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1.
Analyst ; 149(12): 3456-3467, 2024 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-38738996

RESUMO

In this study, an optical sensor is developed, incorporating hydrogen-bonded photonic array dots containing poly(acrylic acid) (PAA) within a polymer cholesteric liquid crystal interpenetrating polymer network (PCLCIPN) framework, thereby effectively controlling porosity. This methodology involves the fabrication of a porous photonic film, subsequent infusion with a hydrogel (PAA), and precise UV-curing to generate patterned array dots. The sensor exhibits exceptional discriminatory capability between methanol and ethanol, accurately discerning their varying concentrations within alcohol solutions. The optical sensing performance of the film is rigorously evaluated through continuous monitoring of wavelength shifts in the transmission spectrum across various alcohol concentrations. Notably, the observed wavelength shifts demonstrate a linear correlation with the concentration of alcohol, thereby enabling precise quantitative analysis of the alcohol solutions. The sensor exhibits a sensitivity of 0.44 nm/% for ethanol concentrations ranging from 5% to 60%, increasing to 2.1 nm/% for concentrations between 60% and 80%. Similarly, for methanol, sensitivities of 0.68 nm/% (5-60%) and 2.2 nm/% (60-80%) are recorded. Remarkably, this sensitivity trend extends seamlessly to 1 : 1 ethanol/methanol ratios, with values of 0.49 nm/% (5-60%) and 2.25 nm/% (60-80%). Furthermore, these sensors demonstrate colorimetric response to different alcohols, rendering them accessible and cost-effective biosensors for visual detection, thus obviating the necessity for complex analytical instruments.

2.
CNS Spectr ; 29(1): 76-82, 2024 02.
Artigo em Inglês | MEDLINE | ID: mdl-37565485

RESUMO

BACKGROUND: Conventional treatment methods have limited effectiveness in addressing late-life depression (LLD) that does not respond well. While a new approach called priming repetitive transcranial magnetic stimulation (rTMS) has shown promise in treating depression in adults, its effectiveness in LLD has not been explored. This study aimed to investigate the impact of priming rTMS on LLD. METHODS: This study investigated the effectiveness of priming rTMS in 31 patients with LLD who did not improve after an adequate trial of antidepressants. Patients were randomly assigned to receive either active priming rTMS or sham priming rTMS. Active priming rTMS was delivered over the right dorsolateral prefrontal cortex for 10 sessions, lasting 31 minutes each, over a period of 2 weeks. RESULTS: The group receiving active priming rTMS demonstrated greater improvements in scores on the Hamilton Rating Scale for Depression (p < 0.037; partial η2 0.141) and the Geriatric Depression Rating Scale (p < 0.045; partial η2 0.131) compared to the sham priming group, with a mild effect size. At the end of the second and fourth weeks, the priming rTMS group achieved a response rate of 50%, while the sham priming group had response rates of 26.7% and 6.7%, respectively. No adverse effects requiring intervention were observed. CONCLUSION: Priming rTMS is well-tolerated for the treatment of LLD and not only reduces the severity of depression but also maintains the achieved response over time.


Assuntos
Depressão , Estimulação Magnética Transcraniana , Adulto , Humanos , Idoso , Estimulação Magnética Transcraniana/métodos , Depressão/terapia , Método Simples-Cego , Resultado do Tratamento , Antidepressivos , Córtex Pré-Frontal , Método Duplo-Cego
3.
Chem Biodivers ; 21(6): e202400059, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38584309

RESUMO

Hepatocellular carcinoma (HCC) arises from precancerous nodules, leading to liver damage and inflammation, which triggers the release of proinflammatory cytokines. Dysregulation of these cytokines can escalate into a cytokine storm, causing severe organ damage. Interestingly, Moringa oleifera (M. oleifera) fruit peel, previously discarded as waste, contains an abundance of essential biomolecules and high nutritional value. This study focuses on the eco-friendly synthesis of silver nanoparticles infused with M. oleifera peel extract biomolecules and their impact on regulating proinflammatory cytokines, as well as their potential anticancer effects against Wistar rats. The freshly synthesized nanoformulation underwent comprehensive characterization, followed by antihepatic cancer evaluation using a diethyl nitrosamine-induced model (at a dose of 200 mg kg-1 BW). The study demonstrates a significant reduction in proinflammatory cytokines such as tumor necrosis factor-α, interleukin-6, interleukin-1ß, and nuclear factor kappa beta (NF-κB). Furthermore, it confirms that the newly biosynthesized silver nanoparticles exhibit additional potential against hepatic cancer due to their capped biomolecules.


