Caregiver's perceptions of COVID-19 vaccination, and intention to vaccinate their children against the disease: a questionnaire based qualitative study.

Coronavirus disease 2019 (COVID-19) vaccine side effects have an important role in the hesitancy of the general population toward vaccine administration. Another reason for vaccine hesitancy might be that healthcare professionals may not address their concerns regarding vaccines appropriately. Regardless, hesitancy in the form of delay, refusal, or acceptance with doubts about its usefulness can limit the downward trajectory of the COVID-19 pandemic. Therefore, the authors conducted a national cross-sectional study (n=306) to assess causes and concerns for vaccine hesitancy in caregivers in Pakistan toward getting their children vaccinated. The questions identified caregivers by socioeconomic demographics, perceived COVID-19 pandemic severity, and concerns toward the COVID-19 vaccine. The majority of the participants were 45-59 years of age (42.8%) with a mean age of 36.11 years (SD: 7.81). A total of 80% of these participants were willing to vaccinate their child with any COVID-19 vaccine. Present comorbidities had a frequency of 28.4% (n=87/306) and only 26.9% (n=66/245) participants were willing to vaccinate their child. Participants with high social standing were 15.4% (n=47/306) with the majority of them being willing to vaccinate their children (45/47). Socioeconomic status (OR:2.911 [0.999-8.483]), and the child's vaccinations being up to date (OR:1.904 [1.078-3.365]) were found to be independent factors for caregivers to be willing to vaccinate their child. Around 62% (n=191/306) were not willing to vaccinate due to the concern for side effects, 67.6% (n=207/306) were not willing because they did not have ample information available, and 51% (n=156/306) were not willing as they were concerned about vaccine effectiveness. Further studies on vaccine safety in the pediatric population are required to improve caregivers' perceptions.

Personal protective equipment and micro-nano plastics: A review of an unavoidable interrelation for a global well-being hazard.

The usage and the demand for personal protective equipments (PPEs) for our day-to-day survival in this pandemic period of COVID-19 have seen a steep rise which has consequently led to improper disposal and littering. Fragmentation of these PPE units has eventually given way to micro-nano plastics (MNPs) emission in the various environmental matrices and exposure of living organisms to these MNPs has proven to be severely toxic. Numerous factors contribute to the toxicity imparted by these MNPs that mainly include their shape, size, functional groups and their chemical diversity. Even though multiple studies on the impacts of MNPs toxicity are available for other organisms, human cell line studies for various plastic polymers, other than the most common ones namely polyethylene (PE), polystyrene (PS) and polypropylene (PP), are still at their nascent stage and need to be explored more. In this article, we cover a concise review of the literature on the impact of these MNPs in biotic and human systems focusing on the constituents of the PPE units and the additives that are essentially used for their manufacturing. This review will subsequently identify the need to gather scientific evidence at the smaller level to help combat this microplastic pollution and induce a more in-depth understanding of its adverse effect on our existence.

Cyclic volatile methyl siloxanes (D4, D5, and D6) as the emerging pollutants in environment: environmental distribution, fate, and toxicological assessments.

Cyclic volatile methyl siloxanes (cVMS) have now become a subject of environmental contamination and risk assessment due to their widespread use and occurrence in different environmental matrices. Due to their exceptional physio-chemical properties, these compounds are diversely used for formulations of consumer products and others implying their continuous and significant release to environmental compartments. This has captured the major attention of the concerned communities on the grounds of potential health hazards to human and biota. The present study aims at comprehensively reviewing its occurrence in air, water, soil, sediments, sludge, dusts, biogas, biosolids, and biota and their environmental behavior as well. Concentrations of cVMS in indoor air and biosolids were higher; however, no significant concentrations were observed in water, soil, and sediments except for wastewaters. No threat to the aquatic organisms has been identified as their concentrations do not exceed the NOEC (maximum no observed effect concentration) thresholds. Mammalian (rodents) toxicity hazards were not very evident except for the occurrence of uterine tumors in very rare cases under long-term chronic and repeated dose exposures in laboratory conditions. Human relevancy to rodents were also not strongly enough established. Therefore, more careful examinations are required to develop stringent weight of evidences in scientific domain and ease the policy making with respect to their production and use so as to combat any environmental consequences.

Cardiovascular disease in pregnancy and its outcome: A prospective study.

