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OBJECTIVES: We focused our study on examining the genotype and allele frequency of IL-6 (rs1800795), TNF-α (rs1800629) and IL-10 (rs1800872) single nucleotide polymorphisms (SNP) on preeclampsia (PE) diagnosed Mexican pregnant women. MATERIAL AND METHODS: A case-control study was designed including 86 preeclampsia patients and 100 normotensives pregnancies from Women's Hospital of Culiacan, Mexico. Genotyping of IL-6, TNF-α and IL-10 was performed using TaqMan SNP Genotyping. RESULTS: Not significant association was found between development of PE and genotypic (p > 0.05) and allelic (p > 0.05) frequencies of IL-6, TNF-α and IL-10 SNPs. Genotype distributions of IL-6 (p = 0.599), TNF-α (p = 0.721) and IL-10 (p = 0.761) polymorphisms in the two groups were in agreement with Hardy-Weinberg equilibrium. CONCLUSIONS: According to the findings, the IL-6, TNF-α and IL-10 SNPs are not exponents of susceptibility to developing PE.
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Interleucina-10 , Pré-Eclâmpsia , Feminino , Humanos , Gravidez , Estudos de Casos e Controles , Frequência do Gene , Predisposição Genética para Doença , Genótipo , Interleucina-10/genética , Interleucina-6/genética , México , Polimorfismo de Nucleotídeo Único , Pré-Eclâmpsia/genética , Fator de Necrose Tumoral alfa/genéticaRESUMO
Resumen OBJETIVO: Determinar la incidencia del espectro del acretismo placentario en pacientes ingresadas a la unidad de cuidados intensivos obstétricos del Hospital de la Mujer, Culiacán, Sinaloa. MATERIALES Y MÉTODOS: Estudio retrospectivo, transversal y descriptivo fundamentado en el análisis de la base de datos del Hospital de la Mujer de pacientes internadas entre los años 2017 a 2020 con diagnóstico de espectro de placenta acreta, referidas o diagnosticadas en la institución e intervenidas para histerectomía por la complicación estudiada. RESULTADOS: Se analizaron 22 pacientes con diagnóstico de acretismo placentario que dieron una incidencia de 0.09%; de éstas, a 1 se le indicó cesárea; 19 de las 22 pacientes tenían antecedente de cicatriz uterina previa, todas con placenta previa. El promedio de edad fue de 30.86 ± 4 años. La cesárea se practicó, en promedio, a las 34 semanas de embarazo con dos técnicas quirúrgicas. El sangrado promedio estimado fue de 1.947 mL. Las complicaciones transoperatorias fueron las lesiones: ureteral (n = 2) y vesical (n = 1). La principal complicación posoperatoria fue la fístula vesicouterina (n = 1). El promedio de estancia fue de 2 días en 16 de las 22 pacientes y de 7 días en las 6 restantes. CONCLUSIONES: Lo importante del acretismo placentario es el diagnóstico oportuno que permita derivar a las pacientes a centros hospitalarios que cuenten con especialistas experimentados en la atención de estos casos.
Abstract OBJECTIVE: To determine the incidence of placental accretism spectrum in pregnant women admitted to the obstetric intensive care unit of the Hospital de la Mujer, Culiacán, Sinaloa. MATERIALS AND METHODS: Retrospective, cross-sectional, descriptive study based on the analysis of the database of the Hospital de la Mujer of patients admitted between 2017 and 2020 with a diagnosis of placenta accreta spectrum, referred or diagnosed at the institution and underwent hysterectomy for the complication studied. RESULTS: Twenty-two patients with a diagnosis of placenta accreta were analysed, giving a prevalence of 0.09%; of these, caesarean section was indicated in 0.2%. 19 of the 22 patients had a history of previous uterine scarring, all with placenta praevia. Mean age was 30.86 ± 4 years. Caesarean section was performed at a mean gestational age of 34 weeks using two surgical techniques. The mean estimated blood loss was 1,947 mL. The most common operative complications were ureteral (n = 2) and bladder (n = 1) injuries. The most common postoperative complication was vesico-uterine fistula (n = 1). The mean length of stay was 2 days in 16 of the 22 patients and 7 days in the remaining 6 patients. CONCLUSIONS: The most important aspect of placenta accreta is early diagnosis, which allows referral to hospital centres with specialists experienced in the management of these cases.
