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Short Review of Ischemia- and Hypoxia-Protective Roles of “Big Potassium” (BK) Channels

1997年

作者： joseph f. HOfMEISTER JOYCE B. RODOWSKI.

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Journal of Biosciences and Medicines 2021年第6期9卷 150-160页

作者： John f. Peppin joseph V. Pergolizzi Alexander Kraus Robert B. Raffa Marian University College of Osteopathic Medicine Indianapolis USA Pikeville University College of Osteopathic Medicine Pikeville Kentucky USA Enalare Therapeutics Inc. Princeton USA NEMA Research Inc. Naples USA Neumentum Inc. Morristown USA University of Arizona College of Pharmacy Tucson USA Temple University School of Pharmacy Philadelphia USA

There is accumulating evidence that the subfamily of large-conductance potassium (“big”, “BK”) channels are involved in diverse, and perhaps coordinated, protective or counteractive responses to local or generalized ischemia and hypoxia. Although widely distributed, the physiological differences among BK channels which results from posttranslational modification (alternative splicing) and co-assembly with auxiliary modulatory subunits (β1-4 and γ1-4), bestows localized differences in subunit composition, distribution, 2nd-messenger coupling, and pharmacologic properties. Due to the ubiquitous nature of BK channels and the multiplicity of subtypes, they have many potential therapeutic applications in the maintenance of oxygen homeostasis, cerebro- and cardio-protection, and stimulation of respiration in response to drug-induced respiratory depression. BK channels may also offer other potentially broad and underrecognized promising targets for novel pharmaceutical development.

关键词： Big potassium Channels BKCa Ischemia Hypoxia Respiratory Stimulation ENA-001

PEPT study of particle motion for different riser exit geometries

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Particuology 2010年第6期8卷 623-630页

作者： Chian Wen Chan Anke Brems Shiva Mahmoudi Jan Baeyens Jonathan Seville David Parker Thomas Leadbeater joseph Gargiuli University of Warwick School of EngineeringCoventryCV4 7 ALUK Katholieke Universiteit Leuven Department of Chemical Engineeringde Croylaan463001LeuvenBelgium University of Birmingham School of Physics and AstronomyBirminghamB22 T15UK

Laboratory and industrial risers are equipped with exits of many different layouts, and numerous publications discuss the influence of riser exit geometry on local and overall solids hydrodynamics in the riser. The present paper reviews literature findings--mostly based upon indirect experimental techniques and often somewhat contradictory, Direct measurement of particle velocity and particle occupancy near and in the riser exit provide a better indication of the effect of riser exit geometry. Positron Emission Particle Tracking （PEPT） was used in this work for the first time to investigate the exit region of the riser, An abrupt or sharp exit causes particles to be knocked out of the gas flow, so forming a recirculation or reflux region in the upper part of the riser. This is much less pronounced with a curved or gradual exit.

关键词： CfB Riser Exit geometries Positron Emission Particle Tracking

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

Effect of Tangnaikang on TGf-β_1-induced transdifferentiation of human renal tubular epithelial HK-2 cells

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Journal of Traditional Chinese Medicine 2013年第3期33卷 388-393页

作者： Lixia Yang Xinhuan Ma Tao Cheng Tonghua Liu Lili Wu Wen Sun Margetts Peter joseph Central Laboratory of Gansu Province Academy of Traditional Chinese Medicine Pharmacy Department Gansu Province Hospital of Traditional Chinese Medicine Institute of Traditional Chinese Medicine Information Gansu Province Academy of Traditional Chinese Medicine Science and Technology Department Beijing University of Traditional Chinese Medicine Department of Nephrology St. Joseph's Hospital of McMaster University

