The SARS-CoV-2 pandemic has confirmed the apocalyptic predictions that virologists have been making for several decades. The challenge the world is facing is that of trying to find a possible treatment, and a viable and expedient option for addressing this challenge is the repurposing of drugs. However, in some cases, although these drugs are approved for use in humans, the mechanisms of action involved are unknown. In this sense, to justify its therapeutic application to a new disease, it is ideal, but not necessary, to know the basic mechanisms of action involved in a drug’s biological effects. This review compiled the available information regarding the various effects attributed to Ivermectin. The controversy over its use for the treatment of COVID-19 is demonstrated by this report that considers the proposal unfeasible because the therapeutic doses proposed to achieve this effect cannot be achieved. However, due to the urgent need to find a treatment, an exhaustive and impartial review is necessary in order to integrate the knowledge that exists, to date, of the possible mechanisms through which the treatment may be helpful in defining safe doses and schedules of Ivermectin.

Cigarette smoking is a known risk factor for the development of lung cancer. We investigated whether circulating microRNA expression levels and their potential diagnostic value are affected by cigarette smoking in adenocarcinoma (AD) patients and healthy (H) participants. In total, 71 female AD patients and 91 H individuals were recruited, including 42 AD never-smokers (AD/CS−), 29 AD smokers (AD/CS+), 54 H never-smokers (H/CS−), and 37 H smokers (H/CS+). PCR array (754 microRNAs) and qPCR were performed on sera from the discovery and validation cohorts, respectively. The expression levels of miR-532-5p, miR-25-3p, and miR-133a-3p were significantly higher in adenocarcinoma patients than in healthy participants, independent of their smoking status. Multivariate analysis showed that levels of miR-133a-3p were independently associated with smoking. ROC analysis showed that only miR-532-5p discriminated AD patients from H controls (AUC: 0.745). However, when making comparisons according to cigarette smoking status, miR-532-5p discriminated AD/CS− patients from H/CS− controls with a higher AUC (AUC:0.762); miR-25-3p discriminated AD/CS+ patients from H/CS+ controls (AUC: 0.779), and miR-133a discriminated AD/CS+ patients from H/CS+ controls with the highest AUC of 0.935. Cancer and lung-cancer-enriched pathways were significantly associated with the three miRNAs; in addition, nicotinate/nicotinamide metabolism, inflammation, and pulmonary hypertension were associated with miR-133a-3p. Our findings highlight how cigarette smoking affects the reliable identification of circulating miRNAs as diagnostic biomarkers in lung cancer and suggest a smoking-dependent pathogenic role of miR-133a-3p in smokers.

Background: Infection by SARS-CoV-2 has been associated with multiple symptoms; however, still, little is known about persistent symptoms and their probable association with the risk of developing pulmonary fibrosis in patients post-COVID-19. Methods: A longitudinal prospective study on health workers infected by SARS-CoV-2 was conducted. In this work, signs and symptoms were recorded of 149 health workers with a positive PCR test for SARS-CoV-2 at the beginning of the diagnosis, during the active infection, and during post-COVID-19 follow-up. The McNemar chi-square test was used to compare the proportions and percentages of symptoms between the baseline and each follow-up period. Results: The signs and symptoms after follow-up were cardiorespiratory, neurological, and inflammatory. Gastrointestinal symptoms were unusual at the disease onset, but unexpectedly, their frequency was higher in the post-infection stage. The multivariate analysis showed that pneumonia (HR 2.4, IC95%: 1.5–3.8, p < 0.001) and positive PCR tests still after four weeks (HR 5.3, IC95%: 2.3-12.3, p < 0.001) were factors associated with the diagnosis of post-COVID-19 pulmonary fibrosis in this study group. Conclusions: Our results showed that pneumonia and virus infection persistence were risk factors for developing pulmonary fibrosis post-COVID-19, after months of initial infection.

