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Enhanced structural stability of adenovirus nanocapsule

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Progress in Natural Science:Materials International 2014年第2期24卷 171-174页

作者： Ding Weng Ziyue Karen Jiang Jing Jin Lily Wu Yunfeng Lu Chemical and Biomolecular Engineering University of California at Los Angeles Tissue Engineering Laboratories VA Boston Healthcare System Department of Orthopaedic Surgery Brigham and Women's Hospital Harvard Medical School Molecular and Medical Pharmacology University of California at Los Angeles Getein Biotechnology Co. Ltd.

Application of viral vector in gene therapy and vaccination is still limited by their structural stability, which significantly increased avoidable cost in storage and transportation. Herein a non-covalent conjugated low-pH degradable nanocapsule has been adopted to stabilize viral vectors. By utilizing a luciferase expressing adenovirus, AdCMVLuc, we succeeded in a raise of over 11 folds in AdCMVLuc’s structural stability after 12 days storage at 4 1℃.

关键词： Non-covalent nanocapsule Adenovirus Structural stability

Metabolic syndrome does not affect sustained virologic response of direct-acting antivirals while hepatitis C clearance improves hemoglobin A1c

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World Journal of Hepatology 2018年第9期10卷 612-621页

作者： Tien S Dong Elizabeth S Aby Jihane N Benhammou Jenna Kawamoto Steven-Huy Han Folasade P May Joseph R Pisegna the vatche and Tamar Manoukian Division of Digestive Diseases University of California Los AngelesDepartment of MedicineUniversity of California David Geffen School of MedicineLos AngelesCA 90095United States Division of Gastroenterology Hepatology and Parenteral NutritionDepartment of MedicineVA Greater Los Angeles Healthcare SystemLos AngelesCA 90073United States the Pfleger Liver Institute Department of SurgeryUniversity of California David Geffen School of MedicineLos AngelesCA 90095United States va Health Services Research and Development Center for the Study of healthcare Innovation Center for the Study of healthcare Innovation Implementation and Policy(CSHIIP)Los AngelesCA 90073United States Jonsson Comprehensive Cancer Center Los AngelesCA 90095United States

AIM To determine whether successful treatment with direc-tacting antivirals(DAA) is associated with improvements in hemoglobin A1 c(HbA1 c) and if type 2 diabetes mellitus(T2 DM) or metabolic syndrome affects sustained virologic response(SVR).METHODS We performed a retrospective analysis of all hepatitis C virus(HCV) patients at the va greater los angeles healthcare system treated with varying DAA therapy between 2014-2016. Separate multivariable logistic regression was performed to determine predictors of HbA1 c decrease ≥ 0.5 after DAA treatment and predictors of SVR 12-wk post treatment(SVR12).RESULTS A total of 1068 patients were treated with DAA therapy between 2014-2016. The presence of T2 DM or metabolic syndrome did not adversely affect SVR12. 106 patients had both HCV and T2 DM. Within that cohort,patients who achieved SVR12 had lower mean HbA1 c pre treatment(7.35 vs 8.60,P = 0.02),and lower mean HbA1 c post-treatment compared to non-responders(6.55 vs 8.61,P = 0.01). The mean reduction in HbA1 c after treatment was greater for those who achieved SVR12 than for non-responders(0.79 vs 0.01,P = 0.03). In adjusted models,patients that achieved SVR12 were more likely to have a HbA1 c decrease of ≥ 0.5 than those that did not achieve SVR12(adjusted OR = 7.24,95%CI: 1.22-42.94). CONCLUSION In HCV patients with T2 DM,successful treatment with DAA was associated with a significant reduction in HbA1 c suggesting that DAA may have a role in improving insulin sensitivity. Furthermore,the presence of T2 DM or metabolic syndrome does not adversely affect SVR12 rates in patients treated with DAA.

