Aluminum oxide and zinc oxide induced nanotoxicity in rat brain, heart, and lung.

Nanomaterials or nanoparticles are commonly used in the cosmetics, medicine, and food industries. Many researchers studied the possible side effects of several nanoparticles including aluminum oxide (Al2O3-nps) and zinc oxide nanoparticles (ZnO-nps). Although, there is limited information available on their direct or side effects, especially on the brain, heart, and lung functions. This study aimed to investigate the neurotoxicity, cardiotoxicity, and lung toxicity induced by Al2O3-nps and ZnO-nps or in combination via studying changes in gene expression, alteration in cytokine production, tumor suppressor protein p53, neurotransmitters, oxidative stress, and the histological and morphological changes. Obtained results showed that Al2O3-nps, ZnO-nps and their combination cause an increase in 8-hydroxy-2´-deoxyguanosine (8-OHdG), cytokines, p53, oxidative stress, creatine kinase, norepinephrine, acetylcholine (ACh), and lipid profile. Moreover, significant changes in the gene expression of mitochondrial transcription factor-A (mtTFA) and peroxisome proliferator activator receptor-gamma-coactivator-1alpha (PGC-1alpha) were also noted. On the other hand, a significant decrease in the levels of antioxidant enzymes, total antioxidant capacity (TAC), reduced glutathione (GSH), paraoxonase 1 (PON1), neurotransmitters (dopamine - DA, and serotonin - SER), and the activity of acetylcholine esterase (AChE) in the brain, heart, and lung were found. Additionally, these results were confirmed by histological examinations. The present study revealed that the toxic effects were more when these nanoparticle doses are used in combination. Thus, Al2O3-nps and ZnO-nps may behave as neurotoxic, cardiotoxic, and lung toxic, especially upon exposure to rats in combination.

COVID-19, oxidative stress, and male reproductive dysfunctions: is vitamin C a potential remedy?

Few peculiarities have been observed in the etiology of coronavirus disease 2019 (COVID-19), one such being its greater prevalence in men than women partly due to the higher expressions of angiotensin-converting enzyme-2 (ACE2) in the male reproductive tissues. Recent scientific reports are in line with some of the evidence-based hypotheses in the initial phase of the COVID-19 pandemic, regarding the involvement of oxidative stress (OS) and oxidant-sensitive pathways in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection-mediated male reproductive disruptions. The seminal dissemination of SARS-CoV-2 or its components, testicular disruptions due to viral infection and oxidative damage in the testis have all been evidenced recently. High-dose of antioxidants, such as vitamin C, have been shown to be a useful treatment for COVID-19 patients, to alleviate systemic inflammation and OS. In addition, vitamin C is a major testicular antioxidant that neutralizes excess reactive oxygen species (ROS), prevents sperm agglutination, prevents lipid peroxidation, recycles vitamin E, and protects against DNA damage. Thus, the present review aims to discuss the mechanism of COVID-19-mediated male reproductive dysfunctions, based on the evidence available so far, and explore the possibility of using vitamin C in alleviating testicular OS and associated damage caused by COVID-19.

Is there impact of the SARS-CoV-2 pandemic on steroidogenesis and fertility?

In December of 2019, several cases of unknown atypical respiratory diseases emerged in Wuhan, Hubei Province in China. After preliminary research, it was stated that the disease is transmittable between humans and was named COVID-19. Over the course of next months, it spread all over the world by air and sea transport and caused a global pandemic which affects life of everyone now-a-days. A large number of countries, have since been forced to take precautions such as curfews, lockdowns, wearing facemasks etc. Even with vaccines being produced in mass numbers, lack of targeted therapy continues to be a major problem. According to studies so far it seems that elderly people are more vulnerable to severe symptoms while children tend to by asymptomatic or have milder form the disease. In our review, we focused on gathering data about the virus itself, its characteristics, paths of transmission, and its effect on hormone production and secretion. In such, there is insufficient information in the literature worldwide, especially the ones that focus on the effect of COVID-19 on individual organs systems within the human body. Hence, the present evidence-based study focused on the possible effects of COVID-19 on adrenal gland and gonads i.e. on the process of steroidogenesis and fertility.

Human Adrenocortical Carcinoma (NCI-H295R) Cell Line as an In Vitro Cell Culture Model for Assessing the Impact of Iron on Steroidogenesis.

