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Acute skin wound healing is a multistage process consisting of a plethora of tightly regulated signaling events in specialized cells. The Thy-1 (CD90) glycoprotein interacts with integrins and the heparan sulfate proteoglycan syndecan 4, generating a trimolecular complex that triggers bi-directional signaling to regulate diverse aspects of the wound healing process. These proteins can act either as ligands or receptors, and they are critical for the successful progression of wound healing. The expression of Thy-1, integrins, and syndecan 4 is controlled during the healing process, and the lack of expression of any of these proteins results in delayed wound healing. Here, we review and discuss the roles and regulatory events along the stages of wound healing that support the relevance of Thy-1, integrins, and syndecan 4 as crucial regulators of skin wound healing.
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The current pandemic caused by SARS-CoV-2 has put public health at risk, being wastewater-based epidemiology (WBE) a potential tool in the detection, prevention, and treatment of present and possible future outbreaks, since this virus enters wastewater through various sources such as feces, vomit, and sputum. Thus, advanced technologies such as advanced oxidation processes (AOP), membrane technology (MT) are identified through a systematic literature review as an alternative option for the destruction and removal of emerging contaminants (drugs and personal care products) released mainly by infected patients. The objectives of this review are to know the implications that the new COVID-19 outbreak is generating and will generate in water compartments, as well as the new challenges faced by wastewater treatment plants due to the change in a load of contaminants and the solutions proposed based on the aforementioned technologies to be applied to preserve public health and the environment.
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BACKGROUND: Syndecans regulate cell migration thus having key roles in scarring and wound healing processes. Our previous results have shown that Thy-1/CD90 can engage both αvß3 integrin and Syndecan-4 expressed on the surface of astrocytes to induce cell migration. Despite a well-described role of Syndecan-4 during cell movement, information is scarce regarding specific Syndecan-4 partners involved in Thy-1/CD90-stimulated cell migration. METHODS: Mass spectrometry (MS) analysis of complexes precipitated with the Syndecan-4 cytoplasmic tail peptide was used to identify potential Syndecan-4-binding partners. The interactions found by MS were validated by immunoprecipitation and proximity ligation assays. The conducted research employed an array of genetic, biochemical and pharmacological approaches, including: PAR-3, Syndecan-4 and Tiam1 silencing, active Rac1 GEFs affinity precipitation, and video microscopy. RESULTS: We identified PAR-3 as a Syndecan-4-binding protein. Its interaction depended on the carboxy-terminal EFYA sequence present on Syndecan-4. In astrocytes where PAR-3 expression was reduced, Thy-1-induced cell migration and focal adhesion disassembly was impaired. This effect was associated with a sustained Focal Adhesion Kinase activation in the siRNA-PAR-3 treated cells. Our data also show that Thy-1/CD90 activates Tiam1, a PAR-3 effector. Additionally, we found that after Syndecan-4 silencing, Tiam1 activation was decreased and it was no longer recruited to the membrane. Syndecan-4/PAR-3 interaction and the alteration in focal adhesion dynamics were validated in mouse embryonic fibroblast (MEF) cells, thereby identifying this novel Syndecan-4/PAR-3 signaling complex as a general mechanism for mesenchymal cell migration involved in Thy-1/CD90 stimulation. CONCLUSIONS: The newly identified Syndecan-4/PAR-3 signaling complex participates in Thy-1/CD90-induced focal adhesion disassembly in mesenchymal cells. The mechanism involves focal adhesion kinase dephosphorylation and Tiam1 activation downstream of Syndecan-4/PAR-3 signaling complex formation. Additionally, PAR-3 is defined here as a novel adhesome-associated component with an essential role in focal adhesion disassembly during polarized cell migration. These novel findings uncover signaling mechanisms regulating cell migration, thereby opening up new avenues for future research on Syndecan-4/PAR-3 signaling in processes such as wound healing and scarring.