关键词： Hepatitis C virus Hemoglobin A1c Diabetes mellitus Direct-acting antivirals Metabolic syndrome

Pomegranate extract inhibits EMT in clear cell renal cell carcinoma in a NF-κB and JNK dependent manner

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Asian Journal of Urology 2015年第1期2卷 38-45页

作者： Jiabin An Yanchuan Guo Ting Wang Allan J.Pantuck Matthew B.Rettig Department of Medicine Division of Hematology-OncologyVA Greater Los Angeles Healthcare SystemLos AngelesCA90073USA Technical Institute of Physics and Chemistry Chinese Academy of ScienceBeijing100190China Department of Urology David Geffen School of Medicine at UCLALos AngelesCA90095USA Department of Medicine Division of Hematology-OncologyDavid Geffen School of Medicine at UCLALos AngelesCA90095USA

Objective:Clear cell renal cell carcinoma(ccRCC)is the most common subtype of renal cell carcinoma(RCC)and is characterized by biallelic inactivation of the von Hippel-Lindau(VHL)tumor suppressor *** effect of VHL inactivation is hypoxia inducible factor alpha(HIFa)-independent constitutive activation of nuclear factor kappa B(NF-κB)and c-jun N-terminal kinase(JNK).Both NF-κB and JNK drive ccRCC growth and epithelial to mesenchymal transition(EMT).The purpose of this study was to determine the biochemical effects of pomegranate juice extracts(PE)on RCC cell ***:The pre-clinical effects of PE on NF-κB,JNK,and the EMT phenotype were assayed,including its effect on proliferation,anchorage-independent growth,and invasion of pVHLdeficient ***:PE inhibits the NF-κB and JNK pathways and consequently inhibits the EMT phenotype of pVHL-deficient *** effects of PE are concentration-dependent and affect not only biochemical markers of EMT(i.e.,cadherin expression)but also functional manifestations of EMT,such as *** effects are manifested within days of exposure to PE when diluted *** dilute concentrations of PE(106 dilution),which do not impact these pathways in the short term,were found to have NF-κB and JNK inhibitory effects and ability to reverse the EMT phenotype following prolonged ***:These findings suggest that PE may mediate inhibition growth of pVHL-deficient ccRCCs and raises the possibility of its use as a dietary adjunct to managing patients with active surveillance for small,localized,incidentally identified renal tumors so as to avoid more invasive procedures such as nephrectomy.

关键词： Pomegranate extract von Hippel-Lindau(VHL)tumor suppressor Clear cell renal cell carcinoma c-Jun N-terminal kinase Epithelial to mesenchymal transition Nuclear factor kappa B

Analytical Image Fusion in the Detection of Intrahepatic Hepatocellular Cancer

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Open Journal of Medical Imaging 2017年第2期7卷 56-61页

作者： Hongyun Zhu Michael L. Goris Department of Veterans Affairs Greater Los Angeles Healthcare System Los Angeles CA USA 1455 Ormsby Drive Sunnyvale CA USA

Purpose: Since HCC lesions are generally characterized by lower Hounsfield unit value (HU) values and higher tracer uptake (SUV or Standardized Uptake values), we intended to determine if normalizing the SUV by the HU, for the lesion and normal liver would improve sensitivity and specificity. Material and Methods: Twenty-three consecutive patients with HCC diagnosed clinically or pathologically underwent C11-Acetate (C11-A) and F18-FDG (FDG) PET/CT imaging before surgery during a 424-day interval. After exclusion of treated or calcified lesions, 44 lesions are included in this study. The original metrics are the maximum SUV (SUVmax) and maximum or average HU (HUmax or HUmean) for lesions and normal liver. For the normal liver, an average SUV (SUVmean) was included. The derived values are the ratios of SUV/HU values. The efficacy is the fraction of outcomes of non-overlapping metrics between lesion and normal liver. Results: For FDG the efficacy is 0.489 for the lesions SUVmax versus normal liver SUVmax. For lesion SUVmax/HUmean versus normal liver SUVmax/HUmax, the efficacy is 1.00. For C11-A the corresponding values are 0.045 and 0.920. Conclusion: Normalizing SUV values for changes in HU values increases the contrast between normal liver and lesions. Analytical fusion can be very effective.

