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Nucleoside modified mRNA-lipid nanoparticles as a new delivery platform for the repair of the injured spinal cord

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Neural Regeneration Research 2025年第8期20卷 2311-2312页

作者： Krisztián Pajer Tamás Bellák antal Nógrádi Department of Anatomy Histology and EmbryologyAlbert Szent-Györgyi Medical SchoolUniversity of SzegedSzegedHungary

Spinal cord injury and treatment opportunities:The adult mammalian spinal cord has a very limited capacity for spontaneous regeneration due to various intrinsic molecular and cellular *** the spinal cord neurons have the capacity to regenerate their axons,the expression of growth inhibitory factors,lack or suppression of proper guidance cues,and profound inflammatory responses do not permit successful regeneration(Khyeam et al.,2021).

关键词： injured capacity modified

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 Nógrádi 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

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

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 Nógrádi 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

Dental evaluation is helpful in the differentiation of functional heartburn and gastroesophageal reflux disease

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世界胃肠病学杂志:英文版 2023年第31期29卷 4774-4782页

作者： Krisztina Helle Anna ZsófiaÁrok Georgina Ollé Márk antal András Rosztóczy Department of Internal Medicine Division of GastroenterologyUniversity of SzegedSzeged 6725Hungary Department of Operative and Esthetic Dentistry University of SzegedSzeged 6725Hungary

BACKGROUND Heartburn is identically the key symptom of both,gastroesophageal reflux disease(GERD)and functional heartburn(FHB),making the differential diagnosis *** manifestations of GERD can be easily examined;therefore,their exploration might be a cheap,widely available,and useful tool in the differentiation of GERD and *** To evaluate the prevalence of dental erosions(DE)and periodontal diseases(PD)in patients with heartburn and their association with GERD and *** A total of 116[M/F:51/65,mean age:54(17-80)years]consecutive patients with heartburn were enrolled for detailed esophageal function and orodental *** Dental disorders were detected in 89%(103/116).Patients with PD+DE had significantly more often pathologic reflux(90.0%vs 27.8%;P<0.05),higher esophagitis scores(1.8 vs 0.9;P<0.05),and a significantly different mean impedance curve(P=0.04)than those without any dental *** opposite approach established that patients with GERD had significantly higher prevalence of DE and PD,especially if both were present(28.9%vs 2.0%;P<0.01),more severe PD(1.5 vs 1.0;P<0.01),and longer history of heartburn(15 years vs 9 years;P<0.01)than those with *** The dental evaluation of patients with heartburn seems to be useful in the differential diagnosis of GERD and *** the studied parameters,the co-appearance of DE and PD seems to be the best predictor of GERD,whereas the absence of dental disorders was mostly observed in FHB.

关键词： Gastroesophageal reflux disease Gastric acid Heartburn Differential diagnosis Epidemiology Oral manifestations Prevalence Risk factors Dental erosion Periodontal diseases

Gut barrier failure biomarkers are associated with poor disease outcome in patients with primary sclerosing cholangitis

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World Journal of Gastroenterology 2017年第29期23卷 5412-5421页

作者： Tamas Tornai Eszter Palyu Zsuzsanna Vitalis Istvan Tornai David Tornai Peter antal-Szalmas Gary L Norman Zakera Shums Gabor Veres antal Dezsofi Gabriella Par Alajos Par Peter Orosz Ferenc Szalay Peter laszlo lakatos Maria Papp Institute of Internal Medicine Department of Gastroenterology University of Debrecen Faculty of Medicine Department of laboratory Medicine University of Debrecen Faculty of Medicine Debrecen Inova Diagnostics Inc.San Diego 1^st Department of Pediatrics Semmelweis University 1^st Department of Medicine University of Pecs Gastroenterology Department of Medicine Borsod-Abauj Zemplen County Hospital 1^st Department of Medicine Semmelweis University

