Impact of COVID-19 Pandemic on Clinical Care of Patients and Psychosocial Health of Affected Families with Chronic Granulomatous Disease: an Observational Study from North India.

Day-to-day clinical management of patients with inborn errors of immunity, including chronic granulomatous disease (CGD), has been affected by the coronavirus disease-2019 (COVID-19) pandemic. There is a dearth of information on impact of this pandemic on clinical care of children with CGD and psychological profile of the caretakers. Among the 101 patients with CGD followed up in our center, 5 children developed infection/complications associated with COVID-19. Four of these children had a mild clinical course, while 1 child developed features of multisystem inflammatory syndrome in children (MISC) requiring intravenous glucocorticoids. Parents and caretakers of CGD patients (n = 21) and 21 healthy adults with similar ages and genders were also evaluated on the following scales and questionnaires: COVID-19 Fear Scale (FCV 19S), Impact of Event Scale (IES-R), Depression, Anxiety, and Stress Scale (DASS 21), Preventive COVID-19 Behavior Scale (PCV 19BS), and a "COVID-19 Psychological wellbeing questionnaire." Median age of the parents/caregivers was 41.76 years (range: 28-60 years). Male:female ratio was 2:1. In the study group, 71.4% had higher IES scores compared to 14.3% in controls. The caregivers had a high prevalence of stress, anxiety, avoidance behavior, and depression compared to controls (p < 0.001). Children with CGD have had predominantly mild infection with COVID-19; however, caregivers/parents of these children were at risk of developing psychological distress. The COVID-19 pandemic has brought to light the importance of patients' and caretakers' mental health which needs periodic assessment and appropriate interventions.

Plasma microRNA expression and immunoregulatory cytokines in an Indian population occupationally exposed to cadmium.

Following its accumulation in the body, cadmium (Cd) exposure is associated with devastating effects on multiple organ system of the human body. The immune system is one of the sensitive targets for Cd-induced toxicity. Recently, studies have demonstrated a significant role of Cd in inducing epigenetic alterations. With this background, the present study was planned to study the changes in candidate microRNA (miRNA) expression associated with immune regulation in occupationally Cd-exposed workers. One hundred individuals involved in welding and metal handicraft manufacturing, while 80 apparently healthy subjects without any prior history of occupational exposure were recruited for the study. Blood Cd level was determined by atomic absorption spectrometry. Serum cytokine levels were measured using an enzyme-linked immunosorbent assay and serum miRNA expression of candidate miRNAs (miR-146a, miR-210, and miR-222) were determined by real-time polymerase chain reaction. The median Cd level (2.40 µg/L) in the occupationally exposed workers was significantly higher than the nonexposed subjects (0.90 µg/L). Among the cytokines, interleukin-4 (IL-4), and tumor necrosis factor-alpha (TNF-α) were significantly higher while IL-2 and IL-10 were significantly lower in the exposed. The expression level of miR-146a and miR-222 were significantly different between the groups with the former showing downregulation and later showing upregulation. Correlation analysis revealed a positive and negative association of miR-222 and miR-146a with blood cadmium level, IL-17 as well as TNF-α, respectively. Furthermore, the in-silico analysis revealed a significant role of the studied miRNAs in various cellular and genetic pathways. The findings of the present study demonstrate significant involvement of Cd-induced alteration in miRNAs in varied immune regulatory changes in exposed individuals.

Unravelling blood-based epigenetic mechanisms: the impact of hsa-miR-146a and histone H3 acetylation in lead-induced inflammation among occupational workers.

