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Silk-based nerve guidance conduits with macroscopic holes modulate the vascularization of regenerating rat sciatic nerve

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neural Regeneration Research 2025年第6期20卷 1789-1800页

作者： Carina Hromada Patrick Heimel Markus Kerbl LászlóGál Sylvia nürnberger Barbara Schaedl James Ferguson nicole Swiadek Xavier Monforte Johannes C.Heinzel antal nógr.di Andreas H.Teuschl-Woller David Hercher Department Life Science Engineering University of Applied Sciences Technikum WienViennaAustria Austrian Cluster for Tissue Regeneration ViennaAustria Ludwig Boltzmann Institute for Traumatology The Research Center in Cooperation with AUVAViennaAustria University Clinic of Dentistry Medical University of ViennaViennaAustria Department of Plastic Reconstructive and Aesthetic SurgeryLandesklinikum Wiener Neustadt2700 Wiener NeustadtAustria Department of Anatomy Histology and EmbryologyAlbert Szent-Györgyi Medical SchoolUniversity of SzegedSzegedHungary Medical University of Vienna Department of Orthopedics and Trauma SurgeryDevision of Trauma SurgeryViennaAustria Department of Hand- PlasticReconstructive and Burn SurgeryBG Unfallklinik TuebingenUniversity of TuebingenTuebingenGermany

Peripheral nerve injuries induce a severe motor and sensory deficit. Since the availability of autologous nerve transplants for nerve repair is very limited, alternative treatment strategies are sought, including the use of tubular nerve guidance conduits(tnGCs). However, the use of tnGCs results in poor functional recovery and central necrosis of the regenerating tissue, which limits their application to short nerve lesion defects(typically shorter than 3 cm). Given the importance of vascularization in nerve regeneration, we hypothesized that enabling the growth of blood vessels from the surrounding tissue into the regenerating nerve within the tnGC would help eliminate necrotic processes and lead to improved regeneration. In this study, we reported the application of macroscopic holes into the tubular walls of silk-based tnGCs and compared the various features of these improved silk^(+) tnGCs with the tubes without holes(silk^(–) tnGCs) and autologous nerve transplants in an 8-mm sciatic nerve defect in rats. Using a combination of micro-computed tomography and histological analyses, we were able to prove that the use of silk^(+) tnGCs induced the growth of blood vessels from the adjacent tissue to the intraluminal neovascular formation. A significantly higher number of blood vessels in the silk^(+) group was found compared with autologous nerve transplants and silk^(–), accompanied by improved axon regeneration at the distal coaptation point compared with the silk^(–) tnGCs at 7 weeks postoperatively. In the 15-mm(critical size) sciatic nerve defect model, we again observed a distinct ingrowth of blood vessels through the tubular walls of silk^(+) tnGCs, but without improved functional recovery at 12 weeks postoperatively. Our data proves that macroporous tnGCs increase the vascular supply of regenerating nerves and facilitate improved axonal regeneration in a short-defect model but not in a critical-size defect model. This study suggests that further optimizatio

关键词： axon regeneration blood vessel functional recovery macroporous nerve lesion peripheral nerve repair sciatic nerve silk-based nerve guidance conduit vascularization

The mutual interaction between the host spinal cord and grafted undifferentiated stem cells fosters the production of a lesion-induced secretome

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neural Regeneration Research 2020年第10期15卷 1844-1845页

作者： Krisztián Pajer Tamás Bellák antal nógr.di Department of Anatomy Histology and Embryology Faculty of Medicine University of Szeged

Pathophysiology of spinal cord injury:Injury to the spinal cord results in loss of gray and white matter i.e.,it produces a segmental spinal cord lesion and,as a consequence leads to a fatal loss of motor,sensory and autonomic *** cord injuries in humans and other mammals are not followed by the replacement of lost neurons and oligodendrocytes and regrowth of injured axons,instead they lead to permanent,fatal and incurable functional *** primary physical injury is followed by a cascade of tissue-decaying events,called secondary injury,which leads to ischemia,vascular disruption,neuroinflammation,excitotoxicity,demyelination and death of neurons and glial cells(Silva et al.,2014;Figure 1A).The direct mechanical disruption of the vasculature results in the increased permeability of the blood-spinal cord *** to the leakiness of blood-spinal cord barrier and production of cytokines by activated microglia,a number of various immune cells(T lymphocytes,neutrophils and monocytes)invade the injury *** macrophages generate a set of inflammatory cytokines such as tumor necrosis factor-α,interleukin(IL)-1α,IL-1β,and IL-6,which may further augment the secondary events(Ahuja et al.,2017).In addition,a number of other disruptive processes contribute to the heterogeneous and time-sensitive pathophysiology of spinal cord injury.