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Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Proteínas de Ciclo Celular/metabolismo , Adesões Focais/metabolismo , Mesoderma/citologia , Mesoderma/metabolismo , Proteínas do Tecido Nervoso/metabolismo , Transdução de Sinais , Sindecana-4/metabolismo , Proteína 1 Indutora de Invasão e Metástase de Linfoma de Células T/metabolismo , Animais , Astrócitos/citologia , Astrócitos/metabolismo , Adesão Celular , Linhagem Celular , Movimento Celular , Polaridade Celular , Fibroblastos/metabolismo , Inativação Gênica , Camundongos , Microtúbulos/metabolismo , Ligação Proteica , Ratos , Antígenos Thy-1/metabolismoRESUMO
Introduction: In Head and Neck (HN) cancer, the High-Risk Human Papillomavirus (hr HPV) infection has been associated in about 40% of these tumors. The hr HPV infection is one of the etiological factors of several epithelial tumors; however, its association with the prognosis has not yet been established for patients with Laryngeal Squamous Cell Carcinoma (LSCC). On the other hand, Epidermal Growth Factor Receptor (EGFR) is a molecular marker widely studied in cancer and its overexpression has been associated with poor prognosis in some types of cancer, including the HN cancer. In the present study, we analyzed EGFR expression and HPV detection in a cohort of Mexican patients with LSCC and define their association with clinical-pathological and survival parameters. Methods: EGFR expression analysis was performed by immunohistochemistry assay. A tissue array was constructed based on 30 paraffin-embedded tissue samples. HPV detection was performed by PCR. The results were then compared with the clinical-pathological variables and outcome measures (Kaplan Meier and Cox analysis). Results: High expression of EGFR was observed in 43% of the samples and 20% of HPV detection. The statistical analyses provided evidence of disassociation between clinical-pathological parameters and EGFR expression, but there was an association with poor prognosis. Interestingly, HPV detection is slightly associated with good prognosis. Conclusion: Both, EGFR overexpression and HPV presence could be associated with an unfavorable prognosis in patients with LSCC, independently of other clinical-pathological factors.
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Carcinoma de Células Escamosas/mortalidade , Neoplasias Laríngeas/mortalidade , Infecções por Papillomavirus/mortalidade , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/virologia , DNA Viral/genética , Receptores ErbB/metabolismo , Feminino , Seguimentos , Humanos , Neoplasias Laríngeas/patologia , Neoplasias Laríngeas/virologia , Masculino , México , Pessoa de Meia-Idade , Papillomaviridae/genética , Papillomaviridae/isolamento & purificação , Infecções por Papillomavirus/patologia , Infecções por Papillomavirus/virologia , Prognóstico , Taxa de SobrevidaRESUMO
In 2010, in a cancer genes census, 291 genes were enumerated. These represent near to the 1 % of the total genes, for which there is enough biological evidence that they belong to a new genes classification, known as the cancer genes. These have been defined as the causal genes for sporadic or familiar cancer, when they mutate. The mutation types for these genes includes amplifications, point mutations, deletions, genomic rearranges, amongst others, which lead to a protein over-expression, muting, production of chimeric proteins or a de novo expression. In conjunction these genomic alterations or those of the genetic expression, when they affect specific genes which contribute to the development of cancer, are denominated as cancer genes. It is possible that the list of these alterations will grow longer due to new strategies being developed, for example, the genomic analysis.
En el año 2010, en un censo de genes del cáncer, se enumeraron 291 genes humanos que representan cerca del 1 % de los genes totales, para los cuales existe suficiente evidencia biológica de que pertenecen a una nueva clasificación de genes: los genes del cáncer. Estos se han definido como los genes causales de cáncer esporádico o cáncer familiar, cuando mutan. El tipo de mutaciones para estos genes del cáncer incluye las amplificaciones, las mutaciones puntuales, las deleciones, los rearreglos genómicos, entre otros, los cuales conducen a una sobreexpresión proteica, silenciamiento, producción de proteínas quiméricas o una expresión de novo. Cuando afectan genes específicos que contribuyen al desarrollo de un cáncer, estas alteraciones genómicas o de la expresión génica son denominadas en conjunto como genes del cáncer. Es posible que esta lista crezca más debido a las nuevas estrategias que se están desarrollando, como, por ejemplo, las de análisis genómico.
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Regulação Neoplásica da Expressão Gênica , Genes Neoplásicos , Mutação , Neoplasias/genética , Genômica , HumanosRESUMO
Cervical cancer (CC) is a multifactorial disease associated to genetic, environmental and epigenetic factors, being the infection by human papillomavirus the main etiologic agent. Additionally, the alteration in the expression of transcription factors has been considered of importance for the development of this tumor. HOX genes encode a group of transcription factors involved in cellular proliferation and differentiation processes during the development of embryonic structures in vertebrates; their aberrant expression is associated with tumorigenesis and metastasis. A range of evidence suggests a role for HOX genes in the development of cervical neoplastic cell. Studies in CC cell lines, primary tumors and premalignant lesions have suggested the involvement of HOXA1, HOXC5, C6, C8 and C10, HOXD9 and HOXD13 in the process of cervical carcinogenesis. Also, the de novo expression of genes HOXB2, B4, B13 and HOXC11-C13 appears to be involved in the process of malignant transformation of cervical epithelial cell. These data would allow to open a field in search of new molecular markers in cervical cancer and the development of new therapeutic strategies for this malignancy.
