Characteristics of peripheral white blood cells in COVID-19 patients revealed by a retrospective cohort study

Background Peripheral hematological changes in severe COVID-19 patients may reflect the immune response during SARS-CoV-2 infection. Characteristics of peripheral white blood cells as early signals were needed to be investigated for clarifying its associations with the fatal outcomes in COVID-19 patients. Methods A retrospective cohort study was performed and the hospitalized COVID-19 patients were recruited in wards of Sino-French New City Branch of Tongji Hospital in Wuhan, Hubei province, China. Characteristics of peripheral white blood cells in survivors and non-survivors were analyzed. Comparison among patients with different level of eosinophils was performed. Results Of 198 patients included in this study, 185 were discharged and 13 died. Levels of eosinophils, lymphocytes and basophils in non-survivors were significantly lower than those in survivors. Death rate in low eosinophils group was higher and no patient died in normal eosinophils group (16.7% vs 0, P < 0.001). The proportion of patients in low eosinophils group who used glucocorticoids was higher than in normal eosinophils group, but glucocorticoids usage was not an indicator for death in subgroup analysis in low eosinophils patients. Moreover, positive correlation was found between the counts of lymphocytes and eosinophils in patients with glucocorticoids use but not in patients without the treatment. Conclusions Hematological changes differed between survivors and non-survivors with COVID-19. Lymphopenia and eosinopenia could be predictors for poor prognosis of COVID-19 patients. Initial counts of eosinophils may guide us in usage of glucocorticoids for COVID-19 treatment.

Expression of Cytokines and Cytokine Receptors-Genes in Patients with Different Forms of Thyroid Pathology in Ukrainian Population

Multiple susceptibility genes can be involved in the development of Hashimoto’s thyroiditis. Some of these genes are implicated in other autoimmune diseases, while others are specific to thyroid autoimmune response. 153 patients with thyroid pathology were enrolled in the study (152 women and 1 man, the average age was 46,02±14,3). They were divided into 3 groups: 16 patients with postoperative hypothyroidism; 65 patients with hypothyroidism resulting from autoimmune thyroiditis, and 72 patients with both AIT and elevated serum an anti-thyroglobulin and anti-thyroid peroxidase antibodies. We used a pathway-specific real-time Polymerase chain reaction array to identify and verify cytokines and receptor pathway-associated gene expression in peripheral white blood cells in randomly selected 12 individuals from each group. In the patients with postoperative hypothyroidism and those with hypothyroidism resulting from autoimmune thyroiditis, the expression of Chemokine (C-X3-C motif) receptor 1, Chemokine (C-X-C motif) receptor 4, Interleukin 6, and Interleukin 6 receptor significantly decreased, while the expression of IL6ST and IL10RA increased. In contrast, mRNA levels of Chemokine (C-X3-C motif) receptor 1, Chemokine (C-X-C motif) receptor 4, Interleukin 6, and Interleukin 6 receptor increased in the autoimmune thyroiditis patients with elevated serum anti-thyroglobulin and anti-thyroid peroxidase antibodies, while the expression of Interleukin 6 signal transducer and Interleukin 10 receptor, alpha decreased in this group of patients. The patients with hypothyroidism resulting from autoimmune thyroiditis and patients with elevated serum anti-thyroglobulin and anti-thyroid peroxidase antibodies had significantly lowered expression of Interleukin 10, while the expression of Interleukin 1, beta and Interleukin 1 receptor, type I was elevated. autoimmune thyroiditis and hypothyroidism affect the mRNA-level expression of cytokines and cytokine receptor genes in a gene-specific manner, and these changes to gene expression can be among the triggers of autoimmune inflammation progression in the thyroid gland. Transcriptional activity of cytokines, inducer, and receptor genes in the peripheral white blood cells can be used as an important minimally invasive prognostic marker of the autoimmune thyroid disease severity.

Cystine/Glutamate Antiporter in Schizophrenia: From Molecular Mechanism to Novel Biomarker and Treatment

Glutamate, a crucial excitatory neurotransmitter, plays a major role in the modulation of schizophrenia’s pathogenesis. New drug developments for schizophrenia have been prompted by the hypoglutamatergic hypothesis of schizophrenia. The cystine/glutamate antiporter system xc− is related to glutamate-release regulation. Patients with schizophrenia were recently discovered to exhibit downregulation of xc− subunits—the solute carrier (SLC) family 3 member 2 and the SLC family 7 member 11. We searched for relevant studies from 1980, when Bannai and Kitamura first identified the protein subunit system xc− in lung fibroblasts, with the aim of compiling the biological, functional, and pharmacological characteristics of antiporter xc−, which consists of several subunits. Some of them can significantly stimulate the human brain through the glutamate pathway. Initially, extracellular cysteine activates neuronal xc−, causing glutamate efflux. Next, excitatory amino acid transporters enhance the unidirectional transportation of glutamate and sodium. These two biochemical pathways are also crucial to the production of glutathione, a protective agent for neural and glial cells and astrocytes. Investigation of the expression of system xc− genes in the peripheral white blood cells of patients with schizophrenia can facilitate better understanding of the mental disorder and future development of novel biomarkers and treatments for schizophrenia. In addition, the findings further support the hypoglutamatergic hypothesis of schizophrenia.

