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Single-cell sorting based on secreted products for functionally defined cell therapies

Microsystems & Nanoengineering 2022年第4期8卷 17-34页

作者： Hiromi Miwa robert Dimatteo Joseph de Rutte Rajesh Ghosh Dino Di Carlo Department of Bioengineering University of California-Los AngelesLos AngelesCA 90095USA Department of Chemical and Biomolecular Engineering University of California-Los AngelesLos AngelesCA 90095USA Partillion Bioscience Los AngelesCA 90095USA Department of Mechanical and Aerospace Engineering University of California-Los AngelesLos AngelesCA 90095USA California NanoSystems Institute(CNSI) University of California-Los AngelesLos AngelesCA 90095USA

Cell therapies have emerged as a promising new class of“living”therapeutics over the last decade and have been particularly successful for treating hematological ***,cellular therapeutics are being developed with the aim of treating almost any disease,from solid tumors and autoimmune disorders to fibrosis,neurodegenerative disorders and even aging ***,their therapeutic potential has remained limited due to the fundamental differences in how molecular and cellular therapies *** the structure of a molecular therapeutic is directly linked to biological function,cells with the same genetic blueprint can have vastly different functional properties(e.g.,secretion,proliferation,cell killing,migration).Although there exists a vast array of analytical and preparative separation approaches for molecules,the functional differences among cells are exacerbated by a lack of functional potency-based sorting *** this context,we describe the need for next-generation single-cell profiling microtechnologies that allow the direct evaluation and sorting of single cells based on functional properties,with a focus on secreted molecules,which are critical for the in vivo efficacy of current cell *** first define three critical processes for single-cell secretion-based profiling technology:(1)partitioning individual cells into uniform compartments;(2)accumulating secretions and labeling via reporter molecules;and(3)measuring the signal associated with the reporter and,if sorting,triggering a sorting event based on these reporter *** summarize recent academic and commercial technologies for functional single-cell analysis in addition to sorting and industrial applications of these *** approaches fall into three categories:microchamber,microfluidic droplet,and lab-on-a-particle ***,we outline a number of unmet needs in terms of the discovery,design and manufacturing of cellular therapeutics a

关键词： therapies sorting realization

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Characterizing motor impulsivity of individuals classified as overweight to obese

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Sports Medicine and Health Science 2023年第4期5卷 314-318页

作者： Kyle D.Flack robert E.Anderson III Kylie F.McFee Bridgette T.Day Department of Dietetics and Human Nutrition College of AgricultureUniversity of KentuckyLexingtonKYUSA

Deficits in the impulse control system are an important predictor of energy intake and body *** classified as overweight to obese may possess these deficits as a general behavioral trait or they may be food*** present study assessed motor impulsivity(ability to suppress a pre-potent response)when presented with food and neutral(non-food)cues,testing if deficits in motor impulsivity is specific to food cues or a general trait among participants classified as overweight to *** proportion of inhibitory failures to no-go targets following food cues(10.8%)was significantly greater than the proportion of inhibitory failures to no-go targets following neutral cues(1.9%,p0.001).These differences remained when covering for sex and *** indicates deficits in food-specific impulse control(as opposed to general impulse control)are present in those classified as overweight to *** the specific aspect of impulse control that is present in this population is needed for the development of future impulse control training interventions that seek to change eating behaviors as a means for weight control.

关键词： Impulsivity Inhibitory control Impulse control Response inhibition Food cues Obesity Go/NoGo task

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Effect of small bowel transit time on accuracy of video capsule endoscopy in evaluating suspected small bowel bleeding

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World Journal of Gastrointestinal Pharmacology and Therapeutics 2022年第6期13卷 88-95页

作者： Nandakumar Mohan Simone Jarrett Alexander Pop Daniel Rodriguez robert Dudnick Internal Medicine Einstein Medical Center PhiladelphiaPhiladelphiaPA 19141United States Division of Gastrointestinal Diseases and Hepatology Einstein Medical Center PhiladelphiaPhiladelphiaPA 19141United States Department of Urban Health and Nutrition Lasalle UniversityPhiladelphiaPA 19141United States