BACKGROUND: Occupational and environmental exposure to lead (Pb) is a persistent health problem majorly in developing countries and has been implied to cause epigenetic alterations. Its effect on histone post-translational modifications is not explored in human population. MicroRNAs are epigenetic modulators reported to be differentially expressed under Pb exposure. The present study was targeted to find plausible association between the role of hsa-miR-146a and global histone (H3) acetylation in Pb-induced inflammation in occupationally exposed workers. MATERIALS AND METHODS: A total of 100 occupationally exposed individuals working in different industries were recruited for the study and divided into 2 groups based on the median Pb levels [low Pb group (Pb < 5 µg/dL) and High Pb group (Pb > 5 µg/dL)]. The Pb levels were measured in whole blood using atomic absorption spectrometry to confirm Pb exposure. Histone H3 acetylation and serum interleukin-6 (IL-6) levels were measured using colorimetric methods and enzyme-linked immunosorbent assay (ELISA), respectively. MicroRNA-146a expression was quantified using TaqMan assay. RESULTS: The median BLL of the study population was 5 µg/dL. BLL, IL-6, and Histone (H3) acetylation increased significantly with the duration of exposure. BLL level showed a significant positive correlation with IL-6 and histone H3 acetylation level. We also found that hsa-miR-146a exhibited significantly increased expression in the high Pb group compared to the low Pb group (Fold change: 2.56; P = 0.014). The linear regression model suggested that BLL has significantly predicted histone H3 acetylation, hsa-miR-146a, and IL-6 in the study subjects. CONCLUSION: The finding that hsa-miR146a was significantly upregulated in individuals with high BLL and had a significant negative correlation with serum IL-6 suggests that Pb-induced oxidative stress likely activates H3 acetylation, which then releases inflammatory cytokines like IL-6.

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.

Effect of occupational co-exposure to lead and cadmium on selected immunomodulatory cytokines.

Occupational exposure to heavy metals like lead (Pb) and cadmium (Cd) is associated with the development of several diseases. The objective of this study was to determine the effect of occupational co-exposure to Pb and Cd on the blood levels of selected immune-modulatory cytokines related to T helper (Th), that is, Th1, interleukin-2 (IL-2), Th2, (IL-4 and IL-10), and Th17, (IL-17) cells. The study comprised 207 individuals divided into two groups: exposed (n = 110) and nonexposed (n = 97). Blood Pb and Cd were determined using Graphite Furnace Atomic Absorption Spectroscopy, and serum levels of cytokines were measured using enzyme-linked immunosorbent assay (ELISA). The study revealed significantly higher blood Pb and Cd levels in the exposed group. A significant decrease in Th1 cytokine-IL-2 and Th2 cytokine-IL-10 was found, while IL-4 (Th2 cytokine) and IL-17 (Th17) levels were higher in the exposed group. In the mixed exposure analysis, among all the selected cytokines, IL-4 levels were significantly different between individuals having higher levels of both Pb and Cd versus lower levels of Pb and Cd. While IL-2 levels were highest among the low Pb and Cd group, the IL-17 levels were highest among individuals with higher Cd levels. The study demonstrated that co-exposure to low levels of Pb and Cd might have an immune-modulatory effect. The data suggested a metal-induced pro-inflammatory immune response.

Risk Factors for Lead Toxicity and its Effect on Neurobehavior in Indian Children.

Lead (Pb) is profoundly used heavy metal despite its known toxic effects. Children in particular are more susceptible to Pb toxicity. Thus, the present study was carried out to estimate the prevalence of lead toxicity in Indian children, to observe serum levels of biochemical parameters and to evaluate psychopathological implications of Pb toxicity using population specific scale-Childhood Psychopathological Measurement Schedule (CPMS) in children. Children between 9 and 15 years of age were included in the study (N = 70). Demographic details and information regarding the source of lead exposure were collected using a self-made questionnaire. All biochemical investigations were performed in Beckman Coulter Auto-analyser AU680 and Blood Lead Levels (BLL) were estimated by Graphite Furnace Atomic Absorption Spectrophotometer. The neurobehavioral state of the children was assessed by a population-specific scale i.e., CPMS, which evaluates for neurobehavior under 8 factors, titled, Low intelligence with behavioural problems, Conduct disorder, Anxiety, Depression, Psychotic symptoms, Special symptoms, Physical illness with emotional problems, and Somatization. The median BLL of the study population was 4.9 µg/dL. Habit of frequently consuming roadside food, proximity of residence to vehicular traffic and educational status of the mother were observed to be significant contributing factors for high BLL (≥ 5 µg/dL). Serum alkaline phosphatase (P = 0.02) and phosphorous levels (P = 0.04) were significantly lower in children belonging to high BLL group. A significantly high adverse neurobehavioral score was observed in high BLL group children compared to low BLL group (P < 0.05). There was high prevalence of Pb toxicity with 50% of children having BLL > 5 µg/dL. Further, certain lifestyle characteristics such as proximity of residence to vehicular traffic, frequent consumption of roadside food and lower educational status of the mother could be possible risk factors for higher Pb exposure in children. Evaluation of neurobehavior in children with high BLL revealed a high prevalence of adverse neurobehavior in them when compared to children in low BLL group.