Clinical and Genetic Analyses and Treatment Outcomes of Patients with Lateralized Overgrowth

Background: The genetic features and management of lateralized overgrowth have been elusive. This study was performed to investigate the genetic profiles and outcomes of propranolol- or alpelisib-treated patients with lateralized overgrowth. Methods: Fifteen patients with lateralized overgrowth were enrolled. Clinical features and whole-body magnetic resonance imaging (WB-MRI) findings were evaluated. Deep sequencing with a customized gene panel of affected tissue and peripheral white blood cells was performed. Propranolol was administered and clinical outcomes were examined. The PIK3CA inhibitor alpelisib was administered via a managed access program. Results: Genetic testing identified PIK3CA (n=7, 46.7%), KRAS (n=2, 13.3%), PTEN (n=1, 6.7%), MAP2K3 (n=1, 6.7%), GNAQ (n=1, 6.7%), TBC1D4 (n=1, 6.7%), and TEK (n=1, 6.7%) mutations. Propranolol was administered in 12 patients, and 7 experienced limited improvement of symptoms. Alpelisib was administered in two patients with a PIK3CA mutation, and the WB-MRI after 1 year of treatment showed a reduction in proliferated masses. Conclusions: Deep sequencing identified diverse genetic features of lateralized overgrowth. Propranolol could be used as an adjuvant therapy for reducing vascular symptoms, but targeted therapy with a PIK3CA inhibitor would be the primary therapeutic strategy for PIK3CA-related overgrowth syndrome.

Association Between Thalassemia and Leucocytic DNA Damage: A Pilot Study

Objectives: Thalassemia with frequent blood transfusion was considered under oxidative stress because of the chance of iron overload. Patients with thalassemia trait with no blood transfusion might also suffered from oxidative stress because of increased iron metabolism. This pilot study was to investigate if patients of alpha or beta thalassemia trait and received no blood transfusion were suffered from oxidative stress in term of DNA damage in peripheral leucocytes. Method: Comet assay was used to measure DNA damage of 20 normal subjects, 8 alpha and 12 beta thalassemia patients who did not received blood transfusion. The baseline and UV-mediated DNA damages of peripheral white blood cells were measured. The degree of DNA damage was quantified by visual scoring under light microscope after staining with Giemsa stain. Results: The mean (± standard deviation) comet score for normal baseline samples was 8.3 ± 6.1 whereas 105.4 ± 15.7 and 69.8 ± 20.3 for alpha and beta thalassemia respectively. While the comet scores were 71.9 ± 19.6, 193.1 ± 21.8 and 211.8 ± 51.6 for normal, alpha and beta thalassemia samples respectively in UV-treated samples. Results showed that both alpha and beta thalassemia patients had higher leucocytic DNA damage in baseline and oxidative stressed samples. Conclusion: Our data suggested thalassemia patients were under oxidative stress even no iron over loaded through transfusion.

Micronucleus Formation Induced by Glyphosate and Glyphosate-Based Herbicides in Human Peripheral White Blood Cells

Glyphosate is the most commonly used herbicide around the world, which led to its accumulation in the environment and consequent ubiquitous human exposure. Glyphosate is marketed in numerous glyphosate-based herbicide formulations (GBHs) that include co-formulants to enhance herbicidal effect of the active ingredient, but are declared as inert substances. However, these other ingredients can have biologic activity on their own and may interact with the glyphosate in synergistic toxicity. In this study, we focused to compare the cytogenetic effect of the active ingredient glyphosate and three marketed GBHs (Roundup Mega, Fozat 480, and Glyfos) by investigating cytotoxicity with fluorescent co-labeling and WST-1 cell viability assay as well as genotoxicity with cytokinesis block micronucleus assay in isolated human mononuclear white blood cells. Glyphosate had no notable cytotoxic activity over the tested concentration range (0–10,000 μM), whereas all the selected GBHs induced significant cell death from 1,000 μM regardless of metabolic activation (S9). Micronucleus (MN) formation induced by glyphosate and its formulations at sub-cytotoxic concentrations (0–100 μM) exhibited a diverse pattern. Glyphosate caused statistically significant increase of MN frequency at the highest concentration (100 μM) after 20-h exposure. Contrarily, Roundup Mega exerted a significant genotoxic effect at 100 μM both after 4- and 20-h exposures; moreover, Glyfos and Fozat 480 also resulted in a statistically significant increase of MN frequency from the concentration of 10 μM after 4-h and 20-h treatment, respectively. The presence of S9 had no effect on MN formation induced by either glyphosate or GBHs. The differences observed in the cytotoxic and genotoxic pattern between the active principle and formulations confirm the previous concept that the presence of co-formulants in the formulations or the interaction of them with the active ingredient is responsible for the increased toxicity of herbicide products, and draw attention to the fact that GBHs are still currently in use, the toxicity of which rivals that of POEA-containing formulations (e.g., Glyfos) already banned in Europe. Hence, it is advisable to subject them to further comprehensive toxicological screening to assess the true health risks of exposed individuals, and to reconsider their free availability to any users.

