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Delayed wound healing are common complications for diabetic patients. In light of chronic hypoxia's delay in wound healing, it is hypothesized that providing a better oxygen environment at the wound site will promote diabetic wound healing. OXY-ExoAloe is an innovative and effective therapy prepared from exosome-like vesicles of aloe vera gel, ginger juice and neem fruit sap. A combination of three herbal, oxygen-delivering and medicinally valued plants was standardized to determine if the combination had the desired effect. Interestingly, when we used OXY-ExoAloe at a particular ratio on a diabetic wound, the herbal therapy speeded up wound healing by reducing swelling, and the severity of the wound. Further, our data suggests that OXY-ExoAloe promoted wound healing by increasing wound oxygenation, reducing inflammation, cytokine production, and matrix remodeling. It is also safe and effective, with no reported side effects.
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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.
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Antagonistas de Receptores de Andrógenos , Endoglina , Neoplasias de Próstata Resistentes à Castração , Receptores Androgênicos , Humanos , Masculino , Resistencia a Medicamentos Antineoplásicos , Células Neoplásicas Circulantes/metabolismo , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Neoplasias de Próstata Resistentes à Castração/metabolismo , Isoformas de Proteínas , Receptores Androgênicos/genética , Receptores Androgênicos/metabolismo , Proteínas de Ligação a RNA , Endoglina/antagonistas & inibidores , Antagonistas de Receptores de Andrógenos/uso terapêutico , Anticorpos Neutralizantes/uso terapêuticoRESUMO
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.
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Monitoramento Ambiental , Ruído dos Transportes , Ferrovias , Humanos , Índia , Monitoramento Ambiental/métodos , Adulto , Masculino , Feminino , Exposição Ambiental/estatística & dados numéricos , Inquéritos e Questionários , Pessoa de Meia-IdadeRESUMO
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.
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Endocitose , Pinocitose , Endocitose/fisiologia , Endossomos , Microdomínios da Membrana/metabolismo , FagocitoseRESUMO
Stromal-epithelial interactions dictate cancer progression and therapeutic response. Prostate cancer (PCa) cells were identified to secrete greater concentration of mitochondrial DNA (mtDNA) compared to noncancer epithelia. Based on the recognized coevolution of cancer-associated fibroblasts (CAF) with tumor progression, we tested the role of cancer-derived mtDNA in a mechanism of paracrine signaling. We found that prostatic CAF expressed DEC205, which was not expressed by normal tissue-associated fibroblasts. DEC205 is a transmembrane protein that bound mtDNA and contributed to pattern recognition by Toll-like receptor 9 (TLR9). Complement C3 was the dominant gene targeted by TLR9-induced NF-κB signaling in CAF. The subsequent maturation complement C3 maturation to anaphylatoxin C3a was dependent on PCa epithelial inhibition of catalase in CAF. In a syngeneic tissue recombination model of PCa and associated fibroblast, the antagonism of the C3a receptor and the fibroblastic knockout of TLR9 similarly resulted in immune suppression with a significant reduction in tumor progression, compared to saline-treated tumors associated with wild-type prostatic fibroblasts. Interestingly, docetaxel, a common therapy for advanced PCa, further promoted mtDNA secretion in cultured epithelia, mice, and PCa patients. The antiapoptotic signaling downstream of anaphylatoxin C3a signaling in tumor cells contributed to docetaxel resistance. The inhibition of C3a receptor sensitized PCa epithelia to docetaxel in a synergistic manner. Tumor models of human PCa epithelia with CAF expanded similarly in mice in the presence or absence of docetaxel. The combination therapy of docetaxel and C3 receptor antagonist disrupted the mtDNA/C3a paracrine loop and restored docetaxel sensitivity.
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Anafilatoxinas/metabolismo , Fibroblastos Associados a Câncer/patologia , DNA Mitocondrial/metabolismo , Docetaxel/farmacologia , Resistencia a Medicamentos Antineoplásicos , Epitélio/patologia , Neoplasias da Próstata/patologia , Animais , Antineoplásicos/farmacologia , Apoptose , Fibroblastos Associados a Câncer/efeitos dos fármacos , Fibroblastos Associados a Câncer/metabolismo , Epitélio/efeitos dos fármacos , Epitélio/metabolismo , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Nus , Comunicação Parácrina , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/metabolismo , Receptor Toll-Like 9/metabolismo , Células Tumorais Cultivadas , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
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.
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Azospirillum brasilense , Fator sigma , Aminoácidos/metabolismo , Azospirillum brasilense/genética , Azospirillum brasilense/metabolismo , Proteínas de Bactérias/química , Regulação Bacteriana da Expressão Gênica , Homeostase , Fator sigma/químicaRESUMO
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.
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COVID-19 , Cianobactérias , Humanos , Cianobactérias/metabolismoRESUMO
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 â¼44 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.
