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Verteporfin synergizes the efflcacy of anti-PD-1 in cholangiocarcinoma

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Hepatobiliary & Pancreatic Diseases International 2022年第5期21卷 485-492页

作者： Jianyang Fu Nicole A McGrath Jihye Lee Xin Wang Gagandeep Brar Changqing Xie Thoracic and Gastrointestinal Malignancies Branch Center for Cancer ResearchNational Cancer InstituteNational Institutes of HealthBethesdaMD 20892USA Sandra and Edward Meyer Cancer Center Weill Cornell MedicineNew YorkNY 10065USA

Background:Cholangiocarcinoma(CCA)is one of the primary hepatobiliary malignant neoplasms with only 10%of 5-year survival *** immunotherapy with the blockade of immune checkpoints has no clear benefit in *** inhibition of YAP1 signaling by verteporfin has shown encouraging results by inhibiting cell proliferation and inducing *** study aimed to evaluate the potential benefit of the combination of verteporfin and anti-programmed cell death 1(PD-1)in CCA mouse ***:We assessed the cytotoxicity of verteporfin in human CCA cell lines in vitro,including both intrahepatic CCA and extrahepatic CCA *** examined the in vitro effect of verteporfin on cell proliferation,apoptosis,and *** evaluated the in vivo efflcacy of verteporfin,anti-PD-1,and a combination of both in subcutaneous CCA mouse ***:Our study showed that verteporfin reduced tumor cell growth and enhanced apoptosis of human CCA tumor cells in vitro in a dose-dependent ***,verteporfin impaired stemness evidenced by reduced spheroid formation and colony formation,decreased numbers of cells with aldehyde dehydrogenase activity and positive cancer stem cell markers(all P<0.05).The combination of verteporfin and anti-PD-1 reduced tumor burden in CCA subcutaneous SB1 tumor model compared to either agent ***:Verteporfin exhibits antitumor effects in both intrahepatic and extrahepatic CCA cell lines and the combination with anti-PD-1 inhibited tumor growth.

关键词： Verteporfin YAP1 Anti-programmed cell death-1 Immunotherapy Cholangiocarcinoma

COVID-19 among African Americans and Hispanics:Does gastrointestinal symptoms impact the outcome?

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World Journal of Clinical Cases 2021年第28期9卷 8374-8387页

作者： Hassan Ashktorab Adeleye Folake Antonio Pizuorno Gholamreza Oskrochi Philip Oppong-Twene NuriTamanna Maryam Mehdipour Dalivand Lisa N Umeh Esther S Moon Abdoul Madjid Kone Abigail Banson Cassandra Federman Edward Ramos Eyitope Ola Awoyemi Boubini Jones Wonni Eric Otto Guttu Maskalo Alexandra Ogando Velez Sheldon Rankine Camelita Thrift Chiamaka Ekwunazu Derek Scholes LakshmiGayathri Chirumamilla Mohd Elmugtaba Ibrahim Brianna Mitchell Jillian Ross Julencia Curtis Rachel Kim Chandler Gilliard Joseph Mathew Adeyinka Laiyemo Angesum Kibreab Edward Lee Zaki Sherif Babak Shokrani Farshad Aduli Hassan Brim Department of Medicine Gastroenterology Division and Cancer CenterHoward University College of MedicineWashingtonDC 20060United States Faculty of Medicine La Universidad del ZuliaMaracaibo 4002ZuliaVenezuela College of Engineering and Technology American University of Middle East KuwaitEgaila 54200Kuwait Department of Biochemistry and Molecular Biology Howard University College of MedicineWashingtonDC 20060United States Pathology and Cancer Center Department of Biochemistry and Molecular BiologyHoward University College of MedicineWashingtonDC 20060United States

