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Knowledge, practice, and barriers to kangaroo mother care as perceived by neonatal intensive care unit nurses in Saudi Arabia

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Journal of Neonatal Nursing 2025年第1期31卷 146-151页

作者： Ismail, Ahmad Alshomrani, Salmah A. Salaghor, Sahar M. Master of Science in Neonatal Intensive Care Nursing Program Nursing Department Fakeeh College for Medical Sciences Jeddah 21461 Saudi Arabia

Introduction: The World Health Organization has recommended kangaroo mother care (KMC) as a safe and cost-effective intervention for neonates. Limited research has been conducted to assess the knowledge, practice, and barriers to KMC in the Neonatal Intensive Care Unit (NICU) in Saudi Arabia. Aim: To assess the knowledge, practice, and barriers to KMC in the NICU in Saudi Arabia as perceived by NICU nurses. Methods: This study employed a cross-sectional correlational design. Data was collected from 97 NICU nurses in two hospitals in Jeddah, Saudi Arabia, using an online survey. The survey covered four main domains: demographic and work-related, knowledge about KMC, practice of KMC, and barriers to KMC. Independent t-test, One-way ANOVA, and Pearson Product-Moment Correlation were used to assess the relationship between study variables and KMC practice. Results: Neonatal ICU nurses possessed a good knowledge level regarding KMC (0.74 ± 0.18). Most NICU nurses reported that KMC was practiced at their units (89%) with a mean of 1.6 times per shift. The mean number of KMC last shift was significantly higher with married NICU nurses (2.0, P ≤ 0.05) and NICU nurses who received training on KMC (1.8, P ≤ 0.05). Significant barriers to KMC were reluctance of the family, fear of accidental extubation and vascular access dislodgement, inadequate time provided to the family, and the family's discomfort with exposing their chest (P ≤ 0.05). Conclusion: Neonatal ICU nurses had adequate knowledge regarding KMC. The NICU nurses reported some barriers to KMC. Interventional programs are needed to overcome these barriers. More research is needed to gain more insights into KMC practice and the factors that influence it in Saudi Arabia. © 2024 Neonatal Nurses Association

关键词： Kangaroo mother care Neonate Neonates NICU Saudi Arabia Skin to skin contact

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Improving the encapsulation of β-carotene by nanoliposomes via potato starch/whey protein coating

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International Journal of Food science and Technology 2024年第4期59卷 2524-2534页

作者： Gu, Jinhui Xu, Tao Pan, Min-hsiung Chiou, Yi-shiou Ding, Baomiao College of Life Science Yangtze University Hubei Jingzhou434025 China Institute of Food Sciences and Technology National Taiwan University Taipei10617 Taiwan Master Degree Program in Toxicology College of Pharmacy Kaohsiung Medical University Kaohsiung City80708 Taiwan

The ability of nanoliposomes (NLs) to encapsulate β-carotene synergistically improved via the potato starch (PS)/whey protein (WP) coating was investigated. The encapsulation efficiency of PS-/WP-coated NL (SP-NL) increased to above 80% compared to that of NL, PS-coated NL, and WP-coated NL. It manifested that the ability of NL to encapsulate β-carotene was significantly enhanced after coating with PS/WP. The encapsulation ability of SP-NL was also influenced by environmental factors (pH, temperature, and ionic strength). Moreover, the storage stability of NL after complexation with PS/WP was effectively enhanced compared to that of NL, PS-coated NL, and WP-coated NL. TEM images showed that SP-NL was fairly spherical, and SP-NL mainly ranged between 100 nm and 500 nm in size. Zeta-potential and particle size indicated that the dispersion of SP-NL was highly stable, and electrostatic forces played a vital role in the stability. Furthermore, the fluorescence polarisation of DPH demonstrated that the decrease in membrane fluidity of NL after PS/WP coating was more obvious from 5.28 to 4.05 compared with that of NL after PS or WP coating, indicating that PS/WP was more effective in increasing the rigidity of the phospholipid layer and improving the structure of the bilayer. The present study suggests that PS/WP coating on NL can be an effective strategy to improve the ability of NL to encapsulate β-carotene and may provide some theoretical support for the development of an effective delivery system for bioactive substances. © 2024 Institute of Food, science and Technology (IFSTTF).

