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1.
J Clin Oncol ; 42(8): 907-914, 2024 Mar 10.
Artículo en Inglés | MEDLINE | ID: mdl-37967307

RESUMEN

PURPOSE: We tested whether blinatumomab (Blina) is effective as a toxicity-sparing alternative to first-line intensive chemotherapy in children and young persons (CYP) with B-ALL who were chemotherapy-intolerant or chemotherapy-resistant. METHODS: Data were collected for consecutive CYP (age 1-24 years) with Philadelphia chromosome-positive or Philadelphia chromosome-negative B-ALL who received Blina as first-line therapy. Blina was given as replacement for postremission intensive chemotherapy to patients with chemotherapy intolerance or resistance. Blina responders received further chemotherapy (Blin-CT) or first remission hematopoietic stem-cell transplant (Blin-HSCT) if indicated. Event-free survival (EFS) and overall survival (OS) of the Blin-CT group were compared with those of matched controls treated with standard chemotherapy in the UKALL 2003 trial. Events were defined as death, relapse, or secondary cancer. RESULTS: From February 2018 to February 2023, 105 patients were treated, of whom 85 were in the Blin-CT group and 20 were in the Blin-HSCT group. A majority of Blin-CT patients received Blina for chemotherapy intolerance (70 of 85, 82%), and the group had a higher-risk profile than unselected patients with B-ALL. Blina was well tolerated with only one patient having a grade 3/4-related toxicity event, and of the 60 patients who were minimal residual disease-positive pre-Blina, 58 of 60 (97%) responded. At a median follow-up of 22 months, the 2-year outcomes of the 80 matched Blin-CT group patients were similar to those of 192 controls (EFS, 95% [95% CI, 85 to 98] v 90% [95% CI, 65 to 93] and OS, 97% [95% CI, 86 to 99] v 94% [95% CI, 89 to 96]). Of the 20 in the HSCT group, three died because of transplant complications and two relapsed. CONCLUSION: Blina is safe and effective in first-line treatment of chemotherapy-intolerant CYP with ALL.


Asunto(s)
Anticuerpos Biespecíficos , Trasplante de Células Madre Hematopoyéticas , Leucemia Mieloide Aguda , Niño , Humanos , Lactante , Preescolar , Adolescente , Adulto Joven , Adulto , Cromosoma Filadelfia , Recurrencia Local de Neoplasia/tratamiento farmacológico , Anticuerpos Biespecíficos/efectos adversos , Leucemia Mieloide Aguda/tratamiento farmacológico
2.
Environ Monit Assess ; 195(7): 820, 2023 Jun 08.
Artículo en Inglés | MEDLINE | ID: mdl-37289326

RESUMEN

With increasing anthropic activities, a myriad of typical contaminants from industries, hospitals, and municipal discharges have been found which fail to be categorized under regulatory standards and are hence considered contaminants of "emerging concern". Since these pollutants are not removed effectively even by the conventional treatment systems, they tend to inflict potential threats to both human and aquatic life. However, microalgae-mediated remediation strategies have recently gained worldwide importance owing to their role in carbon fixation, low operational cost, and production of high-value products. In this study, centric diatom Chaetoceros neogracilis was exposed to different concentrations of estradiol (E2)-induced synthetic media ranging from 0 to 2 mg L-1, and its impact on the antioxidative system of algae was investigated. The results demonstrate that the nutrient stress caused a strong oxidative response elevating the superoxide dismutase (SOD) activity and malondialdehyde (MDA) content in the 2 mg L-1 E2-treated diatom cultures. However, the specific activity of the H2O2 radical scavenging enzymes like catalase (CAT) was inhibited by the E2 treatment, while that of ascorbate peroxidase (APX) remained comparable to the control (0 mg L-1 of E2). Thus, the study reveals the scope of diatoms as potential indicators of environmental stress even under the varying concentration of a single contaminant (E2).