Blood lead and cadmium levels in occupationally exposed workers and their effect on markers of DNA damage and repair.

Occupational exposure to heavy metals like lead and cadmium causes a wide range of biological effects and may elevate the risk of genetic damage. Heavy metal toxicity is now becoming a significant public health problem. There are many discrepancies in the results of the studies on the genotoxicity of heavy metals. Therefore, the study aimed to estimate lead, cadmium, and 8-OHdG levels (8-hydroxy-2-deoxyguanosine) and expression of DNA repair gene OGG1 (8-oxoguanine DNA glycosylase 1) in occupationally heavy metal exposed workers. The study comprised 100 workers, occupationally exposed to lead and cadmium from different factories and 100 controls without history of metal exposure. The lead and cadmium mean ± SD were 5.69 ± 12.07 µg/dL and 3.44 ± 1.33 µg/L in the cases and 1.27 ± 1.10 µg/dL and 1.07 ± 0.67 µg/L in the controls. The 8-OHdG concentration was significantly higher in the cases than the controls. Cadmium showed a significant positive correlation with 8-OHdG in the cases. The expression of OGG1 was significantly down-regulated in the cases compared to the controls. Lead levels did not show any significant correlation with OGG1, whereas cadmium level had a significant positive correlation with OGG1 in the cases. To conclude, the exposure to heavy metals is associated with increased oxidative DNA damage and impaired expression of the DNA repair gene, OGG1.

Assessement of Blood Lead and Cadmium Levels in Occupationally Exposed Workers of Jodhpur, Rajasthan.

In spite of the established knowledge regarding their toxicities, occupational exposure to heavy metals like lead and cadmium still continues because of their wide distribution in environment. Due to lack of awareness, most of the workers usually eat, smoke, drink at their workplace which may aggravate the metal exposure. The present study was planned to assess the blood levels of lead and cadmium in occupationally exposed workers of Jodhpur (India). A total of 110 individuals working in different industrial set ups (furniture, metal handicraft, welders) of Jodhpur district (exposed group), aged between 20 and 60 years and 97 apparently healthy people (controls) with no history of occupational heavy metal exposure aged between 25 and 60 were recruited. Details of personal habits and demographics were recorded by means of self-developed questionnaire. 5 ml of whole blood was drawn from every individual. Metal levels were measured by graphite furnace atomic absorption spectrophotometer. Statistical analysis was done using GraphPad Prism Software. Results showed that Blood Lead Level and Blood Cadmium Level (CdB) were significantly higher in the exposed group as compared to the non-exposed group. Significant age and gender-based differences were found in terms of blood cadmium levels but no such difference was observed in case of blood lead. The study also revealed that higher blood levels of these metals in workers are influenced by their occupational practices, lack of protection against workplace environment pollutants, thus increasing their susceptibility to metal toxicity.

Effect of metallothionein 1A rs8052394 polymorphism on lead, cadmium, zinc, and aluminum levels in factory workers.

