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Caffeic acid phenethyl ester suppresses the expression of androgen receptor variant 7 via inhibition of CDK1 and AKT

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Cancer Gene Therapy 2024年第6期31卷 807-815页

作者： Kuo, Ying-Yu Huo, Chieh Li, Chia-Yang Chuu, Chih-Pin Institute of Cellular and System Medicine National Health Research Institutes Miaoli County Taiwan Graduate Institute of Medicine College of Medicine Kaohsiung Medical University Kaohsiung Taiwan Department of Medical Research Kaohsiung Medical University Kaohsiung Taiwan PhD Program for Aging and Graduate Institute of Basic Medical Science China Medical University Taichung City Taiwan Biotechnology Center National Chung Hsing University Taichung City Taiwan Department of Life Sciences National Central University Taoyuan City Taiwan

Androgen receptor (AR) splice variant 7 (AR-V7) is capable to enter nucleus and activate downstream signaling without ligand. AR-V7 assists the tumor growth, cancer metastasis, cancer stemness, and the evolvement of therapy-resistant prostate cancer (PCa). We discovered that caffeic acid phenethyl ester (CAPE) can repress the expression and downstream signaling of AR-V7 in PCa cells. CAPE blocked the gene transcription, nuclear localization, and protein abundance of AR-V7. CAPE inhibited the expression of U2AF65, SF2 and hnRNPF, which were splicing factors for AR-V7 intron. Additionally, CAPE decreased protein stability of AR-V7 and enhanced the proteosome-degradation of AR-V7. We observed that CDK1 and AKT regulated the expression and stability of AR-V7 via phosphorylation of Ser81 and Ser213, respectively. CAPE decreased the expression of CDK1 and AKT. Overexpression of CDK1 restored the abundance of AR-V7 in CAPE-treated PCa cells. Overexpression of AR-V7, AKT or CDK1 rescued the proliferation of PCa cells under CAPE treatment. Intraperitoneal injection of 10 mg/kg CAPE retarded the growth of 22Rv1 xenografts in nude mice and suppressed the protein levels of AR-V7, CDK1 and AKT in 22Rv1 xenografts. Our study provided the rationale of applying CAPE for inhibition of AR-V7 in prostate tumors. (Figure presented.). © The Author(s), under exclusive licence to Springer Nature America, Inc. 2024.

关键词： Drug development Prostate cancer

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Targeting protein-protein interaction interfaces with antiviral N protein inhibitor in SARS-CoV-2

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Biophysical Journal 2024年第4期123卷 478-488页

作者： Hong, Jhen-Yi Lin, Shih-Chao Kehn-Hall, Kylene Zhang, Kai-Min Luo, Shun-Yuan Wu, Hung-Yi Chang, Sui-Yuan Hou, Ming-Hon Institute of Genomics and Bioinformatics and Department of Life Sciences National Chung Hsing University Taichung Taiwan Bachelor Degree Program in Marine Biotechnology College of Life Sciences National Taiwan Ocean University Keelung Taiwan Department of Biomedical Sciences and Pathobiology Virginia-Maryland College of Veterinary Medicine Virginia Polytechnic Institute and State University Blacksburg VA United States Center for Emerging Zoonotic and Arthropod-borne Pathogens Virginia Polytechnic Institute and State University Blacksburg VA United States Department of Chemistry National Chung Hsing University Taichung Taiwan Graduate Institute of Veterinary Pathobiology College of Veterinary Medicine National Chung Hsing University. Taichung Taiwan Department of Clinical Laboratory Sciences and Medical Biotechnology College of Medicine National Taiwan University Taipei Taiwan PhD Program in Medical Biotechnology National Chung Hsing University Taichung Taiwan Biotechnology Center National Chung Hsing University Taichung Taiwan