Introduction: Prevalence estimates place maternal heart illness anywhere from 0.3 to 3.5 percent. Up to 20.5% of all maternal deaths of non-obstetrical cause are attributable to cardiovascular disease. Aim: The aim of the study was the management of patients with the multidisciplinary approach to maternal cardiovascular disease and its influence on maternal and fetal outcomes in a tertiary care centre. Objectives: 1. To find out the prevalence and spectrum of heart disease in Pregnancy. 2. To find out the outcome of pregnancy with heart disease in a tertiary care centre. Materials and Methods: This prospective study of one year was done on pregnant with heart disease coming to the Obstetrics and Gynaecology department in collaboration with the cardiology department of IGIMS, Patna. A study was done on 65 pregnant with heart disease between the age group 20 to 35 years were compared to a control group of 65 pregnant women who were hospitalised during the same time period but did not have heart disease. All the pregnant women with heart disease were included in this study. Patients with medical disorders like Kidney disease, Liver disease, Pulmonary Disease, Diabetes Mellitus were excluded from the study. We used IBM's SPSS v23 to analyse the collected data. Result: Prevalence of heart disease in pregnancy was 5.8% in present study and mostly of RHD (62.5%), followed by corrected CHD (12.5%) and CHD (10.9%). Patients of NYHA Class I and II (58.5%), Class III (26.2%), and Class IV (15.4%). The mitral valve was most often impacted by RHD (35.3% of all cases), followed by the tricuspid valve (15.0%). Eight (1.1%) people had cardiac surgery for therapeutic reasons. Six percent of all corrective surgeries included closing an atrial septal defect (ASD). The most common kind of congenital abnormality was a ventricular septal defect (VSD, 3%), followed by atrial septal defect (ASD, 1.5%) and pulmonary ductal atresia (PDA, 1.5%). Patients with heart disease had a higher rate of MTP, emergency LSCS and instrumental births than the controls. Deaths during pregnancy were 4 (6.2%) with cardiac disease and no maternal mortality in control group and all belonged to NYHA Class 4 were anaemic. In patients with a left ventricular ejection fraction of 45% or below, death was high. Two women died intrapartum from RHD, and two died postpartum from Peripartum cardiomyopathy. There were significantly more incidences of low-birth-weight infants (36.4%) compared to the control group (p = 0.001). Cases had a statistically significant greater frequency of obstetric problems, as well as an increased risk of developing anaemia, hypertension, hypothyroidism, cholestasis, FGR, and GDM (p-value 0.017). Multiparity, severe valvular lesion, NYHA function class III or IV, arrhythmia, and low ejection fraction were associated with poor maternal outcome in the current study. Conclusion: Maternal morbidity and mortality due to heart disease can be reduced appreciably by antenatal care, early diagnosis, and management with the help of cardiologists and surgery in selected cases.

Self-assembled DNA nanostructure containing oncogenic miRNA-mediated cell proliferation by downregulation of FOXO1 expression.

FOXO1 transcription factor not only limits the cell cycle progression but also promotes cell death as a tumor suppressor protein. Though the expression of FOXO1 is largely examined in breast cancer, the regulation of FOXO1 by miRNA is yet to be explored. In the current study, self-assembled branched DNA (bDNA) nanostructures containing oncogenic miRNAs were designed and transfected to the MCF7 cell line to decipher the FOXO1 expression. bDNA containing oncogenic miRNAs 27a, 96, and 182 synergistically downregulate the expression of FOXO1 in MCF7 cells. The down-regulation is evident both in mRNA and protein levels suggesting that bDNA having miRNA sequences can selectively bind to mRNA and inhibit translation. Secondly, the downstream gene expression of p21 and p27 was also significantly downregulated in presence of miR-bDNA nanostructures. The cell proliferation activity was progressively increased in presence of miR-bDNA nanostructures which confirms the reduced tumor suppression activity of FOXO1 and the downstream gene expression. This finding can be explored to design novel bDNA structures which can downregulate the tumor suppressor proteins in normal cells and induce cell proliferation activity to identify early-phase markers of cancer.

Role of serum C-reactive protein (CRP)/Albumin ratio in predicting the severity of acute pancreatitis: A retrospective cohort.

