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1.
Environ Monit Assess ; 196(6): 543, 2024 May 13.
Article in English | MEDLINE | ID: mdl-38740673

ABSTRACT

In India, railway is the major transportation mode for carrying goods and people. The tracks for the movement of the rail were initially constructed in the city for the pre-eminence and expediency of the vantage of the people. Rapid modernization and increasing population in the city crammed the area around the railway tracks. Moving rail on the tracks passing through the city is not compatible, which is creating problems for the nearby residents. In the urban and suburban regions, the railway noise has become a major problem. This study was conducted to examine the perception of the physiological and psychological effects of railway noise in the nearby areas of railway stations in Delhi, India. For this purpose, 10 sites near the railway station were selected for the study. To assess the impact of railway noise pollution on the health of humans, a questionnaire survey was conducted. The data of 344 individuals were collected through the questionnaire survey and analyzed to get the perception towards railway noise. Noise level was monitored by a Sound Level Meter (SLM) and the equivalent noise level (Leq) in dB(A) was used to compute the noise pollution in three shifts, i.e., morning, noon, and evening time. Results showed that 57.65% of female and 86.11% of male respondents in the survey reported the disturbance due to railway noise. The level of noise pollution was found higher in the evening time as compared to the noon and morning period, which exceeds the limit set by the Central Pollution Control Board (CPCB) at all the monitored locations. Findings of the study show that the primary cause of the health problems is railroad noise, which is negatively impacting the health of the residents, who are living in the proximity of the rail track region. The perception survey reported that headache, sleep disturbance, irritation, and stress are common health issues among the locals residing around the railway track proximity in Delhi.


Subject(s)
Environmental Monitoring , Noise, Transportation , Railroads , Humans , India , Environmental Monitoring/methods , Adult , Male , Female , Environmental Exposure/statistics & numerical data , Surveys and Questionnaires , Middle Aged
2.
Environ Sci Pollut Res Int ; 31(14): 21709-21720, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38393567

ABSTRACT

Continued improvements in living standards and the economic well-being in the megacities have led to a huge surge in vehicular density. The worst environmental outcome of the same has been persistent unsafe urban air quality, thanks to vehicular emission. Further, the existing inspection and maintenance programs, conceived to check such emission remain largely ineffective, particularly in developing countries. This is due to the absence of a thorough assessment of the vehicle's compliance with the in-use emission norms generated through reliable field investigation data. To address this gap, the present comprehensive study collected real-time tailpipe emission data from 2040 cars in Delhi, India. Exhaust emission parameters, namely, CO (carbon monoxide), HC (hydrocarbon), and SE (smoke emission), were recorded from both petrol and diesel-driven cars of private ownership, in collaboration with the emission compliance test centers. The performance of cars was assessed in terms of their compliance with the in-use BS (Bharat Stage) emission norms. The one-of-its-kind study reported the petrol cars to be highly compliant toward the BS IV norm while faring even better toward BS II for both CO and HC emissions (80-90%). The conformance to the HC norm was found to be typically better than that for CO (85-90% versus 75-80%). For the diesel-driven cars, BS III compliance levels were reported relatively better compared to BS IV (90% in the case of the former against 80% in the latter's case). Further, the study puts forward a clear indication that the in-use emission norm and maintenance status of cars have a direct and negative relationship with tailpipe emission parameters. Cars of both overseas and domestic origin have almost equal degrees of compliance with the emission norms (over 80% in any case). The study recommends the incorporation of these two critical vehicular variables, i.e., maintenance status and in-use emission standard in the emission certification policy.


Subject(s)
Air Pollutants , Air Pollution , Automobiles , Air Pollutants/analysis , Air Pollution/analysis , Vehicle Emissions/analysis , Carbon Monoxide/analysis , Gasoline/analysis
3.
Biochem Biophys Rep ; 35: 101501, 2023 Sep.
Article in English | MEDLINE | ID: mdl-37415850

ABSTRACT

Dengue fever is the fastest-growing infectious disease in the world. It is the leading vector-borne viral neglected tropical disease. The most acute immune response to dengue virus infection is dengue shock syndrome and hemorrhagic fever, which is due to the activation of CLEC5A C-type lectin domain family 5, member A (CLEC5A). It is a cell surface receptor, and its well-known ligand is the dengue virus. It gets activated by the attachment of dengue virion, which, as a result, phosphorylates its adaptor protein DAP12 leading to the induction of various pro-inflammatory cytokines. Clinical data suggested that the kidneys and lungs are among the major hit organs in the case of severe dengue infection. Here we predict kidney and lung cancer patients are vulnerable to dengue virus infection as CLEC5A mRNA expression in tumor samples using publicly available software such as TIMER and GEPIA database. We also identified the immunomodulatory role CLEC5A gene therefore targeting it could be a vital tool to cure dengue.

