المؤلفون: Hitti-Malin, Rebekkah, Panneman, Daan, Corradi, Zelia, Boonen, Erica, Astuti, Galuh, Dhaenens, Claire-Marie, Stöhr, Heidi, Weber, Bernhard, Sharon, Dror, Banin, Eyal, Karali, Marianthi, Banfi, Sandro, Ben-Yosef, Tamar, Glavač, Damjan, Farrar, G, Ayuso, Carmen, Liskova, Petra, Dudakova, Lubica, Vajter, Marie, Ołdak, Monika, Szaflik, Jacek, Matynia, Anna, Gorin, Michael, Kämpjärvi, Kati, Bauwens, Miriam, De Baere, Elfride, Hoyng, Carel, Li, Catherina, Klaver, Caroline, Inglehearn, Chris, Fujinami, Kaoru, Rivolta, Carlo, Allikmets, Rando, Zernant, Jana, Lee, Winston, Podhajcer, Osvaldo, Fakin, Ana, Sajovic, Jana, AlTalbishi, Alaa, Valeina, Sandra, Taurina, Gita, Vincent, Andrea, Roberts, Lisa, Ramesar, Raj, Sartor, Giovanna, Luppi, Elena, Downes, Susan, van den Born, L, McLaren, Terri, De Roach, John, Lamey, Tina, Thompson, Jennifer, Chen, Fred, Tracewska, Anna, Kamakari, Smaragda, Sallum, Juliana, Bolz, Hanno, Kayserili, Hülya, Roosing, Susanne, Cremers, Frans

المصدر: Biomolecules. 14(3)

مصطلحات موضوعية: inherited, macula, maculopathies, penetrance, retinal, sequencing, Humans, Mutation, Penetrance, Pedigree, Macular Degeneration, Retina, Phenotype, ATP-Binding Cassette Transporters, Eye Proteins, Cadherin Related Proteins, Nerve Tissue Proteins

الوصف: Inherited macular dystrophies (iMDs) are a group of genetic disorders, which affect the central region of the retina. To investigate the genetic basis of iMDs, we used single-molecule Molecular Inversion Probes to sequence 105 maculopathy-associated genes in 1352 patients diagnosed with iMDs. Within this cohort, 39.8% of patients were considered genetically explained by 460 different variants in 49 distinct genes of which 73 were novel variants, with some affecting splicing. The top five most frequent causative genes were ABCA4 (37.2%), PRPH2 (6.7%), CDHR1 (6.1%), PROM1 (4.3%) and RP1L1 (3.1%). Interestingly, variants with incomplete penetrance were revealed in almost one-third of patients considered solved (28.1%), and therefore, a proportion of patients may not be explained solely by the variants reported. This includes eight previously reported variants with incomplete penetrance in addition to CDHR1:c.783G>A and CNGB3:c.1208G>A. Notably, segregation analysis was not routinely performed for variant phasing-a limitation, which may also impact the overall diagnostic yield. The relatively high proportion of probands without any putative causal variant (60.2%) highlights the need to explore variants with incomplete penetrance, the potential modifiers of disease and the genetic overlap between iMDs and age-related macular degeneration. Our results provide valuable insights into the genetic landscape of iMDs and warrant future exploration to determine the involvement of other maculopathy genes.

وصف الملف: application/pdf

الوصول الحر: https://escholarship.org/uc/item/00w3d2bqTest

المؤلفون: Hayes, D. Peran

المساهمون: University/Department: Universitat Pompeu Fabra. Departament de Ciències Experimentals i de la Salut

مرشدي الرسالة: Solon, Jérôme

المصدر: TDX (Tesis Doctorals en Xarxa)

مصطلحات موضوعية: Dorsal Closure, Biomechanics, Morphogenesis, Actomyosin, Pulsation, Oscillation, Epithelia, Cadherin, Junction