BACKGROUND Obscure small bowel bleeding is defined as gastrointestinal bleeding(GIB)that is unidentifiable with esophagogastroduodenoscopy and a colonoscopy with video capsule endoscopy(VCE)being the next gold standard step for *** bowel transit time(SBTT)is a metric of a VCE study that is defined as the time the capsule takes to travel through the small *** To determine if SBTT within the VCE study,correlates to overall detection of obscure small bowel ***,we attempted to identify any existing correlation between SBTT and re-bleeding after a negative VCE *** This is a single center retrospective analysis of VCE studies performed for overt and occult GIB at Einstein Medical Center,Philadelphia,between 2015 and *** criteria primarily consisted of patients 18 years or older who had a VCE study done as part of the workup for a *** with incomplete VCEs,poor preparation,or with less than 6 mo of follow up were excluded.A re-bleeding event was defined either as overt or occult within a 6-mo *** rebleeding was defined as Visible melena or hematochezia with>2 gm/dL drop in hemoglobin defined an overt re-bleeding event;whereas an unexplained>2 gm/dL drop in hemoglobin with no visible bleeding defined an occult *** Results indicated that there was a significant and positive point biserial correlation between SBTT of 220 min and detection of a bleeding focus with a statistically significant p value of ***,the area under the curve was negligible when trying to identify a threshold time for SBTT to discriminate between risk of re-bleeding events after a negative *** In terms of SBTT and association with accuracy of VCE finding a bleeding focus,220 min was found to be adequate transit time to accurately find a bleeding focus,when *** was found that no threshold SBTT could be identified to help predict re-bleeding after a negative VCE.

关键词： Small bowel transit time Endoscopy Video capsule endoscopy Obscure bleed Small bowel Anemia

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The emerging role of zinc transporters in cellular homeostasisand cancer

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Signal Transduction and Targeted Therapy 2017年第1期2卷 144-155页

作者： Elizabeth Bafaro Yuting Liu Yan Xu robert E Dempski Department of Chemistry and Biochemistry Worcester Polytechnic InstituteWorcesterMassachusettsUSA Department of Obstetrics and Gynecology Indiana University School of MedicineIndianapolisIndianaUSA

Zinc is an essential micronutrient that plays a role in the structural or enzymatic functions of many cellular *** zinc homeostasis involves the opposing action of two families of metal transporters:the ZnT(SLC30)family that functions to reduce cytoplasmic zinc concentrations and the ZIP(SLC39)family that functions to increase cytoplasmic zinc *** in intracellular zinc levels mediated by these transporter families affect signaling pathways involved in normal cell development,growth,differentiation and ***,changes in zinc transporter localization and function resulting in zinc dyshomeostasis have pathophysiological *** dyshomeostasis has been implicated in the progression of *** we review recent progress toward understanding the structural basis for zinc transport by ZnT and ZIP family proteins,as well as highlight the roles of zinc as a signaling molecule in physiological conditions and in various *** zinc is emerging as an important signaling molecule in the development and progression of cancer,the ZnT and ZIP transporters that regulate cellular zinc homeostasis are promising candidates for targeted cancer therapy.

关键词： homeostasis cancer Zinc

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Strategies for PET imaging of the receptor for advanced glycation endproducts(RAGE)

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Journal of Pharmaceutical Analysis 2020年第5期10卷 452-465页

作者： Lindsey R.Drake Allen F.Brooks Jenelle Stauff Phillip S.Sherman Janna Arteaga robert A.Koeppe Aimee Reed Timothy J.Montavon Marc B.Skaddan Peter J.H.Scott Department of Radiology University of MichiganAnn ArborMI48109USA Department of Medicinal Chemistry University of MichiganAnn ArborMI48109USA AbbVie Process Chemistry North ChicagoIL60064USA AbbVie Centralized Medicinal Chemistry North ChicagoIL60064USA AbbVie Translational Imaging North ChicagoIL60064USA

The implication of the receptor for advanced glycation end-products(RAGE)in numerous diseases and neurodegenerative disorders makes it interesting both as a therapeutic target and as an inflammatory *** the context of investigating RAGE as a biomarker,there is interest in developing radiotracers that will enable quantification of RAGE using positron emission tomography(PET)*** have synthesized potential small molecule radiotracers for both the intracellular([18F]InRAGER)and extracellular([18F]RAGER)domains of *** we report preclinical evaluation of both using in vitro(lead panel screens)and in vivo(rodent and nonhuman primate PET imaging)*** radiotracers have high affinity for RAGE and show good brain uptake,but suffer from off-target *** source of the off-target PET signal is not attributable to binding to melatonin receptors,but remains *** have also investigated use of lipopolysaccharide(LPS)-treated mice as a possible animal model with upregulated RAGE for evaluation of new imaging *** of the mouse brain sections revealed increases in RAGE in the male cohorts,but no difference in the female ***,it proves challenging to quantify the changes in RAGE due to off-target binding of the ***,they are appropriate lead scaffolds for future development of 2nd generation RAGE PET radiotracers because of their high affinity for the receptor and good CNS penetration.

