Neoantigen Identification and Dendritic Cell-Based Vaccines for Lung Cancer Immunotherapy.

Immunotherapies can treat many cancers, including difficult-to-treat cases such as lung cancer. Due to its tolerability, long-lasting therapeutic responses, and efficacy in a wide spectrum of patients, immunotherapy can also help to treat lung cancer, which has few treatment choices. Tumor-specific antigens (TSAs) for cancer vaccinations and T-cell therapies are difficult to discover. Neoantigens (NeoAgs) from genetic mutations, irregular RNA splicing, protein changes, or viral genetic sequences in tumor cells provide a solution. NeoAgs, unlike TSAs, are non-self and can cause an immunological response. Next-generation sequencing (NGS) and bioinformatics can swiftly detect and forecast tumor-specific NeoAgs. Highly immunogenic NeoAgs provide personalized or generalized cancer immunotherapies. Dendritic cells (DCs), which originate and regulate T-cell responses, are widely studied potential immunotherapeutic therapies for lung cancer and other cancers. DC vaccines are stable, reliable, and safe in clinical trials. The purpose of this article is to evaluate the current status, limitations, and prospective clinical applications of DC vaccines, as well as the identification and selection of major histocompatibility complex (MHC) class I and II genes for NeoAgs. Our goal is to explain DC biology and activate DC manipulation to help researchers create extremely potent cancer vaccines for patients.

Untargeted Metabolomics and Body Mass in Adolescents: A Cross-Sectional and Longitudinal Analysis.

Obesity in children and adolescents has increased globally. Increased body mass index (BMI) during adolescence carries significant long-term adverse health outcomes, including chronic diseases such as cardiovascular disease, stroke, diabetes, and cancer. Little is known about the metabolic consequences of changes in BMI in adolescents outside of typical clinical parameters. Here, we used untargeted metabolomics to assess changing BMI in male adolescents. Untargeted metabolomic profiling was performed on urine samples from 360 adolescents using UPLC-QTOF-MS. The study includes a baseline of 235 subjects in a discovery set and 125 subjects in a validation set. Of them, a follow-up of 81 subjects (1 year later) as a replication set was studied. Linear regression analysis models were used to estimate the associations of metabolic features with BMI z-score in the discovery and validation sets, after adjusting for age, race, and total energy intake (kcal) at false-discovery-rate correction (FDR) ≤ 0.1. We identified 221 and 16 significant metabolic features in the discovery and in the validation set, respectively. The metabolites associated with BMI z-score in validation sets are glycylproline, citrulline, 4-vinylsyringol, 3'-sialyllactose, estrone sulfate, carnosine, formiminoglutamic acid, 4-hydroxyproline, hydroxyprolyl-asparagine, 2-hexenoylcarnitine, L-glutamine, inosine, N-(2-Hydroxyphenyl) acetamide glucuronide, and galactosylhydroxylysine. Of those 16 features, 9 significant metabolic features were associated with a positive change in BMI in the replication set 1 year later. Histidine and arginine metabolism were the most affected metabolic pathways. Our findings suggest that obesity and its metabolic outcomes in the urine metabolome of children are linked to altered amino acids, lipid, and carbohydrate metabolism. These identified metabolites may serve as biomarkers and aid in the investigation of obesity's underlying pathological mechanisms. Whether these features are associated with the development of obesity, or a consequence of changing BMI, requires further study.

A review on control and abatement of soil pollution by heavy metals: Emphasis on artificial intelligence in recovery of contaminated soil.

"Save Soil Save Earth" is not just a catchphrase; it is a necessity to protect soil ecosystem from the unwanted and unregulated level of xenobiotic contamination. Numerous challenges such as type, lifespan, nature of pollutants and high cost of treatment has been associated with the treatment or remediation of contaminated soil, whether it be either on-site or off-site. Due to the food chain, the health of non-target soil species as well as human health were impacted by soil contaminants, both organic and inorganic. In this review, the use of microbial omics approaches and artificial intelligence or machine learning has been comprehensively explored with recent advancements in order to identify the sources, characterize, quantify, and mitigate soil pollutants from the environment for increased sustainability. This will generate novel insights into methods for soil remediation that will reduce the time and expense of soil treatment.

Production of biopolymers from food waste: Constrains and perspectives.

