Functionalized Metal Nanoparticles in Cancer Therapy.

Currently, there are many studies on the application of nanotechnology in therapy. Metallic nanoparticles are promising nanomaterials in cancer therapy; however, functionalization of these nanoparticles with biomolecules has become relevant as their effect on cancer cells is considerably increased by photothermal and photodynamic therapies, drug nanocarriers, and specificity by antibodies, resulting in new therapies that are more specific against different types of cancer. This review describes studies on the effect of functionalized palladium, gold, silver and platinum nanoparticles in the treatment of cancer, these nanoparticles themselves show an anticancer effect. This effect is further enhanced when the NPs are functionalized with either antibodies, DNA, RNA, peptides, proteins, or folic acid and other molecules. These NPs can penetrate the cell and accumulate in the tumor tissue, resulting in a cytotoxic effect through the generation of ROS, the induction of apoptosis, cell cycle arrest, DNA fragmentation, and a photothermal effect. NP-based therapy is a new strategy that can be used synergistically with chemotherapy and radiotherapy to achieve more effective therapies and reduce side effects.

The Role of microRNAs in Pulp Inflammation.

The dental pulp can be affected by thermal, physical, chemical, and bacterial phenomena that stimulate the inflammatory response. The pulp tissue produces an immunological, cellular, and vascular reaction in an attempt to defend itself and resolve the affected tissue. The expression of different microRNAs during pulp inflammation has been previously documented. MicroRNAs (miRNAs) are endogenous small molecules involved in the transcription of genes that regulate the immune system and the inflammatory response. They are present in cellular and physiological functions, as well as in the pathogenesis of human diseases, becoming potential biomarkers for diagnosis, prognosis, monitoring, and safety. Previous studies have evidenced the different roles played by miRNAs in proinflammatory, anti-inflammatory, and immunological phenomena in the dental pulp, highlighting specific key functions of pulp pathology. This systematized review aims to provide an understanding of the role of the different microRNAs detected in the pulp and their effects on the expression of the different target genes that are involved during pulp inflammation.

Effect of treatment with resiniferatoxin in an experimental model of pulpal inflammatory in mice.

AIM: To evaluate whether treatment with resiniferatoxin (RTX) is capable of lowering the plasma levels of PGE2 and TNF-α, as well as histopathological parameters in inflammation of pulp tissue in a mouse experimental model. METHODOLOGY: Ten groups of six BALB/c mice were formed as follows: healthy group (HC ), healthy group treated with RTX (HRTX ), two groups with pulp inflammation at 14 and 18 hours (PI14 /PI18 ), six groups with pulpal inflammation plus treatment with Ibuprofen (IBU14 /IBU18 ), dexamethasone (DEX14 /DEX18 ) and resiniferatoxin (RTX14 /RTX18 ) at 14 and 18 hours, respectively. Pulpal inflammation was induced through occlusal exposure of the pulp of the maxillary first molar. The plasma levels of PGE2 and TNF-α and the histological parameters of the pulp tissue of the HC and HRTX groups were evaluated at the time of acquiring the animals. In the other groups, the plasma levels of PGE2 and TNF-α and the histopathological parameters were evaluated at 14 and 18 hours after pulp damage. Plasma levels of PGE2 and TNF-α were quantified by ELISA, and the histopathological parameters were evaluated by H/E staining. Statistical significance was determined by one-way analysis of variance (ANOVA) to test for overall differences between group means. RESULTS: A significant increase (*p < .05) in plasma levels of PGE2 and TNF-α occurred 14 and 18 hours after pulp damage. In addition, treatment with RTX significantly decreased (*p < .05) the plasma levels of PGE2 and TNF-α at 14 and 18 hours after pulp damage, as well as the infiltrate of inflammatory cells at 18 hours after pulp damage, similarly to treatment with ibuprofen and dexamethasone. CONCLUSION: It was possible to detect systemic levels of PGE2 and TNF-α at 14 and 18 hours after pulp damage. Likewise, treatment with RTX was associated with an anti-inflammatory effect similar to treatment with ibuprofen and dexamethasone. These findings place resiniferatoxin as a therapeutic alternative in the treatment of inflammatory diseases in Dentistry.

