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1.
J Environ Manage ; 359: 120985, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38677226

RESUMO

Amid rising water contamination from industrial sources, tackling toxic dyes and pathogens is critical. Photocatalysis offers a cost-effective and eco-friendly solution to this pressing challenges. Herein, we synthesized Te4+ and Er3+ doped ZrO2 photocatalysts through hydrothermal method and investigated their efficacy in degrading Congo red (CR) and pathogens under visible light. XRD and Raman Spectroscopy confirm monoclinic and tetragonal mixed-phases without any impurities. Doping-induced defects, reduced crystalline diameter, high surface area, modified bandgap (2.95 eV), photoluminescence quenching, coupled with interfacial polarization, contribute to EZO's excellent dielectric response (1.149 × 106), for achieving remarkable photocatalytic activity, verified by photoelectrochemical measurements, LC-MS and phytotoxicity analysis. Under optimal conditions, EZO achieves 99% CR degradation within 100 min (TOC 79.9%), surpassing ZO (77%) and TZO (84%). Catalyst dosages, dye concentrations, and solution pH effect on EZO's photocatalytic performance are systematically assessed. Scavenging experiment emphasized the pivotal role of · OH in CR degradation with 96.4% efficiency after 4 cycles, affirming its remarkable stability. Moreover, EZO demonstrates ROS-mediated antibacterial activity against E. faecalis and E. coli bacteria under visible light, achieving >97% and >94% inhibition rate with an inhibition zone > 3 mm. Hence, the nanoparticle's dual action offers a practical solution for treating contaminated wastewater, ensuring safe irrigation.


Assuntos
Antibacterianos , Zircônio , Antibacterianos/química , Antibacterianos/farmacologia , Catálise , Zircônio/química , Nanopartículas/química , Érbio/química , Vermelho Congo/química
2.
Biomater Biosyst ; 13: 100090, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38440290

RESUMO

Osteoarthritis (OA) is a chronic musculoskeletal disorder characterized by an imbalance between (synthesis) and catabolism (degradation) in altered homeostasis of articular cartilage mediated primarily by the innate immune system. OA degenerates the joints resulting in synovial hyperplasia, degradation of articular cartilage with damage of the structural and functional integrity of the cartilage extracellular matrix, subchondral sclerosis, osteophyte formation, and is characterized by chronic pain, stiffness, and loss of function. Inflammation triggered by factors like biomechanical stress is involved in the development of osteoarthritis. In OA apart from catabolic effects, anti-inflammatory anabolic processes also occur continually. There is also an underlying chronic inflammation present, not only in cartilage tissue but also within the synovium, which perpetuates tissue destruction of the OA joint. The consideration of inflammation in OA considers synovitis and/or other cellular and molecular events in the synovium during the progression of OA. In this review, we have presented the progression of joint degradation that results in OA. The critical role of inflammation in the pathogenesis of OA is discussed in detail along with the dysregulation within the cytokine networks composed of inflammatory and anti-inflammatory cytokines that drive catabolic pathways, inhibit matrix synthesis, and promote cellular apoptosis. OA pathogenesis, fluctuation of synovitis, and its clinical impact on disease progression are presented here along with the role of synovial macrophages in promoting inflammatory and destructive responses in OA. The role of interplay between different cytokines, structure, and function of their receptors in the inter-cellular signaling pathway is further explored. The effect of cytokines in the increased synthesis and release of matrix-decomposing proteolytic enzymes, such as matrix metalloproteinase (MMPs) and a disintegrin-like and metalloproteinase with thrombospondin motif (ADAMTS), is elaborated emphasizing the potential impact of MMPs on the chondrocytes, synovial cells, articular and periarticular tissues, and other immune system cells migrating to the site of inflammation. We also shed light on the pathogenesis of OA via oxidative damage particularly due to nitric oxide (NO) via its angiogenic response to inflammation. We concluded by presenting the current knowledge about the tissue inhibitors of metalloproteinases (TIMPs). Synthetic MMP inhibitors include zinc binding group (ZBG), non-ZBG, and mechanism-based inhibitors, all of which have the potential to be therapeutically beneficial in the treatment of osteoarthritis. Improving our understanding of the signaling pathways and molecular mechanisms that regulate the MMP gene expression, may open up new avenues for the creation of therapies that can stop the joint damage associated with OA.

