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Inhalation of taraxasterol loaded mixed micelles for the treatment of idiopathic pulmonary fibrosis

Chinese Chemical Letters 2024年第8期35卷 475-480页

作者： Tong Zhang Chao Sun Shubin Yang Zimin Cai Sifeng Zhu Wendian Liu Yun Luan Cheng Wang Key Laboratory of marine Drugs Chinese Ministry of EducationSchool of Medicine and PharmacyOcean University of ChinaQingdao 266003China Central Research Laboratory Department of General Surgerythe Second Hospital of Shandong UniversityJi’nan 250033China Laboratory for marine Drugs and Bioproducts Pilot National Laboratory for Marine Science and TechnologyQingdao 266237China Orthopedics Dept.1 Rushan people’s hospitalRushan 264500China Department of Cardiology the Second Hospital of Shandong UniversityJi’nan 250033China

Idiopathic pulmonary fibrosis(IPF)is a chronic and fatal lung disease characterized by pulmonary inflam-mation,oxidative stress,and excessive extracellular matrix(ECM)*** anti-fibrotic drugs for IPF treatment in the clinic lack selectivity and demonstrate unsatisfactory efficacy,highlighting the urgent necessity for a novel therapeutic ***(TA),which has biological activities against lung injury induced by various factors,is a potential anti-IPF drug due to its anti-inflammatory,antiox-idant and lung-protective ***,the protective effect of TA on IPF has not been confirmed,and its clinical application is limited due to its poor aqueous *** this study,we demonstrated that TA could inhibit epithelial-mesenchymal transition(EMT)and migration of A549 cells by inhibiting the transforming growth factor-β1(TGF-β1)/Smad signaling *** improve the aqueous solubility and pulmonary administration performance of TA,we prepared TA loaded methoxy poly(ethylene glycol)-poly(d,l-lactide)(mPEG-PLA)/d-α-tocopheryl polyethylene glycol succinate(TPGS)mixed polymeric mi-celles(TA-PM).Then a MicroSprayer^(R) Aerosolizer was used to deliver TA-PM once every two days for three weeks to evaluate their therapeutic effects on bleomycin(BLM)-induced IPF *** results demonstrated that inhaled TA-PM significantly inhibited BLM-induced inflammation,oxidative stress and fibrosis in lung ***,TA-PM exhibited high pulmonary deposition and retention by pul-monary administration,along with a favorable safety ***,this study emphasizes the potential of inhaled TA-PM as a promising treatment for IPF,providing a new opportunity for their clinical appli-cation.

关键词： Taraxasterol Idiopathic pulmonary fibrosis Mixed polymeric micelles Pulmonary administration Bleomycin

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Identification of marine natural product Pretrichodermamide B as a STAT3 inhibitor for efficient anticancer therapy

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marine Life Science & Technology 2023年第1期5卷 94-101页

作者： Rui Li Yue Zhou Xinxin Zhang Lujia Yang Jieyu Liu Samantha M.Wightman Ling Lv Zhiqing Liu Chang-Yun Wang Chenyang Zhao School of Medicine and Pharmacy Institute of Evolution&Marine BiodiversityCollege of Food Science and EngineeringOcean University of ChinaQingdao266003China Laboratory for marine Drugs and Bioproducts Qingdao National Laboratory for Marine Science and TechnologyQingdao266237China Department of Cancer Biology Lerner Research InstituteCleveland ClinicClevelandOH44195USA

The Janus kinase(JAK)/signal transducer and activator of transcription 3(STAT3)regulates the expression of various critical mediators of cancer and is considered as one of the central communication nodes in cell growth and *** natural products(MNP)represent great resources for discovery of bioactive lead compounds,especially anti-cancer *** the medium-throughput screening of our in-house MNP library,Pretrichodermamide B,an epidithiodiketopiperazine,was identified as a JAK/STAT3 signaling *** studies identified that Pretrichodermamide B directly binds to STAT3,preventing phosphorylation and thus inhibiting JAK/STAT3 ***,it suppressed cancer cell growth,in vitro,at low micromolar concentrations and demonstrated efficacy in vivo by decreasing tumor growth in a xenograft mouse *** addition,it was shown that Pretrichodermamide B was able to induce cell cycle arrest and promote cell *** study demonstrated that Pretrichodermamide B is a novel STAT3 inhibitor,which should be considered for further exploration as a promising anti-cancer therapy.

