IL-6, IL-10 and TNF-α gene polymorphisms in preeclampsia: a case-control study in a Mexican population.

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.

Twin pregnancy with incomplete hydatidiform mole and coexistent normal live fetus: A case report and review of the literature.

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.

The Role of ncRNAs in the Immune Dysregulation of Preeclampsia.

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.

Propylene Glycol Potentiates the Inhibitory Action of CTZ Paste on Antibiotic-Resistant Enterococcus faecalis Isolated from the Root Canal: An In Vitro Study.

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.

SOX9 knockout decreases stemness properties in colorectal cancer cells.

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.

Evaluation of biocompatibility and angiogenic potential of extracellular matrix hydrogel biofunctionalized with the LL-37 peptide.

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.

An extracellular matrix hydrogel from porcine urinary bladder for tissue engineering: In vitro and in vivo analyses.

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.

Postoperative chronic pain in arthroplasty papillon-lefèvre syndrome: 17-year dental follow-up: case report / Síndrome de papillon-lefèvre: seguimiento dental de 17 años: reporte de caso

Introduction: The present report describes the case of a 12-year-old patient with 17-year follow-up who was previously diagnosed with Papillon-Lefèvre Syndrome (PLS), which is a rare autosomal recessive irregularity in the cathepsin C gene (CTSC) characterized by palmoplantar hyperkeratosis and premature loss of primary and permanent teeth. Case Report: A specific mutation in the c.203 T > G gene inducing loss of function leading to PLS was detected, as was a mutation in the HLA-DRB1*11 allele, which is associated with this syndrome. There is no consanguinity of the parents, and the siblings are entirely healthy. Early identification of the main characteristics of this syndrome is imperative. Accurate diagnosis by genetic analysis allows differential diagnoses and timely comprehensive dental treatment. Conclusions: Additionally, it allows consultation with a dermatologist to maintain or improve the quality of life of patients with this condition due to progressive worsening and severity of the main physical manifestations. Keywords: Papillon-Lefevre Disease; Keratoderma, Palmo-plantar; Cathepsin C; Periodontitis; Skin Diseases, Genetic; Case reports

Introducción: El presente reporte describe el caso de un paciente de 12 años de edad con 17 años de seguimiento a quien previamente se le diagnosticó Síndrome de Papillon-Lefèvre (PLS), el cual es una rara irregularidad autosómica recesiva en el gen de la catepsina C (CTSC) caracterizada por hiperqueratosis palmoplantar y pérdida prematura de dientes primarios y permanentes. Reporte de Caso: Se detectó una mutación específica en el gen c.203 T > G que induce pérdida de función que conduce a PLS, así como una mutación en el alelo HLA-DRB1*11, que se asocia a este síndrome. No presenta consanguinidad de los padres, padres y hermanos totalmente sanos. La identificación temprana de las principales características de este síndrome es imperativa. El diagnóstico certero por análisis genético permite diagnósticos diferenciales y tratamientos odontológicos integrales oportunos. Conclusiones: Adicionalmente, permite la consulta con un dermatólogo para mantener o mejorar la calidad de vida de los pacientes con esta condición debido al progresivo empeoramiento y severidad de las principales manifestaciones físicas.

Metabolomic Analysis of Phytochemical Compounds from Agricultural Residues of Eggplant (Solanum melongena L.).

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.

Cytokine-polymorphisms associated with Preeclampsia: A review.

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.

Dysregulation of KRT19, TIMP1, and CLDN1 gene expression is associated with thyroid cancer.

Thyroid nodules are the main indicators of thyroid cancer, their malignancy is evaluated by cytological analysis and imaging technology, however, there are still cases where the result is not enough to classify thyroid cancer. Therefore, there is a necessity for accurate molecular biomarkers to collaborate in the diagnosis. Here, we analyzed the mRNA relative expression of CLDN1, TIMP1, and KRT19 genes in FNA of malignant (n = 48) and benign (n = 49) thyroid nodules by RT-qPCR analysis to assess their predictive value as cancer biomarkers. We identified a significant overexpression of the three transcripts in malignant nodules, therefore, the evaluation of their predictive capacity to distinguish between benign and malignant nodule as individual biomarkers were evaluated by logistic regression tests, obtaining promising prediction results to rule out cancer; later by random forest to create a stronger model, we included expression results with clinicopathological characteristics, the best model consists of the three-mRNA level expression with patient's history of cancer (AUC = 0.821, accuracy = 85.4% and sensitivity of 81.1%). These results demonstrate a dysregulated expression of CLDN1, KRT19 and TIMP1 in thyroid cancer, thus, represent a promising panel of biomarkers to be evaluated in indeterminate thyroid nodules.

Extracellular matrix hydrogel derived from bovine bone is biocompatible in vitro and in vivo.

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.

First Molecular Characterization of Colletotrichum sp. and Fusarium sp. Isolated from Mangrove in Mexico and the Antagonist Effect of Trichoderma harzianum as an Effective Biocontrol Agent.

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.

Underexpression of circulating miR-145-5p and miR-133a-3p are associated with breast cancer and immunohistochemical markers.

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.

Expression of miR-148b-3p is correlated with overexpression of biomarkers in prostate cancer.

Prostate cancer (PCa) is one of the leading causes of death among men. Genes such as PCA3, PSA, and Fra-1 are suggested to serve as potential tools for the detection of PCa, as they are deregulated during this pathology. A similar event occurs with small non-coding RNAs, called miRNAs, specifically miR-195-5p, miR-133a-3p, and miR-148b-3p, which were analyzed in a Chinese population and suggested to be possible candidates for PCa diagnosis. We evaluated the expression levels of three miRNAs and three genes in tissue samples of PCa and benign prostate disease, such as benign prostatic hyperplasia, or prostatitis, in order to determine their potential as candidates for PCa detection. Our results showed a statistically significant overexpression of 279-fold increase in PSA levels and a 1,012-fold increase in PCA3 levels in PCa patients compared to benign prostate disease patients (p = 0.001 and p = 0.002, respectively). We observed a positive correlation between the expression of miR-148b-3p and the expression of PSA and PCA3 genes, two established biomarkers in PCa. The expression of miR-148b-3p was not related to clinical characteristics, such as age and weight, as observed for the other miRNAs analyzed, suggesting its potential as a biomarker for detection of this pathology.

Therapeutic effect of treatment with metformin and/or 4-hydroxychalcone in male Wistar rats with nonalcoholic fatty liver disease.

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 (1 ml); ii) metformin (200 mg/kg/day); iii) 4-hydroxychalcone (80 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.

SOX9 Stem-Cell Factor: Clinical and Functional Relevance in Cancer.

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.

Histopathological and biochemical changes in the development of nonalcoholic fatty liver disease induced by high-sucrose diet at different times.

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.

Increased Micronuclei Frequency in Oral and Lingual Epithelium of Treated Diabetes Mellitus Patients.

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.

Genetic Polymorphisms of Tumor Necrosis Factor Alpha and Susceptibility to Dengue Virus Infection in a Mexican Population.

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.