Nicolás Serafín-Higuera

Low Proteolytic Clipping of Histone H3 in Cervical Cancer

Chromatin in cervical cancer (CC) undergoes chemical and structural changes that alter the expression pattern of genes. Recently, a potential mechanism, which regulates gene expression at transcriptional levels is the proteolytic clipping of histone H3. However, until now this process in CC has not been reported. Using HeLa cells as a model of CC and human samples from patients with CC, we identify that the H3 cleavage was lower in CC compared with control tissue. Additionally, the histone H3 clipping was performed by serine and aspartyl proteases in HeLa cells. These results suggest that histone H3 clipping operates as part of post-translational modification system in CC.

The HPV16 E7 Oncoprotein Disrupts Dendritic Cell Function and Induces the Systemic Expansion of CD11b+Gr1+ Cells in a Transgenic Mouse Model

Objective. The aim of this study was to analyze the effects of the HPV16 E7 oncoprotein on dendritic cells (DCs) and CD11b+Gr1+ cells using the K14E7 transgenic mouse model. Materials and Methods. The morphology of DCs was analyzed in male mouse skin on epidermal sheets using immunofluorescence and confocal microscopy. Flow cytometry was used to determine the percentages of DCs and CD11b+Gr1+ cells in different tissues and to evaluate the migration of DCs. Results. In the K14E7 mouse model, the morphology of Langerhans cells and the migratory activity of dendritic cells were abnormal. An increase in CD11b+Gr1+ cells was observed in the blood and skin of K14E7 mice, and molecules related to CD11b+Gr1+ chemoattraction (MCP1 and S100A9) were upregulated. Conclusions. These data suggest that the HPV16 E7 oncoprotein impairs the function and morphology of DCs and induces the systemic accumulation of CD11b+Gr1+ cells.

The Antinociceptive Effects of a Tapentadol-Ketorolac Combination in a Mouse Model of Trigeminal Pain is Mediated by Opioid Receptors and ATP-Sensitive K+ Channels

Preclinical Research

Protein translation associated to PERK arm is a new target for regulation of metainflammation: A connection with hepatocyte cholesterol: GALINDO-HERNÁNDEZ et al.

Endoplasmic reticulum stress is a cellular phenomenon that has been associated with metabolic disorders, contributing to the development of obesity, fatty liver disease, and dyslipidemias. Under metabolic overload conditions, in cells with a high protein‐secretory activity, such as hepatocytes and Langerhans β cells, the unfolded protein response (UPR) is critical in to maintain protein homeostasis (proteostasis). UPR integrated by a tripartite signaling system, through activating transcription factor 6, protein kinase R‐like endoplasmic reticulum kinase (PERK), and inositol‐requiring enzyme 1, regulates gene transcription and translation to resolve stress and conserve proteostasis. In the current study, we demonstrated in hepatocytes under metabolic overload by saturated palmitic and stearic fatty acids, through activation of PERK signaling and CCAAT‐enhancer‐binding protein homologous protein (CHOP) transcription factor, an association with the expression of cyclooxygenase 2. More important, isolated exosomes from supernatants of macrophages exposed to lipopolysaccharides can also induce a metainflammation phenomenon, and when treated on hepatocytes, induced a rearrangement in cholesterol metabolism through sterol regulatory element‐binding protein 2 (SREBP2), low‐density lipoprotein receptor (LDLR), apolipoprotein A‐I, and ABCA1. Moreover, we demonstrate the cellular effect of terpene‐derived molecules, such as cryptotanshinone, isolated of plant Salvia brandegeei, regulating metainflammatory conditions through PERK pathway in both hepatocytes and β cells. Our data suggest the presence of a modulatory mechanism on specific protein translation process. This effect could be mediated by eukaryotic initiation factor‐4A, evaluating salubrinal as a control molecule. Likewise, the protective mechanisms of unsaturated fatty acids, such as oleic and palmitoleic acid were confirmed. Therefore, modulation of metainflammation suggests a new target through PERK signaling in cells with a high secretory activity, and possibly the regulation of cholesterol in hepatocytes is promoted via exosomes.

Pharmacological Control of Complications Following to Third Molar Removal: Evidence Based on A Meta-Analysis

AIMS The purpose of this meta-analysis was to evaluate the clinical efficacy of non-steroidal anti-inflammatory drugs and dexamethasone on the trismus, postsurgical pain, facial swelling, as well as the analgesic consumption after third molar surgery. MATERIAL AND METHODS The reports were identified in the most important medical databases. Those studies that met the requirements were fully assessed according to the inclusion and exclusion criteria. The quality of each report was evaluated with the Oxford Quality Scale and using the Cochrane Collaborations risk of bias tool. Each meta-analysis was done using the technique of mean difference and 95% confidence intervals employing a random effects model with the Review Manager 5.3., from the Cochrane Library. Significant statistical difference was accepted when the p value was less than 0.05 on the test of overall effect (Z value). RESULTS Qualitative evaluation was done using the data of 330 patients extracted from seven articles and the quantitative assessment with data of 200 patients from three reports. It was not observed difference among non-steroidal anti-inflammatory drugs and dexamethasone in any of the clinical effectiveness indicators. CONCLUSION The outcomes of our meta-analysis indicate that non-steroidal anti-inflammatory drugs and dexamethasone have good therapeutic effect for the management of inflammatory complications following to third molar surgery.

