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relapsing polychondritis with p-ANCA associated vasculitis: Which triggers the other?

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World journal of Clinical Cases 2014年第12期2卷 912-917页

作者： Ibolya File Csilla Trinn Zsolt Mátyus László Ujhelyi józsef Balla jános Mátyus Institute of Internal Medicine University of Debrecen Clinical Centre H-4032 Debrecen Hungary Borsod-Abaúj-Zemplén County and University Teaching Hospital 2nd Department of Internal Medicine H-3526 Miskolc Hungary

relapsing polychondritis(rP) is a rare autoimmune disease with chronic inflammatory/destructive lesions of the cartilaginous tissues. In one third of the cases it is associated with other autoimmune disorders, mostly with anti-neutrophil cytoplasmic antibody(ANCA) associated vasculitis(AAV). We report three cases of rP with p-ANCA positive AAV. In the first patient rP developed 1.5 years after the onset of AAV. In the others the signs of rP were present before the onset of severe crescent glomerulonephritis. Patients responded well on steroid and cyclophosphamide. In dialysis dependent cases plasmapheresis was also used successfully. During the 2 and 1.5 years of follow up, they were symptom-free, and had stable glomerular filtration rate. The first patient died after four years of follow-up due to the complications of sudden unset pancytopenia,which raises the possibility of associated hemophagocytic syndrome. In the setting of rP or AAV physicians should always be aware of the possibility of sudden or insidious appearance of the other disease.

关键词： relapsing polychondritis Anti-neutrophil cytoplasmic antibody Anti-neutrophil cytoplasmic antibody-associated vasculitis rapidly progressive glomerulonephritis Immunosuppressive treatment

Diversity of foliar endophytes in wind-fallen Picea abies trees

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Fungal Diversity 2012年第3期54卷 69-77页

作者： Ondřej Koukol.Miroslav kol.řík Zuzana kol.řová Petr Baldrian Department of Botany Faculty of ScienceCharles University in PragueBenátská212801 Prague 2Czech Republic Laboratory of Genetics Physiology and Bioengineering of FungiInstitute of Microbiology of the ASCRv.v.i.Vídeňská108314220 Prague 4Czech Republic Laboratory of Environmental Microbiology Institute of Microbiology of the ASCRv.v.i.Vídeňská108314220 Prague 4Czech Republic

The unmanaged Norway spruce montane forests in the Bohemian Forest National Park(Czech republic)suffered from repeated large-scale bark beetle outbreaks in last *** this study,the diversity of culturable foliar endophyte microfungi in needles originating from eleven recently wind-fallen trees in this area was *** aims were to describe their diversity and to determine the relative host and organ specificities of isolated endophyte species to estimate the species pool and abundance of foliar endophytes before the forest *** were isolated from surface-sterilized needles,and the outgrowing strains were identified based on morphological and molecular characteristics(analyses of ITS1,ITS2 and partial 28S rDNA).Fungal communities in the needles were diverse,with ascomycetes(mostly anamorphs of Helotiales)dominating *** most frequent species(Phacidiopycnis sp.,Cistella acuum,Sirococcus *** two species of Chalara)did not correspond with those recorded in previous studies of Picea *** example,the widely distributed Lophodermium piceae was rarely recorded in this *** pattern may be caused by different methods of sterilization and cultivation or by physiological characteristics of the needles,or it may reflect the species distribution in the studied *** of the Helotiales,along with sequences from GenBank,showed substantial overlap in host affinities,most prominently between Pinus and Picea,and also among species from distant plant lineages.

关键词： Morphospecies ITS rDNA Culturable microfungi Phacidiopycnis Host affinity

Heterogeneity of mature oligodendrocytes in the central nervous system

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Neural regeneration research 2025年第5期20卷 1336-1349页

作者： Chao Weng Adam M.r.Groh Moein Yaqubi Qiao-Ling Cui jo Anne Stratton G.r.Wayne Moore jack P.Antel Neuroimmunology Unit Montreal Neurological Institute-HospitalDepartment of Neurology and NeurosurgeryMcGill UniversityMontrealQCCanada Department of Neurology Renmin Hospital of Wuhan UniversityWuhanHubei ProvinceChina