5.
Mitochondrion ; 71: 40-49, 2023 07.
Article in English | MEDLINE | ID: mdl-37211294

ABSTRACT

Circulating DNAs are considered as degraded DNA fragments of approximately 50-200 bp, found in blood plasma, consisting of cell-free mitochondrial and nuclear DNA. Such cell-free DNAs in the blood are found to be altered in different pathological conditions including lupus, heart disease, and malignancies. While nuclear DNAs are being used and being developed as a powerful clinical biomarker in liquid biopsies, mitochondrial DNAs (mtDNAs) are associated with inflammatory conditions including cancer progression. Patients with cancer including prostate cancer are found to have measurable concentrations of mitochondrial DNA in circulation in comparison with healthy controls. The plasma content of mitochondrial DNA is dramatically elevated in both prostate cancer patients and mouse models treated with the chemotherapeutic drug. Cell-free mtDNA, in its oxidized form, induced a pro-inflammatory condition and activates NLRP3-mediated inflammasome formation which causes IL-1ß-mediated activation of growth factors. On the other hand, interacting with TLR9, mtDNAs trigger NF-κB-mediated complement C3a positive feedback paracrine loop and activate pro-proliferating signaling through upregulating AKT, ERK, and Bcl2 in the prostate tumor microenvironment. In this review, we discuss the growing evidence supporting cell-free mitochondrial DNA copy number, size, and mutations in mtDNA genes as potential prognostic biomarkers in different cancers and targetable prostate cancer therapeutic candidates impacting stromal-epithelial interactions essential for chemotherapy response.


Subject(s)
Cell-Free Nucleic Acids , Prostatic Neoplasms , Humans , Male , Animals , Mice , DNA, Mitochondrial/metabolism , Prognosis , Prostatic Neoplasms/genetics , Prostatic Neoplasms/pathology , Mitochondria/metabolism , Tumor Microenvironment
6.
Mol Ther ; 31(1): 78-89, 2023 01 04.
Article in English | MEDLINE | ID: mdl-36045587

ABSTRACT

Androgen receptor signaling inhibitors (ARSIs) are standard of care for advanced prostate cancer (PCa) patients. Eventual resistance to ARSIs can include the expression of androgen receptor (AR) splice variant, AR-V7, expression as a recognized means of ligand-independent androgen signaling. We demonstrated that interleukin (IL)-6-mediated AR-V7 expression requires bone morphogenic protein (BMP) and CD105 receptor activity in both PCa and associated fibroblasts. Chromatin immunoprecipitation supported CD105-dependent ID1- and E2F-mediated expression of RBM38. Further, RNA immune precipitation demonstrated RBM38 binds the AR-cryptic exon 3 to enable AR-V7 generation. The forced expression of AR-V7 by primary prostatic fibroblasts diminished PCa sensitivity to ARSI. Conversely, downregulation of AR-V7 expression in cancer epithelia and associated fibroblasts was achieved by a CD105-neutralizing antibody, carotuximab. These compelling pre-clinical findings initiated an interventional study in PCa patients developing ARSI resistance. The combination of carotuximab and ARSI (i.e., enzalutamide or abiraterone) provided disease stabilization in four of nine assessable ARSI-refractory patients. Circulating tumor cell evaluation showed AR-V7 downregulation in the responsive subjects on combination treatment and revealed a three-gene panel that was predictive of response. The systemic antagonism of BMP/CD105 signaling can support ARSI re-sensitization in pre-clinical models and subjects that have otherwise developed resistance due to AR-V7 expression.


