Glial cells expressing visual cycle genes are vital for photoreceptor survival in the zebrafish pineal gland.

Photoreceptors in the vertebrate eye are dependent on the retinal pigmented epithelium for a variety of functions including retinal re-isomerization and waste disposal. The light-sensitive pineal gland of fish, birds, and amphibians is evolutionarily related to the eye but lacks a pigmented epithelium. Thus, it is unclear how these functions are performed. Here, we ask whether a subpopulation of zebrafish pineal cells, which express glial markers and visual cycle genes, is involved in maintaining photoreceptors. Selective ablation of these cells leads to a loss of pineal photoreceptors. Moreover, these cells internalize exorhodopsin that is secreted by pineal rod-like photoreceptors, and in turn release CD63-positive extracellular vesicles (EVs) that are taken up by pdgfrb-positive phagocytic cells in the forebrain meninges. These results identify a subpopulation of glial cells that is critical for pineal photoreceptor survival and indicate the existence of cells in the forebrain meninges that receive EVs released by these pineal cells and potentially function in waste disposal.

Visceral Adipose Tissue Molecular Networks and Regulatory microRNA in Pediatric Obesity: An In Silico Approach.

Childhood obesity carries an increased risk of metabolic complications, sleep disturbances, and cancer. Visceral adiposity is independently associated with inflammation and insulin resistance in obese children. However, the underlying pathogenic mechanisms are still unclear. We aimed to detect the gene expression pattern and its regulatory network in the visceral adipose tissue of obese pediatric individuals. Using differentially-expressed genes (DEGs) identified from two publicly available datasets, GSE9624 and GSE88837, we performed functional enrichment, protein-protein interaction, and network analyses to identify pathways, targeting transcription factors (TFs), microRNA (miRNA), and regulatory networks. There were 184 overlapping DEGs with six significant clusters and 19 candidate hub genes. Furthermore, 24 TFs targeted these hub genes. The genes were regulated by miR-16-5p, miR-124-3p, miR-103a-3p, and miR-107, the top miRNA, according to a maximum number of miRNA-mRNA interaction pairs. The miRNA were significantly enriched in several pathways, including lipid metabolism, immune response, vascular inflammation, and brain development, and were associated with prediabetes, diabetic nephropathy, depression, solid tumors, and multiple sclerosis. The genes and miRNA detected in this study involve pathways and diseases related to obesity and obesity-associated complications. The results emphasize the importance of the TGF-ß signaling pathway and its regulatory molecules, the immune system, and the adipocytic apoptotic pathway in pediatric obesity. The networks associated with this condition and the molecular mechanisms through which the potential regulators contribute to pathogenesis are open to investigation.

T helper cells in depression: central role of Th17 cells.

Depression is one of the most common neuropsychiatric disorders in the world. While conventional pharmaceutical therapy targets monoaminergic pathway dysfunction, it has not been totally successful in terms of positive outcomes, remission, and preventing relapses. There is an increasing amount of evidence that neuroinflammation may play a significant part in the pathophysiology of depression. Among the key components of the neuroinflammatory pathways already known to be active are the T helper (Th) cells, especially Th17 cells. While various preclinical and clinical studies have reported increased levels of Th17 cells in both serum and brain tissue of laboratory model animals, contradictory results have argued against a pertinent role of Th17 cells in depression. Recent studies have also revealed a role for more pathogenic and inflammatory subsets of Th17 in depression, as well as IL-17A and Th17 cells in non-responsiveness to conventional antidepressant therapy. Despite recent advances, there is still a significant knowledge gap concerning the exact mechanism by which Th17 cells influence neuroinflammation in depression. This review first provides a short introduction to the major findings that led to the discovery of the role of Th cells in depression. The major subsets of Th cells known to be involved in neuroimmunology of depression, such as Th1, Th17, and T regulatory cells, are subsequently described, with an in-depth discussion on current knowledge about Th17 cells in depression.

