Atrazine promotes breast cancer development by suppressing immune function and upregulating MMP expression.

There is evidence that the triazine herbicide atrazine, which is used extensively, is present in both surface water and groundwater, and its interfering effect on immune systems, endocrine systems, and tumours has been reported by laboratory and epidemiological studies. This study explored how atrazine affected 4T1 breast cancer cell development in vitro and in vivo. The obtained results showed that after exposure to atrazine, the cell proliferation and tumour volume were significantly increased and the expression of MMP2, MMP7, and MMP9 was upregulated. The thymus and spleen indices, the CD4 + and CD3 + lymphocyte percentages which from the spleen and inguinal lymph nodes, and the CD4 + /CD8 + ratio were noticeably lower than they were in the control group. Importantly, tumour-infiltrating lymphocytes such as CD4 + , CD8 + , and NK cells were decreased while Treg cells were increased. Moreover, IL-4 was increased and IFN-γ and TNF-α were decreased in the serum and tumour microenvironment. These results suggested that atrazine can suppress systemic as well as local tumour immune function and upregulate MMPs to promote breast tumour development.

Prolonged exposure to the herbicide atrazine suppresses immune cell functions by inducing spleen cell apoptosis in rats.

Atrazine (ATR) is a herbicide used widely worldwide. Because of its prolonged persistence in the environment and accumulation in the body, ATR exposure is a potential threat to human health. Our previous study showed that subacute exposure to ATR suppresses cellular immune function in mice. In this study, the effects of long-term exposure to ATR on rat immunological system function were measured. Four-week-old female Sprague-Dawley (SD) rats were treated with 0.4 µmol/L, 2 µmol/L and 10 µmol/L ATR for 24 weeks. The results showed that the spleen index increased, white blood cells decreased, and monocytes and eosinophils increased. No obvious changes were detected in the numbers of neutrophils and lymphocytes. Th1, Th2, and Th17 cells decreased significantly, while Treg cells increased after long-term ATR exposure. Moreover, serum levels of cytokines, including TNF-α, INF-γ, IL-6, and IL-12, decreased, while IL-1, IL-4, and IL-5 increased. Degenerative changes and cell apoptosis were found in the spleen; Caspase-3 and Caspase-9 were upregulated, and Bcl-2 was downregulated. These results suggested that long-term ATR exposure may inhibit immune system function.

Zinc and selenium supplementation on treated HIV-infected individuals induces changes in body composition and on the expression of genes responsible of naïve CD8+ T cells function.

Background and aim: Deficiency of zinc and selenium is common in persons living with human immunodeficiency virus (PLWHIV) and has been associated with the development of non-AIDS related comorbidities, impaired immune system function and mortality. Micronutrient supplementation on long-term-treated PLWHIV could bring potential clinical and immunological benefits improving their health status and quality of life. The aim of the present study is to analyze the effect of zinc and selenium supplementation on body composition, bone mineral density, CD4+ T-cell counts, metabolic profile and immune system status on clinical stable PLWHIV on long-term antiretroviral therapy (ART). Methods: This is a randomized pilot clinical trial in which we recruited 60 PLWHIV on ART who were assigned to the intervention groups: zinc (30 mg of zinc gluconate), selenium (200 µg of selenium yeast), zinc + selenium (same doses and presentations) or to a control group (without nutritional supplementation) who received supplementation during 6 months. Primary outcome was defined as changes in body composition (weight, muscle and fat mass and bone mineral density) and secondary outcomes as changes in biochemical and immunological parameters (CD4+ T-cell count, cholesterol, glucose, triglycerides and seric zinc and selenium seric concentrations) before and after supplementation. Peripheral blood mononuclear cells (PBMCs) of one individual of each intervention group were analyzed for single cell transcriptomics before and after supplementation. Results: BMI (p = 0.03), fat mass (p = 0.03), and trunk fat (p = 0.01) decreased after 6 months of selenium supplementation. No changes were observed for cholesterol, glucose or triglycerides after supplementation (p > 0.05 in all cases). CD4+ T cells percentage increased after 6 months of selenium supplementation (p = 0.03). On the transcriptome analysis, zinc and selenium supplementation induced changes on de expression of genes associated with the function of naive and memory CD8+ T-cells (p < 0.05 in all cases). Conclusion: Zinc and selenium supplementation could represent a complementary intervention that may improve the health status and immune response of treated PLWHIV.

Immune skeletal dysplasia with neurodevelopmental abnormalities caused by a novel variant of EXTL3 gene in a Chinese family.

BACKGROUND: Immune skeletal dysplasia with neurodevelopmental abnormalities (ISDNA) is an extremely rare, autosomal recessive genetic disorder characterized by various skeletal abnormalities, neurodevelopmental deficits, and abnormal immune system function. ISDNA is caused by variation in the exostosin-like 3 (EXTL3) gene, located on chromosome 8p21.2, whose primary function is the biosynthesis of heparan sulfate (HS) skeleton structure. Only a few variations in the EXTL3 gene have been discovered so far. In these years of development, many pathogenic variants in genetic diseases with genetic and phenotypic heterogeneity have been investigated using whole-exome sequencing (WES) technology. METHODS: In this research, a novel EXTL3 variant was first detected in a patient using WES, which was validated from Sanger sequencing in this family. Family history and clinical information were then collected through comprehensive medical examinations and genetic counseling. In silico prediction was then utilized to confirm the pathogenicity of the variant. RESULTS: A novel homozygous variant, NM_001440: c.2015G>A (p.Arg672Gln) in the EXTL3 gene, was identified using WES, which has never been reported before. Sanger sequencing was performed to confirm that the variant segregated with the disease within the family. CONCLUSION: This research identified a novel pathogenic variant in the EXTL3 gene responsible for ISDNA in a Chinese family. It showed the potential diagnostic role of WES in ISDNA, expanded the EXTL3 gene variation spectrum, and demonstrated that the diagnosis of ISDNA using WES is feasible and effective. More comprehensive genetic counseling and precise prenatal diagnosis for the next pregnancy can also be provided to families with genetic disorders.