关键词： Pretrichodermamide B Signal transducer and activator of transcription 3(STAT3) marine natural products Target protein In vivo anti-cancer efficacy

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Efficacy of endoluminal gastroplication in Japanese patients with proton pump inhibitor-resistant,non-erosive esophagitis

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World Journal of Gastroenterology 2012年第41期18卷 5940-5947页

作者： Kentaro Tokudome Yasushi Funaki Makoto Sasaki Shinya Izawa Yasuhiro Tamura Akihito Iida Naotaka Ogasawara Toshihiro Konagaya Yoshifumi Tokura Kunio Kasugai Division of Gastroenterology Department of Internal MedicineAichi Medical University School of MedicineAichi 480-1195Japan Department of clinical Laboratory Aichi Medical University School of MedicineAichi 480-1195Japan marine clinic NagoyaAichi 460-0002Japan Tokura Yoshifumi Stomach and Intestines Internal Medicine clinic Kyoto 615-8256Japan

AIM： To evaluate the efficacy, safety, and long-term outcomes of endoluminal gastroplication （ELGP） in pa- tients with proton pump inhibitor （PPI）-resistant, non- erosive reflux disease （NERD）. METHODS： The subjects were NERD patients, diag- nosed by upper endoscopy before PPI use, who had symptoms such as heartburn or reflux sensations two or more times a week even after 8 wk of full-dose PPI treatment. Prior to ELGP, while continuing full-dose PPImedication, patients＇ symptoms and quality of life （QOL） were assessed using the questionnaire for the diagno- sis of reflux disease, the frequency scale for symptoms of gastro-esophageal reflux disease （FSSG）, gastroin- testinal symptoms rating scale, a 36-item short-form. In addition, 24-h esophageal pH monitoring or 24-h in- traesophageal pH/impedance （MII-pH） monitoring was performed. The Bard EndoCinchTM was used for ELGP, and 2 or 3 plications were made. After ELGP, all acid reducers were temporarily discontinued, and medica- tion was resumed depending on the development and severity of symptoms. Three mo after ELGP, symptoms, QOL, pH or MII-pH monitoring, number of plications, and PPI medication were evaluated. Further, symptoms, number of plications, and PPI medication were evalu- ated 12 mo after ELGP to investigate long-term effects. RESULTS： The mean FSSG score decreased signifi- cantly from before ELGP to 3 and 12 mo after ELGP （19.1 ：k 10.5 to 10.3 ＋ 7.4 and 9.3 ＋ 9.9, P 〈 0.05, respectively）. The total number of plications decreased gradually at 3 and 12 mo after ELGP （2.4 ＋ 0.8 to 1.2 ：l： 0.8 and 0.8 ：l： 1.0, P 〈 0.05, respectively）. The FSSG scores in cases with no remaining plications and in cases with one or more remaining plications were 4.4 and 2.7, respectively, after 3 too, and 2.0 and 2.8, respectively, after 12 mo, showing no correlation to plication loss. On pH monitoring, there was no differ- ence in the percent time pH 〈 4 from before ELGP to 3 mo after. Impedance monitoring revealed no changes

关键词： Endoluminal gastroplication EsophagealpH Gastro-esophageal reflux disease Non-erosive re-flux disease Proton pump inhibitor-resistant

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Type I interferon signaling facilitates resolution of acute liver injury by priming macrophage polarization

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Cellular & Molecular Immunology 2023年第2期20卷 143-157页

