Diazoxon exposure increases susceptibility to infection by Salmonella Typhimurium.

Various exogenous factors, such as microbiological and chemical contamination condition food security. Salmonella Typhimurium (S. Typhimurium) is the cause of salmonellosis. This bacterium utilizes phagocytosis to create bacterial reservoirs. On the other hand, exposure to chemical contaminants, such as pesticides, increases susceptibility to numerous infections. Therefore, this research aims to evaluate the effect of co-exposure to diazoxon and S. Typhimurium on the in vitro infection dynamics. For this purpose, human mononuclear cells were pre-exposed in vitro to diazoxon and then challenged with S. Typhimurium at 1, 8, and 24 h. Bacterial internalization, actin polymerization, and reactive oxygen species (ROS) were analyzed. Obtained data show that mononuclear cells previously exposed to diazoxon exhibit greater internalization of S. Typhimurium. Likewise, greater ROS production and an increase in actin polymerization were observed. Therefore, in the proposed scenario, obtained data suggest that co-exposure to diazoxon and S. Typhimurium increases susceptibility to acquiring an illness.

In vitro effect of diazoxon on cell signaling and second messengers in Nile tilapia (Oreochromis niloticus) leukocytes.

The physiological and molecular responses of leukocytes are altered by organophosphate pesticides. Some reports have shown that diazinon causes immunotoxic effects; diazoxon, the oxon metabolite of diazinon, is attributed to influence the immune response by affecting the leukocyte cholinergic system. In this study, the in vitro effects of diazoxon on molecules involved in cell signaling (cAMP, IP3, DAG, JAK1, and STAT3), which play a crucial role in the activation, differentiation, and survival of leukocytes, were evaluated. Data indicate that diazoxon leads to a decrease in cAMP concentration and an increase in basal IP3 levels. However, diazoxon does not affect basal levels of JAK1 and STAT3 phosphorylation. Instead, diazoxon inhibits leukocyte responsiveness to phorbol myristate acetate and ionomycin, substances that, under normal conditions, enhance JAK/STAT signaling. These findings demonstrate that diazoxon significantly affects key molecular parameters related to cell signaling.

Hematologic analysis of hospitalized patients and outpatients infected with SARS-CoV-2 and possible use as a prognostic biomarker.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is a global health problem; this has caused thousands of deaths around the world. This infection induces hematologic alterations, and it is necessary to recognize predictive biomarkers to address the need for hospitalization or the severity of the disease. This study aimed to analyze different parameters in outpatients and hospitalized patients infected with SARS-CoV-2 and determine whether hematic biometry can be used for prognosis rapidly. We analyzed 689 patients, of whom 355 were outpatients (162 women and 193 men) and 334 required hospitalization (197 men and 137 women). The average age of the hospitalized patients was 46 years (men, 49 years; women, 52 years), whereas the average age of the outpatients was 49 years (men, 51 years; women, 44 years). Hematologic parameters were analyzed and compared between the outpatients and hospitalized patients. The patients were divided into groups by age and sex. We found that in the hospitalized patients, the erythrocyte, hematocrit, and hemoglobin levels decreased, whereas the outpatients did not experience changes in the erythroid series. In leukocytes, these increased significantly, as they did in neutrophils; however, lymphocytopenia was observed. In the outpatients, we observed normal levels of neutrophils and lymphopenia. We can conclude that hematic biometry can be used as a biomarker, and the relation between neutrophils and lymphocytes is indicated for understanding the development and prognosis of the disease.

Loss of mitochondrial membrane potential (ΔΨm ) in leucocytes as post-COVID-19 sequelae.

The mitochondrial membrane potential (ΔΨm ) is a parameter often used to determine mitochondrial function; therefore, it can be used to determine the integrity and functionality of cells. A decrement of ΔΨm is implicated in several inflammatory-related pathologies, such phenomena can be related to COVID-19 infection. The present work aimed to compare the ΔΨm in leucocytes (human PBMCs; HPBMC) isolated from healthy control (HC) subjects, patients with COVID-19 (C-19), recovered subjects at 40 ± 13 (R1) and 335 ± 20 (R2) days after infection (dai). Obtained data showed that ΔΨm decreased in HPBMC of subjects with C-19, R1, and R2 compared with HC. When analyzing the ΔΨm data by sex, in females, a significant decrease was observed in R1 and R2 groups versus HC. Regarding men, a significant decrease of ΔΨm was observed in R1, with respect to HC, contrary to R2 group, who reestablished this parameter. Obtained results suggest that the loss of ΔΨm could be related to the long-COVID.

Effect of Fucoidan on the Mitochondrial Membrane Potential (ΔΨm) of Leukocytes from Patients with Active COVID-19 and Subjects That Recovered from SARS-CoV-2 Infection.