Metallothioneins (MTs) are low molecular weight cysteine-rich, metal-binding proteins. They are involved in transportation and detoxification of heavy metals, homeostasis of essential metals, and as antioxidation against reactive oxygen species. Polymorphisms in a gene may increase or decrease the expression efficiency of a gene. This study aimed to determine the genetic effect of MT1A rs8052394 on lead (Pb), cadmium (Cd), zinc (Zn), and aluminum (Al) levels in factory workers. The study included 100 occupationally heavy metal exposed workers from different factories around Jodhpur. Pb, Cd, Zn, and Al levels were measured by atomic absorption spectrophotometry. Individuals with the GG genotype had lower Pb, Zn, and Al levels and higher Cd levels than AA and AG genotypes. The genotyping of MT1A rs8052394 was done by the polymerase chain reaction-restriction fragment length polymorphism method (PCR-RFLP). The mean ± standard deviation of Pb, Cd, Zn, and Al was 5.88 ± 13.28 µg/dL, 3.52 ± 1.25 µg/L, 16.45 ± 16.69 µg/dL, and 58.92 ± 58.91 µg/L, respectively. A significant association was found between single-nucleotide polymorphisms (SNPs) of MT1A gene and Cd (p = 0.006) and with Zn levels (p = 0.031) but no association found with Pb and Al levels. Among the study population, 78 participants were homozygote major (AA), 19 were heterozygote (AG), and 3 were homozygote minor (GG). The χ 2 test presented the genotypic distribution of all three genotypes under the Hardy-Weinberg equilibrium (p > 0.05). The frequency of the A allele was 87.5% (175) and the G allele was 12.5% (25). To conclude, polymorphism in rs8052394 of the MT1A gene is associated with increased metal accumulation which in turn may lead to increased toxic effects in the exposed individuals. Factory workers thus, should be more cautious about protecting their health against the toxic effects of heavy metals.

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.

Markers of Endothelial Dysfunction in Kawasaki Disease: An Update.

Kawasaki disease (KD) is a medium vessel vasculitis that has a special predilection for coronary arteries. Cardiovascular complications include the development of coronary artery abnormalities (CAAs) and myocarditis. Endothelial dysfunction (ED) is now recognized to be a key component in the pathogenesis of KD and is believed to contribute to the development of CAAs. ED has been evaluated by several clinical parameters. However, there is paucity of literature on laboratory markers for ED in KD. The evaluation of ED can be aided by the identification of biomarkers such as oxidative stress markers, circulating cells and their progenitors, angiogenesis factors, cytokines, chemokines, cell-adhesion molecules, and adipokines. If validated in multicentric studies, these biomarkers may be useful for monitoring the disease course of KD. They may also provide a useful predictive marker for the development of premature atherosclerosis that is often a concern during long-term follow-up of KD. This review provides insights into the current understanding of the significance of ED in KD.

Cross-talk between immune cells and tumor cells in non-Hodgkin lymphomas arising in common variable immunodeficiency.

INTRODUCTION: CVID is the commonest and most symptomatic primary immune deficiency of adulthood. NHLs are the most prevalent malignancies in CVID. The cross-talk between tumor cells and immune cells may be an important risk factor in lymphomagenesis. AREAS COVERED: The present review highlights immune cell, genetic and histopathological alterations in the CVID-associated NHLs. EXPERT OPINION: CVID patients exhibit some notable immune defects that may predispose to lymphomas. T/NK cell defects including reduced T cells, naïve CD4+T cells, T regs, and Th17 cells, increased CD8+T cells with reduced T cell proliferative and cytokine responses and reduced iNKT and NK cell count and cytotoxicity. B cell defects include increased transitional and CD21low B cells, clonal IgH gene rearrangements, and increased BCMA levels. Increase in IL-9, sCD30 levels, and upregulation of BAFF-BAFFR signaling are associated with lymphomas in CVID. Increased expression of PFTK1, duplication of ORC4L, germline defects in TACI, NFKB1, and PIK3CD, and somatic mutations in NOTCH2 and MYD88 are reported in CVID-associated lymphomas. Upregulation of PD-L1-PD-1 pathway may also promote lymphomagenesis in CVID. These abnormalities need to be explored as prognostic or predictive markers of CVID-associated NHLs by large multicentric studies.

Single-cell RNA sequencing: an emerging tool revealing dysregulated innate and adaptive immune response at single cell level in Kawasaki disease.