关键词： RAGE Neuroimaging Positron emission tomography Radiochemistry Neuroinflammation

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Transgenic UDP-Glucuronosyltransferase 1 （Tg-UGT1） Mice are Protected from Obesity-Induced Type 2 Diabetes

Transgenic UDP-Glucuronosyltransferase 1 （Tg-UGT1） Mice ar...

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第十五届国际药理学大会

作者： Bonzo Jessica Senekeo-Effenberger Kathy Tukey robert University of California San Diego University of California San Diego University of California San Diego

＜正＞ Obesity - induced type 2 diabetes is a growing human health issue in Western societies . Fibrates used to treat diabetes are targeted by glucuronidation for elimination. To examine the contribution of human glucuronidation towards obesity - induced type 2 diabetes, wild type （WT） and Tg - UGT1 male mice were fed a normal diet or a 35% fat diet （HFD）. Mass gain was monitored and diabetic status established. HFD WT mice were insensitive to insulin, retained elevated blood glucose levels, and displayed hyperinsulinemia. HFD Tg - UGT1 mice were protected from these markers of type 2 diabetes. To determine if human UGTIA expression correlated with protection. UGTIA protein levels were measured by Western blot. UGTIA proteins in the small intestine were down- regulated in HFD Tg - UGT1 mice. Time course studies established the point of UGTIA protein reduction in relation to disease onset and disease protection. While it is not clear why down - regulation of the human UGTIA proteins might protect against type 2 diabetes, the reduction may increase the potential for toxicity of drugs in diabetic patients. Supported by USPHS grant gm49135

关键词： Transgenic mice UGT1A diabetes glucuronidation

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Urine albumin excretion: Characterization of normal variability in healthy children

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Open Journal of Pediatrics 2013年第2期3卷 58-64页

作者： John robert Brandt Craig Stephen Wong Aaron Jacobs Amy Otten Staples School of Medicine University of New Mexico Albuquerque USA

Objective: Elevated urine albumin to creatinine ratio (ACR) of >30 mg/gm is a widely agreed upon indicator of pathologic albuminuria in children. However, the most reliable specimen to measure ACR in children remains undefined. We assess the range and limits of upright and supine total albumin and ACR in healthy children. Methods: Healthy children age 6 - 18 years completed 24-hour and split upright and supine urine collections. Upright, supine and 24-hour protein, albumin and creatinine were measured. Primary outcomes are range and variation in urine albumin by diurnal status, age, gender, BMI percentile and Tanner stage. Results: In healthy children, with mean age 12.9 year (sd 3.2), upright ACR was 2-fold greater than supine (13.9 vs 6.8 mg/gm, p = 0.02). The range of ACR was much greater in the upright (2 - 323 mg/gm) compared to the supine (1.7 - 76 mg/gm) samples. The average total 24-hour urine albumin was 8.4 mg (sd 9.8) and the mean ACR was 8.9 mg/gm (sd 11.7). The 24-hour albumin increased with age and Tanner stage, but this relationship was not significant after adjusting for BSA or urine creatinine. A supine or upright ACR of >30 mg/gm was found in 5.4% of each group. However, in all subjects with an elevated ACR on an individual upright or supine sample, a second 1st am ACR sample was normal. Conclusions: In healthy children there is a marked diurnal variability in ACR with a higher value from a daytime sample compared to 1st morning specimen. Screening for pathologic albuminuria should always use a first morning urine specimen.