Fucoidan is a polysaccharide obtained from marine brown algae, with anti-inflammatory, anti-viral, and immune-enhancing properties, thus, fucoidan may be used as an alternative treatment (complementary to prescribed medical therapy) for COVID-19 recovery. This work aimed to determine the ex-vivo effects of treatment with fucoidan (20 µg/mL) on mitochondrial membrane potential (ΔΨm, using a cationic cyanine dye, 3,3'-dihexyloxacarbocyanine iodide (DiOC6(3)) on human peripheral blood mononuclear cells (HPBMC) isolated from healthy control (HC) subjects, COVID-19 patients (C-19), and subjects that recently recovered from COVID-19 (R1, 40 ± 13 days after infection). In addition, ex-vivo treatment with fucoidan (20 and 50 µg/mL) was evaluated on ΔΨm loss induced by carbonyl cyanide 3-chlorophenylhydrazone (CCCP, 150 µM) in HPBMC isolated from healthy subjects (H) and recovered subjects at 11 months post-COVID-19 (R2, 335 ± 20 days after infection). Data indicate that SARS-CoV-2 infection induces HPBMC loss of ΔΨm, even 11 months after infection, however, fucoidan promotes recovery of ΔΨm in PBMCs from COVID-19 recovered subjects. Therefore, fucoidan may be a potential treatment to diminish long-term sequelae from COVID-19, using mitochondria as a therapeutic target for the recovery of cellular homeostasis.

Correlation of hematological parameters and cycle threshold in ambulatory patients with SARS-CoV-2 infection.

INTRODUCTION: Former studies have shown that hematologic parameters are affected by the SARS-CoV-2 infection which has caused a global health problem. Therefore, this research aims to identify the most frequent symptoms and comorbidities in SARS-CoV-2 infected outpatients; besides, to analyze hematological parameters and their correlation with cycle threshold (Ct) values. METHODS: We analyzed a total of sixty outpatients with SARS-CoV-2 infection. They were divided according to sex. Afterward, a questionnaire was carried out to find out their symptoms and comorbidities. Additionally, blood biometry data were correlated with the Ct value, respectively. RESULTS: Sixty patients were analyzed; the mean age was 43 years. All patients were from Nayarit, Mexico. The frequency index showed that the main symptoms were headache and anosmia, and the comorbidities were obesity and smoking. The analysis of blood biometry showed a clear increase in red blood cells (RBC) related parameters in women. In both sexes an increase in the number of white blood cells (WBC) was observed. Also, all the hematological alterations correlated with the grade of infection. CONCLUSION: Headache and anosmia are the most common symptoms according to the frequency index, the main comorbidities were obesity and smoking. Also, there is a Ct value correlation with hematological parameters (WBC, mean corpuscular volume, mean corpuscular hemoglobin, hemoglobin); they can be used as a prognostic marker of infection.

Saliva Pooling Strategy for the Large-Scale Detection of SARS-CoV-2, Through Working-Groups Testing of Asymptomatic Subjects for Potential Applications in Different Workplaces.

OBJECTIVE: To perform an improved large-scale SARS-CoV-2 detection on pooled tests of asymptomatic workers. METHODS: qRT-PCR validation of the SARS-CoV-2 detection in salivae samples and saliva pools and working-group saliva pooling and testing for SARS-CoV-2. RESULTS: We found a high Cycle threshold correlation (r = 0.9099) between swabs and saliva samples. Then, through the pooling strategy, we detected that 18/360 (5%) of individual saliva samples were SARS-CoV-2 positive. Saliva-pooling efficiency (360 of test sample/30 individual PCR) was higher (5.45) than the reported for swabbing group-testing and we spared 82% of the PCR reagents as well as sampling and personal protection equipment. CONCLUSION: Through this simplified and less expensive procedure, we detected in a short time asymptomatic-infected SARS-CoV-2-carriers that were isolated from their co-workers, thus, this methodology can be implemented in different workplaces to ensure consumers that employees are not infectious.

Relationship between LINE-1 methylation pattern and pesticide exposure in urban sprayers.

Recently a relationship has been reported between pesticide exposure and changes in global DNA methylation patterns. Urban sprayers are a particularly vulnerable population because of the high risk of pesticide exposure that their work implies. Therefore, the aim of this study was to estimate the changes in the Long Interspersed Nucleotide Element (LINE-1) in urban sprayers and its relationship with pesticide exposure. The study population consisted of 190 individuals stratified into three study groups: no occupational pesticide exposure; moderate exposure, and high exposure. Pesticide exposure and other external factors such as diet, lifestyle, and others were evaluated through a validated questionnaire, and the butyrylcholinesterase enzyme activity was evaluated spectrophotometrically and used as exposure biomarker. DNA methylation was evaluated by pyrosequencing on bisulfite-treated DNA. The results showed a significant decrease of %5mC in both the moderate- and high-exposure groups with respect to the non-exposed group (p < 0.05). In addition, alcohol intake was associated with a higher percentage of LINE- 1 methylation. In conclusion, our results suggest that occupational pesticide exposure and external factors appears to modify the DNA methylation pattern measured through LINE-1.