Human chorionic gonadotropin regulates cytokine production by lymphocytes from patients with multiple sclerosis.

Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system (CNS) that primarily affects young adults, predominantly females. This was partially attributed to sex differences in immunity, which are influenced by changes in sex hormones occurring during women's life, among other factors. Furthermore, MS patients experience significant improvement in their symptoms during pregnancy when levels of female sex-hormones significantly increase. This phenomenon was attributed to immune adaptations occurring during gestation which are regulated by paternal antigens and sex hormones. The human chorionic gonadotropin (hCG) was shown to have strong immunosuppressive abilities. We aimed to analyze here the capacity of the hCG to regulate pro- and anti-inflammatory cytokine production by PBMC from MS patients. PBMC isolated from 17 MS patients receiving IFNß1a treatment were cultured with or without recombinant or urinary hCG. Cytokine production in the supernatants was assessed using a CBA array and cytokine production by lymphocytes and expression of co-stimulatory molecules in B-lymphocytes were evaluated by flow cytometry. hCG reduced the production of TNF by PBMC from MS patients while lowering the percentages of TNF producing T cells and diminishing the production of TNF by B cells. hCG significantly boosted the production of IL-10 by regulatory T cells and CD19high B cells from MS patients. Furthermore, hCG treatment lowered the percentages of CD80+CD86+ expressing B cells within PBMC from MS patients. Overall, our results described a novel and not yet explored mechanisms of action of hCG in the context of MS.

Transcriptomic Analyses Reveal Insights into the Shared Regulatory Network of Phenolic Compounds and Steviol Glycosides in Stevia rebaudiana.

Stevia rebaudiana (Bertoni) is a highly valuable crop for the steviol glycoside content in its leaves, which are no-calorie sweeteners hundreds of times more potent than sucrose. The presence of health-promoting phenolic compounds, particularly flavonoids, in the leaf of S. rebaudiana adds further nutritional value to this crop. Although all these secondary metabolites are highly desirable in S. rebaudiana leaves, the genes regulating the biosynthesis of phenolic compounds and the shared gene network between the regulation of biosynthesis of steviol glycosides and phenolic compounds still need to be investigated in this species. To identify putative candidate genes involved in the synergistic regulation of steviol glycosides and phenolic compounds, four genotypes with different contents of these compounds were selected for a pairwise comparison RNA-seq analysis, yielding 1136 differentially expressed genes. Genes that highly correlate with both steviol glycosides and phenolic compound accumulation in the four genotypes of S. rebaudiana were identified using the weighted gene co-expression network analysis. The presence of UDP-glycosyltransferases 76G1, 76H1, 85C1, and 91A1, and several genes associated with the phenylpropanoid pathway, including peroxidase, caffeoyl-CoA O-methyltransferase, and malonyl-coenzyme A:anthocyanin 3-O-glucoside-6″-O-malonyltransferase, along with 21 transcription factors like SCL3, WRK11, and MYB111, implied an extensive and synergistic regulatory network involved in enhancing the production of such compounds in S. rebaudiana leaves. In conclusion, this work identified a variety of putative candidate genes involved in the biosynthesis and regulation of particular steviol glycosides and phenolic compounds that will be useful in gene editing strategies for increasing and steering the production of such compounds in S. rebaudiana as well as in other species.

Abordaje terapéutico paliativo de la obstrucción biliar en el cáncer de vesícula irresecable / Palliative therapeutic approach to bile obstruction in irresecable bladder cancer

El cáncer de vesícula es la neoplasia maligna más frecuente del tracto biliar. Con un mal pronóstico, su enfoque terapéutico muchas veces se centra en el tratamiento paliativo debido a que los pacientes suelen recibir un diagnóstico en estadios avanzados de la neoplasia, en los cuales ya no son candidatos para tratamientos quirúrgicos curativos. Por esta razón se utilizan stents o drenajes vesiculares, a fin de reducir el principal síntoma que se presenta: la ictericia, con sus consecuencias, por obstrucción biliar maligna. Este artículo pretende hacer una revisión de la evidencia recolectada en los últimos 5 años (período 2016 - 2021) acerca de los diferentes abordajes mínimamente invasivos en el tratamiento paliativo del cáncer de vesícula, sus resultados clínicos, y las diferencias entre ellos.

Gallbladder cancer is the most common malignancy neoplasm of the bile ducts. With a poor prognosis, its therapeutic approach is often focused on palliative treatment because patients usually receive a diagnosis in advanced stages of the neoplasm, in which they are no longer candidates for curative surgical treatments. For this reason, stents or gallbladder drains are used in order to reduce the main symptom that occurs: jaundice, with its consequences, due to malignant biliary obstruction. This article aims to review the evidence collected in the last 5 years (period 2016 - 2021) about the different minimally invasive approaches in the palliative treatment of gallbladder cancer, their clinical results, and the differences between them.