3.
Clin Cancer Res ; 30(3): 498-505, 2024 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-37955424

RESUMO

PURPOSE: Mutations in BTK, PLCG2, and BCL2 have been reported in patients with progressive disease (PD) on continuous single-agent BTK or BCL2 inhibitor treatment. We tested for these mutations in samples from patients with PD after completion of first-line treatment with fixed-duration ibrutinib plus venetoclax for chronic lymphocytic leukemia (CLL) in the phase II CAPTIVATE study. PATIENTS AND METHODS: A total of 191 patients completed fixed-duration ibrutinib plus venetoclax (three cycles of ibrutinib then 12-13 cycles of ibrutinib plus venetoclax). Genomic risk features [del(11q), del(13q), del(17p), trisomy 12, complex karyotype, unmutated IGHV, TP53 mutated] and mutations in genes recurrently mutated in CLL (ATM, BIRC3, BRAF, CHD2, EZH2, FBXW7, MYD88, NOTCH1, POT1, RPS15, SF3B1, XPO1) were assessed at baseline in patients with and without PD at data cutoff; gene variants and resistance-associated mutations in BTK, PLCG2, or BCL2 were evaluated at PD. RESULTS: Of 191 patients completing fixed-duration ibrutinib plus venetoclax, with median follow-up of 38.9 months, 29 (15%) developed PD. No baseline risk feature or gene mutation was significantly associated with development of PD. No previously reported resistance-associated mutations in BTK, PLCG2, or BCL2 were detected at PD in 25 patients with available samples. Of the 29 patients with PD, 19 have required retreatment (single-agent ibrutinib, n = 16, or ibrutinib plus venetoclax, n = 3); 17 achieved partial response or better, 1 achieved stable disease, and 1 is pending response assessment. CONCLUSIONS: First-line fixed-duration combination treatment with ibrutinib plus venetoclax may mitigate development of resistance mechanisms associated with continuous single-agent targeted therapies, allowing for effective retreatment. See related commentary by Al-Sawaf and Davids, p. 471.


Assuntos
Adenina , Leucemia Linfocítica Crônica de Células B , Piperidinas , Sulfonamidas , Humanos , Adenina/análogos & derivados , Compostos Bicíclicos Heterocíclicos com Pontes/uso terapêutico , Leucemia Linfocítica Crônica de Células B/tratamento farmacológico , Leucemia Linfocítica Crônica de Células B/genética , Mutação , Proteínas Proto-Oncogênicas c-bcl-2/genética , Recidiva
4.
ACS Sens ; 8(4): 1819-1826, 2023 04 28.
Artigo em Inglês | MEDLINE | ID: mdl-37042455

RESUMO

With the development of Internet of Things technology, various sensors are under intense development. Electrostatically formed nanowire (EFN) gas sensors are multigate Si sensors based on CMOS technology and have the unique advantages of ultralow power consumption and very large-scale integration (VLSI) compatibility for mass production. In order to achieve selectivity, machine learning is required to accurately identify the detected gas. In this work, we introduce automatic learning technology, by which the common algorithms are sorted and applied to the EFN gas sensor. The advantages and disadvantages of the top four tree-based model algorithms are discussed, and the unilateral training models are ensembled to further improve the accuracy of the algorithm. The analyses of two groups of experiments show that the CatBoost algorithm has the highest evaluation index. In addition, the feature importance of the classification is analyzed from the physical meaning of electrostatically formed nanowire dimensions, paving the way for model fusion and mechanism exploration.


Assuntos
Nanofios , Compostos Orgânicos Voláteis , Algoritmos , Aprendizado de Máquina , Internet
5.
Innov Syst Softw Eng ; : 1-17, 2022 Jun 02.
Artigo em Inglês | MEDLINE | ID: mdl-35677629

