Estrogen deficiency influences SEC23A gene expression in the odontogenic region of incisors ­ a murine model study / A deficiência de estrógeno influencia a expressão gênica de SEC23A na região odontogênica de incisivos ­ um estudo em modelo murino

Recent scientific evidence suggests a close relationship between estrogen deficiency and vitamin D- related genes. Estrogen and vitamin D were involved with alterations in odontogenesis and tooth eruption process. Objective: The aim of the present study was to evaluate the influence of estrogen deficiency on the expression of genes related to the activation and degradation of vitamin D in the odontogenic region of incisors in a murine model. Material and Methods: This is an experimental clinical study that used female Wistar Hannover rats. The animals were randomly divided into two groups according to the intervention received: Hypoestrogenism Group ­ animals submitted to estrogen deficiency by ovariectomy surgery and Control Group ­ animals submitted to sham surgery. Surgical intervention was performed in the prepubertal period; the animals were followed throughout the pubertal period. After euthanasia, the hemimandibles were removed to evaluate the mRNA expression of the vitamin D-related genes AMDHD1, CYP24A1, NADSYN1 and SEC23A in the odontogenic region of incisors through real time PCR. Student's t test was used to compare means. Kruskal-Wallis test and Dunn's posttest were also used. The level of significance was 5%. Results: SEC23A was overexpressed in the estrogen deficiency condition in the odontogenic region (p=0.021). Conclusion: Estrogen deficiency may influence the expression of the SEC23A gene involved in the activation and degradation of vitamin D in the odontogenic region of incisors in a murine model(AU)

Evidências científicas recentes sugerem uma estreita relação entre a deficiência de estrógeno e os genes relacionados à vitamina D. O estrógeno e a vitamina D estão envolvidos com alterações na odontogênese e no processo de erupção dentária. Objetivo: O objetivo do presente estudo foi avaliar a influência da deficiência de estrógeno na expressão de genes relacionados à ativação e degradação da vitamina D na região odontogênica de incisivos em modelo murino. Material e Métodos: Trata-se de um estudo clínico experimental que utilizou ratas Wistar Hannover fêmeas. Os animais foram divididos aleatoriamente em dois grupos de acordo com a intervenção recebida: Grupo Hipoestrogenismo ­ animais submetidos à deficiência de estrógeno pela cirurgia de ovariectomia e Grupo Controle ­ animais submetidos à cirurgia simulada. A intervenção cirúrgica foi realizada no período pré-púbere; os animais foram acompanhados durante todo o período puberal. Após a eutanásia, as hemimandíbulas foram removidas para avaliar a expressão de mRNA dos genes AMDHD1, CYP24A1, NADSYN1 e SEC23A, relacionados à vitamina D, na região odontogênica de incisivos por meio de PCR em tempo real. O teste t de Student foi utilizado para comparar as médias. Também foram utilizados o teste de Kruskal-Wallis e o pós-teste de Dunn. O nível de significância foi de 5%. Resultados: SEC23A foi superexpresso na condição de deficiência de estrógeno na região odontogênica (p=0,021). Conclusão: A deficiência de estrógeno pode influenciar a expressão do gene SEC23A envolvido na ativação e degradação da vitamina D na região odontogênica de incisivos em modelo murino (AU)

Functional mechanisms of WRKY transcription factors in regulating plant response to abiotic stresses / 生物工程学报

WRKYs is a unique family of transcription factors (TFs) in plants, and belongs to the typical multifunctional regulator. It is involved in the regulation of multiple signaling pathways. This type of transcription factor is characterized to contain about 60 highly conservative amino acids as the WRKY domain, and usually also has the Cys2His2 or Cys2His-Cys zinc finger structure. WRKYs can directly bind to the W-box sequence ((T)(T) TGAC (C/T)) in the promoter region of the downstream target gene, and activate or inhibit the transcription of the target genes by interacting with the target protein. They may up-regulate the expression of stress-related genes through integrating signal pathways mediated by abscisic acid (ABA) and reactive oxygen species (ROS), thus playing a vital role in regulating plant response to abiotic stresses. This review summarizes the advances in research on the structure and classification, regulatory approach of WRKYs, and the molecular mechanisms of WRKYs involved in response to drought and salt stresses, and prospects future research directions, with the aim to provide a theoretical support for the genetic improvement of crop in response to abiotic stresses.