Food is an essential commodity for the survival of any form of life on earth. Yet generation of plethora of food waste has significantly elevated the global concern for food scarcity, human and environment deterioration. Also, increasing use of polymers derived from petroleum hydrocarbons has elevated the concerns towards the depletion of this non-renewable resource. In this review, the use of waste food for the production of bio-polymers and their associated challenges has been thoroughly investigated using scientometric analysis. Various categories of food waste including fruit, vegetable, and oily waste can be employed for the production of different biopolymers including polyhydroxyalkanoates, starch, cellulose, collagen and others. The advances in the production of biopolymers through chemical, microbial or enzymatic process that increases the acceptability of these biopolymers has been reviewed. The comprehensive compiled information may assist researchers for addressing and solving the issues pertaining to food wastage and fossil fuel depletion.

Chronic obstructive pulmonary disease (COPD) in women due to indoor biomass burning: a meta analysis.

Chronic Obstructive Pulmonary Disease (COPD) is attributable to household air pollution and is known to increase the Disability Adjusted Life Years (DALYs), morbidity and mortality and women are most susceptible groups for the exposure. In order to understand the global risk among women with COPD due to exposure of household air pollutants, an evidence-based systematic review and meta-analysis was conducted. Meta regression analysis was carried out to identify potential sources of heterogeneity. The summary estimates of the included studies showed higher prevalence of COPD due to biomass fuel exposure in women. Clinical diagnosis has shown more risk of COPD prevalence compared to diagnosis based on spirometer test alone. However, the data between included studies for both clinical and spirometry-based studies showed higher heterogeneity. The present meta-data analysis has shown that household air pollutants may be a factor associated with increased risk of COPD in women.

Saliva and urine metabolic profiling reveals altered amino acid and energy metabolism in male farmers exposed to pesticides in Madhya Pradesh State, India.

Globally, the human population is exposed to low doses of pesticides due to its extensive use in agriculture. The chronic exposure to pesticides can lead to cancer, depression, anxiety, Parkinson's and Alzheimer's diseases etc. Here, we have made an attempt to use mass spectrometry based metabolomics to investigate the metabolic perturbations induced by the pesticides in the urine and saliva samples of farmers from the Madhya Pradesh State of India. The study was aimed to establish non-invasive matrices like urine and saliva as alternative diagnostic matrices to the occupational exposure studies. Saliva and urine samples were collected from 51 pesticides applicators and acquired metabolic profiles of urine and saliva samples using gas chromatography-mass spectrometry (GC-MS). Multivariate pattern recognition and pathway analysis were used to analyze and interpret the data. Investigation of endogenous metabolic profiles revealed remarkable discrimination in both saliva and urine samples of the exposed population strongly suggesting the changes in metabolic composition within the identified metabolites (for urine samples: accuracy 0.9766, R2 = 0.9130, Q2 = 0.8703; for saliva samples, an accuracy of 0.9961, R2 = 0.9698, Q2 = 0.9637). Thirteen metabolites of urine samples and sixteen metabolites of saliva samples were identified as differential metabolites specific to pesticide exposure. Pathway analysis of differential metabolites revealed that amino acid metabolism, energy metabolism (glycolysis and TCA cycle) and glutathione metabolism (oxidative stress) were found to affect in pesticide exposed population. The present study suggested that GC-MS based metabolomics can help to reveal the metabolic perturbations in human population after pesticides exposure.

Association between PAHs biomarkers and kidney injury biomarkers among kitchen workers with microalbuminuria: A cross-sectional pilot study.

BACKGROUND: To study the association between kidney injury biomarkers and urinary OH-PAH metabolites in kitchen workers, with microalbuminuria. METHODS: A cross-sectional pilot study was conducted among 120 male kitchen workers in a mega kitchen located at Coimbatore, India. Personal and sub-clinical details of study subjects were collected using a questionnaire. Albumin, creatinine, and albumin-creatinine ratio (ACR) were measured using urine dipstick test for the determination of microalbuminuria. Urinary hydroxylated PAHs metabolites (1-NAP, 9-HF, 3-HF, 2-HF, 9-PHN, and 1-OHP) were measured using GC-MS/MS and urinary kidney biomarkers (uNGAL, uCyst-C, uKIM-1, uOPN, and uTIMP-1) were measured using Multiplex Reader. RESULTS: Concentrations of urinary PAHs metabolites (1-NAP, 3-HF, 2-HF, 9-PHN, and 1-OHP) and kidney biomarkers (uKIM-1, uTIMP-1, uCyst-C and uNGAL) were significantly higher among kitchen workers with MAU compared to non-kitchen workers with MAU. Urinary kidney biomarkers viz., uKIM-1, uTIMP-1, uCyst-C, uNGAL, and uOPN showed higher median concentration among the kitchen workers with MAU compared to kitchen workers without MAU. Significant positive correlation was observed for 9-HF with uKIM-1 and uTIMP-1 and 1-OHP with uKIM-1. ACR was also well correlated with urinary kidney biomarkers. ROC analysis showed higher sensitivity and specificity for uKIM-1, uCyst-C, and uNGAL as biomarkers for early prediction of acute kidney injury among kitchen workers. CONCLUSIONS: The PAHs exposure among kitchen workers can lead to kidney injury. This was evident from the association of OH-PAHs and kidney injury biomarkers in kitchen workers with microalbuminuria.

