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Macrophage depletion and Schwann cell transplantation reduce cyst size after rat contusive spinal cord injury

Neural Regeneration Research 2018年第4期13卷 684-691页

作者： Yee-Shuan Lee Lucy H.Funk Jae K.Lee Mary Bartlett Bunge The Miami Project to cure Paralysis University of Miami Miller School of Medicine Department of Neurological Surgery University of Miami Miller School of Medicine Department of Cell Biology University of Miami Miller School of Medicine

Schwann cell transplantation is a promising therapy for the treatment of spinal cord injury（SCI） and is currently in clinical *** our continuing efforts to improve Schwann cell transplantation strategies,we sought to determine the combined effects of Schwann cell transplantation with macrophage *** macrophages are major inflammatory contributors to the acute spinal cord injury,and are the major phagocytic cells,we hypothesized that transplanting Schwann cells after macrophage depletion will improve cell survival and integration with host tissue after *** test this hypothesis,rat models of contusive SCI at thoracic level 8 were randomly subjected to macrophage depletion or *** rat subjected to macrophage depletion,liposomes filled with clodronate were intraperitoneally injected at 1,3,6,11,and 18 days post *** not subjected to macrophage depletion were intraperitoneally injected with liposomes filled with phosphate buffered *** cells were transplanted 1 week post injury in all *** dextran amine（BDA） was injected at thoracic level 5 to evalute axon *** Basso,Beattie,and Bresnahan locomotor test,Gridwalk test,and sensory test using von Frey filaments were performed to assess functional *** was used to detect glial fibrillary acidic protein,neurofilament,and green fluorescent protein（GFP）,and also to visulize BDA-labelled *** GFP labeled Schwann cell and cyst and lesion volumes were quantified using stained *** numbers of BDA-positive axons were also *** 8 weeks after Schwann cell transplantation,there was a significant reduction in cyst and lesion volumes in the combined treatment group compared to Schwann cell transplantation *** changes were not associated,however,with improved Schwann cell survival,axon growth,or locomotor *** combining Schwann cell transplantation with macrophage depletion does improve histopathology of the in

关键词： Schwann cell Iiposome clodrosome clodronate axon regeneration Schwann cell survival neuroprotection glial scar cyst cell transplantation

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Probiotics for antibiotic-associated diarrhea:Do we have a verdict?

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World Journal of Gastroenterology 2014年第47期20卷 17788-17795页

作者： Iyad Issa Rami Moucari Department of Gastroenterology and Hepatology Rafik Hariri University HospitalHamraBeirut 2034-7304 Department of Gastroenterology and Hepatology Advanced Cure Diagnostic CenterUAE 61887Abu Dhabi

Probiotics use has increased tremendously over the past ten *** was coupled with a surge of data relating their importance in clinical *** diarrhea,whose frequency has risen recently,was one of the earliest targets with data published more than ten years ***,available trials suffer from severe discrepancies associated with variability and heterogeneity of several *** published randomized controlled trials and subsequent meta-analyses suggest benefit for probiotics in the prevention of antibiotic-associated *** same seems to also apply when the data is examined for Clostridium difficile-associated ***,the largest randomized double-blind placebo-controlled trial to date examining the use of a certain preparation of probiotics in antibiotic-associated diarrhea showed disappointing results,but it was flawed with several *** commonest species of probiotics studied across most trials is Lactobacillus;however,other types have also shown similar *** have enjoyed an impeccable safety *** a few reports of severe infections sometimes leading to septicemia,most of the available trials confirm their harmless behavior and show similaradverse events compared to *** a consensus dictating its use is still lacking,it would be advisable at this point to suggest prophylactic use of probiotics to certain patients at risk for antibiotic-associated diarrhea or to those who suffered previous episodes.

关键词： Probiotics Antibiotic-associated diarrhea Clostridium difficile Prevention Lactobacillus Bifidobacterium

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Exploiting kinase polypharmacology for nerve regeneration

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Neural Regeneration Research 2016年第1期11卷 71-72页

作者： Hassan Al-Ali John L.Bixby Vance P.Lemmon Miami Project to cure Paralysis University of Miami Center for Computational Science University of Miami Department of Neurological Surgery University of Miami Department of Molecular & Cellular Pharmacology University of Miami

The human central nervous system（CNS）has a markedly poor capacity for regenerating its axons following *** appears to be due to two main causes：1）a developmentally regulated decline in regenerative capacity within mature CNS neurons,and 2）the presence of biological components that constitute barriers to axon regeneration（e.g.,growth-inhibitory molecules）.