Assuntos
Citocinas , Neoplasias Hepáticas , Nanopartículas Metálicas , Moringa oleifera , Extratos Vegetais , Ratos Wistar , Prata , Moringa oleifera/química , Prata/química , Prata/farmacologia , Animais , Nanopartículas Metálicas/química , Citocinas/metabolismo , Citocinas/antagonistas & inibidores , Ratos , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/metabolismo , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Extratos Vegetais/isolamento & purificação , Masculino , Antineoplásicos/farmacologia , Antineoplásicos/química , Antineoplásicos/isolamento & purificação , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patologia , Ensaios de Seleção de Medicamentos Antitumorais , Dietilnitrosamina
4.
Microb Pathog ; 184: 106356, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37743025

RESUMO

The world has witnessed the cruelty of COVID-19 disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The association of COVID-19 with other secondary and bacterial co-infections has tremendously contributed to lung infections. An increased probability of having a secondary lung infection was observed among the post-COVID patients. The treatment of antibiotics has ameliorated the mortality rate. However, the stewardship of antibiotic treatment was linked to increased organ failure. Therefore, the paper discusses the interactions between the virus and host through the ACE2 receptors that contribute to COVID-19 development. Furthermore, the paper provides an invaluable compendium history of SARS-CoV-2 genomic composition. It revolves around most classes of antibiotics used to treat COVID-19 disease and post-COVID lung infections with the complete mechanism. This binds with the exertion of the antibiotics for bacterial infection associated with COVID-19 patients and how beneficial and effective responses have been recorded for the treatment. The application of nanotechnology and possible approaches of nanomedicines is also discussed to its potential usage.


Assuntos
Infecções Bacterianas , COVID-19 , Humanos , COVID-19/complicações , SARS-CoV-2/metabolismo , Antibacterianos/uso terapêutico , Peptidil Dipeptidase A/genética , Pulmão/metabolismo , Infecções Bacterianas/tratamento farmacológico
5.
Inorg Chem ; 62(32): 13069-13080, 2023 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-37535113

RESUMO

The hydrogenation of lignin-derived phenolics to produce valuable chemicals is a promising but challenging task. This study successfully demonstrates the use of sustainable transition metal-based catalysts to hydrogenate lignin-derived phenolics. A defect-induced oxygen vacancy containing H-NbOx prepared from commercial Nb2O5 was employed as a catalyst. H-NbOx exhibited higher oxygen vacancies (158.21 µmol/g) than commercial Nb2O5 (39.01 µmol/g), evaluated from O2-TPD. Upon supporting 10 wt % Ni, a Ni/NiO interface was formed over H-NbOx, which was intrinsically active for the hydrogenation of phenolics. 10Ni/H-NbOx exhibited a two-fold increase in activity than 10Ni/Nb2O5, achieving >99% eugenol conversion and affording ∼94% 4-propyl cyclohexanol selectivity, wherein ∼63% eugenol conversion and ∼73% 4-propyl cyclohexanol selectivity were obtained over 10Ni/Nb2O5. The Ni/NiO formation was confirmed by X-ray photoelectron spectroscopy, HR-TEM, and H2-TPR analysis, while the oxygen vacancies were verified by Raman spectroscopy and O2-TPD analysis. The resulting interface enhanced the synergy between Ni and H-NbOx and facilitated hydrogen dissociation, confirmed by H2-TPD. Remarkably, 10Ni/H-NbOx maintained its catalytic activity for five tested cycles and demonstrated exceptional activity with various phenolics. Our findings highlight the potential of a sustainable transition metal catalyst for the hydrogenation of lignin-derived phenolic compounds, which could pave the path to producing valuable chemicals in an environmentally friendly manner.

