Progress of research on the role of Atoh1 gene in the regeneration of mammalian auditory hair cells / 中华医学遗传学杂志

Atoh1 gene encodes a helix-loop-helix transcription factor which is involved in the generation and differentiation of mammalian auditory hair cells and supporting cells, and regulation of the proliferation of cochlear cells, therefore plays an important role in the pathogenesis and recovery of sensorineural deafness. This study reviews the progress of the Atoh1 gene in hair cell regeneration, with the aim of providing a reference for the study of hair cell regeneration gene therapy for sensorineural deafness.

Regrowth age modifies the leaf anatomy of Brachiaria genotypes / A idade de regeneração modifica a anatomia foliar dos genótipos de Brachiaria

Changes in leaf anatomy were evaluated in genotypes of Brachiaria brizantha, Brachiaria decumbens, Brachiaria ruziziensis and three Brachiaria ruziziensis clones through tissue proportion in internerval and midrib regions at three regrowth ages. Plants were grown and cutting was performed after 60 days. Further, leaves were sampled at 8, 15 and 29 regrowth days and processed with usual plant microtechnique. The internerval region showed higher parenchyma percentage at 15 days for Clone 95 and similar values at 15 and 29 days for Clone 1. The proportion of vascular bundles was lower after 15 days in Clones 1 and 95 and 29 days in B. brizantha. In the midrib, the parenchyma proportion was higher at 29 days in B. brizantha and lower at 15 days in B. ruziziensis. The proportion of vascular bundles was higher at 8 days in B. decumbens, B. brizantha and Clone 1, and lower at 29 days for Clones 97 and 95 and at 8 days in B. ruziziensis. Therefore, the regrowth age modifies the percentage of leaf tissues in Brachiaria genotypes, in which the fibers and vascular bundles increase at 29 days and 8-day-old leaves are not fully developed.

A anatomia foliar foi avaliada em genótipos de Brachiaria brizantha, Brachiaria decumbens, Brachiaria ruziziensis e três clones de Brachiaria ruziziensis; quanto à proporção de tecidos foliares, em três idades de rebrota. As plantas foram cultivadas e cortadas após 60 dias. As folhas foram amostradas aos 8, 15, 29 dias de rebrota e analisadas pela metodologia de microtécnica vegetal. Na região internervural, a proporção de parênquima foi maior aos 15 dias para o Clone 95, e aos 15 e 29 dias para o Clone 1. Proporção de feixes vasculares foi menor aos 15 dias para os Clones 1 e 95 e aos 29 dias para genótipo B. brizantha. Na nervura central, a proporção de parênquima foi maior aos 29 dias para B. brizantha e menor, aos 15 dias, para B. ruziziensis. Proporção dos feixes vasculares foi maior aos 8 dias para genótipo B. decumbens, B. brizantha e para o Clone 1, e menor aos 29 dias para os Clones 97 e 95; aos 8 dias, para genótipo B. ruziziensis. Portanto, a idade de rebrota modifica a porcentagem de tecidos foliares em genótipos de Brachiaria; contudo, fibras e feixes vasculares aumentam aos 29 dias; aos 8 dias, as folhas não estão totalmente desenvolvidas.

microRNA-183 is Essential for Hair Cell Regeneration after Neomycin Injury in Zebrafish

PURPOSE: microRNAs (miRNAs) are non-coding RNAs composed of 20 to 22 nucleotides that regulate development and differentiation in various organs by silencing specific RNAs and regulating gene expression. In the present study, we show that the microRNA (miR)-183 cluster is upregulated during hair cell regeneration and that its inhibition reduces hair cell regeneration following neomycin-induced ototoxicity in zebrafish. MATERIALS AND METHODS: miRNA expression patterns after neomycin exposure were analyzed using microarray chips. Quantitative polymerase chain reaction was performed to validate miR-183 cluster expression patterns following neomycin exposure (500 µM for 2 h). After injection of an antisense morpholino (MO) to miR-183 (MO-183) immediately after fertilization, hair cell regeneration after neomycin exposure in neuromast cells was evaluated by fluorescent staining (YO-PRO1). The MO-183 effect also was assessed in transgenic zebrafish larvae expressing green fluorescent protein (GFP) in inner ear hair cells. RESULTS: Microarray analysis clearly showed that the miR-183 cluster (miR-96, miR-182, and miR-183) was upregulated after neomycin treatment. We also confirmed upregulated expression of the miR-183 cluster during hair cell regeneration after neomycin-induced ototoxicity. miR-183 inhibition using MO-183 reduced hair cell regeneration in both wild-type and GFP transgenic zebrafish larvae. CONCLUSION: Our work demonstrates that the miR-183 cluster is essential for the regeneration of hair cells following ototoxic injury in zebrafish larvae. Therefore, regulation of the miR-183 cluster can be a novel target for stimulation of hair cell regeneration.