关键词： Phospholipids

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Occurrence and risk assessment of glycidyl and 3-monochloropropanediol esters in infant formulas marketed in Taiwan

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Food Additives and Contaminants - Part A 2024年第4期41卷 352-364页

作者： Liu, Chen Wang, Shang-Ta Tan, Choon-Hui Lin, Zih-Ee Lee, Wei-Ju Master Program in Food Safety Taipei Medical University Taipei Taiwan Department of Food Science National Taiwan Ocean University Keelung Taiwan Institute of Food Safety and Risk Management National Taiwan Ocean University Keelung Taiwan Department of Food Science and Nutrition Faculty of Applied Sciences UCSI University Kuala Lumpur Malaysia Waseda Research Institute for Science and Engineering Waseda University Tokyo Japan School of Food Safety Taipei Medical University Taipei Taiwan

Glycidyl esters (GEs) and 3-monochloropropanediol esters (3-MCPDEs) are process contaminants commonly found in refined edible oils which are often added to infant formulas. The Taiwan Food and Drug Administration (TFDA) launched regulations for GEs in infant formulas that went into effect on 1 July 2021. To investigate levels of GEs and 3-MCPDEs in infant formula powder, 45 products were sampled and analysed during 2020–2021. The contents of GEs and 3-MCPDEs in formulas of different brands significantly varied, but their concentrations in all of the formulas complied with European Union (EU) regulations. Infant formulas containing palm oil had significantly higher 3-MCPDE levels in both extracted oils and milk powder than those without palm oil. Concentrations of GEs and 3-MCPDEs in infant formula powder and extracted oils were significantly lower in products from Europe than those from Australia and New Zealand. Infants aged 0–1 years in Taiwan who consumed only infant formula showed a margin of exposure (MoE) exceeding 25,000. Mean consumer exposures to 3-MCPDEs stayed below the tolerable daily intake (TDI), while high exposures at the 95th percentile (P95) exceeded the TDI by 1.7-fold. Herein, we present the changing trends in the risk assessment results of infant formula across various countries in the decade. Implementation of regulations and mitigation strategy effectively reduced the risk of infants being exposed to GEs and 3-MCPDEs through infant formula. © 2024 Taipei medical University.

关键词： Esters

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Overcoming the Blood-Brain Tumor Barrier with Docetaxel-Loaded Mesoporous Silica Nanoparticles for Treatment of Temozolomide-Resistant Glioblastoma

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ACS Applied Materials and Interfaces 2024年第17期16卷 21722-21735页

作者： Hsu, Tsung-I Chen, Yi-Ping Zhang, Rong-Lin Chen, Zih-An Wu, Cheng-Hsun Chang, Wen-Chang Mou, Chung-Yuan Chan, Hardy Wai-Hong Wu, Si-Han Ph.D. Program in Medical Neuroscience College of Medical Science and Technology Taipei Medical University and National Health Research Institutes Taipei110 Taiwan International Master Program in Medical Neuroscience College of Medical Science and Technology Taipei Medical University Taipei110 Taiwan Graduate Institute of Nanomedicine and Medical Engineering Taipei Medical University Taipei110 Taiwan International Ph.D. Program in Biomedical Engineering College of Biomedical Engineering Taipei Medical University Taipei110 Taiwan Nano Targeting & Therapy Biopharma Inc. Taipei110 Taiwan Graduate Institute of Medical Sciences College of Medicine Taipei Medical University Taipei110 Taiwan Department of Chemistry National Taiwan University Taipei106 Taiwan