Subject(s)
Androgen Receptor Antagonists , Endoglin , Prostatic Neoplasms, Castration-Resistant , Receptors, Androgen , Humans , Male , Drug Resistance, Neoplasm , Neoplastic Cells, Circulating/metabolism , Prostatic Neoplasms, Castration-Resistant/drug therapy , Prostatic Neoplasms, Castration-Resistant/metabolism , Protein Isoforms , Receptors, Androgen/genetics , Receptors, Androgen/metabolism , RNA-Binding Proteins , Endoglin/antagonists & inhibitors , Androgen Receptor Antagonists/therapeutic use , Antibodies, Neutralizing/therapeutic use
7.
3 Biotech ; 12(11): 290, 2022 Nov.
Article in English | MEDLINE | ID: mdl-36276465

ABSTRACT

Telomere length is primarily controlled by the enzyme telomerase, but being chromatin structures, telomeres undergo epigenetic regulation for their maintenance and function. Altered telomere length among cancer cells combined with shorter telomere length in cancer-associated stromal cells, strongly implicated with progression to prostate cancer metastasis and cancer death and providing a novel target for therapeutics. Transforming growth factor-ß (TGF-ß) signaling pathways are well-recognized for their role in stromal-epithelial interactions responsible for prostate androgen responsiveness, promoting tumorigenesis. However, the underlying mechanism remains unclear. We sought to establish a role for TGF-ß in the regulation of telomere length in mouse and human prostate fibroblast. Polymerase chain reaction (PCR)-based telomere length measuring methods are widely used due to their repeatability and reproducibility. Using real-time RT-PCR-based telomere length measuring method, we identified that TGF-beta regulates telomere length via increased expression of histone methyltransferase, Suv39h1, which in turn affected histone methylation levels at the telomeric ends. Moreover, treatment of DAPT and non-steroidal antiandrogen bicalutamide demonstrated that notch and androgen signaling co-operated with TGF-ß in regulating stromal telomere length. Telomere variation in tumor cells and non-tumor cells within the tumor microenvironment greatly facilitates the clinical assessment of prostate cancer; therefore, understanding stromal telomere length regulation mechanism will hold significant prospects for cancer treatment, diagnosis, and prognosis. Supplementary Information: The online version contains supplementary material available at 10.1007/s13205-022-03346-5.

8.
PLoS One ; 17(10): e0275753, 2022.
Article in English | MEDLINE | ID: mdl-36201511

ABSTRACT

Myostatin (MSTN) is a negative regulator of skeletal muscle growth, thus it was hypothesized that immunization of hens against MSTN would enhance post-hatch growth and muscle mass via suppression of MSTN activity by anti-MSTN IgY in fertilized eggs. This study investigated the effects of immunization of hens against chicken MSTN (chMSTN) or a MSTN fragment (Myo2) on the growth and muscle mass of offspring. In Experiment 1, hens mixed with roosters were divided into two groups and hens in the Control and chMSTN groups were immunized with 0 and 0.5 mg of chMSTN, respectively. In Experiment 2, hens in the chMSTN group were divided into chMSTN and Myo2 groups while the Control group remained the same. The Control and chMSTN groups were immunized in the same way as Experiment 1. The Myo2 group was immunized against MSTN peptide fragment (Myo2) conjugated to KLH. Eggs collected from each group were incubated, and chicks were reared to examine growth and carcass parameters. ELISA showed the production of IgYs against chMSTN and Myo2 and the presence of these antibodies in egg yolk. IgY from the chMSTN and Myo2 groups showed binding affinity to chMSTN, Myo2, and commercial MSTN in Western blot analysis but did not show MSTN-inhibitory capacity in a reporter gene assay. In Experiment 1, no difference was observed in the body weight and carcass parameters of offspring between the Control and chMSTN groups. In Experiment 2, the body weight of chicks from the Myo2 group was significantly lower than that of the Control or chMSTN groups. The dressing percentage and breast muscle mass of the chMSTN and Myo2 groups were significantly lower than those of the Control group, and the breast muscle mass of Myo2 was significantly lower than that of the chMSTN. In summary, in contrast to our hypothesis, maternal immunization of hens did not increase but decreased the body weight and muscle mass of offspring.