6.
Environ Sci Technol ; 57(17): 6776-6798, 2023 05 02.
Artigo em Inglês | MEDLINE | ID: mdl-37071722

RESUMO

99Technetium (99Tc) is a hazardous radionuclide that poses a serious environmental threat. The wide variation and complex chemistries of liquid nuclear waste streams containing 99Tc often create unique, site specific challenges when sequestering and immobilizing the waste in a matrix suitable for long-term storage and disposal. Therefore, an effective management plan for 99Tc containing liquid radioactive wastes (such as storage (tanks) and decommissioned wastes) will likely require a variety of suitable materials/matrixes capable of adapting to and addressing these challenges. In this review, we discuss and highlight the key developments for effective removal and immobilization of 99Tc liquid waste in inorganic waste forms. Specifically, we review the synthesis, characterization, and application of materials for the targeted removal of 99Tc from (simulated) waste solutions under various experimental conditions. These materials include (i) layered double hydroxides (LDHs), (ii) metal-organic frameworks (MOFs), (iii) ion-exchange resins (IERs) as well as cationic organic polymers (COPs), (iv) surface modified natural clay materials (SMCMs), and (v) graphene-based materials (GBMs). Second, we discuss some of the major and recent developments toward 99Tc immobilization in (i) glass, (ii) cement, and (iii) iron mineral waste forms. Finally, we present future challenges that need to be addressed for the design, synthesis, and selection of suitable matrixes for the efficient sequestration and immobilization of 99Tc from targeted wastes. The purpose of this review is to inspire research on the design and application of various suitable materials/matrixes for selective removal of 99Tc present globally in different radioactive wastes and its immobilization in stable/durable waste forms.


Assuntos
Resíduos Radioativos , Resíduos Radioativos/análise , Minerais , Argila , Tecnécio
7.
Appl Nurs Res ; 69: 151657, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36635012

RESUMO

BACKGROUND: The negative impact of self-stigma among clients with mental illness is well documented. Psychoeducation was found to be an effective measure for managing the treatment gap by reducing the stigma associated with the illness. PURPOSE: The present study investigated the effectiveness of a nurse-led brief psycho-education in reducing self-stigma among clients in the remittent stage of schizophrenia and affective disorders. METHODS: This study used Solomon- four-group design and was carried out at the Institute of mental health, Rohtak, India. A total of 80 participants were consecutively recruited using the block randomization method and as per the sampling criteria. A trained nurse delivered a 30-min individual-based brief psycho-education to the intervention group as per the standard module. The outcome measure was the reduction in the stigma based on a standardized stigma scale during a 1-month follow-up period. RESULTS: The mean age of the participants was 40.48 years (SD = 3.55). Overall, the study observed a significant reduction of stigma scores in the intervention group in the alienation, stereotype endorsement, social withdrawal domain of ISMI during 1-month follow-up (p < 0.001). No interaction effect was found between intervention and pre-test except the social withdrawal domain (p = 0.034). CONCLUSIONS: The nurse-led brief psycho-education has the potential to reduce stigma among clients with mental illness. Our findings open an area of discussion for placing greater attention on nurse-led brief psycho-education in this setting. The study provides pioneer research evidence regarding the involvement of nurses as brief psycho-education therapists among clients attending the tertiary mental health care unit of a lower-middle-income country. Considering the short-term effect of this study, more studies should be conducted in similar settings for an evidence base to advocate supportive nursing care practices in the routine mental health setting.


Assuntos
Transtornos Mentais , Esquizofrenia , Humanos , Adulto , Esquizofrenia/terapia , Papel do Profissional de Enfermagem , Estigma Social , Estereotipagem , Transtornos do Humor
8.
Indian J Crit Care Med ; 27(2): 119-126, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36865508

RESUMO

Introduction: The data of acute kidney injury (AKI), that is, community-acquired AKI (CA-AKI) and hospital-acquired AKI (HA-AKI) among non-COVID patients from intensive care units (ICU) during the coronavirus disease-2019 (COVID-19) pandemic are scarce. We planned to study the change in the profile of such patients compared to the pre-pandemic era. Materials and methods: This prospective observational study was conducted at four ICUs dealing with non-COVID patients at a government hospital in North India, and was aimed at assessing outcomes, and mortality predictors of AKI among non-COVID patients during the COVID-19 pandemic. Renal and patient survival at ICU transfer-out and hospital discharge, ICU and hospital stay duration, mortality predictors, and dialysis requirement at discharge were evaluated. The current or previous COVID-19 infection, previous AKI or chronic kidney disease (CKD), organ donors, and organ transplant patients were excluded. Results: Among the 200 non-COVID-19 AKI patients, diabetes mellitus (DM), primary hypertension, and cardiovascular diseases were the predominant comorbidities in descending order. The commonest cause of AKI was severe sepsis, followed by systemic infections and post-surgery patients. Dialysis requirements at ICU admission during ICU stay and above 30 days were seen in 20.5, 47.5, and 6.5% of patients, respectively. Incidence of CA-AKI and HA-AKI was 1.24:1, whereas dialysis requirement above 30 days was 0.85:1, respectively. The 30-day mortality was 42%. Hepatic dysfunction [hazard ratio (HR): 3.471], septicemia (HR: 3.342), age above 60 years (HR: 4.000), higher sequential organ failure assessment (SOFA) score (HR: 1.107; p = 0.001), anemia (p = 0.003), and low serum iron (p = 0.001) were important mortality predictors in AKI. Conclusion: Compared to the pre-COVID era, CA-AKI was more common than HA-AKI due to restricted elective surgeries during the COVID-19 pandemic. Acute kidney injury with multiorgan involvement and hepatic dysfunction, elderly age with higher SOFA score and sepsis were predictors of adverse renal and patient outcomes. How to cite this article: Singh B, Dogra PM, Sood V, Singh V, Katyal A, Dhawan M, et al. Spectrum, Outcomes, and Mortality Predictors of Acute Kidney Injury among Non-COVID-19 Patients during COVID-19 Pandemic: Data from Four Intensive Care Units. Indian J Crit Care Med 2023;27(2):119-126.