Acute pancreatitis is a disease with a wide spectrum of severity, complications, and outcome with severe life-threatening complications develop in patients leading to high mortality in severe acute pancreatitis. The rationale of this study is to diagnose the severity of acute pancreatitis using a single test ratio, i.e., CRP/albumin ratio which is a combination of markers for systemic inflammation and nutritional status. All those patients with age group 16-80 years who were diagnosed with acute pancreatitis and admitted subsequently to ICU were included. Severe pancreatitis was determined as CT severity score above 7. About 41% patients out of total 225 had severe pancreatitis. CRP/albumin ratio >4.35 had a sensitivity of 87% and accuracy of 76% to predict acute severe pancreatitis. Elevated CRP/albumin ratio was also associated with complications like multi-organ failure OR: 2.31 [1.3-4.2], duodenal thickening OR: 2.25 [1.2-4.2], and ascites OR: 2.90 [1.5-5.6]. Although, the severity of this elevation varied with different age groups, such non-invasive and readily available parameters should be relied upon admission to risk stratify the patients suffering from pancreatitis. CRP/albumin ratio has higher sensitivity and negative predictive value to predict severe pancreatitis than CRP alone and hence give additional advantage as a prognostic marker, although Delong's test to compare AUROC was indifferent (P-value: 0.22).

Use of enzymatic biomarkers of Labeo rohita to study the effect of polybrominated diphenyl ether (BDE- 209) via dietary exposure in laboratory conditions.

Fishes have been widely used as a representative to estimate the health of an aquatic ecosystem. In the present study, Labeo rohita was selected for biomarker study against decabromodiphenyl ether (BDE-209), a persistent organic pollutant (POP), as it is a widely used Indian carp. The results suggested significant effects on the optimum metabolism of Labeo rohita. After 48 to 72 h of exposure, most of the biomarkers such as lactate dehydrogenase (LDH), creatine kinase (CK), serum glutamic pyruvic transaminase (SGPT), serum glutamic oxaloacetic transaminase (SGOT), and hepatosomatic index (HSI) increased drastically indicating the higher index of tissue and liver damage. On the contrary, succinic dehydrogenase (SDH), acetylcholinesterase (AChE), and alkaline phosphatase (ALP) showed a reverse trend suggesting the shifting of fish metabolism towards anaerobic respiration mode because of induced stress. Increased catalase (CAT) activity was also observed, which indicated increased abundance of reactive hydroxyl species and therefore a possible oxidative stress in fishes. It is further suggested to understand and examine the biotransformation characteristics and degradation pathways of polybrominated diphenyl ether (PBDE)s, which would be useful to comprehend their environmental fate.

Regulatory roles of RNA modifications in breast cancer.

Collectively referred to as the epitranscriptome, RNA modifications play important roles in gene expression control regulating relevant cellular processes. In the last few decades, growing numbers of RNA modifications have been identified not only in abundant ribosomal (rRNA) and transfer RNA (tRNA) but also in messenger RNA (mRNA). In addition, many writers, erasers and readers that dynamically regulate the chemical marks have also been characterized. Correct deposition of RNA modifications is prerequisite for cellular homeostasis, and its alteration results in aberrant transcriptional programs that dictate human disease, including breast cancer, the most frequent female malignancy, and the leading cause of cancer-related death in women. In this review, we emphasize the major RNA modifications that are present in tRNA, rRNA and mRNA. We have categorized breast cancer-associated chemical marks and summarize their contribution to breast tumorigenesis. In addition, we describe less abundant tRNA modifications with related pathways implicated in breast cancer. Finally, we discuss current limitations and perspectives on epitranscriptomics for use in therapeutic strategies against breast and other cancers.

Interaction of artemisinin protects the activity of antioxidant enzyme catalase: A biophysical study.

The major antioxidant enzyme catalase is downregulated and the enzyme activity is compromised in various disease conditions such as malarial and cancer. Hence, the restoration and protection of catalase is a promising therapeutic strategy in disease management. In the present study, for the first time we have demonstrated the protective role of well-known anti-malarial drug Artemisinin (ART) on the time and temperature-induced degradation of bovine liver catalase (BLC) activity. The findings at different time intervals and at higher temperature showed the protective role of ART on BLC activity. Molecular docking studies suggested specific binding of ART on BLC through heme group interface which was further supported by cyclic voltammetry and dynamic light scattering study. The stabilization of BLC in presence of ART was mediated through forming a BLC-ART complex with reduced and shifted electrochemical peak and increased hydrodynamic diameter. ART substantially prevents the temperature-induced reduction in α-helical content with simultaneous increment in other secondary structures like antiparallel, parallel, ß-turn and random coils. Nevertheless, the protective role of ART was accepted from the enhanced thermal stability and increased Tm value of BLC in presence of ART at higher temperatures. Our results uncover the mechanism of interaction between ART with BLC and suggest the protective role of ART towards spatiotemporal alteration of BLC by preventing the structural and molecular change in BLC. Thus, the findings advocate ART as a potential therapeutic drug for diseases associated with reduced catalase activity.

miRNA-mediated alteration of sulfatase modifying factor 1 expression using self-assembled branched DNA nanostructures.

