Immunological Activity of Vaccine Systems Containing Liposomal Nanocarriers against Protozoan-Induced Diseases: A Systematic Review.

BACKGROUND: Neglected parasitic diseases constitute a broad spectrum of clinical conditions that, in the chronic phase, lack effective therapies for the target population. The utilization of vaccines based on liposomal nanocarrier systems is emerging, thereby enhancing clinical outcomes in various comorbidities. Consequently, this study aims to assess the immunological activity induced by liposomal nanocarriers against neglected parasitic diseases. METHODS: For the review, the Pubmed, Embase, and Lilacs databases were used using the descriptors vaccine, parasite, and liposome. The following inclusion criteria were adopted: in vivo and in vitro experimental articles. As exclusion criteria: book chapters, editorials, literature reviews and duplicate articles found during the database search. RESULTS: A total of 226 articles were identified, from which 34 were selected for review. The primary diseases identified included Babesia bovis, Entamoeba histolytica, Leishmania braziliensis, Leishmania donovani, Leishmania major, Leishmania infantum, Plasmodium falciparum, Plasmodium chabaudi, Plasmodium chabaudi, Plasmodium yoelii, Toxoplasma gondii and Trypanosoma cruzi. An elevation in cytokines such as GM-CSF, MCP-1, INF-γ, TNF-α, IL-2, IL-4, IL-5, IL-6, IL-10, IL-12, and IL-17 was observed in the studies evaluated regarding the parasitic diseases. Furthermore, cytokines such as IL-4, IL-10, and TGF-ß were diminished with the administration of the vaccine systems in those studies. CONCLUSION: Therefore, the administration of liposomal nanovaccine systems can effectively ameliorate the clinical condition of patients by modulating their immunological profile.

Assessment of differentially expressed genes from in vitro matured human oocytes: A bioinformatics approach.

OBJECTIVE: One of the techniques that has gained much attention is the in vitro maturation of oocytes for patients who use assisted reproduction techniques. However, its results are still inferior to controlled ovarian stimulation methodologies. Understanding the maturation mechanisms based on analyses can help improve this methodology's results. The work aims to identify the central genes differentially expressed in oocytes after in vitro maturation in the germinal vesicle and metaphase II stages. METHODS: This work is a computational analysis. The entire search will be conducted using the Gene Expression Omnibus (GEO) database. To carry out and obtain the data present in the work, an advanced research search was carried out in the GEO database within the period from January 1, 2013, to January 1, 2023. A total of 27 genomic data were available in the GEO database, of which only two were used. RESULTS: Two datasets were identified on the Gene Expression Omnibus database platform: registration data GSE158802 and GSE95477. From the analysis, we identified five downregulated and thirty-six upregulated genes; the central genes that correlated with the main gene proteins found were CLTA and PANK1. CONCLUSIONS: There was a differential regulation of gene expression. The most central ones are related to energy capture.

Immune system cells modulation in patients with reproductive issues: A systematic review approach.

The aim of this study was to carry out a systematic literature review to investigate the main immune cells responsible for implantation failures. We selected papers from PubMed, Embase and Virtual Health Library databases. Eligible articles included publications between January 1, 2010 and April 24, 2022. Inclusion criteria were: observational and case-control studies; and the exclusion criteria were: review papers, letters to the editor, abstracts, animal studies and case reports. We extracted the following information: day of collection, number of patients, control group, age of patients, type of sample used, immune cells and cytokines. As main findings in our mapping, we found that in peripheral blood, CD3+, CD4+, CD8+, CD16+, CD56+, CD57+, CD69+, CD154+, CD158a+, NKp46 cells were increased and the CD4+, CD45+, Foxp3 and NKp46 markers were reduced. From the endometrial biopsies, there was an increase in CD3+, CD4+, CD5+, CD8+, CD16+, CD25+, CD45+, CD56+, CD57+, CD68+, CD127+ and a reduction in CD45+, CD56+, NKp46 and FoxP3 cells. Cytokines found increased in peripheral blood included IL-6, IL-10, IL-17, INF-γ, TGF-ß, TNF-α; while IL-4, IL-6, IL-10, IL-35, FoxP3, TGF-ß, SOCS3 were reduced. As for the biopsies, there was an increase in IL-2, IL-6, IL-17, IL-22, IL-23, INF-A1, INF-B1, INF-γ, TNF-R and a reduction in IL-6, IL-10, INF-γ, TGFß, TNF-α. We concluded that immune cells can be modulated during pregnancy failure, but further studies are needed to elucidate the modulating effect of the immune system on the endometrium of these patients.

