Martha Patricia Sierra-Vargas

An error occurred in the original publication

Background: Post-COVID-19 syndrome is associated with endothelial dysfunction (ED) and various sequelae, particularly in individuals who experienced critical illness during the acute phase, affecting lung function and the musculoskeletal system. L-citrulline, a nonessential amino acid, has been shown to improve endothelial function, systemic inflammation, blood pressure, and physical performance. This study aimed to assess the effects of L-citrulline supplementation on ED and body composition in patients with post-COVID-19 syndrome. Methods: We conducted an open-label randomized controlled clinical trial at the Instituto Nacional de Enfermedades Respiratorias in Mexico City, Mexico, from February 2021 to May 2022. Eligible subjects were adults aged ≥18 years who recovered from COVID-19 and required hospitalization during acute COVID-19. Participants were randomized 1:1 into two groups: (1) the L-citrulline group (4 g/day) and (2) the control group. The intervention lasted three months. Endothelial-related biomarkers, including endothelin-1, sE-selectin, ICAM-1, and VCAM-1, were investigated. Body composition was measured using electrical bioimpedance, and aerobic capacity was assessed with the 6 min walk test (6MWT). Treatment effects were analyzed using two-way repeated-measures ANOVA (group × time). Results: In total, 43 subjects participated in the study. After three months of follow-up, the intervention group showed a decrease in ICAM-1 (−32.59 ng/mg of protein; 95% CI −52.85 to −12.33 vs. −2.31 ng/mg of protein, CI 95%: −21.59 to 16.95, p = 0.034) and an increase in 6MWT (141.2 m; 95% CI: 98.40 to 184 vs. 67.70 m, CI 95%: 30.62 to 104.78, p = 0.011) compared with the control group. No differences in body composition were observed between the groups at follow-up. Conclusions: L-citrulline supplementation for three months decreased ICAM-1 and increased 6MWT.

An excess of pleural fluid production can result in a condition known as pleural effusion, characterized by the accumulation of fluid in the space between the lungs and the chest wall. Malignant pleural effusions are defined as the presence of neoplastic cells in pleural fluid. The presence of malignant pleural effusions has been attributed to lung cancer, which is present in 15% of patients at the time of diagnosis. The development of pleural effusion has been strongly linked to environmental factors, including exposure to air pollution, chemical compounds, and occupational hazards. The present study examines the association between the induction of oxidative stress in malignant pleural effusion and the presence of air pollution metals or metalloids. A search was conducted using the following databases: PubMed, Science Direct, and the Cochrane Library, to identify all original scientific articles published through 30 January 2026. The following search combination terms were utilized: trace elements, heavy metals, metalloids, particulate matter, air pollution, pleural effusion, oxidative stress, antioxidant enzymes, and lung cancer. The findings revealed a higher concentration of zinc in malignant pleural effusions compared to benign pleural effusions, a statistically significant difference. Furthermore, an elevated concentration of trace elements, including copper, chromium, lead, selenium, and iron, has been documented in malignant pleural effusions. However, these observations did not demonstrate statistical significance. With respect to antioxidant activity, an increase in superoxide dismutase activity was observed in malignant pleural effusion, as well as in the oxidative stress markers Lactate Dehydrogenase, Malondialdehyde, and Reactive Oxygen Species Modulator 1. The presence of metals or metalloids of anthropogenic origin identified in pleural effusions has the potential to increase the production of reactive oxygen species, increasing oxidative stress damage and supporting the progression of respiratory diseases, such as lung cancer.

Knee osteoarthritis (OA) is a leading cause of disability worldwide. Oxidative stress (OS), enhanced by exposure to heavy metals such as cadmium (Cd), may contribute to its progression. Cd, present in tobacco smoke, disrupts chondrocyte viability, redox balance, and essential metal homeostasis. This study aimed to determine whether Cd exposure, particularly through smoking, influences the development and severity of knee OA by affecting antioxidant defense, metallothioneins (MTs) expression, arginase II activity, and trace metal levels in blood, synovial fluid (SF), and cartilage. Fifty-one OA patients were stratified by smoking status (non-smokers, ex-smokers, smokers). Cd and other metals were quantified by ICP-MS, along with OS markers (MDA, MGO, AOPPs), antioxidant enzymes (GST, GGT, CAT), prooxidant enzymes (MPO, arginase II), and metallothinein-1A and 2A (MT-1A/2A) levels. Non-parametric tests assessed correlations between Cd and redox markers. Smokers exhibited higher Cd in blood (0.34 ng/mL) and cartilage (26.07 ng/g), with increased GST, GGT, MDA, and AOPPs. Cd correlated positively with MDA (rho = 0.319, P = 0.033). In SF, elevated CAT, GGT, and arginase II activity were found in patients with high Cd levels (Q3), alongside increased MT-2A expression in smokers (P = 0.018). Cd exposure was also linked to an imbalance of essential metals such as selenium (Se). These findings suggest that Cd, mainly from smoking, exacerbates OS, alters redox enzyme activity, induces MT-2A, and disrupts metal homeostasis, potentially mediating OA pathogenesis. Longitudinal studies are warranted to confirm its causal role in disease progression.