Discovery of A New Prognostic Molecular Marker NKX2-3 for Acute Myeloid Leukemia / 中山大学学报(医学科学版)

ObjectiveTo analyze the expression of molecular marker affecting the prognosis of acute myeloid leukemia （AML） patients from bioinformatics database， thus providing an experimental basis for further exploration of a novel molecular marker for the prognosis of AML. MethodsThe prognostic data of 179 AML patients from The Cancer Genome Atlas （TCGA） database were examined for differential gene analysis and survival analysis. The bone marrow samples of 74 healthy individuals （HI） and 542 de novo AML patients in the dataset GSE13159 downloaded from the Gene Expression Omnibus （GEO） database were analyzed to detect the difference in the expression levels of differential target genes. Peripheral blood and bone marrow samples were collected from 18 de novo AML patients and 20 age- and gender-matched healthy controls， and real-time fluorescent quantitative PCR was used to validate the expression levels of the differential genes in the AML patients. ResultsBioinformatics data analysis showed that the optimal cut-off value of Homo sapiens NK2 homeobox 3 （NKX2-3） calculated by R language was 0.051. Survival analysis revealed a statistically poorer overall survival in de novo AML patients with high NKX2-3 expression than in those with low NKX2-3 expression （P = 0.0036）. NKX2-3 was highly expressed in patients with de novo AML than in HI and the difference was statistically significant （P < 0.001）. Real-time fluorescence quantitative PCR verified the expression levels of the NKX2-3 gene in AML patients and confirmed that compared with those in HI， in the de novo AML patients， NKX2-3-1 and NKX2-3-2 were highly expressed and were significantly correlated （P = 0.000， P = 0.000）. ConclusionNKX2-3 is highly expressed in de novo AML patients， and the AML patients with high NKX2-3 expression have poor overal survival. NKX2-3 may be closely related to the clinical outcome and prognosis of AML.

Research progress of artificial intelligence in pathological subtypes classification and gene expression analysis of lung adenocarcinoma / 中国胸心血管外科临床杂志

@#Lung adenocarcinoma is a prevalent histological subtype of non-small cell lung cancer with different morphologic and molecular features that are critical for prognosis and treatment planning. In recent years, with the development of artificial intelligence technology, its application in the study of pathological subtypes and gene expression of lung adenocarcinoma has gained widespread attention. This paper reviews the research progress of machine learning and deep learning in pathological subtypes classification and gene expression analysis of lung adenocarcinoma, and some problems and challenges at the present stage are summarized and the future directions of artificial intelligence in lung adenocarcinoma research are foreseen.

Chemical characterization and effects of volatile oil of Alpinia zerumbet on the quality of collagen deposition and caveolin-1 expression in a muscular fibrosis murine model

Abstract This study evaluated the effect of the volatile oil of Alpinia zerumbet (VOAz) on caveolin-1 gene expression and muscular fibrosis. The rats were immobilized to induce fibrosis of the gastrocnemius muscle, and they were treated with VOAz. Collagen quality was assessed by histology and the expression of the caveolin-1 (CAV-1) gene was evaluated using qPCR. Histomorphological analysis indicated a significant reduction in the perimeter, width, and intensity of collagen in the treated groups, thus showing that the oil was effective in regulating the quality of collagen at the three concentrations. The results of expression levels suggested a decrease in the lesioned group and in two treatment groups (0.0115 µg/g and 0.009 µg/g). However, with the lowest concentration (0.0065 µg/g), no significant difference was observed, with levels similar to those found in healthy tissue. Therefore, the results showed that VOAz has the potential to be a non-invasive and low-cost alternative to aid in the treatment of muscular fibrosis.

Resumo Este estudo avaliou o efeito do óleo volátil de Alpinia zerumbet (OVAz) na expressão do gene da caveolina-1 e na fibrose muscular. Os ratos foram imobilizados para induzir a fibrose do músculo gastrocnêmio, e foram tratados com OVAz. A qualidade do colágeno foi avaliada com histologia e à expressão do gene caveolina-1 (CAV-1) foi avaliada usando qPCR. A análise histomorfológica indicou uma redução significativa no perímetro, largura e intensidade do colágeno nos grupos tratados. Os resultados dos níveis de expressão sugeriram diminuição nos grupos de lesão e em dois grupos de tratamento (0,0115 µg/g e 0,009 µg/g). No entanto, com a menor concentração (0,0065 µg/g), não foi observada diferença significativa, apresentando níveis semelhantes aos encontrados em tecido saudável. O uso do OVAz foi eficaz para reverter as alterações do colágeno causadas pela fibrose, e sua menor concentração apresentou uma possível tendência de aumento na expressão do CAV-1. Portanto, os resultados mostraram que o OVAz tem potencial para ser uma alternativa não invasiva e de baixo custo para auxiliar no tratamento da fibrose muscular.

Chemical characterization and effects of volatile oil of Alpinia zerumbet on the quality of collagen deposition and caveolin-1 expression in a muscular fibrosis murine model / Caracterização química e efeitos do óleo volátil de Alpinia zerumbet na qualidade da deposição do colágeno e expressão da caveolina-1 em modelo murino de fibrose muscular

Abstract This study evaluated the effect of the volatile oil of Alpinia zerumbet (VOAz) on caveolin-1 gene expression and muscular fibrosis. The rats were immobilized to induce fibrosis of the gastrocnemius muscle, and they were treated with VOAz. Collagen quality was assessed by histology and the expression of the caveolin-1 (CAV-1) gene was evaluated using qPCR. Histomorphological analysis indicated a significant reduction in the perimeter, width, and intensity of collagen in the treated groups, thus showing that the oil was effective in regulating the quality of collagen at the three concentrations. The results of expression levels suggested a decrease in the lesioned group and in two treatment groups (0.0115 µg/g and 0.009 µg/g). However, with the lowest concentration (0.0065 µg/g), no significant difference was observed, with levels similar to those found in healthy tissue. Therefore, the results showed that VOAz has the potential to be a non-invasive and low-cost alternative to aid in the treatment of muscular fibrosis.