Asunto(s)
Antioxidantes , Diatomeas , Humanos , Antioxidantes/metabolismo , Diatomeas/metabolismo , Superóxido Dismutasa/metabolismo , Peróxido de Hidrógeno , Monitoreo del Ambiente , Catalasa/metabolismo , Ascorbato Peroxidasas/metabolismo , Estrés Oxidativo
3.
Bioresour Technol ; 354: 127204, 2022 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-35460844

RESUMEN

In the current study, the isolated Methylobacterium sp. ISTM1 simultaneously produced both extracellular polymeric substances (EPS) and polyhydroxyalkanoates (PHA) in a single-step process. The yield of biopolymers (EPS and PHA) was enhanced by optimizing the process parameters of EPS and PHA production. Methylobacterium sp. ISTM1 was able to produce 7.18 ± 0.04 g L-1 EPS and 1.41 ± 0.04 g L-1 PHA simultaneously at optimized culture conditions i.e., 9% molasses and pH 7. The genomic analysis of the strain has identified the involved genes and pathways in the production of EPS and PHA. Both the biopolymers were found non-toxic according to the cytotoxicity analysis. The results of the current study present the potential of the bacterium Methylobacterium sp. ISTM1 produces non-toxic biopolymers by utilizing agro-industrial waste (molasses) that can be harnessed sustainably for various applications.


Asunto(s)
Methylobacterium , Polihidroxialcanoatos , Biopolímeros , Matriz Extracelular de Sustancias Poliméricas , Genómica , Melaza
4.
Bioresour Technol ; 351: 126936, 2022 May.
Artículo en Inglés | MEDLINE | ID: mdl-35247565

RESUMEN

Most of the discarded waste material paves their way to the utmost common dumping grounds, Landfills. Despite their widespread use, the landfill microbiomes are still not well characterized. Metagenomics approach provides insight into the identification of operational parameters influencing the microbiome composition and their biodegradation competencies. The metagenomic DNA was prepared to explore taxonomical community structure, phylogenetic relationships, and functional profile at the same time. A total of 100,021,052 high-quality filtered reads were acquired with a GC abundance of 62.59%. Taxonomical abundance revealed the dominance of phylum Proteobacteria and genes involved in biomolecules metabolism, aromatic compound degradation, stress tolerance, xenobiotic biodegradation etc. were revealed functionally. The intricate heterogeneous environment of landfill revealed well flourished biogeochemical metabolic profiles including nitrogen metabolism. This is the first study for the generated metagenome of Ghazipur landfill and the obtained results propose that microbial communities in landfill settings are far more intricate than expected. It remain mostly unexplored which demands the usage of multiple platforms for a better understanding.


Asunto(s)
Metagenómica , Microbiota , Metagenoma , Microbiota/genética , Filogenia , Instalaciones de Eliminación de Residuos
5.
Environ Sci Pollut Res Int ; 29(26): 38950-38971, 2022 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-35304714

RESUMEN

The increase in demand of fossil fuel uses for developmental activity and manufacturing of goods have resulted a huge emission of global warming gases (GWGs) in the atmosphere. Among all GWGs, CO2 is the major contributor that inevitably causes global warming and climate change. Mitigation strategies like biological CO2 capture through sequestration and their storage into biological organic form are used to minimize the concentration of atmospheric CO2 with the goal to control climate change. Since increasing atmospheric CO2 level supports microbial growth and productivity thus microbial-based CO2 sequestration has remarkable advantages as compared to plant-based sequestration. This review focuses on CO2 sequestration mechanism in bacteria through different carbon fixation pathways, involved enzymes, their role in calcite, and other environmentally friendly biomaterials such as biofuel, bioplastic, and biosurfactant.


Asunto(s)
Dióxido de Carbono , Combustibles Fósiles , Bacterias/metabolismo , Carbono/metabolismo , Dióxido de Carbono/análisis , Secuestro de Carbono , Estudios Prospectivos
6.
Bioresour Technol ; 346: 126642, 2022 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-34973404

RESUMEN

In the recent past, the presence of steroid hormones in marine bodies has led to the eruption of endocrine - disrupting molecules which have detrimental effects on aquatic life. However, the resilience and robustness of diatoms to adsorb and grow under the multitude of nutrient stress allow them to utilize the plethora of such compounds. Hence, in this study, we have implemented this unique ability of diatoms to sustain on simulated steroidal wastewater made of estradiol pills and analyze their corresponding impact on growth, biomass production, and lipid synthesis. We hereby report that with an increasing concentration of estradiol (0.5-2.0 mg L-1) there was an increment in cell numbers, and a 1.5-fold increase in the dry cell weight and lipid content (up to 29.5% DW). Thus, culturing Chaetoceros gracilis in the optimized media had a significant impact on biomass productivity which could further promote the untapped potential of diatoms.