الوصف: The vast diversity of life on Earth develops from relatively uniform beginnings via self-organised movements occurring between groups of cells. Whilst the variety of shapes resulting from morphogenesis is boundless, the number of distinct geometrical and topological changes that it comprises, are limited. The control of biological form arises from an interplay between molecular biology and biomechanics. In this work we adopt a biophysical approach to study the regulation of a topological transformation that occurrs during the development of the fruit fly Drosophila melanogaster. Shortly before the Drosophila embryo transitions into a larva, it first covers its entire body in a single epidermal tissue layer. To achieve this, two layers of epidermis stretch laterally around the embryo and fuse dorsally, sealing a gap that was previously filled by a dying, pulsatile tissue, the amnioserosa (AS). This process is known as dorsal closure, and has drawn significant interest as a model system for other tissue fusion events, such as wound healing and neural tube closure. In this work, we first consider the global control of the process, deriving a biophysical description of the system from first physical principles: namely a force balance at the two corners (canthi) of the opening, and the Young- Laplace relationship around its contour. This represents an advancement on previous work in terms of the simplicity of the model, and the introduction of a term for AS volume loss to a two-dimensional description. In the second part of this thesis, we focus on the role of the pulsatile behaviour of the AS. We report on a new experimental assay for mechanically perturbing the Drosophila embryo. Combining this with the use of a novel method for extracting quantitative information from confocal cell images, we investigate the response of the AS to mechanical stretch. Finally, we propose a dual role for cortical myosin flows in the AS, both to offer structural supportjunctions are stretched, and to promote endocytotically mediated removal of excess junctions.

الوصف (مترجم): La gran diversitat de vida a la terra es va desenvolupar arran d’uns inicis relativament uniformes i mitjançant moviments autoorganitzats que varen ocórrer entre grups de cèl·lules. Mentre que la varietat de formes que sorgeixen de la morfogènesi és il·limitada, el nombre de canvis geomètrics i topològics que la constitueixen és limitat. El control de la forma biològica sorgeix de la interacció entre la biologia molecular i la biomecànica. En aquest treball hem adoptat una aproximació biofísica per estudiar la regulació d’una transformació topològica que té lloc durant el desenvolupament de la mosca de la fruita Drosophila melanogaster. Just abans que l’embrió de Drosophila esdevingui en larva, el seu cos es cobreix amb un únic estrat de teixit epidèrmic. Per aconseguir-lo, dues capes d’epidermis s’estiren lateralment envoltant l’embrió i es fusionen dorsalment, segellant un locus que prèviament estava ple d’un teixit mort i pulsatiu anomenat amnioserosa (AS). Aquest procés es coneix com a "tancament dorsal" i resulta de gran interès com a model per estudiar altres esdeveniments de fusió tissular, com ara la cicatrització de ferides o el tancament del tub neural. Amb aquest projecte, en primer lloc fem una anàlisi del control global del procés, derivant una descripció biofísica del sistema a partir de principis bàsics primordials de la física: aquests principis són una força d’equilibri en els dos cantons (canthi) de l’obertura, i la relació Young-Laplace al voltant del seu contorn. Aquest model representa un avenç en relació a treballs previs com a conseqüència de la seva simplicitat, i la introducció d’un terme per a la pèrdua de volum de l’AS en una descripció de dues dimensions. En la segona part de la tesi, ens centrem en el paper que té el comportament pulsatiu de l’AS, ampliant el coneixement existent sobre un nou assaig experimental que pertorba mecànicament l’embrió de la mosca Drosophila. Combinant aquesta aproximació amb un nou mètode per extreure informa-ció quantitativa d’imatges confocals de les cèl·lules, investiguem la resposta de l’AS a l’estrès mecànic. Finalment, proposem una doble funció per als fluxos corticals de miosina a l’AS: donant suport estructural a les unions que s’estiren i promovent l’eliminació de l’excés d’unions mitjançant l’endocitosi
Programa de doctorat en Biomedicina

وصف الملف: application/pdf

الوصول الحر: http://hdl.handle.net/10803/586069Test

المؤلفون: Sadlecki Pawel, Walentowicz-Sadlecka Malgorzata

المصدر: Open Medicine, Vol 19, Iss 1, Pp 204-30 (2024)

مصطلحات موضوعية: borderline ovarian tumours, molecular features, mutations, genetic mutations, braf, kras, nras, arid1a, cadm1, pik3ca, chek2, claudin-1, erbb2, loss of heterozygosity, pten, microsatellite instability, b-catenin, e-cadherin, brca 1, brca 2, Medicine