Subject(s)
Chickens , Myostatin , Animals , Body Weight , Chickens/genetics , Female , Immunization , Male , Muscle, Skeletal/metabolism , Myostatin/genetics , Peptide Fragments
9.
Comput Biol Med ; 149: 106049, 2022 10.
Article in English | MEDLINE | ID: mdl-36103744

ABSTRACT

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infections generate approximately one million virions per day, and the majority of available antivirals are ineffective against it due to the virus's inherent genetic mutability. This necessitates the investigation of concurrent inhibition of multiple SARS-CoV-2 targets. We show that fortunellin (acacetin 7-O-neohesperidoside), a phytochemical, is a promising candidate for preventing and treating coronavirus disease (COVID-19) by targeting multiple key viral target proteins. Fortunellin supports protective immunity while inhibiting pro-inflammatory cytokines and apoptosis pathways and protecting against tissue damage. Fortunellin is a phytochemical found in Gojihwadi kwath, an Indian traditional Ayurvedic formulation with an antiviral activity that is effective in COVID-19 patients. The mechanistic action of its antiviral activity, however, is unknown. The current study comprehensively evaluates the potential therapeutic mechanisms of fortunellin in preventing and treating COVID-19. We have used molecular docking, molecular dynamics simulations, free-energy calculations, host target mining of fortunellin, gene ontology enrichment, pathway analyses, and protein-protein interaction analysis. We discovered that fortunellin reliably binds to key targets that are necessary for viral replication, growth, invasion, and infectivity including Nucleocapsid (N-CTD) (-54.62 kcal/mol), Replicase-monomer at NSP-8 binding site (-34.48 kcal/mol), Replicase-dimer interface (-31.29 kcal/mol), Helicase (-30.02 kcal/mol), Papain-like-protease (-28.12 kcal/mol), 2'-O-methyltransferase (-23.17 kcal/mol), Main-protease (-21.63 kcal/mol), Replicase-monomer at dimer interface (-22.04 kcal/mol), RNA-dependent-RNA-polymerase (-19.98 kcal/mol), Nucleocapsid-NTD (-16.92 kcal/mol), and Endoribonuclease (-16.81 kcal/mol). Furthermore, we identify and evaluate the potential human targets of fortunellin and its effect on the SARS-CoV-2 infected tissues, including normal-human-bronchial-epithelium (NHBE) and lung cells and organoids such as pancreatic, colon, liver, and cornea using a network pharmacology approach. Thus, our findings indicate that fortunellin has a dual role; multi-target antiviral activities against SARS-CoV-2 and immunomodulatory capabilities against the host.


Subject(s)
COVID-19 Drug Treatment , SARS-CoV-2 , Antiviral Agents/chemistry , Antiviral Agents/pharmacology , Cytokines , Endoribonucleases , Flavonoids , Glycosides , Humans , Methyltransferases , Molecular Docking Simulation , Molecular Dynamics Simulation , Papain , Phytochemicals/pharmacology , RNA
10.
Mol Biol Rep ; 49(11): 11149-11167, 2022 Nov.
Article in English | MEDLINE | ID: mdl-36161579

ABSTRACT

Microbes are a huge contributor to people's health around the world since they produce a lot of beneficial secondary metabolites. Cyanobacteria are photosynthetic prokaryotic bacteria cosmopolitan in nature. Adaptability of cyanobacteria to wide spectrum of environment can be contributed to the production of various secondary metabolites which are also therapeutic in nature. As a result, they are a good option for the development of medicinal molecules. These metabolites could be interesting COVID-19 therapeutic options because the majority of these compounds have demonstrated substantial pharmacological actions, such as neurotoxicity, cytotoxicity, and antiviral activity against HCMV, HSV-1, HHV-6, and HIV-1. They have been reported to produce a single metabolite active against wide spectrum of microbes like Fischerella ambigua produces ambigols active against bacteria, fungi and protozoa. Similarly, Moorea producens produces malygomides O and P, majusculamide C and somocystinamide which are active against bacteria, fungi and tumour cells, respectively. In addition to the above, Moorea sp. produce apratoxin A and dolastatin 15 possessing anti cancerous activity but unfortunately till date only brentuximab vedotin (trade name Adcetris), a medication derived from marine peptides, for the treatment of Hodgkin lymphoma and anaplastic large cell lymphoma has been approved by FDA. However, several publications have effectively described and categorised cyanobacterial medicines based on their biological action. In present review, an effort is made to categorize cyanobacterial metabolites on the basis of their phycochemistry. The goal of this review is to categorise cyanobacterial metabolites based on their chemical functional group, which has yet to be described.