Association of microRNA expression with changes in immune markers in workers with cadmium exposure.

Human exposure to cadmium (Cd) is known to produce severe health effects. Recently, molecular mechanism of Cd toxicity has revealed the role of Cd in causing epigenetic alterations. miRNAs are small, non-coding RNAs which are involved in translational repression of genes. Therefore, the aim of the present study was to evaluate the alterations in expression of miRNAs associated with inflammation, carcinogenesis and, further, study their possible correlation with immune profile, in occupationally Cd exposed workers of Jodhpur. 106 workers from metal handicraft and welding factories were recruited as subjects, while, 80 apparently healthy non-exposed individuals served as control for this study. Blood Cd levels (BCd) were determined by Graphite Furnace Atomic Absorption Spectroscopy (GFAAS). Lymphocyte cell subset were measured by flow cytometry, serum interleukins were assessed by ELISA and miRNA expression was determined by Real Time Polymerase Chain Reaction (RT-PCR). BCd levels were significantly higher in the exposed individuals when compared to the non-exposed, with welders reporting the highest amongst all. Among the lymphocyte subset, exposed group showed significantly higher percentage of Th17 and lower percentage of Treg population. Cytokine profile expressed by exposed workers were predominantly pro-inflammatory in nature. Among, the studied miRNAs, miR-221 was significantly higher in exposed group with a fold change of 3.05. Additionally, miR-221 and miR-155 showed significant positive correlation with Th17 cell %. Regression analysis showed duration of exposure and IL-17 to have significant effect on miR-221 in exposed group. In conclusion, miR-221 was significantly upregulated in exposed and was correlated with immune alteration making it a potential candidate for further exploration of mechanism underlying Cd toxicity.

Alterations in Th17 and Treg Lymphocyte Subset in Workers Occupationally Exposed to Lead.

Occupational exposure to lead (Pb) may have a deleterious effect on health of the workers. Among the various physiological systems, the immune system is one of the most susceptible targets of lead. Previous studies have been inconclusive in establishing the effect of Pb on the immune system. With this background, the aim of our study was to determine the effect of occupational Pb exposure on workers' immune parameters. A total of 110 individuals who were occupationally exposed to Pb and 97 apparently healthy non-exposed individuals were recruited in this study. Blood lead levels (BLL) were determined by atomic absorption spectrophotometry (AAS). Lymphocyte subsets (Th1, Th17, and Tregs) were analyzed using flow cytometry, and the cytokine levels (IL-2, IL-4, IL-6, IL-10, IL-17, and TNF-α) were determined by ELISA. BLL were found to be significantly higher in the exposed group than non-exposed. A significant increase of CD8 cells (%) was observed in the lead-exposed group, while CD4 cells (%), although higher in the exposed group did not differ significantly. Among the T lymphocyte subsets, proportion of Th1 and Tregs was found to be lower in the exposed group with a significant increase in Th17 (%). Additionally, the levels of estimated cytokines suggested a predominant pro-inflammatory response in Pb-exposed workers with significant increase in IL-4, IL-6, and TNF-α, and a significant decrease in IL-2 and IL-10. IL-17 levels did not show any significant difference between the two groups. Increased Th17/Tregs ratio in the exposed group is also suggestive of an increased pro-inflammatory immune response in the exposed group. In conclusion, Pb exposure may induce functional alteration in the immune cells, which may predispose to other abnormalities.

Association Between Circulating Plasmacytoid Dendritic Cell Percentage and Blood Lead Levels in Children.