Aplicación clínica del ácido hialurónico / Clinical application of hyaluronic acid

El ácido hialurónico es un glicosaminoglicano presente en todos los tejidos del cuerpo, matrizextracelular y revistiendo vasos sanguíneos. El ácido hialurónico es igual en todo el cuerpo y debido a estoes biocompatible al ser aplicado en los seres humanos, tiene diversos usos que lo hacen actualmente objeto de investigaciones. En personas con cáncer de pulmón reduce la propagación de células tumorales e incrementa la regeneración de tejido sano. Tambiénse utiliza en tratamientos para la artritis, ya que resulta beneficioso al regenerar cartílago de las articulaciones y por ende un alivio en personas con dichos problemas. El ácido hialurónico ha tenido aceptación en su utilización para el tratamiento estético, teniendo resultados considerables y con duración semipermanente. Otro uso destacable es su aplicación para el ojo seco, que por su presentación en gotas brinda al paciente una hidratación, permitiendoasí curar este mal. Por los múltiples usos del ácido hialurónico es importante estudiar más sobre él, proponiendo nuevas alternativas en diferentes áreas de salud. La metodología usada en la presente revisión, fue la búsqueda sistemática de artículos actualizadosen revistas médicas nacionales e internacionales; posteriormente se filtró la información obtenida basándose en el objetivo general de la revisión: Descripción de las aplicaciones clínicas del ácido hialurònico, en diferentes áreas de la medicina..(AU).

Utilidad del plasma rico en plaquetas en neumología / Usefulness of platelet-rich plasma in pneumology

The use of Platelet-rich plasma (PRP) involves a very complex network of molecular effects favoring tissue regeneration, due the presence of multiple mediators and growth factors. There are several communications about its use on the dental implantology field, plastic surgery and orthpedics. Besides, its utility has been suggested on peripheral nerves regeneration after trauma. In this article we present our experience on the use of PRP on acute injury of the respiratory system. We present a clinical series of 8 patients treated with PRP with positive response. Four of them presenting a massive hemoptysis were treated by direct endoscopic instillation of autologous PRP on the site of lesion; an immediate favorable result was obtained in all of them, without recurrence of bleeding on the follow-up period. A fifth case was a HIV seropositive patient with a spontaneous pneumothorax on intersticial pneumonia. He was treated by direct instillation of PRP through a thoracic tube. Full lung reexpansion was achieved within 72 h. Finally two patients with a respiratory fistula and another patient who suffered a traumatic tracheal rupture were treated with PRP endoscopic instillation, all of them with favorable clinical outcome. The use of autologous products as PRP has shown a good performance in all the clinical situations described, proposing it as a potentially very useful technique, particularly when a minimally invasive approach is required.

El uso de plasma rico en plaquetas (PRP) involucra una compleja red de efectos moleculares que favorecerían la regeneración tisular, dada la presencia en él de múltiples mediadores y factores de crecimiento. Se ha comunicado su uso con éxito en implantología odontológica, cirugía plástica y ortopedia como también se ha sugerido su utilidad en la regeneración de nervios periféricos posterior a trauma. No existe difusión acerca de su uso en patología respiratoria. Comunicamos nuestra experiencia en el uso de PRP en daño agudo del aparato respiratorio. En esta serie de casos, se trataron 4 pacientes con hemoptisis masiva mediante preparación de PRP autólogo previo al procedimiento e instilación vía endoscópica en el sitio del defecto, con buen resultado inmediato y sin recidiva del sangrado al seguimiento; 1 caso de neumotórax espontáneo con infiltrados pulmonares con fracaso del manejo con sonda endopleural (SEP), que resultó ser una neumonía intersticial con quistes pulmonares en un paciente VIH sero-positivo, instilándose PRP por SEP, reexpandiendo el pulmón a las 72 h; 2 pacientes portadores de fístula respiratoria y 1 paciente portador de ruptura traqueal traumática, todos con buena respuesta. El uso de productos autólogos como PRP ha logrado un favorable rendimiento en todas las situaciones clínicas planteadas, lo que lo sitúa como una herramienta con notable potencial de desarrollo particularmente en casos que por sus características particulares requieren de un manejo mínimamente invasivo.