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Poluentes Atmosféricos , Poluição do Ar , Poluentes Atmosféricos/análise , Poluição do Ar/análise , Monitoramento Ambiental , Férias e Feriados , Humanos , Índia , Tamanho da Partícula , Material Particulado/análiseRESUMO
This study was conducted for the metagenomic analysis of stool samples from CRC affected individuals to identify biomarkers for CRC in Hainan, the only tropical island province of China. The gut microbiota of CRC patients differed significantly from that of healthy and reference database cohorts based on Aitchison distance and Bray-Cutis distance but there was no significant difference in alpha diversity. Furthermore, at the species level, 68 species were significantly altered including 37 CRC-enriched, such as, Fusobacterium nucleatum, Parvimonas micra, Gemella morbillorum, Citrobacter portucalensis, Alloprevotella sp., Shigella sonnei, Coriobacteriaceae bacterium, etc. Sixty-seven different metabolic pathways were acquired, and pathways involved in the synthesis of many amino acids were significantly declined. Besides, 2 identified antibiotic resistance genes performed well (area under the receive-operation curve AUC = 0.833, 95% CI 58.51-100%) compared with virulence factor genes. The results of the present study provide region-specific bacterial and functional biomarkers of gut microbiota for CRC patients in Hainan. Microbiota is considered as a non-invasive biomarker for the detection of CRC. Gut microbiota of different geographic regions should be further studied to expand the understanding of markers, especially for the China cohort due to diverse nationalities and lifestyles.
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Neoplasias Colorretais , Biomarcadores , China , Citrobacter , Firmicutes , Gemella , HumanosRESUMO
ECF41 is a large family of bacterial extra-cytoplasmic function (ECF) σ factors. Their role in bacterial physiology or behavior, however, is not known. One of the 10 ECF σ factors encoded in the genome of Azospirillum brasilense Sp245, RpoE10, exhibits characteristic features of the typical ECF41-type σ factors. Inactivation of rpoE10 in A. brasilense Sp245 led to an increase in motility that could be complemented by the expression of rpoE10 By comparing the number of lateral flagella, transcriptome and proteome of A. brasilense Sp245 with its rpoE10::km mutant, we show here that this ECF41-type σ factor is involved in the negative regulation of swimming motility and biogenesis of lateral flagella of A. brasilense Sp245. The genome of A. brasilense Sp245 also encodes two OmpR-type regulators (LafR1 and LafR2), and three flagellins including Laf1, the major flagellin of lateral flagella. Elevated levels of laf1 transcripts and Laf1 protein in the rpoE10::km mutant indicated that RpoE10 negatively regulates the expression of Laf1. The elevated level of LafR1 in the rpoE10::km mutant indicated that LafR1 is also negatively regulated by RpoE10. The loss of motility and Laf1 in the lafR1::km mutant, complemented by lafR1 expression, showed that LafR1 is a positive regulator of Laf1 and motility in A. brasilense In addition, upregulation of laf1::lacZ and lafR1::lacZ fusions by RpoE10, and downregulation of the laf1::lacZ fusion by LafR1 suggests that RpoE10 negatively regulates swimming motility and the expression of LafR1 and Laf1. However, LafR1 positively regulates the swimming motility and Laf1 expression.Importance: Among extra-cytoplasmic function (ECF) σ factors, ECF41-type σ factors are unique due to the presence of a large C-terminal extension in place of a cognate anti- σ factor, which regulates their activity. Despite wide distribution and abundance in bacterial genomes, their physiological or behavioural roles are not known. We show here an indirect negative role of an ECF41-type of σ factor in the expression of lateral flagellar genes and motility in A.brasilense This study suggests that the motility of A. brasilense might be controlled by a regulatory cascade involving RpoE10, an unknown repressor, LafR1 and lateral flagellar genes including Laf1.
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Muscle inflammation is often associated with its expansion. Bladder smooth muscle inflammation-induced cell death is accompanied by hyperplasia and hypertrophy as the primary cause for poor bladder function. In mice, DNA damage initiated by chemotherapeutic drug cyclophosphamide activated caspase 1 through the formation of the NLRP3 complex resulting in detrusor hyperplasia. A cyclophosphamide metabolite, acrolein, caused global DNA methylation and accumulation of DNA damage in a mouse model of bladder inflammation and in cultured bladder muscle cells. In correlation, global DNA methylation and NLRP3 expression was up-regulated in human chronic bladder inflammatory tissues. The epigenetic silencing of DNA damage repair gene, Ogg1, could be reversed by the use of demethylating agents. In mice, demethylating agents reversed cyclophosphamide-induced bladder inflammation and detrusor expansion. The transgenic knock-out of Ogg1 in as few as 10% of the detrusor cells tripled the proliferation of the remaining wild type counterparts in an in vitro co-culture titration experiment. Antagonizing IL-1ß with Anakinra, a rheumatoid arthritis therapeutic, prevented detrusor proliferation in conditioned media experiments as well as in a mouse model of bladder inflammation. Radiation treatment validated the role of DNA damage in the NLRP3-associated caspase 1-mediated IL-1ß secretory phenotype. A protein array analysis identified IGF1 to be downstream of IL-1ß signaling. IL-1ß-induced detrusor proliferation and hypertrophy could be reversed with the use of Anakinra as well as an IGF1 neutralizing antibody. IL-1ß antagonists in current clinical practice can exploit the revealed mechanism for DNA damage-mediated muscular expansion.