Resumo Este estudo avaliou o efeito do óleo volátil de Alpinia zerumbet (OVAz) na expressão do gene da caveolina-1 e na fibrose muscular. Os ratos foram imobilizados para induzir a fibrose do músculo gastrocnêmio, e foram tratados com OVAz. A qualidade do colágeno foi avaliada com histologia e à expressão do gene caveolina-1 (CAV-1) foi avaliada usando qPCR. A análise histomorfológica indicou uma redução significativa no perímetro, largura e intensidade do colágeno nos grupos tratados. Os resultados dos níveis de expressão sugeriram diminuição nos grupos de lesão e em dois grupos de tratamento (0,0115 µg/g e 0,009 µg/g). No entanto, com a menor concentração (0,0065 µg/g), não foi observada diferença significativa, apresentando níveis semelhantes aos encontrados em tecido saudável. O uso do OVAz foi eficaz para reverter as alterações do colágeno causadas pela fibrose, e sua menor concentração apresentou uma possível tendência de aumento na expressão do CAV-1. Portanto, os resultados mostraram que o OVAz tem potencial para ser uma alternativa não invasiva e de baixo custo para auxiliar no tratamento da fibrose muscular.

A Cocktail of Natural Compounds Holds Promise for New Immunotherapeutic Potential in Head and Neck Cancer / 中国结合医学杂志

OBJECTIVE@#To obtain detailed understanding on the gene regulation of natural compounds in altering prognosis of head and neck squamous cell carcinomas (HNSC).@*METHODS@#Gene expression data of HNSC samples and peripheral blood mononuclear cells (PBMCs) of HNSC patients were collected from Gene Expression Omnibus (GEO). Differential gene expression analysis of GEO datasets were achieved by the GEO2R tool. Common differentially expressed gerres (DEGs) were screened by comparing DEGs of HNSC with those of PBMCs. The combination was further analyzed for regulating pathways and biological processes that were affected.@*RESULTS@#Totally 110 DEGs were retrieved and identified to be involved in biological processes related to tumor regulation. Then 102 natural compounds were screened for a combination such that the expression of all 110 commonly DEGs was altered. A combination of salidroside, ginsenoside Rd, oridonin, britanin, and scutellarein was chosen. A multifaceted, multi-dimensional tumor regression was showed by altering autophagy, apoptosis, inhibiting cell proliferation, angiogenesis, metastasis and inflammatory cytokines production.@*CONCLUSIONS@#This study has helped develop a unique combination of natural compounds that will markedly reduce the propensity of development of drug resistance in tumors and immune evasion by tumors. The result is crucial to developing a combinatorial natural therapeutic cocktail with accentuated immunotherapeutic potential.

Association between microRNA expression and risk of male idiopathic infertility in Iraq

SUMMARY OBJECTIVE: The World Health Organization defines infertility as the inability to get pregnant after 12 months of unprotected sexual activity. This study was conducted to estimate the levels of gene expression for two mature miRNAs (i.e., miR-122 and miR-34c-5p) to evaluate susceptibility to male infertility. METHODS: This study included 50 male patients with idiopathic infertility who were admitted to hospital from the period November 2021 to May 2022 and another group consisting of 50 apparently healthy individuals used as controls. RESULTS: miR-122 level was significantly highest in azoospermia and followed by oligospermia, 39.22 (31.88) versus 37.34 (20.45), respectively. In addition, there was a very significant difference in miR-34c-5p levels between the study groups (p<0.05). CONCLUSION: Two miRNAs, namely, miR-34c-5p and miR-122, can be used as predictive and diagnostic biomarkers for infertility.

Evaluation of IL-4, MIP-1α, and MMP-9 gene expression levels in peri-implant tissues in peri-implantitis

Abstract This case-control study evaluated the gene expression levels of interleukin (IL)-4, macrophage inflammatory protein type 1 alpha (MIP-1α), and metalloproteinase (MMP)-9, factors involved in the formation of giant cells in healthy peri-implant tissue and peri-implantitis. Thirty-five subjects (15 healthy and 20 with peri-implantitis), who met the inclusion and exclusion criteria, were included in this study. The peri-implant tissue biopsies were subjected to total RNA extraction, DNAse treatment, and cDNA synthesis. Subsequently, the reaction of real-time PCR was performed to evaluate the gene expression levels of IL-4, MIP-1α, and MMP-9 concerning the reference gene. IL-4 gene expression showed higher (18-fold) values in the Peri-Implantitis Group of Patients when compared with the Healthy (Control) Group (p<0.0001). Although MIP- 1α and MMP-9 gene expression levels were higher in diseased implants, they showed no significant differences (p=0.06 and p=0.2337), respectively. Within the limitations of this study, the results showed that in tissues affected by peri-implantitis, only levels of Il-4 were increased when compared with tissues in the control group.

