Predictors of mortality in hospitalized COVID-19 patients: A Mexican population-based cohort study.

OBJECTIVES: COVID-19 outbreak brings a challenge to healthcare systems. The sex, age, and cardiometabolic comorbidities have been considered risk factors for disease severity. To evaluate the association between risk factors with death as well the risk of death in hospitalized COVID-19 patients. METHODS: The present cross-sectional cohort study, includes hospitalized SARS-CoV-2 confirmed cases. Data analysis was performed using the National COVID-19 Cases Report Database. Pearson's χ2 test and odds ratios (95% CI) were calculated to determine the association between variables. Thereafter, risk of death was evaluated by Cox proportional hazards model. RESULTS: A total of 67 328 inpatients were included; mean age 55.29 years (±15.97). Of total, 42 164 (62.62%) were men, 6 349 (9.43%) were intubated, and 23 873 (35.46%) died. Male sex, age older than 60 years, and cardiometabolic comorbidities were associated with death. Hazard ratio for death in older intubated patients was lower than in non-intubated (HR 1.242, 95%CI, 1.167-1.322; P < 0.001) and (HR 2.128, 95%CI, 2.066-2.193; P < 0.001) respectively. CONCLUSIONS: Tracheal intubation or not is the most important predictor for death in COVID-19 infected patients in this Mexican cohort. Already known risk factors for COVID-19 severity may become less relevant once patients require tracheal intubation.

Interaction of Thalassia testudinum Metabolites with Cytochrome P450 Enzymes and Its Effects on Benzo(a)pyrene-Induced Mutagenicity.

The aim of the present work was to evaluate the effects of Thalassia testudinum hydroethanolic extract, its polyphenolic fraction and thalassiolin B on the activity of phase I metabolizing enzymes as well as their antimutagenic effects. Spectrofluorometric techniques were used to evaluate the effect of tested products on rat and human CYP1A and CYP2B activity. The antimutagenic effect of tested products was evaluated in benzo[a]pyrene (BP)-induced mutagenicity assay by an Ames test. Finally, the antimutagenic effect of Thalassia testudinum (100 mg/kg) was assessed in BP-induced mutagenesis in mice. The tested products significantly (p < 0.05) inhibit rat CYP1A1 activity, acting as mixed-type inhibitors of rat CYP1A1 (Ki = 54.16 ± 9.09 µg/mL, 5.96 ± 1.55 µg/mL and 3.05 ± 0.89 µg/mL, respectively). Inhibition of human CYP1A1 was also observed (Ki = 197.1 ± 63.40 µg/mL and 203.10 ± 17.29 µg/mL for the polyphenolic fraction and for thalassiolin B, respectively). In addition, the evaluated products significantly inhibit (p < 0.05) BP-induced mutagenicity in vitro. Furthermore, oral doses of Thalassia testudinum (100 mg/kg) significantly reduced (p < 0.05) the BP-induced micronuclei and oxidative damage, together with an increase of reduced glutathione, in mice. In summary, Thalassia testudinum metabolites exhibit antigenotoxic activity mediated, at least, by the inhibition of CYP1A1-mediated BP biotransformation, arresting the oxidative and mutagenic damage. Thus, the metabolites of T. testudinum may represent a potential source of chemopreventive compounds for the adjuvant therapy of cancer.

Oxidative Stress as Key Player in Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) Infection.

The emergence of viral respiratory pathogens with pandemic potential, such as severe acute respiratory syndrome coronavirus (SARS-CoV), the pathogenic agent of Covid-19, represent a serious health problem worldwide. Respiratory viral infections are, in general, associated with cytokine production, inflammation, cell death, and other pathophysiological processes, which could be link with a redox imbalance or oxidative stress. These phenomena are substantially increased during aging. Actually, severity and mortality risk of SARS-CoV-2 infection or Covid-19 disease have been associated with the age. The aim of the present work was to contribute with the understanding of the possible link between oxidative stress and the pathogenesis, severity and mortality risk in patients affected by SARS-CoV infection.

Polyphenolic Fraction Obtained From Thalassia testudinum Marine Plant and Thalassiolin B Exert Cytotoxic Effects in Colorectal Cancer Cells and Arrest Tumor Progression in a Xenograft Mouse Model.

