo Huang-Chih Chang Sz-Chiao Wu Hung-Yi Chuang Department of Information Management Tainan University of Technology Tainan 71002 Taiwan Department of Electronic Engineering National Kaohsiung University of Science and Technology Kaohsiung 80778 Taiwan Ph. D. Program in Biomedical Engineering Kaohsiung Medical University Kaohsiung 80708 Taiwan School of Dentistry Kaohsiung Medical University Kaohsiung 80708 Taiwan Drug Development and Value Creation Research Center Kaohsiung Medical University Kaohsiung 80708 Taiwan. Electronic address: chyang@nkust.edu.tw. Department of Electronic Engineering National Kaohsiung University of Science and Technology Kaohsiung 80778 Taiwan. Electronic address: F108152123@nkust.edu.tw. Graduate Institute of Medicine College of Medicine Kaohsiung Medicine University Kaohsiung 80708 Taiwan. Electronic address: u107800007@kmu.edu.tw. Divisions of Pulmonary & Critical Care Medicine Department of Internal Medicine Kaohsiung Chang Gung Memorial Hospital Chang Gung University College of Medicine Kaohsiung 83341 Taiwan Ph.D Program in Environmental and Occupational Medicine and Research Center for Environmental Medicine College of Medicine Kaohsiung Medical University Kaohsiung 80708 Taiwan. Electronic address: kuan2101@yahoo.com.tw. Epidemiology in the Public Health Program College of Health Oregon State University Oregon 97331 USA. Electronic address: wusz550@***. Graduate Institute of Medicine College of Medicine Kaohsiung Medicine University Kaohsiung 80708 Taiwan Ph.D Program in Environmental and Occupational Medicine and Research Center for Environmental Medicine College of Medicine Kaohsiung Medical University Kaohsiung 80708 Taiwan Department of Public Health and Environmental Medicine School of Medicine College of Medicine Kaohsiung Medical University Kaohsiung 80708 Taiwan Department of Occupational and Environmental Medicine Kaohsiung Medicine University Hospital Kaohsiung Medicine University Kaohsiung 80708 Taiwan. Electronic address: ericch@kmu.edu.tw.

Air pollution has become a major global threat to human health. Urbanization and industrialization over the past few decades have increased the air pollution. Plausible connections have been made between air pollutants and dementia. This study used machine learning algorithms (k-nearest neighbors, random forest, gradient-boosted decision trees, eXtreme gradient boosting, and CatBoost) to investigate the association between cognitive impairment and air pollution. data from the Taiwan Biobank and 75 air-pollution-monitoring stations in Taiwan were analyzed to determine individual levels of exposure to air pollutants. The pollutants examined were particulate matter with a diameter of ≤ 2.5 μm (PM), nitrogen dioxide, nitric oxide, carbon monoxide, and ozone. The results revealed that the most strongly correlated with cognitive impairment were ozone, PM, and carbon monoxide levels with adjustment of educational level, age, and household income. The model based on these factors achieved accuracy as high as 0.97 for detecting cognitive impairment, indicating a positive association between air pollutions and cognitive impairment.

关键词： Air pollution Carbon monoxide Cognitive impairment dementia Ozone PM(2.5)

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SWEET: a single-sample network inference method for deciph.ring individual features in disease

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Briefings in bioinformatics 2023年第2期24卷 bbad032页

作者： Hsin-Hua Chen Chun-Wei Hsueh Chia-Hwa Lee Ting-Yi Hao Tzu-Ying Tu Lan-Yun Chang Jih-Chin Lee Chun-Yu Lin Institute of Bioinformatics and Systems Biology National Yang Ming Chiao Tung University Hsinchu 300 Taiwan. School of Medical Laboratory Science and Biotechnology College of Medical Science and Technology Taipei Medical University Taipei 110 Taiwan. TMU Research Center of Cancer Translational Medicine Taipei Medical University Taipei 110 Taiwan. Ph.D. Program in Medical Biotechnology College of Medical Science and Technology Taipei Medical University Taipei Taiwan. Department of Otolaryngology-Head and Neck Surgery Tri-Service General Hospital National Defense Medical Center Taipei 110 Taiwan. Department of Biological Science and Technology National Yang Ming Chiao Tung University Hsinchu 300 Taiwan. Institute of Data Science and Engineering National Yang Ming Chiao Tung University Hsinchu 300 Taiwan. Center for Intelligent Drug Systems and Smart Bio-devices National Yang Ming Chiao Tung University Hsinchu 300 Taiwan. School of Dentistry Kaohsiung Medical University Kaohsiung 807 Taiwan.