Mature oligodendrocytes form myelin sheaths that are crucial for the insulation of axons and efficient signal transmission in the central nervous *** evidence has challenged the classical view of the functionally static mature oligodendrocyte and revealed a gamut of dynamic functions such as the ability to modulate neuronal circuitry and provide metabolic support to *** the recognition of potential heterogeneity in mature oligodendrocyte function,a comprehensive summary of mature oligodendrocyte diversity is *** delve into early 20th-century studies by robertson and río-Hortega that laid the foundation for the modern identification of regional and morphological heterogeneity in mature ***,recent morphologic and functional studies call into question the long-assumed homogeneity of mature oligodendrocyte function through the identification of distinct subtypes with varying myelination ***,modern molecular investigations,employing techniques such as single cell/nucleus rNA sequencing,consistently unveil at least six mature oligodendrocyte subpopulations in the human central nervous system that are highly transcriptomically diverse and vary with central nervous system *** and disease related mature oligodendrocyte variation denotes the impact of pathological conditions such as multiple sclerosis,Alzheimer's disease,and psychiatric ***,caution is warranted when subclassifying mature oligodendrocytes because of the simplification needed to make conclusions about cell identity from temporally confined *** studies leveraging advanced techniques like spatial transcriptomics and single-cell proteomics promise a more nuanced understanding of mature oligodendrocyte *** research avenues that precisely evaluate mature oligodendrocyte heterogeneity with care to understand the mitigating influence of species,sex,central nervous system region,age,and disease,

关键词： aging central nervous system diseases electron microscopy heterogeneity immunohistochemistry myelin sheath natural history neuroglia oligodendroglia single-cell gene expression analysis

Arterial stiffness, vascular calcification and bone metabolism in chronic kidney disease

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World journal of Nephrology 2012年第1期1卷 25-34页

作者： jános Nemcsik István Kiss András Tislér Department of Family Medicine Semmelweis University 1125 Budapest Hungary Division of Angiology and Nephrology Department of Medicine St. Imre Teaching Hospital 1115 BudapestHungary 1st Department of Medicine Semmelweis University 1125 Budapest Hungary

Patients with chronic kidney disease （CKD） have an extremely poor cardiovascular outcome. Arterial stiff-ness, a strong independent predictor of survival in CKD, is connected to arterial media calcification. A huge number of different factors contribute to the increased arterial calcification and stiffening in CKD, a process which is in parallel with impaired bone metabolism. This coincidence was demonstrated to be part of the direct inhibition of calcifcation in the vessels, which is a counterbalancing effect but also leads to low bone turnover. Due to the growing evidence, the defnition of “CKD mineral bone disorder” was created recently, un-derlining the strong connection of the two phenomena. In this review, we aim to demonstrate the mechanisms leading to increased arterial stiffness and the up-to date data of the bone-vascular axis in CKD. We over-view a list of the different factors, including inhibitors of bone metabolism like osteoprotegerin, fetuin-A, pyro-phosphates, matrix Gla protein, osteopontin, fbroblast growth factor 23 and bone morphogenic protein, which seem to play role in the progression of vascular calcif-cation and we evaluate their connection to impaired ar-terial stiffness in the mirror of recent scientifc results.

关键词： Arterial stiffness Vascular calcification Bone metabolism Chronic kidney disease

Clinical significance of granuloma in Crohn's disease

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World journal of Gastroenterology 2005年第20期11卷 3118-3121页

作者： Tamás Molnár László Tiszlavicz Csaba Gyulai Ferenc Nagy jános Lonovics First Department of Medicine Faculty of Medicine University of Szeged H-6720 Szeged Korányi fasor 8. Hungary Department of Pathology Faculty of Medicine University of Szeged H-6720 Szeged Korányi fasor 8. Hungary Department of radiology Faculty of Medicine University of Szeged H-6720 Szeged Korányi fasor 8. Hungary