9.
J Anaesthesiol Clin Pharmacol ; 38(3): 488-491, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36505190

RESUMO

Dislocated hip joint is a painful condition, which requires urgent reduction. Previously, ultrasound (US)-guided pericapsular nerve group (PENG) block has been used for reduction of dislocated prosthetic hip. We have used landmark-guided PENG block in two patients of dislocation of prosthetic hip. We suggest that the landmark-guided technique of PENG block can be used safely and successfully as an alternative technique, where US facility is not available.

10.
J Environ Manage ; 297: 113374, 2021 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-34325367

RESUMO

Population growth and rapid urbanization have put a lot of pressure on the already scarce freshwater around the globe. The availability of freshwater is not only limited but it is non-uniform also. Available desalination technologies help mitigate water shortage; however, these techniques are energy-intensive and unsustainable. Desalination technologies utilizing renewable energy and bio-electrochemical systems have been developed to achieve limited sustainability. With technological advancements, microbial desalination cell (MDC) has been developed which is capable of desalination, wastewater treatment, and power generation simultaneously. This review critically examined the performance of various MDC techniques concerning their stimulus parameters including COD removal, total desalination rate, total dissolved solids reduction rate, Coulombic efficiency, and power density. Limitations of MDCs have also been incorporated in the review. Work on MDC coupled with other robust desalination techniques offering advantages such as better desalination and more water recovery e.g. osmotic-MDC etc. has been included. Researchers have tremendously worked on MDCs with different electro-catalysts. Few of these are not sustainable and costly. Authors have reviewed critically with belief that it will pave a way for the commercialization of this eco-friendly technology.


Assuntos
Fontes de Energia Bioelétrica , Purificação da Água , Tecnologia , Águas Residuárias , Água
11.
Opt Express ; 28(15): 22856-22866, 2020 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-32752539

RESUMO

A 4 mm-aperture hole-patterned liquid crystal (LC) lens has been fabricated using a LC mixture, which consisted of rutile titanium dioxide (TiO2) nanoparticles (NPs) and nematic LC E7, for the first time. The TiO2 NP dopant improves the addressing and operation voltages of the LC lens significantly because it strengthens the electric field surrounding the TiO2 NP and increases the capacitance of lens cell. Unlike the doping of common colloidal NPs, that of rutile TiO2 NPs increases the phase transition temperature and birefringence of the LC mixture, thereby helping enhance the lens power of LC lens. In comparison with a pure LC lens, the TiO2 NP-doped one has approximately 50% lower operation voltage because of the strengthened electric field around the NPs and has roughly 2.8 times faster response time because of the decreased rotational viscosity of the LC mixture and the increased interaction between the LC molecules by the NP dopants. Notably, the doping of rutile TiO2 NPs improves the operation voltage, tunable focusing capability, and response time of LC lens simultaneously. Meanwhile, this method does not degrade the focusing and lens qualities. The imaging performances of TiO2 NP-doped LC lens at various voltages are demonstrated practically by tunable focusing on three objectives at different positions. These results introduce NP in the application of LC lenses.