BACKGROUND The coronavirus disease 2019(COVID-19)disproportionately affected African Americans(AA)and Hispanics(HSP).AIM To analyze the significant effectors of outcome in African American patient population and make special emphasis on gastrointestinal(GI)symptoms,laboratory values and comorbidities METHODS We retrospectively evaluated the medical records of 386 COVID-19 positive patients admitted at Howard University Hospital between March and May *** assessed the symptoms,including the GI manifestations,comorbidities,and mortality,using logistic regression *** Of these 386 COVID-19 positive patients,257(63.7%)were AAs,102(25.3%)HSP,and 26(6.45%)*** were 257(63.7%)AA,102(25.3%)HSP,26(6.45%)*** mean age was 55.6 years(SD=18.5).However,the mean age of HSP was the lowest(43.7 years vs 61.2 for Whites vs 60 for AAs).The mortality rate was highest among the AAs(20.6%)and lowest among HSP(6.9%).Patients with shortness of breath(SOB)(OR2=3.64,CI=1.73-7.65)and elevated AST(OR2=8.01,CI=3.79-16.9)elevated Procalcitonin(OR2=8.27,CI=3.95-17.3),AST(OR2=8.01,CI=3.79-16.9),ferritin(OR2=2.69,CI=1.24-5.82),and Lymphopenia(OR2=2.77,CI=1.41-5.45)had a high mortality *** and fever were common but unrelated to the *** and diabetes mellitus were the most common *** treatment was associated with higher mortality(OR2=5.40,CI=2.72-10.7).Diarrhea was prevalent(18.8%),and GI symptoms did not affect the *** African Americans in our study had the highest mortality as they consisted of an older population and *** is the most important factor along with SOB in determining the mortality ***,elevated liver enzymes,ferritin,procalcitonin and C-reactive protein were associated with poor *** symptoms did not affect the *** should be used judiciously,considering the poor outcomes associated with *** should also be paid to monitor liver function

关键词： COVID-19 Pandemic,Gastrointestinal manifestation Liver African Americans Hispanics

Enhancing Public health Competencies via Action on Salt China—China,2017–2022

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China CDC weekly 2023年第32期5卷 720-723页

作者： Puhong Zhang ASC working group The George Institute for Global HealthChinaBeijingChina.

The Action on Salt China(ASC)project is a noteworthy collaborative venture between China and UK,with the China CDC serving as a key *** objective of this report is to present a case study that demonstrates the significant role of ASC in bolstering the capacity of public health services in ***,this study aims to offer valuable references and provoke thoughtful insight for potential international collaborations in the future.

关键词： venture Action partner

Single-Atomic Site Catalyst Enhanced Lateral Flow Immunoassay for Point-of-Care Detection of Herbicide

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Research 2023年第1期2022卷 63-74页

作者： Zhaoyuan Lyu Shichao Ding Peter Tieu Lingzhe Fang Xin Li Tao Li Xiaoqing Pan Mark H.Engelhard Xiaofan Ruan Dan Du Suiqiong Li Yuehe Lin School of Mechanical and Material Engineering Washington State UniversityPullmanWA 99164USA Department of Chemistry University of CalforniaIrvineIrvineCA 92697USA Department of Chemistry and Biochemistry Northern Ilinois UniversityDeKalbIL 60115USA X-ray Science Division Argonne National LaboratoryLemontIL 60439USA Irvine Materials Research institute(IMRI) Department of Materials Science and EngineeringUniversity of CaliforniaIrvineIrvineCA92697USA Environmental Molecular Sciences Laboratory Pacific Northwest National LaboratoryRichlandWA 99354USA DL ADV-Tech PullmanWA 99163USA

Point-of-care(POC)detection of herbicides is of great importance due to their impact on the environment and potential risks to human ***,we design a single-atomic site catalyst(SASC)with excellent peroxidase-like(POD-like)catalytic activity,which enhances the detection performance of corresponding lateral flow immunoassay(LFIA).The iron single-atomic site catalyst(Fe-SASC)is synthesized from hemin-doped ZIF-8,creating active sites that mimic the Fe active center coordination environment of natural enzyme and their *** to its atomically dispersed iron active sites that result in maximum utilization of active metal atoms,the Fe-SASC exhibits superior POD-like activity,which has great potential to replace its natural ***,the catalytic mechanism of Fe-SASC is systematically *** its outstanding catalytic activity,the Fe-SASC is used as label to construct LFIA(Fe-SASC-LFIA)for herbicide *** 2,4-dichlorophenoxyacetic acid(2,4-D)is selected as a target here,since it is a commonly used herbicide as well as a biomarker for herbicide exposure evaluation.A linear detection range of 1-250 ng/mL with a low limit of detection(LOD)of 0.82 ng/mL has been ***,excellent specificity and selectivity towards 2,4-D have been *** outstanding detection performance of the Fe-SASC-LFIA has also been demonstrated in the detection of human urine samples,indicating the practicability of this POC detection platform for analyzing the 2,4-D exposure level of a *** believe this proposed Fe-SASC-LFIA has potential as a portable,rapid,and high-sensitive POC detection strategy for pesticide exposure evaluation.

