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.

Hypertension and its association with body mass index among the Indian population. Findings from a nationwide survey (NFHS-4), 2015-16.

Background: Globally, hypertension (HTN) and obesity are two cardinal causes of morbidity and mortality. The Asian population shows comorbidities associated with obesity at a much lower body mass index (BMI) than the western population. Aim: The primary objective of the present study was to evaluate the association between BMI and HTN among the adult population. Material and Methods: We did a cross-sectional secondary data analysis of the NFHS-4 datasets, conducted during 2015-16. We included the adult population, that is, ≥19 years of age (93,040 men and 5,46,066 women), and excluded adolescents and pregnant women from our analysis. HTN was the primary dependent variable, while BMI was the primary predictor variable. Other covariates included age, education, place of residence, wealth index, use of alcohol and tobacco, and diabetes. Weighted analysis was done to depict our results. Results: Around 18.7% of men and 13.5% of women were hypertensive, of which 53.86% of males and 38.7% females were either overweight or obese. The odds of living with HTN among obese men and women increased with age, wealth, use of alcohol and tobacco, and comorbidities such as diabetes. The prevalence of HTN was higher even among the underweight adults living with diabetes and those consuming alcohol and tobacco. Conclusion: We reaffirm the significant association between BMI and HTN among adults. The use of the Asian classification of BMI for India and its neighboring countries to assess the burden of obesity would help in planning better interventions. A community-based targeted approach would help in controlling and reducing the prevalence of HTN.

Multi-sectoral implementation interface framework (MIIF) to achieve the objective of tobacco-free Himachal Pradesh.

The limitations observed in achieving the goal of a tobacco-free Himachal Pradesh have necessitated the need to contextualize the existing policy directives in tobacco reduction. Our observation has been that despite having clearly defined policy guidelines and laws, the implementation may not have followed suit. An analysis of the gaps observed had led us to develop an implementation interface framework involving stakeholders from multiple sectors.

Tobacco use and uncontrolled hypertension among Indian men: Insights from the National Family He alth Survey (NFHS-4), 2015-2016.

Background: Tobacco use is a modifiable risk factor for developing cardiovascular diseases, of which hypertension is a major killer. Uncontrolled hypertension (UHT) is a major public health concern that exerts a financial and service burden on the health system. Aim: The current analysis aimed to determine the association between tobacco use and UHT among Indian males. Material and Methods: Data from the 4th National Family Health Survey (NFHS) of 1,04,120 men aged 15-54 years were used. We estimated the adjusted prevalence ratio for having UHT among reported tobacco users and non-users. Results: The prevalence of UHT was the lowest (41.02%) among those who did not consume tobacco in any form. Among tobacco users, those smoking tobacco had the highest prevalence (53.53%) of UHT followed by those using both smoked and smokeless forms of tobacco (43.84%) and those using only smokeless forms of tobacco (42.26%). Factors significantly associated with UHT were alcohol consumption (aPR: 1.30; 95% CI: 1.19-1.43), belonging to the richer wealth quintile (richest quintile- aPR: 1.27; 95% CI: 1.05-1.38), being overweight (aPR: 3.14, 95% CI: 2.35-4.21), and being obese (aPR: 2.89, 95% CI: 2.12-.94). Higher educational status was significantly protective against UHT (aPR: 0.75; 95% CI: 0.63-0.88). Conclusions: Tobacco use is significantly associated with hypertension in Indian men. Addressing tobacco control and prevention of UHT remain the cornerstones for achieving the SDG target 3.4 by 2030, which aims to reduce premature mortality from NCDs by a third by 2030 relative to 2015 levels.

Growth Differentiation Factor-15 as a Candidate Biomarker in Gynecologic Malignancies: A Meta-analysis.