The aim of this in vitro study was to examine the dose-dependent effects of iron as a potential endocrine disruptor in relation to the release of sexual steroid hormones by a human adrenocortical carcinoma (NCI-H295R) cell line. The cells were exposed to different concentrations (3.90, 62.50, 250, 500, 1000 µM) of FeSO4.7H2O and compared with the control group (culture medium without FeSO4.7H2O). Cell viability was measured by the metabolic activity assay. Quantification of sexual steroid production was performed by enzyme-linked immunosorbent assay. Following 48 h culture of the cells in the presence of FeSO4.7H2O, significantly (P < 0.001) increased production of progesterone was observed at the lowest concentration (3.90 µM) of FeSO4.7H2O, whereas the lowest release of progesterone by NCIH295R cells was noted after addition of 1000 µM of FeSO4.7H2O, which did not elicit cytotoxic action (P > 0.05). Testosterone production was substantially increased at the concentrations ≤ 62.50 µM of FeSO4.7H2O. Lower levels of testosterone were recorded in the groups with higher concentrations (≥ 250 µM) of FeSO4.7H2O (P > 0.05). The presented data suggest that iron has no endocrine disruptive effect on the release of sexual steroid hormones, but its toxicity may be reflected at other points of the steroidogenesis pathway.

Immunotherapy for Alzheimer's Disease: Current Scenario and Future Perspectives.

Alzheimer's disease (AD) is a global health concern owing to its complexity, which often poses a great challenge to the development of therapeutic approaches. No single theory has yet accounted for the various risk factors leading to the pathological and clinical manifestations of dementia-type AD. Therefore, treatment options targeting various molecules involved in the pathogenesis of the disease have been unsuccessful. However, the exploration of various immunotherapeutic avenues revitalizes hope after decades of disappointment. The hallmark of a good immunotherapeutic candidate is not only to remove amyloid plaques but also to slow cognitive decline. In line with this, both active and passive immunotherapy have shown success and limitations. Recent approval of aducanumab for the treatment of AD demonstrates how close passive immunotherapy is to being successful. However, several major bottlenecks still need to be resolved. This review outlines recent successes and challenges in the pursuit of an AD vaccine.

Antioxidative effect of dietary flavonoid isoquercitrin on human ovarian granulosa cells HGL5 in vitro.

This study aimed to examine the effect of dietary flavonoid isoquercitrin on ovarian granulosa cells using the immortalized human cell line HGL5. Cell viability, survival, apoptosis, release of steroid hormones 17beta-estradiol and progesterone, and human transforming growth factor-beta2 (TGF-beta2) and TGF-beta2 receptor as well as intracellular reactive oxygen species (ROS) generation were investigated after isoquercitrin treatment at the concentration range of 5-100 microg.ml-1. It did not cause any significant change (p>0.05) in cell viability as studied by AlamarBlue assay in comparison to control. No significant change was observed (p>0.05) in the proportion of live, dead and apoptotic cells as revealed by apoptotic assay using flow cytometry. Similarly, the release of 17beta-estradiol, progesterone, TGF-beta2 and its receptor were not affected significantly (p>0.05) by isoquercitrin as detected by ELISA, in comparison to control. Except for the highest concentration of 100 microg.ml-1, which led to oxidative stress, isoquercitrin exhibited antioxidative activity at lower concentration used in the study (5, 10, 25, and 50 microg.ml-1) by hampering the production of intracellular ROS, in comparison to control, as detected by chemiluminescence assay (p<0.05). Findings of the present study indicate an existence of the antioxidative pathway that involves inhibition of intracellular ROS generation by isoquercitrin in human ovarian granulosa cells.

Ovarian steroid hormone secretion by human granulosa cells after supplementation of sambucus nigra l. extract.

