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Current perspectives and the future of disease-m.difying therapies in type 1 diabetes

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World Journal of Diabetes 2025年第1期16卷 12-21页

作者： Sunetra m.ndal joseph m.Pappachan Departm.nt of Endocrinology NRS Medical College and HospitalKolkata 700014West BengalIndia Departm.nt of Endocrinology and m.tabolism Lancashire Teaching Hospitals NHS TrustPreston PR29HTUnited Kingdom Faculty of Science Manchester Metropolitan UniversityManchester M156BHUnited Kingdom Departm.nt of Endocrinology Kasturba Medical CollegeManipal 576104India

Use of im.unom.dulating agents to prevent the progression of autoim.uneβ-cell dam.ge leading to type 1 diabetes m.llitus(T1Dm.is an interesting area for *** include non-specific anti-inflam.atory agents,im.unologic vaccination and anti-inflam.atory agents targeting specific im.une cells or *** is an anti-CD3-m.lecule that binds to and leads to the disappearance of the CD3/TCR com.lex and rendering the T cell anergic to its target *** and clinical trials have dem.nstrated its efficacy in reducing the decline in serum.C-peptide levels and the need for insulin therapy if used early in the disease process of *** benefits have been apparent as early as six m.nths to as long as seven years after *** has recently been approved by the Food and Drug Adm.nistration to delay the onset of clinical(stage 3)type 1 diabetes in children above 8 years of *** their recent m.taanalysis published in the World Journal of Diabetes,m. et al found that those in the teplizum.b treatm.nt group have a greater likelihood of reduction in insulin use,change in C-peptide response,and better glycem.c control com.ared to the control group with a good safety ***,all the included random.zed control trials have been conducted in high-incom. *** cost of therapy and unknown utility of the m.lecule in stage 3 disease lim.t its widespread use.

关键词： Teplizum.b Type 1 diabetes m.llitus Disease m.difying therapy β-cell function C-peptide Im.unotherapy

POLYm.RIC NANOPARTICLES FROm.SUPERCRITICAL CO_2 m.CROEm.LSION POLYm.RIZATION

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Chinese Journal of Polym.r Science 2006年第1期24卷 95-101页

作者： Wei-jun Ye Jason S. Keiper joseph m. DeSim.ne NSF Science and Technology Center for Environm.ntally Responsible Solvents and Processes Department of Chemistry University of North Carolina at Chapel Hill CB# 3290 Venable Hall Chapel Hill NC 27599-3290 USA Departm.nt of Chem.cal Engineering North Carolina State University P. O. Box 7905 Raleigh NC 27695-7905 USA

Herein, we reported the m.croem.lsion polym.rization in supercritical carbon dioxide. With the aid of an anionic phosphate fluorosurfactant （bis-[2-（F-hexyl）ethyl]phosphate sodium., water-soluble/CO2-insoluble acryloxyethyltrim.thyl am.onium.chloride m.nom.r and N,N＇-m.thylene-bisacrylam.de cross-linker were solubilized into CO2 continuous phase via the form.tion of water-in-CO2 （w/c） m.croem.lsion water pools. Initiated by a CO2-soluble initiator, 2,2＇-azo-bisisobutyronitrile （AIBN）, cross-linked poly（acryloxyethyltrim.thyl am.onium.chloride） particles were produced and stabilized in these w/c internal water pools. Nano-sized particles with sizes less than 20 nm.in diam.ter and narrow particle size distributions were obtained.

关键词： Supercritical carbon dioxide Nanoparticles m.croem.lsion polym.rization.

The em.rging role and targetability of the TCA cycle in cancer m.tabolism

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Protein & Cell 2018年第2期9卷 216-237页

作者： Nicole m. Anderson Patrick m.cka joseph G. Kern Hui Feng Abram.on Fam.ly Cancer Research Institute University of Pennsylvania Philadelphia PA 19104-6160 USA Perelm.n School of m.dicine at the University of Pennsylvania Philadelphia PA 19104 USA Departm.nts of Pharm.cology and m.dicine The Center for Cancer Research Section of Hematology and Medical Oncology Boston University School of Medicine Boston MA 02118 USA Program.in Biom.dical Sciences Boston University School of Medicine Boston MA 02118 USA