Resumo Este estudo caso-controle teve como objetivo avaliar a expressão gênica dos níveis de interleucina (IL)-4, proteína inflamatória de macrófagos tipo alfa 1 (MIP-1α) e metalopreoteinase (MMP)-9, todos fatores envolvidos na formação de células gigantes em tecidos peri-implantares saudáveis e com peri-implantite. Trinta e cinco indivíduos (15 saudáveis e 20 com peri-implantite) foram incluídos nesse estudo seguindo os critérios de inclusão e exclusão. Os tecidos peri-implantares foram submetidos a extração do RNA total, tratamento de DNAse e síntese de cDNA. Subsequentemente, a reação de PCR em tempo real foi realizada para avaliar os níveis da expressão de IL-4, MIP-1α, e MMP-9 em relação ao gene de referência. O nível de expressão de IL-4 foi estatisticamwente maior (18 vezes) nos tecidos de pacientes com peri-implantite quando comparados aos pacientes saudáveis (grupo controle) (p<0,0001). Embora os níveis de expressão de MIP- 1α e MMP-9 apresentassem maiores valores nos implantes doentes, esses níveis não foram estatisticamente significantes (p=0.06 and p=0.2337) respectivamente. Dentro das limitações desse estudo, os resultados mostraram que nos tecidos afetados pela peri-implantite, apenas os nívies de IL-4 estavam aumentados quando comparados ao grupo controle.

Distinct gene expression profiles underlie morphological and etiological differences in pediatric cataracts

Purpose: Pediatric cataract is a major cause of preventable childhood blindness worldwide. Although genetic mutations or infections have been described in patients, the mechanistic basis of human cataract development remains poorly understood. Therefore, gene expression of structural, developmental, profibrotic, and transcription factors in phenotypically and etiologically distinct forms of pediatric cataracts were evaluated. Methods: This cross?sectional study included 89 pediatric cataract subjects subtyped into 1) prenatal infectious (cytomegalovirus, rubella, and combined cytomegalovirus with rubella infection), 2) prenatal non?infectious, 3) posterior capsular anomalies, 4) postnatal, 5) traumatic, and 6) secondary, and compared to clear, non?cataractous material of eyes with the subluxated lenses. Expression of lens structure?related genes (Aqp-0, HspA4/Hsp70, CrygC), transcription factors (Tdrd7, FoxE3, Maf, Pitx 3) and profibrotic genes (Tgf?, Bmp7, ?SmA, vimentin) in surgically extracted cataract lens material were studied and correlated clinically. Results: In cataract material, the lens?related gene expression profiles were uniquely associated with phenotype/etiology of different cataracts. Postnatal cataracts showed a significantly altered FoxE3 expression. Low levels of Tdrd7 expression correlated with posterior subcapsular opacity, whereas CrygC correlated significantly with anterior capsular ruptures. The expression of Aqp0 and Maf was elevated

Identification of novel biomarkers with potential for diagnosis and prognosis of gastric cancer: a bioinformatics approach

INTRODUCTION: Gastric cancer (GC) is the fifth most diagnosed neoplasia and the third leading cause of cancer-related deaths. A substantial number of patients exhibit an advanced GC stage once diagnosed. Therefore, the search for biomarkers contributes to the improvement and development of therapies. OBJECTIVE: This study aimed to identify potential GC biomarkers making use of in silico tools. METHODS: Gastric tissue microarray data available in Gene Expression Omnibus and The Cancer Genome Atlas Program was extracted. We applied statistical tests in the search for differentially expressed genes between tumoral and non-tumoral adjacent tissue samples. The selected genes were submitted to an in-house tool for analyses of functional enrichment, survival rate, histological and molecular classifications, and clinical follow-up data. A decision tree analysis was performed to evaluate the predictive power of the potential biomarkers. RESULTS: In total, 39 differentially expressed genes were found, mostly involved in extracellular structure organization, extracellular matrix organization, and angiogenesis. The genes SLC7A8, LY6E, and SIDT2 showed potential as diagnostic biomarkers considering the differential expression results coupled with the high predictive power of the decision tree models. Moreover, GC samples showed lower SLC7A8 and SIDT2 expression, whereas LY6E was higher. SIDT2 demonstrated a potential prognostic role for the diffuse type of GC, given the higher patient survival rate for lower gene expression. CONCLUSION: Our study outlines novel biomarkers for GC that may have a key role in tumor progression. Nevertheless, complementary in vitro analyses are still needed to further support their potential.

