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Particle elasticity influences polymeric artificial antigen presenting cell effectiveness in vivo via CD8+T cell activation,macrophage uptake,and the protein corona

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Nano Research 2024年第10期17卷 9052-9064页

作者： Savannah E.Est-Witte Sydney R.Shannon Dennis H.gong kaitlyn g.calabresi Jawaun J.Harris kaitlyn Storm Edwin J.Yoo Ariel Isser Vivek P.Jani Natalie K.Livingston Mary O.Omotoso Kelly Rhodes Elana Ben-Akiva Randall A.Meyer Zoe T.Hsieh Simone Sidoli Stephany Y.Tzeng Jonathan P.Schneck Jordan J.green Translational Tissue Engineering Center Institute for NanobiotechnologyDepartment of Biomedical EngineeringJohns Hopkins School of Medicine400 N BroadwayBaltimoreMD 21231USA Institute for Cell Engineering Department of PathologyJohns Hopkins School of Medicine733 N BroadwayBaltimoreMD 21205USA Department of Biochemistry Albert Einstein College of MedicineThe BronxNew York CityNY 10461USA

Adoptive cell therapy(ACT)is an immunotherapy strategy for cancer that has seen widespread clinical *** ACT,patient-derived lymphocytes are stimulated with the antigen of interest ex vivo,proliferated,then returned to the patient to initiate an antigen-specific antitumor *** effective,this process is resource-intensive and logistically impossible for many *** artificial antigen presenting cells(aAPCs)offer a potential“off-the-shelf”alternative to ex vivo *** particulate aAPCs perform well in vitro,they have had limited success in vivo due to poor bioavailability after *** to bioavailability include rapid clearance,unfavorable biodistribution,and inadequate interactions with CD8+T cells at sites of *** properties such as elasticity have been shown to vastly impact the bioavailability and particle-cell interactions,but this has yet to be investigated in the context of aAPCs for in vivo T-cell *** literature likewise indicates that biomaterial properties,especially elasticity,can modulate T-cell activation in *** the goal of creating a more biomimetic,next-generation particulate aAPC,we developed a poly(ethylene)glycol hydrogel particle platform with tunable elasticity to investigate the impact of elasticity on antigen-specific T cell activation for in vivo adoptive *** this knowledge,we were able to gain more precise control over in vivo T cell activation and investigate possible mechanisms including the effects of aAPC elasticity on T cell binding,macrophage uptake,and the protein corona.

关键词： adoptive cell therapy artificial antigen presenting cells particle drug delivery elasticity protein corona poly(ethylene glycol)

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Trans-synaptic degeneration as a mechanism of neurodegeneration in multiple sclerosis

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Neural Regeneration Research 2023年第12期18卷 2682-2684页

作者： Olwen C.Murphy Peter A.calabresi Shiv Saidha Division of Neuroimmunology and Neurological Infections Department of NeurologyJohns Hopkins UniversityBaltimoreMDUSA

Multiple sclerosis(MS) is regarded as an immunemediated,demyelinating disorder of the central nervous system,however neuroaxonal degeneration is accepted as the principal substrate of disability accumulation(Dutta and... 详细信息

关键词： degeneration sclerosis myelin

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Emerging Applications of Optical Coherence Tomography Angiography (OCTA) in neurological research

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Eye and Vision 2018年第1期5卷 107-117页

作者： Liang Wang Olwen Murphy Natalia gonzalez Caldito Peter A.calabresi Shiv Saidha Department of Biology Johns Hopkins UniversityKrieger School of Arts and SciencesBaltimoreMDUSA Division of Neuroimmunology and Neurological Infections Johns Hopkins Hospital600 N.Wolfe St.BaltimoreMD 21287USA

Purpose:To review the clinical and research value of optical coherence tomography angiography(OCTA)in the field of ***:Current literature involving OCTA were reviewed through PubMed using the search terms“optical coherence tomography angiography”,with“multiple sclerosis”,“Alzheimer’s disease”,“optic neuropathy”,or other closely-related ***:OCTA has been applied in research to advance our understanding of the pathobiology of neurological ***-derived blood flow and vessel density measures are altered in multiple sclerosis(MS),Alzheimer’s disease(AD),and various optic neuropathies(ON)in varying regions of the posterior segment vasculature of the *** emerging research findings support the occurrence of retinal vascular alterations across a host of neurological disorders and raise the possibility that vasculopathy can be clinically relevant since it contributes to the pathobiology of several neurological ***:OCTA may be beneficial for neurological *** investigations using OCTA in neurological disorders will help to further validate its clinical and research utilities in terms of characterizing the role of vasculopathy in neurological disorders.