Oxidative stress (OS) occurs when there is an imbalance between oxidants and antioxidants, leading to disruptions in cellular signaling and causing damage to molecules. Glutathione S-transferase (GST) enzymes are crucial for maintaining redox balance by facilitating glutathione conjugation. Increased oxidative damage has been noted during the COVID-19 pandemic, and its persistence may be linked to the onset of long COVID. This systematic review aimed to assess the relationship between GST gene polymorphisms and the prognosis of COVID-19, including long COVID. Adhering to the PRISMA guidelines, a thorough search was carried out in MEDLINE, CENTRAL, PubMed, and EMBASE for studies published from September 2020 to February 2025. Out of an initial selection of 462 articles, ten studies (four concerning COVID-19 severity and six related to long COVID) satisfied the inclusion criteria. The findings regarding GST polymorphisms were not consistent, especially concerning the GSTM1 and GSTT1 isoforms. Nevertheless, evidence indicates a sustained state of oxidative stress in patients with long COVID. The majority of research has focused on cytosolic GSTs, while the functions of microsomal and mitochondrial GST families remain largely unexplored. These findings suggest that further research into the various GST subfamilies and their genetic variants is necessary to enhance our understanding of their impact on COVID-19 severity and the pathophysiology of long COVID.

Objectives: The variability in outcomes among individuals is caused by multiple factors, including genetic variations in drug transporter genes known as ABCs. This study investigates the clinical impact of single nucleotide variants (SNV) in the ABCC1/MRP1, ABCC2/MRP2, and ABCC4/MRP4 genes on the clinical response and relapse of pediatric patients with central nervous system tumors. Methods: In a study involving 111 cancer patients, genotyping of ABCC1/MRP1, ABCC2/MRP2, and ABCC4/MRP4 was conducted using real-time PCR with TaqMan probes. Treatment response was evaluated using the Response Assessment in Neuro-Oncology (RANO) criteria. Results: Univariate and multivariate analyses using the Cox proportional hazards (adjusted) model. Multivariate analysis adjusted for sex and age showed a significant association between ABCC1 r.5540G>C; rs12921623 in the gene and non-response to treatment in the codominant model HR=2.095 (95% CI 1.202-3.650) p= 0.009 and in the dominant model HR= 2.025 (95% CI 1.199 -3.421), p=0. 008 and an increased risk of relapse in the codominant model HR= 9.09 (95% CI 1.04-78.85) p=0.04 and the dominant model HR= 3.912 (95% CI 1.139-13.436) p= 0.03. Furthermore, a significant association was found between ABCC2 c. 3972C>T; rs3740066 and relapse in the recessive model HR=3.5 (95% CI 1.02-12.17) p= 0.04. Conclusions: Our findings indicate that ABCC1 r.5540 G>C SNV and in the ABCC2 c. 3972C>T SNV are significant predictors of non-response and relapse in this group of pediatric patients with central nervous system tumors.

The variability in outcomes among individuals is caused by multiple factors, including genetic variations in drug transporter genes known as ABCs. This study investigates the clinical effect of single-nucleotide variants (SNVs) in the ABCC1/MRP1, ABCC2/MRP2, and ABCC4/MRP4 genes on the clinical response and relapse of pediatric patients with central nervous system tumors. In a cohort-based association study involving 111 cancer patients, genotyping of ABCC1/MRP1, ABCC2/MRP2, and ABCC4/MRP4 was conducted using real-time PCR with TaqMan probes. Treatment response was evaluated using the Response Assessment in Neuro-Oncology (RANO) criteria. Univariate and multivariate analyses were conducted using the Cox proportional hazards (adjusted) model. Multivariate analysis adjusted for sex and age showed a significant association between ABCC1 r.5540out G>C; rs12921623 in the gene and non-response to treatment in the codominant model [HR] 2.095, 95% CI 1.202–3.650, p = 0.009, and in the dominant model [HR] 2.025, 95% CI 1.199–3.421, p = 0.008, and an increased risk of relapse in the codominant model [HR] 9.09, 95% CI 1.04–78.85, p = 0.04, and in the dominant model [HR] 3.912, 95% CI 1.139–13.436, p = 0.03. Furthermore, a significant association was found between ABCC2 c. 3972 C>T; rs3740066 and relapse in the recessive model [HR] 3.5, 95% CI 1.02–12.17, p = 0.04. Our findings indicate that ABCC1 r.5540 G>C SNV and ABCC2 c. 3972 C>T SNV are significant predictors of non-response and relapse in this group of pediatric patients with central nervous system tumors.