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RATIONALE: A pregnancy with incomplete mole is very rare case. Hydatidiform mole (HM) with live fetus is associated with a risk of a wide variety to maternal and fetal complications. The incidence of a normal live fetus and an incomplete mole such as the case we describe is extremely rare. PATIENT CONCERN: We report a case of multiparous 34-year-old at Culiacan Mexico woman with incomplete mole coexisting with normal fetus, pregnant 35.3 weeks who presented anemia grade II. DIAGNOSIS: The initial diagnosis of the mole was by ultrasound. INTERVENTIONS: KERR-type cesarean section and bilateral tubal occlusion. The newborn was morphologically normal, and she did not require intervention or treatment. OUTCOMES: The newborn was feminine, morphologically normal, weighing 2380 g and 47 cm, APGAR score 8 to 9, delivered prematurely, and there was a large placental plate. The blood loss on surgery was estimated at 1000 mL. Histopathology report of an incomplete hydatidiform mole, negative for malignancy. Histopathology diagnostic was confirmed by immunohistochemistry staining for p57KIP2. LESSONS: Although the incidence of this pregnancy is very rare, early recognition, diagnosis and divulge of the cases of medical community is very important for patient care.
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Mola Hidatiforme , Neoplasias Uterinas , Recém-Nascido , Gravidez , Feminino , Humanos , Adulto , Gravidez de Gêmeos , Neoplasias Uterinas/patologia , Cesárea , Placenta/patologia , Mola Hidatiforme/diagnóstico , Feto/patologiaRESUMO
The main complications causing practically 75% of all maternal deaths are severe bleeding, infections, and high blood pressure during pregnancy (preeclampsia (PE) and eclampsia). The usefulness of ncRNAs as clinical biomarkers has been explored in an extensive range of human diseases including pregnancy-related diseases such as PE. Immunological dysregulation show that the Th1/17:Th2/Treg ratio is "central and causal" to PE. However, there is evidence of the involvement of placenta-expressed miRNAs and lncRNAs in the immunological regulation of crucial processes of placenta development and function during pregnancy. Abnormal expression of these molecules is related to immune physiopathological processes that occur in PE. Therefore, this work aims to describe the importance of miRNAs and lncRNAs in immune dysregulation in PE. Interestingly, multiple ncRNAS are involved in the immune dysregulation of PE participating in type 1 immune response regulation, immune microenvironment regulation in placenta promoting inflammatory factors, trophoblast cell invasion in women with Early-Onset PE (EOPE), placental development, and angiogenesis, promotion of population of M1 and M2, proliferation, invasion, and migration of placental trophoblast cells, and promotion of invasion and autophagy through vias such as PI3K/AKT/mTOR, VEGF/VEGFR1, and TLR9/STAT3.
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MicroRNAs , Pré-Eclâmpsia , RNA Longo não Codificante , Humanos , Gravidez , Feminino , Placenta/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Pré-Eclâmpsia/metabolismo , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Trofoblastos/metabolismoRESUMO
This study aimed to evaluate if the change of vehicle for CTZ (Chloramphenicol, Tetracycline, zinc oxide, and Eugenol) paste improves the inhibition of Enterococcus faecalis in vitro. The vehicles evaluated alone and mixed with CTZ were Eugenol, propylene glycol (PG), super-oxidized solution (SOS), grapefruit-seed extract (GSE), and 0.9% saline solution as a negative control. A clinical isolate of E. faecalis was morphologically and biochemically characterized, and its antimicrobial susceptibility was tested using 20 antimicrobial agents. Once characterized, the clinical isolate was cultivated to perform the Kirby-Bauer disc diffusion method with paper discs embedded with the different vehicles mixed or used alone, and incubated at 37 °C for 24 h. Data were analyzed using one-way ANOVA, and the means were compared using Tukey test with a significance level of p < 0.05. For vehicles used alone, GSE presented the greatest inhibition showing a statistically significant difference with the rest of the vehicles. When vehicles were mixed with the CTZ paste, PG showed a greater inhibition with a statistically significant difference from the rest of the vehicles. In conclusion, the vehicle used to mix the CTZ paste plays an important role in the inhibition of E. faecalis in vitro; therefore, we consider that this can be an important factor to achieve success in the use of this technique.