Coronaviruses not only pose significant global public health threats but also cause extensive damage to livestock-based industries. Previous studies have shown that 5-benzyloxygramine (P3) targets the Middle East respiratory syndrome coronavirus (MERS-CoV) nucleocapsid (N) protein N-terminal domain (N-NTD), inducing non-native protein-protein interactions (PPIs) that impair N protein function. Moreover, P3 exhibits broad-spectrum antiviral activity against CoVs. The sequence similarity of N proteins is relatively low among CoVs, further exhibiting notable variations in the hydrophobic residue responsible for non-native PPIs in the N-NTD. Therefore, to ascertain the mechanism by which P3 demonstrates broad-spectrum anti-CoV activity, we determined the crystal structure of the SARS-CoV-2 N-NTD:P3 complex. We found that P3 was positioned in the dimeric N-NTD via hydrophobic contacts. Compared with the interfaces in MERS-CoV N-NTD, P3 had a reversed orientation in SARS-CoV-2 N-NTD. The Phe residue in the MERS-CoV N-NTD:P3 complex stabilized both P3 moieties. However, in the SARS-CoV-2 N-NTD:P3 complex, the Ile residue formed only one interaction with the P3 benzene ring. Moreover, the pocket in the SARS-CoV-2 N-NTD:P3 complex was more hydrophobic, favoring the insertion of the P3 benzene ring into the complex. Nevertheless, hydrophobic interactions remained the primary stabilizing force in both complexes. These findings suggested that despite the differences in the sequence, P3 can accommodate a hydrophobic pocket in N-NTD to mediate a non-native PPI, enabling its effectiveness against various CoVs. © 2024 Biophysical Society

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Potential protective role of ACE-inhibitors and AT1 receptor blockers against levodopa-induced dyskinesias:a retrospective case-control study

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Neural Regeneration Research 2021年第12期16卷 2475-2478页

作者： Elena Contaldi Luca Magistrelli Anna VMilner Marco Cosentino Franca Marino Cristoforo Comi Movement Disorders Centre Neurology UnitDepartment of Translational MedicineUniversity of Piemonte OrientaleNovaraItaly PhD Program in Medical Sciences and Biotechnology University of Piemonte OrientaleNovaraItaly PhD Program in Clinical and Experimental Medicine and Medical Humanities University of InsubriaVareseItaly Center of Research in Medical Pharmacology University of InsubriaVareseItaly Center for Research in Neuroscience University of InsubriaVareseItaly

Growing evidence has highlighted that angiotensin-converting enzyme(ACE)-inhibitors(ACEi)/AT1 receptor blockers(ARBs)may influence the complex interplay between dopamine and the renin-angiotensin system in the nigrostriatal pathway,thus affecting the development of levodopa-induced dyskinesia in Parkinson’s disease(PD).In the present study,we analyzed whether the use of this class of medication was associated with a reduced occurrence of levodopa-induced dyskinesia,using electronically-stored information of idiopathic PD patients enrolled at Novara University Hospital“Maggiore della Carità”.We conducted a retrospective case-control study identifying PD patients with dyskinesias(PwD;n=47)as *** each PwD we selected a non-dyskinetic control(NoD),nearly perfectly matched according to sex,Unified Parkinson’s Disease Rating Scale(UPDRS)part III score,and duration of antiparkinsonian *** logistic regression was used to evaluate whether dyskinesias were associated with ACEi/ARBs ***-four PD patients were included,aged 72.18±9 years,with an average disease duration of 10.20±4.8 years and 9.04±4.9 years of antiparkinsonian *** mean UPDRS part III score was 18.87±7.6 and the median HY stage was *** the NoD group,25(53.2%)were users and 22(46.8%)non-users of ACEi/***,in the PwD group,11(23.4%)were users and 36 non-users(76.6%)of this drug class(Pearson chi-square=8.824,P=0.003).Concerning general medication,there were no other statistically significant differences between *** controlling for tremor dominant phenotype,levodopa equivalent daily dose,HY 3-4,and disease duration,ACEi/ARBs use was a significant predictor of a lower occurrence of dyskinesia(OR=0.226,95%CI:0.080-0.636,P=0.005).Therefore,our study suggests that ACEi/ARBs may reduce levodopa-induced dyskinesia occurrence and,thanks to good tolerability and easy management,represent a feasible choice when dealing with the treatment of hypertension in PD patients.