Molecular Dynamics of a N-Cyclohexyl-1,2,4-Oxadiazole Derivative as a Reversible Cruzain Inhibitor in Trypanosoma cruzi.

BACKGROUND: Chagas disease kills around 10,000 people yearly, primarily in Latin America, where it is prevalent. Current treatment has limited chronic effectiveness, is unsafe, and has substantial side effects. As a result, the use of oxadiazole derivatives and similar heterocyclic compounds as bioisosteres are well known, and they are prospective candidates in the hunt for novel anti-Trypanosoma cruzi chemicals. Recent research has revealed that the cysteine protease cruzain from T. cruzi is a validated target for disease treatment. OBJECTIVE: Thus, using a molecular dynamics simulation, the current study attempted to determine if a significant interaction occurred between the enzyme cruzain and its ligand. RESULTS: Interactions with the catalytic site and other critical locations were observed. Also, the RMSD values suggested that the molecule under research had stable interactions with its target. CONCLUSION: Finally, the findings indicate that the investigated molecule 2b can interfere enzymatic activity of cruzain, indicating that it might be a promising antichagasic drug.

Impact of sperm DNA fragmentation on the clinical outcome of assisted reproduction techniques: a systematic review of the last five years.

OBJECTIVE: To elucidate through a systematic literature review the impact sperm DNA fragmentation has on embryos from assisted reproduction techniques. DATA SOURCE: Studies from the "PubMed", "Embase", and "BVS" databases were analyzed. STUDIES SELECTION: The articles selected in the review included: cohort and case-control studies that addressed the proposed theme, published between January 1, 2017, and January 31, 2022, in English, Portuguese, and Spanish. As inclusion criteria: cohort and case-control articles. As exclusion criteria: articles outside the scope of the research, review articles, case reports, articles using animal models, abstracts, letters to the editor, and articles found duplicates in the databases. DATA COLLECTION: Number of couples or cycles; age (men/women); collection type; DNA damage (%); assisted reproduction activity and techniques. DATA SYNTHESIS: In in vitro fertilization, a reduction in fertilization rate, blastocyst rate, and embryo quality was observed. In addition to implantation and increased abortion rates in patients with high sperm DNA fragmentation. High rates of sperm DNA fragmentation in intracytoplasmic sperm injection led to reduced blastocyst production rate, embryo quality, implantation, and live birth rate, and in intrauterine insemination, a reduction in pregnancy rate. CONCLUSION: Sperm DNA fragmentation was a potential limiting factor for assisted reproduction techniques.

Oxadiazole Derivatives as Anticancer and Immunomodulatory Agents: A Systematic Review.