While temozolomide (TMZ) has been a cornerstone in the treatment of newly diagnosed glioblastoma (GBM), a significant challenge has been the emergence of resistance to TMZ, which compromises its clinical benefits. Additionally, the nonspecificity of TMZ can lead to detrimental side effects. Although TMZ is capable of penetrating the blood-brain barrier (BBB), our research addresses the need for targeted therapy to circumvent resistance mechanisms and reduce off-target effects. This study introduces the use of PEGylated mesoporous silica nanoparticles (MSN) with octyl group modifications (C8-MSN) as a nanocarrier system for the delivery of docetaxel (DTX), providing a novel approach for treating TMZ-resistant GBM. Our findings reveal that C8-MSN is biocompatible in vitro, and DTX@C8-MSN shows no hemolytic activity at therapeutic concentrations, maintaining efficacy against GBM cells. Crucially, in vivo imaging demonstrates preferential accumulation of C8-MSN within the tumor region, suggesting enhanced permeability across the blood-brain tumor barrier (BBTB). When administered to orthotopic glioma mouse models, DTX@C8-MSN notably prolongs survival by over 50%, significantly reduces tumor volume, and decreases side effects compared to free DTX, indicating a targeted and effective approach to treatment. The apoptotic pathways activated by DTX@C8-MSN, evidenced by the increased levels of cleaved caspase-3 and PARP, point to a potent therapeutic mechanism. Collectively, the results advocate DTX@C8-MSN as a promising candidate for targeted therapy in TMZ-resistant GBM, optimizing drug delivery and bioavailability to overcome current therapeutic limitations. © 2024 The Authors. Published by American Chemical Society.

关键词： Tumors

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Preclinical Assessment of Enhanced Chemodynamic Therapy by an FeMnOx-Based Nanocarrier: Tumor-Microenvironment-Mediated Fenton Reaction and ROS-Induced Chemotherapeutic for Boosted Antitumor Activity

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ACS Applied Materials and Interfaces 2023年第48期15卷 55258-55275页

作者： Dirersa, Worku Batu Kan, Tzu-Chun Getachew, Girum Wibrianto, Aswandi Ochirbat, Sonjid Rasal, Akash Chang, Jungshan Chang, Jia-Yaw Department of Chemical Engineering National Taiwan University of Science and Technology Taiwan Taipei106335 Taiwan Graduate Institute of Medical Sciences College of Medicine Taipei Medical University Taipei11031 Taiwan International Master/Ph.D. Program in Medicine College of Medicine Taipei Medical University Taipei11031 Taiwan International Ph.D. Program for Cell Therapy and Regeneration Medicine College of Medicine Taipei Medical University Taipei11031 Taiwan

In recent studies, iron-containing Fenton nanocatalysts have demonstrated significant promise for clinical use due to their effective antitumor activity and low cytotoxicity. A new approach was reported in this work utilizing cation exchange synthesis to fabricate FeMnOx nanoparticles (NPs) that boost Fenton reactions and responses to the tumor microenvironment (TME) for chemodynamic therapy (CDT) and chemotherapy (CT). Within the TME, the redox metal pair of Fe2+/Mn2+ helps break down endogenous hydrogen peroxide (H2O2) into very harmful hydroxyl radicals (•OH) while simultaneously deactivating glutathione (GSH) to boost CDT performance. To further enhance the therapeutic potential, FeMnOx NPs were encapsulated with thioketal-linked camptothecin (CPT-TK-COOH), a reactive oxygen species (ROS)-responsive prodrug, achieving a high CPT-loading capacity of up to 51.1%. Upon ROS generation through the Fenton reaction, the prodrug TK linkage was disrupted, releasing 80% of the CPT payload within 48 h. Notably, FeMnOx@CPT exhibited excellent dual-modal imaging capabilities, enabling magnetic resonance and fluorescence imaging for image-guided therapy. In vitro studies showed the cytocompatibility of FeMnOx NPs using MDA-Mb-231 and 4T1 cells, but in the presence of H2O2, they induced significant cytotoxicity, resulting in 80% cell death through CDT and CT effects. Upon intravenous administration, FeMnOx@CPT displayed remarkable tumor accumulation, which enhanced tumor suppression in xenografts through improved CDT and CT effects. Moreover, no significant adverse effects were observed in the FeMnOx NP-treated animals. In the current study, the FeMnOx@CPT anticancer platform, with its boosted •OH-producing capability and ROS-cleavable drug release, has been validated utilizing in vitro and animal studies, suggesting its capacity as a viable strategy for clinical trials. © 2023 American Chemical Society.