Lead (Pb) exposure is known to cause T helper 1 (Th1) to T helper 2 (Th2) shift in the immune response. The mechanism responsible for these effects is unclear. Plasmacytoid dendritic cells (pDCs) are known as the principal secretor of type 1 interferons (IFNs), which have a stimulatory effect on Th1 differentiation. However, no previous study has explored the effect of Pb on pDCs. Thus, the present study was conducted to explore the correlation between circulating pDC count, serum IFNα (pan) levels, and blood lead levels (BLLs) in children environmentally exposed to Pb. A total of 82 school-going children were recruited from government and private schools in Jodhpur. BLL, pDC percentages, and serum IFNα (pan) levels were estimated by atomic absorption spectrometry, flow cytometry, and ELISA, respectively, in 82 samples. The participants were divided as per BLL quartiles into 4 groups: (A) BLL < 3 µg/dL (n = 21), (B) BLL = 3-4.08 µg/dL (n = 20), (C) BLL = 4.08-6.17 µg/dL (n = 20), and (D) BLL > 6.17 µg/dL (n = 21). Only in category D, pDC percentages showed a significant positive correlation with BLL (Spearman's R = 0.5). Therefore, this preliminary data suggests that BLL might modulate pDC levels in a dose-dependent manner.

Estimation of lymphocyte subsets and cytokine levels in workers occupationally exposed to cadmium.

INTRODUCTION: Occupational exposure to Cadmium (Cd) may have serious health effect on workers. However, little is known about its effect on immune system. Moreover, previous studies have been inconclusive in stating the effect of Cd on immune system. The aim of our study was to estimate immune parameters in workers occupationally exposed to Cd. MATERIAL AND METHODS: 110 individuals occupationally exposed to Cd and 97 apparently healthy non-exposed individuals were recruited for this study. Blood Cadmium levels were determined by AAS. Lymphocyte subset were analyzed using flow cytometry and the cytokine levels were determined by ELISA. RESULTS: Exposed group have significantly higher levels of B-Cd. % of CD8 cells were higher in exposed while % of CD4 cells showed a decreasing trend in the exposed group. Among the CD3CD4 T cell subsets Th1 (%) and Tregs (%) cells were lower while Th17 (%) were higher in exposed group. Increased levels of IL-4 (Th2), IL-6 (Th2) and TNF- α (Th1) and decreased levels of IL-2 (Th1) and IL-10 (Tregs) were observed in Cd exposed workers which is indicative of a predominant pro-inflammatory response in Cd exposed workers. IL-17 (Th17) levels did not show any significant difference between the two groups. Increased Th17/Tregs ratio in the exposed group is also suggestive of an increased pro-inflammatory immune response in exposed group. CONCLUSION: To conclude, even low level of exposure to Cd in occupational settings is associated with alterations in Th17 cells, which may further predispose an individual to other systemic abnormalities.

Inflammation, Immunity and Immunogenetics in COVID-19: A Narrative Review.

The novel Coronavirus Disease 2019 (COVID-19), that began in Wuhan Province, China was labelled as an International Public Health Emergency on January 30, 2020 and later was declared a pandemic by the World Health Organisation (WHO) on March 11, 2020. The causative agent, SARS-CoV-2 was the third coronavirus responsible for causing major disease outbreaks in human population after Severe Acute Respiratory Syndrome (SARS) and Middle East Respiratory Syndrome (MERS) caused by SARS-CoV and MERS-CoV respectively. The patients of COVID-19 present with a clinical feature resembling mild form of viral pneumonia which in certain cases progress to a severe form characterised by adult respiratory distress syndrome (ARDS) and/or multiorgan failure leading to death. The transition from mild to severe form of COVID-19 is affected by a lot of factors like age, co-morbidities etc. In the absence of an absolute cure, it is essential to explore the molecular pathogenesis of the disease to identify people at risk of developing severity so that alternative treatment modalities may be planned. The aim of this review is to provide an update on the general characteristics of SARS-CoV-2 and highlight the inflammatory changes and immune dysregulation that may help in identification of molecular predictors of disease severity.

Circulating T helper 17 and IFN-γ positive Th17 cells in Major Depressive Disorder.

