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Dynamic glial response and crosstalk in demyelination-remyelination and neurodegeneration processes

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Neural Regeneration Research 2021年第7期16卷 1359-1368页

作者： Tianci Chu Lisa B.E.Shields Wenxin Zeng Yi Ping Zhang Yuanyi Wang Gregory N.barnes Christopher b.shields Jun Cai Pediatric Research Institute Department of PediatricsUniversity of Louisville School of MedicineLouisvilleKYUSA Norton Neuroscience Institute Norton HealthcareLouisvilleKYUSA Department of Spine Surgery The First Hospital of Jilin UniversityChangchunJilin ProvinceChina Department of Neurology University of Louisville School of MedicineLouisvilleKYUSA Department of Pharmacology and Toxicology University of LouisvilleLouisvilleKYUSA Department of Neurological Surgery University of Louisville School of MedicineLouisvilleKYUSA

Multiple sclerosis is an autoimmune disease in which the immune system attacks the myelin sheath in the central nervous system.It is characterized by blood-brain barrier dysfunction throughout the course of multiple sclerosis, followed by the entry of immune cells and activation of local microglia and astrocytes.Glial cells(microglia, astrocytes, and oligodendrocyte lineage cells) are known as the important mediators of neuroinflammation, all of which play major roles in the pathogenesis of multiple sclerosis.Network communications between glial cells affect the activities of oligodendrocyte lineage cells and influence the demyelination-remyelination process.A finely balanced glial response may create a favorable lesion environment for efficient remyelination and neuroregeneration.This review focuses on glial response and neurodegeneration based on the findings from multiple sclerosis and major rodent demyelination models.In particular, glial interaction and molecular crosstalk are discussed to provide insights into the potential cell-and molecule-specific therapeutic targets to improve remyelination and neuroregeneration.

关键词： astrocyte crosstalk demyelination glial response microglia/macrophage multiple sclerosis neurodegeneration neuroinflammation oligodendrocyte lineage cells remyelination

Personalized chemotherapy in clear cell adenocarcinoma of the urethra:A case report

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World Journal of Clinical Oncology 2020年第4期11卷 243-249页

作者： Lisa B.E.Shields Arash Rezazadeh Kalebasty Norton Neuroscience Institute Norton HealthcareLouisvilleKY 40202United States Norton Cancer Institute Norton HealthcareLouisvilleKY 40202United States

bACKGROUND Clear cell adenocarcinoma of the urethra is a rare type of aggressive cancer with a poor prognosis.Clear cell carcinoma of the urethra represents less than 0.02%of all malignancies in women.Adenocarcinomas account for 10%of female urethral carcinomas,of which 40%are the clear cell variant.Determining the presence or absence of certain mutations through genetic testing may predict whether a patient with cancer may benefit from a particular chemotherapy regimen.CASe SUMMARY A 40-year-old woman presented with a 3-year history of slow urinary flow and a 3-mo history of urinary urgency and frequency as well as gross hematuria.An abdominal and pelvic computed tomography scan demonstrated enlarged lymph nodes in the abdomen and pelvis.A biopsy of a left inguinal lymph node microscopically confirmed a metastatic adenocarcinoma of the urethra.Specialized genetic testing determined personalized chemotherapy.She was treated successfully with a non-platinum-based chemotherapy consisting of paclitaxel and bevacizumab.Following 3 cycles of paclitaxel and bevacizumab,she attained significant clinical improvement,and response by FDG-Positron emission tomography(PeT)imaging showed a definite improvement in size and metabolic activity.She achieved complete response after 6 cycles of therapy by PeT scan.The patient concluded 11 cycles of paclitaxel and bevacizumab,and a subsequent PeT scan confirmed progression of metastatic disease.The patient was then treated with two cycles of doxorubicin after which a PeT scan revealed a mixed response to the treatment.CONCLUSION We report the first case of a patient with metastatic clear cell adenocarcinoma of the urethra who underwent personalized chemotherapy after testing for cancer gene alterations.Our unique case represents the safe and effective use of nonplatinum-based chemotherapy in clear cell adenocarcinoma of the urethra.