关键词： Chemotherapy

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Engineering H2O2 Self-Supplying Platform for Xdynamic Therapies via Ru-Cu Peroxide Nanocarrier: Tumor Microenvironment-Mediated Synergistic Therapy

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ACS Applied Materials and Interfaces 2024年第19期16卷 24172-24190页

作者： Dirersa, Worku Batu Kan, Tzu-Chun Chang, Jungshan Getachew, Girum Ochirbat, Sonjid Kizhepat, Shamsa Wibrianto, Aswandi Rasal, Akash Chen, Hung-An Ghule, Anil Vithal Chou, Tzung-Han Chang, Jia-Yaw Department of Chemical Engineering National Taiwan University of Science and Technology Taipei106335 Taiwan Graduate Institute of Medical Sciences College of Medicine Taipei Medical University Taipei11031 Taiwan International Master/Ph.D. Program in Medicine College of Medicine Taipei Medical University Taipei11031 Taiwan International Ph.D. Program for Cell Therapy and Regeneration Medicine College of Medicine Taipei Medical University Taipei11031 Taiwan Green Nanotechnology Laboratory Department of Chemistry Shivaji University Kolhapur416004 India Department of Chemical and Materials Engineering National Yunlin University of Science and Technology Yunlin64002 Taiwan

Of the most common, hypoxia, overexpressed glutathione (GSH), and insufficient H2O2 concentration in the tumor microenvironment (TME) are the main barriers to the advancment of reactive oxygen species (ROS) mediated Xdynamic therapies (X = photo, chemodynamic, chemo). Maximizing Fenton catalytic efficiency is crucial in chemodynamic therapy (CDT), yet endogenous H2O2 levels are not sufficient to attain better anticancer efficacy. Specifically, there is a need to amplify Fenton reactivity within tumors, leveraging the unique attributes of the TME. Herein, for the first time, we design RuxCu1-xO2-Ce6/CPT (RCpCCPT) anticancer nanoagent for TME-mediated synergistic therapy based on heterogeneous Ru-Cu peroxide nanodots (RuxCu1-xO2 NDs) and chlorine e6 (Ce6), loaded with ROS-responsive thioketal (TK) linked-camptothecin (CPT). The Ru-Cu peroxide NDs (RCp NDs, x = 0.50) possess the highest oxygen vacancy (OV) density, which grants them the potential to form massive Lewis’s acid sites for peroxide adsorption, while the dispersibility and targetability of the NDs were improved via surface modification using hyaluronic acid (HA). In TME, RCpCCPT degrades, releasing H2O2, Ru2+/3+, and Cu+/2+ ions, which cooperatively facilitate hydroxyl radical (•OH) formation and deactivate antioxidant GSH enzymes through a cocatalytic loop, resulting in excellent tumor therapeutic efficacy. Furthermore, when combined with laser treatment, RCpCCPT produces singlet oxygen (1O2) for PDT, which induces cell apoptosis at tumor sites. Following ROS generation, the TK linkage is disrupted, releasing up to 92% of the CPT within 48 h. In vitro investigations showed that laser-treated RCpCCPT caused 81.5% cell death from PDT/CDT and chemotherapy (CT). RCpCCPT in cancer cells produces red-blue emission in images of cells taking them in, which allows for fluorescence image-guided Xdynamic treatment. The overall results show that RCp NDs and RCpCCPT are more biocompatible and have excellent Xdynamic the

关键词： Oxidation

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Cryptotanshinone Suppresses the STAT3/BCL-2 Pathway to Provoke Human Bladder Urothelial Carcinoma Cell Death

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Environmental Toxicology 2025年第4期40卷 624-635页

作者： Tung, Min-Che Chang, Ge-Man Dai, Wen-Chyi Hsu, Chen-Hsuan Chang, Hsiang-Chun Yang, Wei-Ting Ho, Yann-Jen Lu, Chien-Hsing Chen, Yi-Hsin Chang, Chia-Che Division of Urology Department of Surgery Tungs' Taichung MetroHarbor Hospital Taichung Taiwan Graduate Institute of Biomedical Sciences National Chung Hsing University Taichung Taiwan Doctoral Program in Biotechnology Industrial Innovation and Management National Chung Hsing University Taichung Taiwan Department of Life Sciences National Chung Hsing University Taichung Taiwan Department of Obstetrics and Gynecology Taichung Veterans General Hospital Taichung Taiwan Doctoral Program in Translational Medicine National Chung Hsing University Taichung Taiwan Department of Nephrology Taichung Tzu Chi Hospital Buddhist Tzu chi Medical Foundation Taichung Taiwan School of Medicine Tzu Chi University Hualein Taiwan Department of Artificial Intelligence and Data Science National Chung Hsing University Taichung Taiwan Master Program in Precision Health Rong Hsing Research Center for Translational Medicine The iEGG and Animal Biotechnology Research Center National Chung Hsing University Taichung Taiwan Department of Medical Laboratory Science and Biotechnology Asia University Taichung Taiwan Department of Medical Research China Medical University Hospital Taichung Taiwan