Asunto(s)
Diatomeas , Preparaciones Farmacéuticas , Biomasa , Estradiol , Lípidos
7.
Emerg Nurse ; 30(3): 33-40, 2022 May 03.
Artículo en Inglés | MEDLINE | ID: mdl-35018749

RESUMEN

Sickle cell disease is a group of inherited blood disorders characterised by atypical haemoglobin molecule structures (haemoglobin S) which can manifest as painful vaso-occlusive crises, chronic anaemia and progressive organ damage. This article aims to raise greater awareness of sickle cell disease, its acute manifestations and the potential for rapid clinical deterioration that can occur in patients with this condition. The article outlines the main aspects of the assessment and management of patients presenting to the emergency department (ED) with vaso-occlusive crisis, describes the barriers to effective care that they commonly experience and explains how their care could be improved. The authors emphasise the importance of timely management of these patients by ED staff, including emergency nurses.


Asunto(s)
Anemia de Células Falciformes , Anemia de Células Falciformes/complicaciones , Anemia de Células Falciformes/diagnóstico , Servicio de Urgencia en Hospital , Humanos , Dolor , Manejo del Dolor
8.
Chemosphere ; 287(Pt 3): 132321, 2022 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-34563778

RESUMEN

Agroforestry, an integration of farming system with woody perennials leads to the generation of potential agroforestry residues. The conventional treatment of agroforestry waste includes landfilling, thermal management, and decomposition which is accompanied with their own share of disadvantages. The ample amount of residues and products needs effective management to reap the economic and environmental benefits. The channel of waste collection, transportation, and recycle or valorization into products like biofuel, fertilizers, biochar, industrial chemicals is essential to maintain a circular sustainable bioeconomy. Global market value of biowaste to bioenergy (BtB) technology is roughly US $25.32 billion and is projected to enhance to US $40 billion by 2023. Employment of an appropriate pretreatment technology such as fermentation, hydrolysis, gasification etc. is going to elevate the degree of valorization along with surpassing the mobilization barrier. The sustainability assessment of the management process can be achieved with multiple models including technoeconomic analysis, life cycle assessment and multi criteria approach which are dependent on both hard and soft indices. Additionally, the loopholes of the agroforestry sectors would be managed by the introduction of appropriate policies which are undertaken globally by the Orlando and Lugo declarations, food and agriculture organization, Millennium Development Goals, Global Research Alliance and Guidelines for Sustainable Agriculture and Rural Development. The present review envisaged the agroforestry waste management strategy and its sustainability assessment primarily based upon Social, Economic and Environmental parameters without tormenting the future generations.


Asunto(s)
Agricultura Forestal , Administración de Residuos , Agricultura , Biocombustibles , Reciclaje
9.
Arch Dis Child Educ Pract Ed ; 107(3): 169-174, 2022 06.
Artículo en Inglés | MEDLINE | ID: mdl-33832961

RESUMEN

Children with sickle cell disease can develop life-threatening and painful crises that require prompt assessment and efficient management by healthcare professionals in the emergency or acute care setting. Due to migration patterns and improved survival rates in high-prevalence countries, there is an increased tendency to encounter these patients across the UK. These factors warrant regular revisions in sickle cell crisis management, along with education for medical personnel and patients to improve clinical care and patient management. The focus of this article is on the initial assessment and management of acute paediatric sickle cell complications in the emergency setting. Specific case studies, including acute pain crises, trauma, splenic sequestration, aplastic crises, acute chest syndrome, infection, avascular necrosis, osteomyelitis and stroke, are discussed. Due to the current COVID-19 pandemic, we have also reviewed specific concerns around this patient group.


Asunto(s)
Anemia de Células Falciformes , COVID-19 , Anemia de Células Falciformes/complicaciones , Anemia de Células Falciformes/diagnóstico , Anemia de Células Falciformes/terapia , Niño , Servicio de Urgencia en Hospital , Humanos , Pandemias , Derivación y Consulta
10.
Bioresour Technol ; 337: 125418, 2021 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-34153867

RESUMEN

The current study demonstrates the enhanced production capability of strain Cupriavidus sp. ISTL7 for polyhydroxyalkanoates (PHA) using acetate and glucose (4.93 ± 0.4571 g L-1) which was characterised analytically by GC-MS, FTIR and NMR analysis. Whole genome sequencing of strain ISTL7 unveiled an array of PHA metabolism genes which included phaA, phaB and phaC. Life cycle assessment of the protocol established that the production was most sustainable with the carbon source acetate. + Glucose as compared to acetate/glucose alone. It also concluded that solvent extraction of PHA and energy consumption during the process requires optimization to sustain the production on ecological fronts. Additionally, acetoacetyl-CoA reductase (phaB) gene was molecularly cloned, expressed and purified (27 KDa, 2.63 mg/ml). Conclusively, Cupriavidus sp. ISTL7 is a potential strain for PHA production with a scope of improvement on energy fronts which would transform the production environmentally and economically appealing.