El cáncer cervicouterino (CaCU) es una enfermedad multifactorial que se asocia a factores genéticos, ambientales y epigenéticos, y cuyo principal agente etiológico es la infección por el virus del papiloma humano. Además, la alteración en la expresión de factores de transcripción ha sido considerada de importancia para el desarrollo de esta neoplasia. Los genes HOX codifican un grupo de factores de transcripción que participan en los procesos de proliferación y diferenciación celular durante el desarrollo de las estructuras embrionarias en los vertebrados; y su expresión aberrante ha sido asociada con oncogénesis y metástasis. Una serie de evidencias sugiere un papel importante para los genes HOX en el desarrollo neoplásico de la célula cervical. Estudios realizados en líneas celulares de CaCU, lesiones premalignas y tumores primarios han sugerido el involucramiento de HOXA1, HOXC5, C6, C8 y C10, HOXD9 y HOXD13 en el proceso de carcinogénesis cervical. Asimismo, la expresión de novo de los genes HOXB2, B4, B13 y HOXC11-C13 parece estar involucrada en el proceso de transformación maligna de la célula del epitelio cervical. Estos datos permitirían abrir un campo en la búsqueda de nuevos marcadores moleculares en cáncer cervical y en el desarrollo de nuevas estrategias terapéuticas para atender esta neoplasia.
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Biomarcadores Tumorais/genética , Genes Homeobox , Neoplasias do Colo do Útero/genética , Carcinogênese/genética , Feminino , Marcadores Genéticos , Humanos , Metástase Neoplásica/genéticaRESUMO
INTRODUCCIÓN: El quiste de colédoco (QC) es una patología infrecuente, caracterizada por una dilatación de vía biliar intra o extrahepática. Constituye una lesión congénita, representado 1% de las lesiones biliares benignas. Tiene una incidencia de 1 en 100.000 a 150.000 habitantes. Es más frecuente en mujeres, y su etiología es desconocida. En adultos los síntomas son inespecíficos; predominando dolor abdominal e ictericia. PRESENTACIÓN DEL CASO: Mujer de 61 años con cólico abdominal en hipocondrio derecho de tres días, vómitos e ictericia. Al ingreso hospitalario presentaba leucocitosis, hiperbilirrubinemia, aumento de fosfatasa alcalina, transaminasas y amilasa. Se plantearon los diagnósticos de ictericia obstructiva, pancreatitis y quiste hidatídico complicado, por lo que se realiza tomografía computada (TC) de abdomen evidenciando dilatación sacular intra y extrahepática, compatible con QC tipo IV-a. Se realizó colecistectomía y coledocostomía con sonda T de urgencia por evolución a colangitis con resultados favorables. DISCUSIÓN: Los QC son una causa rara de ictericia obstructiva. En Chile existen escasos datos estadísticos al respecto. Se manifiesta con una sintomatología inespecífica, sobretodo en adultos. El diagnóstico se realiza con hallazgos de laboratorio concordantes con ictericia colestásica, donde los estudios imagenológicos como ultrasonido y TC tienen un rol importante, pese a que en algunas ocasiones pueden pasar inadvertido. Es primordial un alto índice de sospecha para el diagnóstico y un tratamiento oportuno debido a su importante riesgo de progresión a colangiocarcinoma
INTRODUCTION: Choledochal cysts (CCs) is a rare disease characterized by dilatation of the intrahepatic or extrahepatic bile duct, which is about 1% of all benign biliary lesions. Its incidence is 1:100,000 to 150,000 habitants. It is more common in females, and its etiology is unknown. In adults the symptoms are nonspecific, predominantly abdominal pain and jaundice. CASE REPORT: 61 year old female patient with three days of severe abdominal colic in the right upper quadrant, whit both vomiting and jaundice. On admission, she presents leukocytosis, hyperbilirubinemia, and increased levels of alkaline phosphatase, transaminases and amylase. Diagnosis of obstructive jaundice, pancreatitis and complicated hydatid cyst arising. The abdominal CT Scan reveals intra and extrahepatic saccular dilatations, compatible with a type IV-a CCs. Both cholecystectomy and T-tube choledochotomy were done by evolution to cholangitis with favorable results and satisfactory postoperative. DISCUSSION: CCs is a rare cause of obstructive jaundice, and in this regard, there are few data described in Chile, Its diagnosis requires a high index of suspicion because of its nonspecific symptoms found mostly in adults. Despite this, the diagnosis is determined with laboratory findings consistent with cholestatic jaundice and support diagnostic imaging such as ultrasound, CT Scan, among others. Although the imaging findings, it may not be detected. A correct diagnosis and appropriate treatment is essential because of its high risk of progression to cholangiocarcinoma. Currently the patient is waiting for resection of extrahepatic bile duct and Roux-en-Y hepatic jejunostomy which is the optimal treatment.