To assess the prevalence of a panel of serologic markers that reflect gut barrier dysfunction in a mixed cohort of pediatric and adult primary sclerosing cholangitis (PSC) patients. METHODSSera of 67 PSC patients [median age (range): 32 (5-79) years, concomitant IBD: 67% and cirrhosis: 20%] were assayed for the presence of antibodies against to F-actin (AAA IgA/IgG) and gliadin (AGA IgA/IgG)] and for serum level of intestinal fatty acid-binding protein (I-FABP) by ELISA. Markers of lipopolysaccharide (LPS) exposure [LPS binding protein (LBP)] and various anti-microbial antibodies [anti-OMP Plus IgA and endotoxin core IgA antibody (EndoCAb)] were also determined. Poor disease outcome was defined as orthotopic liver transplantation and/or liver-related death during the follow-up [median: 99 (14-106) mo]. One hundred and fifty-three healthy subjects (HCONT) and 172 ulcerative colitis (UC) patients were the controls. RESULTSA total of 28.4%, 28.0%, 9% and 20.9% of PSC patients were positive for AAA IgA, AAA IgG, AGA IgA and AGA IgG, respectively. Frequencies of AAA IgA and AAA IgG (P AAA IgA posvsneg: 365 vs 166 pg/mL, P = 0.011), but not with serum LBP level. CONCLUSIONPresence of IgA type AAA identified PSC patients with progressive disease. Moreover, it is associated with enhanced mucosal immune response to various micr

关键词： Primary sclerosing cholangitis Gut barrier dysfunction Intestinal fatty acid-binding protein Anti-F-actin antibody Anti-gliadin antibody

Presepsin teardown- pitfalls of biomarkers in the diagnosis and prognosis of bacterial infection in cirrhosis

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World Journal of Gastroenterology 2016年第41期22卷 9172-9185页

作者： Maria Papp Tamas Tornai Zsuzsanna Vitalis Istvan Tornai David Tornai Tamas Dinya Andrea Sumegi Peter antal-Szalmas Department of Internal Medicine Division of Gastroenterology University of Debrecen Faculty of Medicine Department of laboratory Medicine University of Debrecen Faculty of Medicine Debrecen Institute of Surgery University of Debrecen Faculty of Medicine Vascular Biology Thrombosis and Haemostasis Research Group Hungarian Academy of Sciences

AIM To evaluate the diagnostic and prognostic value of presepsin in cirrhosis-associated bacterial infections. METHODS Two hundred and sixteen patients with cirrhosis were enrolled. At admission, the presence of bacterial infections and level of plasma presepsin, serum C-reactive protein(CRP) and procalcitonin(PCT) were evaluated. Patients were followed for three months to assess the possible association between presepsin level and short-term *** Present 34.7 of patients had bacterial infection. Presepsin levels were significantly higher in patients with infection than without(median, 1002 pg/m L vs 477 pg/m L, P lar to PCT and superior to CRP(AUC-ROC: 0.85, 0.85 and 0.66, respectively, P = NS for presepsin vs PCT and P 1206 pg/m L sensitivity, specificity, positive predictive values and negative predictive values were as follows: 87.5%, 74.5%, 61.8% and 92.7%. The accuracy of presepsin, however, decreased in advanced stage of the disease or in the presence of renal failure, most probably because of the significantly elevated presepsin levels in non-infected patients. 28-d mortality rate was higher among patients with > 1277 pg/m L compared to those with ≤ 1277 pg/m L(46.9% vs 11.6%, P < 0.001). In a binary logistic regression analysis, however, only PCT(OR = 1.81, 95%CI: 1.09-3.01, P = 0.022) but neither presepsin nor CRP were independent risk factor for 28-d mortality after adjusting with MELD score and leukocyte *** Presepsin is a valuable new biomarker for defining severe infections in cirrhosis, proving same efficacy as PCT. However, it is not a useful marker of short-term mortality.

关键词： Presepsin Cirrhosis Bacterial infection Organ failure Mortality