Publications by authors named "Andras Nagy"

358 Publications

Paradigm shift in the vascular surgery of the lower extremity at the Department of Vascular Surgery, University of Szeged, Hungary

Orv Hetil 2021 06 13;162(24):943-951. Epub 2021 Jun 13.

1 Szegedi Tudományegyetem, Általános Orvostudományi Kar, Szent-Györgyi Albert Klinikai Központ, Sebészeti Klinika, Szeged, Semmelweis u. 8., 6720.

Összefoglaló. Bevezetés: Az endovascularis intervenciókat kezdetben radiológusok alkalmazták, manapság, megfelelő képzést követően, jó eredménnyel végeznek ilyen beavatkozásokat érsebészek is. Ezt a világszerte uralkodóvá váló szemléletet kívántuk meghonosítani a Szegedi Tudományegyetemen, melynek bevezetése nélkül előrevetíthető az érsebészet működésének átalakulása az érrekonstrukciós beavatkozások csökkenésével. Célkitűzés: Egyetemünkön radiológus- és érsebész-munkacsoport végez perifériás érintervenciókat. Célunk a két intézet alsó végtagi endovascularis tevékenységének összehasonlítása volt. Módszer: Vizsgálatunkba a Szegedi Tudományegyetemen 2012. 01. 01. és 2019. 12. 31. között alsó végtagi endovascularis beavatkozásokon átesett betegeket válogattuk be. A betegeket a rizikófaktoraik, a kezelt anatómiai régiók, a hospitalizációs idő és a szövődmények tekintetében hasonlítottuk össze. Egyéves utánkövetés során vizsgáltuk a 'redo' műtétek , az amputációk és a halálozások gyakoriságát. Eredmények: A beavatkozásokat 653 esetben radiológus, 573 esetben érsebész végezte. Az érműtőben infrainguinalis (63,2%), a radiológián suprainguinalis érintervenciók (68,6%) történtek nagyobb arányban. A percutan végzett beavatkozásokat vizsgálva a hospitalizációs időben (2,5 ± 4,4 nap vs. 2,4 ± 2,5 nap, p = 0,78), valamint a minimálisan invazív módon végzett beavatkozások utáni szövődmények gyakoriságában (30/653 - 4,6% és 11/257 - 4,3%, p = 0,837) nem volt különbség a két betegcsoport között. 'Redo' műtétek (73/485 - 15,1% és 33/562 - 5,9%, p<0,001) és amputációk (31/485 - 6,4% és 12/562 - 2,1%, p<0,001) gyakrabban fordultak elő az érműtőben kezelt betegek körében, ebben a csoportban azonban a kritikus végtagischaemia előfordulása is gyakoribb volt (45,4% és 38,6%, p = 0,016). A mortalitásban nem volt szignifikáns különbség (5,8% és 3,9%, p = 0,16). Következtetés: A szoliter érelváltozások kezelését mindkét intézet hasonló hatásfokkal végezte. A több anatómiai régiót érintő betegség miatt érműtőben végzett beavatkozások utáni szövődmények előfordulása kissé magasabbnak bizonyult. Orv Hetil. 2021; 162(24): 943-951.

Summary:

Introduction: Endovascular interventions were initially performed by radiologists. Nowadays properly trained vascular surgeons also effectively perform these interventions. We wished to apply this widespread practice at our university because without this advancement the number of reconstructive surgeries was expected to decrease significantly.

Objective: Both radiologists and vascular surgeons perform endovascular interventions at our university. We compared the outcomes of lower extremity endovascular interventions between the two institutes.

Method: We included patients who underwent lower extremity endovascular interventions between 01. 01. 2012 and 31. 12. 2019. We compared the risk factors, treated anatomical regions, hospitalization time and complication rate. During the one-year follow-up, we examined the occurrence of redo surgeries, amputations and mortality.

Results: 653 interventions were performed by radiologists and 573 by vascular surgeons. Vascular surgeons carried out more interventions in the infrainguinal region (63.2%), while radiologists in the suprainguinal region (68.6%). The hospitalization time after percutaneous interventions (2.5 ± 4.4 days vs. 2.4 ± 2.5 days, p = 0.78), and the rate of complications after minimally invasive interventions did not show significant difference (30/653 - 4.6% vs. 11/257 - 4.3%, p = 0.837). Redo surgeries (73/485 - 15.1% vs. 33/562 - 5.9%, p<0.001) and amputations (31/485 - 6.4% vs. 12/562 - 2.1%, p<0.001) occurred more frequently in the surgical group. However, the incidence of chronic limb ischaemia was also higher (45.4% vs. 38.6%, p = 0.016). There was no significant difference in the mortality (5.8% vs. 3.9%, p = 0.16).

Conclusion: Both institutes had similar efficacy in performing peripheral interventions on solitary vascular lesions. Complications occurred more frequently in the surgical group, but the majority of these patients had extended atherosclerotic diseases. Orv Hetil. 2021; 162(24): 943-951.
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http://dx.doi.org/10.1556/650.2021.32099DOI Listing
June 2021

Ketoconazole-p aminobenzoic cocrystal, an improved antimycotic drug formulation, does not induce skin sensitization on the skin of BALBc mice.

Inflammopharmacology 2021 Jun 4;29(3):721-733. Epub 2021 Jun 4.

Department of Physiology, University of Medicine and Pharmacy Iuliu Hatieganu, 400006, Cluj-Napoca, Romania.

Fungal infections are a growing global health problem. Therefore, our group has synthetized and characterized an improved antimycotic by co-crystallization of ketoconazole and para-amino benzoic acid, named KET-PABA. The aim was to increase bioavailability, biocompatibility, and efficiency of the parent drug-ketoconazole. Based on our previous results showing the cocrystal improved physical properties, such as stability in suspension, solubility, as well as antimycotic efficiency compared to ketoconazole, the current study investigated the local possible side effects induced on the skin of BALBc mice by the application of KET-PABA cocrystal, in view of a further use as a topically applied antimycotic drug. A specific test (mouse ear-swelling test) was used, combined with the histopathological examination and the measurement of pro and anti-inflammatory cytokines and inflammation mediators. KET-PABA application was safe, without signs of skin sensitization shown by the mouse ear sensitization test, or histopathology. KET-PABA strongly inhibited proinflammatory cytokines such as IL1 α, IL1 β, IL6 and TNF α, and other proinflammatory inducers such as NRF2, compared to vehicle. KET-PABA had no effect on the levels of the anti-inflammatory cytokine IL10, or proinflammatory enzyme COX2 and had minimal effects on the activation of the NF-κB pathway. Overall, KET-PABA application induced no sensitization, moreover, it decreased the skin levels of proinflammatory molecules. The lack of skin sensitization effects on BALBc mice skin along with the inhibition of the proinflammatory markers show a good safety profile for topical applications of KET-PABA and show promise for a further clinical use in the treatment of cutaneous mycosis.
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http://dx.doi.org/10.1007/s10787-021-00834-7DOI Listing
June 2021

Ketoconazole-p aminobenzoic cocrystal, an improved antimycotic drug formulation, does not induce skin sensitization on the skin of BALBc mice.