Asunto(s)
Cupriavidus necator , Cupriavidus , Polihidroxialcanoatos , Animales , Cupriavidus/genética , Cupriavidus necator/genética , Estadios del Ciclo de Vida , Secuenciación Completa del Genoma
11.
Bioresour Technol ; 330: 124981, 2021 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-33756182

RESUMEN

Syringyl monomeric units are the most common intermediates encountered during hardwood lignin degradation. In the present study, efficient utilization of syringaldehyde (SAld), syringic acid (SAc) by Burkholderia sp. ISTR5 (R5) has been shown. The proteogenomic analysis of Burkholderia sp. ISTR5 was done to understand the enzymes involved in the degradation of syringaldehyde and syringic acid. Various proteins such as aldehyde dehydrogenase, laccase, and oxidoreductases were highly upregulated during growth on syringaldehyde and syringic acid. R5 completely transformed both the substrates SAld and SAc to other hydrocarbons in 48 h and 24 h, respectively. Moreover, bioconversion of syringyl lignins followed an unusual pathway and accumulated a considerable amount of industrially valuable chemical malic acid in the reaction titer. This study shows the robust chassis of R5 to cope with the aromatic aldehydic stress and simultaneous bioconversion into valuable products for an efficient biorefinery.


Asunto(s)
Burkholderia , Lignina , Malatos , Oxidorreductasas
12.
Environ Res ; 192: 110277, 2021 01.
Artículo en Inglés | MEDLINE | ID: mdl-33069701

RESUMEN

The present study discusses the genomic analysis of Bacillus sp. ISTL8 along with the production of EPS (Extracellular polymeric substances) using carbofuran, a toxic carbamate pesticide. Bacillus strain was isolated from landfill soil and evaluated for high growth rates and EPS production. One strain, renamed ISTL8 grew on a broad range of carbon sources, including toxic carbofuran, while producing copious EPS. Growth assays verified the strain to be thermophilic, low salt tolerant, and with a preference for neutral pH. SEM (Scanning Electron Microscopy) was used for morphological characterization of the EPS while the monomeric composition, bonding patterns and functional groups were deduced by GC-MS (Gas Chromatography-Mass Spectrometry), 1H and 13C NMR (Nuclear Magnetic Resonance) and FTIR (Fourier Transform Infrared Spectroscopy). The production of EPS using carbofuran (carbamate pesticide) as a carbon source was found to be 6.20 ± 0.29 g L-1 containing 61.17% w/w carbohydrates, 29.72% w/w proteins and 6.11% w/w lipids (of dry EPS). The potential cytotoxicity of EPS was evaluated with 3- (4,5-dimethyl thiazol-2-Yl) -2,5-diphenyl tetrazolium bromide (MTT) assay and found non-toxic (2.25%). WGS (Whole genome sequencing) was performed for the strain Bacillus sp. ISTL8 producing EPS; an array of genes putatively involved in the EPS production were identified in several different genomic locations, guiding potential genetic manipulation studies in the future. The results highlight the potency of a bacterial isolate Bacillus sp. ISTL8 to produce non-cytotoxic EPS using carbofuran that can be further harnessed for environmental and commercial applications. Additionally, WGS revealed an array of EPS specific genes which can be effectively engineered for much enhanced production.


Asunto(s)
Bacillus , Matriz Extracelular de Sustancias Poliméricas , Bacillus/genética , Genómica , Suelo , Espectroscopía Infrarroja por Transformada de Fourier
13.
Bioresour Technol ; 320(Pt B): 124439, 2021 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-33246798

RESUMEN

The strain Burkholderia sp. ISTR5 (R5) was studied for polyhydroxyalkanoate (PHA) production on Kraft lignin (KL) and lignosulfonate (LS) as substrates. During the initial screening, the maximum PHA mass fraction in biomass produced on KL and LS was 23% and 18%, respectively, at 96 h. PHA production on KL was further optimized using the Box-Behnken Design (BBD) model of Response Surface Methodology (RSM). After optimization, a 42.5% increase in PHA production and a 32.2% increase in the total cell biomass was observed. PHA was characterized by GC-MS, TEM, FTIR, NMR, and fluorescence microscopy. It was found to be a small chain length PHA with a copolymer of poly (hydroxybutyrate-co-hydroxyvalerate) (PHBV). The degradation of PHBV was also studied using this strain; it was observed that R5 completely degraded PHBV in 120 h. Genomic and proteomic analysis of R5 revealed numerous enzymes for the metabolism of lignin degradation and PHA production.