AIM: Granuloma is considered the hallmark of microscopic diagnosis in Crohn's disease (CD), but granulomas can be detected in only 21-60% of CD patients. The aim of this study was to evaluate the frequency of granulomas by multiple endoscopic biopsies in patients with CD and to examine whether group of patients with or without granuloma exhibit a different clinical course. METHODS: Fifty-six patients with newly diagnosed CD were included in the study. jejunoscopy, enteroclysis and ileo-colonoscopy were performed in all patients. At least two biopsy specimens from each examined gastrointestinal segment were examined microscopically searching granuloma. The clinical course was followed in all patients, and extraintestinal manifestations as well as details of any immunosuppressive therapy and surgical intervention were noted. rESULTS: Granuloma was found in 44.6% of the cases (25 patients). Patients with granuloma had higher activity parameters at the time of the biopsies. Extraintestinal manifestations were observed and surgical interventions were performed more often in the granuloma group. The need of immunosuppressive therapy was significantly more frequent in the patients with granuloma. Granuloma formation is mote often seen in younger patients, and mainly in the severe, active penetrating disease. CONCLUSION: The significantly higher frequency of surgical interventions and immunosuppressive therapy suggests that granuloma formation is associated with a more severe disease course during the first years of CD.

关键词： Crohn's disease Granuloma Activity Complication

Tilted pulse front pumping techniques for efficient terahertz pulse generation

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Light(Science & Applications) 2023年第11期12卷 2291-2308页

作者： Gyorgy Toth Gyula Polonyi janos Hebling University of Pecs Pecs 7624Hungary Szentagothai research Centre Pecs 7624Hungary HUN-rEN-PTE High-Field Terahertz research Group Pecs 7624Hungary

Optical rectification of femtosecond laser pulses has emerged as the dominant technique for generating single-and few-cycle terahertz(THz)*** advent of the tilted pulse front pumping(TPFP)velocity matching technique,proposed and implemented two decades ago,has ushered in significant advancements of these THz sources,which are pivotal in the realm of THz pump-probe and material control experiments,which need THz pulses with microjoule energies and several hundred kV/cm electric field ***,these THz sources are poised to play a crucial role in the realization of THz-driven particle accelerators,necessitating millijoule-level pulses with tens of MV/cm electric field *** has enabled the efficient velocity matching in lithium niobate crystals renowned for their extraordinary high nonlinear ***,its adaptation to semiconductor THz sources has resulted in a two-hundred-times enhancement in conversion *** this comprehensive review,we present the seminal achievements of the past two *** expound on the conventional TPFP setup,delineate its scaling limits,and elucidate the novel generation TPFP configurations proposed to surmount these constraints,accompanied by their preliminary ***,we provide an in-depth analysis of the THz absorption,refractive index,and nonlinear coefficient spectra of lithium niobate and widely used semiconductors employed as THz generators,which dictate their suitability as THz *** underscore the far-reaching advantages of tilted pulse front pumping,not only for LN and semiconductor-based THz sources but also for selected organic crystal-based sources and Yb-laserpumped GaP sources,previously regarded as velocity-matched in the literature.

关键词： pumping pulse realization

Spastin and alsin protein interactome analyses begin to reveal key canonical pathways and suggest novel druggable targets

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Neural regeneration research 2025年第3期20卷 725-739页

作者： Benjamin r.Helmold Angela Ahrens Zachary Fitzgerald P.Hande Ozdinler Department of Neurology Feinberg School of MedicineNorthwestern UniversityChicagoILUSA Center for Molecular Innovation and Drug Discovery Center for Developmental TherapeuticsChemistry of Life Processes InstituteNorthwestern UniversityEvanstonILUSA Mesulam Center for Cognitive Neurology and Alzheimer’s Disease Feinberg School of MedicineNorthwestern UniversityChicagoILUSA Feinberg School of Medicine Les Turner ALS Center at Northwestern UniversityChicagoILUSA

Developing effective and long-term treatment strategies for rare and complex neurodegenerative diseases is challenging. One of the major roadblocks is the extensive heterogeneity among patients. This hinders understanding the underlying disease-causing mechanisms and building solutions that have implications for a broad spectrum of patients. One potential solution is to develop personalized medicine approaches based on strategies that target the most prevalent cellular events that are perturbed in patients. Especially in patients with a known genetic mutation, it may be possible to understand how these mutations contribute to problems that lead to neurodegeneration. Protein–protein interaction analyses offer great advantages for revealing how proteins interact, which cellular events are primarily involved in these interactions, and how they become affected when key genes are mutated in patients. This line of investigation also suggests novel druggable targets for patients with different mutations. Here, we focus on alsin and spastin, two proteins that are identified as “causative” for amyotrophic lateral sclerosis and hereditary spastic paraplegia, respectively, when mutated. Our review analyzes the protein interactome for alsin and spastin, the canonical pathways that are primarily important for each protein domain, as well as compounds that are either Food and Drug Administration–approved or are in active clinical trials concerning the affected cellular pathways. This line of research begins to pave the way for personalized medicine approaches that are desperately needed for rare neurodegenerative diseases that are complex and heterogeneous.