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Humanos , Feminino , Pessoa de Meia-Idade , Cisto do Colédoco/cirurgia , Cisto do Colédoco/complicações , Cisto do Colédoco/diagnóstico por imagem , Colecistectomia , Tomografia Computadorizada por Raios X , Colangite , Coledocolitíase , Icterícia Obstrutiva/etiologia , Hiperbilirrubinemia/etiologiaRESUMO
Cell adhesion to the extracellular matrix proteins occurs through interactions with integrins that bind to Arg-Gly-Asp (RGD) tripeptides, and syndecan-4, which recognizes the heparin-binding domain of other proteins. Both receptors trigger signaling pathways, including those that activate RhoGTPases such as RhoA and Rac1. This sequence of events modulates cell adhesion to the ECM and cell migration. Using a neuron-astrocyte model, we have reported that the neuronal protein Thy-1 engages αVß3 integrin and syndecan-4 to induce RhoA activation and strong astrocyte adhesion to their underlying substrate. Thus, because cell-cell interactions and strong cell attachment to the matrix are considered antagonistic to cell migration, we hypothesized that Thy-1 stimulation of astrocytes should preclude cell migration. Here, we studied the effect of Thy-1 expressing neurons on astrocyte polarization and migration using a wound-healing assay and immunofluorescence analysis. Signaling molecules involved were studied by affinity precipitation, western blotting and the usage of specific antibodies. Intriguingly, Thy-1 interaction with its two receptors was found to increase astrocyte polarization and migration. The latter events required interactions of these receptors with both the RGD-like sequence and the heparin-binding domain of Thy-1. Additionally, prolonged Thy-1-receptor interactions inhibited RhoA activation while activating FAK, PI3K and Rac1. Therefore, sustained engagement of integrin and syndecan-4 with the neuronal surface protein Thy-1 induces astrocyte migration. Interestingly we identify here, a cell-cell interaction that despite initially inducing strong cell attachment, favors cell migration upon persistent stimulation by engaging the same signaling receptors and molecules as those utilized by the extracellular matrix proteins to stimulate cell movement.
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Astrócitos/citologia , Comunicação Celular , Movimento Celular/fisiologia , Integrina alfaVbeta3/metabolismo , Oligopeptídeos/metabolismo , Sindecana-4/metabolismo , Antígenos Thy-1/metabolismo , Animais , Astrócitos/metabolismo , Western Blotting , Adesão Celular , Polaridade Celular , Proliferação de Células , Células Cultivadas , Imunofluorescência , Proteína-Tirosina Quinases de Adesão Focal/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Fosforilação , Ratos , Transdução de Sinais , Cicatrização , Proteínas rac1 de Ligação ao GTP/metabolismo , Proteína rhoA de Ligação ao GTP/metabolismoRESUMO
BACKGROUND: Cervical cancer (CC) is a common malignancy in women worldwide. Cervical tumorigenesis involves a multistep process in which accumulations of genetic alterations are present. Homeotic genes, such as HOX gene re-expression, have been reported in a wide variety of tumors. METHODS: In order to know the role of HOX B4 gene expression in CC, in the present study, two-dimensional polyacrylamide gel electrophoresis, matrix-assisted laser desorption/ionization, and time-of-flight mass spectrometry were used for differential screening of protein expression in CC. Immunohistochemical analysis was performed on the cervical tissue microarray (TMA) to detect the Hox B4 protein. RESULTS: Hox B4 peptide was detected among 15 increased spots differentially observed in CC. Using TMA, Hox B4 protein was also immunodetected in the nuclei of cervical epithelial tumor cells, while in normal cervical epithelium, it was absent. Interestingly, it was possible to detect the Hox B4 protein in the precursor lesions. CONCLUSIONS: Hox B4 protein is present in the precursor lesions as CC cells, suggesting that Hox B4 could be a protein related to the neoplastic state (non-differentiated cells) of human cervical epithelium.