Bladder cancer is one of the most common human malignancies worldwide. Aberrant activation of signal transducer and activator of transcription 3 (STAT3) is crucial to driving malignant progression and predicting poor prognosis of multiple human cancers, including bladder cancer, making STAT3 a promising target of cancer therapeutics. Cryptotanshinone (CTS) is an anticancer ingredient of Danshen (Salvia miltiorrhiza), a top-graded Chinese medicinal herb. However, whether CTS targets STAT3 to exert its cytotoxic effect on human bladder cancer remains unknown. Herein, we demonstrated that CTS is cytotoxic to multiple human urinary bladder transitional cell carcinoma (TCC) cell lines while sparing normal human urothelial cells. CTS provoked apoptosis-dependent bladder TCC cytotoxicity, as apoptosis blockage by z-VAD-fmk markedly rescued the clonogenicity of CTS-treated cells. Besides, CTS was found to suppress constitutive and interleukin 6-inducible activation of STAT3, evidenced by the downregulation of STAT3 tyrosine 705 phosphorylation and BCL2, a recognized STAT3 transcriptional target. Notably, ectopic expression of a dominant-active STAT3 mutant (STAT3-C) or BCL-2 alleviated CTS-induced apoptosis and clonogenicity inhibition, thus confirming STAT3 blockade as a pivotal mechanism of CTS's cytotoxic action on bladder TCC cells. Lastly, immunoblotting revealed that CTS lowered the levels of active JAK2, an upstream kinase that mediates STAT3 tyrosine 705 phosphorylation. Altogether, we conclude that the blockade of the JAK2/STAT3/BCL-2 antiapoptotic signaling axis is a vital mechanism whereby CTS provokes bladder cancer cytotoxicity. The current evidence implicates CTS's potential to be translated into a bladder cancer therapeutic agent. © 2024 Wiley Periodicals LLC.

关键词： Cell death

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Demethoxymurrapanine, an indole-naphthoquinone alkaloid, inhibits the proliferation of oral cancer cells without major side effects on normal cells

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Environmental Toxicology 2024年第3期39卷 1221-1234页

作者： Chuang, Ya-Ting Yen, Ching-Yu Shiau, Jun-Ping Chang, Fang-Rong Duh, Chang-Yih Sung, Ping-Jyun Chen, Kuan-Liang Tsai, Yi-Hong Tang, Jen-Yang Jeng, Jiiang-Huei Sheu, Jyh-Horng Chang, Hsueh-Wei Department of Biomedical Science and Environmental Biology PhD Program in Life Sciences College of Life Science Kaohsiung Medical University Kaohsiung Taiwan School of Dentistry Taipei Medical University Taipei Taiwan Department of Oral and Maxillofacial Surgery Chi-Mei Medical Center Tainan Taiwan Division of Breast Oncology and Surgery Department of Surgery Kaohsiung Medical University Hospital Kaohsiung Medical University Kaohsiung Taiwan Graduate Institute of Natural Products Kaohsiung Medical University Kaohsiung Taiwan Department of Marine Biotechnology and Resources National Sun Yat-sen University Kaohsiung Taiwan National Museum of Marine Biology and Aquarium Pingtung Taiwan Department of Pharmacy and Master Program College of Pharmacy and Health Care Tajen University Pingtung Taiwan School of Post-Baccalaureate Medicine Kaohsiung Medical University Kaohsiung Taiwan Department of Radiation Oncology Kaohsiung Medical University Hospital Kaohsiung Medical University Kaohsiung Taiwan School of Dentistry College of Dental Medicine Kaohsiung Medical University Kaohsiung Taiwan Department of Dentistry Kaohsiung Medical University Hospital Kaohsiung Taiwan Department of Dentistry National Taiwan University Hospital Taipei Taiwan Department of Medical Research China Medical University Hospital China Medical University Taichung Taiwan Department of Medical Research Kaohsiung Medical University Hospital Kaohsiung Taiwan Center for Cancer Research Kaohsiung Medical University Kaohsiung Taiwan