BACKGROUND: Tumor plasticity processes impact the treatment of different types of cancer; as an effect of this, the bioprospecting of therapies from natural and/or synthetic compounds that can regulate or modulate the immune system has increased considerably. Oxadiazole derivatives are structures that exhibit diverse biological activities. Therefore, this review aimed to evaluate the activity of oxadiazole compounds against tumor cell lines and their possible immune-mediated mechanisms. METHODS: A search in PubMed, Web of Science, and Science Direct databases was carried out on studies published from January 1, 2004, to January 31, 2022, using "oxadiazole" in combination with the other descriptors "cancer" and "macrophage". Only experimental in vitro and in vivo articles were included. A similar search strategy was used in the Derwent Innovation Index database for technology mapping. The search was performed on Drugbank using the descriptor oxadiazole for commercial mapping. RESULTS: 23 oxadiazole studies were included in this review, and some biological activities linked to antitumoral and immunomodulation were listed. Oxadiazole derivatives inhibited tumor cell growth and proliferation, blocked cell cycle, modulated mitochondrial membrane potential, presented immunoregulatory activity by different mechanisms reducing proinflammatory cytokines levels and acted directly as selective inhibitors of the COX enzyme. There was an increase in oxadiazole patent publications in the last 11 years, with emphasis on chemistry, pharmacy and biotechnology applied to microbiology areas. Compounds with 1,2,4-oxadiazole isomer are predominant in patent publications and approved drugs as observed in the technological and commercial mapping. CONCLUSION: Therefore, oxadiazole derivatives are therapeutic molecules that can be considered promising for the development of cancer therapies.

Anti-Leishmania infantum in vitro effect of n-cyclohexyl-1,2,4-oxadiazole and its ADME/TOX parameters.

Leishmaniasis is a disease that represents a serious global health problem with a potentially fatal outcome in some cases. Leishmania spp. is transmitted by the bite of a sandfly and the disease is endemic in 98 countries. Treatment is carried out with toxic drugs and not consistently effective, so there is a need for new treatments. Oxadiazoles are five-membered heterocyclic compounds, and their antileishmanial activity is well documented in the literature. Specifically, n-cyclohexyl-1,2,4-oxadiazole (2b) was designed to obtain the simplified molecular data line entry system (SMILES). The approach for predicting pharmacokinetic properties used was pkCSM-Pharmacokinetics and ADME/TOX parameters were achieved. SMILES of 2b and Amphotericin B (ANF B) were submitted to the server and the results were compared. The cytotoxic action of 2b on host cells (LLC-MK2) was also evaluated, using MTT salt and antileishmanial activity against Leishmania infantum promastigotes at different concentrations for 24 h. The molecule 2b studied here demonstrated low toxicity in LLC-MK2 cells even at the highest concentration (1000 µM) with cell viability of 69%. Furthermore, it demonstrated anti-L. infantum action with cell viability of 13% at the highest concentration (1000 µM), while (ANF B) (16 µg/mL) demonstrated cell viability of 7%, justifying the need for further studies with n-cyclohexyl-1.2,4-oxadiazole employing experimental models of leishmaniasis.

Antiparasitary and antiproliferative activities in vitro of a 1,2,4-oxadiazole derivative on Trypanosoma cruzi.

Chagas disease (CD) is a neglected disease, prevalent and endemic in Latin America, but also present in Europe and North America. The main treatment used for this disease is benznidazole, but its efficacy is variable in the chronic phase and presents high toxicity. So, there is a need for the development of new therapeutic agents. The five-membered heterocyclic 1,2,4-oxadiazole ring has received attention for its unique properties and a broad spectrum of biological activities and is therefore a potential candidate for the development of new drugs. Thus, the aim of this study was to evaluate the activity of the N-cyclohexyl-3-(3-methylphenyl)-1,2,4-oxadiazol-5-amine (2) on the evolutionary forms of Trypanosoma cruzi strain Y, as well as its mechanisms of action and in silico theoretical approach. The results by computational method showed an interaction of the 1,2,4-oxadiazole (2) with TcGAPDH, cruzain, and trypanothione reductase, showing good charge distribution and affinity in those three targets. Furthermore, cytotoxicity in LLC-MK2 cells was performed by the MTT method. In the assays with different parasite forms, the tested compound showed similar time-dependent concentration effect. The evaluation of the antiamastigote effect between the two concentrations tested showed a reduction in the number of infected cells and also in the number of amastigotes per infected cell. By flow cytometry, the compound (2) displayed alterations suggestive of necrotic events. Finally, in scanning electron microscopy structural alterations were present, characteristic of necrosisin the epimastigote forms. Overall, the 1,2,4-oxadiazole derivative (2) here evaluated opens perspectives to the development of new antichagasic agents.