关键词： ACR Albuminuria Albumin to Creatinine Ratio Microalbuminuria Proteinuria

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肝素酶Ⅰ对合成的肝素五糖的酶解作用及对其抗Xa因子活性的影响(英文)

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青岛海洋大学学报（自然科学版） 2001年第4期31卷 529-535页

作者：于广利管华诗 robert J.Linhardt Jawed Fareed 青岛海洋大学海洋药物与食品研究所青岛266003 Division of Medicinal and Natural Products Chemistry Department of Pathology and Pharmacology

研究肝素酶 (来源于 Flavobacterum heparinase,EC4 .2 .2 .7)对人工合成的且含有与抗凝血酶特定结合位点的肝素五糖 (SHP)的酶解作用 ,并对酶解作用的动力学进行研究。利用强阴离子高效液相色谱 (SAX- HPL C)对酶解混合物进行分离 ... 详细信息

研究肝素酶 (来源于 Flavobacterum heparinase,EC4 .2 .2 .7)对人工合成的且含有与抗凝血酶特定结合位点的肝素五糖 (SHP)的酶解作用 ,并对酶解作用的动力学进行研究。利用强阴离子高效液相色谱 (SAX- HPL C)对酶解混合物进行分离 ,利用质谱 (ESIMS)和核磁共振波谱 (1H- NMR)技术对得到的二糖和三糖的结构进行确证。研究结果表明 ,这种被作为肝素反向试剂的肝素酶可水解人工所合成的肝素五糖 ,从而使之丧失抗 Xa因子活性。

关键词：肝素酶Ⅰ 合成肝素五糖抗Xa因子活性酶解作用抗凝血酶Ⅲ 海洋药物

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Intervertebral disc development and disease-related genetic polymorphisms

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Genes & Diseases 2016年第3期3卷 171-177页

作者： Jason W.Ashley Motomi Enomoto-Iwamoto Lachlan J.Smith robert L.Mauck Danny Chan Joseph Lee Martin F.Heyworth Howard An Yejia Zhang Department of Orthopedic Surgery Perelman School of MedicineUniversity of PennsylvaniaUSA Department of Surgery Division of Orthopaedic SurgeryChildren’s Hospital of PhiladelphiaPhiladelphiaPAUSA School of Biomedical Sciences The University of Hong KongHong Kong Department of Orthopedic Surgery University of ChicagoChicagoILUSA Corporal Michael J.Crescenz Veterans Affairs Medical Center PhiladelphiaPAUSA Department of Medicine Perelman School of MedicineUniversity of PennsylvaniaUSA Department of Orthopedic Surgery Rush University Medical CenterChicagoILUSA Department of Physical Medicine&Rehabilitation Perelman School of MedicineUniversity of PennsylvaniaUSA

The intervertebral disc(IVD)comprises a gelatinous inner core(nucleus pulposus;NP)and concentric rings(annulus fibrosus;AF).The NP,an important structure for shock absorption in the vertebrate spinal motion segment,can be traced back to the notochord in ontogenetic *** vertebrates,the notochord undergoes mucinoid changes,and had been considered vestigial until ***,observed correlations between IVD degeneration and back pain in humans have renewed interest in the IVD in biomedical *** its mechanical contribution to development,the notochord is also an essential signaling center,which coordinates formation of the neural tube and *** pertinent signaling molecules,particularly TGF-b and bone morphogenetic proteins(BMPs),continue to play roles in the adult tissues and have been utilized for tissue *** factors are major determinants of who will develop IVD degeneration and related back pain,and seem to correlate better with disc degeneration and back pain than do external forces on the *** summary,the spinal column is a landmark development in *** directing the development of the IVD may also contribute to its maintenance,degeneration,and ***,structural genes as well as genes responsible for maintenance of the structure are related to IVD ***,genes responsible for inflammation may play a dual role in exacerbating degeneration or facilitating repair responses depending on the context.

关键词： Back pain Development Intervertebral disc(IVD) Notochord Regeneration

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18 需要客观检验

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国际地震动态 1999年第7期20卷 18-19页

作者： robert J.Geller 日本东京大学研究生科学院

Ｗｙｓｓ在这次争论的第五周的信中说我在第三周的文章里出现了一个“重大错误”。我在这里解释为什么对此断言不能接受，并用更通俗的内容摆出我的反驳意见。需要可检验的算法无疑所有读者都学过牛顿的万有引力定律：Ｆ＝Ｇｍ１ｍ２／... 详细信息

Ｗｙｓｓ在这次争论的第五周的信中说我在第三周的文章里出现了一个“重大错误”。我在这里解释为什么对此断言不能接受，并用更通俗的内容摆出我的反驳意见。需要可检验的算法无疑所有读者都学过牛顿的万有引力定律：Ｆ＝Ｇｍ１ｍ２／ｒ２一位伟大的科学家发现了这个定律...

关键词：地震预报客观检验地震前兆误报

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