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Hiperplasia/metabolismo , Inflamação/metabolismo , Fator de Crescimento Insulin-Like I/metabolismo , Interleucina-1beta/metabolismo , Músculo Liso/patologia , Animais , Apoptose/genética , Proteínas de Transporte/genética , Proteínas de Transporte/metabolismo , Caspase 1/metabolismo , Dano ao DNA/efeitos dos fármacos , DNA Glicosilases/metabolismo , Humanos , Hiperplasia/patologia , Inflamação/genética , Inflamação/patologia , Fator de Crescimento Insulin-Like I/genética , Proteína Antagonista do Receptor de Interleucina 1/farmacologia , Camundongos , Músculo Liso/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR , Transdução de Sinais/efeitos dos fármacos , Bexiga Urinária/metabolismo , Bexiga Urinária/patologiaRESUMO
The MYC transcription factor plays a crucial role in the regulation of cell cycle progression, apoptosis, angiogenesis, and cellular transformation. Due to its oncogenic activities and overexpression in a majority of human cancers, it is an interesting target for novel drug therapies. MYC binding to the E-box (5'-CACGTGT-3') sequence at gene promoters contributes to more than 4000 MYC-dependent transcripts. Owing to its importance in MYC regulation, we designed a novel sequence-specific DNA-binding pyrrole-imidazole (PI) polyamide, Myc-5, that recognizes the E-box consensus sequence. Bioinformatics analysis revealed that the Myc-5 binding sequence appeared in 5'- MYC binding E-box sequences at the eIF4G1, CCND1, and CDK4 gene promoters. Furthermore, ChIP coupled with detection by quantitative PCR indicated that Myc-5 has the ability to inhibit MYC binding at the target gene promoters and thus cause downregulation at the mRNA level and protein expression of its target genes in human Burkitt's lymphoma model cell line, P493.6, carrying an inducible MYC repression system and the K562 (human chronic myelogenous leukemia) cell line. Single i.v. injection of Myc-5 at 7.5 mg/kg dose caused significant tumor growth inhibition in a MYC-dependent tumor xenograft model without evidence of toxicity. We report here a compelling rationale for the identification of a PI polyamide that inhibits a part of E-box-mediated MYC downstream gene expression and is a model for showing that phenotype-associated MYC downstream gene targets consequently inhibit MYC-dependent tumor growth.
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Linfoma de Burkitt/genética , Elementos E-Box/efeitos dos fármacos , Imidazóis/química , Nylons/química , Proteínas Proto-Oncogênicas c-myc/antagonistas & inibidores , Pirróis/química , Animais , Apoptose/efeitos dos fármacos , Sítios de Ligação/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Ciclina D1/genética , Quinase 4 Dependente de Ciclina/genética , Proteínas de Ligação a DNA , Elementos E-Box/genética , Fator de Iniciação Eucariótico 4G/genética , Humanos , Camundongos , Camundongos SCID , Nylons/síntese química , Regiões Promotoras Genéticas , Ligação Proteica/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-myc/genética , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
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.
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Poluentes Atmosféricos , Poluição do Ar , Automóveis , Poluentes Atmosféricos/análise , Poluição do Ar/análise , Emissões de Veículos/análise , Monóxido de Carbono/análise , Gasolina/análiseRESUMO
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.
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Ácidos Nucleicos Livres , Neoplasias da Próstata , Humanos , Masculino , Animais , Camundongos , DNA Mitocondrial/metabolismo , Prognóstico , Neoplasias da Próstata/genética , Neoplasias da Próstata/patologia , Mitocôndrias/metabolismo , Microambiente TumoralRESUMO
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.
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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.
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Poluentes Atmosféricos , Poluição do Ar , Humanos , Poluentes Atmosféricos/análise , Férias e Feriados , Material Particulado/análise , Monitoramento Ambiental/métodos , Poluição do Ar/análise , ÍndiaRESUMO
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.
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Galinhas , Miostatina , Animais , Peso Corporal , Galinhas/genética , Feminino , Imunização , Masculino , Músculo Esquelético/metabolismo , Miostatina/genética , Fragmentos de PeptídeosRESUMO
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.
Assuntos
Rios , Poluentes Químicos da Água , Humanos , Qualidade da Água , Sistemas de Informação Geográfica , Águas Residuárias , Monitoramento Ambiental , Índia , Poluentes Químicos da Água/análise , Poluição da Água/análiseRESUMO
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.
Assuntos
Poluentes Atmosféricos , Poluição do Ar , Automóveis , Poluição do Ar/análise , Poluentes Atmosféricos/análise , Emissões de Veículos/análise , Veículos Automotores , Fumaça , Políticas , Gasolina/análiseRESUMO
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.