关键词： catalyst replace dispersed

Comparison of L-band and X-band differential interferometric synthetic aperture radar for mine subsidence monitoring in central Utah

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International Journal of Mining Science and Technology 2017年第1期27卷 159-163页

作者： Jessica M.Wempen Michael K.McCarter Department of Mining Engineering University of UtahSalt Lake City 84112USA

Differential interferometric synthetic aperture radar(DIn SAR), a satellite-based remote sensing technique, has potential application for measuring mine subsidence on a regional scale with high spatial and temporal resolutions. However, the characteristics of synthetic aperture radar(SAR) data and the effectiveness of DIn SAR for subsidence monitoring depend on the radar band(wavelength). This study evaluates the effectiveness of DIn SAR for monitoring subsidence due to longwall mining in central Utah using L-band(24 cm wavelength) SAR data from the advanced land observing satellite(ALOS)and X-band(3 cm wavelength) SAR data from the Terra SAR-X mission. In the Wasatch Plateau region of central Utah, which is characterized by steep terrain and variable ground cover conditions, areas affected by longwall mine subsidence are identifiable using both L-band and X-band DIn ***, using L-band data, subsidence magnitudes are measurable. Compared to X-band, L-band data are less affected by signal saturation due to large deformation gradients and by temporal decorrelation due to changes in the surface conditions over time. The L-band data tend to be stable over relatively long periods(months). Short wavelength X-band data are strongly affected by signal saturation and temporal decorrelation, but regions of subsidence are typically identifiable over short periods(days). Additionally,though subsidence magnitudes are difficult to precisely measure in the central Utah region using X-band data, they can often be reasonably estimated.

关键词： Mine subsidence DInSAR Terra SAR-X ALOS Interferometry

Prostate-associated gene 4 （PAGE4）, an intrinsically disordered cancer/testis antigen, is a novel therapeutic target for prostate cancer

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Asian Journal of Andrology 2016年第5期18卷 695-703页

作者： Prakash Kulkarni A Keith Dunker Keith Weninge John Orban institute for Bioscience and Biotechnology Research University of Maryland Rockville MD 20850 USA Center for Computational Biology and Bioinformatics Department of Biochemistry and Molecular Biology Indiana University School of Medicine and Informatics Indianapolis IN 46202 USA Department of Physics North Carolina State University Raleigh NC 27695 USA Department of Chemistry and Biochemistry University of Maryland College Park MD 20742 USA.

Prostate-associated gene 4 （PAGE4） is a remarkably prostate-specific Cancer/Testis Antigen that is highly upregulated in the human fetal prostate and its diseased states but not in the adult normal gland. PAGE4 is an intrinsically disordered protein （IDP） that functions as a stress-response protein to suppress reactive oxygen species as well as prevent DNA damage. In addition, PAGE4 is also a transcriptional regulator that potentiates transactivation by the oncogene c-Jun, c-Jun forms the AP-1 complex by heterodimerizing with members of the Fos family and plays an important role in the development and pathology of the prostate gland, underscoring the importance of the PAGE4/c-Jun interaction. HIPK1, also a component of the stress-response pathway, phosphorylates PAGE4 at T51 which is critical for its transcriptional activity. Phosphorylation induces conformational and dynamic switching in the PAGE4 ensemble leading to a new cellular function. Finally, bioinformatics evidence suggests that the PAGE4 mRNA could be alternatively spliced resulting in four potential isoforms of the polypeptide alluding to the possibility of a range of conformational ensembles with latent functions. Considered together, the data suggest that PAGE4 may represent the first molecular link between stress and prostate cancer （PCa）. Thus, pharmacologically targeting PAGE4 may be a novel opportunity for treating and managing patients with PCa, especially patients with low-risk disease.