Participation of ATP-sensitive K+ channels and μ-opioid receptors in the antinociceptive synergism of the paracetamol-tapentadol co-administration in the formalin-induced pain assay in mice

Preclinical Research & Development

Molecular Markers of Anticancer Drug Resistance in Head and Neck Squamous Cell Carcinoma: A Literature Review

This manuscript provides an update to the literature on molecules with roles in tumor resistance therapy in head and neck squamous cell carcinoma (HNSCC). Although significant improvements have been made in the treatment for head and neck squamous cell carcinoma, physicians face yet another challenge—that of preserving oral functions, which involves the use of multidisciplinary therapies, such as multiple chemotherapies (CT) and radiotherapy (RT). Designing personalized therapeutic options requires the study of genes involved in drug resistance. This review provides an overview of the molecules that have been linked to resistance to chemotherapy in HNSCC, including the family of ATP-binding cassette transporters (ABCs), nucleotide excision repair/base excision repair (NER/BER) enzymatic complexes (which act on nonspecific DNA lesions generated by gamma and ultraviolet radiation by cross-linking and forming intra/interchain chemical adducts), cisplatin (a chemotherapeutic agent that causes DNA damage and induces apoptosis, which is a paradox because its effectiveness is based on the integrity of the genes involved in apoptotic signaling pathways), and cetuximab, including a discussion of the genes involved in the cell cycle and the proliferation of possible markers that confer resistance to cetuximab.

Periodontitis may modulate long-non coding RNA expression

Periodontitis is a chronic inflammatory disease that compromises the integrity of the periodontium. Despite extensive research involving periodontitis, the detailed mechanisms underlying periodontal inflammation remain unclear. However, new important expression regulators have been emerging, such as non-coding RNAs, which are important determinants in the molecular control of the inflammatory process. Taking into consideration the vital role of non-coding RNAs, we determined for the first time the expression profiles of different long non-coding RNAs (lncRNAs) that are implicated in inflammation. In this study, we take periodontal samples of healthy subjects, patients with gingivitis and with periodontitis. In both disease groups, the lncRNA OIP5-AS1 expression levels were lower than levels in healthy subjects (P < 0.05). This study reveals new insights into the relative levels of OIP5-AS1 lncRNA in healthy, gingivitis and periodontal tissue, which may have important applications as a potential biomarker with protagonist activity in the development and manifestation of destructive periodontitis.

Epigenetic mechanisms in odontogenic tumors: A literature review

OBJECTIVE Epigenetic mechanisms, such as DNA methylation, regulate important biological processes as gene expression and it was suggested that these phenomena play important roles in the carcinogenesis and tumor biology. The aim of this review is to provide the current state of knowledge about epigenetic alterations, focusing mainly on DNA methylation, reported in odontogenic tumors. DESIGN Literatures were searched based in the combination of the following keywords: odontogenic tumors, epigenetics, DNA methylation, histone modifications, non-coding RNA, microRNA, DNA methyltransferases. Electronic databases (Medline/PubMed, Scopus and Web of Science) were screened. RESULTS The analysis of epigenetic alterations in different tumors has rapidly increased; however, limited information is available about epigenetic mechanisms involved in the formation of odontogenic tumors. DNA methylation is the most studied epigenetic modification in these tumors and the participation of non-coding RNAs in odontogenic tumors has been recently addressed. Differential expression of DNA methyltransferases, altered DNA methylation patterns and aberrant expression of non-coding RNAs were reported in odontogenic tumors. CONCLUSIONS Current studies suggest epigenetics as an emerging mechanism, possibly implicated in etiopathogenesis of odontogenic tumors. Deeper understanding of the epigenetic abnormalities in these tumors could show potential applications as biomarkers or therapeutic possibilities in the future.

Myeloid derived suppressor cell: A new player in periodontal disease?

Periodontal disease can be initiated by a shift from a symbiotic to a dysbiotic microbial community. An increase in the recruitment of leukocytes and production of inflammatory cytokines, chemokines and oxidative stress are generated by this shift. In periodontitis, an exacerbated, poorly specific and effective inflammatory response is mounted. Moreover, failure in the inflammation resolving mechanism leads to establishment of a chronic inflammatory process, resulting in the progressive destruction of bone and soft tissue. In different diseases presenting chronic inflammation some important players of immune response are defectives. Thus, an immunosuppressive environment could be induced during chronic inflammation. Myeloid derived suppressor cells (MDSC), a heterogenic group of immature myeloid cells with potent immune suppressive activity, are increased in several acute and chronic inflammatory diseases. Dysbiosis-mediated inflammation can induce increased frequency of MDSC. In addition, mediators generated in diverse inflammatory diseases have demonstrated to promote expansion, activation and recruitment of MDSC, similar mediators have been described in periodontal disease. MDSC promote generation of nitric oxide (NO) and reactive oxygen species (ROS). Furthermore, MDSC can differentiate in functional osteoclasts. We hypothesize that MDSC are generated during periodontal disease. Review of literature evaluating this hypothesis and possible implications are assed in this work. It encourages the study of MDSC in this common disease.