الوصف: Borderline ovarian tumours (BOTs) show intriguing characteristics distinguishing them from other ovarian tumours. The aim of the systematic review was to analyse the spectrum of molecular changes found in BOTs and discuss their significance in the context of the overall therapeutic approach. The systematic review included articles published between 2000 and 2023 in the databases: PubMed, EMBASE, and Cochrane. After a detailed analysis of the available publications, we qualified for the systematic review: 28 publications on proto-oncogenes: BRAF, KRAS, NRAS, ERBB2, and PIK3CA, 20 publications on tumour suppressor genes: BRCA1/2, ARID1A, CHEK2, PTEN, 4 on adhesion molecules: CADM1, 8 on proteins: B-catenin, claudin-1, and 5 on glycoproteins: E-Cadherin. In addition, in the further part of the systematic review, we included eight publications on microsatellite instability and three describing loss of heterozygosity in BOT. Molecular changes found in BOTs can vary on a case-by-case basis, identifying carcinogenic mutations through molecular analysis and developing targeted therapies represent significant advancements in the diagnosis and treatment of ovarian malignancies. Molecular studies have contributed significantly to our understanding of BOT pathogenesis, but substantial research is still required to elucidate the relationship between ovarian neoplasms and extraneous disease, identify accurate prognostic indicators, and develop targeted therapeutic approaches.

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/2391-5463Test

الوصول الحر: https://doaj.org/article/61b5980ba5e544b385458d81e31cafd0Test

المؤلفون: Tian-long Wang, Xiao-juan Miao, Yan-rong Shuai, Hao-ping Sun, Xiao Wang, Min Yang, Nan Zhang

المصدر: Scientific Reports, Vol 14, Iss 1, Pp 1-9 (2024)

مصطلحات موضوعية: FAT atypical cadherin 1 (FAT1), Diffuse large B cell lymphoma (DLBCL), Yes1 associated transcriptional regulator (YAP1), Heterogeneous nuclear ribonucleoprotein D (HNRNPD), m6A, ALKBH5, Medicine, Science

الوصف: Abstract Emerging evidence shows that FAT atypical cadherin 1 (FAT1) mutations occur in lymphoma and are associated with poorer overall survival. Considering that diffuse large B cell lymphoma (DLBCL) is the category of lymphoma with the highest incidence rate, this study aims to explore the role of FAT1 in DLBCL. The findings demonstrate that FAT1 inhibits the proliferation of DLBCL cell lines by downregulating the expression of YAP1 rather than by altering its cellular localization. Mechanistic analysis via meRIP-qPCR/luciferase reporter assays showed that FAT1 increases the m6A modification of YAP1 mRNA 3′UTR and the subsequent binding of heterogeneous nuclear ribonucleoprotein D (HNRNPD) to the m6A modified YAP1 mRNA, thus decreasing the stability of YAP1 mRNA. Furthermore, FAT1 increases YAP1 mRNA 3′UTR m6A modification by decreasing the activity of the TGFβ-Smad2/3 pathway and the subsequent expression of ALKBH5, which is regulated at the transcriptional level by Smad2/3. Collectively, these results reveal that FAT1 inhibits the proliferation of DLBCL cells by increasing the m6A modification of the YAP1 mRNA 3’UTR via the TGFβ-Smad2/3-ALKBH5 pathway. The findings of this study therefore indicate that FAT1 exerts anti-tumor effects in DLBCL and may represent a novel target in the treatment of this form of lymphoma.

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/2045-2322Test

الوصول الحر: https://doaj.org/article/72c3a5788cf044f098d6751f5970792aTest

المؤلفون: Zhengrui Li, Yuan Liu, Xufeng Huang, Qi Wang, Rao Fu, Xutao Wen, Ji’an Liu, Ling Zhang

المصدر: BMC Oral Health, Vol 24, Iss 1, Pp 1-13 (2024)

مصطلحات موضوعية: Fusobacterium nucleatum, Oral squamous cell carcinoma, Cell proliferation, CDH1(E-Cadherin), β-catenin, Phosphorylation, Dentistry, RK1-715

الوصف: Abstract Background Fusobacterium nucleatum (F. nucleatum) is a microbial risk factor whose presence increases the risk of oral squamous cell carcinoma (OSCC) progression. However, whether it can promote the proliferation of OSCC cells remains unknown. Methods In this study, we investigated F. nucleatum effect on OSCC cell proliferation using in vitro and in vivo experiments. Results Our results showed that F. nucleatum promoted OSCC cell proliferation, doubling the cell count after 72 h (CCK-8 assay). Cell cycle analysis revealed G2/M phase arrest. F. nucleatum interaction with CDH1 triggered phosphorylation, upregulating downstream protein β-catenin and activating cyclinD1 and Myc. Notably, F. nucleatum did not affect noncancerous cells, unrelated to CDH1 expression levels in CAL27 cells. Overexpression of phosphorylated CDH1 in 293T cells did not upregulate β-catenin and cycle-related genes. In vivo BALB/c nude experiments showed increased tumor volume and Ki-67 proliferation index after F. nucleatum intervention. Conclusion Our study suggests that F. nucleatum promotes OSCC cell proliferation through the CDH1/β-catenin pathway, advancing our understanding of its role in OSCC progression and highlighting its potential as a therapeutic target.