Inflammopharmacology 2021 Jun 4;29(3):721-733. Epub 2021 Jun 4.

Department of Physiology, University of Medicine and Pharmacy Iuliu Hatieganu, 400006, Cluj-Napoca, Romania.

Fungal infections are a growing global health problem. Therefore, our group has synthetized and characterized an improved antimycotic by co-crystallization of ketoconazole and para-amino benzoic acid, named KET-PABA. The aim was to increase bioavailability, biocompatibility, and efficiency of the parent drug-ketoconazole. Based on our previous results showing the cocrystal improved physical properties, such as stability in suspension, solubility, as well as antimycotic efficiency compared to ketoconazole, the current study investigated the local possible side effects induced on the skin of BALBc mice by the application of KET-PABA cocrystal, in view of a further use as a topically applied antimycotic drug. A specific test (mouse ear-swelling test) was used, combined with the histopathological examination and the measurement of pro and anti-inflammatory cytokines and inflammation mediators. KET-PABA application was safe, without signs of skin sensitization shown by the mouse ear sensitization test, or histopathology. KET-PABA strongly inhibited proinflammatory cytokines such as IL1 α, IL1 β, IL6 and TNF α, and other proinflammatory inducers such as NRF2, compared to vehicle. KET-PABA had no effect on the levels of the anti-inflammatory cytokine IL10, or proinflammatory enzyme COX2 and had minimal effects on the activation of the NF-κB pathway. Overall, KET-PABA application induced no sensitization, moreover, it decreased the skin levels of proinflammatory molecules. The lack of skin sensitization effects on BALBc mice skin along with the inhibition of the proinflammatory markers show a good safety profile for topical applications of KET-PABA and show promise for a further clinical use in the treatment of cutaneous mycosis.
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http://dx.doi.org/10.1007/s10787-021-00834-7DOI Listing
June 2021

Transplantation of Human Cortically-Specified Neuroepithelial Progenitor Cells Leads to Improved Functional Outcomes in a Mouse Model of Stroke.

Front Cell Neurosci 2021 29;15:654290. Epub 2021 Apr 29.

Faculty of Medicine, Institute of Medical Science, University of Toronto, Toronto, ON, Canada.

Stroke is a leading cause of death and long-term disability worldwide. Current therapeutic options are limited in terms of their time for implementation and efficacy in promoting recovery. Cell transplantation has been shown to have promise in several animal models however significant challenges remain, including the optimal source of cells to promote neural repair. Here, we report on the use of a population of human ESC derived, cortically specified, neuroepithelial precursor cells (cNEPs) that are neurally restricted in their lineage potential. CNEPs have the potential to give rise to mature neural cell types following transplantation, including neurons, astrocytes and oligodendrocytes. With a view towards translation, we sought to determine whether this human cell source was effective in promoting improved functional outcomes following stroke. Undifferentiated cNEPs were transplanted in a pre-clinical endothelin-1 (ET-1) model of ischemic motor cortical stroke in immunocompromised SCID-beige mice and cellular and functional outcomes were assessed. We demonstrate that cNEP transplantation in the acute phase (4 days post-stroke) improves motor function as early as 20 days post-stroke, compared to stroke-injured, non-transplanted mice. At the time of recovery, a small fraction (<6%) of the transplanted cNEPs are observed within the stroke injury site. The surviving cells expressed the immature neuronal marker, doublecortin, with no differentiation into mature neural phenotypes. At longer survival times (40 days), the majority of recovered, transplanted mice had a complete absence of surviving cNEPS. Hence, human cNEPs grafted at early times post-stroke support the observed functional recovery following ET-1 stroke but their persistence is not required, thereby supporting a by-stander effect rather than cell replacement.
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http://dx.doi.org/10.3389/fncel.2021.654290DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8116536PMC
April 2021

An Optical-Flow-Based Method to Quantify Dynamic Behavior of Human Pluripotent Stem Cell-Derived Cardiomyocytes in Disease Modeling Platforms.

Methods Mol Biol 2021 May 13. Epub 2021 May 13.

Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, ON, Canada.

Human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) hold great promise for cardiovascular disease modeling, drug screening and personalized medicine. A crucial requirement to establish an hPSC-CM-based disease model is the availability of a reliable differentiation protocol and a functional assessment of phenotypic properties of CMs in a disease context. Characterization of relative changes in contractile behavior of CMs can provide insight not only about drug effects but into the pathogenesis of cardiovascular diseases. Image-based optical-flow analysis, which applies a speckle tracking algorithm to videomicroscopy of hPSC-CMs, is a noninvasive method to quantitatively assess the dynamics of mechanical contraction of the CMs. This method offers an efficient characterization of contractile cycles. It quantifies contraction velocity field, beat rate, contractile strain and contraction-relaxation strain rate profile, which are important phenotypic characteristics of CMs.
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http://dx.doi.org/10.1007/7651_2021_382DOI Listing
May 2021

The anabolic effect of inorganic polyphosphate on chondrocytes is mediated by calcium signalling.

J Orthop Res 2021 Mar 14. Epub 2021 Mar 14.

Institute of Biomaterials and Biomedical Engineering, University of Toronto, Toronto, Ontario, Canada.