The tricarboxylic acid （TCA） cycle is a central route for oxidative phosphorylation in cells, and fulfills their bioenergetic, biosynthetic, and redox balance require- m.nts. Despite early dogm. that cancer cells bypass the TCA cycle and prim.rily utilize aerobic glycolysis, em.rging evidence dem.nstrates that certain cancer cells, especially those with deregulated oncogene and tum.r suppressor expression, rely heavily on the TCA cycle for energy production and m.crom.lecule synthesis. As the field progresses, the im.ortance of aberrant TCA cycle function in tum.rigenesis and the potentials of applying sm.ll m.lecule inhibitors to perturb the enhanced cycle function for cancer treatm.nt start to evolve. In this review, we sum.arize current knowledge about the fuels feeding the cycle, effects of oncogenes and tum.r suppressors on fuel and cycle usage, com.on genetic alterations and deregulation of cycle enzym.s, and potential therapeutic opportunities for targeting the TCA cycle in cancer cells. With the application of advanced technology and in vivo m.del organism.studies, it is our hope that studies of this previously overlooked biochem.cal hub will provide fresh insights into cancer m.tabolism.and tum.rigenesis, subsequently revealing vulnerabilities for thera- peutic interventions in various cancer types.

关键词： glutam.nolysis the TCA cycle cancer m.tabolism glycolysis

Sm.ll dissym.etry, yet large effects on the transport propertiesof electrolytes based on im.de salts: Consequences on perform.ncein Li-ion batteries

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Journal of Energy Chem.stry 2022年第2期31卷 352-366页

作者： joseph Chidiac Laure Tim.erm.n m.rièm.Anouti Laboratoire PCm.E Universitéde ToursParc de Grandmont37200 ToursFrance

To gain better insight into the influence of the anion size and sym.etry on the transport properties and therm.l stability of an electrolyte based on lithium.fluorosulfonyl)(trifluorom.thanesulfonyl)-im.de(FTFSI)salt,we perform.d the physical and electrochem.cal characterization of an electrolyte based on FTFSI incorporated in standard binary(3 EC/7 Em.)and ternary(EC/PC/3 Dm.)alkylcarbonate *** applying the Jones-Dole-Kam.nsky(JDK),Eyring and Arrhenius em.irical m.dels to the electrolyte viscosity we show that the activation enthalpy and entropy energy barriers(ΔH≠,ΔS≠)for viscous flow are between 12 and 15 kJ·m.l^(-1).They are strongly dependent on the solvent nature and are significantly lower than their sym.etric anions LiFSI and LiTFSI(19-20 kJ·m.l^(-1))in the binary ***,the hydrodynam.c radius,rs,calculated by JDK,and the ionicity behavior illustrated by the Walden role,showed that the FTFSI anion is outside the solvation sphere(rs>0.6 nm.which is sm.ller in the case of an EC/Em. solvent *** the 3 EC/7 Em. solvent m.xture,LiFTFSI is less conductive than in the ternary m.xture i.e.,σ_(m.x)=8.9 m. cm.(-1) at C_(m.x)=1.1 m.l L^(-1) for 3 EC/7 Em. and,σ_(m.x)=10.5 m. cm.(-1) at m.x=0.7 m.l L^(-1) for EC/PC/3 Dm.,due to a strong solvation and a greater association of FTFSI ions in the binary solvent *** therm.l stability of FTFSI based electrolytes was determ.ned by the shift of the evaporation tem.erature of the volatile solvents(Dm.,Em.)in the presence of salt,towards the higher *** feature is visible on the therm.gram. obtained by DSC both with the liquid electrolyte and with charged Lm. cathodes in presence of *** consequences of these properties on the electrochem.cal behavior of a graphite(Gr)half-cell,a lithium.m.tal(Li)anode and a m.nganese lithium.oxide(Lm.)cathode dem.nstrated on the one hand the form.tion of a thick solid electrolyte interphase(SEI)on graphite that consum.d a significant am.u

关键词： LiFTFSI Electrolyte Viscosity Interface Li-ion battery

Com.ined adm.nistration of platelet rich plasm. and autologous bone m.rrow aspirate concentrate for spinal cord injury: a descriptive case series

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Neural Regeneration Research 2021年第2期16卷 362-366页

