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Seropharmacological Study on Osteogenic Effects of Post-Absorption Ingredients of An Osteoprotective Herbal Formula

Chinese Journal of Integrative Medicine 2017年第1期23卷 25-32页

作者： SIU Wing-sum KO Chun-hay WONG Hing-lok GAO Si SHUM Wai-ting LAU Clara Bik-san hung lung-kim LEUNG Ping-chung Institute of Chinese Medicine Chinese University of Hong KongHong KongChina State Key Laboratory of Phytochemistry and Plant Resources in West China Chinese University of Hong KongHong KongChina Department of Orthopaedics and Traumatology Chinese University of Hong KonqHong KongChina

Objective： To further investigate the in vitro effects of an osteoprotective herbal formula ＂ELP＂（Herba Epimedii, Fructus Ligustri Lucidi and Fructus Psora/eae） using seropharmacological approach. Methods： Rats were fed with ELP or its individual component herbs for 2 days. The serum containing the post-absorbed ingredients of the herbal items were collected for cell culture using UMR106 cell, RAW264.7 cell and mesenchymal stem cell （MSC） isolated from the bone marrow of the rats. The effects of the herbal-containing serum on cell toxicity were detected by 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide assay; bromodeoxyuridine assay was conducted to measure the cell proliferation of UMR106 cell and MSC; cell activity was measured using colorimetric method, and mRNA expression of runt-related transcription factor 2 （Runx2）, alkaline phosphatase （ALP） and osteopontin （OPN） of UMR106 and MSC as well as matrix metalloproteinase 9 （MMP-9）, tartrate-resistant acid phosphatase （TRAP） and cathepsin K of RAW264.7 were analyzed using real-time reverse-transcription polymerase chain reaction. Results： ELP and its component serum exhibited no cytotoxic effects on the cells. The ELP-containing serum increased the proliferation of UMR106 cell and MSC by 25.7% and 14.4%, respectively and the alkaline phosphatase activity of MSC was increased by 42.6%. On the contrary, it inhibited the RAW264.7 cell differentiation by 29.2%. ELP serum upregulated the Runx2 expression of UMR and MSC by 1.18 fold and 1.27 fold, respectively. It also upregulated ALP and OPN expression in MSC by 1.69- and 2.12-fold, respectively. On the other hand, ELP serum down-regulated MMP-9 and cathepsin K expression of RAW264.7 cell by 0.46- and 0.36-fold, respectively. Conclusions： The serum of the animals fed with ELP contains active ingredients which are effective in promoting osteogenesis and inhibiting osteoclastogenesis.

关键词： osteoporosis seropharmacology osteogenesis herbal formula

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Targeting the RAS/RAF/MAPK pathway for cancer therapy: from mechanism to clinical studies

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Signal Transduction and Targeted Therapy 2024年第1期9卷 173-210页

作者： Md Entaz Bahar Hyun Joon kim Deok Ryong kim Department of Biochemistry and Convergence Medical Sciences and Institute of Medical Science Gyeongsang National UniversityCollege of MedicineJinjuSouth Korea Department of Anatomy and Convergence Medical Sciences and Institute of Medical Science Gyeongsang National UniversityCollege of MedicineJinjuSouth Korea

Metastatic dissemination of solid tumors,a leading cause of cancer-related mortality,underscores the urgent need for enhanced insights into the molecular and cellular mechanisms underlying metastasis,chemoresistance,and the mechanistic backgrounds of individuals whose cancers are prone to *** most prevalent signaling cascade governed by multi-kinase inhibitors is the mitogen-activated protein kinase(MAPK)pathway,encompassing the RAS–RAF–MAPK kinase(MEK)–extracellular signal-related kinase(ERK)*** kinase is a primary mediator of the MAPK pathway,responsible for the sequential activation of downstream targets,such as MEK and the transcription factor ERK,which control numerous cellular and physiological processes,including organism development,cell cycle control,cell proliferation and differentiation,cell survival,and *** in this signaling cascade are associated with diseases such as *** inhibitors(RAFi)combined with MEK blockers represent an FDAapproved therapeutic strategy for numerous RAF-mutant cancers,including melanoma,non-small cell lung carcinoma,and thyroid ***,the development of therapy resistance by cancer cells remains an important ***,an intracellular lysosome-dependent catabolic recycling process,plays a critical role in the development of RAFi resistance in ***,targeting RAF and autophagy could be novel treatment strategies for RAF-mutant *** this review,we delve deeper into the mechanistic insights surrounding RAF kinase signaling in tumorigenesis and ***,we explore and discuss the ongoing development of next-generation RAF inhibitors with enhanced therapeutic ***,this review sheds light on the functional interplay between RAF-targeted therapies and autophagy in cancer.