Asunto(s)
Polihidroxialcanoatos , Proteogenómica , Biomasa , Lignina , Poliésteres , Proteómica
14.
Environ Pollut ; 269: 116176, 2021 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-33307397

RESUMEN

Polycyclic aromatic hydrocarbons (PAHs) such as pyrene are universal contaminants existing in the environment which have known cancer-causing and mutagenic characteristics. A psychrophilic bacterial strain Shewanella sp. ISTPL2 was isolated from the sediment sample collected from the Pangong lake, Jammu & Kashmir, India. In our previous study, the pyrene degradation potential of the ISTPL2 strain was studied in both mineral salt media as well as in soil artificially spiked with different concentrations of pyrene. Whole-genome sequencing of ISTPL2 strain in the current study highlighted the key genes of pyrene metabolism, including alcohol dehydrogenase and ring hydroxylating dioxygenase alpha-subunit. Pyrene cytotoxicity was evaluated on HepG2, a human hepato-carcinoma cell line. The cytotoxicity of the organic extract decreased with the increasing duration of bacterial treatment. To develop a more sustainable biodegradation approach, the potential impacts were evaluated for human health and ecosystem using life-cycle assessment (LCA) following the ReCiPe methodology for the considered PAH. The results implemented that global warming potential (GWP) had the highest impact, whereas both ecotoxicity and human toxicity had least from this study.


Asunto(s)
Hidrocarburos Policíclicos Aromáticos , Shewanella , Animales , Biodegradación Ambiental , Ecosistema , Humanos , India , Estadios del Ciclo de Vida , Pirenos/toxicidad , Shewanella/genética
15.
J Hazard Mater ; 409: 124496, 2021 05 05.
Artículo en Inglés | MEDLINE | ID: mdl-33187797

RESUMEN

Phthalates are a group of emerging xenobiotic compounds commonly used as plasticizers. In recent times, there has been an increasing concern over the risk of phthalate exposure leading to adverse effects to human health and the environment. Therefore, it is necessary to not only understand the current status of phthalate pollution, their sources, exposure routes and health impacts, but also identify remediation technologies for mitigating phthalate pollution. Present review article aims to inform its readers about the ever increasing data on health burdens posed by phthalates and simultaneously highlights the recent advancements in research to alleviate phthalate contamination from environment. The article enumerates the major phthalates in use today, traces their environmental fate, addresses their growing health hazard concerns and largely focus on to provide an in-depth understanding of the different physical, chemical and biological treatment methods currently being used or under research for alleviating the risk of phthalate pollution, their challenges and the future research perspectives.

16.
Environ Res ; 191: 110064, 2020 12.
Artículo en Inglés | MEDLINE | ID: mdl-32846180

RESUMEN

In the current study, EPS producing strain Parapedobacter sp. ISTM3 was isolated from Mawsmai cave, Meghalaya, India. The strain ISTM3 showed enhanced EPS production (4.65 ± 0.10 g L-1) at optimized parameters, i.e., pH 8 and 3% molasses as a carbon source. The extracted EPS was structurally characterized by GC-MS, NMR, and FTIR analysis to investigate its monomer compositions, functional groups, and linkage analysis. GC-MS study confirmed the heteropolymeric nature of EPS, whereas the FTIR study confirmed the presence of an aliphatic group, amine group, uronic acid, and saccharides group in the EPS structure. Biosorption of heavy metals by EPS from an aqueous solution was investigated by using heavy metals mixture (Zn2+, Cu2+, Pb2+, Cr6+, Fe2+, and Cd2+) with 20 mg L-1 concentration of each metal. EPS showed the highest removal efficiency and metal adsorption capability for Cr6+ as compared to other heavy metals studied. Also, metal adsorption capability (19.032 mg g-1) and removal efficiency (95.10%) of Cr6+ by EPS were further increased in acidic conditions (pH 5.0). FTIR and SEM-EDX analysis confirmed the biosorption mechanism of EPS. The Freundlich and Langmuir adsorption isotherms were employed to discover the biosorption parameters for Cr6+ uptake with a concentration range of 10-200 mg L-1 by EPS (1 g L-1). The Langmuir model was found to better fit the Cr6+ adsorption by EPS having a maximum adsorption capacity of 33.783 mg g-1. With this, the present study highlights the EPS production potential of Parapedobacter sp. ISTM3, as well as the potential of extracted EPS for heavy metals removals via adsorption.