关键词： regeneration alterations mature markedly constitute regenerative barriers phenotypic similarity inhibit

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Dissemination profile of perioperative tumor cells in peripheral blood of colorectal cancer patients detected by multiple marker genes

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Science China Chemistry 2009年第12期52卷 2257-2263页

作者： YAN Feng LIU ZhiAn ZHAO JianHua JU HuangXian Tumor Hospital of Jiangsu Province Jiangsu Institute of Cancer Prevention and CureNanjing 210009China MOE Key Laboratory of Analytical Chemistry for Life Science Department of ChemistryNanjing UniversityNanjing 210093China

This work proposes a method to assess the molecular profile of perioperative circulating tumor cells in peripheral blood (PB) of colorectal cancer patients for differentiating the dissemination process of tumor cells. Two-point quantification of multiple marker genes was designed for describing the profile. The expression levels of cytokeratin 20 (CK20),carcino-embryonic antigen (CEA) and survivin mRNA in PB and tumor tissue samples in 37 colorectal cancer patients from 1 d pre-operation to 2 h postoperation were detected with real-time quantitative reverse transcription-polymerase chain reaction. β-Actin mRNA was used as internal control to standardize the results of different mRNA expression levels. The data analysis using Stata statistical packages,Chi-Square test and Mann-Whitney test indicated the expression level of CEA mRNA in PB increased significantly,while those of CK20 and survivin mRNA decreased significantly. Quantitative comparison with tumor tissues indicated that the increase of CEA mRNA level in PB coincided with the decrease of CK20 and survivin mRNA levels in different tumor cells. These results showed surgical manipulation caused tumor cells shedding into blood from primary tumor tissue and significant increase of CEA mRNA level,while occult tumor cells with high expression levels of CK20 and survivin mRNA before surgery decreased after surgery.

关键词： real-time quantitative RT-PCR multimarker genes circulating tumor cells colorectal cancer

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Yemazhui(Herba Eupatorii Lindleyani)ameliorates lipopolysaccharide-induced acute lung injury via modulation of the toll-like receptor 4/nuclear factor kappa-B/nod-like receptor family pyrin domain-containing 3 protein signaling pathway and intestinal flor

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Journal of Traditional Chinese Medicine 2024年第2期44卷 303-314页

作者： REN Li HAI Yang YANG Xue LUO Xianqin Chongqing Key Laboratory of Traditional Chinese Medicine for Prevention and cure of Metabolic Diseases College of Traditional Chinese MedicineChongqing Medical UniversityChongqing 400016China College of Basic Medicine Chongqing Medical UniversityChongqing 400016China

OBJECTIVE:To investigate the impact of Yemazhui(Herba Eupatorii Lindleyani,HEL)against lipopolysaccharide(LPS)-induced acute lung injury(ALI)and explore its underlying mechanism in ***:The chemical constituents of HEL were analyzed by ultra-high performance liquid chromatographyquadrupole time-of-flight mass spectrometry ***,HEL was found to suppress LPS-induced ALI in ***-week-old male Sprague-Dawley rats were randomly divided into 6 groups:control,LPS,Dexamethasone(Dex),HEL low dose 6 g/kg(HEL-L),HEL medium dose 18 g/kg(HEL-M)and HEL high dose 54 g/kg(HEL-H)*** model rats were intratracheally injected with 3 mg/kg LPS to establish an ALI *** counts,lung wet/dry weight ratio,as well as myeloperoxidase(MPO)activity were determined followed by the detection with hematoxylin and eosin staining,enzyme linked immunosorbent assay,quantitative real time polymerase chain reaction,western blotting,immunohistochemistry,and ***,to explore the effect of HEL on ALI-mediated intestinal flora,we performed 16s rRNA sequencing analysis of intestinal ***:HEL attenuated LPS-induced inflammation in lung tissue and intestinal flora *** study indicated that HEL suppressed the lung coefficient and wet/dry weight ratio of LPS-induced ALI in rats,inhibited leukocytes exudation and MPO activity,and improved the pathological injury of lung *** addition,HEL reduced the expression of tumor necrosis factoralpha,interleukin-1beta(IL-1β)and interleukin-6(IL-6)in bronchoalveolar lavage fluid and serum,and inhibited nuclear displacement of nuclear factor kappa-B p65(NF-κBp65).And 18 g/kg HEL also reduced the expression levels of toll-like receptor 4(TLR4),myeloid differentiation factor 88,NF-κBp65,phosphorylated inhibitor kappa B alpha(phospho-IκBα),nod-like receptor family pyrin domain-containing 3 protein(NLRP3),IL-1β,and interleukin-18(IL-18)in lung tissue,and regulated intestinal flora disturban

关键词： Yemazhui(Herba Eupatorii Lindleyani) acute lung injury anti-inflammation toll-like receptor 4 nuclear factor kappa-B nod-like receptor family pyrin domain-containing 3 protein signal transduction gastrointestinal microbiome