Beneficial effects of Sambucus nigra L. (black elder) as a traditional medicine have been associated with the phytoconstituents including polyphenols, terpenes and lectins. Various antioxidant rich natural products have also been implicated with improvement of reproductive health and fertility, however, the effect of Sambucus nigra on the ovarian cell functions has not been investigated yet. The objectives of the present study were to screen the polyphenols in the elderflower and elderberry extracts, and to examine the secretion activity of steroid hormones 17beta-estradiol and progesterone by human ovarian granulosa cells HGL5 after supplementation of the extracts at a concentration range of 12.5 to 100 microg.ml-1. Qualitative as well as quantitative screening of polyphenols by high-performance liquid chromatography with diode-array detector (HPLC-DAD) analysis revealed rutin to be the most abundant polyphenol in both elderflower and elderberry extracts. In culture, neither elderflower nor elderberry extract caused any significant impact (p>0.05) in cell viability as studied by AlamarBlue assay in comparison to control. However, a dose-dependent stimulation of 17beta-estradiol release was detected by ELISA after supplementation of elderflower (at 50 microg.ml-1; p<0.01) and elderberry (at 100 microg.ml-1; p<0.05) extracts at higher doses used in the study. On the other hand, both elderflower and elderberry extracts stimulated the secretion of progesterone by HGL5 cells at a lower dose (12.5 microg.ml-1; p<0.05), as compared to control. Therefore, elderflower and elderberry extracts may have the potential to regulate steroidogenesis in ovarian cells.

In vitro assessment of the impact of nickel on the viability and steroidogenesis in the human adrenocortical carcinoma (NCI-H295R) cell line.

Nickel is a ubiquitous environmental pollutant, which has various effects on reproductive endocrinology. In this study, human adrenocortical carcinoma (NCI-H295R) cell line was used as an in vitro biological model to study the effect of nickel chloride (NiCl2) on the viability and steroidogenesis. The cells were exposed to different concentrations (3.90; 7.80; 15.60; 31.20; 62.50; 125; 250 and 500 microM) of NiCl2 and compared with control group (culture medium without NiCl2). The cell viability was measured by the metabolic activity assay. Production of sexual steroid hormones was quantified by enzyme linked immunosorbent assay. Following 48 h culture of the cells in the presence of NiCl2 a dose-dependent depletion of progesterone release was observed even at the lower concentrations. In fact, lower levels of progesterone were detected in groups with higher doses (>/=125 microM) of NiCl2 (P<0.01), which also elicited cytotoxic action. A more prominent decrease in testosterone production (P<0.01) was also noted in comparison to that of progesterone. On the other hand, the release of 17beta-estradiol was substantially increased at low concentrations (3.90 to 62.50 microM) of NiCl2. The cell viability remained relatively unaltered up to 125 microM (P>0.05) and slightly decreased from 250 microM of NiCl2 (P<0.05). Our results indicate endocrine disruptive effect of NiCl2 on the release of progesterone and testosterone in the NCI-H295R cell line. Although no detrimental effect of NiCl2 (

Coenzyme Q10 ameliorates cadmium induced reproductive toxicity in male rats.

This study aimed at investigating the protective role of CoQ10 against cadmium (Cd)-induced reproductive toxicity in male rats. Adult male Wistar rats were exposed to an acute dose of Cd (25 mg/kg bwt; Cd group), Cd+CoQ10 (25 mg/kg bwt Cd+10 mg CoQ10; Cd-Q10 group) and distilled water (control) in vivo for 15 consecutive days and semen quality was assessed. A significant reduction was noted in sperm concentration, progressive motility, morphology and DNA integrity in both Cd- and Cd-Q10 groups in comparison to control indicating Cd-induced testicular lipid per oxidation (LPO) and decline in indigenous antioxidant defense system as measured by total antioxidant capacity (TAC) (p<0.05). However, simultaneous co-administration of CoQ10 along with Cd (Cd-Q10 group) was able to improve sperm concentration, motility, progressive motility, morphology, DNA integrity, and testicular TAC as well as lower LPO compared to Cd group (p<0.05). Results indicate that used dose of CoQ10 is capable of moderately ameliorating reproductive toxicity of Cd by improving semen quality and reducing testicular oxidative stress.

Human sperm handling in intracytoplasmic sperm injection processes: In vitro studies on mouse oocyte activation, embryo development competence and sperm oxidation-reduction potential.

Polyvinylpyrrolidone (PVP) and hyaluronic acid (HA) are routinely used in handling spermatozoa for intracytoplasmic sperm injection (ICSI). As there are still concerns about possible adverse effects on the embryo, this study investigated sperm handling in a mouse ICSI model to (i) evaluate oocyte activation after injection of spermatozoa selected for rotational or linear motion in PVP; (ii) assess the effect of sperm selection in PVP, HA and medium on oocyte activation; (iii) examine the effects of PVP and HA on parthenogenetic oocyte activation and embryo development; and (iv) assess the oxidation-reduction potential (ORP) of spermatozoa exposed to PVP, HA or medium. Oocyte activation was higher when spermatozoa exhibited rotational motion rather than linear motion (79% vs. 52%; p = .05). There was no difference in oocyte activation and embryo development after parthenogenetic oocyte activation after sperm injection using PVP, HA or medium-incubated spermatozoa. PVP-selected spermatozoa exhibited lower (p < .0001) ORP levels than using HA. Thus, results indicate that the sperm handling method and the type of medium used impact ICSI outcomes. Overall, sperm incubation in PVP, HA and medium yields similar outcomes with regard to oocyte activation and embryo development. However, PVP provides more antioxidative protection than HA and should therefore be preferred for sperm manipulation.