Effects of Photobiomodulation Therapy on Lung Function and Inflammatory Factors in Patients with COVID-19 During Acute Stage.

Objective: We aimed to evaluate the effects of photobiomodulation therapy on the respiratory function and laboratory parameters in COVID-19 participants with respiratory involvement. Methods: A randomized, double-blind controlled design was used. This study was conducted at Koosar Hospital. Thirty participants with COVID-19 who were hospitalized met the inclusion criteria and were randomly assigned to two groups. Patients were treated with a program of five sessions of high-power photobiomodulation (intervention group) and placebo photobiomodulation (control group). Both groups received standard treatment. Outcomes were assessed before and after the intervention (two sessions), according to the immune system function and laboratory tests for the respiratory rate (RR), oxygen saturation, and inflammatory factors, including C-reactive protein (CRP), white blood cells, and interleukin-6 (IL-6), as well as complete blood count (CBC), hematocrit, hemoglobin, and ferritin. Results: Findings indicated that the values of ferritin, erythrocyte sedimentation ratio, CRP, IL-6, O2 saturation, and RR were significantly improved after the intervention in both groups (p < 0.05). Independent T-test analyses also indicated significant differences in the CRP, IL-6, and O2 saturation in the photobiomodulation group compared with the control group after the five-session intervention (p < 0.05). Conclusions: Application of photobiomodulation is recommended for treatment of respiratory problems in patients with COVID-19 to improve clinical signs and control inflammatory factors. Clinical Trial Registration: IRCT2017070934969N1.

The immunomodulatory effects of antihypertensive therapy: A review.

Hypertension remains the leading preventable risk factor for stroke and coronary artery disease, significantly contributing to all-cause global mortality and predisposing patients to renal and heart failure, as well as peripheral vascular disease. Due to the widespread usage of antihypertensive drugs, global mean blood pressure has remained unchanged or even slightly decreased over the past four decades. However, considering the broad spectrum of mechanisms involved in the action of antihypertensive drugs and the prevalence of their target receptors on immune cells, possible immunomodulatory effects which may exert beneficial effects of lowering blood pressure but also potentially alter immune function should be considered. In this review, we attempt to assess the consequences to immune system function of administering the five most commonly prescribed groups of antihypertensive drugs and to explain the mechanisms behind those interactions. Finally, we show potential gaps in our understanding of the effects of antihypertensive drugs on patient health. With regard to the widespread use of these drugs in the adult population worldwide, the discussed results may be of vital importance to evidence-based decision-making in daily clinical practice.

Screening of key biomarkers and immune infiltration in Pulmonary Arterial Hypertension via integrated bioinformatics analysis.

This study aimed to screen key biomarkers and investigate immune infiltration in pulmonary arterial hypertension (PAH) based on integrated bioinformatics analysis. The Gene Expression Omnibus (GEO) database was used to download three mRNA expression profiles comprising 91 PAH lung specimens and 49 normal lung specimens. Three mRNA expression datasets were combined, and differentially expressed genes (DEGs) were obtained. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses and the protein-protein interaction (PPI) network of DEGs were performed using the STRING and DAVID databases, respectively. The diagnostic value of hub gene expression in PAH was also analyzed. Finally, the infiltration of immune cells in PAH was analyzed using the CIBERSORT algorithm. Total 182 DEGs (117 upregulated and 65 downregulated) were identified, and 15 hub genes were screened. These 15 hub genes were significantly associated with immune system functions such as myeloid leukocyte migration, neutrophil migration, cell chemotaxis, Toll-like receptor signaling pathway, and NF-κB signaling pathway. A 7-gene-based model was constructed and had a better diagnostic value in identifying PAH tissues compared with normal controls. The immune infiltration profiles of the PAH and normal control samples were significantly different. High proportions of resting NK cells, activated mast cells, monocytes, and neutrophils were found in PAH samples, while high proportions of resting T cells CD4 memory and Macrophages M1 cell were found in normal control samples. Functional enrichment of DEGs and immune infiltration analysis between PAH and normal control samples might help to understand the pathogenesis of PAH.

Neurogenic Flare Response following Image-Guided Focused Ultrasound in the Mouse Peripheral Nervous System in Vivo.

Focused ultrasound (FUS) has been used to non-invasively elicit or inhibit motor neuronal activity in the mouse peripheral nervous system in vivo. However, less is known about whether FUS elicits immune system responses associated with peripheral sensory neuronal activity. In this study, we sought to determine that non-invasive ultrasound image-guided FUS can elicit the neurogenic axon reflex of peripheral nerves in the mouse sciatic nerve. The local vasodilation in the plantar view of the hind paw detected with a high-resolution laser Doppler imager indicated neurogenic flare responses after FUS stimulation. The effects of FUS were compared with control groups, where a distinct pattern of blood flow changes was observed only in FUS-elicited neurogenic flare responses. The findings indicate that image-guided FUS elicits local axon reflexes in vivo with a high degree of specificity and penetration depth.