INTRODUCTION: Kawasaki disease [KD] is a systemic disorder characterized by acute febrile illness due to widespread medium-vessel vasculitis, mainly affecting children. Despite the ongoing advanced research into the disease pathophysiology and molecular mechanisms, the exact etiopathogenesis of KD is still an enigma. Recently, single-cell RNA sequencing [scRNA-seq], has been utilized to elucidate the pathophysiology of KD at a resolution higher than that of previous methods. AREA COVERED: In the present article, we re-emphasize the pivotal role of this high-resolution technique, scRNA-seq, in the characterization of immune cell transcriptomic profile and signaling/response pathways in KD and explore the diagnostic, prognostic, and therapeutic potential of this new technique in KD. Using combinations of the search phrases 'KD, scRNA-seq, CAA, childhood vasculitis' a literature search was carried out on Scopus, Google Scholar, and PubMed until the beginning of 2024. EXPERT OPINION: scRNA-seq presents a transformative tool for dissecting KD at the cellular level. By revealing rare cell populations, gene expression alterations, and disease-specific pathways, scRNA-seq aids in understanding the intricacies of KD pathogenesis. This review will provide new insights into pathogenesis of KD and the field of applications of scRNA-seq in personalized therapeutics for KD in the future.

Epstein-Barr virus-driven lymphoproliferation in inborn errors of immunity: a diagnostic and therapeutic challenge.

INTRODUCTION: Inborn errors of immunity (IEI) are a group of genetically heterogeneous disorders with a wide-ranging clinical phenotype, varying from increased predisposition to infections to dysregulation of the immune system, including autoimmune phenomena, autoinflammatory disorders, lymphoproliferation, and malignancy. Lymphoproliferative disorder (LPD) in IEI refers to the nodal or extra-nodal and persistent or recurrent clonal or non-clonal proliferation of lymphoid cells in the clinical context of an inherited immunodeficiency or immune dysregulation. The Epstein-Barr virus (EBV) plays a significant role in the etiopathogenesis of LPD in IEIs. In patients with specific IEIs, lack of immune surveillance can lead to an uninhibited proliferation of EBV-infected cells that may result in chronic active EBV infection, hemophagocytic lymphohistiocytosis, and LPD, particularly lymphomas. AREAS COVERED: We intend to discuss the pathogenesis, diagnosis, and treatment modalities directed toward EBV-associated LPD in patients with distinct IEIs. EXPERT OPINION: EBV-driven lymphoproliferation in IEIs presents a diagnostic and therapeutic problem that necessitates a comprehensive understanding of host-pathogen interactions, immune dysregulation, and personalized treatment approaches. A multidisciplinary approach involving immunologists, hematologists, infectious disease specialists, and geneticists is paramount to addressing the diagnostic and therapeutic challenges posed by this intriguing yet formidable clinical entity.

Microbiome and Its Dysbiosis in Inborn Errors of Immunity.

Inborn errors of immunity (IEI) can present with infections, autoimmunity, lymphoproliferation, granulomas, and malignancy. IEIs are due to genetic abnormalities that disrupt normal host-immune response or immune regulation. The microbiome appears essential for maintaining host immunity, especially in patients with a defective immune system. Altered gut microbiota in patients with IEI can lead to clinical symptoms. Microbial dysbiosis is the consequence of an increase in pro-inflammatory bacteria or a reduction in anti-inflammatory bacteria. However, functional and compositional differences in microbiota are also involved. Dysbiosis and a reduced alpha-diversity are well documented, particularly in conditions like common variable immunodeficiency. Deranged microbiota is also seen in Wiskott-Aldrich syndrome, severe combined immunodeficiency, chronic granulomatous disease, selective immunoglobulin-A deficiency, Hyper IgE syndrome (HIGES), X-linked lymphoproliferative disease-2, immunodysregulation, polyendocrinopathy, enteropathy, x-linked syndrome, and defects of IL10 signalling. Distinct gastrointestinal, respiratory, and cutaneous symptoms linked to dysbiosis are seen in several IEIs, emphasizing the importance of microbiome identification. In this study, we discuss the processes that maintain immunological homeostasis between commensals and the host and the disruptions thereof in patients with IEIs. As the connection between microbiota, host immunity, and infectious illnesses is better understood, microbiota manipulation as a treatment strategy or infection prevention method would be more readily employed. Therefore, optimal prebiotics, probiotics, postbiotics, and fecal microbial transplantation can be promising strategies to restore the microbiota and decrease disease pathology in patients with IEIs.