Growth differentiation factor-15 (GDF-15), though emerged as a novel marker in gynecological cancers, is yet to be recognized in clinical diagnostics. Eligible studies were sorted from multiple online databases, namely PubMed, Cochrane, ClinicalTrials.gov, Google Scholar, Web of Science, Embase, Scopus, LILACS, and Opengrey. From six studies, histopathologically diagnosed cases without prior treatment, and with diagnostic accuracy data for GDF-15 in gynecological cancers, were included. Our meta-analysis shows that GDF-15 has pooled diagnostic odds ratio of 12.74 at 80.5% sensitivity and 74.1% specificity, and an area under the curve of 0.84. Hence, GDF-15 is a potential marker to differentiate gynecological malignancy from non-malignant tumors.

Role of urinary Neutrophil Gelatinase-Associated Lipocalin (NGAL), Monocyte Chemoattractant Protein-1(MCP-1), and Interleukin-6(IL-6) as biomarkers in pediatric patients with hydronephrosis.

OBJECTIVES: The decision to surgically intervene in a hydronephrotic kidney in children is based on many debatable guidelines, some requiring repeated ultrasounds or renal scans. Urinary proteins have the potential to reflect renal disorders and hence can be the alternatives to such scans. Here, we aim to assess the role of urinary Neutrophil Gelatinase-Associated Lipocalin, Monocyte Chemoattractant Protein-1, and Interleukin-6 (IL-6) in such patients. METHODS: Seventeen children had obstructive hydronephrosis requiring pyeloplasty (UPJO), while seven were kept on conservative management in view of non-obstructive dilation (NOD). Urine samples were measured for the three urinary proteins at the time of presentation and following pyeloplasty using commercially available ELISA kits. RESULTS: The levels of all three urinary proteins were significantly higher in patients with UPJO children compared to the NOD group. Cut-off values to differentiate obstructive from non-obstructive hydronephrosis were obtained. A significant fall in the post-operative value of urinary IL-6 was also observed. CONCLUSION: This study highlights the potentiality of urinary proteins as biomarkers in identifying children with hydronephrosis and picking out the ones with obstructive hydronephrosis who will require pyeloplasty. The drop in levels after pyeloplasty can be employed to evaluate the effectiveness of pyeloplasty when sent serially.

ABC transporters in breast cancer: their roles in multidrug resistance and beyond.

ATP-binding cassette (ABC) transporters are membrane-spanning proteins involved in cholesterol homeostasis, transport of various molecules in and out of cells and organelles, oxidative stress, immune recognition, and drug efflux. They are long implicated in the development of multidrug resistance in cancer chemotherapy. Existing clinical and molecular evidence has also linked ABC transporters with cancer pathogenesis, prognostics, and therapy. In this review, we aim to provide a comprehensive update on all ABC transporters and their roles in drug resistance in breast cancer (BC). For solid tumours such as BC, various ABC transporters are highly expressed in less differentiated subtypes and metastases. ABCA1, ABCB1 and ABCG2 are key players in BC chemoresistance. Restraining these transporters has evolved as a possible mechanism to reverse this phenomenon. Further, ABCB1 and ABCC1 are important in BC prognosis. Newer therapeutic approaches have been developed to target all these molecules to dysregulate their effect, reduce cell viability, induce apoptosis, and increase drug sensitivity. In the future, targeted therapy for specific genetic variations and upstream or downstream molecules can help improve patient prognosis.

Selenium Levels in Occupationally Lead Exposed Workers of Rajasthan.

Occupational and environmental exposure to Lead (Pb) has profound detrimental effects on human health. The underlying mechanism of lead toxicity is not fully understood but antioxidant imbalance is suggested to be a key player in its pathogenesis. Selenium (Se) being a vital component of antioxidant system in the body, has been linked to many health benefits in humans. Selenium levels in occupationally Pb exposed individuals has not been explored in Indian setup. The aim of the present study is to find out the association of Se with blood lead levels (BLL) in occupationally Pb exposed individuals. In the present study 91 occupationally Pb exposed workers employed in handicraft and paint industries were recruited after taking informed consent. The demographic details were noted on self-generated questionnaire. The BLL and Se were measured using GFAAS (Thermofisher Scientific, Waltham, USA). Samples were run in duplicate after ensuring quality control. The mean Pb and Se levels in the study population were 5.5 ± 5.6 µg/dl (0.42-31.76 µg/dl) and 105.5 ± 23.8 µg/dl (46.4-189.6 µg/dl) respectively. BLL was significantly higher in tobacco chewers and those occupationally exposed to Pb for more than 5 years. Significantly low Se levels were observed in individuals with high BLL. Statistically significant negative linear relationship was noted between BLL and Se. The negative correlation of Se with BLL indicates the antagonistic relationship between these metals.