Inorganic polyphosphates (polyP) are polymers composed of phosphate residues linked by energy-rich phosphoanhydride bonds. As polyP can bind calcium, the hypothesis of this study is that polyP enters chondrocytes and exerts its anabolic effect by calcium influx through calcium channels. PolyP treatment of cartilage tissue formed in 3D culture by bovine chondrocytes showed an increase in proteoglycan accumulation but only when calcium was also present at a concentration of 1.5 mM. This anabolic effect could be prevented by treatment with either ethylene glycol-bis(β-aminoethyl ether)-N,N,N',N'-tetraacetic acid or the calcium channel inhibitors gadolinium and nifedipine. Calcium and polyP cotreatment of chondrocytes in monolayer culture resulted in calcium oscillations that were polyP chain length specific and were inhibited by gadolinium and nifedipine. The calcium influx resulted in increased gene expression of sox9, collagen type II, and aggrecan which was prevented by treatment with either calphostin, an inhibitor of protein kinase C, and W7, an inhibitor of calmodulin; suggesting activation of the protein kinase C-calmodulin pathway. Tracing studies using  4',6-diamidino-2-phenylindole, Mitotracker Red, and/or Fura-AM staining showed that polyP was detected in the nucleus, mitochondria, and intracellular vacuoles suggesting that polyP may also enter the cell. PolyP colocalizes with calcium in mitochondria. This study demonstrates that polyP requires the influx of calcium to regulate chondrocyte matrix production, likely via activating calcium signaling. These findings identify the mechanism regulating the anabolic effect of polyP in chondrocytes which will help in its clinical translation into a therapeutic agent for cartilage repair.
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http://dx.doi.org/10.1002/jor.25032DOI Listing
March 2021

In Vitro Suppression of T Cell Proliferation Is a Conserved Function of Primary and Immortalized Human Cancer-Associated Fibroblasts.

Int J Mol Sci 2021 Feb 12;22(4). Epub 2021 Feb 12.

Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Clayton 3800, Australia.

T cell immunotherapy is now a mainstay therapy for several blood-borne cancers as well as metastatic melanoma. Unfortunately, many epithelial tumors respond poorly to immunotherapy, and the reasons for this are not well understood. Cancer-associated fibroblasts (CAFs) are the most frequent non-neoplastic cell type in most solid tumors, and they are emerging as a key player in immunotherapy resistance. A range of immortalized CAF lines will be essential tools that will allow us to understand immune responses against cancer and develop novel strategies for cancer immunotherapy. To study the effect of CAFs on T cell proliferation, we created and characterized a number of novel immortalized human CAFs lines (Im-CAFs) from human breast, colon, and pancreatic carcinomas. Im-CAFs shared similar phenotypes, matrix remodeling and contraction capabilities, and growth and migration rates compared to the primary CAFs. Using primary isolates from breast carcinoma, colorectal carcinoma, and pancreatic ductal adenocarcinoma, we report that CAFs across major tumor types are able to potently suppress T cell proliferation in vitro. Im-CAFs retained this property. Im-CAFs are a key tool that will provide important insights into the mechanisms of CAF-mediated T cell suppression through techniques such as CRISPR-Cas9 modification, molecular screens, and pipeline drug testing.
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http://dx.doi.org/10.3390/ijms22041827DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7918788PMC
February 2021

The Impact of Composites with Silicate-Based Glasses and Gold Nanoparticles on Skin Wound Regeneration.

Molecules 2021 Jan 25;26(3). Epub 2021 Jan 25.

Faculty of Veterinary Medicine, University of Agricultural Science and Veterinary Medicine, 400372 Cluj-Napoca, Romania.

The silver content of the skin regeneration ointments can influence its regeneration process but in the meantime, it can take the benefit of the antibacterial properties of silver by avoiding the bacterial infection of an open wound. In the current study, the skin healing and regeneration capacity of bioactive glass with spherical gold nanocages (BGAuIND) in the Vaseline ointments were evaluated in vivo comparing the bioactive glass (BG)-Vaseline and bioactive glass with spherical gold (BGAuSP)-Vaseline ointments. Spherical gold nanocages are stabilized with silver and as a consequence the BGAuIND exhibits great antibacterial activity. Histological examination of the cutaneous tissue performed on day 8 indicates a more advanced regeneration process in rats treated with BGAuSP-Vaseline. The histopathological examination also confirms the results obtained after 11 days post-intervention, when the skin is completely regenerated at rats treated with BGAuSP-Vaseline compared with the others groups where the healing was incomplete. This result is also confirmed by the macroscopic images of the evolution of wounds healing. As expected, the silver content influences the wound healing process but after two weeks, for all of the post-interventional trials from the groups of rats, the skin healing was completely.
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http://dx.doi.org/10.3390/molecules26030620DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7866013PMC
January 2021

Percutaneous ultrasound guided PEG-coated gold nanoparticles enhanced radiofrequency ablation in liver.

Sci Rep 2021 Jan 14;11(1):1316. Epub 2021 Jan 14.

3rd Medical Department, "Iuliu Hatieganu" University of Medicine and Pharmacy Cluj-Napoca, Cluj-Napoca, Romania.

To investigate the effects of PEG-coated gold nanoparticles on ablation zone volumes following in vivo radiofrequency ablation of porcine liver. This prospective study was performed following institutional animal care and committee approval was used. Radiofrequency ablations were performed in the livers of ten Sus scrofa domesticus swines. During each ablation, 10 mL (mL) of Peg-coated gold nanoparticles at two different concentrations (0.5 mg/mL and 0.01 mg/mL) were injected through the electrode channel into the target zone. For the control group, 10 mL of physiological saline was used. Five to ten minutes after each ablation, contrast enhanced ultrasound (CEUS) was performed to evaluate the volume of the coagulation zone. On day five we performed another CEUS and the animals were sacrificed. Treated tissues were explanted for quantification of the ablation zones' volumes. Hematoxylin and eosin (H&E) staining was also performed for histologic analysis. A total of 30 ablations were performed in the livers. The mean coagulation zone volume as measured by CEUS on day 5 after RFA was: 21.69 ± 3.39 cm, 19.22 ± 5.77 cm, and 8.80 ± 3.33 cm for N1, N2 and PS respectively. The coagulation zone volume after N1 and N2 treatments was significantly higher compared to PS treatment (p < 0.001 and p = 0.025 respectively). There was no difference between N1 and N2 treatment (p = 0.60). In our proof-of concept, pilot study we have shown for the first time that when injected directly into the target tissue during RFA, gold nanoparticles can substantially increase the coagulation zone.
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http://dx.doi.org/10.1038/s41598-020-79917-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7809408PMC
January 2021

Per-pass analysis of acute ischemic stroke clots: impact of stroke etiology on extracted clot area and histological composition.