Subject(s)
COVID-19 , Cyanobacteria , Humans , Cyanobacteria/metabolism
11.
Biochem Biophys Rep ; 32: 101350, 2022 Dec.
Article in English | MEDLINE | ID: mdl-36164562

ABSTRACT

Lung cancer is one of the most frequently diagnosed malignant tumors and the leading cause of cancer-related death worldwide. Mainly, Non-small-cell lung cancer (NSCLC), which accounts for more than eighty-five percent of all lung cancers, consists of two major subtypes: lung adenocarcinoma (LUAD) and squamous cell carcinoma (LUSC). Novel coronavirus disease (COVID-19) affected millions of people caused by acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) around the globe. Lung cancer patients and COVID-19 present unique and unfortunate lethal combinations because the lungs are the primary target organ of SARS-CoV-2 infection. Clinical studies have demonstrated that an over-activated inflammatory response associated with severe COVID-19 cases is characterized by excessive auto-amplifying cytokine release, which is defined as a "cytokine storm." ACE2 and TMPRSS2 receptors play an essential role in SARS-CoV-2 infection; therefore, using in silico analysis, we did correlation analysis with immune infiltration markers in LUAD and LUSC patient groups. Our study identified a promising correlation between immune-modulators and receptor proteins (ACE-2 and TMPRSS2), creating a domain that requires further laboratory studies for clinical authentication.

12.
Environ Sci Pollut Res Int ; 29(56): 84434-84450, 2022 Dec.
Article in English | MEDLINE | ID: mdl-35780270

ABSTRACT

Keeping in view the significant number of diesel-driven passenger cars in the existing light motor vehicle fleet in Delhi, India, a case study on smoke emission measurement from 460 number of such cars was conducted. Smoke exhaust data was collected from the diesel cars while the vehicles presented themselves for periodic renewal of pollution under control (PUC) certification at authorized emission testing centers across Delhi, India. Along with the smoke emission, various vehicle- and engine-related aspects, supposed to affect tailpipe smoke emission, were also recorded aiming at data analysis for two datasets, namely whole and top 5 makes. The smoke density under no-loading condition in the free acceleration test mode was measured. The study reported a strong correlation between vehicle parameters, such as age, mileage, maintenance category, emission norm, and engine aspiration; and the smoke emission (R2 values for vehicle age and mileage vs. smoke emission for whole dataset = 0.872 and 0.873, respectively). Top 5 make-wise correlations fared even better (R2 for age and mileage vs. emission in the range of 0.85-0.92 and 0.86-0.93, respectively). Further, the predictive emission equations using best-fit trendlines were also developed for both datasets. Such equations may be used by the car manufacturers to adopt a suitable strategy for tuning of engine or vehicle as such, to retain their cars in the longer state of compliance to the extant emission norms. Further, the study recommends to include vehicle mileage as an important factor in upgrading the existing inspection and maintenance programs, especially in the developing countries.


Subject(s)
Air Pollutants , Air Pollution , Automobiles , Air Pollution/analysis , Air Pollutants/analysis , Vehicle Emissions/analysis , Motor Vehicles , Smoke , Policy , Gasoline/analysis
13.
Environ Sci Pollut Res Int ; 29(54): 81954-81969, 2022 Nov.
Article in English | MEDLINE | ID: mdl-35739453

ABSTRACT

The river Gomti, one of India's most polluted rivers, passing through Lucknow, Uttar Pradesh, India, has been selected for this study. An attempt has been made to assess its water quality status by combining the water quality index (WQI) and synthetic pollution index (SPI). Further, the data integration with the geographic information system (GIS) along with twelve water quality parameters for the seven sampling stations (S1 to S7) over 5 years (2013-2017) has been performed. The study area showed a variation of WQI from 78.993 to 249.388 and SPI from 0.868 to 2.096 in 5 years. The map interpolated through GIS revealed that the WQI falls into the category of severely polluted (76-100) and unsuitable for human consumption (> 100), while SPI lies in the category of moderately polluted (0.5-1.0) and severally polluted (1.0-3.0). The BOD and COD were found to significantly influence the WQI and SPI scores. With the constant release of waste effluents into the river, all selected parameters increased from S1 to S7. Based on the study, effective wastewater management is immediately required to improve water quality and support any sustainable river restoration plan.