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Background: Colorectal cancer (CRC) is a leading cause of death worldwide. SRY-box transcription factor 9 (SOX9) participates in organogenesis and cell differentiation in normal tissues but has been involved in carcinogenesis development. Cancer stem cells (CSCs) are a small population of cells present in solid tumors that contribute to increased tumor heterogeneity, metastasis, chemoresistance, and relapse. CSCs have properties such as self-renewal and differentiation, which can be modulated by many factors. Currently, the role of SOX9 in the maintenance of the stem phenotype has not been well elucidated, thus, in this work we evaluated the effect of the absence of SOX9 in the stem phenotype of CRC cells. Methods: We knockout (KO) SOX9 in the undifferentiated CRC cell line HCT116 and evaluated their stemness properties using sphere formation assay, differentiation assay, and immunophenotyping. Results: SOX9-KO affected the epithelial morphology of HCT116 cells and stemness characteristics such as its pluripotency signature with the increase of SOX2 as a compensatory mechanism to induce SOX9 expression, the increase of KLF4 as a differentiation feature, as well as the inhibition of the stem cell markers CD44 and CD73. In addition, SOX9-KO cells gain the epithelial-mesenchymal transition (EMT) phenotype with a significant upregulation of CDH2. Furthermore, our results showed a remarkable effect on first- and second-sphere formation, being SOX9-KO cells less capable of forming high-size-resistant spheres. Nevertheless, CSCs surface markers were not affected during the differentiation assay. Conclusions: Collectively, our findings supply evidence that SOX9 promotes the maintenance of stemness properties in CRC-CSCs.
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BACKGROUND: Biomaterials must allow revascularization for a successful tissue regeneration process. Biomaterials formulated from the extracellular matrix (ECM) have gained popularity in tissue engineering because of their superior biocompatibility, and due to their rheological properties, ECM-hydrogels can be easily applied in damaged areas, allowing cell colonization and integration into the host tissue. Porcine urinary bladder ECM (pUBM) retains functional signaling and structural proteins, being an excellent option in regenerative medicine. Even some small molecules, such as the antimicrobial cathelicidin-derived LL-37 peptide have proven angiogenic properties. OBJECTIVE: The objective of this study was to evaluate the biocompatibility and angiogenic potential of an ECM-hydrogel derived from the porcine urinary bladder (pUBMh) biofunctionalized with the LL-37 peptide (pUBMh/LL37). METHODS: Macrophages, fibroblasts, and adipose tissue-derived mesenchymal stem cells (AD-MSC) were exposed pUBMh/LL37, and the effect on cell proliferation was evaluated by MTT assay, cytotoxicity by quantification of lactate dehydrogenase release and the Live/Dead Cell Imaging assays. Moreover, macrophage production of IL-6, IL-10, IL-12p70, MCP-1, INF-γ, and TNF-α cytokines was quantified using a bead-based cytometric array. pUBMh/LL37 was implanted directly by dorsal subcutaneous injection in Wistar rats for 24 h to evaluate biocompatibility, and pUBMh/LL37-loaded angioreactors were implanted for 21 days for evaluation of angiogenesis. RESULTS: We found that pUBMh/LL37 did not affect cell proliferation and is cytocompatible to all tested cell lines but induces the production of TNF-α and MCP-1 in macrophages. In vivo, this ECM-hydrogel induces fibroblast-like cell recruitment within the material, without tissue damage or inflammation at 48 h. Interestingly, tissue remodeling with vasculature inside angioreactors was seen at 21 days. CONCLUSIONS: Our results showed that pUBMh/LL37 is cytologically compatible, and induces angiogenesis in vivo, showing potential for tissue regeneration therapies.
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Catelicidinas , Hidrogéis , Ratos , Suínos , Animais , Hidrogéis/química , Catelicidinas/análise , Catelicidinas/metabolismo , Catelicidinas/farmacologia , Fator de Necrose Tumoral alfa/análise , Fator de Necrose Tumoral alfa/metabolismo , Fator de Necrose Tumoral alfa/farmacologia , Ratos Wistar , Matriz Extracelular/química , Materiais Biocompatíveis/química , Engenharia Tecidual/métodos , Alicerces Teciduais/químicaRESUMO
BACKGROUND: The necessity to manufacture scaffolds with superior capabilities of biocompatibility and biodegradability has led to the production of extracellular matrix (ECM) scaffolds. Among their advantages, they allow better cell colonization, which enables its successful integration into the hosted tissue, surrounding the area to be repaired and their formulations facilitate placing it into irregular shapes. The ECM from porcine urinary bladder (pUBM) comprises proteins, proteoglycans and glycosaminoglycans which provide support and enable signals to the cells. These properties make it an excellent option to produce hydrogels that can be used in regenerative medicine. OBJECTIVE: The goal of this study was to assess the biocompatibility of an ECM hydrogel derived from the porcine urinary bladder (pUBMh) in vitro using fibroblasts, macrophages, and adipose-derived mesenchymal stem cells (AD-MCSs), as well as biocompatibility in vivo using Wistar rats. METHODS: Effects upon cells proliferation/viability was measured using MTT assay, cytotoxic effects were analyzed by quantifying lactate dehydrogenase release and the Live/Dead Cell Imaging assay. Macrophage activation was assessed by quantification of IL-6, IL-10, IL-12p70, MCP-1, and TNF-α using a microsphere-based cytometric bead array. For in vivo analysis, Wistar rats were inoculated into the dorsal sub-dermis with pUBMh. The specimens were sacrificed at 24 h after inoculation for histological study. RESULTS: The pUBMh obtained showed good consistency and absence of cell debris. The biocompatibility tests in vitro revealed that the pUBMh promoted cell proliferation and it is not cytotoxic on the three tested cell lines and induces the production of pro-inflammatory cytokines on macrophages, mainly TNF-α and MCP-1. In vivo, pUBMh exhibited fibroblast-like cell recruitment, without tissue damage or inflammation. CONCLUSION: The results show that pUBMh allows cell proliferation without cytotoxic effects and can be considered an excellent biomaterial for tissue engineering.