Cumene hydroperoxide induced changes in oxidation-reduction potential in fresh and frozen seminal ejaculates.

Oxidation-reduction potential (ORP) is a newer integrated measure of the balance between total oxidants (reactive oxygen species-ROS) and reductants (antioxidants) that reflects oxidative stress in a biological system. This study measures ORP and evaluates the effect of exogenous induction of oxidative stress by cumene hydroperoxide (CH) on ORP in fresh and frozen semen using the MiOXSYS Analyzer. Semen samples from healthy donors (n = 20) were collected and evaluated for sperm parameters. All samples were then flash-frozen at -80°C. Oxidative stress was induced by CH (5 and 50 µmoles/ml). Static ORP (sORP-(mV/106 sperm/ml) and capacity ORP (cORP-µC/106 sperm/ml) were measured in all samples before and after freezing. All values are reported as mean ± SEM. Both 5 and 50 µmoles/ml of CH resulted in a significant decline in per cent motility compared to control in pre-freeze semen samples. The increase in both pre-freeze and post-thaw semen samples for sORP was higher in the controls than with 50 µmoles/ml of CH. The change from pre-freeze to post-thaw cORP was comparable. The system is a simple, sensitive and portable tool to measure the seminal ORP and its dynamic impact on sperm parameters in both fresh and frozen semen specimens.

Ovarian steroid hormone secretion activity examined after supplementation of green tea extract.

This study aimed at examining the secretion activity of steroid hormones progesterone and 17beta-estradiol by porcine ovarian granulosa cells after addition of green tea extract. Granulosa cells were incubated with green tea extract (at doses of 0.01, 0.1, 1, 10 and 100 microg.ml(-1). Another set of cells were incubated with green tea extract at the above doses along with additional supplementation of follicle stimulating hormone (FSH) at 10 microg.ml(-1). Release of hormones by granulosa cells was assessed by EIA after 24 h exposure. Secretion of steroid hormones was not affected either by green tea extract alone or after FSH supplementation with green tea extract. Results indicate that ovarian steroidogenesis is not affected by green tea under conditions used in the experiment.

Incidence of Cryptosporidium andersoni in diarrheal patients from southern Assam, India: a molecular approach.

The distribution and public health significance of Cryptosporidium species and genotypes in humans and bovine differ across geographical areas. Cryptosporidium species causes a disease known as cryptosporidiosis in humans and animals. To characterize the prevalence of cryptosporidiosis in humans in southern Assam, India, stool samples (n = 1119) of diarrhea patients were collected from different hospitals and from the community during the period January 2014 to July 2016. Fecal smears were examined microscopically for Cryptosporidium species using modified acid fast staining and were screened to ascertain the presence of Cryptosporidium antigen by enzyme-linked immunosorbent assay (ELISA). The genomic DNA of positive fecal samples were analyzed by nested polymerase chain reaction (PCR), which were subsequently genotyped by PCR-restriction fragment length polymorphism (RFLP), based on small subunit (SSU) 18S rRNA. It was found that the prevalence of Cryptosporidium spp. was high during the monsoon season. The average infection rate of Cryptosporidium spp. was found to be 2.4% (27/1119) microscopically. When subjected to nested PCR using amplification of the 18S rRNA gene, Cryptosporidium was found to be 8.57% (98/1119). Based on the 18S rRNA gene, two Cryptosporidium spp., namely Cryptosporidium andersoni (6.97%: 78/1119) and Cryptosporidium parvum (1.7%: 20/1119), were identified. Cryptosporidium andersoni infections were found to be of either zoonotic or anthroponotic origin. The prevalence was statistically significant (p = 0.03, R2 = 0.042) considering age, gender, and cast.