Indoor air pollution and its association with poor lung function, microalbuminuria and variations in blood pressure among kitchen workers in India: a cross-sectional study.

BACKGROUND: The present study is an attempt to explore the association between kitchen indoor air pollutants and physiological profiles in kitchen workers with microalbuminuria (MAU) in north India (Lucknow) and south India (Coimbatore). METHODS: The subjects comprised 145 control subjects, 233 kitchen workers from north India and 186 kitchen workers from south India. Information related to the personal and occupational history and health of the subjects at both locations were collected using a custom-made questionnaire. Worker lung function was measured using a spirometer. Blood pressure was monitored using a sphygmomanometer. Urinary MAU was measured using a urine analyzer. Indoor air monitoring in kitchens for particulate matter (PM), total volatile organic compounds (TVOC), carbon dioxide (CO2) and carbon monoxide (CO) was conducted using indoor air quality monitors. The size and shape of PM in indoor air was assessed using a scanning electron microscope (SEM). Fourier transform infrared (FTIR) spectroscopy was used to detect organic or inorganic compounds in the air samples. RESULTS: Particulate matter concentrations (PM2.5 and PM1) were significantly higher in both north and south Indian kitchens than in non-kitchen areas. The concentrations of TVOC, CO and CO2 were higher in the kitchens of north and south India than in the control locations (non-kitchen areas). Coarse, fine and ultrafine particles and several elements were also detected in kitchens in both locations by SEM and elemental analysis. The FTIR spectra of kitchen indoor air at both locations show the presence of organic chemicals. Significant declines in systolic blood pressure and lung function were observed in the kitchen workers with MAU at both locations compared to those of the control subjects. A higher prevalence of obstruction cases with MAU was observed among the workers in the southern region than in the controls (p < 0.01). CONCLUSIONS: Kitchen workers in south India have lower lung capacities and a greater risk of obstructive and restrictive abnormalities than their north Indian counterparts. The study showed that occupational exposure to multiple kitchen indoor air pollutants (ultrafine particles, PM2.5, PM1, TVOC, CO, CO2) and FTIR-derived compounds can be associated with a decline in lung function (restrictive and obstructive patterns) in kitchen workers with microalbuminuria. Further studies in different geographical locations in India among kitchen workers on a wider scale are required to validate the present findings.

Heat and PAHs Emissions in Indoor Kitchen Air and Its Impact on Kidney Dysfunctions among Kitchen Workers in Lucknow, North India.

Indoor air quality and heat exposure have become an important occupational health and safety concern in several workplaces including kitchens of hotels. This study investigated the heat, particulate matter (PM), total volatile organic compounds (TVOCs) and polycyclic aromatic hydrocarbons (PAHs) emissions in indoor air of commercial kitchen and its association with kidney dysfunctions among kitchen workers. A cross sectional study was conducted on 94 kitchen workers employed at commercial kitchen in Lucknow city, North India. A questionnaire-based survey was conducted to collect the personal and occupational history of the kitchen workers. The urine analysis for specific gravity and microalbuminuria was conducted among the study subjects. Indoor air temperature, humidity, wet/ dry bulb temperature and humidex heat stress was monitored during cooking activities at the kitchen. Particulate matter (PM) for 1 and 2.5 microns were monitored in kitchen during working hours using Hazdust. PAHS in indoor air was analysed using UHPLC. Urinary hydroxy-PAHs in kitchen workers were measured using GC/MS-MS. Higher indoor air temperature, relative humidity, PM1 and PM2.5 (p<0.001) was observed in the kitchen due to cooking process. Indoor air PAHs identified are Napthalene, fluorine, acenaphthene, phenanthrene, pyrene, chrysene and indeno [1,2,3-cd) pyrene. Concentrations of all PAHs identified in kitchen were above the permissible OSHA norms for indoor air. Specific gravity of urine was significantly higher among the kitchen workers (p<0.001) as compared to the control group. Also, the prevalence of microalbuminuria was higher (p<0.001) among kitchen workers. Urinary PAH metabolites detected among kitchen workers were 1-NAP, 9-HF, 3-HF, 9-PHN and 1-OHP. Continuous heat exposure in kitchens due to cooking can alter kidney functions viz., high specific gravity of urine in kitchen workers. Exposure to PM, VOCs and PAHs in indoor air and presence of urinary PAHs metabolites may lead to inflammation, which can cause microalbuminuria in kitchen workers, as observed in the present study.