作者： Qiaoling Song Shyamasree Datta Xue Liang Xiaohan Xu Paul Pavicic Xiaonan Zhang Yuanyuan Zhao Shan Liu Jun Zhao Yuting Xu Jing Xu Lihong Wu Zhihua Wu Minghui Zhang Zhan Zhao Chunhua Lin Yuxin Wang Peng Han Peng Jiang Yating Qin Wei Li Yingying Zhang Yonglun Luo Ganes Sen George R.Stark Chenyang Zhao Thomas Hamilton Jinbo Yang Key Laboratory of marine Drugs Ministry of EducationSchool of Medicine and PharmacyOcean University of ChinaQingdaoChina Department of Inflammation and Immunity Lerner Research InstituteCleveland Clinic FoundationClevelandOHUSA Shyamasree Datta Paul PavicicGanes Sen&Thomas Hamilton Lars Bolund Institute of Regenerative MedicineQingdao-Europe Advanced Institute for Life SciencesBGI-QingdaoBGI-ShenzhenShenzhenChina Innovation Center of marine Drug Screening&Evaluation Qingdao National Laboratory for Marine Science and TechnologyQingdaoChina Department of Radiation Affiliated Hospital of Qingdao UniversityQingdaoChina Department of Urology Yantai Yuhuangding HospitalYantaiChina Department of Cancer Biology Lerner Research InstituteCleveland Clinic FoundationClevelandOHUSA

Due to their broad functional plasticity,myeloid cells contribute to both liver injury and recovery during acetaminophen overdose-induced acute liver injury(APAP-ALI).A comprehensive understanding of cellular diversity and intercellular crosstalk is essential to elucidate the mechanisms and to develop therapeutic strategies for APAP-ALI ***,we identified the function of IFN-I in the myeloid compartment during *** single-cell RNA sequencing,we characterized the cellular atlas and dynamic progression of liver CD11b+cells post APAP-ALI in WT and STAT2 T403A mice,which was further validated by immunofluorescence staining,bulk RNA-seq,and functional experiments in vitro and in *** identified IFN-I-dependent transcriptional programs in a three-way communication pathway that involved IFN-I synthesis in intermediate restorative macrophages,leading to CSF-1 production in aging neutrophils that ultimately enabled Trem2+restorative macrophage maturation,contributing to efficient liver ***,we uncovered the heterogeneity of hepatic myeloid cells in APAP-ALI at single-cell resolution and the therapeutic potential of IFN-I in the treatment of APAP-ALI.

关键词： APAP-ALI IFN-I Macrophage polarization scRNA-seq STAT2 T403 phosphorylation CSF1+neutrophil

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Inhibition of gastric perception of mild distention by omeprazole in volunteers

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World Journal of Gastroenterology 2012年第39期18卷 5576-5580页

作者： Akihito Iida Hiroshi Kaneko Toshihiro Konagaya Yasushi Funaki Kentaro Tokudome Shinya Izawa Yasuhiro Tamura Mari Mizuno Naotaka Ogasawara Makoto Sasaki Kunio Kasugai Division of Gastroen-terology Department of Internal MedicineSchool of MedicineAichi Medical UniversityAichi 480-1195Japan Department of Internal Medicine Hoshigaoka Maternity HospitalAichi 464-0026Japan marine clinic NagoyaAichi 460-0002Japan