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/1472-6831Test

الوصول الحر: https://doaj.org/article/79906c3c5394478bb35706e2cc4f7995Test

المؤلفون: Jizhen Wei, Min Zhang, Pin Li, Zhongyuan Deng, Xinming Yin, Shiheng An, Xianchun Li

المصدر: Journal of Integrative Agriculture, Vol 23, Iss 5, Pp 1604-1617 (2024)

مصطلحات موضوعية: Bt crops, cadherin, Cry toxin, receptor, resistance mechanism, Agriculture (General), S1-972

الوصف: Helicoverpa zea is a major target pest of pyramided transgenic crops expressing Cry1, Cry2 and/or Vip3Aa proteins from Bacillus thuringiensis (Bt) in the United States. Laboratory-selected Cry1Ac/Cry2Ab cross resistance and field-evolved practical dual resistance of H. zea to these two toxins have been widely reported. Whether the widespread Cry1Ac/Cy2Ab dual resistance of H. zea has resulted from the selection of one shared or two independent resistance mechanisms by pyramided Bt crops remains unclear. Cadherin is a well-confirmed receptor of Cry1Ac and a suggested receptor of Cry2Ab in at least three Lepidopteran species. To test whether cadherin may serve as one shared mechanism for the cross and dual resistance of H. zea to Cry1Ac and Cry2Ab, we cloned H. zea cadherin (HzCadherin) cDNA and studied its functional roles in the mode of action of Cry1Ac and Cry2Ab by gain- and loss-of-function analyses. Heterologous expression of HzCadherin in H. zea midgut, H. zea fat body and Sf9 cells made all three of these cell lines more susceptible to activated Cry1Ac but not activated Cry2Ab, whereas silencing HzCadherin of H. zea midgut and fat body cells significantly reduced the susceptibility to Cry1Ac but not Cry2Ab. Likewise, suppressing HzCadherin with siRNA made H. zea larvae resistant to Cry1Ac. These results clearly demonstrate that HzCadherin is not a receptor for Cry2Ab, and thus it is unlikely to serve as one shared mechanism for the cross and dual resistance of H. zea to Cry1Ac and Cry2Ab.

وصف الملف: electronic resource

العلاقة: http://www.sciencedirect.com/science/article/pii/S2095311923003842Test; https://doaj.org/toc/2095-3119Test

الوصول الحر: https://doaj.org/article/1e6cdef8dea746149d658b294e71b77bTest

المؤلفون: Estalella Mercadé, Laia

المساهمون: University/Department: Universitat Autònoma de Barcelona. Departament de Cirurgia

مرشدي الرسالة: Artigas Raventós, Vicenç, Céspedes Navarro, Maria Virtudes, Trias Folch, Manel

المصدر: TDX (Tesis Doctorals en Xarxa)

مصطلحات موضوعية: Càncer colorectal, Cáncer colorectal, Colorectal cancer, Metàstasis hepàtiques colorectals, Metástasis hepáticas colorectales, E-caderina, E-cadherin, Ciències de la Salut