Recently, extracting inherent biological system information (e.g. cellular networks) from genome-wide expression profiles for developing personalized diagnostic and therapeutic strategies has become increasingly important. However, accurately constructing single-sample networks (SINs) to capture individual characteristics and heterogeneity in disease remains challenging. Here, we propose a sample-specific-weighted correlation network (SWEET) method to model SINs by integrating the genome-wide sample-to-sample correlation (i.e. sample weights) with the differential network between perturbed and aggregate networks. For a group of samples, the genome-wide sample weights can be assessed without prior knowledge of intrinsic subpopulations to address the network edge number bias caused by sample size differences. Compared with the state-of-the-art SIN inference methods, the SWEET SINs in 16 cancers more likely fit the scale-free property, display higher overlap with the human interactomes and perform better in identifying three types of cancer-related genes. Moreover, integrating SWEET SINs with a network proximity measure facilitates characterizing individual features and therapy in diseases, such as somatic mutation, mut-driver and essential genes. Biological experiments further validated two candidate repurposable drugs, albendazole for head and neck squamous cell carcinoma (HNSCC) and lung adenocarcinoma (LUAd) and encorafenib for HNSCC. By applying SWEET, we also identified two possible LUAd subtypes that exhibit distinct clinical features and molecular mechanisms. Overall, the SWEET method complements current SIN inference and analysis methods and presents a view of biological systems at the network level to offer numerous clues for further investigation and clinical translation in network medicine and precision medicine.

关键词： drug repurposing gene expression network inference network medicine precision medicine single-sample network

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Biological evaluation of sulfonate and sulfate analogues of lithocholic acid: A bioisosterism-guided approach towards the discovery of potential sialyltransferase inhibitors for antimetastatic study

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Bioorganic & medicinal chemistry letters 2024年 105卷 129760页

作者： Ser John Lynon P Perez Chia-Ling Chen Tzu-Ting Chang Wen-Shan Li Institute of Chemistry Academia Sinica Taipei 115 Taiwan Department of Applied Chemistry National Yang Ming Chiao Tung University Hsinchu 300 Taiwan Sustainable Chemical Science and Technology Taiwan International Graduate Program Academia Sinica Taipei 115 Taiwan Biomedical Translation Research Center Academia Sinica Taipei 115 Taiwan. Institute of Chemistry Academia Sinica Taipei 115 Taiwan. Biomedical Translation Research Center Academia Sinica Taipei 115 Taiwan Department of Medicinal and Applied Chemistry College of Life Science Kaohsiung Medical University Kaohsiung 807 Taiwan Ph.D. Program in Drug Discovery and Development Industry College of Pharmacy Taipei Medical University Doctoral Degree Program in Marine Biotechnology National Sun Yat-Sen University Kaohsiung 804 Taiwan Department of Chemistry College of Science Tamkang University New Taipei City 251 Taiwan. Electronic address: wenshan@gate.sinica.edu.tw.

The naturally occurring bile acid lithocholic acid (LCA) has been a crucial core structure for many non-sugar-containing sialyltranferase (ST) inhibitors documented in literature. With the aim of elucidating the impact of the terminal carboxyl acid substituent of LCA on its ST inhibition, in this present study, we report the (bio)isosteric replacement-based design and synthesis of sulfonate and sulfate analogues of LCA. Among these compounds, the sulfate analogue SPP-002 was found to selectively inhibit N-glycan sialylation by at least an order of magnitude, indicating a substantial improvement in both potency and selectivity when compared to the unmodified parent bile acid. Molecular docking analysis supported the stronger binding of the synthetic analogue in the enzyme active site. Treatment with SPP-002 also hampered the migration, adhesion, and invasion of MdA-MB-231 cells in vitro by suppressing the expression of signaling proteins involved in the cancer metastasis-associated integrin/FAK/paxillin pathway. In totality, these findings offer not only a novel structural scaffold but also valuable insights for the future development of more potent and selective ST inhibitors with potential therapeutic effects against tumor cancer metastasis.

关键词： Cancer metastasis Integrin-FAK-paxillin signaling pathway Lithocholic acid Sialyltransferase inhibitor

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