关键词： angiotensin-converting enzyme inhibitors AT1 receptor blockers dyskinesias hypertension levodopa motor complications neuroinflammation Parkinson’s disease renin-angiotensin system

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Enhanced IGF-IIRα Expression Exacerbates Lipopolysaccharide-Induced Cardiac Inflammation, Hypertrophy, and Apoptosis Through Calcineurin Activation

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Environmental Toxicology 2024年第11期39卷 5173-5186页

作者： Boonha, Khwanchit Kuo, Wei-Wen Tsai, Bruce Chi-Kang Hsieh, Dennis Jine-Yuan Lin, Kuan-Ho Lu, Shang-Yeh Kuo, Chia-Hua Yang, Liang-Yo Huang, Chih-Yang Graduate Institute of Biomedical Sciences China Medical University Taichung Taiwan Cardiovascular and Mitochondrial Related Disease Research Center Hualien Tzu Chi Hospital Buddhist Tzu Chi Medical Foundation Hualien Taiwan Faculty of Tropical Medicine Mahidol University Bangkok Thailand Department of Biological Science and Technology College of Life Sciences China Medical University Taichung Taiwan PhD Program for Biotechnology Industry China Medical University Taichung Taiwan School of Pharmacy China Medical University Taichung Taiwan Department of Medical Laboratory and Biotechnology Chung Shan Medical University Taichung Taiwan Clinical Laboratory Chung Shan Medical University Hospital Taichung Taiwan Department of Emergency Medicine China Medical University Hospital Taichung Taiwan College of Medicine China Medical University Taichung Taiwan Division of Cardiovascular Medicine Department of Internal Medicine China Medical University Hospital Taichung Taiwan Laboratory of Exercise Biochemistry University of Taipei Taipei Taiwan Institute of Sports Sciences University of Taipei Taipei Taiwan Department of Kinesiology and Health Science College of William and Mary WilliamsburgVA United States School of Physical Education and Sports Science Soochow University Suzhou China Department of Physiology School of Medicine College of Medicine China Medical University Taichung Taiwan Laboratory for Neural Repair China Medical University Hospital Taichung Taiwan Department of Medical Research China Medical University Hospital China Medical University Taichung Taiwan Department of Medical Laboratory Science and Biotechnology Asia University Taichung Taiwan Center of General Education Buddhist Tzu Chi Medical Foundation Tzu Chi University of Science and Technology Hualien Taiwan

Cardiovascular disease is one of the leading causes of death worldwide and has a high prevalence. Insulin-like growth factor-II receptor α (IGF-IIRα) acts as a stress-inducible negative regulator. This study focused on the substantial impact of heightened expression of IGF-IIRα in cardiac myoblasts and its association with the exacerbation of cardiac dysfunction. Using lipopolysaccharide (LPS)-induced H9c2 cardiac myoblasts as a model for sepsis, we aimed to elucidate the molecular interactions between IGF-IIRα and LPS in exacerbating cardiac injury. Our findings demonstrated a synergistic induction of cardiac inflammation and hypertrophy by LPS stimulation and IGF-IIRα overexpression, leading to decreased cell survival. Excessive calcineurin activity, triggered by this combined condition, was identified as a key factor exacerbating the negative effects on cell survival. Cellular changes such as cell enlargement, disrupted actin filaments, and upregulation of hypertrophy-related and inflammation-related proteins contributed to the overall hypertrophic and inflammatory responses. Overexpression of IGF-IIRα also exacerbated apoptosis induced by LPS in H9c2 cardiac myoblasts. Inhibiting calcineurin in LPS-treated H9c2 cardiac myoblasts with IGF-IIRα overexpression effectively reversed the detrimental effects, reducing cell damage and mitigating apoptosis-related cardiac mechanisms. Our study suggests that under sepsis-like conditions in the heart with IGF-IIRα overexpression, hyperactivation of calcineurin worsens cardiac damage. Suppressing IGF-IIRα and calcineurin expression could be a potential intervention to alleviate the impact of the illness and improve cardiac function. © 2024 Wiley Periodicals LLC.

关键词： Heart

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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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Ellagic acid protects against angiotensin II-induced hypertrophic responses through ROS-mediated MAPK pathway in H9c2 cells

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Environmental Toxicology 2024年第5期39卷 3253-3263页

作者： Lee, Ya-Che Jou, Yeong-Chin Chou, Wan-Ching Tsai, Kun-Ling Shen, Cheng-Huang Lee, Shin-Da Department of Urology Ditmanson Medical Foundation Chiayi Christian Hospital Chia-Yi City Taiwan Department of Urology St. Martin De Porres Hospital Chia-Yi City Taiwan Department of Health and Nutrition Biotechnology College of Medical and Health Science Asia University Taichung City Taiwan Department of Physical Therapy College of Medicine National Cheng Kung University Tainan City Taiwan Institute of Allied Health Science College of Medicine National Cheng Kung University Tainan City Taiwan Department of Biomedical Sciences National Chung Cheng University Chia-Yi Min Hsiung Taiwan Department of Physical Therapy College of Medical and Health Science Asia University Taichung City Taiwan Department of Physical Therapy PhD program in Healthcare Science China Medical University Taichung Taiwan