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.

La quimiorresistencia es la principal razón de la eficacia limitada de la terapia contra el cáncer e involucra una serie de vías de señalización, como factores epigenéticos, transportadores de fármacos, mecanismos de reparación de daños del ADN, inhibición de la muerte celular, transición epitelio-mesénquima y metabolismo de los fármacos. Las enzimas del citocromo P450 son hemoproteínas catalíticas que metabolizan compuestos endógenos y exógenos, y su expresión influye en la respuesta del tratamiento. En esta revisión descriptiva se examina la asociación entre la expresión o la presencia de polimorfismos de enzimas de citocromo P450 y la quimiorresistencia en cáncer de pulmón. Se realizó una búsqueda en las bases de datos de PubMed y Science Direct utilizando los términos en inglés: “chemotherapy”, “lung cancer” y “CYP450”. Se incluyeron los estudios ex vivo e in vitro de origen humano, publicados en los últimos 5 años. Fueron excluidos los trabajos de revisión, metaanálisis y de modelos animales. Los resultados de la búsqueda revelaron un total de 173artículos(2020-2024), incluidos tres estudios transversales que involucraron un total de 179 pacientes (ex vivo) y dos estudios con modelos in vitro, en los que se evaluó la expresión o la presencia de polimorfismos de enzimas de citocromo P450 asociados con la respuesta al tratamiento. La información seleccionada describe que la expresión o los polimorfismos de algunas isoformas de enzimas de citrocromo P450, incluidas1A2, 2A6, 3A4, 1B1, 2C8, 2C9, 27C1, 2D6,participan en la quimiorresistencia en cáncer pulmonar.

Background: SARS-CoV-2 is a systemic disease that affects endothelial function and leads to coagulation disorders, increasing the risk of mortality. Blood levels of endothelial biomarkers such as Von Willebrand Factor (VWF), Thrombomodulin or Blood Dendritic Cell Antigen-3 (BDCA3), and uUokinase (uPA) increase in patients with severe disease and can be prognostic indicators for mortality. Therefore, the aim of this study was to determine the effect of VWF, BDCA3, and uPA levels on mortality. Methods: From May 2020 to January 2021, we studied a prospective cohort of hospitalized adult patients with polymerase chain reaction (PCR)-confirmed COVID-19 with a SaO2 ≤ 93% and a PaO₂/FiO₂ ratio < 300. In-hospital survival was evaluated from admission to death or to a maximum of 60 days of follow-up with Kaplan-Meier survival curves and Cox proportional hazard models as independent predictor measures of endothelial dysfunction. Results: We recruited a total of 165 subjects (73% men) with a median age of 57.3 ± 12.9 years. The most common comorbidities were obesity (39.7%), hypertension (35.4%) and diabetes (30.3%). Endothelial biomarkers were increased in non-survivors compared to survivors. According to the multivariate Cox proportional hazard model, those with an elevated VWF concentration ≥ 4870 pg/ml had a hazard ratio (HR) of 4.06 (95% CI: 1.32–12.5) compared to those with a lower VWF concentration adjusted for age, cerebrovascular events, enoxaparin dose, lactate dehydrogenase (LDH) level, and bilirubin level. uPA and BDCA3 also increased mortality in patients with levels ≥ 460 pg/ml and ≥ 3600 pg/ml, respectively. Conclusion: The risk of mortality in those with elevated levels of endothelial biomarkers was observable in this study.

Solid tumors frequently experience hypoxia or low O₂ levels. In these conditions, hypoxia‐inducible factor 1 alpha (HIF‐1α) is activated and acts as a transcription factor that regulates cancer cell adaptation to O₂ and nutrient deprivation. HIF‐1α controls gene expression associated with various signaling pathways that promote cancer cell proliferation and survival. MicroRNAs (miRNAs) are 22‐nucleotide noncoding RNAs that play a role in various biological processes essential for cancer progression. This review presents an overview of how hypoxia regulates the expression of multiple miRNAs in the progression of cancer cells.