Resiniferatoxin promotes adult worm expulsion in Trichinella spiralis-infected rats by Th2 immune response modulation.

BACKGROUND: The immune response during T spiralis infection is characterized by an increase in eosinophils and mast cells, as well as Th2 cytokine production, such as interleukin (IL)-4, IL-10 and IL-13, promoting T spiralis expulsion from the host. However, this response damages the host, favouring the parasite survival. In the search for new pharmacological strategies that protect against T spiralis infection, a recent study showed that treatment with resiniferatoxin (RTX) modulates the Th1 cytokines production, reducing muscle parasite burden. OBJECTIVE: To evaluate the effect of RTX treatment on the Th2 cytokines production, the number of eosinophils, mast cells and the intestinal expulsion of T spiralis. METHODS: Serum levels of IL-4, IL-10 and IL-13 were quantified by ELISA; the number of eosinophils, mast cells and the adult worms of T spiralis in the small intestine was quantified. RESULTS: RTX treatment increased serum levels of IL-4, IL-10 and IL-13, and it decreases intestinal eosinophilia, however, favours the mastocytosis, promoting T spiralis intestinal expulsion. CONCLUSIONS: These findings suggest that RTX is capable to modulate the Th2 immune response, promoting T spiralis expulsion, which contributes to the defence against T spiralis infection, placing the RTX as a potential immunomodulatory drug.

Correlación del factor neurotrófico derivado del cerebro con los componentes que integran el síndrome metabólico infantil / Correlation of brain derived neurotrophic factor with the components that integrate the child metabolic syndrome

La obesidad infantil representa un factor importante en el desarrollo del síndrome metabólico (SM). En este sentido el factor neurotrófico derivado del cerebro (BDNF: Brain Derived Neurotrophic Factor) interviene en el metabolismo energético así como en vías que controlan el peso corporal y desórdenes metabólicos. El objetivo de este estudio fue determinar si hay una correlación entre el BDNF con los marcadores que definen al síndrome metabólico en una población infantil de México. Se integraron al estudio 100 niños con un rango de edad de 5-13 años, se estratificaron en tres grupos, normo peso, sobrepeso y obesidad, a los cuales se les determinaron las variables antropométricas, percentil de la tensión arterial sistólica y diastólica, concentraciones séricas de glucosa, triglicéridos, colesterol de alta densidad (HDL) y BDNF. Se aplicó ANOVA y una correlación de Pearson. Los resultados muestran que la prevalencia de SM utilizando los criterios de Cook y Weiss fue del 14%, mientras que por la Federación Internacional de Diabetes (IDF) es del 11%. La circunferencia de cintura, triglicéridos, colesterol HDL, presión arterial sistólica/diastólica y glucosa, mostraron diferencias significativas entre los grupos estudiados (*p<0,001). El BDNF se correlacionó positivamente con la desviación estándar del índice de masa corporal de acuerdo con la edad (DE-IMCE) (p=0,01), el percentil del perímetro de la cintura (p=0,00), la presión arterial sistólica (p=0,01) y las concentraciones plasmáticas de glucosa (p=0,02). Estos datos muestran que existe una correlación entre el BDNF con la DE-IMCE, la circunferencia de la cintura, la presión arterial sistólica y glucosa(AU)

Childhood obesity represents an important factor in the development of metabolic syndrome (MS). In this sense, the brain derived neurotrophic factor (BDNF) is involved in energy metabolism as well as in pathways that control body weight and metabolic disorders. The objective of this study was to determine if there is a correlation between BDNF with the markers that define the metabolic syndrome in a child population in Mexico. The study included 100 children with an age range of 5-13 years, stratified into three groups, normal weight, overweight and obesity, which were determined anthropometric variables, percentile of systolic and diastolic blood pressure, concentrations serum glucose, triglycerides, high density cholesterol (HDL) and BDNF. ANOVA and Pearson correlation were applied. The results show that the prevalence of MS using the Cook and Weiss criteria was 14%, while for the International Diabetes Federation (IDF) it is 11%. Waist circumference, triglycerides, HDL cholesterol, systolic/diastolic blood pressure and glucose showed significant differences between the groups studied (*p<0.001). The BDNF was positively correlated with the standard deviation of the body mass index according to age (DE-IMCE) (p=0.01), the percentile of the waist circumference (p=0.00), systolic blood pressure (p=0.01) and plasma glucose concentrations (p=0.02). These data show that there is a correlation between BDNF with DE-IMCE, waist circumference, systolic blood pressure and glucose(AU)

The microRNA landscape of cutaneous squamous cell carcinoma.