DNA damage-induced ephrin-B2 reverse signaling promotes chemoresistance and drives EMT in colorectal carcinoma harboring mutant p53.

Mutation in the TP53 gene positively correlates with increased incidence of chemoresistance in different cancers. In this study, we investigated the mechanism of chemoresistance and epithelial-to-mesenchymal transition (EMT) in colorectal cancer involving the gain-of-function (GOF) mutant p53/ephrin-B2 signaling axis. Bioinformatic analysis of the NCI-60 data set and subsequent hub prediction identified EFNB2 as a possible GOF mutant p53 target gene, responsible for chemoresistance. We show that the mutant p53-NF-Y complex transcriptionally upregulates EFNB2 expression in response to DNA damage. Moreover, the acetylated form of mutant p53 protein is recruited on the EFNB2 promoter and positively regulates its expression in conjunction with coactivator p300. In vitro cell line and in vivo nude mice data show that EFNB2 silencing restores chemosensitivity in mutant p53-harboring tumors. In addition, we observed high expression of EFNB2 in patients having neoadjuvant non-responder colorectal carcinoma compared with those having responder version of the disease. In the course of deciphering the drug resistance mechanism, we also show that ephrin-B2 reverse signaling induces ABCG2 expression after drug treatment that involves JNK-c-Jun signaling in mutant p53 cells. Moreover, 5-fluorouracil-induced ephrin-B2 reverse signaling promotes tumorigenesis through the Src-ERK pathway, and drives EMT via the Src-FAK pathway. We thus conclude that targeting ephrin-B2 might enhance the therapeutic potential of DNA-damaging chemotherapeutic agents in mutant p53-bearing human tumors.

Copper-induced changes in reproductive functions: in vivo and in vitro effects.

The goal of this study is to summarize the current knowledge on the effects of one of the essential metals, copper (Cu) on the reproductive system. The development of past four decades addressing effects of Cu on reproductive organs is reviewed. The most relevant data obtained from in vivo and in vitro experiments performed on humans and other mammals, including effects of copper nanoparticles (CuNPs) on the reproductive functions are presented. Short term Cu administration has been found to exert deleterious effect on intracellular organelles of rat ovarian cells in vivo. In vitro administration in porcine ovarian granulosa cells releases insulin-like growth factor (IGF-I), steroid hormone progesterone (P(4)), and induces expression of peptides related to proliferation and apoptosis. Adverse effect of Cu on male reproductive functions has been indicated by the decrease in spermatozoa parameters such as concentration, viability and motility. Copper nanoparticles are capable of generating oxidative stress in vitro thereby leading to reproductive toxicity. Toxic effect of CuNPs has been evident more in male mice than in females. Even though further investigations are necessary to arrive at a definitive conclusion, Cu notably influences the reproductive functions by interfering with both male and female reproductive systems and also hampers embryo development in dose-dependent manner.

Possible intracellular regulators of female sexual maturation.

Protein kinases, transcription factors and other apoptosis- and proliferation-related proteins can regulate reproduction, but their involvement in sexual maturation remains to be elucidated. The general aim of the in vivo and in vitro experiments with porcine ovarian granulosa cells was to identify possible intracellular regulators of female sexual maturation. For this purpose, proliferation (expression of proliferating cell nuclear antigen - PCNA, mitogen-activated protein kinases - ERK 1,2 related MAPK and cyclin B1), apoptosis (expression of the apoptotic protein Bax and apoptosis regulator Bcl-2 protein), expression of some protein kinases (cAMP dependent protein kinase - PKA, cGMP-dependent protein kinase - PKG, tyrosine kinase - TK) and cAMP responsive element binding protein 1 (CREB-1) was examined in granulosa cells isolated from ovaries of immature and mature gilts. Expression of PCNA, ERK1,2 related MAPK, cyclin B1, Bcl-2, Bax, PKA, CREB-1, TK and PKG in porcine granulosa cells were detected by immunocytochemistry. Sexual maturation was associated with significant increase in the expression of Bcl-2, Bax, PKA, CREB-1 and TK and with decrease in the expression of ERK1,2 related MAPK, cyclin B1 and PKG in granulosa cells. No significant difference in PCNA expression was noted. The present data obtained from in vitro study indicate that sexual maturation in females is influenced by puberty-related changes in porcine ovarian signaling substances: increase in Bcl-2, Bax, PKA, CREB-1, TK and decrease in ERK1,2 related MAPK, cyclin B1 and PKG. It suggests that these signaling molecules could be potential regulators of porcine sexual maturation.