The early myocardial response of hypertension is an elevation of angiotensin-II (Ang-II) concentration, leading to heart failure and cardiac hypertrophy. This hypertrophic event of the heart is mediated by the interaction of Ang type 1 receptors (AT-R1), thereby modulating NADPH oxidase activity in cardiomyocytes, which alters redox status in cardiomyocytes. Ellagic acid (EA) has anti-inflammatory and anti-oxidative capacities. Thus, EA has potential preventive effects on cardiovascular diseases and diabetes. In the last decades, because the protective effect of EA on Ang-II-induced hypertrophic responses is unclear, this study aims to investigate the protective effect of EA in cardiomyocytes. H9c2 cells were treated to Ang-II 1 μM for 24 h to induce cellular damage. We found that EA protected against Ang-II-increased cell surface area and pro-hypertrophic gene expression in H9c2. EA reduced Ang-II-caused AT-R1 upregulation, thereby inhibiting oxidative stress NADPH oxidase activation. EA mitigated Ang-II-enhanced p38 and extracellular-signal-regulated kinase (ERK) phosphorylation. Moreover, EA treatment under Ang-II stimulation also reversed NF-κB activity and iNOS expression. This study shows that EA protects against Ang-II-induced myocardial hypertrophy and attenuates oxidative stress through reactive oxygen species-mediated mitogen-activated protein kinase signaling pathways in H9c2 cells. Thus, EA may be an effective compound for preventing Ang-II-induced myocardial hypertrophy. © 2024 Wiley Periodicals LLC.

关键词： Oxidative stress

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Chlorine-containing polyacetoxybriarane diterpenoids from the octocoral Junceella fragilis

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RSC Advances 2024年第24期14卷 17195-17201页

作者： Do, Hai Nhat Chen, Yu-Ta Chien, Su-Ying Chen, You-Ying Zhang, Mingzi M. Tsou, Lun Kelvin Chen, Jih-Jung Wen, Zhi-Hong Lo, Yi-Hao Zheng, Li-Guo Sung, Ping-Jyun Department of Marine Biotechnology and Resources National Sun Yat-sen University Kaohsiung804201 Taiwan National Museum of Marine Biology & Aquarium Pingtung944401 Taiwan Department of Family Medicine Zuoying Armed Forces General Hospital Kaohsiung813204 Taiwan Instrumentation Center National Taiwan University Taipei106319 Taiwan Institute of Molecular and Genomic Medicine National Health Research Institutes Miaoli350401 Taiwan Institute of Biotechnology and Pharmaceutical Research National Health Research Institutes Miaoli350401 Taiwan Department of Pharmacy School of Pharmaceutical Sciences National Yang Ming Chia Tung University Taipei112304 Taiwan Shu-Zen Junior College of Medicine and Management Kaohsiung821004 Taiwan Institute of Medical Science and Technology National Sun Yat-sen University Kaohsiung804201 Taiwan Doctoral Degree Program in Marine Biotechnology National Sun Yat-sen University Kaohsiung804201 Taiwan Chinese Medicine Research and Development Center China Medical University Hospital Taichung404394 Taiwan Graduate Institute of Natural Products Kaohsiung Medical University Kaohsiung807378 Taiwan PhD Program in Pharmaceutical Biotechnology Fu Jen Catholic University New Taipei City242062 Taiwan

The chemical screening of an octocoral identifed as Junceella fragilis has led to the isolation of five chlorinated briarane-type diterpenoids, including three known metabolites, gemmacolide X (1), frajunolide I (2), and fragilide F (3), along with two new analogs, 12α-acetoxyfragilide F (4) and 12α-acetoxyjunceellin (5). Single-crystal X-ray diffraction analysis was carried out to determine the absolute configurations of 1 and 2, while the structures of new compounds 4 and 5 were ascertained with 2D NMR experiments. Briaranes 1 and 3-5 were active in enhancing alkaline phosphatase (ALP) activity. © 2024 The Royal Society of Chemistry.