Effects of BlueM® against Streptococcus mutans biofilm and its virulence gene expression

Abstract This study evaluated the antimicrobial capacity of BlueM® mouthwash against the bacterium Streptococcus mutans and its influence on gbpA gene expression as well as its cytotoxic effect on fibroblast cells. BlueM® showed antimicrobial activity, with MIC and MBC values of 0.005% and 0.01%, respectively. The MBIC was 6.25% for S. mutans. CFU count and confocal microscopy revealed significant effect of BlueM® on S. mutans biofilm pre-formed on dentin surfaces. Interestingly, the analysis of gbpA gene expression indicated a decrease in gene expression after 15 min of treatment with BlueM® at a concentration of 25%. Moreover, BlueM® exhibited low levels of cytotoxicity. In conclusion, our results showed the antimicrobial effectiveness of BlueM® against S. mutans, its ability to modulate the expression of the gbpA gene and its low cytotoxicity. This study supports the therapeutic potential of BlueM® as an alternative agent for the control of oral biofilm.

Resumo Este estudo avaliou a capacidade antimicrobiana do enxaguatório BlueM® contra a bactéria Streptococcus mutans e sua influência na expressão do gene gbpA, bem como seu efeito citotóxico em células de fibroblastos. BlueM® apresentou atividade antimicrobiana, com valores de CIM e CBM de 0,005% e 0,01%, respectivamente. O MBIC foi de 6,25% para S. mutans. A contagem de UFC e a microscopia confocal revelaram efeito significativo do BlueM® no biofilme de S. mutans pré-formado nas superfícies de dentinas. Curiosamente, a análise da expressão do gene gbpA, indicou uma diminuição na expressão do gene após 15 min de tratamento com BlueM® na concentração de 25%. Além disso, BlueM® exibiu baixos níveis de citotoxicidade. Em conclusão, nossos resultados mostraram a eficácia antimicrobiana do BlueM® contra S. mutans, sua capacidade de modular a expressão do gene gbpA e sua baixa citotoxicidade. Este estudo apoia o potencial terapêutico do BlueM® como agente alternativo para o controle do biofilme oral.

O papel dos RNAs longos não codificantes na insuficiência cardíaca: uma revisão de literatura / The role of non-coding long RNAs in heart failure: a literature review / El papel de las RNAs largas no codificantes en la insuficiencia cardiaca: una revisión de la literatura

A Insuficiência Cardíaca (IC) é uma das principais causas de internação hospitalar no mundo e tem um elevado grau de morbidade e mortalidade, sendo um grave problema de saúde pública. Os lncRNAs (RNAs longo não codificantes), têm funções regulatórias transcricionais e/ou pós transcricionais bem complexas e que ainda não são totalmente claras, mas que podem exercer influência sobre as doenças cardiovasculares, dentre elas a IC. Assim o estudo teve como objetivo identificar na literatura o papel dos lncRNAs na patogênese da IC por meio de uma revisão integrativa com busca sistemática. Foram considerados elegíveis para leitura e composição do estudo 33 artigos e os principais papéis dos lncRNA na IC foram relatados como possíveis marcadores biológicos para diagnóstico e prognóstico da doença devido a sua expressividade na corrente sanguínea. Além disso, os lncRNAs podem estar relacionados à capacidade funcional uma vez que o aumento ou diminuição de sua expressão promove redução da apoptose de células endoteliais, melhora a disfunção cardíaca, distúrbios de contratilidade e dos canais de cálcio em pacientes com IC. Portanto, os lncRNAs parecem estar envolvidos na patogênese e/ou fisiopatologia da IC, podendo ser utilizados como biomarcadores genéticos com sensibilidade e especificidade semelhantes ou superiores aos empregados atualmente no diagnóstico e prognóstico da IC.

Heart Failure (HF) is one of the main causes of hospitalization worldwide and has a high degree of morbidity and mortality being considered a public health pro- blem. lncRNAs (non-coding long RNAs) have very complex transcriptional and/or post- transcriptional regulatory functions that are still not entirely clear but may influence car- diovascular diseases, including HF. Thus, the study aimed to identify in the literature the role of lncRNAs in the pathogenesis of HF through an integrative review with a systema- tic search. A total of 33 articles were considered eligible for reading and composition of the study. The roles of lncRNA in HF were reported as possible biological markers for the diagnosis and prognosis of the disease due to its expressiveness in the bloodstream. In addition, lncRNAs may be related to functional capacity since the increase or decrease in their expression promotes a reduction in endothelial cell apoptosis, and improves car- diac dysfunction, contractility, and calcium channel disorders in patients with HF. The- refore, lncRNAs seem to be involved in the pathogenesis and/or pathophysiology of HF and can be used as genetic biomarkers with sensitivity and specificity similar or superior to those currently employed in the diagnosis and prognosis of HF.