Subject(s)
Rivers , Water Pollutants, Chemical , Humans , Water Quality , Geographic Information Systems , Wastewater , Environmental Monitoring , India , Water Pollutants, Chemical/analysis , Water Pollution/analysis
14.
J Environ Manage ; 317: 115459, 2022 Sep 01.
Article in English | MEDLINE | ID: mdl-35751297

ABSTRACT

Since the air pollution and noise generated from fireworks are related to air quality and human health, the regulatory bodies had implemented the eco-friendly "Green Crackers" in megacity Delhi, India, to celebrate Diwali 2019 with the permission of a specific time slot (8:00 p.m. to 10:00 p.m.). The present study was conducted on a residential educational institute campus to evaluate the particle number size distribution (PNSD) of green cracker emissions. During the Diwali event period, the high peak of particle number concentration (PNC) reached 1.7 × 105 # cm-3 with a geometric mean diameter (GMD) of ∼44 nm. The average PNC increment on Diwali day was 138% and 97% compared to pre (October 26, 2019) and post (October 28, 2019) Diwali period, respectively, including 468%, 142%, 65%, 75% on pre-Diwali and 485%, 110%, 32%, 26% on post- Diwali 2019 period in terms of Nucleation mode (10 nm < Dp < 20 nm), Small Aitken mode (20 nm < Dp < 50 nm), Large Aitken mode (50 nm < Dp < 100 nm), and Accumulation mode (100 nm < Dp < 1000 nm), respectively. Unlike traditional firework emissions, green crackers had a high UFP/Ntotal ratio of 0.72, including Nucleation mode-0.35, Aitken mode-0.30, and Accumulation mode 0.35, distinguishing it from other pre-and post-Diwali particle number size distribution-dN/dlogDp curves. These observations indicate that green crackers emit more particles with smaller diameters than traditional crackers. Recommendations for using green crackers for Diwali celebrations may be an option if lower size-diameter particle emission could be controlled by changing the material composition of the green crackers. More research studies need to be conducted to assess atmospheric emissions of green crackers and their health impacts to evaluate whether they are better or worse than traditional crackers.


Subject(s)
Air Pollutants , Air Pollution , Air Pollutants/analysis , Air Pollution/analysis , Environmental Monitoring , Holidays , Humans , India , Particle Size , Particulate Matter/analysis
15.
3 Biotech ; 12(5): 116, 2022 May.
Article in English | MEDLINE | ID: mdl-35547012

ABSTRACT

Arsenic and chromium are the most common environmental toxicants prevailing in nature. Hence, the present study endeavors to investigate the salutary effects of Coenzyme Q10 (CoQ10), Biochanin A (BCA), and Phloretin (PHL) on the combined neurotoxic impact of arsenic and chromium in the Swiss albino mice (Mus musculus). Sodium meta-arsenite (100 ppm) and potassium dichromate (75 ppm) were given orally in conjugation with CoQ10 (10 mg/kg), BCA & PHL (50 mg/kg each) in accordance with body weight per day for the 2 weeks experimental duration. Weight reduction was figured out in the exposed toxic group of arsenic and chromium in contrast with the comparison group (control), and with the selected anti-oxidants treatment, it rose significantly to the basal status (p < 0.05). The concentration of arsenic and chromium was reduced significantly (p < 0.001) amidst all the natural compounds co-medicated groups. Anti-oxidant indicators, viz. lipid peroxidation (LPO) and protein carbonyl content (PCC), were found elevated, with reduction observed in the levels of superoxide dismutase (SOD), reduced glutathione (GSH), glutathione s-transferase (GST), and total thiols (TT) in the arsenic and chromium, co-exposed mice. The alterations in redox homeostasis were well corroborated with the estimations of cholinesterase's enzymes (p < 0.05) along with DNA fragmentation assay and altered Nrf2 signaling. The administration of CoQ10, BCA, and PHL ameliorated the effects of arsenic and chromium induced oxidative stress in the exposed mice. Our research unfolds the remedial outcome of these natural compounds contrary to the combined arsenic and chromium associated-neurotoxicity in the experimental model.