关键词： Oncology Clear cell adenocarcinoma Urethra Chemotherapy Personalized Genetic testing Case report

Thromboembolic events in metastatic testicular cancer treated with cisplatin-based chemotherapy

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World Journal of Clinical Oncology 2021年第3期12卷 183-194页

作者： Lisa B.E.Shields Michael W Daniels Nataliya Mar Arash Rezazadeh Kalebasty Norton Neuroscience Institute Norton HealthcareLouisvilleKY 40202United States Department of bioinformatics and biostatistics University of LouisvilleLouisvilleKY 40292United States Division of Hematology/Oncology Department of MedicineUCI Medical CenterOrangeCA 92868United States

bACKGROUND Testicular germ cell tumor(TGCT)is the most curable solid tumor and most common cancer among men 18-39 years.While cisplatin-based chemotherapy has significantly lengthened the survival of patients with TGCT,it is associated with a high rate of thromboembolic events(Tee).AIM To summarize our single-center experience highlighting patients who were diagnosed with TGCT and received platinum-based chemotherapy,with special attention to those patients who suffered a Tee.MeTHODS A retrospective analysis of the medical records and imaging studies of 68 consecutive individuals who were diagnosed with TGCT and received platinumbased chemotherapy at our Institution in a metropolitan community between January 1,2014 and December 31,2019.ReSULTS A total of 19(28%)patients experienced a Tee following orchiectomy which occurred during chemotherapy in 13(68%)of these patients.Patients with a higher pathologic stage(stage III)were significantly(P=0.023)more likely to experience a Tee compared to patients who had a lower stage.Additionally,patients who were treated with 3 cycles of bleomycine,etoposide,and cisplatin and 1 cycle of etoposide and cisplatin or 4 cycles of etoposide and cisplatin were significantly 5(P=0.02)times more likely to experience a Tee compared to patients who were treated with only 3 cycles of bleomycine,etoposide,and cisplatin.CONCLUSION Due to numerous factors that predispose to a Tee such as large retroperitoneal disease,higher clinical stage,greater number of chemotherapy cycle,central venous catheter,cigarette smoking,and possible cannabis use,high-risk ambulatory patients with TGCT treated with cisplatin-based chemotherapy may benefit from prophylactic anticoagulation.Randomized studies to evaluate the safety and efficacy of prophylactic anticoagulants are warranted in this young patient population generally devoid of medical co-morbidities.

关键词： Oncology Testicular cancer Thromboembolic Cisplatin Pulmonary embolism Thromboprophylaxis

Concurrent renal cell carcinoma and hematologic malignancies: Nine case reports

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World Journal of Clinical Oncology 2020年第8期11卷 644-654页

作者： lisa be shields Arash Rezazadeh Kalebasty Norton Neuroscience Institute Norton HealthcareLouisvilleKY 40202United States Norton Cancer Institute Norton HealthcareLouisvilleKY 40202United States

bACKGROUND The presence of renal cell carcinoma(RCC)and hematologic malignancies(HM)in the same patient is rarely observed.Three primary findings have been described in these patients,including male gender and lymphoid malignancy predominance,and the HM are usually diagnosed before or simultaneously with the RCC.There is a lack of evidence about clinical outcomes in this setting.We report the common characteristics of 9 patients diagnosed with concurrent RCC and HM and their clinical course and response to treatment.CASe SUMMARY Four(44%)patients were diagnosed with RCC prior to the HM,the diagnosis was simultaneous in 4(44%)patients,and 1(11%)patient was diagnosed with the HM prior to the RCC.No patients were treated with cytotoxic chemotherapy or radiation between the diagnosis of RCC and HM.Several unique features were seen in our case series,such as 3 simultaneous cancers in 1(11%)patient,a splenectomy leading to remission of diffuse large b cell lymphoma without the use of chemotherapy in 1(11%)patient,chemotherapy and rituximab for lymphoma resulting in a complete response in primary RCC in 1(11%)patient,and immunotherapy providing an excellent response for primary renal leiomyosarcoma in 1(11%)patient.CONCLUSION These findings highlight the potential role of immune system dysregulation in patients with the diagnosis of RCC and HM whereby the first malignancy predisposes to the second through an immunomodulatory effect.HM have the potential of being confused with lymph node metastasis from kidney cancer.Lymph node biopsy may be necessary at the time of initial diagnosis or in cases of mixed response to therapy.Long-term medical surveillance is warranted when a patient is diagnosed with RCC or HM.Clinicians should be aware of the higher prevalence of male gender and lymphoid malignancy with concurrent RCC and HM and that either of these conditions may be diagnosed first or they may be diagnosed simultaneously.