Asunto(s)
Matriz Extracelular de Sustancias Poliméricas , Metales Pesados , Adsorción , Matriz Extracelular de Sustancias Poliméricas/química , Concentración de Iones de Hidrógeno , India , Cinética , Metales Pesados/análisis
17.
Trends Biotechnol ; 38(9): 963-975, 2020 09.
Artículo en Inglés | MEDLINE | ID: mdl-32818444

RESUMEN

Burkholderia, a bacterial genus comprising more than 120 species, is typically reported to inhabit soil and water environments. These Gram-negative bacteria harbor a variety of aromatic catabolic pathways and are thus potential organisms for bioremediation of sites contaminated with aromatic pollutants. However, there are still substantial gaps in our knowledge of these catabolic processes that must be filled before these pathways and organisms can be harnessed for biotechnological applications. This review presents recent discoveries on the catabolism of monoaromatic and polycyclic aromatic hydrocarbons, as well as of heterocyclic compounds, by a diversity of Burkholderia strains. We also present a perspective on the beneficial features of Burkholderia spp. and future directions for their potential utilization in the bioremediation and bioconversion of aromatic compounds.


Asunto(s)
Biodegradación Ambiental , Burkholderia/metabolismo , Hidrocarburos Policíclicos Aromáticos/metabolismo , Contaminantes del Suelo/metabolismo , Burkholderia/genética , Compuestos Orgánicos/metabolismo , Compuestos Orgánicos/toxicidad , Hidrocarburos Policíclicos Aromáticos/toxicidad , Microbiología del Suelo , Contaminantes del Suelo/toxicidad
18.
J Cancer Res Clin Oncol ; 146(11): 2777-2815, 2020 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-32705365

RESUMEN

PURPOSE: Nuclear respiratory factor 1 (NRF1) drives estrogen-dependent breast tumorigenesis. Herein we examined the impact of NRF1 activity on the aggressiveness and disparate molecular signature of breast cancer in Black, White, Asian, and Hispanic women. METHODS: NRF1 activity by transcription factor target enrichment analysis and causal NRF1-target gene signatures by Bayesian Network Inference with Java Objects (BANJO) and Markov Chain Monte Carlo (MCMC)-based gene order were examined in The Cancer Genome Atlas (TCGA) breast cancer cohorts. RESULTS: We are the first to report increased NRF1 activity based on its differential effects on genome-wide transcription associated with luminal A and B, HER2+ and triple-negative (TN) molecular subtypes of breast cancer in women of different race/ethnicity. We observed disparate NRF1 motif-containing causal gene signatures unique to Black, White, Asian, and Hispanic women for luminal A breast cancer. Further gene order searches showed molecular heterogeneity of each subtype of breast cancer. Six different gene order sequences involving CDK1, HMMR, CCNB2, CCNB1, E2F1, CREB3L4, GTSE1, and LMNB1 with almost equal weight predicted the probability of luminal A breast cancer in whites. Three different gene order sequences consisting of CCNB1 and GTSE1, and CCNB1, LMNB1, CDK1 or CASP3 predicted almost 100% probability of luminal B breast cancer in whites; CCNB1 and LMNB1 or GTSE predicted 100% HER2+ breast cancer in whites. GTSE1 and TUBA1C combined together predicted 100% probability of developing TNBC in whites; NRF1, TUBA1B and BAX with EFNA4, and NRF1 and BTRC predicated 100% TNBC in blacks. High expressor NRF1 TN breast tumors showed unfavorable prognosis with a high risk of breast cancer death in white women. CONCLUSION: Our findings showed how sensitivity to high NRF1 transcriptional activity coupled with its target gene signatures contribute to racial differences in luminal A and TN breast cancer subtypes. This knowledge may be useful in personalized intervention to prevent and treat this clinically challenging problem.