Sulfatase enzymes catalyze sulfate ester hydrolysis, thus deficiencies of sulfatases lead to the accumulation of biomolecules resulting in several disorders. One of the important sulfatases is estrone sulfatase that converts inactive estrone sulfate to active estradiol. Posttranslational modification of highly conserved cysteine residue leads to unique formylglycine in the active site of sulfatases being critical for its catalytic activity. The essential factor responsible for this modification of sulfatase is Sulfatase-Modifying Factor 1 (SUMF1). The role of estrone sulfatase is well evident in breast cancer progression. However, the function and regulation of SUMF1 in cancer are not studied. In the present study, for the first time, we have assessed the expression of SUMF1 in breast cancer and report the oncogenic behavior upon overexpression of SUMF1. Although increased expression or activity of SUMF1 is anticipated based on its function, the expression of SUMF1 was found to be reduced in breast cancer cells at both mRNA and protein levels. An estrogen receptor (ER) dependent expression of SUMF1 was observed and higher SUMF1 expression is associated with improved breast cancer patient survival in ER-positive cases. However, high SUMF1 expression leads to reduced median survival in ER-negative breast cancer patients. Putative binding sites for miRNAs-106b-5p, 128-3p and 148b-3p were found at 3'-UTR of SUMF1. Since self-assembled branched DNA (bDNA) structures have emerged as a highly efficient strategy for targeting multiple miRNAs simultaneously, we studied the alteration in SUMF1 expression using bDNA nanostructures with a complementary sequence to miRNAs. The findings suggest the involvement of co-regulators and repressors in miRNA-mediated SUMF1 expression in breast cancer cells and reveal the therapeutic potential of SUMF1 in endocrine-related malignancies.

The benzene metabolite p-benzoquinone inhibits the catalytic activity of bovine liver catalase: A biophysical study.

The current communication reports the inhibitory effect of para-benzoquinone (p-BQ) on the structure and function of bovine liver catalase (BLC), a vital antioxidant enzyme. Both BLC and p-BQ were dissolved in respective buffers and the biophysical interaction was studied at physiological concentrations. For the first time our data reveals an enthalpy-driven interaction between BLC and p-BQ which is due to hydrogen bonding and van der Waals interactions. The binding affinity of p-BQ with BLC is nearly 2.5 folds stronger in MOPS buffer than Phosphate buffer. Importantly, the binding affinity between BLC and p-BQ was weak in HEPES buffer as compared to other buffers being the strongest in Tris buffer. Molecular docking studies reveal that binding affinity of p-BQ with BLC differ depending upon the nature of buffers rather than on the participating amino acid residues of BLC. This is further supported by the differential changes in secondary structures of BLC. The p-BQ-induced conformational change in BLC was evident from the reduced BLC activity in presence of different buffers in the following order, Phosphate>MOPS>Tris>HEPES. The absorbance peak of BLC was gradually increased and fluorescence spectra of BLC were drastically decreased when BLC to p-BQ molar ratio was incrementally enhanced from 0 to 10,000 times in presence of all buffers. Nevertheless, the declined activity of BLC was positively correlated with the reduced fluorescence and negatively correlated with the enhanced absorbance. Electrochemical study with cyclic voltammeter also suggests a direct binding of p-BQ with BLC in presence of different buffers. Thus, p-BQ-mediated altered secondary structure in BLC results into compromised activity of BLC.

EZH2 knockdown in tamoxifen-resistant MCF-7 cells unravels novel targets for regaining sensitivity towards tamoxifen.