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Hidrogéis , Engenharia Tecidual , Ratos , Suínos , Animais , Engenharia Tecidual/métodos , Hidrogéis/farmacologia , Alicerces Teciduais , Bexiga Urinária , Ratos Wistar , Fator de Necrose Tumoral alfa/metabolismo , Fator de Necrose Tumoral alfa/farmacologia , Matriz ExtracelularRESUMO
The eggplant is a fruit rich in natural products and produced worldwide. However, its cultivation generates a large amount of scarcely used agricultural residues with poor chemical characterization. This study aimed to identify and quantify the metabolome and determine the composition of select phytochemicals and the overall antioxidant capacity of various anatomical parts of the plant. The plant's root, leaf, stem, and fruit were analyzed by quantitative mass spectrometry-based untargeted metabolomics and chemoinformatics, and phytochemicals were quantified by spectrophotometric analysis. Moreover, we determined the total antioxidant capacity of the distinct plant parts to infer a possible biological effect of the plant's metabolites. Various secondary metabolites were identified as terpenes, phenolic compounds, alkaloids, and saponins, distributed throughout the plant. The leaf and fruit presented the highest concentration of phenolic compounds, flavonoids, anthocyanins, and alkaloids, accompanied by the highest antioxidant capacity. Although the stem and root showed the lowest abundance of secondary metabolites, they provided around 20% of such compounds compared with the leaf and fruit. Overall, our study improved the understanding of the eggplant metabolome and concluded that the plant is rich in secondary metabolites, some with antioxidant properties, and shows potential nutraceutical and biopharmaceutical applications.
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Saponinas , Solanum melongena , Solanum melongena/química , Antocianinas/química , Antioxidantes/química , Cromatografia Líquida de Alta Pressão , Compostos Fitoquímicos/análise , Frutas/química , Fenóis/química , Flavonoides/análise , Extratos Vegetais/química , Metabolômica , Saponinas/análise , Terpenos/análiseRESUMO
BACKGROUND: Preeclampsia (PE) is a syndromic disorder that affects 2% to 8% of pregnancies and is diagnosed principally when hypertension appears in the second-d half of pregnancy. WHO estimates the incidence of PE to be seven times higher in developing countries than in developed countries. Severe preeclampsia/eclampsia is one of the most important causes of maternal mortality, associated with 50,000 to 100,000 annual deaths globally as well as serious fetal and neonatal morbidity and mortality, especially in developing countries. Even though evidence from family-based studies suggest PE has a heritable component, its etiology, and specific genetic contributions remain unclear. Many studies examining the genetic factors contributing to PE have been conducted, most of them are focused on single nucleotide polymorphisms (SNPs). Given that PE has a very important inflammatory component, is mandatory to examine cytokine-SNPs for elucidating all mechanisms involved in this pathology. In this review, we describe the most important cytokine-polymorphisms associated with the onset and development of PE. We aim to provide current and relevant evidence in this regard. METHODS: We searched English databases such as PubMed and the National Center for Biotechnology Information. The publication time of the papers was set from the establishment of the databases to February 2022. All studies about Th1/Th2/Th17 cytokines polymorphisms were included in our study. RESULTS: SNPs in IFN-γ, TNF-α, IL-4, IL-6, IL-10, IL-17A, and IL-22 are associated with the development, early-onset and severity of PE, being the Th1/Th2/Th17 responses affected by the presence of these SNPs. CONCLUSIONS: The changes in Th1/Th2/Th17 response modify processes such as placentation, control of inflammation, and vascular function. Nonetheless, association studies have shown different results depending on sample size, diagnostic, and population.