J Neurointerv Surg 2020 Dec 9. Epub 2020 Dec 9.

Department of Interventional and Diagnostic Neuroradiology, Sahlgrenska University Hospital, Göteborg, Sweden.

Background: Initial studies investigating correlations between stroke etiology and clot composition are conflicting and do not account for clot size as determined by area. Radiological studies have shown that cardioembolic strokes are associated with shorter clot lengths and lower clot burden than non-cardioembolic clots.

Objective: To report the relationship between stroke etiology, extracted clot area, and histological composition at each procedural pass.

Methods: As part of the multi-institutional RESTORE Registry, the Martius Scarlett Blue stained histological composition and extracted clot area of 612 per-pass clots retrieved from 441 patients during mechanical thrombectomy procedures were quantified. Correlations with clinical and procedural details were investigated.

Results: Clot composition varied significantly with procedural passes; clots retrieved in earlier passes had higher red blood cell content (H4=11.644, p=0.020) and larger extracted clot area (H4=10.730, p=0.030). Later passes were associated with significantly higher fibrin (H4=12.935, p=0.012) and platelets/other (H4=15.977, p=0.003) content and smaller extracted clot area. Large artery atherosclerotic (LAA) clots were significantly larger in the extracted clot area and more red blood cell-rich than other etiologies in passes 1-3. Cardioembolic and cryptogenic clots had similar histological composition and extracted clot area across all procedural passes.

Conclusion: LAA clots are larger and associated with a large red blood cell-rich extracted clot area, suggesting soft thrombus material. Cardioembolic clots are smaller in the extracted clot area, consistent in composition and area across passes, and have higher fibrin and platelets/other content than LAA clots, making them stiffer clots. The per-pass histological composition and extracted clot area of cryptogenic clots are similar to those of cardioembolic clots, suggesting similar formation mechanisms.
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http://dx.doi.org/10.1136/neurintsurg-2020-016966DOI Listing
December 2020

Large Artery Atherosclerotic Clots are Larger than Clots of other Stroke Etiologies and have Poorer Recanalization rates.

J Stroke Cerebrovasc Dis 2021 Jan 24;30(1):105463. Epub 2020 Nov 24.

Department of Interventional and Diagnostic Neuroradiology, Sahlgrenska University Hospital, Institute of Clinical Sciences, Gothenburg, Sweden; Department of Radiology, Sahlgrenska Academy at University of Gothenburg, Sweden.

Objectives: There is a paucity of knowledge in the literature relating to the extent of clot burden and stroke etiology. In this study, we measured the Extracted Clot Area (ECA) retrieved during endovascular treatment (EVT) and investigated relationships with suspected etiology, administration of intravenous thrombolysis and recanalization.

Materials And Methods: As part of the multi-institutional RESTORE registry, the ECA retrieved during mechanical thrombectomy was quantified using ImageJ. The effect of stroke etiology (Large-artery atherosclerosis (LAA), Cardioembolism, Cryptogenic and other) and recombinant tissue plasminogen activator (rtPA) on ECA and recanalization outcome (mTICI) was assessed. Successful recanalization was described as mTICI 2c-3.

Results: A total of 550 patients who underwent EVT with any clot retrieved were included in the study. The ECA was significantly larger in the LAA group compared to all other etiologies. The average ECA size of each etiology was; LAA=109 mm, Cardioembolic=52 mm, Cryptogenic=47 mm and Other=52 mm (p=0.014*). LAA patients also had a significantly poorer rate of successful recanalization (mTICI 2c-3) compared to all other etiologies (p=0.003*). The administration of tPA was associated with a smaller ECA in both LAA (p=0.007*) and cardioembolic (p=0.035*) groups.

Conclusion: The ECA of LAA clots was double the size of all other etiologies and this is associated with a lower rate of successful recanalization in LAA stroke subtype. rtPA administration prior to thrombectomy was associated with reduced ECA in LAA and CE clots.
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http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2020.105463DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7755299PMC
January 2021

Pyeloureteric magnetic anastomosis device to simplify laparoscopic pyeloplasty: a proof-of-concept study.

BJU Int 2021 Apr 3;127(4):409-411. Epub 2021 Jan 3.

Department of Pediatric Surgery, Medical Faculty Mannheim (UMM), University of Heidelberg, Mannheim, Germany.

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http://dx.doi.org/10.1111/bju.15301DOI Listing
April 2021

Deficiency of the serine peptidase Kallikrein 6 does not affect the levels and the pathological accumulation of a-synuclein in mouse brain.

J Neurochem 2021 Jun 19;157(6):2024-2038. Epub 2020 Oct 19.

Center for Basic Research, Biomedical Research Foundation Academy of Athens, Athens, Greece.

Several lines of evidence indicate that the propagation of misfolded α-synuclein (α-syn) plays a central role in the progression and manifestation of Parkinson's disease. Pathogenic α-syn species can be present in the extracellular space. Thus, the identification and modulation of the key enzymes implicated in extracellular α-syn turnover becomes vital. Kallikrein peptidase 6 has been identified as one of the major α-syn degrading enzymes and has been implicated in the clearance of extracellular α-syn. However, the physiological role of this enzyme in regulating α-syn, in vivo, still remains elusive. Here, by utilizing Klk6 knock-out (Klk6 ) mice as our experimental model, we provide insight into the physiologic relevance of endogenous KLK6 expression on α-syn processing. Behavioral phenotyping showed that Klk6 mice display no gross behavioral abnormalities. Further in vivo characterization of this mouse model, in the context of α-syn accumulation, showed that KLK6 deletion had no impact on the protein levels of intracellular or extracellular α-syn. Upon in vivo administration of α-syn pre-formed fibrils (PFF), α-syn pathologic accumulations were evident both in the brains of Klk6 mice and wt mice without significant differences. Intrastriatal delivery of active KLK6, did not affect secreted α-syn levels observed in the A53T α-syn over-expressing mice. These findings suggest that in the in vivo setting of PFF pathology induction, KLK6 alone is not able to modulate pathology transmission. Our study raises implications for the use of recombinant α-syn fibrils in α-syn turnover studies.
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http://dx.doi.org/10.1111/jnc.15199DOI Listing
June 2021

The administration of rtPA before mechanical thrombectomy in acute ischemic stroke patients is associated with a significant reduction of the retrieved clot area but it does not influence revascularization outcome.