Antitumor and Antiparasitic Activity of Antimicrobial Peptides Derived from Snake Venom: A Systematic Review Approach.

BACKGROUND: In a scenario of increased pathogens with multidrug resistance phenotypes, it is necessary to seek new pharmacological options. This fact is responsible for an increase in neoplasms and multiresistant parasitic diseases. In turn, snake venom- derived peptides exhibited cytotoxic action on fungal and bacterial strains, possibly presenting activities in resistant tumor cells and parasites. Therefore, the aim of this work is to verify an antitumor and antiparasitic activity of antimicrobial peptides derived from snake venom. METHODS: For this purpose, searches were performed in the Pubmed, Embase and Virtual Health Library databases by combining the descriptors peptides, venom and snake with antitumor/ antiparasitic agent and in silico. The inclusion criteria: in vitro and in vivo experimental articles in addition to in silico studies. The exclusion criteria: articles that were out of scope, review articles, abstracts, and letters to the reader. Data extracted: peptide name, peptide sequence, semi-maximal inhibitory concentration, snake species, tumor lineage or parasitic strain, cytotoxicity, in vitro and in vivo activity. RESULTS: In total 164 articles were found, of which 14 were used. A total of ten peptides with antiproliferative activity on tumor cells were identified. Among the articles, seven peptides addressed the antiparasitic activity. CONCLUSION: In conclusion, snake venom-derived peptides can be considered as potential pharmacological options for parasites and tumors, however more studies are needed to prove their specific activity.

The impact of fake news on social media and its influence on health during the COVID-19 pandemic: a systematic review.

PURPOSE: As the new coronavirus disease propagated around the world, the rapid spread of news caused uncertainty in the population. False news has taken over social media, becoming part of life for many people. Thus, this study aimed to evaluate, through a systematic review, the impact of social media on the dissemination of infodemic knowing and its impacts on health. METHODS: A systematic search was performed in the MedLine, Virtual Health Library (VHL), and Scielo databases from January 1, 2020, to May 11, 2021. Studies that addressed the impact of fake news on patients and healthcare professionals around the world were included. It was possible to methodologically assess the quality of the selected studies using the Loney and Newcastle-Ottawa Scales. RESULTS: Fourteen studies were eligible for inclusion, consisting of six cross-sectional and eight descriptive observational studies. Through questionnaires, five studies included measures of anxiety or psychological distress caused by misinformation; another seven assessed feeling fear, uncertainty, and panic, in addition to attacks on health professionals and people of Asian origin. CONCLUSION: By analyzing the phenomenon of fake news in health, it was possible to observe that infodemic knowledge can cause psychological disorders and panic, fear, depression, and fatigue.

Potential Repurposing of Drugs with Anti-SARS-CoV-2 Activity in Preclinical Trials: A Systematic Review.

COVID-19 is an emerging outbreak similar to previous pandemics caused by Severe Acute Respiratory Syndrome (SARS) and Middle East Respiratory Syndrome (MERS). Till date, SARS-CoV-2 infection is still spreading, representing a major threat to public health, where several control measures are being practiced in order to culminate its spread. The research and development of new drugs require a lot of funding in addition to being a slow and costly process. As a result, new techniques have been proposed to streamline this process. The repositioning or repurposing of drugs represents an attractive strategy, presenting a promising way to introduce new drugs. Currently, numerous reused drugs are already available in the market and are in practice. In this review, it was observed that the antiviral drugs Entricitabine and Tenofovir display potential therapeutic efficacy in preclinical studies. Therefore, in silico analyses were considered a potential tool for predicting the effectiveness of drugs, mainly as an effective approach to encourage a complementary in vitro and in vivo antiviral evaluation.