الوصف: INTRODUCCIÓ: El carcinoma colorectal representa una de les neoplàsies més prevalents i la segona causa de mort per càncer en el món occidental. En el moment del diagnòstic, aproximadament el 25-30% dels pacients presentaran metàstasis hepàtiques sincròniques (estadi IV) i el 25% desenvoluparan metàstasis hepàtiques durant l’evolució de la malaltia, la majoria durant els 3 anys del diagnòstic del tumor primari. Tot i que la cirurgia de resecció hepàtica és considerada l’únic tractament capaç d’oferir una supervivència a llarg termini en els pacients amb metàstasis hepàtiques, essent aquesta als 5 anys del 25 al 40% en diferents sèries i, de fins al 58% amb l’ús de quimioteràpia perioperatòria, entre el 60 i el 85% dels casos presentaran recurrència de la malaltia durant els 2 següents anys de la resecció hepàtica. A part dels factors clínic-patològics associats a mal pronòstic pel que fa a supervivència global i lliure de malaltia, és necessari l’estudi de factors moleculars que ens ajudin a comprendre les diferències evolutives entre pacients amb un estadiatge similar de la malaltia. Segons resultats previs, es proposa que la proteïna epitelial transmembrana E-caderina pot tenir una funció oncogènica associada al seu grau de proteòlisis i translocació al citosol i/o nucli cel·lular. HIPÒTESI: La prevalença d’E-caderina proteolitzada localitzada en el citosol i/o nucli de la cèl·lula tumoral comportaria major agressivitat i capacitat d’invasió tumoral i permetria explicar les diferències en l’evolució clínica dels pacients. MATERIAL I MÈTODES: A partir d’una mostra de 242 pacients intervinguts de metàstasis hepàtiques d’origen colorectal entre els anys 1998 i 2009, es procedeix a l’estudi de les supervivències global, lliure de malaltia i supervivències segons el patró de recurrència. Es realitza un anàlisis bi i multivariant dels factors clínic-patològics dels pacients associats a mal pronòstic. Finalment, es procedeix a l’anàlisi de l’expressió nuclear d’E-caderina, mitjançant tècniques d’immunohistoquímica, en les mostres quirúrgiques de les metàstasis hepàtiques resecades. RESULTATS: La mediana de supervivència dels 242 pacients des de la cirurgia de resecció hepàtica fou de 51 mesos. El 71% dels pacients presentaren recurrència, amb un interval lliure de malaltia de 22 mesos de mediana. Pel que fa al patró de recurrència dels pacients intervinguts d’una primera cirurgia de metàstasis hepàtiques d’origen colorectal, la localització única hepàtica (47%), constitueix per una banda, el lloc de major recurrència de la malaltia i per altra, la localització amb un menor interval lliure de malaltia, amb una mediana de 13 mesos. Els pacients de millor pronòstic són els que presenten recurrència pulmonar única, tant una millor supervivència lliure de malaltia, de 18 mesos, com una millor supervivència global des de l’hepatectomia inicial (52 mesos). La mediana de supervivència global dels pacients amb E-caderina nuclear negativa en les mostres de MHCCR és de 82 mesos, mentre que la mediana pels pacients amb positivitat per a E-caderina nuclear és de 30 mesos. CONCLUSIONS: D’entre el total de pacients que presenten recurrència després d’una cirurgia de metàstasis hepàtiques, la localització pulmonar és la de millor pronòstic, pel que cal considerar el tractament quirúrgic d’aquests pacients sempre que sigui possible (cirurgia curativa R0 i pacient operable). L’edat, l’afectació ganglionar (N1 i 2), la presència d’invasió perineural, el nombre de metàstasis ≥ 3 i la presència d’E-caderina nuclear, són factors de risc independents de pitjor supervivència global. Igualment, les quatre darreres variables coincideixen com a factors de risc independents predictius de recurrència de la malaltia. La presència d’E-caderina nuclear en les mostres de metàstasis hepàtiques, s’associa a pitjor pronòstic en quant a supervivència global, supervivència lliure de malaltia i major risc de recurrència després d’una primera intervenció curativa de resecció per metàstasis hepàtiques d’origen colorectal (p<0.001).