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Pré-Eclâmpsia , Citocinas/genética , Feminino , Humanos , Recém-Nascido , Interleucina-10/genética , Interleucina-17/genética , Interleucina-4/genética , Interleucina-6/genética , Polimorfismo de Nucleotídeo Único , Pré-Eclâmpsia/diagnóstico , Pré-Eclâmpsia/genética , Gravidez , Fator de Necrose Tumoral alfa/genéticaRESUMO
BACKGROUND: Nowadays, biomaterials used as a scaffold must be easy to deliver in the bone defect area. Extracellular matrix (ECM) hydrogels are highly hydrated polymers that can fill irregular shapes and act as bioactive materials. OBJECTIVE: This work aims to show the effects of ECM hydrogels derived from bovine bone (bECMh) on proliferation, cytotoxicity and expression of pro-inflammatory cytokines in three cells types involved in tissue regeneration, as well as biocompatibility in vivo. METHODS: In vitro, we used an extract of bECMh to test it on macrophages, fibroblasts, and adipose-derived mesenchymal stem cells (AD-MCSs). Cell proliferation was measured using the MTT assay, cytotoxicity was measured by quantifying lactate dehydrogenase release and the Live/Dead Cell Imaging assays. Concentrations of IL-6, IL-10, IL-12p70, MCP-1 and TNF-α were quantified in the supernatants using a microsphere-based cytometric bead array. For in vivo analysis, Wistar rats were inoculated into the dorsal sub-dermis with bECMh, taking as reference the midline of the back. The specimens were sacrificed at 24 h for histological study. RESULTS: In vitro, this hydrogel behaves as a dynamic biomaterial that increases fibroblast proliferation, induces the production of pro-inflammatory cytokines in macrophages, among which MCP-1 and TNF-α stand out. In vivo, bECMh allows the colonization of host fibroblast-like and polymorphonuclear cells, without tissue damage or inflammation. CONCLUSIONS: The results indicate that bECMh is a biocompatible material that could be used as a scaffold, alone or in conjunction with cells or functional biomolecules, enhancing proliferation and allowing the filling of bone defects to its further regeneration.
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Hidrogéis , Alicerces Teciduais , Ratos , Animais , Bovinos , Hidrogéis/farmacologia , Fator de Necrose Tumoral alfa , Ratos Wistar , Matriz Extracelular , Materiais Biocompatíveis/farmacologiaRESUMO
The aim of this study was to characterize potential fungal species affecting mangrove species in Mexico. The phytopathogens were identified based on morphological and molecular characteristics using internal transcribed spacer (ITS1/ITS4) primers then sequenced and compared with the other related sequences in GenBank (NCBI). Three fungal species were identified as Colletotrichum queenslandicum (Weir and Johnst, 2012) from black mangrove (Avicennia germinans); Colletotrichum ti (Weir and Johnst, 2012) from white mangrove (Laguncularia racemosa) and buttonwood mangrove (Conocarpus erectus); Fusarium equiseti (Corda) from red mangrove (Rhizophora mangle). In addition, C. ti and F. equiseti were identified from mango Mangifera indica L. sampled close by the mangrove area. This study provides first evidence of anthracnose on four mangrove species caused by Colletotrichum and Fusarium species in the "Términos" coastal lagoon in Campeche State southern Mexico. This is the first time that C. queenslandicum and C. ti are reported in Mexico. F. equiseti has not been reported affecting M. indica and R. mangle until the present work. Little is known regarding fungal diseases affecting mangroves in Mexico. These ecosystems are protected by Mexican laws and may be threatened by these pathogenic fungus. This is the first report of the effect of Trichoderma harzianum TRICHO-SIN as an effective biological control against of Colletotrichum and Fusarium species.