16.
Proteins ; 90(11): 1926-1943, 2022 11.
Article in English | MEDLINE | ID: mdl-35579112

ABSTRACT

In Azospirillum brasilense, an extra-cytoplasmic function σ factor (RpoE10) shows the characteristic 119 amino acid long C-terminal extension found in ECF41-type σ factors, which possesses three conserved motifs (WLPEP, DGGGR, and NPDKV), one in the linker region between the σ2 and σ4 , and the other two in the SnoaL_2 domain of the C-terminal extension. Here, we have described the role of the two conserved motifs in the SnoaL_2 domain of RpoE10 in the inhibition and activation of its activity, respectively. Truncation of the distal part of the C-terminal sequence of the RpoE10 (including NPDKV but excluding the DGGGR motif) results in its promoter's activation suggesting autoregulation. Further truncation of the C-terminal sequence up to its proximal part, including NPDKV and DGGGR motif, abolished promoter activation. Replacement of NPDKV motif with NAAAV in RpoE10 increased its ability to activate its promoter, whereas replacement of DGGGR motif led to reduced promoter activation. We have explored the dynamic modulation of σ2 -σ4 domains and the relevant molecular interactions mediated by the two conserved motifs of the SnoaL2 domain using molecular dynamics simulation. The analysis enabled us to explain that the NPDKV motif located distally in the C-terminus negatively impacts transcriptional activation. In contrast, the DGGGR motif found proximally of the C-terminal extension is required to activate RpoE10.


Subject(s)
Azospirillum brasilense , Sigma Factor , Amino Acids/metabolism , Azospirillum brasilense/genetics , Azospirillum brasilense/metabolism , Bacterial Proteins/chemistry , Gene Expression Regulation, Bacterial , Homeostasis , Sigma Factor/chemistry
17.
Interdiscip Sci ; 14(4): 863-878, 2022 Dec.
Article in English | MEDLINE | ID: mdl-35394619

ABSTRACT

The SARS-CoV-2 infection affects the lungs, heart, kidney, intestine, olfactory epithelia, liver, and pancreas and brings forward multi-organ dysfunctions (MODs). However, mechanistic details of SARS-CoV-2-induced MODs are unclear. Here, we have investigated the role of pancreatic secretory proteins to mechanistically link COVID-19 with MODs using single-cell transcriptome analysis. Secretory proteins were identified using the Human Protein Atlas. Gene ontology, pathway, and disease enrichment analyses were used to highlight the role of upregulated pancreatic secretory proteins (secretome). We show that SARS-CoV-2 infection shifts the expression profile of pancreatic endocrine cells to acinar and ductal cell-specific profiles, resulting in increased expression of acinar and ductal cell-specific genes. Among all the secretory proteins, the upregulated expression of IL1B, AGT, ALB, SPP1, CRP, SERPINA1, C3, TFRC, TNFSF10, and MIF was mainly associated with disease of diverse organs. Extensive literature and experimental evidence are used to validate the association of the upregulated pancreatic secretome with the coagulation cascade, complement activation, renin-angiotensinogen system dysregulation, endothelial cell injury and thrombosis, immune system dysregulation, and fibrosis. Our finding suggests the influence of an upregulated secretome on multi-organ systems such as nervous, cardiovascular, immune, digestive, and urogenital systems. Our study provides evidence that an upregulated pancreatic secretome is a possible cause of SARS-CoV-2-induced MODs. This finding may have a significant impact on the clinical setting regarding the prevention of SARS-CoV-2-induced MODs.