BACKGROUND: Acquired resistance to drug involves multilayered genetic and epigenetic regulation. Inhibition of EZH2 has proven to reverse the tamoxifen resistance back to the sensitive state in breast cancer. However, the molecular players involved in EZH2-mediated effects on tamoxifen-resistant MCF-7 cells are unknown. This study was conducted to understand the global change in proteome profile of tamoxifen-resistant MCF-7 breast cancer cells upon EZH2 knockdown. METHODS: Tamoxifen resistance MCF-7 breast cancer cells were established using increasing concentrations of 4-hydroxy tamoxifen. Using label free proteomics approach, we studied the alteration in total proteome in resistant cells as well as cells transfected with siEZH2 in comparison to sensitive and cells transfected with non-targeting siRNA. RESULTS: Here, we report list of proteins that were previously not recognized for their role in tamoxifen resistance and hold a close association with breast cancer patient survival. Proteins Annexin A2, CD44, nucleosome assembly protein 1, and lamin A/C were among the most upregulated protein in tamoxifen-resistant cells that were found to be abrogated upon EZH2 knockdown. The study suggests the involvement for various proteins in acquiring resistance towards tamoxifen and anticipates further research for investigating their therapeutic potentials. CONCLUSION: Overall, we propose that targeting EZH2 or the molecules down the cascade might be helpful in reacquiring sensitivity to tamoxifen in breast cancer.

Glutathione reductase and catalase as potential biomarkers for synergistic intoxication of pesticides in fish.

Synergy occurs when chemicals give pronounced effect on combination in contrast to their individual effect. The objective of this study was to investigate the synergistic effect of pesticides carbaryl (C) and methyl parathion (MP) on oxidative stress biomarkers viz catalase (CAT), glutathione reductase (GSSG-R) including different enzymes like lactate dehydrogenase (LDH), succinate dehydrogenase (SDH) and acetyl cholinesterase (AChE) in different tissues of carps Catla catla. Fishes were exposed to 6.25 mg/L of MP and 2.3 mg/L of C in mixture (one-third of LC50 value). CAT and GSSG-R were studied in gills, brain, liver and muscle of carp were found to be elevated significantly (p < 0.005). LDH activity increased significantly (p < 0.005) in synergistic group, there was a seven-fold (748%) increase in LDH activity in muscle compared to individual studies with same pesticides. Contrary to LDH, sudden decrease in SDH activity was accounted. Significant (p < 0.005) decrease in AChE activity after initial 24 h was remarkable addressing to the shift in neurotransmission pathway in organism. Significant increase was observed in activity of CAT and GSSG-R in all tissues compared to control fishes in individual as well as synergistic (MP + C) group suggesting that CAT and GSSG-R can be a potential biomarker of oxidative stress when studied in combination.

Genome-wide expression analysis reveals six contravened targets of EZH2 associated with breast cancer patient survival.

Several pioneering work have established that apart from genetic alterations, epigenetic modifications contribute significantly in tumor progression. Remarkable role of EZH2 in cancer highlights the importance of identifying its targets. Although much emphasis has been placed in recent years in designing drugs and inhibitors targeting EZH2, less effort has been given in exploring its existing targets that will help in understanding the oncogenic role of EZH2 in turn which may provide a more stringent method of targeting EZH2. In the present study, we validated six direct targets of EZH2 that are GPNMB, PMEPA1, CoL5A1, VGLL4, POMT2 and SUMF1 associated with cancer related pathways. Upon EZH2 knockdown, more than two fold increase in the target gene expression was evident. CHIP-qPCR performed in both MCF-7 and MDA-MDA-231 confirmed the in-vivo binding of EZH2 on its identified target. Thirty invasive breast carcinoma cases with their adjacent normal tissues were included in the study. Immunohistochemistry in primary breast tumor tissue array showed tumor dependent expression of EZH2. Array of MERAV expression database revealed the strength of association of EZH2 with its target genes. Real time PCR performed with RNA extracted from breast tumor tissues further authenticated the existing negative correlation between EZH2 and its target genes. Pearson correlation coefficient & statistical significance computed using the matrix provided in the database strengthened the negative correlation between identified target genes and EZH2. KM plotter analysis showed improved relapse-free survival with increased expression of PMEPA1, POMT2, VGLL4 and SUMF1 in breast cancer patients indicating their therapeutic potential. While investigating the relevance of these target genes, different mutations of them were found in breast cancer patients. Seeking the clinical relevance of our study, following our recent publication that reports the role of EZH2 in nicotine-mediated breast cancer development and progression, we observed significant reduced expression of SUMF1 in breast cancer patient samples with smoking history in comparison to never-smoked patient samples.

