World Health Organization (WHO) has prioritized the infectious emerging diseases such as Coronavirus Disease (COVID-19) in terms of research and development of effective tests, vaccines, antivirals, and other treatments. Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV-2), the etiological causative agent of COVID-19, is a virus belonging to risk group 3 that requires Biosafety Level (BSL)-3 laboratories and the corresponding facilities for handling. An alternative to these BSL-3/-4 laboratories is to use a pseudotyped virus that can be handled in a BSL-2 laboratory for study purposes. Recombinant Vesicular Stomatitis Virus (VSV) can be generated with complementary DNA from complete negative-stranded genomic RNA, with deleted G glycoprotein and, instead, incorporation of other fusion protein, like SARS-CoV-2 Spike (S protein). Accordingly, it is called pseudotyped VSV-SARS-CoV-2 S. In this review, we have described the generation of pseudotyped VSV with a focus on the optimization and application of pseudotyped VSV-SARS-CoV-2 S. The application of this pseudovirus has been addressed by its use in neutralizing antibody assays in order to evaluate a new vaccine, emergent SARS-CoV-2 variants (delta and omicron), and approved vaccine efficacy against variants of concern as well as in viral fusion-focused treatment analysis that can be performed under BSL-2 conditions.
Severe acute respiratory syndrome (SARS)-coronavirus (CoV)-2 infection in children and adolescents primarily causes mild or asymptomatic coronavirus disease 2019 (COVID-19), and severe illness is mainly associated with comorbidities. However, the worldwide prevalence of COVID-19 in this population is only 1%–2%. In Mexico, the prevalence of COVID-19 in children has increased to 10%. As serology-based studies are scarce, we analyzed the clinical features and serological response (SARS-CoV-2 structural proteins) of children and adolescents who visited the Hospital Infantil de México Federico Gómez (October 2020–March 2021). The majority were 9-year-old children without comorbidities who were treated as outpatients and had mild-to-moderate illness. Children aged 6–10 years and adolescents aged 11–15 years had the maximum number of symptoms, including those with obesity. Nevertheless, children with comorbidities such as immunosuppression, leukemia, and obesity exhibited the lowest antibody response, whereas those aged 1–5 years with heart disease had the highest levels of antibodies. The SARS-CoV-2 spike receptor-binding domain-localized peptides and M and E proteins had the best antibody response. In conclusion, Mexican children and adolescents with COVID-19 represent a heterogeneous population, and comorbidities play an important role in the antibody response against SARS-CoV-2 infection.
Prostate cancer (PCa) ranks second in incidence and sixth in deaths globally. The treatment of patients with castration-resistant prostate cancer (CRPC) continues to be a significant clinical problem. Emerging evidence suggests that prostate cancer progression toward castration resistance is associated with paracrine signals from the stroma. SFRP1 is one of the extracellular proteins that modulate the WNT pathway, and it has been identified as a mediator of stromal epithelium communication. The WNT pathway is involved in processes such as cell proliferation, differentiation, cell anchoring, apoptosis, and cell cycle regulation as well as the regulation of stem cell populations in the prostatic epithelium. In the present study, we explored the role of exogenous SFRP1 on the stem cell phenotype in prostate cancer. The results reveal that cancer stem cell markers are significantly increased by exogenous SFRP1 treatments, as well as the downstream target genes of the Wnt/-catenin pathway. The pluripotent transcription factors SOX2, NANOG, and OCT4 were also up-regulated. Furthermore, SFRP1 promoted prostate cancer stem cell (PCSC) properties in vitro, including tumorsphere formation, migration, bicalutamide resistance, and decreased apoptosis. Taken together, our results indicate that SFRP1 participates in the paracrine signaling of epithelial cells, influencing them and positively regulating the stem cell phenotype through deregulation of the WNT/β-catenin pathway, which could contribute to disease progression and therapeutic failure. This research increases our molecular understanding of how CRPC progresses, which could help us find new ways to diagnose and treat the disease.
Bisphenol A (BPA) is a ubiquitous synthetic compound used as a monomer in the production of polycarbonate plastics and epoxy resins. Even at low doses, BPA has been associated with the molecular progression of diseases such as obesity, metabolic syndrome, and hormone-regulated cancers due to its activity as an endocrine-disrupting chemical (EDC). Consequently, the use of BPA has been regulated worldwide by different health agencies. BPA structural analogs such as bisphenol S and bisphenol F (BPS and BPF) have emerged as industrial alternatives, but their biological activity in the molecular progression of cancer remains unclear. Prostate cancer (PCa) is a hormone-dependent cancer, and the role of BPA structural analogs in PCa progression is still undescribed. In this work, we use an in vitro model to characterize the transcriptomic effect of low-concentration exposure to bisphenol A, S, or F in the two main stages of the disease: androgen dependency (LNCaP) and resistance (PC-3). Our findings demonstrated that the low concentration exposure to each bisphenol induced a differential effect over PCa cell lines, which marks the relevance of studying the effect of EDC compounds through all the stages of the disease.
Despite of the capacity that several drugs have for specific inhibition of the androgen receptor (AR), in most cases, PCa progresses to an androgen-independent stage. In this context, the development of new targeted therapies for prostate cancer (PCa) has remained as a challenge. To overcome this issue, new tools, based on nucleic acids technology, have been developed. Aptamers are small oligonucleotides with a three-dimensional structure capable of interacting with practically any desired target, even large targets such as mammalian cells or viruses. Recently, aptamers have been studied for treatment and detection of many diseases including cancer. In PCa, numerous works have reported their use in the development of new approaches in diagnostics and treatment strategies. Aptamers have been joined with drugs or other specific molecules such as silencing RNAs (aptamer–siRNA chimeras) to specifically reduce the expression of oncogenes in PCa cells. Even though these studies have shown good results in the early stages, more research is still needed to demonstrate the clinical value of aptamers in PCa. The aim of this review was to compile the existing scientific literature regarding the use of aptamers in PCa in both diagnosis and treatment studies. Since Prostate-Specific Membrane Antigen (PSMA) aptamers are the most studied type of aptamers in this field, special emphasis was given to these aptamers.
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