Subject(s)
COVID-19 , Humans , SARS-CoV-2 , Angiotensinogen , Multiple Organ Failure , Renin , Secretome , Pancreas , Gene Expression Profiling
18.
Subcell Biochem ; 98: 3-14, 2022.
Article in English | MEDLINE | ID: mdl-35378700

ABSTRACT

Eukaryotic cells are capable of internalizing different types of cargo by plasma membrane ruffling and forming vesicles in a process known as endocytosis. The most extensively characterized endocytic pathways are clathrin-coated pits, lipid raft/caveolae-mediated endocytosis, phagocytosis, and macropinocytosis. Macropinocytosis is unique among all the endocytic processes due to its nonselective internalization of extracellular fluid, solutes, and membrane in large endocytic vesicles known as macropinosomes with unique susceptibility toward Na+/H+ exchanger inhibitors. Range of cell types capable of macropinocytosis and known to play important role in different physiological processes, which include antigen presentation, nutrient sensing, migration, and signaling. Understanding the physiological function of macropinocytosis will be helpful in filling the gaps in our knowledge and which can be exploited to develop novel therapeutic targets. In this chapter, we discuss the different molecular mechanisms that initiate the process of macropinocytosis with special emphasis on proteins involved and their diversified role in different cell types.


Subject(s)
Endocytosis , Pinocytosis , Endocytosis/physiology , Endosomes , Membrane Microdomains/metabolism , Phagocytosis
19.
Epigenomics ; 14(5): 279-293, 2022 03.
Article in English | MEDLINE | ID: mdl-35184601

ABSTRACT

Head and neck squamous cell carcinoma (HNSCC) is the sixth most prevalent form of cancer worldwide. Despite advancements made in treatment strategies, the fatality rate of HNSCC is very high. An accumulating body of evidence suggests that epigenetic modification of histones plays an influential role in the development and progression of the disease. In this review we discuss the role of epigenetic modifications in HNSCC and the inter-relationships of human papillomavirus oncoproteins and histone-modifying agents. Further, we explore the possibility of identifying these modifications as biomarkers for their use as drugs in treatment strategies.


Head and neck squamous cell carcinoma (HNSCC) is the most common kind of head and neck cancer. HNSCC can develop therapeutic resistance, making therapy more difficult. Many studies have found that epigenetic events play a key role in HNSCC. Better understanding epigenetic regulation could help discovery of biomarkers that help detect and diagnose HNSCC. This review will present recent studies, showing the importance of epigenetic regulation targeting histone modifications in the development of HNSCC.


Subject(s)
Head and Neck Neoplasms , Histones , Epigenesis, Genetic , Head and Neck Neoplasms/drug therapy , Head and Neck Neoplasms/genetics , Histone Code , Histones/metabolism , Humans , Squamous Cell Carcinoma of Head and Neck/genetics
20.
Environ Sci Pollut Res Int ; 29(57): 86247-86259, 2022 Dec.
Article in English | MEDLINE | ID: mdl-34981384

ABSTRACT

Diwali (the festival of lights and crackers) is celebrated grandly, resulting in a significant drop in the city's air quality. To study the impact of the judicial prohibition in Delhi to improve air quality, a comprehensive and comparative analysis was conducted over two consecutive years, namely 2015-2016 (when no significant regulations on the sale or usage of firecrackers were imposed) and 2017-2018 (when radically different regulations were implemented). Data on PM10, PM2.5, NOx, and CO were analysed, and their trends and levels with various regulations in place were compared. In 2017, the concentrations of PM10, PM2.5, NOx, and CO were reduced by 50%, 50%, 71%, and 64%, respectively, compared to 2016. However, in 2018, there was an increase of 32% in PM10 and PM2.5 concentrations, as well as a 25% increase in CO concentrations, with the exception of NOx, which decreased to 25% on Diwali day. The data was also examined in conjunction with the entire timeline of the various court rulings and regulations imposed in Delhi. The questionnaire survey study revealed that, despite the legislation in place, ambient air quality continued to deteriorate, necessitating a deeper dive into the policy's structure and implementation to fine-tune its feasibility and applications. Air pollution-related health effects were recognized by 82% of participants. Despite this, only 13% of people were observed without a mask, and only 12% of people were aware of green crackers as of 2018. To combat this deteriorating situation, the national capital must enact radical and well-thought-out legislation and regulations governing firecrackers, as well as raise public awareness amongst its citizens.


Subject(s)
Air Pollutants , Air Pollution , Humans , Air Pollutants/analysis , Holidays , Particulate Matter/analysis , Environmental Monitoring/methods , Air Pollution/analysis , India
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