La Insuficiencia Cardiaca (IC) es una de las principales causas de hospita- lización en el mundo y tiene un alto grado de morbimortalidad considerándose un pro- blema de salud pública. Los lncRNAs (ARN largos no codificantes) tienen funciones re- guladoras transcripcionales y/o post-transcripcionales muy complejas que aún no están del todo claras pero que pueden influir en las enfermedades cardiovasculares, incluida la IC. Así pues, el estudio se propuso identificar en la literatura el papel de los lncRNAs en la patogénesis de la IC mediante una revisión integradora con una búsqueda sistemática. Un total de 33 artículos fueron considerados elegibles para su lectura y composición del estudio. Las funciones de los lncRNA en la IC se señalaron como posibles marcadores biológicos para el diagnóstico y pronóstico de la enfermedad debido a su expresividad en el torrente sanguíneo. Además, los lncRNAs pueden estar relacionados con la capacidad funcional, ya que el aumento o disminución de su expresión promueve una reducción de la apoptosis de las células endoteliales y mejora la disfunción cardiaca, la contractilidad y los trastornos de los canales de calcio en pacientes con IC. Por tanto, los lncRNAs parecen estar implicados en la patogénesis y/o fisiopatología de la IC y pueden ser utili- zados como biomarcadores genéticos con sensibilidad y spe-cificidad similares o superi- ores a los empleados actualmente en el diagnóstico y pronóstico de la IC.

The effects of repeated doses of xylazine-ketamine and medetomidineketamine anesthesia on DNA damage in the liver and kidney

Purpose: This study evaluated the DNA damage caused by repeated doses of xylazine-ketamine and medetomidine-ketamine anesthesia in the liver and kidneys. Methods: In this study, 60 rats were used. The rats were divided into group 1 (xylazine-ketamine), and group 2 (medetomidine-ketamine), and these anesthetic combinations were administered to the rats at repeated doses with 30-min intervals. The effects of these anesthetic agents on the tumor necrosis factor-alpha gene for DNA damage were investigated. Results: According to the gene expression results, it was observed that a single dose of xylazine-ketamine was 2.9-fold expressed, while first and second repeat doses did not show significant changes in expression levels. However, in the case of the third repetition, it was observed to be 3.8-fold overexpressed. In the case of medetomidine-ketamine administration, it was observed that a single-dose application resulted in a 1.04-fold expression, while the first and the third repeat doses showed a significant down expression. The samples from the second repeat dose administration group were found to have insignificant levels of expression. Conclusions: This study can contribute to understanding the safe anesthetic combination in research and operations in which xylazine-ketamine and medetomidine-ketamine combinations are used.

Voltage-gated sodium channels gene expression in Burning Mouth Syndrome: a case-control study

Abstract Burning mouth syndrome (BMS) is a condition characterized by painful symptoms of the oral mucosa, despite the absence of any clinical signs. Its etiology is unknown, and there is still no effective treatment to date. Current evidence has shown neuropathic impairment in BMS patients. Neuropathic pain can be related to the dysfunction of voltage-gated sodium channels, considering that these receptors regulate the induction of action potentials in nociceptive neurons. This study evaluated the gene expression of voltage-gated sodium channels Na v 1.7, Na v 1.8 and Na v 1.9 in these patients. The gene expressions of these channels were assessed by real time RT-PCR analysis of fresh-frozen tongue biopsies in a case-control study composed of 12 patients with BMS, and 5 healthy control patients, proportionally matched by sex and age, and analyzed using the 2^(-Delta Delta CT) method. There was no statistically significant difference between the analyzed groups, despite the increase in Na v 1.7 (fold-change = 3.13, p = 0.52) and decrease in Na v 1.9 (fold-change = 0.45, p = 0.36) gene expression in the BMS group. The Na v 1.8 gene was not expressed in any of the samples analyzed. Although the gene expression in the voltage-gated sodium channels in BMS under study seems to be comparable with that of the normal oral mucosa, the functionality of these channels in BMS has not yet been identified, thus suggesting that further research is needed to better understand these voltage-gated sodium channels.

Does resveratrol favor peri-implant bone repair in rats with ovariectomy-induced osteoporosis? Gene expression, counter-torque and micro-CT analysis