Marine plants are important sources of pharmacologically active metabolites. The aim of the present work was to evaluate the cytotoxic and antitumor activity of a polyphenolic fraction obtained from Thalassia testudinum marine plant and thalassiolin B in human colorectal cancer cells. Human cancer cell lines, including HCT15, HCT116, SW260, and HT29 were treated with tested products for cytotoxicity evaluation by crystal violet assay. The potential proapoptotic effect of these natural products was assessed by flow cytometry in HCT15 cells at 48 h using Annexin V-FITC/propidium iodide. In addition, reactive oxygen species (ROS) generation was measured by fluorescence using DCFH-DA staining, and sulfhydryl concentration by spectrophotometry. The in vivo antitumor activity of the polyphenolic fraction (25 mg/kg) was evaluated in a xenograft model in nu/nu mice. In vivo proapoptotic effect was also evaluated by immunohistochemistry using anti-caspase 3 and anti-Bcl-2 antibodies. The results showed that tested products exert colorectal cancer cell cytotoxicity. Besides, the tested products induced a significant increase (p < 0.05) of intracellular ROS generation, and a depletion of sulfhydryl concentration in HCT15 cells. The polyphenolic fraction arrested tumor growth and induced apoptosis in the xenograft mice model. These results demonstrate the cytotoxic activity of T. testudinum metabolites associated, at least, with ROS overproduction and pro-apoptotic effects. Here we demonstrated for the first time the antitumor activity of a T. testudinum polar extract in a xenograft mice model. These results suggest the potential use of T. testudinum marine plant metabolites as adjuvant treatment in cancer therapy.

Chemoprotective effects of Ulva lactuca (green seaweed) aqueous-ethanolic extract against subchronic exposure to benzo(a)pyrene by CYP1A1 inhibition in mice.

The protective effect of the supplementation with an aqueous-ethanolic extract obtained from Ulva lactuca (Delile) green seaweed on benzo[a] pyrene-induced damage in mice was evaluated. Animals were treated with oral doses of U. lactuca extract (100 and 400 mg/kg) for 9 weeks. They were exposed to 50 mg/kg of oral doses of benzo(a)pyrene starting from the second week and up to the fifth week. Groups treated with benzo(a)pyrene only (second to fifth weeks), sunflower oil (vehicle, 9 weeks), or U. lactuca extract (100 and 400 mg/kg, 9 weeks) were also included in the study. The treatment with 400 mg/kg of the extract ameliorated the oxidative damage, decreased IL-1ß and TNF-α levels, and favorably regulated the antioxidant defenses compared with benzo(a)pyrene-exposed group. The benzo(a)pyrene-induced DNA damage was also reduced, as it was evidenced by the lower micronucleus formation in U. lactuca extract-supplemented animals. The extract protected the hepatic tissue, and it reduced the liver activity/expression of CYP1A1. These results altogether suggested a chemoprotective effect of U. lactuca extract against benzo(a)pyrene-induced-toxicity in mice, probably associated with an inhibitory effect of carcinogen bioactivation.

Medical ozone promotes Nrf2 phosphorylation reducing oxidative stress and pro-inflammatory cytokines in multiple sclerosis patients.

Oxidative stress and inflammation play key roles in the pathogenesis of Multiple sclerosis (MS). Different drugs have been used in the clinical practice, however, there is not a completely effective treatment. Due to its potential therapeutic action, medical ozone represents a promising approach for neurodegenerative disorders. The aim of the present study was to address the role of ozone therapy on the cellular redox state in MS patients. Ozone (20µg/ml) was administered three times per week during a month by rectal insufflation. The effect of ozone therapy on biomarkers of oxidative stress and inflammation was addressed by spectrophotometric and immunoenzymatic assays. Furthermore, we investigated the action of ozone on CK2 expression and Nrf2 phosphorylation by western blotting analysis. Medical ozone significantly improved (P < 0.05) the activity of antioxidant enzymes and increased the levels of cellular reduced glutathione. In accordance, a significant reduction (P < 0.05) of oxidative damage on lipids and proteins was observed in ozone-treated patients. As well, the levels of pro-inflammatory cytokines TNFα and IL-1ß were lower after ozone treatment. Ozone therapy incremented the CK2 expression together with Nrf2 phosphorylation in mononuclear cells of MS patients. These findings suggest that ozone´s antioxidant and anti-inflammatory effects might be partially associated with an induction of Nrf2 phosphorylation and activation. These results provide new insights on the molecular events modulated by ozone, and pointed out ozone therapy as a potential therapeutic alternative for MS patients.