J Thromb Thrombolysis 2021 Feb 16;51(2):545-551. Epub 2020 Sep 16.

Department of Physiology and Galway Neuroscience Centre, School of Medicine, National University of Ireland, Galway, University Road, Galway, Ireland.

Both intravenous thrombolysis (IVT) and mechanical thrombectomy (MT) are evidence-based treatments for acute ischemic stroke (AIS) in selected cases. Recanalization may occur following IVT without the necessity of further interventions or requiring a subsequent MT procedure. IVT prior to MT (bridging-therapy) may be associated with benefits or hazards. We studied the retrieved clot area and degree of recanalization in patients undergoing MT or bridging-therapy for whom it was possible to collect thrombus material. We collected mechanically extracted thrombi from 550 AIS patients from four International stroke centers. Patients were grouped according to the administration (or not) of IVT before thrombectomy and the mechanical thrombectomy approach used. We assessed the number of passes for clot removal and the mTICI (modified Treatment In Cerebral Ischemia) score to define revascularization outcome. Gross photos of each clot were taken and the clot area was measured with ImageJ software. The non-parametric Kruskal-Wallis test was used for statistical analysis. 255 patients (46.4%) were treated with bridging-therapy while 295 (53.6%) underwent MT alone. By analysing retrieved clot area, we found that clots from patients treated with bridging-therapy were significantly smaller compared to those from patients that underwent MT alone (H = 10.155 p = 0.001*). There was no difference between bridging-therapy and MT alone in terms of number of passes or final mTICI score. Bridging-therapy was associated with significantly smaller retrieved clot area compared to MT alone but it did not influence revascularization outcome.
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http://dx.doi.org/10.1007/s11239-020-02279-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7886731PMC
February 2021

The levels of reprogramming factors influence the induction and maintenance of pluripotency: the case of CD1 mouse strain cells.

Int J Dev Biol 2021 ;65(4-5-6):365-376

Departamento de Genética del Desarrollo y Fisiología Molecular, Instituto de Biotecnología, Universidad Nacional Autónoma de México, Cuernavaca, Mor., México.

The amount of proteins of the regulatory pluripotency network can be determinant for somatic cell reprogramming into induced pluripotent stem cells (iPSCs) as well as for the maintenance of pluripotent stem cells (PSCs). Here, we report a transposon-based reprogramming system (PB-Booster) that allowed high expression levels of a polycistronic transgene containing K O and () and showed increased reprogramming efficiency of fresh mouse embryonic fibroblasts (MEFs) into iPSCs under low, but not under high, expression levels. In contrast, MEFs after 2 passages derived into a similar number of iPSC colonies as fresh MEFs at a high MKOS dose, but this number was reduced at a low MKOS dose. Timing of reprogramming was not affected by expression levels but, importantly, exogenous expression in established PSCs caused a significant cell loss. At high but not at low expression levels, MEFs of the CD1 strain produced more initial cell clusters than iPSCs and, although reprogrammed at a similar efficiency as MEFs of the 129/Sv strain, iPSCs could not be maintained in the absence of exogenous . In CD1-iPSCs, , , and expression levels were reduced when compared with the levels in PSCs derived from the 129/Sv strain. Culture of CD1-iPSCs in medium with MEK and GSK3β inhibitors allowed their self-renewal in the absence of exogenous , but the expression levels of , , and were only partially increased. Despite the reduced levels of those pluripotency factors, CD1-iPSC kept high capacity for contribution to chimeric mouse embryos. Therefore, levels of regulatory pluripotency factors influence reprogramming initiation and PSC maintenance without affecting their differentiation potential .
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http://dx.doi.org/10.1387/ijdb.200233lcDOI Listing
January 2021

Hydrogel-mediated co-transplantation of retinal pigmented epithelium and photoreceptors restores vision in an animal model of advanced retinal degeneration.

Biomaterials 2020 10 30;257:120233. Epub 2020 Jul 30.

Institute of Biomedical Engineering, University of Toronto, Toronto, ON, M5S 3G9, Canada; Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, ON, M5S 3E1, Canada; Institute of Medical Science, University of Toronto, Toronto, ON, M5S 1A8, Canada; Chemical Engineering and Applied Chemistry, University of Toronto, Toronto, ON, M5S 3E5, Canada; Department of Chemistry, University of Toronto, Toronto, ON, M5S 3H6, Canada. Electronic address:

We demonstrate a novel approach to reverse advanced stages of blindness using hydrogel-mediated delivery of retinal pigmented epithelium (RPE) and photoreceptors directly to the degenerated retina of blind mice. With sodium iodate (NaIO) injections in mice, both RPE and photoreceptors degenerate, resulting in complete blindness and recapitulating the advanced retinal degeneration that is often observed in humans. We observed vision restoration only with co-transplantation of RPE and photoreceptors in a hyaluronic acid-based hydrogel, and not with transplantation of each cell type alone as determined with optokinetic head tracking and light avoidance assays. Both RPE and photoreceptors survived significantly better when co-transplanted than in their respective single cell type controls. While others have pursued transplantation of one of either RPE or photoreceptors, we demonstrate the importance of transplanting both cell types with a minimally-invasive hydrogel for vision repair in a degenerative disease model of the retina.
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http://dx.doi.org/10.1016/j.biomaterials.2020.120233DOI Listing
October 2020

Universal Stem Cells: Making the Unsafe Safe.

Cell Stem Cell 2020 08;27(2):198-199

Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, ON M5T3H7, Canada; Australian Regenerative Medicine Institute, Monash University, Melbourne, VIC 3800, Australia; Department of Obstetrics and Gynecology, University of Toronto, Toronto, ON M5G1E2, Canada; Institue of Medical Science, University of Toronto, Toronto, ON M5S1A8, Canada. Electronic address:

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http://dx.doi.org/10.1016/j.stem.2020.07.004DOI Listing
August 2020

Hepatoprotective effects of silymarin coated gold nanoparticles in experimental cholestasis.

Mater Sci Eng C Mater Biol Appl 2020 Oct 25;115:111117. Epub 2020 May 25.

Physiology Department, "Iuliu Hatieganu" University of Medicine and Pharmacy, Cluj Napoca, Romania.