关键词： RAF insight mechanism

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Prognostic factors of early recurrence after complete cytoreductive surgery and hyperthermic intraperitoneal chemotherapy

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World Journal of Clinical Cases 2024年第27期12卷 6057-6069页

作者： Chao-Yu Chen Tzu-Hao Huang Li-Wen Lee Jrhau lung Yu-Che Ou Chien-Hui hung Huei-Chieh Chuang Min-Chi Chen Ting-Yao Wang Department of Obstetrics and Gynecology Chang Gung Memorial HospitalChiayi 613Taiwan Graduate Institute of Clinical Medical Sciences College of MedicineChang Gung UniversityTaoyuan 333Taiwan Department of Early Childhood Care and Education Shu-Zen Junior College of Medicine and ManagementKaohsiung 821Taiwan Division of General Surgery Department of SurgeryChang Gung Memorial HospitalChiayi 613Taiwan Department of Diagnostic Radiology Chang Gung Memorial HospitalChiayi 613Taiwan College of Medicine Chang Gung UniversityTaoyuan 333Taiwan Department of Medical Research and Development Chang Gung Memorial HospitalChiayi 613Taiwan Department of Obstetrics and Gynecology Kaohsiung Chang Gung Memorial HospitalKaohsiung 833Taiwan Department of Anatomic Pathology Chang Gung Memorial HospitalChiayi 613Taiwan Department of Public Health Chang Gung UniversityTaoyuan 333Taiwan Division of Hematology and Oncology Department of Internal MedicineChang Gung Memorial HospitalChiayi 613Taiwan

BACKGROUND Although cytoreductive surgery(CRS)and hyperthermic intraperitoneal chemotherapy(HIPEC)offer the potential for long-term survival in peritoneal carcinomatosis,outcomes following CRS/HIPEC vary *** To identify the clinical factors associated with progression-free survival(PFS)after complete CRS/HIPEC in patients with colorectal/high-grade appendiceal,ovarian,and gastric *** We retrospectively evaluated the risk of recurrence within 1 year after CRS/HIPEC and its impact on overall survival(OS)in patients recruited between 2015 and *** regression models were used to assess the prognostic factors for the risk of recurrence within 1 ***–Meier survival curves and Cox proportional hazards models were used to evaluate the association between recurrence and *** Of the 80 enrolled patients,39 had an unfavorable PFS(12 was associated with a lower rate of achieving CC-0(P=0.027).The favorable PFS group had a significantly longer OS(median 81.7 mo vs 17.0 mo,P<0.001).CONCLUSION Achieving CC-0 was associated with a lower early recurrence rate and improved long-term *** study underscores the importance of selecting appropriate candidates for CRS/HIPEC to manage peritoneal carcinomatosis.

关键词： Peritoneal metastasis Cytoreductive surgery Hyperthermic intraperitoneal chemotherapy Predictor Recurrence

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SARS-CoV-2 aberrantly elevates mitochondrial bioenergetics to induce robust virus propagation

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Signal Transduction and Targeted Therapy 2024年第6期9卷 2702-2715页

作者： Hye Jin Shin Wooseong Lee Keun Bon Ku Gun Young Yoon Hyun-Woo Moon Chonsaeng kim Mi-Hwa kim Yoon-Sun Yi Sangmi Jun Bum-Tae kim Jong-Won Oh Aleem Siddiqui Seong-Jun kim Department of Convergent Research of Emerging Virus Infection Korea Research Institute of Chemical TechnologyDaejeon 34114Republic of Korea Gyeongnam Biohealth Research Center Gyeongnam Branch InstituteKorea Institute of ToxicologyJinju 52834Republic of Korea Center for Research Equipment Korea Basic Science InstituteCheongjuChungcheongbuk-do 28119Republic of Korea Department of Biotechnology Yonsei UniversitySeoul 03722Republic of Korea Division of Infectious Diseases School of MedicineUniversity of CaliforniaSan DiegoLa JollaCA 92093USA Present address:Department of Microbiology Chungnam National University School of MedicineDaejeon 35015Republic of Korea

Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)is a‘highly transmissible respiratory pathogen,leading to severe multiorgan ***,knowledge regarding SARS-CoV-2-induced cellular alterations is *** this study,we report that SARSCoV-2 aberrantly elevates mitochondrial bioenergetics and activates the EGFR-mediated cell survival signal cascade during the early stage of viral ***-CoV-2 causes an increase in mitochondrial transmembrane potential via the SARS-CoV-2 RNAnucleocapsid cluster,thereby abnormally promoting mitochondrial elongation and the OXPHOS process,followed by enhancing ATP ***,SARS-CoV-2 activates the EGFR signal cascade and subsequently induces mitochondrial EGFR trafficking,contributing to abnormal OXPHOS process and viral *** EGFR inhibitors remarkably reduce SARS-CoV-2 propagation,among which vandetanib exhibits the highest antiviral *** of SARS-CoV-2-infected cells with vandetanib decreases SARS-CoV-2-induced EGFR trafficking to the mitochondria and restores SARS-CoV-2-induced aberrant elevation in OXPHOS process and ATP generation,thereby resulting in the reduction of SARS-CoV-2 ***,oral administration of vandetanib to SARS-CoV-2-infected hACE2 transgenic mice reduces SARS-CoV-2 propagation in lung tissue and mitigates SARS-CoV-2-induced lung *** also exhibits potent antiviral activity against various SARS-CoV-2 variants of concern,including alpha,beta,delta and omicron,in in vitro cell culture *** together,our findings provide novel insight into SARS-CoV-2-induced alterations in mitochondrial dynamics and EGFR trafficking during the early stage of viral infection and their roles in robust SARS-CoV-2 propagation,suggesting that EGFR is an attractive host target for combating COVID-19.

关键词： alterations aberrant thereby

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Jun12682,a potent SARS-CoV-2 papain-like protease inhibitor with exceptional antiviral efficacy in mice

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Acta Pharmaceutica Sinica B 2024年第9期14卷 4189-4192页

作者： Mianling Yang Meehyein kim Peng Zhan Department of Medicinal Chemistry Key Laboratory of Chemical Biology(Ministry of Education)School of Pharmaceutical SciencesShandong UniversityJi’nan 250012China Infectious Diseases Therapeutic Research Center Korea Research Institute of Chemical Technology(KRICT)Daejeon 34114Republic of Korea

Recently,a collaborative research study published in Science,led by Jun Wang,Xufang Deng,Eddy Arnold,and Francesc Xavier Ruiz1,identified a series of potent small molecule inhibitors that specifically target SARS-CoV-2 papain-like protease(PLpro).The study demonstrated nanomolar PLpro inhibitory potency with Ki values ranging from 13.2 to 88.2 nmol/*** employing a structure-based drug design strategy,the researchers discovered an exceptionally promising compound,named Jun12682,that effectively targets both the newly discovered ubiquitin Val70(Val70Ub)-binding site and the known blocking loop(BL2)groove near the S4 subsite of ***,studies on the mechanism of action revealed that Jun12682 inhibits the deubiquitinating and deISGylating activities of PLpro,which are crucial for antagonizing the host’s innate immune response upon viral *** biology studies confirmed the“two-pronged”binding mode of Jun12682,aligning perfectly with their drug design ***,Jun12682 exhibited potent antiviral activity against SARS-CoV-2 and its variants,including nirmatrelvir-resistant mutants,in Caco-2 cells(EC50:0.44e2.02 mmol/L).It is noteworthy that its oral administration significantly improved survival rates and alleviated both lung virus loads and histopathological lesions in a lethal SARS-CoV-2 mouse *** conclusion。

关键词： SARS-CoV-2 Papain-like protease Broad-spectrum Anti-drug resistance Drug candidate

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TonEBP expression is essential in the IL-1β–induced migration and invasion of human A549 lung cancer cells

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Oncology Research 2024年第1期32卷 151-161页

作者： HEE JU SONG TAEHEE kim HAN NA CHOI SOO JIN kim SANG DO LEE Department of Physiology School of MedicineChungnam National UniversityDaejeon35015Korea

lung cancer has the highest mortality rate among all cancers,in part because it readily *** tumor microenvironment,comprising blood vessels,fibroblasts,immune cells,and macrophages[including tumor-associated macrophages(TAMs)],is closely related to cancer cell growth,migration,and *** secrete several cytokines,including interleukin(IL)-1β,which participate in cancer migration and invasion.p21-activated kinase 1(PAK1),an important signaling molecule,induces cell migration and invasion in several ***responsive enhancer-binding protein(TonEBP)is also known to participate in cancer cell growth,migration,and ***,the mechanisms by which it increases lung cancer migration remain ***,in this study,we aimed to elucidate the mechanisms by which IL-1βand TonEBP affect lung cancer cell migration and *** found that A549 cocultured-MΦ-secreted IL-1βinduced A549 cell migration and invasion via the PAK1 *** deficiency reduced A549 cell migration and invasion and increased responsiveness to IL-1β–induced migration and ***1 phosphorylation,which was promoted by IL-1β,was reduced when TonEBP was *** results suggest that TonEBP plays an important role in IL-1βinduction and invasiveness of A549 cells via the PAK1 *** findings could be valuable in identifying potential targets for lung cancer treatment.