关键词： HCC (Hepatocellular Cancer)

Signaling pathways in osteogenesis and osteoclastogenesis:Lessons from cranial sutures and applications to regenerative medicine

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Genes & Diseases 2015年第1期2卷 57-68页

作者： Justin B.Maxhimer James P.Bradley Justine C.Lee Division of Plastic and Reconstructive Surgery UCLA David Geffen School of MedicineCAUSA Division of Plastic and Reconstructive Surgery Temple University/St.Christopher’s Hospital for ChildrenPAUSA Division of Plastic and Reconstructive Surgery Greater Los Angeles VA Healthcare SystemUSA

One of the simplest models for examining the interplay between bone formation and resorption is the junction between the cranial *** only roughly a quarter of patients diagnosed with craniosynostosis have been linked to known genetic disturbances,the molecular mechanisms elucidated from these studies have provided basic knowledge of bone *** work has translated to methods and advances in bone tissue *** this review,we examine the current knowledge of cranial suture biology derived from human craniosynostosis syndromes and discuss its application to regenerative medicine.

关键词： Craniosynostosis OPG Osteoclast RANK RANKL Tissue engineering Osteogenesis Signaling

Induction of CXC chemokines in human mesenchymal stem cells by stimulation with secreted frizzled-related proteins through non-canonical Wnt signaling

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World Journal of Stem Cells 2015年第11期7卷 1262-1273页

作者： David S Bischoff Jian-Hua Zhu Nalini S Makhijani Dean T Yamaguchi Research Service VA Greater Los Angeles Healthcare System Department of Medicine David Geffen School of Medicine at UCLA

AIM: To investigate the effect of secreted frizzledrelated proteins(s FRPs) on CXC chemokine expression in human mesenchymal stem cells(h MSCs).METHODS: CXC chemokines such as CXCL5 and CXCL8 are induced in h MSCs during differentiation with osteogenic differentiation medium(OGM) and may be involved in angiogenic stimulation during bone repair. h MSCs were treated with conditioned medium(CM) from L-cells expressing non-canonical Wnt5 a protein, or with control CM from wild type L-cells, or directly with s FRPs for up to 10 d in culture. m RNA expression levels of both CXCL5 and CXCL8 were quantitated by real-time reverse transcriptase-polymerase chain reaction and secreted protein levels of these proteins determined by ELISA. Dose-(0-500 ng/m L) and time-response curves were generated for treatment with s FRP1. Signal transduction pathways were explored by western blot analysis with pan- or phosphorylation-specific antibodies, through use of specific pathway inhibitors, and through use of si RNAs targeting specific frizzled receptors(Fzd)-2 and 5 or thereceptor tyrosine kinase-like orphan receptor-2(Ro R2) prior to treatment with s FRPs. RESULTS: CM from L-cells expressing Wnt5 a, a noncanonical Wnt, stimulated an increase in CXCL5 m RNA expression and protein secretion in comparison to control L-cell CM. s FRP1, which should inhibit both canonical and non-canonical Wnt signaling, surprisingly enhanced the expression of CXCL5 at 7 and 10 d. Dickkopf1, an inhibitor of canonical Wnt signaling prevented the s FRPstimulated induction of CXCL5 and actually inhibited basal levels of CXCL5 expression at 7 but not at 10 d post treatment. In addition, all four s FRPs isoforms induced CXCL8 expression in a dose- and time-dependent manner with maximum expression at 7 d with treatment at 150 ng/m L. The largest increases in CXCL5 expression were seen from stimulation with s FRP1 or s FRP2. Analysis of mitogen-activated protein kinase signaling pathways in the presence of OGM sh

关键词： CXC chemokines Mesenchymal stem cell Osteogenesis Differentiation Wnt signaling pathway Frizzled-related protein Frizzled receptors

Nucleoside reverse transcriptase inhibitors and Kamuvudines inhibit amyloid-βinduced retinal pigmented epithelium degeneration