Cutaneous squamous cell carcinoma (cSCC) is a keratinocyte-derived skin tumor. It is the second-most-common cancer affecting the Caucasian population and is responsible for >20% of all skin-cancer-related deaths. The estimated incidence of non-melanoma skin cancer in the USA is >1000000 cases per year, of which roughly 20-30% are squamous cell carcinoma. To better understand and treat this challenging cancer, current research focuses on development of novel strategies to improve the understanding of tumor biogenesis on an individual basis. microRNAs are becoming important biomarkers in the diagnosis, prognosis and treatment of cSCC. This review describes the current knowledge on miRNA expression in cSCC and its role as a biomarker for personalized medicine.

EVALUACIÓN DE ANTICUERPOS ANTI-Trichinella spiralis OBTENIDOS POR INMUNIZACIONES SUBLINGUALES Y CONVENCIONALES CON LA PROTEÍNA 45kDa / Evaluation of Anti-Trichinella spiralis Obtained by Sublingual and Conventional Immunizations with the 45kDa Protein

RESUMEN La trichinellosis es una enfermedad parasitaria zoonótica y cosmopolita, se debe al consumo de carne deficientemente cocida, principalmente proveniente del cerdo, diversos estudios avalan la eficacia de la administración de inmunoterapia. Se ha caracterizado un antígeno inmunodominante de 45 kDa y se plantea como objetivo evaluar la presencia de anticuerpos IgA, IgM e IgG antti-Trichinella spiralis a lo largo de la infección, así como el comportamiento en la administración de la inmunización de 45 kDa de Trichinella spiralis (T. spiralis) administrado por vía sublingual y vía parenteral. Se utilizaron 36 murinos (Long Evans), seis para la infección y purificación del antígeno de 45 kDa, 30 para formar los grupos de trabajo, control sano (cinco murinos), control infectado (cinco murinos), y 20 para los grupos experimentales, se inmunizaron dos grupos con cuatro dosis (0, 7, 14 y 21 días) del inmunógeno de 45 KDa de T. spiralis, uno por vía sublingual y otro por vía parenteral y se retaron con 500 larvas infectantes (LI) de T. spiralis siete días después de la ultima inmunización y dos grupos más se infectaron con 500 LI y se inmunizaron a las cuatro semanas postinfección por ambas vías. La respuesta se evaluó por inmunofluorescencia indirecta (IFI) por microscopia confocal para determinar la respuesta humoral con anticuerpos de clase IgG, IgM e IgA.

ABSTRACT Trichinellosis is a cosmopolitan zoonotic disease produced mainly by the consumption of poorly cooked swine meat. Several studies have probed the efficiency of immunotherapy as a method for the treatment of trichinellosis. In this work, a 45 kDa immunodominant antigen was characterized, and the presence of IgA, IgM and IgG antti-Trichinella spiralis antibodies was evaluated during the course of the infection. In addition, the differences between sublingual and parenteral administration of the 45 kDa T. spiralis antigen were determined. Long Evans rats were used both to purify the 45 kDa antigen and to evaluate the immune response produced in six different groups: healthy and infected controls; two groups of immunized murines (sublingually and parenterally) with four doses of the 45 kDa T. spiralis immunogen administered at days 0, 7, 14 and 21 and challenged with 500 T. spiralis infective larvae (IL) 7 days after the last immunization; and finally, two groups of murines infected with 500 IL ofT. spiralis, immunized at week 4 post infection by the same two routes. The humoral response was evaluated by indirect immunofluorescence by confocal microscopyin order to determine the presence of IgA, IgM and IgG antibodies.