关键词： Metabolites

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Menarche - a journey into womanhood: age at menarche and health-related outcomes in East Asians

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Human Reproduction 2024年第6期39卷 1336-1350页

作者： Chiou, Jian-Shiun Lin, Ying-Ju Chang, Cherry Yin-Yi Liang, Wen-Miin Liu, Ting-Yuan Yang, Jai-Sing Chou, Chen-Hsing Lu, Hsing-Fang Chiu, Mu-Lin Lin, Ting-Hsu su Liao, Chiu-Chu Huang, Shao-Mei Chou, I-Ching Li, Te-Mao Huang, Peng-Yan Chien, Tzu-Shun Chen, Hou-Ren Tsai, Fuu-Jen PhD Program for Health Science and Industry College of Health Care China Medical University Taichung Taiwan Department of Health Services Administration China Medical University Taichung Taiwan Genetic Center Department of Medical Research China Medical University Hospital Taichung Taiwan School of Chinese Medicine College of Chinese Medicine China Medical University Taichung Taiwan Division of Minimal Invasive Endoscopy Surgery Department of Obstetrics and Gynecology China Medical University Hospital Taichung Taiwan School of Medicine College of Medicine China Medical University Taichung Taiwan Million-Person Precision Medicine Initiative Department of Medical Research China Medical University Hospital Taichung Taiwan Department of Medical Research China Medical University Hospital China Medical University Taichung Taiwan Laboratory for Statistical and Translational Genetics RIKEN Center for Integrative Medical Sciences Yokohama Japan Department of Pediatrics China Medical University Children's Hospital Taichung Taiwan Graduate Institute of Integrated Medicine China Medical University Taichung Taiwan Division of Medical Genetics China Medical University Children's Hospital Taichung Taiwan Department of Medical Laboratory Science and Biotechnology Asia University Taichung Taiwan

STUDY QUESTION: Are there associations of age at menarche (AAM) with health-related outcomes in East Asians? SUMMARY ANSWER: AAM is associated with osteoporosis, Type 2 diabetes (T2D), glaucoma, and uterine fibroids, as demonstrated through observational studies, polygenic risk scores, genetic correlations, and Mendelian randomization (MR), with additional findings indicating a causal effect of BMI and T2D on earlier AAM. WHAT IS KNOWN ALREADY: Puberty timing is linked to adult disease risk, but research predominantly focuses on European populations, with limited studies in other groups. STUDY DESIGN, SIZE, DURATION: We performed an AAM genome-wide association study (GWAS) with 57 890 Han Taiwanese females and examined the association between AAM and 154 disease outcomes using the Taiwanese database. Additionally, we examined genetic correlations between AAM and 113 diseases and 67 phenotypes using Japanese GWAS summary statistics. PARTICIPANTS/MATERIALS, SETTING, METHODS: We performed AAM GWAS and gene-based GWAS studies to obtain summary statistics and identify potential AAM-related genes. We applied phenotype, polygenic risk scores, and genetic correlation analyses of AAM to explore health-related outcomes, using multivariate regression and linkage disequilibrium score regression analyses. We also explored potential bidirectional causal relationships between AAM and related outcomes through univariable and multivariable MR analyses. MAIN RESULTS AND THE ROLE OF CHANCE: Fifteen lead single-nucleotide polymorphisms and 24 distinct genes were associated with AAM in Taiwan. AAM was genetically associated with later menarche and menopause, greater height, increased osteoporosis risk, but lower BMI, and reduced risks of T2D, glaucoma, and uterine fibroids in East Asians. Bidirectional MR analyses indicated that higher BMI/T2D causally leads to earlier AAM. LIMITATIONS, REASONS FOR CAUTION: Our findings were specific to Han Taiwanese individuals, with genetic correlatio

关键词： age at menarche genetic correlation genome-wide association study Mendelian randomization polygenic risk score

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Commentary on small-volume biopsy of follicular lymphoma: Practical issues in the molecular era

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Cancer cytopathology 2024年第3期132卷 136-138页

作者： Chien-Chin Chen Department of Pathology Ditmanson Medical Foundation Chia-Yi Christian Hospital Chiayi Taiwan. Department of Biotechnology and Bioindustry Sciences College of Bioscience and Biotechnology National Cheng Kung University Tainan Taiwan. Department of Cosmetic Science Chia Nan University of Pharmacy and Science Tainan Taiwan. PhD Program in Translational Medicine Rong Hsing Research Center for Translational Medicine National Chung Hsing University Taichung Taiwan.