Evaluation of DNA Damage and Expressions of DNA Repair Gene in Occupationally Lead Exposed Workers (Jodhpur, India).

Occupational exposure to lead (Pb) remains a significant concern for worker's health working in different factories. There are many discrepancies among the results regarding the studies of genotoxicity of Pb. The present study aimed to evaluate DNA damage and expressions of DNA repair genes (OGG1, XRCC1, and XPD) in occupationally Pb-exposed workers of Jodhpur, India. The study consisted of 100 occupationally Pb-exposed workers and 100 controls (non-exposed) with no history of occupational exposure. Pb levels were determined by atomic absorption spectrophotometry, serum 8-hydroxy-2-deoxyguanosine (8-OHdG) concentrations were measured by ELISA, and expressions of DNA repair genes (OGG1, XRCC1, and XPD) were estimated by RT-PCR. The results indicated significantly higher levels of Pb in the exposed group as compared with the non-exposed group (p < 0.0001). Serum 8-OHdG concentrations were significantly higher (p < 0.0083), and all three DNA repair genes were significantly downregulated (fold change: OGG1, 0.188; XRCC1, 0.125; XPD, 0.133) in the Pb-exposed group as compared with the non-exposed. In conclusion, the study findings suggest that Pb exposure is associated with increased DNA damage and reduced DNA repair capacity, which may lead to serious health issues in occupationally Pb-exposed workers.

Evaluation of oxidative stress and pro-inflammatory cytokines in occupationally cadmium exposed workers.

BACKGROUND: Cadmium (Cd) exposure in environmental and occupational settings is a major public health concern. Cd exposure is associated with the production of free radicle and reactive oxygen species. The aim of the present study is to evaluate the effect of occupational exposure to Cd on oxidative stress and pro-inflammatory biomarkers in the workers. METHODS: 100 occupationally exposed individuals working in the metal handicraft industry and welding industry were recruited from the industrial area of Jodhpur, Rajasthan. Blood Cd levels were estimated using atomic absorption spectroscopy. Serum Total Antioxidant Capacity (TAC), Catalase (CAT), Superoxide Dismutase (SOD), and Malondialdehyde (MDA) levels were measured by colorimetric method to assess oxidative status and serum IL-6 and TNF-α were measured by ELISA to assess inflammatory status. RESULTS: The median Cd levels in the study population was 2.40µg/L, with welders having significantly higher Cd levels than metal handicraft workers. Among the oxidative stress markers, TAC and CAT were significantly lower, while MDA was significantly higher in subjects with high Cd levels. The Cd levels showed a significant negative and positive correlation with TAC and MDA, respectively. IL- 6 and TNF-α did not show a significant difference between the study groups, but both had an inverse correlation with antioxidant enzymes. CONCLUSION: Occupational exposure to even low levels of Cd may result in oxidative stress in workers primarily via decrease in antioxidant enzymes and increasing lipid peroxidation. Increased oxidative stress in turn may result in immune cell activation which may result in increased concentration of pro-inflammatory cytokine in the exposed workers.

Assessment of circulating miR-20b, miR-221, and miR-155 in occupationally lead-exposed workers of North-Western India.