关键词： prostate-associated Gene 4 cancer/testis antigen intrinsically disordered protein prostate cancer c-Jun AP-1 proteininteraction networks homeodomain-interacting protein 1

Syntheses of Two Potential Ligands for Tc-99m Labeling as Diagnosis Agents of Alzheimer's Disease

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Chinese Journal of Chemistry 2003年第7期21卷 824-832页

作者：庄治平孔一田美萍小野正博侯元淳孔繁渊 Department of Radiology Universisy of Pennsylvania Room 305 3700 Market StreetPhiladelphia Pennsylvania19104 USA Department of Pharmacology University of Pennsylvania Room 305 3700 Market Street PhiladelphiaPennsylvania19104 USA

Two types of ligands-biphenyl and stilbene derivatives, -which can be labeled with Tc-99m for the diagnosis of Alzheimer' s disease (AD) have been synthesized successfully. The key steps in these two syntheses involved Suzuki reaction and Wittig reaction respectively. The new discovered debromination reaction may be expanded to the compounds with double or triple bond adjacent to the carbon atom bearing the bromine atoms. These types of syntheses provide a route to a series of biphenyl and stilbene derivatives that will benefit the search of new imaging agents for AD.

关键词： Alzheimer' s disease imaging agent diagnosis,biphenyl stilbene Suzuki reaction Wittig reaction

Herbal drug discovery for the treatment of nonalcoholic fatty liver disease

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Acta Pharmaceutica Sinica B 2020年第1期10卷 3-18页

作者： Tingting Yan Nana Yan Ping Wang Yangliu Xia Haiping Hao Guangji Wang Frank JGonzalez Laboratory of Metabolism Center for Cancer ResearchNational Cancer InstituteNational Institutes of HealthBethesdaMD 20892USA State Key Laboratory of Natural Medicines Key Laboratory of Drug Metabolism and PharmacokineticsChina Pharmaceutical UniversityNanjing 210009China institute of Interdisciplinary Integrative Medicine Research Shanghai University of Traditional Chinese MedicineShanghai 201203China School of Life Science and Medicine Dalian University of TechnologyPanjin 124221China

Few medications are available for meeting the increasing disease burden of nonalcoholic fatty liver disease(NAFLD)and its progressive stage,nonalcoholic steatohepatitis(NASH).Traditional herbal medicines(THM)have been used for centuries to treat indigenous people with various symptoms but without clarified modern-defined disease types and *** modern times,NAFLD was defined as a common chronic disease leading to more studies to understand NAFLD/NASH pathology and *** have garnered increased attention for providing therapeutic candidates for treating *** this review,a new model called"multiple organs-multiple hits"is proposed to explain mechanisms of NASH *** this proposed model,the effects and mechanisms of the frequentlystudied THM-yielded single anti-NAFLD drug candidates and multiple herb medicines are reviewed,among which silymarin and berberine are already under ***-sanctioned phase 4 clinical ***,experimental designs for anti-NAFLD drug discovery from THM in treating NAFLD are *** opportunities and challenges of reverse pharmacology and reverse pharmacokinetic concepts-guided strategies for THM modernization and its global recognition to treat NAFLD are *** mechanistic evidence is being generated to support the beneficial role of THM in treating NAFLD and anti-NAFLD drug discovery.

关键词： Natural products Fatty liver Metabolic syndrome TCM NAFLD

Application of DInSAR for short period monitoring of initial subsidence due to longwall mining in the mountain west United States

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International Journal of Mining Science and Technology 2020年第1期30卷 33-37页

作者： Jessica M.Wempen Department of Mining Engineering University of UtahSalt Lake City 84112USA

Differential Interferometric Synthetic Aperture Radar(DInSAR),a satellite-based remote sensing technique,has application for monitoring subsidence with high resolution over short *** uses radar images to measure centimeter-level surface *** the images,ground resolution can be relatively high,with each data point(pixel)representing the average displacement over an area of several square *** image data are acquired regularly which allows subsidence to be monitored sequentially over short periods;imaging periods typically range from weeks to *** subsidence over short periods with high spatial resolution has potential to provide insight into the dynamics of subsidence and into relationships between mine advance and *** this study,for three longwall mines in the western United States,initial subsidence occurring at the start of longwall advance is quantified over short periods(12–72 days).C-band interferometric wide swath Synthetic Aperture Radar(SAR)images from the Sentinel satellites are used to quantify the ***,the data show initial development of subsidence,expansion of the subsidence trough,and the advance of subsidence in the direction of mining.

关键词： Longwall mining Interferometry Subsidence