关键词： mutual Figure injuries

Restoration of Motor Function through Delayed Intraspinal Delivery of Human IL-10-Encoding nucleoside-Modified mRnA after Spinal Cord Injury

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Research 2023年第4期2023卷 131-144页

作者： LászlóGál Tamás Bellák Annamária Marton Zoltán Fekécs Drew Weissman Dénes Török Rachana Biju Csaba Vizler Rebeka Kristóf Mitchell B.Beattie Paulo J.C.Lin norbert Pardi antal nógr.di Krisztián Pajer Department of Anatomy Histology and EmbryologyAlbert Szent-Györgyi Medical SchoolUniversity of SzegedSzegedHungary national Biotechnology Laboratory Institute of GeneticsBiological Research CentreSzegedHungary Institute of Biochemistry Biological Research CentreSzegedHungary Department of Medicine University of PennsylvaniaPhiladelphiaPA19104USA Acuitas Therapeutics VancouverBCV6T 1Z3Canada

Efficient in vivo delivery of anti-inflammatory proteins to modulate the microenvironment of an injured spinal cord and promote neuroprotection and functional recovery is a great ***-modified messenger RnA(mRnA)has become a promising new modality that can be utilized for the safe and efficient delivery of therapeutic ***,we used lipid nanoparticle(LnP)-encapsulated human interleukin-10(hIL-10)-encoding nucleoside-modified mRnA to induce neuroprotection and functional recovery following rat spinal cord contusion *** administration of hIL-10 mRnA-LnP to rats led to a remarkable reduction of the microglia/macrophage reaction in the injured spinal segment and induced significant functional recovery compared to ***,hIL-10 mRnA treatment induced increased expression in tissue inhibitor of matrix metalloproteinase 1 and ciliary neurotrophic factor levels in the affected spinal segment indicating a time-delayed secondary effect of IL-105 d after *** results suggest that treatment with nucleoside-modified mRnAs encoding neuroprotective factors is an effective strategy for spinal cord injury repair.

关键词： protective Restoration utilized

Reversibility of visual field defects through induction of brain plasticity: vision restoration, recovery and rehabilitation using alternating current stimulation

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neural Regeneration Research 2020年第10期15卷 1799-1806页

作者： Bernhard A.Sabel Ying Gao Andrea antal Institute of Medical Psychology Medical FacultyOtto-von-Guericke University of MagdeburgMagdeburgGermany Center for Behavioral and Brain Sciences(CBBS) MagdeburgGermany Sabel Vision Restoration Center MagdeburgGermany Department of Clinical neurophysiology University Medical Center GottingenGottingenGermany

For decades visual field defects were considered irreversible because it was thought that in the visual system the regeneration potential of the neuronal tissues is ***,there is always some potential for partial recovery of the visual field defect that can be achieved through induction of *** refers to the ability of the brain to change its own functional architecture by modulating synaptic *** is maintained throughout life and just as neurological rehabilitation can improve motor coordination,visual field defects in glaucoma,diabetic retinopathy or optic neuropathy can be improved by inducing *** ophthalmology many new treatment paradigms have been tested that can induce neuroplastic changes,including non-invasive alternating current *** with alternating current stimulation(e.g.,30 minutes,daily for 10 days using transorbital electrodes and^10 Hz)activates the entire retina and parts of the *** and functional magnetic resonance imaging studies revealed local activation of the visual cortex,global reorganization of functional brain networks,and enhanced blood flow,which together activate neurons and their *** future of low vision is optimistic because vision loss is indeed,partially reversible.

关键词： alternating current stimulation glaucoma low vision optic nerve rehabilitation recovery stress vision vision restoration therapy visual field

Budesonide induces complete remission in autoimmune hepatitis

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World Journal of Gastroenterology 2006年第9期12卷 1362-1366页

作者： antal Csepregi Christoph R(o|¨)cken Gerhard Treiber Peter Malfertheiner Department of Gastroenterology Hepatology and Infectious DiseasesOtto-von-Guericke UniversityLeipziger Str 4439120 MagdeburgGermany Institute of Pathology Otto-von-Guericke University Leipziger Str 4439120 MagdeburgGermany

AIM： Prednisone and azathioprine represent the standard treatment for autoimmune hepatitis （AIH）. However, only 65% of the patients enter complete histological remission. Recently, budesonide （BUD） was reported to be a promising alternative. In this study we assessed the efficacy and safety of BUD in AIH. METHODS： Eighteen patients （12 women, 6 men; mean age 45.4±21 years） with AIH were treated with BUD （Budenofalk） 3 mg thrice daily and followed up for at least 24 wk. Seven patients also had features of primary biliary cirrhosis （n = 5） or primary sclerosing cholangitis （n = 2）. Advanced liver fibrosis or cirrhosis was present in RESULTS： Fifteen （83%） patients had a complete clinical and biochemical remission. Ten patients, including five with acute hepatitis, were given BUD as first-line therapy, of which seven enter remission. Three patients, two with liver cirrhosis, did not improve. All patients with second-line therapy experienced long-term remission. A histological remission was also seen in three patients. Clinically relevant BUD-induced side effects were recorded only in patients with liver cirrhosis （n = 4）. COnCLUSIOn： BUD is effective in remission induction in the majority of our patients with AIH. Side effects and treatment failure was mainly observed in patients with liver cirrhosis.