关键词： Optical coherence tomography angiography Neurology Multiple sclerosis Alzheimer’s disease Optic neuropathy

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Microvascular blood flow velocities measured with a retinal function imager: inter-eye correlations in healthy controls and an exploration in multiple sclerosis

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Eye and Vision 2018年第1期5卷 260-268页

作者： Liang Wang Ohemaa Kwakyi James Nguyen Esther Ogbuokiri Olwen Murphy Natalia gonzalez Caldito Laura Balcer Elliot Frohman Teresa Frohman Peter A.calabresi Shiv Saidha Department of Neurology Johns Hopkins University School of MedicineBaltimoreMDUSA Departments of Neurology Population Health and OphthalmologyNew York University School of MedicineNew YorkNYUSA Departments of Neurology and Ophthalmology University of Texas Austin Dell Medical SchoolAustinTXUSA

Background:The retinal microcirculation has been studied in various diseases including multiple sclerosis(MS).However,inter-eye correlations and potential differences of the retinal blood flow velocity(BFV)remain largely unstudied but may be important in guiding eye selection as well as the design and interpretation of studies assessing or utilizing retinal *** primary aim of this study was to determine inter-eye correlations in BFVs in healthy controls(HCs).Since prior studies raise the possibility of reduced BFV in MS eyes,a secondary aim was to compare retinal BFVs between MS eyes,grouped based on optic neuritis(ON)history and HC ***:Macular arteriole and venule BFVs were determined using a retinal function imager(RFI)in both eyes of 20 *** eye from a total of 38 MS patients comprising 13 eyes with ON(MSON)and 25 eyes without ON(MSNON)history were similarly imaged with ***:OD(right)and OS(left)BFVs were not significantly different in arterioles(OD:3.95±0.59 mm/s;OS:4.08±0.60 mm/s,P=0.10)or venules(OD:3.11±0.46 mm/s;OS:3.23±0.52 mm/s,P=0.06)in *** strong inter-eye correlations were also found between arteriolar(r=0.84,Pgnificantly lower than in HC eyes(P=0.009 and P=0.005,respectively).Similarly,arteriolar(3.59±0.69 mm/s)and venular(2.80±0.45 mm/s)BFVs in MSON eyes were also significantly lower than in HC eyes(P=0.046 and P=0.048,respectively).Arteriolar and venular BFVs in MSON and MSNON eyes did not differ from each other(P=0.42 and P=0.48,respectively).Conclusions:Inter-eye arteriolar and venular BFVs do not differ significantly in HCs and are strongly *** findings support prior observations that arteriolar and venular BFVs may be reduced in MS ***,this seems to be the case in both MS eyes with and without a history of ON,raising the possibility of global blood flow alterations in ***

关键词： Inter-eye correlation Blood flow velocity Retinal function imager Neurology Multiple sclerosis Optic neuropathy

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那他珠单抗联合β-1a干扰素治疗复发型多发性硬化症

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世界核心医学期刊文摘(神经病学分册) 2006年第8期 3-4页

作者： Rudick R.A. Stuart W.H. calabresi P.A. 郭俊 Mellen C enter for Multiple Sclerosis Treatment and Research Cleveland Clinic Foundation 9500 Euclid Ave. Cleveland OH 44195 United States Dr.