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.

Application of nano-sized multi-template imprinted polymer for simultaneous extraction of polycyclic aromatic hydrocarbon metabolites in urine samples followed by ultra-high performance liquid chromatographic analysis.

Nano-sized molecularly imprinted polymer (nMIP) was synthesized through precipitation polymerization method and used it as solid phase extraction (SPE) sorbent for the selective and simultaneous extraction of hydroxylated metabolites of polycyclic aromatic hydrocarbons (PAHs) from urine followed by ultra-high performance liquid chromatography (UHPLC) analysis coupled with the fluorescent detector (FLD). Multi-template imprinting approach was used in the synthesis of nMIP by taking 1-naphthol, 9-phenanthrol and 9-hydroxyfluorene as templates, methacrylic acid (MAA) as a monomer, ethyleneglycoldimethacrylate (EGDMA) as a crosslinker and AIBN as an initiator. The synthesized nMIP exhibit the highest degree of binding affinity in comparison to non-imprinted polymer (NIP), and its binding affinity found to be in the range of 50-90% for all five metabolites tested. Method exhibits good linearity over a range of concentrations of metabolites with a R(2) value ranges from 0.9789 to 0.9921. Limit of detection (LOD) and limit of quantitation (LOQ) in urine samples were found to be in the range of 0.33-2.6 and 0.99-8ngmL(-1), respectively. Precision study shows that intra and inter-day precision was found to be less than 10%. The application of nMIP as SPE sorbent offers an effective and selective affinity towards the PAH metabolite's and found to be an alternative to the conventional sorbent for PAH metabolite's extraction from the biological samples. The developed nMIP offers wide advantages like simultaneous determination of PAH metabolites with improved sensitivity and found to be cost-effective for the routine analysis.

Gender Disparity in Lung Function Abnormalities among a Population Exposed to Particulate Matter Concentration in Ambient Air in the National Capital Region, India.

BACKGROUND: The World Health Organization (WHO) global air quality study shows that 27 Indian cities, including New Delhi, are among the one hundred cities with the worst air quality globally. The scope of airway obstruction cases among residents in locations with critical air pollution levels like particulate matter (PM) pollutants PM2.5 and PM1 has not been addressed in the National Capital region, India. OBJECTIVES: The present cross-sectional study was undertaken to assess the forced expiratory volume in one second (FEV1) % predicted abnormalities among residents living in the National Capital Region, India with respect to their exposure to particulate matter pollutants (PM1, PM2.5) in ambient air. METHODS: Eight hundred and fifty-four residents, including 433 men and 421 women ranging in age from 18-70 years, living in the National Capital Region (NCR) of India participated in the study. Particulate matter concentrations in ambient air (PM2.5 and PM1) were monitored at 10 residential locations in the National Capital Region, India (New Okhla Industrial Development Authority (NOIDA) and Gurgaon). The lung function test (FEV1) was conducted using a spirometer. RESULTS: The Indian Air Quality Index showed either very poor or severe levels for PM2.5 at all study locations. A significant negative linear relationship was found between higher concentrations of PM1 and reduced FEV1% predicted values (r = -0.8, p < 0.05). The prevalence of airway obstruction cases (79.6%, odds ratio 1.96, confidence interval 1.42-2.71) was higher (p<0.001) among female subjects compared to their male counterparts. Even though there was a significant decline in FEV1% predicted among 80% of cases in women, only 19.24% cases were in the moderate category and 6.18% cases in the severe category. The severe category of FEV1% predicted cases showed greater respiratory symptoms than the other two categories, which denotes higher risk among those in the severe category. The present study shows that obstruction cases increased from 1.97 to 7.40% and 2.73 to 14.93% in women, with a corresponding increase in PM1 and PM2.5 from the minimum to maximum concentration. CONCLUSIONS: Since the women in this study were non-smokers, the PM in ambient air can be considered to be the major reason for the decline in lung function. The sources of PM pollutants in the study locations are large scale infrastructural development activities such as building and road construction activities. Narrowed lung airways can alter the airway caliber or resistance and flow rates proportional to the airway radius, especially in smaller airways. The present study suggests the need for policy makers and stake holders to take the necessary steps to identify PM sources and reduce the emissions of PM concentrations in ambient air.