关键词： Budesonide Autoimmune hepatitis Complete remission Adverse events

Acute exacerbation of autoimmune hepatitis induced by Twinrix

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World Journal of Gastroenterology 2005年第26期11卷 4114-4116页

作者： antal Csepregi Gerhard Treiber Christoph R(o|¨)cken Peter Malfertheiner Department of Gastroenterology Hepatology and Infectious Diseases Department of Pathology Otto-von-Guericke University Leipziger Str. 44 Magdeburg 39120 Germany

We report on a 26-year-old man who presented with severe jaundice and elevated serum liver enzyme activities after having received a dose of Twinrix? In his past medical history, jaundice or abnormal liver function tests were never recorded. Following admission, an elevated immunoglobulin G level and antinuclear antibodies at a titer of 320 with a homogenous pattern were found. Histology of a liver biopsy showed marked bridging liver fibrosis and a chronic inflammation, compatible with autoimmune hepatitis. Treatment was started with budesonide and ursodeoxycholic acid, and led to complete normalization of the pathological liver function tests. We believe that Twinrix led to an acute exacerbation of an unrecognized autoimmune hepatitis in our patient. The pathogenesis remains to be clarified. It is tempting to speculate that inactivated hepatitis A virus and/or recombinant surface antigen of the hepatitis B virus -as seen in patients with chronic hepatitis C and unrecognized autoimmune hepatitis who were treated with interferon alpha-might have been responsible for disease exacerbation.

关键词： Twinrix Autoimmune hepatitis Budesonide

Immune dysfunction in cirrhosis

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World Journal of Gastroenterology 2014年第10期20卷 2564-2577页

作者： nora Sipeki Peter antal-Szalmas Peter L Lakatos Maria Papp Institute of Medicine Department of Gastroenterology University of Debrecen H-4032 DebrecenHungary Department of Laboratory Medicine University of Debrecen H-4032 Debrecen Hungary 1st Department of Medicine Semmelweis University H-1083 Budapest Hungary

Innate and adaptive immune dysfunction,also referred to as cirrhosis-associated immune dysfunction syndrome,is a major component of cirrhosis,and plays a pivotal role in the pathogenesis of both the acute and chronic worsening of liver *** the evolution of the disease,acute decompensation events associated with organ failure(s),so-called acute-on chronic liver failure,and chronic decompensation with progression of liver fibrosis and also development of disease specific complications,comprise distinct clinical entities with different immunopathology *** bacterial translocation associated with systemic endotoxemia and increased occurrence of systemic bacterial infections have substantial impacts on both clinical *** and chronic exposure to bacteria and/or their products,however,can result in variable clinical *** immune status of patients is not constant during the illness;consequently,alterations of the balance between pro-and anti-in-flammatory processes result in very different dynamic *** this review we give a detailed overview of acquired immune dysfunction and its consequences for *** demonstrate the substantial influence of inherited innate immune dysfunction on acute and chronic inflammatory processes in cirrhosis caused by the pre-existing acquired immune dysfunction with limited compensatory ***,we highlight the current facts and future perspectives of how the assessment of immune dysfunction can assist clinicians in everyday practical decision-making when establishing treatment and care strategies for the patients with end-stage liver *** and efficient recognition of inappropriate performance of the immune system is essential for overcoming complications,delaying progression and reducing mortality.

关键词： Cirrhosis Immune dysfunction Endotoxemia

Black locust(Robinia pseudoacacia L.)as a multi-purpose tree species in Hungary and Romania:a review

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Journal of Forestry Research 2018年第6期29卷 1449-1463页

作者： Valeriu-norocel nicolescu Cornelia Hernea Beatrix Bakti Zsolt Keseru Borbála antal Károly Rédei Faculty of Silviculture and Forest Engineering Transylvania University of BrassovSirul Beethoven no.1500123 BrasovRomania Faculty of Horticulture and Forestry Banat’s University of Agricultural Sciences and Veterinary Medicine“King Michael I of Romania”from Timi.oaraCalea Aradului 119300645 TimisoaraRomania Department of Plantation Forestry National Agricultural Research and Innovation Centre Forest Research InstituteFarkasszigetPu¨spo¨klada′ny 4150Hungary Hungarian Horticultural Propagation Material non-profit Ltd. Sa′rva′rBudapestHungary

Black locust(Robinia pseudoacacia L.) was the first north-American tree species imported to Europe at the beginning of the seventeenth century. It is commonly planted worldwide because of its adaptability to environmental stresses, its valuable wood, easy propagation, frequent and abundant seed production, excellent coppicing,high seedling survival, and relatively high wood yield. In Europe, Romania and Hungary have the most highly-developed black locust growing techniques and *** a result of increasing interest in black locust in many countries, this review aims to provide a comprehensive overview of state-of-the-art site requirements, propagation, improvement and management(including growth and yield as well as use in energy plantations).

关键词： Robinia pseudoacacia Site requirements Selection Propagation Silviculture

Spontaneous and visible light-induced ultraweak photon emission from rat eyes

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Spontaneous and visible light-induced ultraweak photon emiss...