Follicular lymphoma (FL) is a common subtype of non-Hodgkin lymphoma derived from germinal center B-cells. Small-volume biopsies (SVBs), including fine-needle aspiration, needle core biopsy, and cell blocks, are often used for the assessment of patients with FL. Recently, Fitzpatrick et al. found that additional biopsies were frequently needed to supplement SVB for the initial diagnosis of FL. However, regardless of the type of SVB used, additional biopsies were usually not necessary for assessments for transformed or recurrent FL. Their multi-institutional study reflects the fact that SVB may be sufficient for clinical decision-making in these medical settings, although surgical excision is the gold standard for a definitive diagnosis of FL. With ancillary tests and advances in molecular testing, SVB has become increasingly popular and helpful, although there are practical limitations.

关键词： biopsy core needle fine-needle aspiration follicular lymphoma hematology lymphoma

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Synthesis of bioactive evodiamine and rutaecarpine analogues under ball milling conditions

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Organic and Biomolecular Chemistry 2024年第13期22卷 2620-2629页

作者： Hu, Hao-Chun Yu, Szu-Yin Tsai, Yi-Hong Hsieh, Pei-Wen Wang, Hui-Chun Chen, Yan-Ning Chuang, Ya-Ting Lee, Min-Yu Chang, Hsueh-Wei Wu, Yang-Chang Chang, Fang-Rong Szatmári, István Fülöp, Ferenc Graduate Institute of Natural Products College of Pharmacy Kaohsiung Medical University Kaohsiung80708 Taiwan Institute of Pharmaceutical Chemistry HUN-REN-Stereochemistry Research Group University of Szeged Szeged6720 Hungary Graduate Institute of Natural Products School of Traditional Chinese Medicine College of Medicine Chang Gung University Taoyuan333 Taiwan Institute of Pharmacognosy University of Szeged Szeged6720 Hungary Department of Pharmacy and Master Program College of Pharmacy and Health Care Tajen University Pingtung County907101 Taiwan Graduate Institute of Biomedical Sciences College of Medicine Chang Gung University Taoyuan333 Taiwan Department of General Surgery Chang Gung Memorial Hospital Chiayi613 Taiwan Department of Biomedical Science and Environmental Biology PhD Program in Life Sciences College of Life Science Kaohsiung Medical University Kaohsiung80708 Taiwan Graduate Institute of Medicine College of Medicine Kaohsiung Medical University Kaohsiung80708 Taiwan Department of Otorhinolaryngology-Head and Neck Surgery Fu Jen Catholic University Hospital Fu Jen Catholic University New Taipei City242062 Taiwan School of Medicine College of Medicine Fu Jen Catholic University New Taipei City242062 Taiwan Chinese Medicine Research and Development Center China Medical University Hospital Taichung404 Taiwan Graduate Institute of Integrated Medicine China Medical University Taichung404 Taiwan Drug Development and Value Creation Research Center Kaohsiung Medical University Kaohsiung807378 Taiwan Department of Medical Research Kaohsiung Medical University Hospital Kaohsiung Medical University Kaohsiung807378 Taiwan Department of Marine Biotechnology and Resources National Sun Yat-sen University Kaohsiung80424 Taiwan

Mechanochemical reactions achieved by processes such as milling and grinding are promising alternatives to traditional solution-based chemistry. This approach not only eliminates the need for large amounts of solvents, thereby reducing waste generation, but also finds applications in chemical and materials synthesis. The focus of this study is on the synthesis of quinazolinone derivatives by ball milling, in particular evodiamine and rutaecarpine analogues. These compounds are of interest due to their diverse bioactivities, including potential anticancer properties. The study examines the reactions carried out under ball milling conditions, emphasizing their efficiency in terms of shorter reaction times and reduced environmental impact compared to conventional methods. The ball milling reaction of evodiamine and rutaecarpine analogues resulted in yields of 63-78% and 22-61%, respectively. In addition, these compounds were tested for their cytotoxic activity, and evodiamine exhibited an IC50 of 0.75 ± 0.04 μg mL−1 against the Ca9-22 cell line. At its core, this research represents a new means to synthesise these compounds, providing a more environmentally friendly and sustainable alternative to traditional approaches. © 2024 The Royal Society of Chemistry.

关键词： Ball milling

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