The present study reports the green synthesis of hybrid organic-inorganic gold nanocomposites using silymarin as reducing and capping agent. The structure of the silymarin loaded gold nanoparticles was investigated by using the appropriate analysis tools such as UV-Vis and Fourier-transform infrared spectroscopy (FTIR), and Transmission electron microscopy (TEM) techniques. TEM micrographs demonstrated that the gold nanoparticles were spherical in shape, well distributed and their mean size was about 10 nm. The in vivo hepatoprotective and antifibrogenic properties after bile duct ligation in rats of the silymarin coated gold nanoparticles were assessed. The changes regarding the blood tests and the liver histopathology were compared to the standard administration of silymarin. Silymarin loaded gold nanoparticles improved liver function, reduced cholestasis and oxidative stress parameters, with the increase of antioxidant support, and reduced inflammation and fibrosis in the liver of rats with extrahepatic cholestasis.
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http://dx.doi.org/10.1016/j.msec.2020.111117DOI Listing
October 2020

Systemic and Local Biocompatibility Assessment of Graphene Composite Dental Materials in Experimental Mandibular Bone Defect.

Materials (Basel) 2020 May 31;13(11). Epub 2020 May 31.

Department of Polymer Composites, Babes-Bolyai University, Institute of Chemistry Raluca Ripan, 30 Fantanele Street, 400294 Cluj-Napoca, Romania.

The main objective of this research is to demonstrate the biocompatibility of two experimental graphene dental materials by in vitro and in vivo tests for applications in dentistry. The novel graphene dental materials, including one restorative composite and one dental cement, were subjected to cytotoxicity and implantation tests by using a rat model of a non-critical mandibular defect. In vitro cytotoxicity induced by materials on human dental follicle stem cells (restorative composite) and dysplastic oral keratinocytes (dental cement) was investigated at 37 °C for 24 h. After in vivo implantation, at 7 weeks, bone samples were harvested and subjected to histological investigations. The plasma biochemistry, oxidative stress, and sub-chronic organ toxicity analysis were also performed. The resulting cytotoxicity tests confirm that the materials had no toxic effects against dental cells after 24 h. Following graphene dental materials implantation, the animals did not present any symptoms of acute toxicity or local inflammation. No alterations were detected in relative organ weights and in correlation with hepatic and renal histological findings. The materials' lack of systemic organ toxicity was confirmed. The outcomes of our study provided further evidence on the graphene dental materials' ability for bone regeneration and biocompatibility.
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http://dx.doi.org/10.3390/ma13112511DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7321491PMC
May 2020

Recapitulating kidney development in vitro by priming and differentiating mouse embryonic stem cells in monolayers.

NPJ Regen Med 2020 20;5. Epub 2020 Apr 20.

1Lunenfeld Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, ON Canada.

In order to harness the potential of pluripotent stem cells, we need to understand how to differentiate them to our target cell types. Here, we developed a protocol to differentiate mouse embryonic stem cells (ESCs) to renal progenitors in a step-wise manner. Microarrays were used to track the transcriptional changes at each stage of differentiation and we observed that genes associated with metanephros, ureteric bud, and blood vessel development were significantly upregulated as the cells differentiated towards renal progenitors. Priming the ESCs and optimizing seeding cell density and growth factor concentrations helped improve differentiation efficiency. Organoids were used to determine the developmental potential of the renal progenitor cells. Aggregated renal progenitors gave rise to organoids consisting of LTL+/E-cadherin+ proximal tubules, cytokeratin+ ureteric bud-derived tubules, and extracellular matrix proteins secreted by the cells themselves. Over-expression of key kidney developmental genes, , , , and paralogs, during differentiation did not improve differentiation efficiency. Altogether, we developed a protocol to differentiate mouse ESCs in a manner that recapitulates embryonic kidney development and showed that precise gene regulation is essential for proper differentiation to occur.
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http://dx.doi.org/10.1038/s41536-020-0092-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7171095PMC
April 2020

Postauthorization safety surveillance study of antihaemophilic factor (recombinant) reconstituted in 2 mL sterile water for injection in children with haemophilia A.

Haemophilia 2020 May 27;26(3):478-486. Epub 2020 Apr 27.

Baxalta US Inc., a member of the Takeda group of companies, Lexington, MA, USA.

Introduction: Antihaemophilic factor (recombinant) (rAHF; ADVATE ) is approved for prophylaxis and treatment of bleeding in children and adults with haemophilia A. Reconstitution in 2 mL sterile water for injection instead of 5 mL allows for a 60% reduction in infusion volume and administration time, but could increase the likelihood of hypersensitivity and infusion-related reactions, especially in children.

Aim: To assess local tolerability, safety and effectiveness of rAHF 2 mL during routine clinical practice factor VIII (FVIII) replacement (on-demand and prophylaxis) in children with severe (FVIII < 1%) or moderately severe (FVIII 1%-2%) haemophilia A.

Methods: This was a prospective, non-interventional, postauthorization safety surveillance study (NCT02093741). Eligible patients were previously treated with rAHF and had a negative inhibitor test result during ≤10 exposure days prior to study entry.

Results: Of 65 patients enrolled (0-11 years of age), 54 and 11 had severe and moderately severe haemophilia A, respectively; 56 patients received prophylaxis, and 11 had ≤50 exposure days, of which 4 had ≤4 exposure days. No patients reported local hypersensitivity reactions, treatment-related adverse events or developed inhibitors. Investigators rated overall effectiveness of rAHF 2 mL prophylaxis as excellent or good. Ninety-four bleeding events in 34 patients were treated. Haemostatic effectiveness was rated as excellent or good for 75.8% of bleeds; 86.2% of bleeds required 1 or 2 infusions.

Conclusion: In children with severe/moderately severe haemophilia A, no hypersensitivity reactions were reported with rAHF 2 mL treatment, and the safety and effectiveness are consistent with data previously reported for rAHF 5 mL.
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http://dx.doi.org/10.1111/hae.13997DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7383916PMC
May 2020

Ketoconazole--aminobenzoic Acid Cocrystal: Revival of an Old Drug by Crystal Engineering.

Mol Pharm 2020 03 7;17(3):919-932. Epub 2020 Feb 7.

Department of Physiology, Iuliu Haţieganu University of Medicine and Pharmacy, Clinicilor 1, 400006 Cluj-Napoca, Romania.