Polimorfismos genéticos e endometriose: a contribuição dos genes que regulam a função vascular e o remodelamento de tecidos / Genetic polymorphisms and endometriosis: contribution of genes that regulate vascular function and tissue remodeling

A endometriose é uma doença ginecológica benigna caracterizada pela presença e crescimento de células endometriais fora do útero. Fatores genéticos, endócrinos, imunológicos e ambientais têm sido sugeridos em sua patogênese. Um grande número de estudos tem relacionado polimorfismos genéticos como um fator que contribui para o desenvolvimento da endometriose. Nesta revisão, apresentamos uma descrição detalhada da contribuição de polimorfismos genéticos nos genes que regulam a função vascular e o remodelamento do tecido em endometriose (AHSG, EGFR, EGF, VEGF, endostatina, PAI-1, ACE e MMPs). Alguns polimorfismos dos genes VEGF (-460 C/T, +405 G/C, +936 C/T), PAI, MMP-1, 2 e 3 foram amplamente estudados, enquanto outros dos genes AHSG, EGF, endostatina e VEGF (-1154 G/A, -2578 A/C), não. Nesse último caso, estudos adicionais tornam-se necessários para confirmar os achados encontrados pelos poucos trabalhos que analisaram esses polimorfismos de único nucleotídeo (SNP). Além disso, os estudos que encontraram associação positiva ou negativa do SNP com endometriose enfatizam a importância de estudos com grande número de casos-controles para confirmar os achados por eles publicados. A análise por haplótipo foi realizada apenas para os genes VEGF (-460, +405, -1154 e -2578), ACE (-240/2350) e MMP-1, 2, 3 e 9, e, na maioria deles, não houve associação com endometriose. Dos oito trabalhos que analisaram haplótipos do gene VEGF, cinco deles não os associaram à endometriose. Os haplótipos dos genes ACE e MMP-2 não foram associados à endometriose, enquanto aqueles dos genes MMP-1, 3 e 9 foram relacionados a risco elevado da doença.

Endometriosis is a benign gynecological disease characterized by the presence and growth of endometrial cells outside the uterus. Genetic, endocrine, immunological, and environmental factors have been suggested in its pathogenesis. A great number of studies have related genetic polymorphisms as a factor that contributes to the development of endometriosis. This review presents a detailed description of the contribution of genetic polymorphisms in genes that regulate vascular function and tissue remodeling in endometriosis (alpha 2-HS glycoprotein [AHSG], epidermal growth factor receptor [EGFR], vascular endothelial growth factor [VEGF], endostatin, plasminogen activator inhibitor 1 [PAI-1], angiotensin I-converting enzyme [ACE], and matrix metalloproteinases [MMPs]). Some polymorphisms of the VEGF (-460 C/T, +405 G/C, +936 C/T), PAI, MMP-1, 2, and 3 genes were widely studied, while polymorphisms of the AHSG, EGF, endostatin, and VEGF (-1154 G/A, -2578 A/C) genes were not. In this latter case, additional studies are required to confirm the findings of the few studies that have analyzed these single nucleotide polymorphisms (SNPs). Additionally, studies that found a positive or negative association of SNP with endometriosis emphasize the relevance of studies with a large number of control cases to confirm their findings. The haplotype analysis was performed only for the VEGF (-460, +405, -1154 and -2578), ACE (-240/2350) and MMP-1, 2, 3, and 9 genes, and in most of them, there was no association with endometriosis. Of the eight works that analyzed haplotypes of the VEGF gene, five did not associate them with endometriosis. Haplotypes of ACE and MMP-2 genes were not associated with endometriosis, while those of MMP-1, 3, and 9 genes were related to a high risk for the disease.

Influence of genotype and explant source on indirect organogenesis by in vitro culture of leaves of Melia azedarach L

In vitro regeneration of shoots from leaf explants of the Paradise tree (Melia azedarach L.) was studied. Three different portions (proximal portion, distal portion and rachis of the leaflets) of three developmental stages (folded, young still expanding and completely expanded) of leaves of 10-15 year old plants of seven genotypes were cultured on Murashige and Skoog (1962) medium (MS) supplemented with 1 mg x l(-1) benzylaminopurine (BAP) + 0.1 mg x l(-1) kinetin (KIN) + 3 mg x l(-1) adenine sulphate (ADS). The rachis of the leaflets of the completely expanded leaves was found to be the most responsive tissue, in most of the genotypes employed. Shoot regeneration occurred in leaf explants of all the genotypes tested. The best genotype for shoot regeneration was clone 4. Rooting was induced on MS medium supplemented with 2.5 mg x l(-1) 3-indolebutyric acid, IBA, (4 days) followed by subculture on MS lacking growth regulators (26 days). Complete plants were transferred to soil.