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BACKGROUND: MicroRNAs (miRNAs) are involved in the regulation of genes with important roles in cancer. Therefore, they represent interesting targets as biomarkers for early detection, follow-up, and prognosis of the disease. CONTEXT: In early stages of breast cancer, differences in the expression of miR-148b-3p, miR-145-5p and miR-133a-3p have been reported. AIMS: To compare the expression of miR-148b-3p, miR-145-5p and miR-133a-3p in serum samples from female patients with and without breast cancer. SETTING AND DESIGN: Case control study. MATERIALS AND METHODS: We quantified the expression by real-time polymerase chain reaction of miR-148b-3p, miR-145-5p, and miR-133a-3p in serum samples from 27 breast cancer (BC) and 17 benign breast tumor patients. STATISTICAL ANALYSIS USED: Comparison between groups with categorical variables was made using the Pearson's Chi-square test. Comparative analysis for continuous variables between two groups was performed using the Student's t-test. One-way analysis of variance (ANOVA) was used for multigroup comparison, followed by Tukey HSD analysis. RESULTS: The use of contraceptives and a high number of births were identified as risk factors for BC. We observed that miR-145-5p expresses in low levels in BC and positively diagnosed Her2 patients. In addition, BC patients with either ductal carcinoma or positive molecular diagnosis for estrogen receptor, progesterone receptor, luminal A, or Her2 negative, presented a decreased expression of miR-133a-3p. CONCLUSIONS: We observed an existing association between the molecular characteristics of BC and levels of circulating miR-133a-3p and miR-145-5p, proving the potential role of miRNAs as biomarkers for BC.
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Neoplasias da Mama/sangue , MicroRNAs/biossíntese , Biomarcadores Tumorais/biossíntese , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Estudos de Casos e Controles , Feminino , Humanos , Imuno-Histoquímica , MicroRNAs/sangue , MicroRNAs/genética , Pessoa de Meia-Idade , Receptor ErbB-2/metabolismo , Receptores de Estrogênio/metabolismo , Receptores de Progesterona/metabolismoRESUMO
Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease in the world. Despite the impact of this pathology in the population, nowadays there is no specific treatment for this disease, focusing its treatment on risks factors. However, it is imperative the existence of a specific treatment, due to this, the aim of this study was to determine the therapeutic effect of treatment with metformin, 4-hydroxychalcone or co-treatment on male Wistar rats with NAFLD. Wistar rats were divided into two groups with free access to either tap water or 50% sucrose (NAFLD) during 25 weeks. After 20 weeks of induction each were divided into four groups that received daily p.o. administration of: i) saline solution (1â¯ml); ii) metformin (200â¯mg/kg/day); iii) 4-hydroxychalcone (80â¯mg/kg/day) and i.v.) co-treatment (metformin plus 4-hydroxychalcone at the doses mentioned above), for 5 weeks. In healthy rats: metformin and co-treatment modified food and total caloric intake and induced diarrhea; but none of the treatments changed the other parameters evaluated. Meanwhile in rats with NAFLD: i) metformin inhibited hepatic total cholesterol and TGF-ß, increased diarrhea frequency, and slightly decreased liver steatosis, and fibrosis; ii) 4-hydroxychalcone decreased IL-6, TNF-α and TGF-ß, increased IL-10, and markedly decreased liver steatosis and fibrosis; and iii) co-treatment markedly decreased food intake, total caloric intake, and body weight, increased diarrhea; increased IL-10, showing and intermediate effect on decrease TNF-α, TGF-ß, liver steatosis and fibrosis. Our results showed that 4-hydroxychalcone treatment was the most effective among the treatments tested against NAFLD.
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Chalconas/farmacologia , Metformina/farmacologia , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Animais , Chalconas/uso terapêutico , Colágeno/biossíntese , Citocinas/sangue , Diarreia/complicações , Interações Medicamentosas , Ingestão de Alimentos/efeitos dos fármacos , Fígado/efeitos dos fármacos , Fígado/metabolismo , Fígado/patologia , Masculino , Metformina/uso terapêutico , Hepatopatia Gordurosa não Alcoólica/sangue , Hepatopatia Gordurosa não Alcoólica/complicações , Hepatopatia Gordurosa não Alcoólica/patologia , Nutrientes/metabolismo , Ratos , Ratos WistarRESUMO
Transcriptional and epigenetic embryonic programs can be reactivated in cancer cells. As result, a specific subset of undifferentiated cells with stem-cells properties emerges and drives tumorigenesis. Recent findings have shown that ectoderm- and endoderm-derived tissues continue expressing stem-cells related transcription factors of the SOX-family of proteins such as SOX2 and SOX9 which have been implicated in the presence of cancer stem-like cells (CSCs) in tumors. Currently, there is enough evidence suggesting an oncogenic role for SOX9 in different types of human cancers. This review provides a summary of the current knowledge about the involvement of SOX9 in development and progression of cancer. Understanding the functional roles of SOX9 and clinical relevance is crucial for developing novel treatments targeting CSCs in cancer.