Lead (Pb), a toxic heavy metal, is capable of inducing several adverse health effects following its accumulation in the body. Lead is a potential carcinogen, capable of causing multisystem alterations. Recent reports identify small regulatory RNA molecules-miRNAs-which show differential expression in individuals exposed to similar levels of lead. These miRNAs can become potential molecular biomarkers of lead toxicity in the future and may unravel the possible molecular pathways through which this metal may exert its toxic manifestations. The present study aimed to assess the circulating levels of miRNA-20b, 221, and 155 in occupationally lead-exposed workers and correlate them with blood lead levels. One hundred ten participants working in various factories of Jodhpur and 97 participants not occupationally exposed to lead were recruited after obtaining due informed consent. Blood lead level (BLL) was estimated by graphite furnace atomic absorption spectrophotometry (GF-AAS). Circulating miRNAs were isolated from serum by Qiagen miRNA isolation kit and converted to cDNA by commercial kit. Expression profiles of miR-20b, miR-221, and miR-155 were performed in RT-PCR using Qiagen miRNA PCR assays. The blood lead level (mean ± SD) of occupationally lead-exposed subjects was 6.94 ± 11.96 µg/dL while that of non-exposed was 2.39 ± 4.66 µg/dL. Out of the three miRNAs, miR-155 and miR-221 were significantly upregulated, while miR-20b did not show significant difference among study groups. The fold change of miR-20b, miR-221 and miR-155 expression were 1.08, 2.71 and 2.07 respectively. Functional analysis revealed that these miRNAs have the potential to trigger various genes and cellular pathways. The findings of our study highlight the importance of miRNA dysregulation in lead-exposed individuals that may contribute to the systemic effects of lead toxicity.

Association of blood lead levels with neurobehavior and BDNF expression in school going children.

BACKGROUND: Childhood Lead (Pb) toxicity has been an ongoing concern for decades; however, its underlying pathogenesis remains unclear. Although its prevalence has come down in developed countries (USA, Europe); it is relatively high in low to middle-income countries of South-East Asia. The current study aimed to evaluate the association of blood lead levels (BLLs) with neurobehavioral alterations and changes in Brain-Derived Neurotropic Factor (BDNF) expression in Indian school children. METHODOLOGY: School going children in age group of 9-15 years (N = 72) were included in the study. Neurobehavioral changes were assessed using Childhood Psychopathological Measurement Schedule (CPMS) and BLL were measured by Graphite Furnace Atomic Absorption Spectrophotometry (GFAAS). BDNF mRNA expression and serum BDNF levels were assessed by Real-Time PCR and ELISA, respectively. RESULTS: Median BLL was 4.95 µg/dL (IQR = 4.47), very close to the recommended toxic cut off levels (<5 µg/dL). BLLs had a direct correlation with both CPMS scores and BDNF expression. Depression was found to be significantly higher in boys than in girls with high BLLs. BDNF mRNA expression and serum BDNF levels were higher among children with high BLL, although not to significant levels. CONCLUSION: We report a significant association of neurobehavioral changes with the prevalence of high Pb levels in Indian children. Additionally significant correlation of BDNF with BLL in these children suggests a causal role of BDNF in Pb induced neurological damage.

Levels of lead, aluminum, and zinc in occupationally exposed workers of North-Western India.

OBJECTIVES: Metals including lead (Pb), aluminum (Al), and zinc (Zn) are widely used in factories such as welding, handicrafts, and paint. Occupational exposure to such metals causes a wide range of biological effects, depending upon the metal levels and duration of exposure. Accumulation of these metals may lead to several adverse health effects such as neurodegenerative diseases and cancer. The study aimed to evaluate Pb, Al, and Zn levels in occupationally exposed workers of North-Western India and create awareness about its toxicity and adverse outcomes. METHODS: The study included 120 factory workers (exposed) and 100 healthy controls (nonexposed); age ranged 18-78 years. Blood Pb and serum Al was estimated by graphite furnace atomic absorption spectrophotometry and serum Zn was estimated by flame atomic absorption spectrophotometry (ICE 3000, Thermo Fisher Scientific). RESULTS: Results indicated significantly higher levels of Pb, Al, and Zn in the exposed than the nonexposed. No significant difference was observed in metal levels, based on age and duration of exposure. Painters showed higher blood Pb, whereas welders were found to have higher serum Al and Zn levels. CONCLUSIONS: To conclude, workers showed higher levels of metals and it may cause deleterious effects on the health of workers occupationally exposed to these metals. Appropriate maintenance regarding worker's safety and hygiene is required to protect them from the harmful effects of these toxic metals.