AIM： To evaluate the effects of omeprazole on gastric mechanosensitivity in humans. METHODS： A double lumen polyvinyl tube with a plas- tic bag was introduced into the stomach of healthy volunteers under fluorography and connected to a barostat device. Subjects were then positioned so they were sitting comfortably, and the minimal distending pressure （MDP） was determined after a 30-rain adap- tation period. Isobaric distensions were performed in stepwise increments of 2 mmHg （2 min each） starting from the MDR Subjects were instructed to score feel- ings at the end of every step using a graphic rating scale： 0, no perception; 1, weak/vague; 2, weak but significant; 3, moderate/vague; 4, moderate but signifi- cant; 5, severe discomfort; and 6, unbearable pain. Af- ter this first test, subjects received omeprazole （20 mg, after dinner） once daily for 1 wk. A second test was performed on the last day of treatment. RESULTS： No adverse effects were observed. Mean MDP before and after treatment was 6.3 - 0.3 mmHg and 6.2：1：0.5 mmHg, respectively. One subject before and 2 after treatment did not reach a score of 6 at the maximum bag volume of 750 mL. After omeprazole, there was a significant increase in the distension pres- sure required to reach scores of 1 （P = 0.019） and 2 （P = 0.017） as compared to baseline. There were no changes in pressure required to reach the other scores after treatment. Two subjects before and one after omeprazole rated their abdominal feeling 〈 1 at MDP, and mean （±SE） abdominal discomfort scores at MDP were 0.13±0.09 and 0.04±0.04, respectively. Mean scores induced by each MDP ＋ 2, 4, 6, 8, 10, 12, 14, 16, 18 and 20 （mmHg） were 1.1±0.3, 2.0±0.4, 2.9±0.5, 3.3±0.4, 4.6±0.3, 5.2±0.3, 5.5±0.2, 5.5±0.3, 5.7±0.3, and 5.4, respectively. After omepra- zole, abdominal feeling scores for the same incremen- tal pressures over MDP were 0.3±0.1, 0.8±0.1, 2.0±0.4, 2.8±0.4, 3.8±0.4, 4.6±0.4, 4.9±0.3, 5.4±0.4, 5.2±0.6, and 5.0±1.0, respectively. A signif- icant

关键词： Functional dyspepsia Acid exposure Ome-prazole Barostat test Mechanosensitivity

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Cytotoxic effects of betaxolol on healthy corneal endothelial cells both in vitro and in vivo

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International Journal of Ophthalmology(English edition) 2014年第1期7卷 14-21页

作者： Ying Miao Qian Sun Qian Wen Yue Qiu Yuan Ge Miao-Miao Yu Ting-Jun Fan Key Laboratory for Corneal Tissue Engineering College of Marine Life SciencesOcean University of China

AIM: To demonstrate the cytotoxic effect of betaxolol and its underlying mechanism on human corneal endothelial cells(HCE cells) in vitro and cat corneal endothelial cells(CCE cells) in vivo,providing experimental basis for safety anti-glaucoma drug usage in clinic of ophthalmology. ·METHODS: In vivo and in vitro experiments were conducted to explore whether and how betaxolol participates in corneal endothelial cell injury. The in vitro morphology,growth status,plasma membrane permeability,DNA fragmentation,and ultrastructure of HCE cells treated with 0.021875-0.28g/L betaxolol were examined by light microscope,3-(4,5)-dimethylthiahiazo(-z-y1)-3,5-di-phenytetrazoliumromide(MTT) assay,acridine orange(AO)/ethidium bromide(EB) double-fluorescent staining,DNA agarose gel electrophoresis,and transmission electron microscope(TEM). The in vivo density,morphology,and ultrastructure of CCE cells,corneal thickness,and eye pressure of cat eyes treated with 0.28g/L betaxolol were investigated by specular microscopy,applanation tonometer,alizarin red staining,scanning electron microscope(SEM),and TEM. · RESULTS: Exposure to betaxolol at doses from 0.0875g/L to 2.8g/L induced morphological and ultrastructural changes of in vitro cultured HCE cells such as cytoplasmic vacuolation,cellular shrinkage,structural disorganization,chromatin condensation,and apoptotic body appearance. Simultaneously,betaxolol elevated plasma membrane permeability and induced DNA fragmentation of these cells in a dose-dependent manner in AO/EB staining. Furthermore,betaxolol at adose of 2.8g/L also induced decrease of density of CCE cells in vivo,and non-hexagonal and shrunk apoptotic cells were also found in betaxolol-treated cat corneal endothelia. ·CONCLUSION: Betaxolol has significant cytotoxicity on HCE cells in vitro by inducing apoptosis of these cells,and induced apoptosis of CCE cells in vivo as well. The findings help provide new insight into the apoptosis-inducing effect of anti-glaucoma drugs