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The high intake of sweetened drinks is associated with obesity and insulin resistance. These pathologies are directly related to the development of nonalcoholic fatty liver disease (NAFLD), considered a condition of metabolic syndrome (MS). Due to their increasing worldwide prevalence, experimental animal models have been developed to gain a better understanding of its physiopathology; notwithstanding, few studies have evaluated its progression in association with MS and ingestion of sweetened drinks. Therefore, the aim of this study was to understand the pathophysiologic characteristics of NAFLD related to sucrose concentration and time of ingestion in rats. Wistar rats were divided into 2 groups with free access to either tap water or 30% sucrose, and euthanized at 12, 16, or 20 weeks; and 2 additional groups were given free access to either 40% or 50% sucrose and were euthanized at 20 weeks. Biochemical parameters and levels of serum cytokines were measured, and histology was performed. Ingestion of 30% sucrose induced liver steatosis until 16 weeks (grade 2) and 20 weeks (grade 3). Meanwhile, during 20 weeks, 40% sucrose induced grade 5 of nonalcoholic steatohepatitis (NASH) and 50% sucrose induced grade 6 of NASH and fibrosis. This study demonstrated that increasing time of induction and concentration of sucrose ingestion resulted in a higher grade of NAFLD.
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Sacarose Alimentar/administração & dosagem , Sacarose Alimentar/efeitos adversos , Hepatopatia Gordurosa não Alcoólica/etiologia , Hepatopatia Gordurosa não Alcoólica/patologia , Animais , Peso Corporal/fisiologia , Citocinas/sangue , Masculino , Hepatopatia Gordurosa não Alcoólica/sangue , Obesidade/sangue , Obesidade/etiologia , Obesidade/patologia , Ratos , Ratos Wistar , Fatores de TempoRESUMO
Diabetes mellitus (DM) is a metabolic disease characterized by persistent high levels of glucose in plasma. Chronic hyperglycemia is thought to increase oxidative stress and the formation of free radicals that in turn damage cells. Thus, we decided to determine the frequency of nuclear abnormalities in epithelial cells from cheek and tongue mucosa of DM patients with type 1 (DM1, treated only with insulin) and type 2 (DM2, treated with metformin) using the buccal micronucleus cytome (BMCyt) assay. Micronuclei frequency in cheek epithelial cells was higher in both DM1 (0.75 ± 0.31, P < 0.001) and DM2 (0.52 ± 0.27, P < 0.001) patients, as compared to healthy controls (0.07 ± 0.06). Similarly, micronuclei frequency in tongue epithelium was increased in DM1 (0.81 ± 0.22, P < 0.001) and DM2 (0.41 ± 0.21, P < 0.001) groups, in comparison to controls (0.06 ± 0.05). Besides, we found a positive correlation between micronuclei frequency and the onset time of DM2 in both cheek (ρ = 0.69, P < 0.001) and tongue epithelial cells (ρ = 0.71, P < 0.001), but not with onset time of DM1 or age of the patients. Considering all this, we pose that BMCyt could serve as a fast and easily accessible test to assess genotoxic damage during dental visits of DM patients, helping to monitor their disease.
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Diabetes Mellitus Tipo 1/diagnóstico , Diabetes Mellitus Tipo 2/diagnóstico , Epitélio/metabolismo , Mucosa Bucal/metabolismo , Bochecha/patologia , Dano ao DNA/efeitos dos fármacos , Diabetes Mellitus Tipo 1/tratamento farmacológico , Diabetes Mellitus Tipo 1/metabolismo , Diabetes Mellitus Tipo 1/patologia , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/patologia , Epitélio/patologia , Feminino , Humanos , Insulina/uso terapêutico , Masculino , Metformina/uso terapêutico , Testes para Micronúcleos/métodos , Pessoa de Meia-Idade , Mucosa Bucal/patologia , Estresse Oxidativo/efeitos dos fármacos , Língua/metabolismo , Língua/patologiaRESUMO
To evaluate the association of the -308 and -238 tumor necrosis factor alpha (TNF-α) gene polymorphisms with clinical manifestations of dengue and TNF-α serum levels in a northwestern Mexican population. The study populations included dengue fever (DF) and dengue hemorrhagic fever (DHF) patients, and a group of healthy controls (HCs) without history of dengue. Polymerase chain reaction-restriction fragment length polymorphism and Enzyme-Linked Immunosorbent Assay were performed to determine genotypes and serum concentration of TNF-α, respectively. There were no significant differences in alleles, genotypes, and haplotype frequencies between patients and HCs. However, when patients were separated into DF and DHF, there was an increased prevalence of the -308 GA genotype in HCs compared to DHF (odds ratio [OR] = 0.129, 95% confidence interval [CI] = 0.018-0.945, p = 0.025), as well as the GG haplotype (OR = 0.49, 95% CI = 0.273-0.880, p = 0.01757) in DF. The genotypes of both polymorphisms were not associated with hematologic manifestations. Serum TNF-α levels were significantly higher in patients than in HCs (p = 0.004). Our results suggest a minimal effect of the -308 and -238 TNF-α gene polymorphisms in dengue patients and that their increased serum levels of TNF-α are independent of genotypes.