关键词： Oncology Renal cell cancer Hematologic malignancy Lymphoma Immune system Immunotherapy Case report

Hardening effects in Superhard Transition-Metal borides

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Accounts of Materials Research 2022年第1期3卷 100-109页

作者： lisa e.Pangilinan Shanlin Hu Spencer G.Hamilton Sarah H.Tolbert Richard b.Kaner Department of Chemistry and biochemistry University of CaliforniaLos Angeles(UCLA)Los AngelesCalifornia 90095United States Department of Chemistry and biochemistry Department of Materials Science and Engineeringand California NanoSystems Institute(CNSI)University of CaliforniaLos Angeles(UCLA)Los AngelesCalifornia 90095United States

CONSPeCTUS:Mechanical hardness is a physical property used to gauge the applications of materials in the manufacturing and machining industries.because of their high hardness and wear resistance,superhard materials(Vickers hardness,Hv≥40 GPa)are commonly used as cutting tools and abrasives.Although diamond is the hardest known material used for industrial applications,its synthesis requires both high pressure and high temperature.Interest in the field of superhard materials research has led to the search for alternatives with high hardness and thermal stability at low cost.The discovery of novel ultraincompressible,superhard materials has largely developed through trial and error along two paths.In one approach,researchers combine light elements,such as boron,carbon,nitrogen,and oxygen,often at high pressure,to replicate the highly directional,dense,covalent bonds of diamond.In the second approach,these light elements(b,C,N,and O)are combined with highly incompressible,electron-rich transition metals to form dense covalently bonded networks at ambient pressure.

关键词： Transition boron gauge

长期运动训练对脊髓损伤大鼠功能及运动神经元形态的影响及机制

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长期运动训练对脊髓损伤大鼠功能及运动神经元形态的影响及机制

Liver transplantation in the era of non-alcoholic fatty liver disease/metabolic(dysfunction)associated fatty liver disease:the dilemma of the steatotic liver graft on transplantation and recipient survival

中华医学会第十五次全国物理医学与康复学学术会议

作者：王红星 Naikui Liu Yiping Zhang Lingxiao Deng Chen Chen lisa shields Christopher b shields 励建安 Xiaoming Xu 南京医科大学第一附属医院康复医学科 Spinal Cord and brain Injury Research Group Stark Neurosciences Research Institute Department of Neurological Surgery Indiana University School of Medicine

＜正＞目的探讨运动训练对脊髓损伤大鼠功能及运动神经元形态影响及其机制。方法成年SD大鼠33只分为假手术组（Sham）、对照组（SCI）和训练组（SCI—Tr）。采用IH撞击器制作T9脊髓损伤模型,Sham组只暴露脊髓。SCI-Tr术后1周开始运动训...

＜正＞目的探讨运动训练对脊髓损伤大鼠功能及运动神经元形态影响及其机制。方法成年SD大鼠33只分为假手术组（Sham）、对照组（SCI）和训练组（SCI—Tr）。采用IH撞击器制作T9脊髓损伤模型,Sham组只暴露脊髓。SCI-Tr术后1周开始运动训练,共16周。采用bbb评分、网格步行、热敏和痛觉评定。取材前48h各组取4只大鼠右胫前肌（TA）、左比目鱼肌（Sol）注射bHRP示踪标记神经元。余大鼠取材前6天右TA、左Sol注射荧光金和快速兰,免疫荧光检测bDNF、Synaptophysin表达。

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Hepatobiliary Surgery and Nutrition 2022年第3期11卷 425-429页

作者： Seren M.Gedallovich Daniela P.Ladner lisa b.VanWagner Division of Palliative Medicine Department of MedicineUniversity of California San FranciscoSan FranciscoCAUSA Division of Organ Transplantation Department of SurgeryNorthwestern University Feinberg School of MedicineChicagoILUSA Division of Gastroenterology&Hepatology Department of MedicineNorthwestern University Feinberg School of MedicineChicagoILUSA Division of epidemiology Department of Preventive MedicineNorthwestern University Feinberg School of MedicineChicagoILUSA

Liver transplantation remains the only curative therapy for end-stage liver disease and there is a well-established shortage of transplantable deceased donor organs to meet the growing demand of waitlisted patients.Steatotic liver grafts represent the most common type of so-called extended criteria donor(eCD)grafts aimed at ameliorating this disparity.However,steatotic grafts are associated with increased post-transplant complications and graft failure(1).Hepatic graft steatosis is strongly correlated with the high prevalence of non-alcoholic fatty liver disease(NAFLD)and metabolic(dysfunction)associated fatty liver disease(MAFLD)in the general population.NAFLD and MAFLD are related,but not equivalent,liver disorders that are linked with obesity and diabetes(2).Global prevalence of NAFLD is estimated at~25%and rising(3).Models predict that NAFLD prevalence will increase by 21%to affect 100.9 million persons worldwide by 2030(4).As more donors have NAFLD,the steatotic liver graft will continue to be a challenge for liver transplantation.but,promising efforts(e.g.,organ pump with defatting agents)are under way,aimed at expanding the donor pool in the coming years.Herein,we briefly summarize approaches for assessment of hepatic steatosis,describe recipient outcomes associated with the use of steatotic liver grafts,and highlight strategies that may be used to mitigate risk considering the ongoing NAFLD/MAFLD epidemic.