Emission from open burning of municipal solid waste in India.

Open burning of Municipal Solid Waste (MSW) is a potential non-point source of emission, which causes greater concern especially in developing countries such as India. Lack of awareness about environmental impact of open burning, and ignorance of the fact, i.e. 'Open burning is a source of emission of carcinogenic substances' are major hindrances towards an appropriate municipal solid waste management system in India. The paper highlights the open burning of MSW practices in India, and the current and projected emission of 10 major pollutants (dioxin, furans, particulate matter, carbon monoxide, sulphur oxides, nitrogen oxides, benzene, toluene, ethyl benzene and 1-hexene) emitted due to the open burning of MSW. Waste to Energy potential of MSW was also estimated adopting effective biological and thermal techniques. Statistical techniques were applied to analyse the data and current and projected emission of various pollutants were estimated. Data pertaining to population, MSW generation and its collection efficiency were compiled for 29 States and 7 Union Territories. Thereafter, emission of 10 pollutants was measured following methodology prescribed in Intergovernmental Panel on Climate Change guideline for National Greenhouse Gas Inventories, 2006. The study revealed that people living in Metropolitan cities are more affected by emissions from open burning.

Estrogen-related receptors alpha, beta and gamma expression and function is associated with transcriptional repressor EZH2 in breast carcinoma.

BACKGROUND: Orphan nuclear receptors ERRα, ERRß and ERRγ that belong to NR3B or type IV nuclear receptor family are well studied for their role in breast cancer pathophysiology. Their homology with the canonical estrogen receptor dictates their possible contributing role in mammary gland development and disease. Although function and regulation of ERRα, ERRγ and less about ERRß is reported, role of histone methylation in their altered expression in cancer cells is not studied. Transcriptional activity of nuclear receptors depends on co-regulatory proteins. The present study for the first time gives an insight into regulation of estrogen-related receptors by histone methylation specifically through methyltransferase EZH2 in breast cancer. METHODS: Expression of ERRα, ERRß, ERRγ and EZH2 was assessed by immunohistochemistry in four identical tissue array slides that were prepared as per the protocol. The array slides were stained with ERRα, ERRß, ERRγ and EZH2 simultaneously. Array data was correlated with expression in MERAV expression dataset. Pearson correlation coeficient r was calculated from the partial matrix expression values available at MERAV database to study the strength of association between EZH2 and three orphan nuclear receptors under study. By western blot and real time PCR, their correlated expression was studied in breast cancer cell lines MCF-7, MDA-MB-231, T47D and MDA-MB-453 including normal breast epithelial MCF-10A cells at both protein and RNA level. Regulation of ERRα, ERRß, ERRγ by EZH2 was further investigated upon overexpression and silencing of EZH2. The interaction between ERRs and EZH2 was validated in vivo by CHIP-qPCR. RESULTS: We found a negative correlation between estrogen-related receptors and Enhancer of Zeste Homolog 2, a global repressor gene. Immunohistochemistry in primary breast tumors of different grades showed a correlated expression of estrogen-related receptors and EZH2. Their correlated expression was further validated using online MERAV expression dataset where a negative correlation of variable strengths was observed in breast cancer. Ectopic expression of EZH2 in low EZH2-expressing normal breast epithelial cells abrogated their expression and at the same time, its silencing enhanced the expression of estrogen-related receptors in cancerous cells. Global occupancy of EZH2 on ERRα and ERRß was observed in-vivo. CONCLUSION: Our findings identify EZH2 as a relevant coregulator for estrogen-related receptors in breast carcinoma.

Nicotine associated breast cancer in smokers is mediated through high level of EZH2 expression which can be reversed by methyltransferase inhibitor DZNepA.