Background: Interferon beta is used to modify the course of relapsing multiple sclerosis. Despite interferon beta therapy, many patients have relapses. Natalizumab, an α 4 integrin antagonist, appeared to be safe and effective alone and when added to interferon beta- 1a in preliminary studies. Methods: We randomly assigned 1171 patients who, despite interferon beta- 1a therapy, had had at least one relapse during the 12- month period before randomization to receive continued interferon beta- 1a in combination with 300 mg of natalizumab (589 patients) or placebo (582 patients) intravenously every 4 weeks for up to 116 weeks. The primary end points were the rate of clinical relapse at 1 year and the cumulative probability of disability progression sustained for 12 weeks, as measured by the Expanded Disability Status Scale, at 2 years. Results: Combination therapy resulted in a 24 percent reduction in the relative risk of sustained disability progression (hazard ratio, 0.76; 95 percent confidence interval, 0.61 to 0.96; P = 0.02). Kaplan- Meier estimates of the cumulative probability of progression at two years were 23 percent with combination therapy and 29 percent with interferon beta- 1a alone. Combination therapy was associated with a lower annualized rate of relapse over a two- year period than was interferon beta- 1a alone (0.34 vs. 0.75, Pging lesions on T2- weighted magnetic resonance imaging (0.9 vs. 5.4, Pgitis, sinus congestion, and peripheral edema. Two cases of progressive multifocal leukoencephalopathy, one of which was fatal, were diagnosed in natalizumab- treated patients. Conclusions: Natalizumab added to interferon beta- 1a was significantly more effective than interferon beta- 1a alone in patients with relapsing multiple sclerosis. Additional research is needed to elucidate the benefits and risks of this combination treatment.

关键词：多发性硬化症那他珠单抗干扰素抗病毒药复发型

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Role of sex hormones in gastrointestinal motility in pregnant and non-pregnant rats

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World Journal of gastroenterology 2016年第25期22卷 5761-5768页

作者： Juliana Fernandes Matos Madileine Francely Americo Yuri Karen Sinzato gustavo Tadeu Volpato Luciana Aparecida Corá Marcos Felipe Freitas calabresi Ricardo Brandt Oliveira Debora Cristina Damasceno Jose Ricardo Arruda Miranda Sao Paulo State University BotucatuSP 18618-970Brazil Instituto de Ciencias Biologicas e da Saude Federal University of Mato GrossoBarra do GarcasMT 78600-000Brazil Universidade Estadual de Ciencias da Saude de Alagoas MaceioAL 57010-300Brazil Sao Paulo University Ribeirao PretoSP 14049-900Brazil

AIM: To correlate gastric contractility, gastrointestinal transit, and hormone levels in non-pregnant(estrous cycle) and pregnant rats using noninvasive techniques. METHODS: Female rats(n = 23) were randomly divided into(1) non-pregnant,(contractility, n =6; transit, n = 6); and(2) pregnant(contractility, n = 5; transit, n = 6). In each estrous cycle phase or at 0, 7, 14, and 20 d after the confirmation of pregnancy, gastrointestinal transit was recorded by AC biosusceptometry(ACB), and gastric contractility was recorded by ACB and electromyography. After each recording, blood samples were obtained for progesterone and estradiol determination. RESULTS: In the estrous cycle, despite fluctuations of sex hormone levels, no significant changes in gastrointestinal motility were observed. Days 7 and 14 of pregnancy were characterized by significant changes in the frequency of contractions(3.90 ± 0.42 cpm and 3.60 ± 0.36 cpm vs 4.33 ± 0.25 cpm) and gastric emptying(168 ± 17 min and 165 ± 15 min vs 113 ± 15 min) compared with day 0. On these same days, progesterone levels significantly increased compared with control(54.23 ± 15.14 ng/m L and 129.96 ± 30.52 ng/mL vs 13.25 ± 6.31 ng/mL). On day 14, we observed the highest level of progesterone and the lowest level of estradiol compared with day 0(44.3 ± 15.18 pg/mL vs 24.96 ± 5.96 pg/mL). CONCLUSION: gastrointestinal motility was unaffected by the estrous cycle. In our data, high progesterone and low estradiol levels can be associated with decreased contraction frequency and slow gastric emptying.

关键词： Reproductive physiological process Sex hormones gastrointestinal motility Magnetic fields gastric emptying

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