الوصف (مترجم): INTRODUCTION: Colorectal carcinoma (CRC) is one of the most prevalent cancer and the second leading cause of cancer-related mortality in Western countries. Approximately 25-30% of CRC patients present synchronous liver metastases at time of diagnosis and an expected 25% will develop liver metastases during the course of the disease, mostly within the first 3 years. Liver resection surgery is considered the only treatment capable of providing long-term survival in patients with liver metastases. Results from different series show a five-year survival rate of 25-40% and up to 58% with the use of per-operative chemotherapy. Nonetheless, an estimated 60 to 85% of patients will present recurrent disease during the 2 year-period following liver resection. In addition to the clinicopathologic features associated with poor prognosis in terms of disease-free and overall survival, it is esssential to study the molecular factors that might help us understand the differences in clinical behavior among patients with similar stage of disease. According to previous results, it has been proposed that the epithelial protein called E-cadherin could have an oncogenic role associated with the degree of proteolysis and its translocation to the cytosol and/or cell nucleus. HYPOTHESIS: The prevalence of proteolysed E-cadherin in the cytosol and/or nucleus of tumor cells is associated to an increased grade of tumor aggressiveness. MATERIAL AND METHODS: A total of 242 patients operated on for colorectal liver metastases between 1998 and 2009 were retrospectively assessed for overall and disease-free survival as well as for specific survival related to recurrence location. Univariate and multivariate analyses were used to assess the predictive value of clinicopathological variables for both disease-free and overall survival. Furthermore, immunohistochemical analysis of E-cadherin nuclear expression in surgical samples of liver metastases was performed. RESULTS: The median survival of the 242 patients was 51 months. Seventy-one percent of these patients developed recurrent disease, with a median disease-free survival of 22 months. Liver only (47%) was the most frequent site of recurrent disease after surgery for CRC liver metastases and accounted for the lowest disease-free interval (median 13 months). On the other hand, patients with lung only recurrence had the best disease free survival (median 18 months) and overall survival rates (median 52 months). Patients with negative E-cadherin nuclear expression had a better median overall survival when compared to those with positive expression (82 vs 30 months, p<0.001). CONCLUSIONS: In patients presenting recurrent disease after surgery for CRC liver metastases, those with lung metastatic disease have shown the best outcome. Surgical treatment should be considered and attempted in this group of patients whenever possible (R0 surgery in a fit patient). Age, lymph node involvement (N1 –N2), perineural invasion, number of liver metastasis (≥ 3) and the presence of nuclear E-cadherin are all independent risk factors associated with a worse overall survival, and are also independent predictive factors of recurrent disease. After primary curative resection of CRC liver metastases, the presence of nuclear E-cadherin in liver metastasis samples has been associated with a greater risk of recurrence and worse prognosis when considering overall survival and disease-free survival (p<0.001).

وصف الملف: application/pdf

الوصول الحر: http://hdl.handle.net/10803/298318Test

المؤلفون: Sharafutdinov, Irshad, Tegtmeyer, Nicole, Rohde, Manfred, Olofsson, Annelie, Ur Rehman, Zia, Arnqvist, Anna, Backert, Steffen

المصدر: Cells. 13(3)

مصطلحات موضوعية: Campylobacter, E-cadherin, occludin, serine protease HtrA, tight junctions

الوصف: Fundamental functions of the intestinal epithelium include the digestion of food, absorption of nutrients, and its ability to act as the first barrier against intruding microbes. Campylobacter jejuni is a major zoonotic pathogen accounting for a substantial portion of bacterial foodborne illnesses. The germ colonizes the intestines of birds and is mainly transmitted to humans through the consumption of contaminated poultry meat. In the human gastrointestinal tract, the bacterium triggers campylobacteriosis that can progress to serious secondary disorders, including reactive arthritis, inflammatory bowel disease and Guillain–Barré syndrome. We recently discovered that C. jejuni serine protease HtrA disrupts intestinal epithelial barrier functions via cleavage of the tight and adherens junction components occludin, claudin-8 and E-cadherin. However, it is unknown whether epithelial damage is mediated by the secreted soluble enzyme, by HtrA contained in shed outer-membrane vesicles (OMVs) or by another mechanism that has yet to be identified. In the present study, we investigated whether soluble recombinant HtrA and/or purified OMVs induce junctional damage to polarized intestinal epithelial cells compared to live C. jejuni bacteria. By using electron and confocal immunofluorescence microscopy, we show that HtrA-expressing C. jejuni bacteria trigger efficient junctional cell damage, but not soluble purified HtrA or HtrA-containing OMVs, not even at high concentrations far exceeding physiological levels. Instead, we found that only bacteria with active protein biosynthesis effectively cleave junctional proteins, which is followed by paracellular transmigration of C. jejuni through the epithelial cell layer. These findings shed new light on the pathogenic activities of HtrA and virulence strategies of C. jejuni.