The 1:1 cocrystal of the antifungal agent ketoconazole with -aminobenzoic acid was successfully crystallized and systematically characterized by a physical and pharmacological point of view. Crystal structure determination confirmed the cocrystal identity, giving full insight in its crystal packing and degree of disorder. Powder dissolution measurements revealed a 10-fold aqueous solubility increase that induces a 6.7-fold oral bioavailability improvement compared to ketoconazole. cell assays showed a good toxicity profile of the cocrystal with lower oxidative stress and inflammation and enhanced antifungal activity against several species. The study of the cocrystal indicated similar pharmacokinetic profiles and liver toxicity with increased transaminases, as reported for ketoconazole. Notably, besides minor signs of inflammation, no morphological changes in liver parenchyma or signs of fibrosis and necrosis were detected. The enhanced solubility and oral bioavailability of the cocrystal over ketoconazole, together with the improved antifungal activity and good / toxicity, indicate its potential use as an alternative antifungal agent to the parent drug. Our results bring evidence of cocrystallization as a successful approach for bioavailability improvement of poorly soluble drugs.
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http://dx.doi.org/10.1021/acs.molpharmaceut.9b01178DOI Listing
March 2020

Genetic aberrations in iPSCs are introduced by a transient G1/S cell cycle checkpoint deficiency.

Nat Commun 2020 01 10;11(1):197. Epub 2020 Jan 10.

Department of Basic Medical Sciences for Radiation Damages, National Institute of Radiological Sciences, National Institutes for Quantum and Radiological Science and Technology, Chiba, 263-8555, Japan.

A number of point mutations have been identified in reprogrammed pluripotent stem cells such as iPSCs and ntESCs. The molecular basis for these mutations has remained elusive however, which is a considerable impediment to their potential medical application. Here we report a specific stage at which iPSC generation is not reduced in response to ionizing radiation, i.e. radio-resistance. Quite intriguingly, a G1/S cell cycle checkpoint deficiency occurs in a transient fashion at the initial stage of the genome reprogramming process. These cancer-like phenomena, i.e. a cell cycle checkpoint deficiency resulting in the accumulation of point mutations, suggest a common developmental pathway between iPSC generation and tumorigenesis. This notion is supported by the identification of specific cancer mutational signatures in these cells. We describe efficient generation of human integration-free iPSCs using erythroblast cells, which have only a small number of point mutations and INDELs, none of which are in coding regions.
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http://dx.doi.org/10.1038/s41467-019-13830-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6954237PMC
January 2020

Köszöntő dr. Jámbor Gyula születésnapjára.

Authors:
András Nagy

Magy Seb 2019 12;72(4):172

Sebészeti Osztály, Pest Megyei Flór Ferenc Kórház 2143 Kistarcsa, Semmelweis tér 1.

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http://dx.doi.org/10.1556/1046.72.2019.4.4DOI Listing
December 2019

Rb1/Rbl1/Vhl loss induces mouse subretinal angiomatous proliferation and hemangioblastoma.

JCI Insight 2019 11 14;4(22). Epub 2019 Nov 14.

Research Laboratory of Ophthalmology and Vision Sciences, State Key Laboratory of Biotherapy, and.

Von Hippel-Lindau (Vhl) protein inhibits hypoxia-inducible factor (Hif), yet its deletion in murine retina does not cause the extensive angiogenesis expected with Hif induction. The mechanism is unclear. Here we show that retinoblastoma tumor suppressor (Rb1) constrains expression of Hif target genes in the Vhl-/- retina. Deleting Rb1 induced extensive retinal neovascularization and autophagic ablation of photoreceptors in the Vhl-/- retina. RNA-sequencing, ChIP, and reporter assays showed Rb1 recruitment to and repression of certain Hif target genes. Activating Rb1 by deleting cyclin D1 induced a partial defect in the retinal superficial vascular plexus. Unexpectedly, removing Vhl suppressed retinoblastoma formation in murine Rb1/Rbl1-deficient retina but generated subretinal vascular growths resembling retinal angiomatous proliferation (RAP) and retinal capillary hemangioblastoma (RCH). Most stromal cells in the RAP/RCH-like lesions were Sox9+, suggesting a Müller glia origin, and expressed Lgals3, a marker of human brain hemangioblastoma. Thus, the Rb family limit Hif target gene expression in the Vhl-/- retina, and removing this inhibitory signal generates new models for RAP and RCH.
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http://dx.doi.org/10.1172/jci.insight.127889DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6948866PMC
November 2019

Synaptic Dysfunction in Human Neurons With Autism-Associated Deletions in PTCHD1-AS.

Biol Psychiatry 2020 01 29;87(2):139-149. Epub 2019 Jul 29.

Developmental and Stem Cell Biology Program, The Hospital for Sick Children, Toronto, Ontario, Canada; Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada. Electronic address:

Background: The Xp22.11 locus that encompasses PTCHD1, DDX53, and the long noncoding RNA PTCHD1-AS is frequently disrupted in male subjects with autism spectrum disorder (ASD), but the functional consequences of these genetic risk factors for ASD are unknown.

Methods: To evaluate the functional consequences of PTCHD1 locus deletions, we generated induced pluripotent stem cells (iPSCs) from unaffected control subjects and 3 subjects with ASD with microdeletions affecting PTCHD1-AS/PTCHD1, PTCHD1-AS/DDX53, or PTCHD1-AS alone. Function of iPSC-derived cortical neurons was assessed using molecular approaches and electrophysiology. We also compiled novel and known genetic variants of the PTCHD1 locus to explore the roles of PTCHD1 and PTCHD1-AS in genetic risk for ASD and other neurodevelopmental disorders. Finally, genome editing was used to explore the functional consequences of deleting a single conserved exon of PTCHD1-AS.

Results: iPSC-derived neurons from subjects with ASD exhibited reduced miniature excitatory postsynaptic current frequency and N-methyl-D-aspartate receptor hypofunction. We found that 35 ASD-associated deletions mapping to the PTCHD1 locus disrupted exons of PTCHD1-AS. We also found a novel ASD-associated deletion of PTCHD1-AS exon 3 and showed that exon 3 loss altered PTCHD1-AS splicing without affecting expression of the neighboring PTCHD1 coding gene. Finally, targeted disruption of PTCHD1-AS exon 3 recapitulated diminished miniature excitatory postsynaptic current frequency, supporting a role for the long noncoding RNA in the etiology of ASD.