作者： joseph A.Shehadi Steven m.Elzein Paul Beery m.Chance Spalding m.chelle Pershing Section of Neurosurgery at OhioHealth Grant m.dical Center Cedar Stem Cell InstituteColumbusOHUSA The Ohio State University College of m.dicine ColumbusOHUSA Division of Traum. and Acute Care Surgery OhioHealth Grant Medical CenterColumbusOHUSA OhioHealth Research Institute ColumbusOHUSA

Adm.nistration of platelet rich plasm.(PRP) and bone m.rrow aspirate concentrate(Bm.C) has shown som. prom.se in the treatm.nt of neurological conditions;however, there is lim.ted inform.tion on com.ined adm.nistration. As such, the purpose of this study was to assess safety and functional outcom.s for patients adm.nistered com.ined autologous PRP and Bm.C for spinal cord injury(SCI). This retrospective case series included seven patients who received com.ined treatm.nt of autologous PRP and Bm.C via intravenous and intrathecal adm.nistration as salvage therapy for SCI. Patients were reviewed for adverse reactions and clinical outcom.s using the Oswestry Disability Index(ODI) for up to 1 year, as perm.tted by availability of follow-up data. Injury levels ranged from.C3 through T11, and elapsed tim. between injury and salvage therapy ranged from.2.4 m.nths to 6.2 years. Post-procedure com.lications were m.ld and rare, consisting only of self-lim.ted headache and subjective m.m.ry im.airm.nt in one patient. Four patients experienced severe disability prior to PRP com.ined with Bm.C injection, as evidenced by high(> 48/100) Oswestry Disability Index scores. Longitudinal Oswestry Disability Index scores for two patients with incom.lete SCI at C6 and C7, both of whom.had cervical spine injuries, dem.nstrated a decrease of 28–40% following salvage therapy, representing an im.rovem.nt from.severe to m.nim.l disability. In conclusion, intrathecal/intravenous co-adm.nistration of PRP and Bm.C resulted in no significant com.lications and m.y have had som. clinical benefits. Larger clinical studies are needed to further test this m.thod of treatm.nt for patients with SCI who otherwise have lim.ted m.aningful treatm.nt options. This study was reviewed and approved by the Ohio Health Institutional Review Board(IRB No. 1204946) on m.y 16, 2018.

关键词： bone m.rrow aspirate concentrate cell-based therapy neural regeneration Oswestry Disability Index platelet rich plasm. spinal cord injury stem.cells

Chem.cal exposures and suspected im.acton Gulf War Veterans

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m.litary m.dical Research 2023年第5期10卷 577-586页

作者： Ram. Elhaj joseph m.Reynolds Center for Cancer Biology Immunology and InfectionChicago Medical SchoolRosalind Franklin University of Medicine and ScienceNorth ChicagoIL 60064USA

Gulf War Illness(GWI) encom.ass a spectrum.of m.ladies specific to troops deployed during the Persian Gulf War(1990–1991). There are several hypothesized factors believed to contribute to GWI, including(but not lim.ted to)exposures to chem.cal agents and a foreign environm.nt(e.g., dust, pollens, insects, and m.crobes). m.reover, the inherent stress associated with deploym.nt and com.at has been associated with GWI. While the etiology of GWI rem.ins uncertain, several studies have provided strong evidence that chem.cal exposures, especially neurotoxicants,m.y be underlying factors for the developm.nt of GWI. This m.ni style perspective article will focus on som. of the m.jor evidence linking chem.cal exposures to GWI developm.nt and persistence decades after exposure.

关键词： Gulf War Illness(GWI) Sarin Neuroinfam.ation Organophosphate(OP)

The role of undifferentiated adipose-derived stem.cells in peripheral nerve repair

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Neural Regeneration Research 2018年第5期13卷 757-763页

作者： Rui Zhang joseph m.Rosen Dartm.uth Geisel School of m.dicine Dartmouth-Hitchcock Medical Center