In vitro changes in secretion activity of rat ovarian fragments induced by molybdenum.

The aim of this in vitro study was to examine the secretion activity (progesterone, 17beta-estradiol and insulin-like growth factor-I) of rat ovarian fragments after molybdenum (Mo) addition. Rat ovarian fragments were incubated with ammonium molybdate (NH(4))(6)Mo(7)O(24).4H(2)O at the doses 90, 170, 330 and 500 microg.ml(-1) for 24 h and compared with control group without Mo addition. Release of progesterone (P(4)), estradiol (17beta-estradiol) and insulin-like growth factor I (IGF-I) by ovarian fragments was assessed by radioimmunoassay (RIA). Data show that P(4) release by ovarian fragments was not affected by (NH(4))(6).Mo(7)O(24).4H(2)O addition at all the doses used (90-500 microg.ml(-1)). However, addition of ammonium molybdate was found to cause a significant (P<0.05) dose-dependent decrease (at the doses 90, 170 and 500 microg.ml(-1)) in release of 17beta-estradiol by ovarian fragments in comparison to control. Also, addition of ammonium molybdate significantly (P<0.05) inhibited IGF-I release at all the doses (90-500 microg.ml(-1)) used in the study. Results suggest ammonium molybdate induced inhibition in the release of growth factor IGF-I and its dose-dependent effect on secretion of steroid hormone 17beta-estradiol but not progesterone. These data contribute to new insights regarding the mechanism of action of Mo on rat ovarian functions.

miR-125b promotes cell death by targeting spindle assembly checkpoint gene MAD1 and modulating mitotic progression.

The spindle assembly checkpoint (SAC) is a 'wait-anaphase' mechanism that has evolved in eukaryotic cells in response to the stochastic nature of chromosome-spindle attachments. In the recent past, different aspects of the SAC regulation have been described. However, the role of microRNAs in the SAC is vaguely understood. We report here that Mad1, a core SAC protein, is repressed by human miR-125b. Mad1 serves as an adaptor protein for Mad2 - which functions to inhibit anaphase entry till the chromosomal defects in metaphase are corrected. We show that exogenous expression of miR-125b, through downregulation of Mad1, delays cells at metaphase. As a result of this delay, cells proceed towards apoptotic death, which follows from elevated chromosomal abnormalities upon ectopic expression of miR-125b. Moreover, expressions of Mad1 and miR-125b are inversely correlated in a variety of cancer cell lines, as well as in primary head and neck tumour tissues. We conclude that increased expression of miR-125b inhibits cell proliferation by suppressing Mad1 and activating the SAC transiently. We hypothesize an optimum Mad1 level and thus, a properly scheduled SAC is maintained partly by miR-125b.

Hematological, immunological, and cardiovascular changes in individuals residing in a polluted city of India: a study in Delhi.

Exposure to poor air quality is associated with a multitude of hematological and immunological alterations. Cardio vascular diseases, rather than respiratory ailments, are the most important cause of death from air pollution exposure. Thus, hematological, immunological and cardiovascular alterations in healthy individuals exposed to vehicular pollution (one of the leading source of air pollution in growing metropolitan cities) are investigated in this study. A total number of 2218 (21-65 years old) adults residing in Delhi participated in this study. As control, 642 age and sex matched healthy subjects from the rural areas of Uttaranchal were enrolled. Arterial blood pressure (BP) was measured by a sphygmomanometer. Blood samples were collected and routine hematology was done. Lymphocyte subset analysis and platelet P-selectin expression was measured by flow cytometry. Air quality data was collected from Central and State Pollution Control Boards and was also measured onsite by portable, battery-operated laser photometer. The prevalence of hypertension was nearly 4-times higher in Delhi when compared to the control. Platelet P-selectin was remarkably upregulated in residents of Delhi. They had depleted number of CD4+ T-helper cells and CD19+ B cells but elevated level of CD56+ natural killer cells. Altered lymphocyte subtypes and increased number of P-selectin-positive platelets suggest altered immunity (that may compromise body's defense against infections) and hypercoagulable state, a risk factor for cardiovascular diseases. The current study has identified poor air quality of Delhi as a key contributor to several adverse health conditions experienced by the general population of the city, which not only makes the quality of life compromised but also put them at a greater risk of developing cardiovascular ailments later in life.