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AAV8 transduction capacity is reduced by prior exposure to endosome-like pH conditions

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Neural Regeneration Research 2021年第5期16卷 851-855页

作者： Jeffrey ALowell Kar Men Mah John LBixby Vance PLemmon Miami Project to cure Paralysis University of MiamiMiamiFLUSA Department of Neurological Surgery University of MiamiMiamiFLUSA Department of Molecular and Cellular Pharmacology University of MiamiMiamiFLUSA

Adeno-associated virus(AAV)is an essential instrument in the neuroscientist’s toolkit,which allows delivery of DNA to provide labeling with fluorescent proteins or genetic instructions to regulate gene *** the field of neural regeneration,the transduction of neurons enables the observation and regulation of axon growth and regeneration,and in the future will likely be a mechanism for delivering molecular therapies to promote sprouting and regeneration after central nervous system *** formulations of AAV preparations permit efficient viral transduction under physiologic conditions,but an improved understanding of the mechanistic limitations of AAV transduction may facilitate production of more resilient AAV strains for investigative and therapeutic *** studied AAV transduction in the context of prior exposure of AAV serotype 8(AAV8)to environmental pH within the range encountered during endosomal endocytosis(pH 7.4 to pH 4.4),during which low pH-triggered structural and autoproteolytic changes to the viral capsid are believed to be necessary for endosome escape and virus *** to the fundamental nature of these processes,we hypothesized that premature exposure of AAV8 particles to acidic pH would decrease viral transduction of HT1080 cells in vitro,as measured by fluorescent reporter gene expression using high-content imaging *** found that increasingly acidic incubation conditions were associated with concomitant reductions in transduction efficiency,and that quantitative levels of reporter gene expression in transduced cells were similarly *** biggest decrease in transduction occurred between pH 7.4 and pH 6.4,suggesting the possible co-occurrence of a pH-associated event and viral inactivation within that *** together,these findings indicate that exposure of AAV8 to acidic pH for as little as 1 hour is deleterious to transduction *** studies are necessary to understand the pH-associated

关键词： adeno-associated virus autolytic capsid low pH protease proteolytic temperature trafficking transduction viral inactivation

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Facilitating transparency in spinal cord injury studies using data standards and ontologies

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Neural Regeneration Research 2014年第1期9卷 6-7页

作者： Vance P.Lemmon Saminda Abeyruwan Ubbo Visser John L.Bixby Department of Neurological Surgery University of Miami Miami Project to cure Paralysis University of Miami Center for Computational Science University of Miami Department of Computer Science University of Miami Molecular&Cellular Pharmacology University of Miami

Progress in developing robust therapies for spinal cord injury （SCI）, trau- matic brain injury （TBI） and peripheral nerve injury has been slow. A great deal has been learned over the past 30 years regarding both the intrinsic factors and the environmental factors that regulate axon growth, but this large body of information has not yet resulted in clinically available thera- peutics. This therapeutic bottleneck has many root causes, but a consensus is emerging that one contributing factor is a lack of standards for experi- mental design and reporting. The absence of reporting standards, and even of commonly accepted definitions of key words, also make data mining and bioinformatics analysis of neural plasticity and regeneration difficult, if not impossible. This short review will consider relevant background and poten- tial solutions to this problem in the axon regeneration domain.

关键词： data Facilitating transparency in spinal cord injury studies using data standards and ontologies SCI

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Central role of Yes-associated protein and WW-domain-containing transcriptional co-activator with PDZ-binding motif in pancreatic cancer development

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World Journal of Gastroenterology 2019年第15期25卷 1797-1816页

作者： Enrique Rozengurt Guido Eibl Department of Medicine David Geffen School of Medicine University of California at Los Angeles cure: Digestive Diseases Research Center Department of Surgery David Geffen School of Medicine University of California at Los Angeles

Pancreatic ductal adenocarcinoma(PDAC) remains a deadly disease with no efficacious treatment options. PDAC incidence is projected to increase, which may be caused at least partially by the obesity epidemic. Significantly enhanced efforts to prevent or intercept this cancer are clearly warranted. Oncogenic KRAS mutations are recognized initiating events in PDAC development, however, they are not entirely sufficient for the development of fully invasive *** genetic alterations and/or environmental, nutritional, and metabolic signals, as present in obesity, type-2 diabetes mellitus, and inflammation, are required for full PDAC formation. We hypothesize that oncogenic KRAS increases the intensity and duration of the growth-promoting signaling *** exciting studies from different laboratories indicate that the activity of the transcriptional co-activators Yes-associated protein(YAP) and WW-domaincontaining transcriptional co-activator with PDZ-binding motif(TAZ) play a critical role in the promotion and maintenance of PDAC operating as key downstream target of KRAS signaling. While initially thought to be primarily an effector of the tumor-suppressive Hippo pathway, more recent studies revealed that YAP/TAZ subcellular localization and co-transcriptional activity is regulated by multiple upstream signals. Overall, YAP has emerged as a central node of transcriptional convergence in growth-promoting signaling in PDAC cells. Indeed, YAP expression is an independent unfavorable prognostic marker for overall survival of PDAC. In what follows, we will review studies implicating YAP/TAZ in pancreatic cancer development and consider different approaches to target these transcriptional regulators.