Therapeutic Effects of Resiniferatoxin Related with Immunological Responses for Intestinal Inflammation in Trichinellosis.

The immune response against Trichinella spiralis at the intestinal level depends on the CD4+ T cells, which can both suppress or promote the inflammatory response through the synthesis of diverse cytokines. During the intestinal phase, the immune response is mixed (Th1/Th2) with the initial predominance of the Th1 response and the subsequent domination of Th2 response, which favor the development of intestinal pathology. In this context, the glucocorticoids (GC) are the pharmacotherapy for the intestinal inflammatory response in trichinellosis. However, its therapeutic use is limited, since studies have shown that treatment with GC suppresses the host immune system, favoring T. spiralis infection. In the search for novel pharmacological strategies that inhibit the Th1 immune response (proinflammatory) and assist the host against T. spiralis infection, recent studies showed that resiniferatoxin (RTX) had anti-inflammatory activity, which decreased the serum levels of IL-12, INF-γ, IL-1ß, TNF-α, NO, and PGE2, as well the number of eosinophils in the blood, associated with decreased intestinal pathology and muscle parasite burden. These researches demonstrate that RTX is capable to inhibit the production of Th1 cytokines, contributing to the defense against T. spiralis infection, which places it as a new potential drug modulator of the immune response.

Identificación de microRNAs en carcinoma cutáneo de células escamosas (CCE) / Identification of microRNAs in cutaneous squamous cell carcinoma (cSCC)

El carcinoma cutáneo de células escamosas (CCE) es el segundo cáncer de piel ms común en humanos, el cual puede llegar a ser invasivo y mostrar un curso agresivo. El CCE inicia en las células escamosas de la capa epidérmica. Así mismo, la epidermis se compone de tejido queratinizado que se regenera continuamente a partir de células basales y reemplaza a las células muertas. Estudios sobre el proceso de diferenciación celular, muestran que los microRNAs (miRNAs) están involucrados en el proceso de formación de la piel, y se ha reportado que alteraciones en la transcripción, procesamiento y expresión de los miRNAs afecta a la señalización celular, esencial en la proliferación, invasión, apoptosis y diferenciación células malignas. Los miRNAs son una familia de reguladores epigenéticos de pequeñas moléculas endógenas no codificantes de RNAs de aproximadamente 25 nucleótidos de longitud, y están involucrados en la patogénesis de cáncer en humanos como reguladores de factores de crecimiento transformantes y metástasis. Se hizo una revisión sistemática usando las principales bases de datos bibliográficas (PubMed/MEDLINE, Science) y revistas públicas en internet. Los criterios de inclusión y exclusión fueron predefinidos (carcinoma cutáneo, miRNAs, biogénesis) y también un conjunto de variables para analizar las características de los artículos seleccionados (expresión y el papel de los miRNAs en el CCE, que no han sido bien estudiadas).

The cutaneous squamous cell carcinoma (cSCC) is the second most common skin cancer in humans, which can become invasive and show an aggressive course. CSCC starts in the epidermal layer of squamous cells. Also, the epidermis is composed of keratinized tissue that continuously regenerate from basal cells and replace the dead cells. Studies about cell differentiation process, shows that microRNAs (miRNAs) are involved in the process of skin formation, and has been reported that alterations intranscription, processing and expression of miRNAs, affect the function of the cell signaling, essential the proliferation, invasion, apoptosis and differentiation of malignant cells. MiRNAs are an epigenetic regulators family of small noncoding endogenous molecules of RNAs, about 25 nucleotides in length, and are involved in the pathogenesis of human cancer in the regulation of transformant growth factors and metastasis. We performed a systematic review using major electronic bibliographic databases (PubMed/MEDLINE, Sciencie) and public journals on the internet. Inclusion and exclusion criteria were pre-defined (cutaneous carcinoma, miRNAs, and biogenesis) and also a set of variables to analyze the characteristics of the selected reports (the expression and role of miRNAs in the cSCC, what has not been well studied).