Herbal melanin modulates PGE2 and IL-6 gastroprotective markers through COX-2 and TLR4 signaling in the gastric cancer cell line AGS.

We reported a gastric anti-ulcerogenic effect of the Nigella sativa (L.)-derived herbal melanin (HM) using rat models. However, the molecular mechanisms underlying this HM gastroprotective effect remain unknown. Cyclooxygenase-2 (COX-2)-catalyzed prostaglandin E2 (PGE2) and toll-like receptor 4 (TLR4)-mediated interleukin-6 (IL-6) production and secretion play major roles in gastric mucosal protection. In the current study, the human gastric carcinoma epithelial cell line AGS was used as a model to investigate the effect of HM on TLR4, COX-2, glycoprotein mucin 4 protein and gene expression using immuno-cyto-fluorescence staining, Western blot technology, and reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Gastroprotective markers PGE2 and IL-6 production and secretion were also assessed using an enzyme-linked immunosorbent assay (ELISA). Bacterial lipopolysaccharides (LPS), well-known inducers of TLR4, COX-2, PGE2 and IL-6 expression, were used as a positive control. We showed that HM upregulated its main receptor TLR4 gene and protein expression in AGS cells. HM increased, in a dose- and time-dependent manner, the secretion of PGE2 and the expression of COX-2 mRNA and protein, which was detected in the nucleus, cytoplasm and predominantly at the intercellular junctions of the AGS cells. In addition, HM enhanced IL-6 production and secretion, and upregulated the mucin 4 gene expression, the hallmarks of gastroprotection. To check whether HM-induced PGE2 and IL-6 through TLR4 signaling and COX-2 generated, AGS cells were pre-treated with a TLR4 signaling inhibitor TAK242 and the COX-2 inhibitor NS-398. A loss of the stimulatory effects of HM on COX-2, PGE2 and IL-6 production and secretion was observed in TAK242 and NS-398-pre-treated AGS cells, confirming the role of TLR4 signaling and COX-2 generated in the HM gastroprotective effects. In conclusion, our results showed that HM enhances TLR4/COX-2-mediated secretion of gastroprotective markers PGE2 and IL-6, and upregulates mucin 4 gene expression in the human gastric epithelial cell line AGS, which may contribute to the promising beneficial gastroprotective effect of HM for human gastric prevention and treatment.

Chemical characterization of PM10 and PM2.5 combusted firecracker particles during Diwali of Lucknow City, India: air-quality deterioration and health implications.

Urban air pollution is a growing menace leading to human discomfort, increased hospitalizations, morbidity, and mortality. This study deals with deteriorated air quality due to firecracker bursting during Diwali in Lucknow. Inhalable particulates and gaseous pollutants were monitored during Diwali 2020 using air samplers. Elements, ions, and surface morphology of particles were analyzed using ICP-MS, ion chromatograph, and SEM-EDX, respectively. PM10, PM2.5, SO2, and NO2 were 558, 352, 44, and 86 µg/m3 during Diwali night and 233, 101, 17, and 40 µg/m3 on pre-Diwali night while 241, 122, 24, and 43 µg/m3 on Diwali day. Concentrations surged for PM10: 139% and 132%, PM2.5: 249% and 189%, SO2: 159% and 83%, and NO2: 115% and 100% on Diwali night compared to pre-Diwali night and corresponding Diwali day, respectively. Al, K, Ba, and B showed dominance in PM10 whereas Zn, Al, Ba, and K in PM2.5 on Diwali night. The order of metal abundance in PM2.5 was Cd < Co < Ag < As < Cr < Ni < Cu < Bi < Pb < Mn < Sr < Fe < B < Zn < Al < Ba < K. Cations NH4+, K+, Mg2+, Ca2+, and anions F-, Cl-, NO3-, Br-, NO2-, SO4-2, PO43- showed a 2-8 fold increase on Diwali night relative to pre-Diwali night. Average metal concentrations varied by 2.2, 1.6, and 0.09 times on Diwali than pre-Diwali in residential, commercial, and industrial areas, respectively. PM10 concentration increased by 458% and 1140% while PM2.5, 487%, and 2247% than respective NAAQS and WHO standards. Tiny firecracker particles vary in toxicity as compared to vehicular emissions and have enhanced bioavailability leading to severe threat in terms of LRI, COPD, and atherosclerosis for city dwellers. It is imperative to recognize the present status of ambient air quality and implement regulatory strategies for emission reduction.