12.
J Biochem Mol Toxicol ; 34(11): e22567, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32729651

RESUMO

MicroRNAs (miRs) are non-protein-coding small RNAs that control the gene expression posttranscriptionally. miRs can regulate different cellular functions as well as many pathological conditions. Dysregulated miR expression profiles have been identified in different cancer types including lung cancer, breast cancer, and prostate cancer. The expression of miRs varies according to their roles in each specific cancer type. Although many miRs and their target genes have been identified in different cancers, data are still scant to validate those target genes and the mechanistic role of these miRs. The possibility of targeting cancer-associated miRs is suggested to open a new field for cancer therapy. Therapeutic strategies targeting miRs involve neutralization of the oncogenic miRs by antagomirs using locked nucleic acid oligonucleotides, miR sponges, or the restoration/overexpression of tumor-suppressing miRs that are downregulated or depleted in cancers. Although it is suggested that therapeutic applications of miRs in different pathological conditions will make a huge revolution in gene therapy, there is still an enormous challenge in employing these strategies efficiently in cancer inhibition, seemingly, due to the complexity of cancer and the current inefficient development of delivery systems for the therapeutic miRs.


Assuntos
Neoplasias da Mama/genética , Regulação Neoplásica da Expressão Gênica/fisiologia , MicroRNAs/fisiologia , Linhagem Celular Tumoral , Feminino , Humanos
13.
Bioorg Chem ; 99: 103775, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32222618

RESUMO

We have designed and synthesized 2-methoxy-3-(thiophen-2-ylmethyl)quinoline containing amino carbinols as possible anti-tubercular agents to combat the disease. These molecules were synthesized by tethering amino ether linkage with hydroxyl group to diarylquinoline skeleton; hydroxyl and amine chains were engrafted on diaryl ring. They were evaluated against strain (H37Ra) of Mycobacterium tuberculosis and most of compounds showed in vitro antitubercular activity. Two compounds having diaryl quinoline hydroxyl amino ether scaffold and three compounds having diaryl amino alkyl carbinol core showed activities at 6.25 µg/mL. This study explores diaryl carbinol prototype as inhibitor against Mycobacterium tuberculosis.


Assuntos
Antituberculosos/farmacologia , Metanol/farmacologia , Mycobacterium tuberculosis/efeitos dos fármacos , Antituberculosos/síntese química , Antituberculosos/química , Relação Dose-Resposta a Droga , Metanol/análogos & derivados , Metanol/química , Testes de Sensibilidade Microbiana , Estrutura Molecular , Relação Estrutura-Atividade
14.
Environ Monit Assess ; 191(12): 781, 2019 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-31786659

RESUMO

Prolonged consumption of fluoride-contaminated water poses health problems like dental and skeletal fluorosis in many parts of the world including India. In regions with acute water scarcity, it demands immediate intervention like de-fluoridation of water before consumption. In the current study, fluoride-resistant bacteria were isolated from fluoride-contaminated groundwater and soil samples collected from Dungarpur district, India, for their potential use in defluoridation. Out of a total of 53 bacterial isolates that were recovered and screened for fluoride resistance, three highly fluoride-resistant isolates DWC1, DWC2 and DWB5, resistant to up to 9200 mg L-1, 7200 mg L-1 and 5200 mg L-1 fluoride respectively, were characterized and identified as Aeromonas sp., Brevibacterium sp. and Paenibacillus sp. respectively. The fluoride removal capacity of isolates DWC1, DWC2, DWB5 and a consortium of all the three isolates was found to be 68.7%, 73.4%, 76.7 % and 70.1% respectively on nutrient broth supplemented with NaF (2000 mg L-1) after 8 days of incubation. Defluoridation conditions for the strain showing the best result (Paenibacillus sp.) were optimized for real fluoride-rich water collected from Ajmer District, India, using the Taguchi design of experiment. A defluoridation of up to 73.3% was observed at 40 °C temperature and pH 8 with inoculum: water ratio of 2:1 after 8 days of incubation. To the best of our knowledge, the defluoridation capacity of Paenibacillus sp. is the highest reported in literature to date for real water samples and could be investigated in further detail for commercial application.