Assuntos
Dengue/genética , Predisposição Genética para Doença , Polimorfismo de Nucleotídeo Único , Dengue Grave/genética , Fator de Necrose Tumoral alfa/genética , Adulto , Alelos , Estudos de Casos e Controles , Dengue/sangue , Dengue/imunologia , Feminino , Genótipo , Haplótipos , Humanos , Masculino , México , Pessoa de Meia-Idade , Dengue Grave/sangue , Dengue Grave/imunologia , Fator de Necrose Tumoral alfa/sangue , Fator de Necrose Tumoral alfa/imunologiaRESUMO
Extracellular matrix (ECM) is a rich network of proteins and proteoglycans that has proved to be very useful in tissue regeneration. Porcine ECM has been proposed as a biological scaffold, and urinary bladder matrix (UBM) has demonstrated superior biological properties; however, its use in human treatment requires ensuring that it is DNA free. Several protocols have been used for decellularization and to demonstrate the absence of DNA, but until now, a porcine housekeeping gene for quantifying DNA by real-time quantitative PCR (qPCR) has been limiting. The aim of this study was to propose a protocol to quantify the DNA content of decellularized UBM by qPCR for the beta-actin gene (ACTB). A total of 20 porcine bladders were used, and each bladder was divided into three pieces: one as a control and the others decellularized with either SDS or Triton X-100 detergent. The presence of DNA was assessed by histology, spectrophotometry, conventional PCR, and qPCR for the ACTB. Histological analysis demonstrated the absence of nuclei using both protocols. Spectrophotometrical evaluation resulted in DNA concentrations of 1561.4 ± 357.1 and 1211.9 ± 635.2 ng of DNA/mg dry weight after the SDS and Triton X-100 protocols, respectively. DNA was not detected in any protocol by conventional PCR. In contrast, using qPCR, we found 3.9 ± 2.8 ng of DNA/mg dry weight in the Triton X-100 protocol. Therefore, the use of qPCR is a reliable method to quantify residual DNA content after decellularization procedures.
Assuntos
Actinas/genética , DNA/análise , Matriz Extracelular/fisiologia , Engenharia Tecidual/métodos , Alicerces Teciduais , Bexiga Urinária/citologia , Animais , Núcleo Celular/genética , Detergentes/farmacologia , Humanos , Octoxinol/farmacologia , Reação em Cadeia da Polimerase , Dodecilsulfato de Sódio/farmacologia , Espectrofotometria , SuínosRESUMO
Intervertebral disc degeneration (IDD) is the most common diagnosis in patients with back pain, a leading cause of musculoskeletal disability worldwide. Several conditions, such as occupational activities, gender, age, and obesity, have been associated with IDD. However, the development of this disease has strong genetic determinants. In this study, we explore the possible association between rs1800587 (c.-949C>T) of interleukin-1 alpha (IL1A) and rs2228570 (c.2T>V) and rs731236 (c.1056T>C) of vitamin D receptor (VDR) gene polymorphisms and the development of IDD in northwestern Mexican Mestizo population. Gene polymorphisms were analyzed by polymerase chain reaction followed by restriction fragment length polymorphism, in two groups matched by age and gender: patients with symptomatic lumbar IDD (n = 100) and subjects with normal lumbar-spine MRI-scans (n = 100). Distribution of the mutated alleles in patients and controls was 27.0% versus 28.0% (P = 0.455) for T of rs1800587 (IL1A); 53.0% versus 58.0% (P = 0.183) for V of rs2228570 (VDR); and 18.0% versus 21.0% (P = 0.262) for C of rs731236 (VDR). Our results showed no association between the studied polymorphisms and IDD in this population. This is the first report on the contribution of gene polymorphisms on IDD in a Mexican population.