OBJECTIVE： To explore the function of Tangnai- kang （TNK） in the prevention and treatment of re- nal interstitial fibrosis through transdifferentiation of the human renal tubular epithelial cell line HK-2 induced bytransforming growth factor-β1 （TGf-β1）. METHODS： HK-2 cells cultured in dulbecco＇s modi- fied eagle medium/f12 （1：1） with 10% fetal calf se- rum were divided into six groups： blank control group, TGf-β1 group （TGf-β1 10 ng/mL）, serum con- trol group （TGf-β1 10 ng/mL ＋ 10% serum）, treat- ment group 1 （TGf-β1 10 ng/mL ＋ 5% TNK serum）, treatment group 2 （TGf-β1 10 ng/mL＋10% TNK se-rum）, and treatment group 3 （TGf-β1 10 ng/mL＋ 20% TNK serum）. Cell proliferation was detected by 4,5-Dimethylthiazol-2-yl）-2,5-diphenyltetrazoliu m bromide assay. Expression of a-smooth muscle ac- tin （a-SMA） and E-cadherin were observed by im- munohistochemical assay. The contents of collagen Ⅰ （Col Ⅰ）, collagen Ⅲ（ColⅢ）, and fibronectin （fN） in the culture medium supernatant were detected by ELISA. RESULTS： E-cadherin was expressed and α-SMA was not expressed in normal HK-2 cells. In HK-2 cells cultured with TGf-β1, α-SMA expression signifi- cantly increased, HK-2 cells significantly proliferat- ed, and secretion of Col Ⅰ, Col Ⅲ, and fN significantly increased compared with the blank control group （all P〈0.05）. In the HK-2 cells cultured with TGf-β1 and TNK serum, the expression of α-SMA signifi- cantly decreased, the expression of E-cadherin sig- nificantly increased, and the cell proliferation and the secretion of Col Ⅰ, Col Ⅲ and fN were significant- ly inhibited compared with the TGf-β1 group （all P〈 0.05. CONCLUSION： TNK can inhibit cell proliferation and reduce secretion of Col Ⅰ, Col Ⅲ, and *** in- dicates that TNK can inhibit transdifferentiation of human renal tubular epithelial cells induced by TGf-β1, with the effect of preventing and treating renal interstitial fibrosis.

关键词： Transforming growth factor beta 1 Epi-thelial cells Cell proliferation Cell Transdifferentia-tion Tangnaikang

Hypoestoxide inhibits tumor growth in the mouse CT26 colon tumor model

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World Journal of Gastroenterology 2007年第34期13卷 4586-4588页

作者： Emmanuel A Ojo-Amaize Howard B Cottam Olusola A Oyemade joseph I Okogun Emeka J Nchekwube Immune Modulation Inc. 2273B South Cactus Avenue Bloomington California 92316 United States

AIM: To evaluate the effect of the natural diterpenoid, hypoestoxide (HE) on the growth of established colon cancer in mice. METHODS: The *** mouse colon carcinoma cell line was grown and expanded in vitro. following the expansion, BALB/c mice were inoculated s.c. with viable tumor cells. After the tumors had established and developed to about 80-90 mm3, the mice were started on chemotherapy by oral administration of HE, 5-fluorouracil (5-fU) or combination. RESULTS: The antiangiogenic HE has previously been shown to inhibit the growth of melanoma in the B16f1 tumor model in C57BL/6 mice. Our results demonstrate that mean volume of tumors in mice treated with oral HE as a single agent or in combination with 5-fU, were significantly smaller (> 60%) than those in vehicle control mice (471.2 mm3 vs 1542.8 mm3, P ficant reductions in tumor burden resulted in pronounced mean survival times (MST) and increased life spans (ILS) in the treated mice. CONCLUSION: These results indicate that HE is an effective chemotherapeutic agent for colorectal cancer in mice and that HE may be used alone or in combination with 5-fU.

关键词： Hypoestoxide 5-fluorouracil Colon, Cancer Mice

Expansion of GARP-Expressing CD4^(+)CD25^(-)foxP3^(+)T Cells and SATB1Association with Activation and Coagulation in Immune Compromised HIV-1-Infected Individuals in South Africa

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Virologica Sinica 2021年第5期36卷 1133-1143页

作者： Eman Teer Danzil E.joseph Leanne Dominick Richard H.Glashoff M.faadiel Essop Centre for Cardio-Metabolic Research in Africa(CARMA) Department of Physiological SciencesStellenbosch UniversityStellenbosch 7600South Africa Division of Medical Microbiology and Immunology Department of PathologyStellenbosch University and NHLSCape Town 7505South Africa

Although antiretroviral treatment lowers the burden of human immunodeficiency virus(HIV)-related disease,it does not always result in immunological *** manifests as persistent chronic inflammation,immune activation or exhaustion that can promote the onset of *** the exact function of regulatory T(Treg)cells in HIV remains unclear,this cross-sectional study investigated three expression markers(forkhead box protein P3[fOXP3],glycoprotein A repetitions predominant[GARP],special AT-rich sequence binding protein 1[SATB1])and compared their expansion between CD4^(+)CD25^(-)and CD4^(+)CD25^(++)T ***-matched study subjects were recruited(Western Cape,South Africa)and sub-divided:HIV-negative subjects(n=12),HIV-positive na(i|")ve treated(n=22),HIV-positive treated based on CD4 count cells/μL(CD4>500 and CD41000)(n=34).Markers of immune activation(CD38)and coagulation(CD142)on T cells(CD8)were assessed by flow cytometry together with fOXP3,GARP and SATB1 expression on CD4^(+)CD25^(-)and CD4^(+)CD25^(++)T *** levels of interleukin-10(IL-10;anti-inflammatory marker),IL-6(inflammatory marker)and D-dimer(coagulation marker)were *** study revealed three major findings in immuno-compromised patients with virological failure(CD41000):(1)the expansion of the unconventional Treg cell subset(CD4^(+)CD25^(-)fOXP3^(+))is linked with disease progression markers;(2)increased GARP expression in the CD4^(+)CD25^(-)and CD4^(+)CD25^(++)subsets;and(3)the identification of a strong link between CD4^(+)CD25^(-)SATB1+cells and markers of immune activation(CD8^(+)CD38^(+))and coagulation(CD8^(+)CD142^(+)and D-dimer).