Assuntos
Bactérias , Fluoretos , Água Doce , Purificação da Água , Bactérias/efeitos dos fármacos , Bactérias/metabolismo , Farmacorresistência Bacteriana , Fluoretos/análise , Fluoretos/metabolismo , Fluoretos/farmacologia , Água Doce/química , Água Doce/microbiologia , Índia , Poluentes Químicos da Água/análise , Poluentes Químicos da Água/metabolismo , Poluição da Água , Purificação da Água/métodos
15.
Semin Cancer Biol ; 47: 1-17, 2017 12.
Artigo em Inglês | MEDLINE | ID: mdl-28502611

RESUMO

Mitochondria are complex intracellular organelles that have long been identified as the powerhouses of eukaryotic cells because of the central role they play in oxidative metabolism. A resurgence of interest in the study of mitochondria during the past decade has revealed that mitochondria also play key roles in cell signaling, proliferation, cell metabolism and cell death, and that genetic and/or metabolic alterations in mitochondria contribute to a number of diseases, including cancer. Mitochondria have been identified as signaling organelles, capable of mediating bidirectional intracellular information transfer: anterograde (from nucleus to mitochondria) and retrograde (from mitochondria to nucleus). More recently, evidence is now building that the role of mitochondria extends to intercellular communication as well, and that the mitochondrial genome (mtDNA) and even whole mitochondria are indeed mobile and can mediate information transfer between cells. We define this promiscuous information transfer function of mitochondria and mtDNA as "momiome" to include all mobile functions of mitochondria and the mitochondrial genome. Herein, we review the "momiome" and explore its role in cancer development, progression, and treatment.


Assuntos
Genoma Mitocondrial , Mitocôndrias/genética , Mitocôndrias/metabolismo , Transdução de Sinais , Animais , Comunicação Celular , Transformação Celular Neoplásica/genética , Transformação Celular Neoplásica/metabolismo , Suscetibilidade a Doenças , Espaço Extracelular/metabolismo , Humanos , Espaço Intracelular/metabolismo
16.
J Biol Chem ; 292(50): 20694-20706, 2017 12 15.
Artigo em Inglês | MEDLINE | ID: mdl-29066618

RESUMO

The normal cellular function requires communication between mitochondria and the nucleus, termed mitochondria-to-nucleus retrograde signaling. Disruption of this mechanism has been implicated in the development of cancers. Many proteins are known modulators of retrograde signaling, but whether microRNAs (miRNAs) are also involved is unknown. We conducted an miRNA microarray analysis using RNA from a parental cell line, a Rho0 line lacking mitochondrial DNA (mtDNA) and a Rho0 line with restored mtDNA. We found that miR-663 was down-regulated in the mtDNA-depleted Rho0 line. mtDNA restoration reversed this miRNA to parental level, suggesting that miR-663 may be epigenetically regulated by retrograde signaling. By using methylation-specific PCR and bisulfite sequencing we demonstrate that miR-663 promoter is epigenetically regulated not only by genetic but also by pharmacological disruption of oxidative phosphorylation (OXPHOS). Restoration of OXPHOS Complex I inhibitor-induced miR-663 expression by N-acetylcysteine suggested that reactive oxygen species (ROS) play a key role in epigenetic regulation of miR-663. We determined that miR-663 regulates the expression of nuclear-encoded respiratory chain subunits involved in Complexes I, II, III, and IV. miR-663 also controlled the expression of the Complexes I (NDUFAF1), II (SDHAF2), III (UQCC2), and IV (SCO1) assembly factors and was required for stability of respiratory supercomplexes. Furthermore, using luciferase assays, we found that miR-663 directly regulates UQCC2. The anti-miR-663 reduced OXPHOS complex activity and increased in vitro cellular proliferation and promoted tumor development in vivo in mice. We also found that increased miR-663 expression in breast tumors consistently correlates with increased patient survival. We provide the first evidence for miRNA controlling retrograde signaling, demonstrating its epigenetic regulation and its role in breast tumorigenesis.


Assuntos
Neoplasias da Mama/metabolismo , Núcleo Celular/metabolismo , Epigênese Genética , Regulação Neoplásica da Expressão Gênica , MicroRNAs/metabolismo , Mitocôndrias/metabolismo , Transdução de Sinais , Animais , Neoplasias da Mama/enzimologia , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Núcleo Celular/efeitos dos fármacos , Núcleo Celular/patologia , DNA Mitocondrial/metabolismo , Inibidores Enzimáticos/farmacologia , Epigênese Genética/efeitos dos fármacos , Feminino , Deleção de Genes , Perfilação da Expressão Gênica , Humanos , Camundongos Nus , MicroRNAs/antagonistas & inibidores , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/patologia , Transplante de Neoplasias , Fosforilação Oxidativa/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , RNA/metabolismo , RNA Neoplásico/antagonistas & inibidores , RNA Neoplásico/metabolismo , Transdução de Sinais/efeitos dos fármacos , Carga Tumoral
17.
Appl Environ Microbiol ; 84(23)2018 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-30217849