Obesity and COVID-19: what makes obese host so vulnerable?

The disease (COVID-19) novel coronavirus pandemic has so far infected millions resulting in the death of over a million people as of Oct 2020. More than 90% of those infected with COVID-19 show mild or no symptoms but the rest of the infected cases show severe symptoms resulting in significant mortality. Age has emerged as a major factor to predict the severity of the disease and mortality rates are significantly higher in elderly patients. Besides, patients with underlying conditions like Type 2 diabetes, cardiovascular diseases, hypertension, and cancer have an increased risk of severe disease and death due to COVID-19 infection. Obesity has emerged as a novel risk factor for hospitalization and death due to COVID-19. Several independent studies have observed that people with obesity are at a greater risk of severe disease and death due to COVID-19. Here we review the published data related to obesity and overweight to assess the possible risk and outcome in Covid-19 patients based on their body weight. Besides, we explore how the obese host provides a unique microenvironment for disease pathogenesis, resulting in increased severity of the disease and poor outcome.

Assessing hazardous risks of indoor airborne polycyclic aromatic hydrocarbons in the kitchen and its association with lung functions and urinary PAH metabolites in kitchen workers.

BACKGROUND: Indoor air pollution is associated with decreased pulmonary function but the relative impact of pollution from kitchen sources on health risks in kitchen workers is not well-known or studied. A study was conducted to measure the kitchen indoor air quality including PAHs estimation and risk assessment based on reported PAHs in indoor air in a central kitchen at North India. METHODS: A cross sectional study was undertaken to assess the lung function status using spirometer and urinary PAH metabolite measurements using GC-MS/MS among 94 male kitchen workers and their corresponding controls. Assessment of the indoor air quality levels was evaluated using standard methods. RESULTS: All the indoor air pollutants were within the recommended guidelines except CO, TVOC and PAH emission in the kitchen. Incremental life time cancer risk (ICLR) based on indoor air PAH measurements indicates potential for carcinogenic risk. Significant lung function decline was observed among kitchen workers as compared to controls after adjusting for smoking habits. Urinary PAH metabolites were detected in kitchen workers and measured concentrations were comparatively higher than control subjects. CONCLUSION: The decline in lung functions after adjustment for confounders and detection of urinary PAH metabolites in kitchen workers can be associated with higher concentrations of PAHs, CO and TVOCs in kitchen indoor air.

Polycyclic aromatic hydrocarbons and their quinones modulate the metabolic profile and induce DNA damage in human alveolar and bronchiolar cells.