وصف الملف: electronic

الوصول الحر: https://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-222651Test
https://doi.org/10.3390/cells13030224Test
https://umu.diva-portal.org/smash/get/diva2:1852809/FULLTEXT01.pdfTest

المؤلفون: Gupta Aashi

المصدر: Journal of Pharmacy and Bioallied Sciences, Vol 16, Iss 6, Pp 1838-1842 (2024)

مصطلحات موضوعية: e- cadherin, epithelial dysplasia, immunohistochemistry, oral squamous cell carcinoma, Pharmacy and materia medica, RS1-441, Analytical chemistry, QD71-142

الوصف: BackgroundCancers arising in the oral cavity are more commonly of squamous cell carcinomas. E-cadherin is a calcium-dependant transmembrane glycoprotein of the type-1 cadherin superfamily is an invasion/tumor suppressor gene, which plays a vital role in epithelial cell–cell adhesion. Epithelial E-cadherin expression loss increases tumor invasiveness and metastasis. AimTo determine the expression of E-cadherin in oral epithelial dysplasia (OED) and oral squamous cell carcinoma (OSCC). Materials and MethodsAnalysis of E-cadherin expression in 10 cases of normal mucosa, 15 cases of various grades of OED, 15 cases of OSCC. Statistical AnalysisThe data were calculated using Chi-square test and analysis of variance test (ANOVA). ResultsAn intragroup comparison of staining intensity and staining location for OED showed a highly significant difference between mild and moderate grade (P < 0.001). A significant difference of staining intensity was noted among well and moderately differentiated grades, and well and poorly differentiated grades of OSCC. A comparison of staining location among well and poorly differentiated grades of OSCC was found to be significant. ConclusionExpression loss is observed as the severity of the lesion progresses in both OSCC and OED. The increased loss of expression in oral squamous cell carcinoma poorer the prognosis.

وصف الملف: electronic resource

العلاقة: https://journals.lww.com/10.4103/jpbs.jpbs_38_24Test; https://doaj.org/toc/0976-4879Test; https://doaj.org/toc/0975-7406Test

الوصول الحر: https://doaj.org/article/c57ef16a3a8c4e0ba667ea7824895dbdTest

المؤلفون: Aurélie Joussaume, Chryso Kanthou, Olivier E. Pardo, Lucie Karayan-Tapon, Omar Benzakour, Fatima Dkhissi

المصدر: Current Issues in Molecular Biology, Vol 46, Iss 4, Pp 3278-3293 (2024)

مصطلحات موضوعية: protein S, TAM receptors, vascular permeability, endothelial cell biology, vascular endothelial cadherin, actin remodeling, Biology (General), QH301-705.5

الوصف: Protein S (PROS1) is a vitamin K-dependent anticoagulant factor, which also acts as an agonist for the TYRO3, AXL, and MERTK (TAM) tyrosine kinase receptors. PROS1 is produced by the endothelium which also expresses TAM receptors, but little is known about its effects on vascular function and permeability. Transwell permeability assays as well as Western blotting and immunostaining analysis were used to monitor the possible effects of PROS1 on both endothelial cell permeability and on the phosphorylation state of specific signaling proteins. We show that human PROS1, at its circulating concentrations, substantially increases both the basal and VEGFA-induced permeability of endothelial cell (EC) monolayers. PROS1 induces p38 MAPK (Mitogen Activated Protein Kinase), Rho/ROCK (Rho-associated protein kinase) pathway activation, and actin filament remodeling, as well as substantial changes in Vascular Endothelial Cadherin (VEC) distribution and its phosphorylation on Ser665 and Tyr685. It also mediates c-Src and PAK-1 (p21-activated kinase 1) phosphorylation on Tyr416 and Ser144, respectively. Exposure of EC to human PROS1 induces VEC internalization as well as its cleavage into a released fragment of 100 kDa and an intracellular fragment of 35 kDa. Using anti-TAM neutralizing antibodies, we demonstrate that PROS1-induced VEC and c-Src phosphorylation are mediated by both the MERTK and TYRO3 receptors but do not involve the AXL receptor. MERTK and TYRO3 receptors are also responsible for mediating PROS1-induced MLC (Myosin Light Chain) phosphorylation on a site targeted by the Rho/ROCK pathway. Our report provides evidence for the activation of the c-Src/VEC and Rho/ROCK/MLC pathways by PROS1 for the first time and points to a new role for PROS1 as an endogenous vascular permeabilizing factor.

وصف الملف: electronic resource

العلاقة: https://www.mdpi.com/1467-3045/46/4/205Test; https://doaj.org/toc/1467-3037Test; https://doaj.org/toc/1467-3045Test

الوصول الحر: https://doaj.org/article/7eb8813ce6a24d078a0b98f358bbfe47Test