关键词： ALS2 alsin amyotrophic lateral sclerosis hereditary spastic paraplegia neurodegenerative diseases personalized medicine precision medicine protein interactome protein-protein interactions SPAST spastin

Women in visual neural regeneration research

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Neural regeneration research 2025年第2期20卷 489-490页

作者： Tonia S.rex David j.Calkins Vanderbilt Eye Institute Vanderbilt University Medical CenterNashvilleTNUSA

The year 2024 marks the 60^(th)anniversary of Title IX and 25 years since the New York Times revealed bias against female faculty members at the Massachusetts Institute of *** take an opportunity here to examine the state of gender bias in a relatively new yet already prominent field,neural regeneration in the visual system,for which there is a well-defined context useful for this *** National Eye Institute(NEI)provided the first round of research funding for its Audacious Goals Initiative(AGI)on visual neural regeneration in 2013 and the last round in ***,we focus on this *** sources included PubMed,the National Science Foundation(NSF),the NEI,the Blue ridge Institute for Medical research and data from the major professional organization for eye and vision research,the Association for research in Vision and Ophthalmology(ArVO).

关键词： neural visual Times

CYP24A1 inhibition facilitates the anti-tumor effect of vitamin D3 on colorectal cancer cells

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World journal of Gastroenterology 2013年第17期19卷 2621-2628页

作者： jános P Kósa Péter Horváth jános Wlfling Dóra Kovács Bernadett Balla Péter Mátyus Evelin Horváth Gábor Speer István Takács Zsolt Nagy Henrik Horváth Péter Lakatos 1 st Department of Internal Medicine Semmelweis University Department of Organic Chemistry University of Szeged Department of Organic Chemistry Semmelweis University

AIM:The effects of vitamin D3 have been investigated on various tumors, including colorectal cancer (CrC). 25-hydroxyvitamin-D3-24-hydroxylase (CYP24A1), the enzyme that inactivates the active vitamin D3 metabolite 1,25-dihydroxyvitamin D3 (1,25-D3), is considered to be the main enzyme determining the biological halflife of 1,25-D3. During colorectal carcinogenesis, the expression and concentration of CYP24A1 increases significantly, suggesting that this phenomenon could be responsible for the proposed efficacy of 1,25-D3 in the treatment of CrC. The aim of this study was to investigate the anti-tumor effects of vitamin D3 on the human CrC cell line Caco-2 after inhibition of the cytochrome P450 component of CYP24A1 activity. METHODS:We examined the expression of CYP24A1 mrNA and the effects of 1,25-D3 on the cell line Caco-2 after inhibition of CYP24A1. Cell viability and proliferation were determined by means of sulforhodamine-B staining and bromodeoxyuridine incorporation, respectively, while cytotoxicity was estimated via the lactate dehydrogenase content of the cell culture supernatant. CYP24A1 expression was measured by realtime reverse transcription polymerase chain reaction. A number of tetralone compounds were synthesized to investigate their CP24A1 inhibitory activity. rESULTS:In response to 1,25-D3, CYP24A1 mrNA expression was enhanced significantly, in a time- and dose-dependent manner. Caco-2 cell viability and proliferation were not influenced by the administration of 1,25-D3 alone, but were markedly reduced by coadministration of 1,25-D3 and KD-35, a CYP24A1-inhibiting tetralone. Our data suggest that the mechanism of action of co-administered KD-35 and 1,25-D3 does not involve a direct cytotoxic effect, but rather the inhibition of cell proliferation. CONCLUSION:These findings demonstrate that the selective inhibition of CYP24A1 by compounds such as KD-35 may be a new approach for enhancement of the anti-tumor effect of 1,25-D3 on CrC.

关键词： Colorectal cancer CYP24A1 inhibition Vitamin D3 Tetralone derivatives Caco-2 cell culture