Comparison of Clinical Characteristics of Adolescent Women With Different Subtypes of Anorexia Nervosa With First Episode and Without Treatment

Background This study compared whether differences between different anorexia nervosa(AN)subtypes(R-AN,B-AN) in multiple organ complications. Methods Peripheral white blood cells (WBCs),thyroid function,etc, were measured in 53 patients (R-AN = 30,B-AN = 23)and compared 55 healthy controls (HCs) Results Compared with HCs, significant differences between R-AN in T, P, DBP, SBP WBC, PRL, TT4, TSH, FT3, FT4, TT3, TP, HGB, RBC,, EDI total score and DT, I, ID, IA ,BD, P and MF. Compared with HCs, significant differences between B-AN in DBP, WBC, PRL, TT4, FT3, FT4, TT3, TP, HGB, RBC,, EDI total score, DT, BD, I, ID, and IA and differences in PLT and P. significant differences between R-AN and B-AN in T, P, DBP, SBP, PRL, TSH, B, FT4, and HGB. In R-AN, BMI negatively correlated with amenorrhea, and PRL EDI total score, DT, BD, and P positively correlated with DBP, SBP, HGB and GLB. In B-AN, BMI negatively correlated with amenorrhea, PRL, EDI total score, and DT, and B, BD, positively correlated with T and DBP. Conclusion The effects of R-AN and B-AN on T, P, DBP, SBP, PRL TSH, B, FT4, and HGB were different, and BMI played a role in the changes.

Genetics of Iron Metabolism and Premenstrual Symptoms: A Mendelian Randomization Study

ABSTRACT Background Many women of reproductive age experience adverse psychological and physiological premenstrual symptoms. These symptoms may last for most of the reproductive years and can negatively affect the quality of life of many women. Some studies have examined the role of micronutrients in premenstrual symptoms, but the research on iron has been limited. Objectives The objective of this study was to evaluate the effects of genetic predictors of iron overload and low iron status on premenstrual symptoms using Mendelian randomization. Methods We examined 254 White females aged 20–29 y from the Toronto Nutrigenomics and Health Study. DNA was isolated from peripheral white blood cells and genotyped for the homeostatic regulatory iron gene (HFE; rs1800562 and rs1799945), transmembrane protease serine 6 (TMPRSS6; rs482026), transferrin receptor 2 (TFR2; rs3811647), and transferrin (TF; rs738584) polymorphisms. Risk of iron overload or low iron status was determined based on combined genotypes. Binomial logistic regressions were carried out to examine the association between genetic risk of iron overload or low iron status and the presence of premenstrual symptoms. Results Compared with participants with typical risk of iron overload, those with an elevated risk of iron overload were less likely to experience premenstrual symptoms of confusion (OR: 0.13; 95% CI: 0.02, 1.00), headaches (OR: 0.28; 95% CI: 0.08, 0.98), and nausea (OR: 0.13; 95% CI: 0.02, 0.99) after adjusting for BMI, age, and vitamin C and calcium intake. No associations were seen with the other symptoms. There were also no associations between low iron status genotypes and premenstrual symptoms. Conclusions This Mendelian randomization study demonstrates that women with an elevated risk of iron overload may have a lower risk of experiencing some premenstrual symptoms (headache, confusion, and nausea), suggesting that iron status could impact the risk of certain premenstrual symptoms.

The network interplay of type 1 interferon and toll-like receptor signaling cascades hallmarks the immune response against Candida spp. infections

Here we employed a stepwise, integrative, and systems immunology approach to unravel the human immune responses to C. albicans and C. auris by analyzing publicly available human transcriptome data. Modular gene co-expression analysis revealed an interplay between Toll-like Receptors (TLR) and Interferon (IFN) networks. Enrichment analyses and hierarchical clustering revealed that this relationship is consistently triggered in peripheral white blood cells, peripheral blood mononuclear cells, and dendritic cell transcriptomes, involving IFN-γ, IFN-α/β- (e.g., ISGs, IRFs, SOCS, and GBPs) and TLR-associated molecules (TLR3,4,7/8,9, and TRAF-mediated NF-κB). These TLR- and IFN-associated genes cluster and increase their correlation levels after Candida stimulation, forming a highly interconnected interferome network, which contains an immune overlap with the anti-viral responses. Notably, our analysis shed new lights on the molecular basis of several genes associated with inborn errors of immunity that cause host susceptibility to fungal infections such as Candida spp., which reinforce our transcriptomic findings.