Conclusions: Our genetic findings provide strong evidence that PTCHD1-AS deletions are risk factors for ASD, and human iPSC-derived neurons implicate these deletions in the neurophysiology of excitatory synapses and in ASD-associated synaptic impairment.
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http://dx.doi.org/10.1016/j.biopsych.2019.07.014DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6948145PMC
January 2020

Engineering universal cells that evade immune detection.

Nat Rev Immunol 2019 12 15;19(12):723-733. Epub 2019 Aug 15.

Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Ontario, Canada.

The prospect of transplanting cells and tissues without the risk of immune rejection or the need for powerful immunosuppressive drugs is the 'holy grail' of transplantation medicine. Now, with the advent of pluripotent stem cells, CRISPR-Cas9 and other gene-editing technologies, the race to create 'off-the-shelf' donor cells that are invisible to the immune system ('universal cells') has started. One important approach for creating such cells involves the manipulation of genes required for immune recognition, in particular HLA class I and II proteins. Other approaches leverage knowledge of immune-cloaking strategies used by certain bacteria, viruses, parasites, the fetus and cancer cells to induce tolerance to allogeneic cell-based therapies by modifying cells to express immune-suppressive molecules such as PD-L1 and CTLA4-Ig. Various academic groups as well as biotechnology and pharmaceutical companies are on the verge of bringing these therapies into the clinic.
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http://dx.doi.org/10.1038/s41577-019-0200-1DOI Listing
December 2019

Coronary stent implantation for acute basilar artery occlusion with underlying stenosis.

EuroIntervention 2020 Dec 18;16(12):e1021-e1028. Epub 2020 Dec 18.

Department Section of Neurointervention, Semmelweis University Department of Neurosurgery, National Institute of Clinical Neurosciences, Budapest, Hungary.

Aims: Our aim was to study the effectiveness of coronary stent implantation during the endovascular treatment (EVT) of acute basilar artery occlusion (BAO) with occlusion-underlying intracranial atherosclerotic stenosis (ICAS).

Methods And Results: We retrospectively analysed 91 consecutive BAO patients who underwent EVT between February 2014 and January 2019 in a single, high-volume neurointerventional centre. We studied the effect of immediate coronary stent implantation on the clinical outcome of BAO with occlusion-underlying stenosis. BAO patients with underlying ICAS (n=41) were characterised by longer symptom-onset-to-reperfusion times (231 min vs 173 min, p=0.0020), lower TICI 2b-3 reperfusion rates (65.85% vs 90.00%, p=0.0084), and higher overall mortality (HR 2.021, p=0.0417) compared to the BAO cases without ICAS (n=50). The patients undergoing stenting (n=18) had lower residual basilar artery (BA) stenosis (14.7% vs 81.0%, p<0.0001), higher chance for functional recovery (OR 7.6, p=0.0250) and higher chance of survival (HR 4.163, p=0.0026) compared to the BAO-ICAS cases treated without coronary stents (n=21).

Conclusions: The immediate treatment of the occlusion-underlying stenosis with coronary stents and dual antiplatelet therapy (DAPT) in BAO was associated with improved overall survival and better functional outcomes.
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http://dx.doi.org/10.4244/EIJ-D-19-00519DOI Listing
December 2020

Conversion of human and mouse fibroblasts into lung-like epithelial cells.

Sci Rep 2019 06 21;9(1):9027. Epub 2019 Jun 21.

Program in Developmental & Stem Cell Biology, SickKids Research Institute, Hospital for Sick Children, Toronto, ON, Canada.

Cell lineage conversion of fibroblasts to specialized cell types through transdifferentiation may provide a fast and alternative cell source for regenerative medicine. Here we show that transient transduction of fibroblasts with the four reprogramming factors (Oct4, Sox2, Klf4, and c-Myc) in addition to the early lung transcription factor Nkx2-1 (also known as Ttf1), followed by directed differentiation of the cells, can convert mouse embryonic and human adult dermal fibroblasts into induced lung-like epithelial cells (iLEC). These iLEC differentiate into multiple lung cell types in air liquid interface cultures, repopulate decellularized rat lung scaffolds, and form lung epithelia composed of Ciliated, Goblet, Basal, and Club cells after transplantation into immune-compromised mice. As proof-of-concept, differentiated human iLEC harboring the Cystic Fibrosis mutation dF508 demonstrated pharmacological rescue of CFTR function using the combination of lumacaftor and ivacaftor. Overall, this is a promising alternative approach for generation of patient-specific lung-like progenitors to study lung function, disease and future regeneration strategies.
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http://dx.doi.org/10.1038/s41598-019-45195-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6588580PMC
June 2019

24-Hour Near-Infrared Spectroscopy Monitoring of Acute Ischaemic Stroke Patients Undergoing Thrombolysis or Thrombectomy: A Pilot Study.

J Stroke Cerebrovasc Dis 2019 Aug 8;28(8):2337-2342. Epub 2019 Jun 8.

Department of Neurology, Albert Szent-Györgyi Clinical Center, University of Szeged, Szeged, Hungary. Electronic address:

Introduction: Monitoring of acute ischaemic stroke patients during thrombolysis or thrombectomy is based mostly on frequent physical examinations, since no objective measurement of cerebrovascular haemodynamics is available in routine clinical practice. Near-infrared spectroscopy (NIRS) is a bed-side, noninvasive assessment tool that could help monitor these patients and potentially guide therapeutic interventions. Our goal in this pilot study was to investigate whether NIRS is a suitable method to monitor leptomeningeal collateral circulation via changes in cortical oxygen saturation in the first 24 hours of acute ischaemic stroke.

Patients And Methods: Our study included 5 patients with acute anterior circulation infarcts. All patients received thrombolytic therapy and 1 had thrombectomy. 24-hour continuous NIRS monitoring was performed on all participants.

Results: We aimed to give a detailed description of each NIRS recording and explain how the observed findings could correlate with changes in anterior watershed territory collateral circulation and clinical outcome.

Conclusion: Our pilot study supports the use of NIRS monitoring in acute ischaemic stroke. We believe that this technique could provide real-time information on the dynamic changes of leptomeningeal collateral circulation and help monitor the effects of thrombolysis and thrombectomy.
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http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2019.05.026DOI Listing
August 2019
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