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.

Organophosphate-Pesticide-Mediated Immune Response Modulation in Invertebrates and Vertebrates.

Organophosphate pesticides (OPs) have greatly facilitated food production worldwide, and their use is not limited to agriculture and the control of pests and disease vectors. However, these substances can directly affect the immune response of non-target organisms. In this sense, exposure to OPs can have negative effects on innate and adaptive immunity, promoting deregulation in humoral and cellular processes such as phagocytosis, cytokine expression, antibody production, cell proliferation, and differentiation, which are crucial mechanisms for host defense against external agents. This review focuses on the scientific evidence of exposure to OPs and their toxic effects on the immune system of non-target organisms (invertebrates and vertebrates) from a descriptive perspective of the immuno-toxic mechanisms associated with susceptibility to the development of bacterial, viral, and fungal infectious diseases. During the exhaustive review, we found that there is an important gap in the study of non-target organisms, examples of which are echinoderms and chondrichthyans. It is therefore important to increase the number of studies on other species directly or indirectly affected by Ops, to assess the degree of impact at the individual level and how this affects higher levels, such as populations and ecosystems.

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.

Post-COVID-19 Syndrome in Outpatients and Its Association with Viral Load.

INTRODUCTION: The COVID-19 pandemic is the result of the SARS-CoV-2 virus, which has caused more than 100 million infections and more than 2.5 million deaths worldwide, representing a serious public health problem. The gold method for detecting this virus is qRT-PCR, which is a semiquantitative technique where the viral load can be established through its cycle threshold (Ct). It has also been reported that COVID-19 generates long-term symptoms (post-COVID-19). METHODS: After three months, a survey was performed on 70 COVID-19 confirmed patients; subsequently, we divided them into four groups (persistent symptoms, chemo-sensitive, cognitive issues, and changes in habit) in order to determine the correlation between viral load and post-COVID-19 symptoms. RESULTS: Data show that fatigue, nervousness, anosmia, and diet changes are common long-term symptoms; in addition, a negative correlation was found between viral load and the number of post-COVID-19 symptoms. CONCLUSION: COVID-19 generates long-term symptoms which can cause problems with psychological and social repercussions.

Comparative Analysis of Age, Sex, and Viral Load in Outpatients during the Four Waves of SARS-CoV-2 in A Mexican Medium-Sized City.

Governments have implemented measures to minimize SARS-CoV-2 spread. However, these measures were relaxed, and the appearance of new variants has prompted periods of high contagion known as waves. In Mexico, four waves distributed between July and August 2020, January and February 2021, August and September 2021, and January and February 2022 have appeared. Current health policies discourage mass sampling, preferring to focus on the corrective treatment of severe cases. Outpatients are only advised to undergo brief voluntary confinement and symptomatic treatment, with no follow-up. Therefore, the present study aimed to analyze sex, age, and viral load in outpatients during the four waves in a medium-sized city in Mexico. For each wave, the date of peak contagion was identified, and data were collected within ±15 days. In this regard, data from 916 patients (434 men and 482 women) were analyzed. The age range of positive patients (37-45 years) presented a higher frequency during the first and third waves, while 28-36 years was the most frequent age range during the second and fourth waves, while the viral load values were significantly higher, for both sexes, during the fourth wave. Obtained data of COVID-19 prevalence in population segments can be used for decision-making in the design of effective public health policies.

SARS-CoV-2 Transmission Risk Model in an Urban Area of Mexico, Based on GIS Analysis and Viral Load.

The COVID-19 pandemic highlighted health systems vulnerabilities, as well as thoughtlessness by governments and society. Due to the nature of this contingency, the use of geographic information systems (GIS) is essential to understand the SARS-CoV-2 distribution dynamics within a defined geographic area. This work was performed in Tepic, a medium-sized city in Mexico. The residence of 834 COVID-19 infected individuals was georeferenced and categorized by viral load (Ct). The analysis took place during the maximum contagion of the first four waves of COVID-19 in Mexico, analyzing 158, 254, 143, and 279 cases in each wave respectively. Then heatmaps were built and categorized into five areas ranging from very low to very high risk of contagion, finding that the second wave exhibited a greater number of cases with a high viral load. Additionally, a spatial analysis was performed to measure urban areas with a higher risk of contagion, during this wave this area had 19,203.08 km2 (36.11% of the city). Therefore, a kernel density spatial model integrated by meaningful variables such as the number of infected subjects, viral load, and place of residence in cities, to establish geographic zones with different degrees of infection risk, could be useful for decision-making in future epidemic events.

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.

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.