Recent studies show substantial growth-promoting properties of nicotine (NIC) in cancer, which is a combined outcome of genetic and epigenetic alterations. However, the role of epigenetic modifiers in response to NIC in breast cancer is less studied. In the present study, for the first time we have shown NIC-induced enhanced EZH2 expression. Six pairs of smoking-associated breast cancer patient tissues were analyzed. Samples from smoking breast cancer patients showed distinguished enhanced EZH2 expression in comparison to non-smoking ones. The upregulation in EZH2, which is due to NIC, was further confirmed in breast carcinoma cell lines using 10 µM NIC, 1 µM DZNepA, and EZH2si. The upregulation of EZH2 was concomitant with upregulation in Myc and α9-nAChR. The xenograft of breast cancer cells in BALB/c nude mice in the presence or absence of NIC showed significantly higher tumor uptake in the NIC injected group, which clearly demonstrates the effect of NIC in breast cancer progression. Interestingly, DZNepA considerably suppressed the NIC-mediated tumor growth. CHIP-qPCR assay confirmed the increased Myc enrichment on EZH2 promoter upon NIC treatment, thereby strengthening our findings that there exists an association between NIC, Myc, and EZH2. Overall, the present study identifies a strong association between NIC and EZH2 particularly in the progression of breast cancer in smokers through a novel axis involving nAChR and Myc. Moreover, the findings provide preliminary evidence suggesting potential of high level of EZH2 expression as a prognostic marker in smoking-associated breast cancer.

Transcriptome analysis of genes associated with breast cancer cell motility in response to Artemisinin treatment.

BACKGROUND: Well-known anti-malarial drug artemisinin exhibits potent anti-cancerous activities. In-vivo and in-vitro studies showed its anti-tumor and immunomodulatory properties signifying it as a potent drug candidate for study. The studies of mechanisms of cell movement are relevant which can be understood by knowing the involvement of genes in an effect of a drug. Although cytotoxicity and anti-proliferative activity of artemisinin is evident, the genes participating in its anti-migratory and reduced invasive effect are not well studied. The present study reports the alteration in the expression of 84 genes involved in cell motility upon artemisinin treatment in MCF-7 breast cancer cells using pathway focused gene expression PCR array. In addition, the effect of artemisinin on epigenetic modifier HDACs is studied. METHODS: We checked the functional stimulus of artemisinin on cell viability, migration, invasion and apoptosis in breast cancerous cell lines. Using qRT-PCR and western blot, we validated the altered expression of relevant genes associated with proliferation, migration, invasion, apoptosis and mammary gland development. RESULTS: Artemisinin inhibited cell proliferation of estrogen receptor negative breast cancer cells with fewer efficacies in comparison to estrogen receptor positive ones. At the same time, cell viability and proliferation of normal breast epithelial MCF10A cells was un-affected. Artemisinin strongly inhibited cancer cell migration and invasion. Along with orphan nuclear receptors (ERRα, ERRß and ERRγ), artemisinin altered the ERα/ERß/PR/Her expression status of MCF-7 cells. The expression of genes involved in the signaling pathways associated with proliferation, migration, invasion and apoptosis was significantly altered which cooperatively resulted into reduced growth promoting activities of breast cancer cells. Interestingly, artemisinin exhibited inhibitory effect on histone deacetylases (HDACs). CONCLUSIONS: Upregulated expression of tumor suppressor genes along with reduced expression of oncogenes significantly associated with growth stimulating signaling pathways in response to artemisinin treatment suggests its efficacy as an effective drug in breast cancer treatment.

Investigation of polybrominated diphenyl ethers in old consumer products in India.

Polybrominated diphenyl ethers (PBDEs) used extensively over the past 3 decades as flame retardants in most types of polymers, all over the world, have been identified as global pollutants. PBDEs pose various health problems such as thyroid hormone disruption, permanent learning and memory impairment, behavioral changes, hearing deficits, delayed puberty onset, fetal malformations, and possibly cancer. Many measurements of PBDEs in various matrices from Sweden, Holland, Japan, the USA, and elsewhere have been reported, but few measurements are available for India. In this study, a preliminary screening of different congeners of PBDEs has been performed in different old electronic and consumer products with an objective to build capacity in order to analyze PBDEs and BFRs. Six different samples, foam from upholstery, motherboard of a computer, children toy composite sample, old vanishing window blind sample, electrical wire sample, and PVC flooring sample, were collected and analyzed for the presence of the following PBDE congeners: BDE-28, BDE-47, BDE-99, BDE-100, BDE-153, BDE-154, BDE-183, and BDE-209. It was found that three out of six samples were positive for the presence of PBDEs. Three congeners were detected in the samples, i.e., BDE-47, BDE-153, and BDE-209, of which, highest concentration was of BDE-209. Among the samples, motherboard of computer showed the highest concentration of BDE-209 followed by window blind and foam from upholstery. The results of this preliminary investigation indicate that PBDEs are still present in the old consumer products which can be an important additional source of exposure to the population.