FOXM1 mediates GDF-15 dependent stemness and intrinsic drug resistance in breast cancer.

BACKGROUND: Stemness, a key component of breast cancer (BC) heterogeneity, is responsible for chemoresistance. Growth differentiation factor-15 (GDF-15) induces drug resistance and stemness in BC cells. In this study, the expressions and interactions of GDF-15, FOXM1, and stemness (OCT4 and SOX2), and drug resistance (ABCC5) markers were evaluated in BC. METHODS AND RESULTS: 40 diagnosed BC patients and 40 healthy controls were included in this study. Serum GDF-15 was significantly raised (p < 0.001) in BC patients. Expressions of GDF-15, OCT4, SOX2, and FOXM1 in BC tissue and cell lines (MCF-7 and MDA-MB-231) were determined by RT-PCR, while phosphorylated AKT (p-AKT) was analyzed by Western blot. Not only were the fold change expressions higher in cancer tissue as compared to surrounding control tissue, but a higher expression was observed for all the genes along with p-AKT in MDA-MB-231 cells compared to MCF-7. Tissue GDF-15 was significantly associated with ABCC5 (p < 0.001), OCT4 (p = 0.002), SOX2 (p < 0.001), and FOXM1 (p < 0.001). To further analyze the signaling pathway involved in stemness and drug resistance in BC, GDF-15 knockdown was performed, which reduced the expression of p-AKT, FOXM1, OCT4 and SOX2, and ABCC5, whereas recombinant GDF-15 treatment reversed the same. In silico analyses in UALCAN revealed a similar picture for these genes to that of BC tissue expression. CONCLUSIONS: GDF-15 promotes stemness and intrinsic drug resistance in BC, possibly mediated by the p-AKT/FOXM1 axis.

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.

Selenium, oxidative stress and inflammatory markers in handicraft workers occupationally exposed to lead.

Occupational Lead (Pb) exposure increases reactive oxygen species and has been reported to impact inflammatory response by modulating intracellular signaling pathways. Selenium (Se) a vital component of the antioxidant system that plays an important role in modulating cytokines. The present study evaluated Se, malondialdehyde (MDA), total antioxidant capacity (TAC) and cytokines (IL-6, TNF-α, IL-10, IL-17a) in 81 Pb exposed male workers. The median (range) of blood lead level (BLL) and Se were 5 (0.50-31.76) µg/dL and 104 (46.9-189.6) µg/L respectively. The Se, TAC levels were decreased, and MDA, IL-6 levels were increased in the high Pb group (>5µg/dL). Blood lead level independently predicted oxidative stress and antioxidant status. Selenium, TAC levels negatively and MDA, IL-6 levels positively correlated with BLL. Association of Se with IL-6 and TAC suggests some probable role of Se in the underlined mechanism of Pb toxicity.

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.

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.

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.

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.

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.

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.

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.

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.

Growth differentiation factor 15 and its role in carcinogenesis: an update.

Growth differentiation factor-15 (GDF-15) is a novel cytokine secreted by a variety of cells like macrophages, adipocytes, normally expressed in high amounts by placenta. It is also highly expressed in multiple carcinomas like Colon, Breast, Pancreas, Liver, and Ovarian. Several reports on serum GDF-15 as a potential biomarker for diagnosis and prognosis of cancer are hampered by the lack of robust data, with large sample size and critical patient recruitment. However, experimental accounts on cancer tumors, cell lines, and animal models suggest GDF-15's role in cancer progression via endothelial mesenchymal transition, angiogenesis, metastasis, drug resistance and even stemness of various cancers. GDF-15 could be the point of amalgamation for the various hallmarks of cancer and can prove a useful therapeutic target in cancer. The current review was conceptualized with a thought of critically appraising the existing information of GDF-15 in carcinogenesis.