Abstract This study investigated the influence of resveratrol on peri-implant repair and its effects on bone-related markers in ovariectomy-induced osteoporosis in rats. Animals were divided into: OVX+PLAC (n = 10): ovariectomized animals treated with placebo; OVX+RESV (n = 10): OVX treated with resveratrol; OVX+PLAC+ZOL (n = 10): OVX treated with PLAC and zoledronate; OVX+RESV+ZOL (n = 10): OVX treated with RESV and ZOL; and SHOVX+PLAC (n = 10): sham ovariectomy treated with PLAC. RESV and PLAC were administrated after ovariectomy and ZOL after six weeks after OVX, until the end of experiment. One implant was inserted in each tibiae of animals 18 weeks after ovariectomy. After 4 weeks, one implant was removed for counter-torque, and peri-implant tissue was collected for mRNA quantification of several osteogenic markers by PCR. The other tibia was submitted to micro-computed tomography analysis. Reduced counter-torque values, bone-implant contact (BIC) and bone volume fraction (BV/TV), and higher bone porosity (BP) were detected in OVX+PLAC group when compared to SHOVX+PLAC (p < 0.05). OVX+RESV rats presented lower BIC, BV/TV, and trabecular number (Tb.N), and augmented BP and trabecular spacing (Tb.Sp) when compared to SHOVX+PLAC (p < 0.05). Higher Tb.N and connectivity density (Conn.Dn) and reduced Tb.Sp were observed in OVX rats treated with ZOL, independently of RESV, when compared to OVX+PLAC and OVX+RESV groups (p < 0.05), whereas the combination ZOL+RESV promoted lower BP when compared to OVT+PLAC and OVX+RESV (p < 0.05). Gene expression was not influenced by RESV (p > 0.05), whereas ZOL promoted up-regulation of BMP-2 (p<0.05). RESV did not improve peri-implant bone repair in rats with ovariectomy-induced osteoporosis.

Estrogen deficiency influences TNF-α and IL-1ß gene expression in the odontogenic region of dental hypofunctional condition / A deficiência de estrógeno influencia a expressão gênica de TNF-α e IL-1ß na região odontogênica de dentes em hipofunção

Objetivo: Evidências científicas sugerem que a deficiência de estrógeno e fatores genéticos influenciam o desenvolvimento do sistema estomatognático. Este estudo teve como objetivo avaliar a influência da deficiência de estrógeno na expressão gênica de TNF-α, IL-1ß, IL-6 e IL-10 durante o desenvolvimento dentário em modelo murino. Material e Métodos: Ratas Wistar Hannover foram divididas em dois grupos de acordo com a intervenção recebida: Grupo Hipoestrogenismo - cirurgia de ovariectomia e Grupo Controle - cirurgia fictícia. Para avaliar o desenvolvimento dentário, o incisivo inferior foi escolhido. O modelo de hipofunção dos incisivos inferiores foi realizado por ajuste incisal. O incisivo homólogo exercia hiperfunção dentária. Os animais foram avaliados durante todo o período puberal. Após a eutanásia, as hemimandíbulas foram removidas para avaliar a expressão gênica do TNF-α, IL-1ß, IL-6 e IL-10 na região odontogênica dos incisivos por meio de PCR em tempo real. Foi realizado o teste de Kruskal-Wallis e o pós-teste de Dunn. O nível de significância foi de 5%. Resultados: Houve diferenças estatisticamente significativas na expressão gênica de TNF-α e IL-1ß entre os grupos hipoestrogenismo e controle sob condição de hipofunção dentária (p=0,0084, p=0,0072, respectivamente). Conclusão: A deficiência de estrógeno influencia a expressão gênica de TNF-α e IL-1ß na região odontogênica de dentes hipofuncionais (AU)

Objective: Scientific evidence suggests that estrogen deficiency and genetic factors have an influence on the development of the stomatognathic system. This study aimed to evaluate the influence of estrogen deficiency on the gene expression of TNF-α, IL-1ß, IL-6 and IL-10 during dental development in a murine model. Material and Methods: Wistar Hannover rats were divided into two groups according to the intervention received: Hypoestrogenism Group - ovariectomy surgery and Control Group - fictitious surgery. To evaluate the dental development, the lower incisor was chosen. The mandibular incisor hypofunction model was performed by incisal adjustment. The homologous incisor exerted a hyperfunction. The animals were evaluated throughout the pubertal period. After euthanasia, the hemimandibles were removed to evaluate the gene expression of the TNF-α, IL-1ß, IL-6 and IL-10 in the odontogenic region of the incisors through real time PCR. Kruskal-Wallis test and Dunn's posttest were performed. The level of significance was 5%. Results: There were statistically significant differences of TNF-α and IL-1ß gene expression between the hypoestrogenism and control groups under hypofunction condition (p=0.0084, p=0.0072, respectively). Conclusion: Estrogen deficiency influences TNF-α and IL-1ß gene expression in the odontogenic region of the hypofunctional teeth. (AU)

Superexpressão Gênica PTEN em Tecidos Miocárdicos de Pacientes de Cirurgia de Revascularização Miocárdica / Overexpression of the PTEN Gene in Myocardial Tissues of Coronary Bypass Surgery Patients