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Signal Transduction and Targeted Therapy 2021年第5期6卷 1526-1534页

作者： Siddharth Narendran Felipe Pereira Praveen Yerramothu Ivana Apicella Shao-bin Wang Kameshwari Ambati Shuichiro Hirahara Younghee Kim Meenakshi Ambati Vidya L.Ambati Peirong Huang Akhil varshney Yosuke Nagasaka Shinichi Fukuda Kirstie L.Baker Kenneth M.Marion Jan M.Deussing Srinivas R.Sadda Bradley D.Gelfand Jayakrishna Ambati Center for Advanced Vision Science University of Virginia School of MedicineCharlottesvilleVAUSA Department of Ophthalmology University of Virginia School of MedicineCharlottesvilleVAUSA Aravind Eye Care system MaduraiIndia Departamento de Oftalmologia e Ciências Visuais Escola Paulista de MedicinaUniversidade Federal de São PauloSão PauloBrazil Center for Digital Image Evaluation CharlottesvilleVAUSA Doheny Eye Institute Los AngelesLos AngelesCAUSA Molecular Neurogenetics Department of Stress Neurobiology and NeurogeneticsMax Planck Institute of PsychiatryMunichGermany Department of Ophthalmology David Geffen School of MedicineUniversity of California–Los AngelesLos AngelesCAUSA Department of Biomedical Engineering University of Virginia School of MedicineCharlottesvilleVAUSA Department of Pathology University of Virginia School of MedicineCharlottesvilleVAUSA Department of Microbiology Immunologyand Cancer BiologyUniversity of Virginia School of MedicineCharlottesvilleVAUSA

Nonfibrillar amyloid-βoligomers(AβOs)are a major component of drusen,the sub-retinal pigmented epithelium(RPE)extracellular deposits characteristic of age-related macular degeneration(AMD),a common cause of global *** report that AβOs induce RPE degeneration,a clinical hallmark of geographic atrophy(GA),a vision-threatening late stage of AMD that is currently *** demonstrate that AβOs induce activation of the NLRP3 inflammasome in the mouse RPE in vivo and that RPE expression of the purinergic ATP receptor P2RX7,an upstream mediator of NLRP3 inflammasome activation,is required for AβO-induced RPE *** classes of small molecule inflammasome inhibitors—nucleoside reverse transcriptase inhibitors(NRTIs)and their antiretrovirally inert modified analog Kamuvudines—both inhibit AβOs-induced RPE *** findings crystallize the importance of P2RX7 and NLRP3 in a disease-relevant model of AMD and identify inflammasome inhibitors as potential treatments for GA.

关键词： degeneration activation upstream

Corticotropin-releasing factor receptor subtype 2 in human colonic mucosa: Down-regulation in ulcerative colitis

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World Journal of Gastroenterology 2013年第9期19卷 1416-1423页

作者： Ekaterini Chatzaki Peter A Anton Mulugeta Million Maria Lambropoulou Theodoros Constantinidis George Kolios Yvette Taché Dimitri E Grigoriadis Neurocrine Biosciences Inc. San Diego CA 92121 United States Laboratory of Pharmacology Faculty of Medicine Democritus University of Thrace 68100 Alexandroupolis Greece Center for HIV Prevention Research Division of Digestive Diseases University of California at Los Angeles and VA Greater Los Angeles Healthcare System Los Angeles CA 90073 United States Digestive Diseases Research Center and Center for Neurobiology of Stress Division of Digestive Diseases University of California at Los Angeles and VA Greater Los Angeles Healthcare System Los Angeles CA 90073 United States Laboratory of Histology-Embryology Faculty of Medicine Democritus University of Thrace 68100 Alexandroupolis Greece Laboratory of Hygiene and Environmental Protection Faculty of Medicine Democritus University of Thrace 68100 Alexandroupolis Greece