The release of particulate pollutants into the air through burning of coal, crude oil, diesel, coal tar, etc. raises concerns of potential health hazards to the exposed human population. Polycyclic aromatic hydrocarbons (PAHs) are major toxic constituents of particulate matter (PM), which upon ingestion get metabolized to even more toxic metabolites such as quinones. The PAHs levels were assessed in both respirable particulate matter (RSPM, <10µM size) and suspended particulate matter (SPM, >10µM size) of urban ambient air (UAA) and that of major contributors viz. diesel exhaust particles (DEPs) and coal tar combustions emissions (CTCE). Seven US Environmental Protection Agency (USEPA) prioritized PAHs in RSPM and 10 in SPM were detected in UAA. Ten and 15 prioritized PAHs, respectively, were also detected in diesel exhaust particles (DEP) and coal tar combustion emission (CTCE) evidencing their release in the air. These PM associated PAHs for UAA, DEP and CTCE showed significant increase (p<0.05) in mutagenicity and mammalian genotoxicity in the order CTCE>DEP>UAA. Human lung alveolar (A549) and bronchiolar (BEAS-2B) cells when treated with PAH-metabolites viz. 1,4-benzoquinone (1,4-BQ), hydroquinone (HQ), 1,2-naphthoquinone (1,2-NQ), 1,4-naphthoquinone (1,4-NQ) and 9,10-phenanthroquinone (9,10-PQ) showed metabolic modulation in these cell lines with significant depletion of principal cellular metabolites viz. NADP, uracil, asparagines, glutamine, and histidine and accumulation of di-methyl amine and beta-hydroxybutyrate, identified using (1)H NMR spectroscopy. These results suggest that PAH-quinones induce genotoxic effects by modulating the metabolic machinery inside the cells by a combined effect of oxidative stress and energy depletion. Our data for metabolic profiling of human lung cells could also help in understanding the mechanism of toxicity of other xenobiotics.

Seasonal trends of PM2.5 and PM10 in ambient air and their correlation in ambient air of Lucknow city, India.

The PM(10) concentration (µg/m(3)) in Lucknow city at 4 locations in three different seasons ranged between 148.6-210.8 (avg. 187.2 ± 17.1) during summer, 111.8-187.6 (avg. 155.7 ± 22.7) during monsoon and 199.3-308.8 (avg. 269.3 ± 42.9) during winter while PM(2.5) ranged between 32.4-67.2 (avg. 45.6 ± 10.9), 25.6-68.9 (avg. 39.8 ± 4.6) and 99.3-299.3 (avg. 212.4 ± 55.0) during respective seasons. The mass fraction ratio of PM(2.5) ranged between 0.22-0.92 (avg. 0.42 ± 0.26) and was significantly high during winter season indicating their composition.

Indoor exposure to respirable particulate matter and particulate-phase PAHs in rural homes in North India.

In order to evaluate the exposure of the northern India rural population to polyaromatic hydrocarbon (PAH) inhalation, indoor pollution was assessed by collecting and analyzing the respirable particulate matter PM2.5 and PM10 in several homes of the village Bhithauli near Lucknow, UP. The home selection was determined by a survey. Given the nature of biomass used for cooking, homes were divided into two groups, one using all kinds of biomass and the second type using plant materials only. Indoor mean concentrations of PM2.5 and associated PAHs during cooking ranged from 1.19±0.29 to 2.38±0.35 and 6.21±1.54 to 12.43±1.15 µg/m3, respectively. Similarly, PM10 and total PAHs were in the range of 3.95±1.21 to 8.81±0.78 and 7.75±1.42 to 15.77±1.05 µg/m3, respectively. The pollutant levels during cooking were significantly higher compared to the noncooking period. The study confirmed that indoor pollution depends on the kind of biomass fuel used for cooking.

Identification of polycyclic aromatic hydrocarbons in unleaded petrol and diesel exhaust emission.

Inhalation of emissions from petrol and diesel exhaust particulates is associated with potentially severe biological effects. In the present study, polycyclic aromatic hydrocarbons (PAHs) were identified from smokes released by the automobile exhaust from petrol and diesel. Intensive sampling of unleaded petrol and diesel exhaust were done by using 800-cm(3) motor car and 3,455-cm(3) vehicle, respectively. The particulate phase of exhaust was collected on Whatman filter paper. Particulate matters were extracted from filter paper by using Soxhlet. PAHs were identified from particulate matter by reverse phase high performance liquid chromatography using C(18) column. A total of 14 PAHs were identified in petrol and 13 in case of diesel sample after comparing to standard samples for PAH estimation. These inhalable PAHs released from diesel and petrol exhaust are known to possess mutagenic and carcinogenic activity, which may present a potential risk for the health of inhabitants.