Resumo Fundamento: A doença arterial coronariana é um distúrbio complexo que causa morte em todo o mundo. Um dos genes envolvidos no desenvolvimento dessa doença pode ser o PTEN. Objetivos: Nosso objetivo foi investigar a expressão gênica e proteica do PTEN em amostras de tecido e sangue retiradas de pacientes submetidos à cirurgia de revascularização miocárdica. Métodos: Foram realizados estudos moleculares no Centro de estudos do genoma humano e células-tronco da Universidade Erciyes (GENKOK). Amostras do apêndice atrial direito e de sangue foram coletadas da veia central de 22 pacientes submetidos à cirurgia de revascularização miocárdica antes de iniciar e terminar a circulação extracorpórea. A expressão do PTEN foi determinada usando PCR quantitativo em tempo real e análise de Western Blot. O nível de significância aceito foi de p<0,05. Resultados: Não houve diferença significativa na expressão gênica do PTEN em amostras de sangue coletadas antes e depois da circulação extracorpórea. Entretanto, foi observado um aumento substancial nos níveis de expressão gênica e proteica de P-PTEN e PTEN nas amostras de tecido. A expressão gênica miocárdica PTEN aumentou significativamente ao final da circulação extracorpórea. A expressão gênica do PTEN no período pós-circulação extracorpórea aumentou em comparação com o período pré-circulação extracorpórea, mas não foi um aumento significativo em comparação com sujeitos saudáveis do grupo de controle. Conclusão: Este estudo revelou pela primeira vez o papel do gene PTEN analisando a expressão de mRNA e de proteína em pacientes com revascularização miocárdica, que se manifesta tanto em tecido miocárdico quanto em amostras de sangue. O aumento dos níveis de PTEN pode ser um marcador no tecido miocárdico para pacientes com doença arterial coronariana.

Abstract Background: Coronary artery disease is a complex disorder that causes death worldwide. One of the genes involved in developing this disease may be PTEN. Objectives: This study aimed to investigate the PTEN gene and protein expression in tissue and blood samples taken from coronary bypass surgery patients. Methods: Molecular studies were performed at Erciyes University Genome and Stem Cell Center (GENKOK). Right atrial appendage and blood samples were taken from the central vein of 22 coronary bypass surgery patients before starting and ending cardiopulmonary bypass. PTEN expression was determined using quantitative real-time PCR and western blot analysis. The significance level was accepted as p<0.05. Results: There was no significant difference in the PTEN gene expression in blood samples taken before and after cardiopulmonary bypass. However, a substantial increase in both protein and gene expression levels of P-PTEN and PTEN was observed in the tissue samples. Myocardial expression of the PTEN gene was significantly increased at the end of the cardiopulmonary bypass. PTEN gene expression in the post-cardiopulmonary bypass period was increased when compared to the pre-bypass period, but it was insignificant when compared to healthy controls. Conclusion: This study first revealed the role of the PTEN gene by analyzing both mRNA and protein expression in coronary bypass patients, appearing in both myocardial tissue and blood samples. Increased levels of PTEN may be a marker in myocardial tissue for patients with coronary artery disease.

Effects of the juçara fruit (Euterpe edulis Martius) pulp and lyophilized extract on NRF2, KEAP1, SOD1, and GPX2 expression in human colorectal cancer cell lines

We investigated the effects of the juçara fruit (Euterpe edulis Martius) pulp and lyophilized extract on the expression of cytoprotective genes nuclear factor erythroid 2 (NF-E2)-related factor 2 (NRF2), kelch-like ECH-associated protein 1 (KEAP1), superoxide dismutase (SOD1), and glutathione peroxidase (GPX2) in human colorectal cancer cell lines (HT-29 and Caco-2). Cells were cultured for 24 h in Dulbecco's Modified Eagle's Medium containing juçara fruit pulp (5, 10, or 50 mg/mL) or lyophilized extract (0.05, 0.1, or 0.5 mg/mL), and gene expression was quantified using real-time quantitative reverse transcription polymerase chain reaction. All studied genes showed significant variation in gene expression among different concentrations of pulp or lyophilized extract. Overall, the expression of the selected genes decreased in both cell lines following exposure to the pulp or lyophilized extract in a dose-dependent manner for most of the concentrations studied. In summary, our study showed that the compounds in juçara fruit inhibited the expression of cytoprotective genes associated with the antioxidant response and that, although not cytotoxic at the concentrations studied, they could potentially block the activation of the NRF2/KEAP1 pathway.

Impact of a modified implant macrogeometry on biomechanical parameters and bone-related markers in rats

Abstract This study investigated the impact of a modified implant macrogeometry on peri-implant healing and its effect on bone-related molecules in rats. Eighteen rats received one implant in each tibia: the control group received implants with conventional macrogeometry and the test group received implants with modified macrogeometry. After 30 days, the implants were removed for biomechanical analysis and the bone tissue around them was collected for quantifying gene expression of OPN, Runx2, β-catenin, BMP-2, Dkk1, and RANKL/OPG. Calcein and tetracycline fluorescent markers were used for analyzing newly formed bone at undecalcified sections of the tibial implants. These fluorescent markers showed continuous bone formation at cortical bone width and sparse new bone formed along the medullary implant surface in both groups. However, higher counter-torque values and upregulation of OPN expression were achieved by test implants when compared to controls. The modified macrogeometry of implants optimized peri-implant healing, favoring the modulation of OPN expression in the osseous tissue around the implants.