关键词： organs graft donor

A Role for GIbbeReLLIN 2-OXIDASe6 and Gibberellins in Regulating Nectar Production

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Molecular Plant 2016年第5期9卷 753-756页

作者： lisa b. Wiesen Ricci L. bender Travis Paradis Alexie Larson M. Ann D.N. Perera basil J. Nikolau Neil e. Olszewski Clay J. Carter Department of Plant biology University of Minnesota Saint PaulMN 55108 USA Department of biochemistry Biophysics & Molecular Biology Iowa State University Ames IA 50011 USA W.M.Keck Metabolomics Research Laboratory Iowa State University Ames IA 50011 USA Department of Plant biology University of Minnesota Twin Cities 1445 Gortner Avenue 250 Biological Sciences Center Saint Paul MN 55108 USA

Dear editor The regulation of nectar production is dependent on hormonal signaling. For example, Arabidopsis PIN6, which encodes an auxin efflux transporter family protein, was identified as a nectary-enriched gene whose expression level was positively correlated to total nectar production （bender et al., 2013）. Furthermore, jasmonic acid （JA） levels peak in brassica flowers just prior to anthesis and promote nectar secretion （Radhika et al., 2010）. While auxin and JA have been demonstrated to play roles in the regulation of nectar production,

关键词： GIbbeReLLIN genetics NeCTARINe ReSeARCH

efficacy and Safety of NVX-CoV2373 in Adults in the United States and Mexico

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四川生理科学杂志 2021年第10期43卷 1796-1796页

作者： lisa M Dunkle From Novavax Gaithersburg (L.M.D. G.A. K.S. W.W. I.C. G.M.G. F.D.) the University of Maryland School of Medicine Baltimore (K.L.K. M.A.M. K.M.N.) the National Institute of Allergy and Infectious Diseases Bethesda (J.H.) and Walter Reed Army Institute of Research Silver Spring (J.A.A.) - all in Maryland FAICIC Clinical Research Veracruz (A.Q.B.H.) and Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán Mexico City (G.M.R.-P.) - both in Mexico Research Your Health Plano (J.M.A.) and the Texas Center for Drug Development Houston (V.G.-F.) - both in Texas M3-Wake Research Raleigh (W.L.H.) M3-Emerging Medical Research Durham (D.B.M.) and the University of North Carolina School of Medicine Chapel Hill (C.L.G.) - all in North Carolina SIMeDHealth Gainesville (D.M.D.) and Velocity Clinical Research Hallandale Beach (B.E.S.) - both in Florida the University of Nebraska Medical Center Omaha (D.F.F.) the University of Washington Medical Center (R.S.M. R.W.C. A.L.G.) and Fred Hutchinson Cancer Research Center (L.C.) Seattle and Lummi Indian Health Center Bellingham (D.C.L.) - all in Washington the Atlanta Center for Medical Research Atlanta (R.A.R.) and IACT Health Columbus (J.K.K.) - both in Georgia Velocity Clinical Research-Providence Warwick RI (D.L.F.) WR ClinSearch Chattanooga TN (M.M.) MedPharmics Metairie LA (R.J.J.) and black Hills Center for American Indian Health Rapid City SD (J.A.H.).

background:NVX-CoV2373 is an adjuvanted,recombinant spike protein nanoparticle vaccine that was shown to have clinical efficacy for the prevention of coronavirus disease 2019(Covid-19)in phase 2b-3 trials in the United Kingdom and South Africa,but its efficacy had not yet been tested in North America.Methods:We conducted a phase 3,randomized,observer-blinded,placebo-controlled trial in the United States and Mexico during the first half of 2021 to evaluate the efficacy and safety of NVX-CoV2373 in adults(≥18 years of age)who had not had severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection.Participants were randomly assigned in a 2:1 ratio to receive two doses of NVX-CoV2373 or placebo 21 days apart.The primary objective was to determine vaccine efficacy against reverse-transcriptase-polymerase-chain-reaction-confirmed Covid-19 occurring at least 7 days after the second dose.Vaccine efficacy against moderate-to-severe disease and against different variants was also assessed.

关键词： vaccine doses prevention