关键词： betaxolol cytotoxicity apoptosis human corneal endothelial cells cat corneal endothelial cells

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Small incision lenticule extraction (SMILE) history, fundamentals of a new refractive surgery technique and clinical outcomes

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Eye and Vision 2014年第1期1卷 9-20页

作者： Dan Z Reinstein Timothy J Archer marine Gobbe London Vision clinic 138 Harley StreetLondon W1G 7LAUK Department of Ophthalmology Columbia University Medical CenterNew YorkNYUSA Centre Hospitalier National d’Ophtalmologie ParisFrance

This review summarizes the current status of the small incision lenticule extraction(SMILE)*** the early work by Sekundo et *** Shah et al.,SMILE has become increasingly *** accuracy of the creation of the lenticule with the VisuMax femtosecond laser(Carl Zeiss Meditec)has been verified using very high-frequency(VHF)digital ultrasound and optical coherence tomography(OCT).Visual and refractive outcomes have been shown to be similar to those achieved with laser in situ keratomileusis(LASIK),notably in a large population reported by Hjortdal,Vestergaard et *** in terms of the change in corrected distance visual acuity(CDVA)has also been shown to be similar to *** was expected that there would be less postoperative dry eye after SMILE compared to LASIK because the anterior stroma is disturbed only by the small incision,meaning that the anterior corneal nerves should be less affected.A number of studies have demonstrated a lower reduction and faster recovery of corneal sensation after SMILE than *** studies have also used confocal microscopy to demonstrate a lower decrease in subbasal nerve fiber density after SMILE than *** potential biomechanical advantages of SMILE have been modeled by Reinstein et *** on the non-linearity of tensile strength through the *** have reported a similar change in Ocular Response Analyzer(Reichert)parameters after SMILE and LASIK,however,these have previously been shown to be unreliable as a representation of corneal *** options after SMILE are *** addition applications of the SMILE procedure are also discussed including the potential for cryo-preservation of the lenticule for later reimplantation(Mohamed-Noriega,Angunawela,Lim et al.),and a new procedure referred to as endokeratophakia in which a myopic SMILE lenticule is implanted into a hyperopic patient(Pradhan et al.).Finally,studies reporting microdistortions in Bowman’s layer and cor

关键词： Small incision lenticule extraction(SMILE) Laser in situ keratomileusis(LASIK) Lenticule Cap Dry eye Corneal sensation Corneal innervation Corneal biomechanics Endokeratophakia

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Integrins as attractive targets for cancer therapeutics

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Acta Pharmaceutica Sinica B 2021年第9期11卷 2726-2737页

作者： Meng Li Ying Wang Mengwei Li Xuezhen Wu Sarra Setrerrahmane Hanmei Xu National Institutes for Food and Drug Control Beijing 102629China State Key Laboratory of Natural Medicines Ministry of Educationthe Engineering Research Center of Synthetic Polypeptide Drug Discovery and Evaluation of Jiangsu ProvinceDepartment of Marine PharmacyChina Pharmaceutical University Nanjing 211198ChinaAffiliated Hospital of Chifeng CollegeInner Mongolia Autonomous Region 024005China

Integrins are transmembrane receptors that have been implicated in the biology of various human physiological and pathological *** molecules facilitate cell-extracellular matrix and cell-cell interactions,and they have been implicated in fibrosis,inflammation,thrombosis,and tumor *** role of integrins in tumor progression makes them promising targets for cancer treatment,and certain integrin antagonists,such as antibodies and synthetic peptides,have been effectively utilized in the clinic for cancer ***,we discuss the evidence and knowledge on the contribution of integrins to cancer ***,we summarize the clinical attempts targeting this family in anti-cancer therapy development.