关键词： lung cancer TonEBP Tumor microenvironment Tumor-associated macrophage IL-1β

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Neural Wiskott-Aldrich syndrome protein(N-WASP)promotes distant metastasis in pancreatic ductal adenocarcinoma via activation of LOXL2

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Oncology Research 2024年第4期32卷 615-624页

作者： HYUNG SUN kim YUN SUN LEE SEUNG MYUNG DONG HYO JUNG kim DA EUN LEE HYEON WOONG KANG MYEONG JIN kim JOON SEONG PARK Department of Surgery Gangnam Severance HospitalYonsei University College of MedicineSeoulKorea Department of Surgery Graduate School of Medical ScienceBrain Korea 21 ProjectYonsei University College of MedicineSeoulKorea Gibiome Co. Ltd.Gyeonggi-doKorea

Pancreatic ductal adenocarcinoma(PDAC)is one of the most aggressive solid malignancies.A specific mechanism of its metastasis has not been *** this study,we investigated whether Neural Wiskott-Aldrich syndrome protein(N-WASP)plays a role in distant metastasis of *** found that N-WASP is markedly expressed in clinical patients with *** analysis showed a notably more distant metastatic pattern in the N-WASP-high group compared to the N-WASP-low group.N-WASP was noted to be a novel mediator of epithelialmesenchymal transition(EMT)via gene expression profile *** of N-WASP in pancreatic cancer cells significantly inhibited cell invasion,migration,and *** also observed positive association of lysyl oxidase-like 2(LOXL2)and focal adhesion kinase(FAK)with the N-WASP-mediated response,wherein EMT and invadopodia function were *** N-WASP and LOXL2 depletion significantly reduced the incidence of liver and lung metastatic lesions in orthotopic mouse models of pancreatic *** results elucidate a novel role for N-WASP signaling associated with LOXL2 in EMT and invadopodia function,with respect to regulation of intercellular communication in tumor cells for promoting pancreatic cancer *** findings may aid in the development of therapeutic strategies against pancreatic cancer.

关键词： Pancreatic cancer Neural Wiskott-Aldrich syndrome protein(N-WASP)signaling Metastasis Epithelial-mesenchymal transition(EMT) Lysyl oxidase-like 2(LOXL2)

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Solitary extraovarian primary peritoneal carcinoma with direct invasion into the liver,diaphragm and lung without peritoneal dissemination or distant metastasis

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Hepatobiliary & Pancreatic Diseases International 2024年第3期23卷 322-325页

作者： Billy Ho hung Cheung Wong Hoi She Siu Lun Ho Albert Chi Yan Chan Chung Mau Lo Tan To Cheung Department of Surgery The University of Hong KongHong KongChina Department of Pathology The University of Hong KongHong KongChina

To the Editor:Extraovarian primary peritoneal carcinoma(EOPPC)is an uncommon malignancy with many similarities to epithelial ovarian carcinoma in histological,clinical,and etiological aspects[1].This phenomenon is explained by their common embryonal origin,in which both develop from the coelomic epithelium in the early embryological *** their similarities,the incidence of EOPPC is significantly lower than that of epithelial ovarian carcinoma(6.78 cases per million vs.120.5 cases per million)[1].