Antioral cancer drugs need a greater antiproliferative impact on cancer than on normal cells. Demethoxymurrapanine (DEMU) inhibits proliferation in several cancer cells, but an in-depth investigation was necessary. This study evaluated the proliferation-modulating effects of DEMU, focusing on oral cancer and normal cells. DEMU (0, 2, 3, and 4 μg/mL) at 48 h treatments inhibited the proliferation of oral cancer cells (the cell viability (%) for Ca9-22 cells was 100.0 ± 2.2, 75.4 ± 5.6, 26.0 ± 3.8, and 15.4 ± 1.4, and for CAL 27 cells was 100.0 ± 9.4, 77.2 ± 5.9, 57.4 ± 10.7, and 27.1 ± 1.1) more strongly than that of normal cells (the cell viability (%) for S-G cells was 100.0 ± 6.6, 91.0 ± 4.6, 95.0 ± 2.6, and 95.8 ± 5.5), although this was blocked by the antioxidant N-acetylcysteine. The presence of oxidative stress was evidenced by the increase of reactive oxygen species and mitochondrial superoxide and the downregulation of the cellular antioxidant glutathione in oral cancer cells, but these changes were minor in normal cells. DEMU also caused greater induction of the subG1 phase, extrinsic and intrinsic apoptosis (annexin V and caspases 3, 8, and 9), and DNA damage (γH2AX and 8-hydroxy-2-deoxyguanosine) in oral cancer than in normal cells. N-acetylcysteine attenuated all these DEMU-induced changes. Together, these data demonstrate the preferential antiproliferative function of DEMU in oral cancer cells, with the preferential induction of oxidative stress, apoptosis, and DNA damage in these cancer cells, and low cytotoxicity toward normal cells. © 2023 Wiley Periodicals LLC.

关键词： Oxidative stress

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Fucoxanthin induces human melanoma cytotoxicity by thwarting the JAK2/STAT3/BCL-xL signaling axis

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Environmental Toxicology 2024年第6期39卷 3356-3366页

作者： Kuo, Min-Yung Dai, Wen-Chyi Chang, Jie-Li Chang, Jo-Shu Lee, Tse-Min Chang, Chia-Che Pediatric Surgery Division Department of Surgery Tungs' Taichung MetroHarbor Hospital Taichung Taiwan Doctoral Program in Biotechnology Industrial Innovation and Management National Chung Hsing University Taichung Taiwan Taichung Municipal Taichung First Senior High School Taichung Taiwan Department of Chemical and Materials Engineering Research Center for Smart Sustainable Circular Economy Tunghai University Taichung Taiwan Department of Life Sciences National Chung Hsing University Taichung Taiwan Department of Marine Biotechnology and Resources National Sun Yat-sen University Kaohsiung Taiwan Graduate Institute of Biomedical Sciences Master Program in Precision Health Doctoral Program in Translational Medicine Rong Hsing Research Center for Translational Medicine The iEGG and Animal Biotechnology Research Center National Chung Hsing University Taichung Taiwan Department of Medical Laboratory Science and Biotechnology Asia University Taichung Taiwan Department of Medical Research China Medical University Hospital Taichung Taiwan Traditional Herbal Medicine Research Center Taipei Medical University Hospital Taipei Taiwan