RESUMO

The genome of Azospirillum brasilense encodes five RpoH sigma factors: two OxyR transcription regulators and three catalases. The aim of this study was to understand the role they play during oxidative stress and their regulatory interconnection. Out of the 5 paralogs of RpoH present in A. brasilense, inactivation of only rpoH1 renders A. brasilense heat sensitive. While transcript levels of rpoH1 were elevated by heat stress, those of rpoH3 and rpoH5 were upregulated by H2O2 Catalase activity was upregulated in A. brasilense and its rpoH::km mutants in response to H2O2 except in the case of the rpoH5::km mutant, suggesting a role for RpoH5 in regulating inducible catalase. Transcriptional analysis of the katN, katAI, and katAII genes revealed that the expression of katN and katAII was severely compromised in the rpoH3::km and rpoH5::km mutants, respectively. Regulation of katN and katAII by RpoH3 and RpoH5, respectively, was further confirmed in an Escherichia coli two-plasmid system. Regulation of katAII by OxyR2 was evident by a drastic reduction in growth, KatAII activity, and katAII::lacZ expression in an oxyR2::km mutant. This study reports the involvement of RpoH3 and RpoH5 sigma factors in regulating oxidative stress response in alphaproteobacteria. We also report the regulation of an inducible catalase by a cascade of alternative sigma factors and an OxyR. Out of the three catalases in A. brasilense, those corresponding to katN and katAII are regulated by RpoH3 and RpoH5, respectively. The expression of katAII is regulated by a cascade of RpoE1→RpoH5 and OxyR2.IMPORTANCEIn silico analysis of the A. brasilense genome showed the presence of multiple paralogs of genes involved in oxidative stress response, which included 2 OxyR transcription regulators and 3 catalases. So far, Deinococcus radiodurans and Vibrio cholerae are known to harbor two paralogs of OxyR, and Sinorhizobium meliloti harbors three catalases. We do not yet know how the expression of multiple catalases is regulated in any bacterium. Here we show the role of multiple RpoH sigma factors and OxyR in regulating the expression of multiple catalases in A. brasilense Sp7. Our work gives a glimpse of systems biology of A. brasilense used for responding to oxidative stress.


Assuntos
Azospirillum brasilense/enzimologia , Catalase/genética , Regulação Bacteriana da Expressão Gênica , Regulação Enzimológica da Expressão Gênica , Proteínas de Choque Térmico/metabolismo , Proteínas Repressoras/metabolismo , Fator sigma/metabolismo , Fatores de Transcrição/metabolismo , Azospirillum brasilense/genética , Azospirillum brasilense/metabolismo , Catalase/metabolismo , Proteínas de Choque Térmico/genética , Peróxido de Hidrogênio/metabolismo , Estresse Oxidativo , Regiões Promotoras Genéticas , Proteínas Repressoras/genética , Fator sigma/genética , Fatores de Transcrição/genética
18.
Anal Biochem ; 552: 45-49, 2018 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-28322800

RESUMO

Somatic human cells contain thousands of copies of mitochondrial DNA (mtDNA). In eukaryotes, natural transfer of mtDNA into the nucleus generates nuclear mitochondrial DNA (NUMT) copies. We name this phenomenon as "numtogenesis". Numtogenesis is a well-established evolutionary process reported in various sequenced eukaryotic genomes. We have established a molecular tool to rapidly detect and analyze NUMT insertions in whole genomes. To date, NUMT analyses depend on deep genome sequencing combined with comprehensive computational analyses of the whole genome. This is time consuming, cumbersome and cost prohibitive. Further, most laboratories cannot accomplish such analyses due to limited skills. We report the development of single-molecule mtFIBER FISH (fluorescence in situ hybridization) to study numtogenesis. The development of mtFIBER FISH should aid in establishing a role for numtogenesis in cancers and other human diseases. This novel technique should help distinguish and monitor cancer stages and progression, aid in elucidation of basic mechanisms underlying tumorigenesis and facilitate analyses of processes related to early detection of cancer, screening and/or cancer risk assessment.