关键词： peritoneal invasion metastasis

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Prevalence and risk factors for impaired renal function among Asian patients with nonalcoholic fatty liver disease

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Hepatobiliary & Pancreatic Diseases International 2024年第3期23卷 241-248页

作者： Chao Sun George Boon-Bee Goh Wan-Cheng Chow Wah-Kheong Chan Grace Lai-hung Wong Wai-Kay Seto Yi-Hsiang Huang Han-Chieh Lin I-Cheng Lee Hye Won Lee Seung Up kim Vincent Wai-Sun Wong Jian-Gao Fan Center for Fatty Liver Disease Department of GastroenterologyXinhua Hospital Affiliated to Shanghai Jiao Tong University School of MedicineShanghai Key Lab of Pediatric Gastroenterology and NutritionShanghai 200092China Department of Gastroenterology&Hepatology Singapore General HospitalSingaporeSingapore Gastroenterology and Hepatology Unit Department of MedicineFaculty of MedicineUniversity of MalayaKuala LumpurMalaysia Department of Medicine and Therapeutics and State Key Laboratory of Digestive Disease The Chinese University of Hong KongHong KongChina Department of Medicine The University of Hong KongHong KongChina Institute of Clinical Medicine National Yang Ming Chiao Tung University School of MedicineTaipeiTaiwanChina Division of Gastroenterology and Hepatology Taipei Veterans General HospitalTaipeiTaiwanChina Faculty of Medicine National Yang Ming Chiao Tung University School of MedicineTaipeiTaiwanChina Department of Internal Medicine Yonsei University College of MedicineSeoulKorea

Background:Nonalcoholic fatty liver disease(NAFLD)is associated with impaired renal function,and both diseases often occur alongside other metabolic ***,the prevalence and risk factors for impaired renal function in patients with NAFLD remain *** objective of this study was to identify the prevalence and risk factors for renal impairment in NAFLD ***:All adults aged 18-70 years with ultrasound-diagnosed NAFLD and transient elastography examination from eight Asian centers were enrolled in this prospective *** fibrosis and cirrhosis were assessed by FibroScan-aspartate aminotransferase(FAST),Agile 3+and Agile 4 *** renal function and chronic kidney disease(CKD)were defined by an estimated glomerular filtration rate(eGFR)with value of<90 mL/min/1.73 m^(2) and<60 mL/min/1.73 m^(2),respectively,as estimated by the CKD-Epidemiology Collaboration(CKD-EPI)***:Among 529 included NAFLD patients,the prevalence rates of impaired renal function and CKD were 37.4%and 4.9%,*** multivariate analysis,a moderate-high risk of advanced liver fibrosis and cirrhosis according to Agile 3+and Agile 4 scores were independent risk factors for CKD(P<0.05).Furthermore,increased fasting plasma glucose(FPG)and blood pressure were significantly associated with impaired renal function after controlling for the other components of metabolic syndrome(P<0.05).Compared with patients with normoglycemia,those with prediabetes[FPG≥5.6 mmol/L or hemoglobin A1c(HbA1c)≥5.7%]were more likely to have impaired renal function(P<0.05).Conclusions:Agile 3+and Agile 4 are reliable for identifying NAFLD patients with high risk of *** glycemic control in the prediabetic stage might have a potential renoprotective role in these patients.

关键词： Nonalcoholic fatty liver disease Impaired renal function Agile 3+ Agile 4 Metabolic syndrome

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The SARS-CoV-2 spike protein induces lung cancer migration and invasion in a TLR2-dependent manner

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Cancer Communications 2024年第2期44卷 273-277页

作者： Mi-Jeong kim Ji Young kim Ji Hye Shin Juhee Son Yeeun Kang Soo-Kyung Jeong Duk-Hwan kim Kyun-Hwan kim Eunyoung Chun Ki-Young Lee Department of Immunology Samsung Biomedical Research InstituteSungkyunkwan University School of MedicineSuwonRepublic of Korea Research and Development Center CHA Vaccine InstituteSeongnam-siRepublic of Korea Department of Molecular Cell Biology Sungkyunkwan University School of MedicineSuwonRepublic of Korea Department of Precision Medicine Sungkyunkwan University School of MedicineSuwonRepublic of Korea Department of Health Sciences and Technology Samsung Advanced Institute for Health Sciences&TechnologySamsung Medical CenterSungkyunkwan UniversitySeoulRepublic of Korea

Dear editor,Severe acute respiratory syndrome coronavirus2(SARS-CoV-2)infection can lead to severe outcomes in patients with cancer[1].It has been reported that patients with lung cancers disproportionately manifest severe COVID-19 with a high rate of hospitalization and death[2].Notably,the SARS-CoV-2 Spike(S)protein can induce hyper-inflammation in both epithelial cells and macrophages through toll-like receptor(TLR)1/TLR2 or TLR2/6-dependent nuclear factor-kappaB(NF-κB)path-way[3].However,molecular and cellular evidence on whether the SARS-CoV-2 virus affects the severity of lung cancer patients through TLR1/2 or TLR2/6 signaling remains unclear.

关键词： lung TLR2 invasion

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