AIM: To assess corticotropin-releasing factor receptor 2 (CRF 2 ) expression in the colon of healthy subjects and patients with ulcerative colitis (UC). METHODS: We examined CRF2 gene and protein expression in the distal/sigmoid colonic mucosal biopsies from healthy subjects and patients with UC (active or disease in remission), human immunodeficiency virus (HIV) and functional bowel disease (FBD) by reverse transcriptionpolymerase chain reaction and immunofluorescence. RESULTS: Gene expression of CRF2 was demonstrated in the normal human colonic biopsies, but not in the human colorectal adenocarcinoma cell line Caco2. Receptor protein localization showed immunoreactive CRF 2 receptors in the lamina propria and in the epithelial cells of the distal/sigmoid biopsy samples. Interestingly, CRF 2 immunoreactivity was no longer observed in epithelial cells of patients with mild-moderately active UC and disease in remission, while receptor protein expression did not change in the lamina propria. No differences in CRF 2 expression profile were observed in distal/sigmoid intestinal biopsies from HIV infection and FBD patients, showing no signs of inflammation. CONCLUSION: The down-regulation of the CRF2 receptor in the distal/sigmoid biopsies of UC patients is indicative of change in CRF 2 signalling associated with the process of inflammation.

关键词： Colonic mucosa Corticotropin-releasing factor Corticotropin-releasing factor receptor Human immunodeficiency virus Ulcerative colitis Urocortin

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PET/CT在前列腺癌放疗规划中的应用

中华核医学与分子影像杂志 2020年第9期40卷 567-576页

作者：李冠男(译) 李林(审校) Jeremie Calais Minsong Cao Nicholas G.Nickols 四川大学华西医院核医学科成都610041 Ahmanson Translational Imaging Division Department of Molecular and Medical PharmacologyUCLALos AngelesCalifornia Department of Radiation Oncology UCLALos AngelesCalifornia Department of Radiation Oncology VA Greater Los Angeles Healthcare SystemLos AngelesCalifornia

放疗及根治性前列腺切除术是局限性前列腺癌的最终治疗选择。根治性前列腺切除术后前列腺特异抗原水平升高提示前列腺癌复发,此类患者仍可通过挽救性放疗治愈。为了使治愈机会最大化,放疗靶区应包括疾病的所有范围。因此,无论是根治性... 详细信息

放疗及根治性前列腺切除术是局限性前列腺癌的最终治疗选择。根治性前列腺切除术后前列腺特异抗原水平升高提示前列腺癌复发,此类患者仍可通过挽救性放疗治愈。为了使治愈机会最大化,放疗靶区应包括疾病的所有范围。因此,无论是根治性还是挽救性放疗,准确估计疾病位置对放疗规划至关重要。目前一线显像方法对前列腺癌的早期分期和生化复发的检测灵敏度均有限。将PET纳入前列腺癌患者的常规评估可以提高分期的准确性和放疗计划的规范性。目前,18F-脱氧葡萄糖(FDG)PET/CT已被常规用于多种癌症的放疗规划,但其对前列腺癌的灵敏度较低。其他评估前列腺癌的PET探针包括18F-NaF、11C-乙酸盐、11C或18F标记的胆碱、抗1-氨基酸-3-18F-氟环丁烷-1羧酸(18F-fluciclovine)和68Ga或18F标记的配体,均可与前列腺特异膜抗原(PSMA)结合。PSMA似乎是最灵敏和特异的配体,但其尚未获得美国食品与药品监督管理局(FDA)的新药申请批准。回顾性和前瞻性研究显示,PET/CT对前列腺放疗计划可能有潜在的重要价值。将患者随机分配到常规放疗计划与PET/CT辅助放疗计划的前瞻性试验或许可以得出很有意义的临床结果。目前正在进行前瞻性临床试验,评估利用18F-fluciclovine PET/CT对具有临床终点的挽救性放疗进行规划;建议进行前瞻性试验,评估PSMA PET/CT对前列腺放疗计划的临床影响。

关键词：前列腺肿瘤前列腺特异膜抗原 PET/CT 辐射