INTRODUCTION: Animal models of depression have reported elevated levels of T helper 17 (Th17) and T helper 1 (Th1) cells along with a decrease in T regulatory (Treg) cell percentage. However, there is ambiguity in the results of clinical studies investigating Th17 cells in Major Depressive Disorder (MDD). No studies have investigated the role of Interferon gamma positive Th17 cells (IFNγ+ Th17) in MDD yet. METHODS: The study population included 53 patients of first episode, drug naïve MDD patients, and 53 non-psychiatric healthy volunteers as healthy controls. Th17, Th1, IFNγ+ Th17 and Treg cell percentages were assessed by flow cytometry. RESULTS: The mean (±SD) percentage of Th17 cells in cases (1.87 ± 1.03) was significantly higher than the mean in controls (1.1 ± 0.94) (p < 0.001). There was no significant difference in the Treg percentages between the cases (2.1 ± 2.0) and controls (2.23 ± 0.95). The Th17:Treg ratio was significantly higher in cases (5.41 ± 10.84) compared to the controls (0.69 ± 0.89) (p < 0.05). Further analysis of data has also revealed that IFNγ+ Th17 subsets secreted more IL-17 in cases (515.7 ± 423.4) compared to controls (509.6 ± 337.4). Intracellular IL-17 levels in this subset also showed a weak though insignificant positive correlation with HDRS scores in the cases. CONCLUSION: Elevated circulating Th17 cell percentage and Th17:Treg ratio in MDD cases thus add to the evidence suggesting Th17 mediated pro-inflammatory state in MDD. The study also provides preliminary findings of the more pathogenic IFNγ+ Th17 cell subset in MDD.

Association of circulating BDNF levels with BDNF rs6265 polymorphism in schizophrenia.

Schizophrenia is a severe neuropsychiatric disorder affecting 1% of the world population. Disturbances in neuronal development and synaptic connections are important factors in the pathogenesis of schizophrenia. Brain derived neurotrophic factor (BDNF), a member of the neurotrophin family, plays a critical role in the development of neurons. Among several polymorphisms reported in BDNF, the rs6265 polymorphism is known to be associated with many neuropsychiatric diseases. This study was aimed to determine the effect of BDNF rs6265 functional polymorphism on serum BDNF concentration in patients with schizophrenia. In total, 50 schizophrenia patients and 50 controls were recruited after obtaining written informed consent. Serum BDNF levels were estimated using the ELISA method and BDNF rs6265 polymorphism was genotyped using T-ARMS PCR. Serum BDNF levels were decreased significantly in schizophrenia patients when compared to the healthy controls (p < 0.0001). Further, the rs6265 polymorphism was also not associated with the schizophrenia (p = 0.41). Intragroup analysis between different genotypes revealed no association between the serum BDNF levels and rs6265 polymorphism. Our results suggest that the functional polymorphism rs6265 is not associated with serum BDNF levels, which is in line with previous findings, which indicates that serum BDNF levels depend more on diagnostic effect than genetic effect. Replication studies on a larger study population are needed.

Association of raised blood lead levels in pregnant women with preeclampsia: A study at tertiary centre.

OBJECTIVE: This study aims to find the blood lead levels in pregnant women and its association with pre-eclampsia. MATERIAL AND METHODS: The study included 44 healthy pregnant females and 23 pre-eclamptic women. Demographic data and common risk factors for lead toxicity were recorded including age, residence, occupation, husband occupation, passive smoking, use of cosmetics, kajal, surma, receiving supplements/vitamins, history of house remodelling, plumbing, source of potable water, paint in house, use of lead-glazed ceramic and pica. Venous blood was collected and lead level was determined by atomic absorption spectrometry. RESULTS: The mean blood lead level was 2.38 ± 2.43 ug/dL in controls and 3.42 ± 2.18 ug/dL in preeclamptic women which was significantly higher (p = 0.0132). Strong correlation of BLL was observed with blood pressure in pre-eclamptic women. Pre-eclamptic patients were observed to be at increased risk of being lead exposed in terms of occupation and living conditions. CONCLUSION: Higher blood lead level is associated with increased risk of preeclampsia. Patients should be counselled for lifestyle modification to prevent complications.