Niveles de IgG anti-SARSCoV- 2 en población infantil de Nayarit, México, como biomarcador de inmunidad comunitaria. Estudio de caso a 17 meses de la pandemia por Covid-19.

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Analysis of B Cell Migration by Intravital Microscopy.

During immune responses, B cells home to lymph nodes (LNs), where they encounter antigens. Homing starts with capture and L-selectin-dependent rolling on the activated endothelium of high endothelial venules (HEV). After recognition of chemokines presented on HEV, activation of B cell integrins occurs mediating firm arrest. Subsequently, B cells crawl to the spot of extravasation to enter the LN. Extravasation can be visualized and quantified in vivo by intravital microscopy (IVM) of the inguinal LN. Here, we describe an established protocol that permits detailed in vivo analysis of B cell recruitment to LN under sterile inflammatory conditions. We describe data acquisition, exportation, quantification, and statistical analysis using specialized software. IVM of LN is a powerful technique that can provide a better understanding of B cell migratory behavior during inflammation in vivo.

Intermittent rolling is a defect of the extravasation cascade caused by Myosin1e-deficiency in neutrophils.

Neutrophil extravasation is a migratory event in response to inflammation that depends on cytoskeletal dynamics regulated by myosins. Myosin-1e (Myo1e) is a long-tailed class-I myosin that has not yet been studied in the context of neutrophil-endothelial interactions and neutrophil extravasation. Intravital microscopy of TNFα-inflamed cremaster muscles in Myo1e-deficient mice revealed that Myo1e is required for efficient neutrophil extravasation. Specifically, Myo1e deficiency caused increased rolling velocity, decreased firm adhesion, aberrant crawling, and strongly reduced transmigration. Interestingly, we observed a striking discontinuous rolling behavior termed "intermittent rolling," during which Myo1e-deficient neutrophils showed alternating rolling and jumping movements. Surprisingly, chimeric mice revealed that these effects were due to Myo1e deficiency in leukocytes. Vascular permeability was not significantly altered in Myo1e KO mice. Myo1e-deficient neutrophils showed diminished arrest, spreading, uropod formation, and chemotaxis due to defective actin polymerization and integrin activation. In conclusion, Myo1e critically regulates adhesive interactions of neutrophils with the vascular endothelium and neutrophil extravasation. Myo1e may therefore be an interesting target in chronic inflammatory diseases characterized by excessive neutrophil recruitment.

Class I myosins: Highly versatile proteins with specific functions in the immune system.

Connections established between cytoskeleton and plasma membrane are essential in cellular processes such as cell migration, vesicular trafficking, and cytokinesis. Class I myosins are motor proteins linking the actin-cytoskeleton with membrane phospholipids. Previous studies have implicated these molecules in cell functions including endocytosis, exocytosis, release of extracellular vesicles and the regulation of cell shape and membrane elasticity. In immune cells, those proteins also are involved in the formation and maintenance of immunological synapse-related signaling. Thus, these proteins are master regulators of actin cytoskeleton dynamics in different scenarios. Although the localization of class I myosins has been described in vertebrates, their functions, regulation, and mechanical properties are not very well understood. In this review, we focused on and summarized the current understanding of class I myosins in vertebrates with particular emphasis in leukocytes.

Regulatory IFN-γ-producing killer dendritic cells are enhanced in B6.MLR-Faslpr /J lupus-prone mice.

A novel cell population denominated IFN-γ-producing killer dendritic cells (IKDCs) have been recently described. These cells are lymphocytes lacking B- or T- receptors, but they can be identified by the presence of B220+ CD38+ CD49b+ and low CD11c, among other cell surface markers. The main characteristics of IKDCs are the production of IFN-γ and the ability to spontaneously kill tumor cells. We found that this population increases in B6.MLR-Faslpr /J mice. Interestingly, IKDCs increase with age and are more abundant in mice older than 6 months onward. To analyze whether these cells have any role in the induction of the lupus-like phenotype in the B6.MLR-Faslpr /J mice, IKDCs were purified and transferred into 6-month-old B6.MRL-Faslpr /J mice, then the presence of anti-nuclear antibodies (ANAS) and anti-dsDNA antibodies were analyzed 2 and 4 months after the transfer. The results showed a reduction in the levels of these autoantibodies and increased survival of these mice, indicating that these cells may have a regulatory function. In vitro assays demonstrated that IKDCs reduced the proliferation of both autoreactive B and T cells, suggesting that these may be the mechanisms used by these cells to ameliorate the lupus-like phenotype in the B6.MRL-Faslpr /J mice.