Melanoma is the most lethal skin malignancy. Fucoxanthin is a marine carotenoid with significant anticancer activities. Intriguingly, Fucoxanthin's impact on human melanoma remains elusive. Signal Transducer and Activator of Transcription 3 (STAT3) represents a promising target in cancer therapy due to its persistent activation in various cancers, including melanoma. Herein, we revealed that Fucoxanthin is cytotoxic to human melanoma cell lines A2758 and A375 while showing limited cytotoxicity to normal human melanocytes. Apoptosis is a primary reason for Fucoxanthin's melanoma cytotoxicity, as the pan-caspase inhibitor z-VAD-fmk drastically abrogated Fucoxanthin-elicited clonogenicity blockage. Besides, Fucoxanthin downregulated tyrosine 705-phosphorylated STAT3 (p-STAT3 (Y705)), either inherently present in melanoma cells or inducible by interleukin 6 (IL-6) stimulation. Notably, ectopic expression of STAT3-C, a dominant-active STAT3 mutant, abolished Fucoxanthin-elicited melanoma cell apoptosis and clonogenicity inhibition, supporting the pivotal role of STAT3 blockage in Fucoxanthin's melanoma cytotoxicity. Moreover, Fucoxanthin lowered BCL-xL levels by blocking STAT3 activation, while ectopic BCL-xL expression rescued melanoma cells from Fucoxanthin-induced killing. Lastly, Fucoxanthin was found to diminish the levels of JAK2 with dual phosphorylation at tyrosine residues 1007 and 1008 in melanoma cells, suggesting that Fucoxanthin impairs STAT3 signaling by blocking JAK2 activation. Collectively, we present the first evidence that Fucoxanthin is cytotoxic selectively against human melanoma cells while sparing normal melanocytes. Mechanistically, Fucoxanthin targets the JAK2/STAT3/BCL-xL antiapoptotic axis to provoke melanoma cell death. This discovery implicates the potential application of Fucoxanthin as a chemopreventive or therapeutic strategy for melanoma management. © 2024 Wiley Periodicals LLC.

关键词： Carotenoids

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Involvement of matrix metalloproteinase 1 and urokinase-type plasminogen activator in the PKCα-p38 MAPK pathway-mediated progression of human liver cancer cells

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Drug Development Research 2023年第4期84卷 767-776页

作者： Ye, Je-Chiuan Hsieh, Yih-Shou Chen, Pei-Ni Liu, Jer-Yuh Hsieh, Yi-Hsien Department of Bachelor's Degree Program for Indigenous Peoples in Senior Health and Care Management National Taitung University Taitung Taiwan Master Program in Biomedical Science National Taitung University Taitung Taiwan Department of Biochemistry School of Medicine Chung Shan Medical University Taichung Taiwan Clinical Laboratory Chung Shan Medical University Hospital Taichung Taiwan Institute of Medicine Chung Shan Medical University Taichung Taiwan Department of Medical Research Chung Shan Medical University Hospital Taichung Taiwan Center for Molecular Medicine China Medical University Hospital Taichung Taiwan Graduate Institute of Biomedical Sciences China Medical University Taichung Taiwan

Our previous studies have shown that the plasminogen activator (PA) and matrix metalloproteinases (MMPs) proteinase systems were highly expressed in highly malignant liver cancer cells and regulated by PKCα. This study investigates whether the PKCα regulation of PA and MMPs systems is conducted through p38 mitogen-activated protein kinase (MAPK) signaling and the pathway is responsible for promoting cell progression. We found that the expressions of p38 MAPK in both highly malignant HA22T/VGH and SK-Hep-1 liver cancer cells were higher than that in other lower malignancy liver cancer cells. Since PKCα activates p38 MAPK in progression of liver cancer, we suspected the PKCα/p38 MAPK signaling pathway to be involved in the regulation of MMPs and PA systems. When SK-Hep-1 cells were treated with SB203580 or DN-p38, only MMP-1 and u-PA mRNA expressions decreased. The p38 MAPK inhibition also decreased the cell migration and invasion. In addition, the mRNA decay assays showed that the higher expressions of MMP-1 and u-PA mRNA in SK-Hep-1 cells were due to the alteration of mRNA stability by p38 MAPK inhibition. Zymography of SK-Hep-1 cells treated with siPKCα vector also showed the decrease of the activity of MMP-1 and u-PA and confirmed changes in mRNA level. Furthermore, only the transfection of MKK6 to the siPKCα-treated SK-Hep-1 stable clone cell restored the attenuation of MMP-1 and u-PA expressions. The treatment of SK-Hep-1 cells with either inhibitor of MMP-1 or u-PA reduced migration, and the reduction was enhanced with both inhibitors. In addition, tumorigenesis was also reduced with both inhibitors. These data suggest a novel finding that MMP-1 and u-PA are critical components in PKCα/MKK6/p38 MAPK signaling pathway which mediates liver cancer cell progression, and that the targeting of both genes may be a viable approach in liver cancer treatment. © 2023 The Authors. Drug Development Research published by Wiley Periodicals LLC.

关键词： liver cancer MMP-1 p38 MAPK PKCα u-PA

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