关键词： Integrins Extracellular matrix Tumor progression Targeted drug Antagonists clinical trial

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Beneficial effects of fucoidan in patients with chronic hepatitis C virus infection

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World Journal of Gastroenterology 2012年第18期18卷 2225-2230页

作者： Naoki Mori Kazunori Nakasone Koh Tomimori Chie Ishikawa Department of Microbiology and Oncology Graduate School of MedicineUniversity of the RyukyusNishiharaOkinawa 903-0215Japan Nakasonekazu Medical clinic NahaOkinawa 902-0062Japan Department of Psychiatry Naha City HospitalNahaOkinawa 902-8511Japan Transdisciplinary Research Organization for Subtropics and Island Studies University of the RyukyusNishiharaOkinawa 903-0213Japan

AIM:To evaluate the effects of fucoidan,a complex sulfated polysaccharide extract from marine seaweed,on hepatitis C virus(HCV) RNA load both in vitro and in ***:HCV-1b replicon-expressing cells were cultured in the presence of fucoidan obtained from Cladosiphon okamuranus Tokida cultivated in Okinawa,Japan,and quantified the level of HCV *** an open-label uncontrolled study,15 patients with chronic hepatitis C,and HCV-related cirrhosis and hepatocellular carcinoma were treated with fucoidan(0.83 g/d) for 12 *** clinical symptoms,biochemical tests,and HCV RNA levels were assessed before,during,and after ***:Fucoidan dose-dependently inhibited the expression of HCV *** 8-10 mo of treatment with fucoidan,HCV RNA levels were significantly lower relative to the *** same treatment also tended to lower serum alanine aminotransferase levels,and the latter correlated with HCV RNA ***,the improved laboratory tests did not translate into significant clinical *** had no serious adverse ***:Our findings suggest that fucoidan is safe and useful in the treatment of patients with HCVrelated chronic liver *** controlled clinical trials are needed to confirm the present findings.

关键词： Fucoidan Hepatitis C virus Replicon

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Self-enhanced photothermal-chemodynamic antibacterial agents for synergistic anti-infective therapy

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Chinese Chemical Letters 2023年第2期34卷 452-457页

作者： Ning Guo Yu Xia Yuxi Duan Quanxin Wu Le Xiao Yaxin Shi Bin Yang Yun Liu Guangdong Key Laboratory for Research and Development of Natural Drugs School of PharmacyGuangdong Medical UniversityZhanjiang 524023China The Sixth Affiliated Hospital of Guangzhou Medical University Qingyuan People's HospitalDepartment of Biomedical EngineeringSchool of Basic Medical SciencesGuangzhou Medical UniversityGuangzhou 511436China The marine Biomedical Research Institute of Guangdong Zhanjiang 524023China

Cu_(2-x)S nanostructures have been intensively studied as outstanding chemodynamic therapy(CDT)and good photothermal therapy(PTT)antibacterial agents due to their highly efficient Cu(Ⅰ)-initiated Fenton-like catalytic activity and good photothermal conversion ***,they still suffer from shortage of Cu(Ⅰ)supply in the long-term and comparatively low inherent photothermal conversion ***,we constructed a self-enhanced synergistic PTT/CDT nanoplatform(Cu_(1.94)S@MPN)by coating Cu_(1.94)S nanoparticles with Fe(Ⅲ)/tannic acid based metal-polyphenol networks(MPN).Activated by the acidic bacterial infection microenvironment,Cu_(1.94)S@MPN could be decomposed to continuously release Cu(Ⅱ),Fe(Ⅲ)ions and tannic *** the result of tannic acid-involved Cu and Fe redox cycling,Cu(Ⅰ)/Fe(Ⅱ)-rich CDT could be achieved through the highly accelerated catalytic Fenton/Fenton-like *** importantly,experimental results demonstrated that Cu_(1.94)S@MPN exhibited both excellent photothermal antibacterial and photothermal-enhanced CDT properties to eradicate bacteria in vitro and in ***,this novel nanotherapeutics has great potential to become a clinic candidate for anti-infective therapy in future.

关键词： Antibacterial Self-enhanced Photothermal therapy Chemodynamic therapy Anti-infective therapy

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