关键词： Human immunodeficiency virus(HIV) Regulatory T cells(Treg) Immune activation Progression markers Glycoprotein A repetitions predominant(GARP) forkhead box protein P3(fOXP3)

Initial Experience with Tricortical Iliac Crest Bone Graft and Human Amniotic Allograft in Evans Calcaneal Osteotomy

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Stem Cell Discovery 2015年第2期5卷 11-17页

作者： J. joseph Anderson Adam f. Gough Myron H. Hansen Zflan Swayzee New Mexico Bone & Joint Institute Alamogordo NM USA Silver Medicine Group Silver City NM USA Cactus foot & Ankle Gilbert AZ USA

Background: Adult acquired flatfoot deformity is generally mediated with an Evans procedure where a wedge of bone is placed into the calcaneus to better align the foot and decrease the deformity. The purpose of this study was to assess the efficacy and safety of human amniotic allograft applied to allogeneic tri-cortical grafts in Evans calcaneal osteotomy. Methods: The medical records of patients who had Evans calcaneal osteotomy with implantation of tri-cortical iliac crest bone graft with human anmiotic allograft for surgical management of adult acquired flatfoot deformity with 2 years follow-up data were reviewed. Results: A total of 63 patients (mean age: 33.3 yr, range: 18 - 66 yr) were enrolled with adult acquired flatfoot deformity. Median time to weight-bearing was 6 weeks. Time to wearing normal shoes was 10 weeks, and time to radiographic healing was 16 weeks. Conclusions: The use of human amniotic allograft did not diminish the long term outcome of procedure or the short term benchmarks for healing after surgery. There were no nonunion, wound dehiscence, infection, or allergic or immune reaction reported. This retrospective study demonstrated that tri-cortical iliac crest bone graft and HAA could be safely used in Evans calcaneal osteotomy with favorable results.

关键词： Adult Acquired flatfoot Deformity Bone Graft Calcaneal Osteotomy Evans Procedure Human Amniotic Allograft

Regional TEC modelling over Africa using deep structured supervised neural network

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Geodesy and Geodynamics 2020年第5期11卷 367-375页

作者： Mefe Moses joseph Danasabe Dodo Lazarus Mustapha Ojigi Kola Lawal Department of Geomatics Ahmadu Bello UniversityZariaKadunaNigeria Centre for Geodesy and Geodynamics NASRDAToroBauchi StateNigeria

A deep structured supervised neural network(NN) model has been developed for modelling of ionospheric vertical total electron content(VTEC) using observations from over 100 Global Navigation Satellite System continuously operating reference stations(GNSS CORS) across Africa. The study covers all available data during low, moderate and declining phases of solar cycle 24, from 2009 to 2017. Optimal network parameters combination for the regional model includes a combination of spatio-temporal parameters(latitude, longitude, year, day of the year, hour), geomagnetic and solar parameters(f10.7, AE,Dst indices), hidden layer of 20 neurons and a feedforward network with Levenberge Marquardt backpropagation algorithm. The validation and the test curves do not indicate overfitting and the performance curves of the training, validation and test data show a very similar trend. Thus, the performance of the optimal network with learning data is in sync with the data not assimilated in the learning *** African Regional Ionospheric Tec Model(ARITM) developed in this study reproduces the known spatiotemporal features of the equatorial and low-latitudes ionosphere quite well. The ARITM performs well to a considerably high degree of precision within the Africa region by comparison with the global ionospheric maps(GIMs) and the formosa Satellite-3 Constellation Observing System for Meteorology,Ionosphere & Climate(fORMOSAT-3/COSMIC) observations. The results suggest that the developed model can efficiently be adopted as a substitute for single station ionospheric model for any single GNSS station within Africa, avoiding the need for developing independent multiple single station ionospheric models for each of the existing and future GNSS stations within the African region.

关键词： latitude Regional equatorial

Microsoft Office Professional edition 2003

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Microsoft Office Professional edition 2003