关键词： Pancreatic cancer Yes-associated protein and WW-domain-containing transcriptional co-activator with PDZ-binding motif Oncogenic Kras Obesity Signaling network and loops

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Stimulation by nizatidine,a histamine H_2-receptor antagonist,of duodenal HCO_3^-secretion in rats:relation to anti-cholinesterase activity

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World Journal of Gastroenterology 2000年第5期6卷 651-658页

作者： Koji Takeuchi Shoji Kawauchi Hideo Araki Shigeru Ueki Osamu Furukawa Department of Pharmacology and Experimental Therapeutics Kyoto Pharmaceutical UniversityMisasagiYamashinaKyoto 607-8414Japan cure Bldg.114Suite 217 West LA VAMC 11301 Wilshire Blvd.Los AngelesCA 90073

AIM To examine whether nizatidine stimulates duodenal HCO_3^- secretion in rats by inhibiting AChE activity. METHODS Under pentobarbital anesthesia,a proximal duodenal loop was perfused with saline,and the HCO_3 secretion was measured at pH 7.0 using a pH-stat method and by adding 10mM ***,neostigmine,carbachol or famotidine was administered *** a single injection. RESULTS Intravenous administration of nizatidine(3-30 mg/kg)dose-dependently increased duodenal HCO_3^- secretion,and the effect at 10mg/kg was equivalent to that obtained by carbachol at 0.01 mg/*** nizatidine action was observed at the same dose range that inhibited acid secretion and enhanced gastric motility,mimicked by *** of neostigmine(0.03 mg/kg),and significantly attenuated by bilateral vagotomy and prior s.c. administration of atropine but not by indomethacin,a cyclooxygenase inhibitor,or N^G-nitro-L-arginine methyl ester,a NO synthase *** HCO_3^- secretory response to acetylcholine(0.001 mg/kg)was significantly potentiated by the concurrent administration of nizatidine(3mg/kg,i.v.).The IC_(50)of nizatidine for AChE of rat erythrocytes was 1.4×10^(-6)M,about 12 times higher than that of *** famotidine(>10^(-3)M, 30mg/kg,i.v.)nor cisapride(> 10^(-3)M, 3mg/kg,i.v.)had any influence on AChE activity or duodenal HCO_3^- *** damage induced by acid perfusion(100 mM HCI for 4 h)in the presence of indomethacin was significantly prevented by nizatidine and neostigmine,at the doses that increased the HCO_3^- secretion. CONCLUSION Nizatidine stimulates duodenal HCO_3^- secretion,in both vagal-dependent and atropine-sensitive manners,and the action is associated with the anti-AChE activity of this agent.

关键词： nizatidine histamine H_2 receptor blockaders duodenal HCO_3^-secretion cholinesterase inhibitors rats

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Treatment with analgesics after mouse sciatic nerve injury does not alter expression of wound healingassociated genes

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Neural Regeneration Research 2016年第1期11卷 144-149页

作者： Matt C.Danzi Dario Motti Donna L.Avison John L.Bixby Vance P.Lemmon The Miami Project to cure Paralysis University of MiamiLois Pope LIFE Center Department of Surgery Leonard M. Miller School of Medicine University of Miami Department of Neurological Surgery University of Miami Department of Molecular and Cellular Pharmacology University of Miami

Animal models of sciatic nerve injury are commonly used to study neuropathic pain as well as axon regeneration. Administration of post-surgical analgesics is an important consideration for animal welfare, but the actions of the analgesic must not interfere with the scientific goals of the experiment. In this study, we show that treatment with either buprenorphine or acetaminophen following a bilateral sciatic nerve crush surgery does not alter the expression in dorsal root ganglion（DRG） sensory neurons of a panel of genes associated with wound healing. These findings indicate that the post-operative use of buprenorphine or acetaminophen at doses commonly suggested by Institutional Animal Care and Use Committees does not change the intrinsic gene expression response of DRG neurons to a sciatic nerve crush injury, for many wound healing-associated genes. Therefore, administration of post-operative analgesics may not confound the results of transcriptomic studies employing this injury model.

关键词： acetaminophen analgesics axon buprenorphine dorsal root ganglia gene expression peripheral nerve injuries regeneration sciatic nerve wound healing

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