Asunto(s)
Neoplasias de la Mama/etnología , Neoplasias de la Mama/genética , Factor Nuclear 1 de Respiración/genética , Transcriptoma/genética , Adulto , Femenino , Humanos , Persona de Mediana Edad
19.
Int J Mol Sci ; 21(14)2020 Jul 10.
Artículo en Inglés | MEDLINE | ID: mdl-32664313

RESUMEN

Most of environment-related diseases often result from multiple exposures of abiotic and/or biotic stressors across various life stages. The application of environmental DNA/RNA (eDNA/eRNA) to advance ecological understanding has been very successfully used. However, the eminent extension of eDNA/eRNA-based approaches to estimate human exposure to biotic and/or abiotic environmental stressors to understand the environmental causes of chronic diseases has yet to start. Here, we introduce the potential of eDNA/eRNA for bio-monitoring of human exposome and health effects in the real environmental or occupational settings. This review is the first of its kind to discuss how eDNA/eRNA-based approaches can be applied for assessing the human exposome. eDNA-based exposome assessment is expected to rely on our ability to capture the genome- and epigenome-wide signatures left behind by individuals in the indoor and outdoor physical spaces through shedding, excreting, etc. Records of eDNA/eRNA exposome may reflect the early appearance, persistence, and presence of biotic and/or abiotic-exposure-mediated modifications in these nucleic acid molecules. Functional genome- and epigenome-wide mapping of eDNA offer great promise to help elucidate the human exposome. Assessment of longitudinal exposure to physical, biological, and chemical agents present in the environment through eDNA/eRNA may enable the building of an integrative causal dynamic stochastic model to estimate environmental causes of human health deficits. This model is expected to incorporate key biological pathways and gene networks linking individuals, their geographic locations, and random multi-hits of environmental factors. Development and validation of monitoring of eDNA/eRNA exposome should seriously be considered to introduce into safety and risk assessment and as surrogates of chronic exposure to environmental stressors. Here we highlight that eDNA/eRNA reflecting longitudinal exposure of both biotic and abiotic environmental stressors may serve as records of human exposome and discuss its application as molecular tools for understanding the toxicogenomics basis of environment-related health deficits.


Asunto(s)
ADN Ambiental/genética , Monitoreo del Ambiente/métodos , ARN/genética , Estrés Fisiológico/genética , Animales , Enfermedad Crónica , Ambiente , Exposoma , Humanos , Medición de Riesgo
20.
Sci Total Environ ; 731: 139074, 2020 Aug 20.
Artículo en Inglés | MEDLINE | ID: mdl-32417476

RESUMEN

The environment of a high altitude brackish water lake presents an unprecedented reservoir for the microbial community with adaptability towards surviving stressful conditions. Pangong lake is a high altitude brackish water lake of the Himalayas situated in the eastern part of Ladakh (Indian Tibet), at the height of 4250 m above the sea level. Shotgun metagenomics sequencing of Pangong Lake sediments was performed to examine the taxonomic diversity and functional adaptations of the resident psychrophilic and psychrotolerant microbial communities of the lake (September; a temperature of ±10 °C). Proteobacteria was the most prominent phylum, and Methylophaga, Halomonas, and Marinobacter were mainly abundant at the genus level. Enzyme pathways responsible for methane metabolism, nitrogen metabolism, sulfur reduction, benzoate, and xylene degradation appeared to be complete in the metagenomic dataset. Stress response genes responsible for adaption to pH, cold, salt tolerance, osmotic stress, and oxidative stress were also found in abundance in the metagenome. We compared the Pangong lake metagenome sample to sediments and water samples from three different aquatic habitats, namely saline lake, freshwater lakes and marine ecosystem using MG-RAST server against RefSeq and Subsystem databases. The Pangong lake microbial community contains six unique genera. Regression analysis using metagenome samples suggested that Pangong lake was most closely related to the Trophic South Pacific Ocean (R2 = 0.971) and Socompa lake ecosystem (R2 = 0.991) at phylum and functional level II, respectively. Our study signifies that the functional metabolic potentiality of Pangong lake is strongly influenced by the taxonomic structure and environmental conditions. We are reporting the metagenome of the sediment sample of the Pangong lake, which unveils the microbial diversity and their functional potential.


Asunto(s)
Lagos , Metagenoma , Bacterias/genética , Sedimentos Geológicos , Metagenómica , Océano Pacífico , Filogenia , Tibet
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