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ABSTRACT Five new benzannulated steroid spiroketals were synthesized by Pd‐catalyzed spiroketalization of 5α and 5β‐alkynediols derived from stigmasterol and sitosterol. The detailed nuclear magnetic resonance (NMR) and X‐ray characterization of the newly obtained spiroketals are presented. While the obtained compounds showed null or very low cytotoxicity, two of them inhibited more than 60% of the nitrous oxide production in J774A.1 macrophages stimulated with LPS, showing promising properties as anti‐inflammatory agents. [ABSTRACT FROM AUTHOR]

COVID-19 vaccine evaluations are mainly focused on antibody analyses, but there is growing interest in measuring the cellular immune responses from the researchers evaluating these vaccines. The cellular responses to several COVID-19 vaccines have been studied using the enzyme-linked immunospot (ELISPOT) assay for IFN-γ. However, the ELISPOT assay is no longer used only for research purpose and so the performance of this assay must be validated. Since the bioanalytical validation of ELISPOT-IFN-γ is essential for evaluating the method's effectiveness and establishing confidence in a vaccine's immunogenicity, the present work validates the ELISPOT-IFN-γ assay's performance in determining the frequency of IFN-γ-producing cells after stimulation with the SARS-CoV-2 spike protein. The validation was performed in peripheral blood mononuclear cells from volunteers immunized with anti-COVID-19 vaccines. According to the findings, the LOD was 17 SFU and the LLOQ was 22 SFU, which makes the method highly sensitive and suitable for evaluating low levels of cellular responses. The procedure's accuracy is confirmed by the correlation coefficients for the spike protein and anti-CD3+, being 0.98 and 0.95, respectively. The repeatability and intermediate precision tests were confirmed to be reliable by obtaining a coefficient of variation of ≤25%. The results obtained in this validation enable the assay to be employed for studying antigen-specific cells and evaluating cellular responses to vaccines. [ABSTRACT FROM AUTHOR]

Chagas disease is a complex zoonosis. Clinically, it presents in two distinct phases, acute and chronic. The ability of patients to respond to Trypanosoma cruzi infection depends on the balance between inflammatory and anti-inflammatory responses, in which cytokines play a key regulatory role. In this review, we discuss the role of cytokines in regulating the host response and as mediators of cardiac injury by inducing profibrotic alterations. The importance of characterizing cytokine profiles as biomarkers of the evolution of cardiac damage in T.-cruzi-infected individuals is also emphasized. [ABSTRACT FROM AUTHOR]

The increasing importance of azaheterocyclic phosphonates in the agrochemical, synthetic, and medicinal field has provoked an intense search in the development of synthetic routes for obtaining novel members of this family of compounds. This updated review covers methodologies established since 2004, focusing on the synthesis of azaheterocyclic phosphonates, of which the phosphonate moiety is directly substituted onto to the azaheterocyclic structure. Emphasizing recent advances, this review classifies newly developed synthetic approaches according to the ring size and providing information on biological activities whenever available. Furthermore, this review summarizes information on various methods for the formation of C–P bonds, examining sustainable approaches such as the Michaelis–Arbuzov reaction, the Michaelis–Becker reaction, the Pudovik reaction, the Hirao coupling, and the Kabachnik–Fields reaction. After analyzing the biological activities and applications of azaheterocyclic phosphonates investigated in recent years, a predominant focus on the evaluation of these compounds as anticancer agents is evident. Furthermore, emerging applications underline the versatility and potential of these compounds, highlighting the need for continued research on synthetic methods to expand this interesting family. [ABSTRACT FROM AUTHOR]

In plants, small RNAs (sRNAs), mainly microRNAs (miRNAs) and small interfering RNAs (siRNAs), have been described as key regulators of plant development, growth, and abiotic and biotic responses. Despite reports indicating the involvement of certain sRNAs in regulating the interaction between Botrytis cinerea (a major necrotrophic fungal phytopathogen) and host plants, there remains a lack of analysis regarding the potential regulatory roles of plant sRNAs during early stages of the interaction despite early immune responses observed then during infection. We present the first transcriptome-wide analysis of small RNA expression on the early interaction between the necrotrophic fungus Botrytis cinerea and the model plant Arabidopsis thaliana. We found that evolutionary conserved A. thaliana miRNAs were the sRNAs that accumulated the most in the presence of B. cinerea. The upregulation of miR167, miR159 and miR319 was of particular interest because these, together with their target transcripts, are involved in the fine regulation of the plant hormone signaling pathways. We also describe that miR173, which triggers the production of secondary siRNAs from TAS1 and TAS2 loci, as well as secondary siRNAs derived from these loci, is upregulated in response to B. cinerea. Thus, at an early stage of the interaction there are transcriptional changes of sRNA-guided silencing pathway genes and of a subset of sRNAs that targeted genes from the PPR gene superfamily, and these may be important mechanisms regulating the interaction between A. thaliana and B. cinerea. This work provides the basis for a better understanding of the regulation mediated by sRNAs during early B. cinerea-plant interaction and may help in the development of more effective strategies for its control. [ABSTRACT FROM AUTHOR]

Background & objectives: Chagas disease is a vector-borne life-threatening illness originally confined to the Americas. Seroprevalence studies have been reported in the Mexican state of Chiapas; nevertheless, no clinical/cardiological studies have been conducted to detect underage cases. The aim of the present work was to detect underage cases in the Mexican state of Chiapas. Methods: A serological screening by ELISA was conducted on 1556 blood samples from school pupils; seropositiv- ity was confirmed by indirect ELISA and indirect immunofluorescence. Seropositive cases were clinically assessed in a hospital, and electrocardiographic and echocardiographic studies were performed. Descriptive statistics were used for analysis. Results: Seropositivity was confirmed in three cases in the population under study (0.19%). Cardiological studies confirmed the presence of alterations associated to Chagasic cardiomyopathy in two of the three patients. Interpretation & conclusion: The conditions for an active transmission of T. cruzi infection are met in the rural localities under study. Additionally, the presence of Chagasic cardiomyopathy in underage patients highlights the relevance of an early detection of cases to provide specific treatment at the onset of the infection and to implement epidemiological surveillance as suggested by PAHO/WHO.