Assuntos
Núcleo Celular/metabolismo , DNA Mitocondrial/metabolismo , Hibridização in Situ Fluorescente/métodos , Transporte Biológico , Linhagem Celular Tumoral , Núcleo Celular/genética , Humanos
19.
Int Braz J Urol ; 44(2): 323-329, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29144630

RESUMO

INTRODUCTION: For dorsal onlay graft placement, unilateral urethral mobilization is less invasive than standard circumferential urethral mobilization. Apart from success in terms of patency of urethra, other issues like sexual function, overall quality of life and patient satisfaction remain important issues while comparing outcomes of urethroplasty. AIM: To prospectively compare the objective as well as subjective outcomes of two approaches. MATERIALS AND METHODS: Between July 2011 and January 2015, 136 adult males having anterior urethral stricture with urethral lumen ≥ 6 Fr. were prospectively assigned between two groups by alternate randomization. Operative time, complications, success rate (no obstructive symptoms, no need of any postoperative intervention, Q max > 15mL/sec), sexual functions (using Brief Male Sexual Function Inventory) were compared. RESULTS: Baseline parameters were similar in both groups (68 in each group). Overall success rate was similar in both groups (89 % and 91 % respectively). Improvement in total LUTS scores was similar in groups. Changes in overall health status (VAS and EQ 5D) was equal in both groups. Erectile function score was significantly decreased in DO than DL group while ejaculatory function and sexual desire remained stable after urethroplasty in both groups. CONCLUSIONS: In anterior urethral stricture buccal mucosa graft provides satisfactory results as onlay technique. No technique whether dorsolateral and dorsal techniques is superior to other. Dorsolateral technique needs minimal urethral mobilization and should be preferred whenever feasible.


Assuntos
Estreitamento Uretral/cirurgia , Procedimentos Cirúrgicos Urológicos Masculinos/métodos , Adulto , Humanos , Satisfação do Paciente , Estudos Prospectivos , Qualidade de Vida , Resultado do Tratamento , Procedimentos Cirúrgicos Urológicos Masculinos/efeitos adversos
20.
J Bacteriol ; 199(13)2017 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-28439037

RESUMO

Azospirillum brasilense Sp7 uses glycerol as a carbon source for growth and nitrogen fixation. When grown in medium containing glycerol as a source of carbon, it upregulates the expression of a protein which was identified as quinoprotein alcohol dehydrogenase (ExaA). Inactivation of exaA adversely affects the growth of A. brasilense on glycerol. A determination of the transcription start site of exaA revealed an RpoN-dependent -12/-24 promoter consensus. The expression of an exaA::lacZ fusion was induced maximally by glycerol and was dependent on σ54 Bioinformatic analysis of the sequence flanking the -12/-24 promoter revealed a 17-bp sequence motif with a dyad symmetry of 6 nucleotides upstream of the promoter, the disruption of which caused a drastic reduction in promoter activity. The electrophoretic mobility of a DNA fragment containing the 17-bp sequence motif was retarded by purified EraR, a LuxR-type transcription regulator that is transcribed divergently from exaA EraR also showed a positive interaction with RpoN in two-hybrid and pulldown assays.IMPORTANCE Quinoprotein alcohol dehydrogenase (ExaA) plays an important role in the catabolism of alcohols in bacteria. Although exaA expression is thought to be regulated by a two-component system consisting of EraS and EraR, the mechanism of regulation was not known. This study shows the details of the regulation of expression of the exaA gene in A. brasilense We have shown here that exaA of A. brasilense is maximally induced by glycerol and harbors a σ54-dependent promoter. The response regulator EraR binds to an inverted repeat located upstream of the exaA promoter. This study shows that a LuxR-type response regulator (EraR) binds upstream of the exaA gene and physically interacts with σ54 The unique feature of this regulation is that EraR is a LuxR-type transcription regulator that lacks the GAFTGA motif, a characteristic feature of the enhancer binding proteins that are known to interact with σ54 in other bacteria.


Assuntos
Oxirredutases do Álcool/metabolismo , Azospirillum brasilense/enzimologia , RNA Polimerases Dirigidas por DNA/metabolismo , Regulação Bacteriana da Expressão Gênica/fisiologia , Glicerol/metabolismo , Proteínas Repressoras/metabolismo , Transativadores/metabolismo , Azospirillum brasilense/genética , Azospirillum brasilense/metabolismo , RNA Polimerases Dirigidas por DNA/genética , Regulação Enzimológica da Expressão Gênica/fisiologia , Proteínas Repressoras/genética , Transativadores/genética
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