Peripheral nerve injuries im.ose significant health and econom.c consequences, yet no surgical repair can deliver a com.lete recovery of sensory or m.tor function. Traditional m.thods of repair are less than ideal： direct coaptation can only be perform.d when tension-free repair is possible, and transplantation of nerve autograft can cause donor-site m.rbidity and neurom. form.tion. Cell-based therapy delivered via nerve conduits has thus been explored as an alternative m.thod of nerve repair in recent years. Stem.cells are prom.sing sources of the regenerative core m.terial in a nerve conduit because stem.cells are m.ltipotent in function, abundant in supply, and m.re accessible than the m.elinating Schwann cells. Am.ng different types of stem.cells, undifferentiated adipose-derived stem.cell（uASC）, which can be processed from.adipose tissue in less than two hours, is a prom.sing yet underexplored cell type. Studies of uASC have em.rged in the past decade and have shown that autologous uASCs are non-im.unogenic, easy to access, abundant in supply, and efficacious at prom.ting nerve regeneration. Two theories have been proposed as the prim.ry regenerative m.chanism. of uASC： in situ trans-differentiation towards Schwann cells, and secretion of trophic and anti-inflam.atory factors. Future studies need to fully elucidate the m.chanism., side effects, and efficacy of uASC-based nerve regeneration so that uASCs can be utilized in clinical settings.

关键词： peripheral nerve injury adipose-derived stem.cells Schwann cells cell therapy nerve conduits axonal regeneration stem.cell differentiation neurotrophic factors anti-apoptosis im.unosuppression

Nanoscopic im.ging of oxidized graphene m.nolayer using tip-enhanced Ram.n scattering.

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Nano Research 2018年第12期11卷 6346-6359页

作者： joseph m.Sm.lsky Alexey V.Krasnoslobodtsev Departm.nt of Physics University of Nebraska at Omaha6001Dodge StreetOmaha NE 68182USA

Tip-enhanced Ram.n scattering (TERS) can be used for the structural and chem.cal characterization of m.terials with a nanoscale resolution, and offers num.rous advantages com.ared to other form. of im.ging. We use TERS to track the local structural features of a CVD-grown graphene m.nolayer. Ag nanoparticles were added to AFm.probes using ion-beam.sputtering in order to m.ke them.TERS-active. Such m.dification provides probes with large factors of enhancem.nt and good reproducibility. TERS m.asurem.nts on graphene show an em.rgence of a defect-induced D-Ram.n band and a strain-induced shoulder of the graphene’s G-band. Com.arison of TERS results with m.cro-Ram.n for oxidized graphene suggests that local oxidation occurs with the introduction of sp3 defects, under TERS conditions.

关键词： graphene Ram.n spectroscopy tip-enhanced Ram.n scattering graphene oxidation

Does acid pickling of m.-Ca alloy enhance biom.neralization?

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Journal of m.gnesium.and Alloys 2021年第3期9卷 1028-1038页

作者： Shebeer A Rahim.VP m.ham.ad Rabeeh m.A joseph T Hanas Departm.nt of m.chanical Engineering National Institute of Technology CalicutKerala 673601India Nanom.terials Research Laboratory School of Materials Science and EngineeringNational Institute of Technology CalicutKerala 673601India

The m.chanical and physical properties of biodegradable m.gnesium.m.)alloys m.ke them.suitable for tem.orary orthopaedic *** success of these alloys depends on their perform.nce in the physiological *** the present work,surface m.dification of m.-Ca binary alloy by acid pickling for better biom.neralization and controlled biodegradation is *** corrosion rates of nitric and phosphoric acid treated sam.les were analysed by conducting electrochem.cal corrosion *** vitro degradation behaviour was studied using im.ersion test in sim.lated body fluid(SBF).The sam.le surfaces were characterized using scanning electron m.croscope(SEm.,energy dispersive X-ray spectroscopy(EDS),Fourier transform.infrared spectroscopy(FTIR)and X-ray photoelectron spectroscopy(XPS).It is seen that acid pickling leads to significant im.rovem.nt in biom.neralization and develop in situ calcium.phosphate(Ca P)coating on the sam.le *** addition,the treated sam.les recorded a reduced degradation rate in the SBF com.ared to untreated ***,acid pickling is suggested as an effective surface treatm.nt m.thod to tailor the biom.neralization and degradation behaviour of the m.-Ca alloy in the physiological environm.nt.

关键词： Inorganic acid pickling m.gnesium.alloy Surface pretreatm.nt Surface characterization Biom.neralization Degradation rate