RESUMO

The outbreak of 2019 novel coronavirus (COVID-19) has triggered unprecedented challenges and put the whole world in a parlous condition. The impacts of COVID-19 is a matter of grave concern in terms of fatality rate, socio-economical condition, health infrastructure. It is obvious that only pharmaceutical solutions (vaccine) cannot eradicate this pandemic completely, and effective strategies regarding lockdown measures, restricted mobility, emergency services to users-in brief data-driven decision system is of utmost importance. This necessitates an efficient data analytics framework, data infrastructure to store, manage pandemic related information, and distributed computing platform to support such data-driven operations. In the past few decades, Internet of Things-based devices and applications have emerged significantly in various sectors including healthcare and time-critical applications. To be specific, health-sensors help to accumulate health-related parameters at different time-instances of a day, the movement sensors keep track of mobility traces of the user, and helps to assist them in varied conditions. The smartphones are equipped with several such sensors and the ability of low-cost connected sensors to cover large areas makes it the most useful component to combat pandemics such as COVID-19. However, analysing and managing the huge amount of data generated by these sensors is a big challenge. In this paper we have proposed a unified framework which has three major components: (i) Spatial Data Infrastructure to manage, store, analyse and share spatio-temporal information with stakeholders efficiently, (ii) Cloud-Fog-Edge-based hierarchical architecture to support preliminary diagnosis, monitoring patients' mobility, health parameters and activities while they are in quarantine or home-based treatment, and (iii) Assisting users in varied emergency situation leveraging efficient data-driven techniques at low-latency and energy consumption. The mobility data analytics along with SDI is required to interpret the movement dynamics of the region and correlate with COVID-19 hotspots. Further, Cloud-Fog-Edge-based system architecture is required to provision healthcare services efficiently and in timely manner. The proposed framework yields encouraging results in taking decisions based on the COVID-19 context and assisting users effectively by enhancing accuracy of detecting suspected infected people by ∼ 24% and reducing delay by ∼ 55% compared to cloud-only system.

6.
J Environ Manage ; 298: 113546, 2021 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-34435573

RESUMO

Microbial Fuel Cell (MFC) is an innovative bio-electrochemical approach which converts biochemical energy inherent in wastewater into electrical energy, thus contributing to circular economy. Five electrogenic bacteria, Kocuria rosea (GTPAS76), two strains of Bacillus circulans (GTPO28 and GTPAS54), and two strains of Corynebacterium vitaeruminis (GTPO38 and GTPO42) were isolated from a common effluent treatment plant (CETP) and were used individually as well as in consortium form to run double chambered "H" type microbial fuel cell. Individually they could produce voltage in the range of 0.4-0.7 V in the MFC systems. Consortium developed using GTPO28, GTPO38, GTPAS54 and GTPAS76 were capable of producing voltage output of 0.8 V with 81.81 % and 64 % COD and BOD reduction, respectively. The EPS production capacity and electricity generation by the isolated bacteria correlated significantly (r = 0.72). Various parameters like, effect of preformed biofilm, length of salt bridge and its reuse, aeration, substrate concentration and external resistance were studied in detail. The study emphasizes on improving the commercialization aspect of MFC with repeated use of salt bridge and improving wastewater treatment potential after optimization of MFC system. Polarization curve and power density trends were studied in optimized MFC. A maximum power density and current density achieved were 18.15 mW/m2 and 370.37 mA/m2, respectively using 5 mM sodium benzoate. This study reports the use of sodium benzoate as a substrate along with reusing of the salt bridge in MFC study with promising results for BOD and COD reduction, proving it to be futuristic technology for bio-based circular ecosystem development.


Assuntos
Fontes de Energia Bioelétrica , Hidrocarbonetos Aromáticos , Bacillus , Biodegradação Ambiental , Corynebacterium , Ecossistema , Eletricidade , Eletrodos , Micrococcaceae , Águas Residuárias
7.
Arch Dis Child ; 106(3): 283-285, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-32086234

RESUMO

BACKGROUND: There is scarcity of data on impact of rituximab on anthropometrical parameters (weight, height and body mass index i.e. BMI SD score (SDS)) among children with steroid-dependent nephrotic syndromes (SDNS). METHODS: Multicentre retrospective review. RESULTS: 102 children with SDNS (male: 63%; n=64), median age 7 (IQR: 4.3-9.6) years, received a total of 217 rituximab infusions (total 110 cycles). At median follow-up of 2.1 (IQR: 1.3-2.8) years, 58 (57%) children were off steroids and a significant fall in steroid threshold for relapse was noted (median 0.6; IQR 0.4-0.9 to median 0.3; IQR 0.12 - 0.5 mg/kg/alternate day, p=0.005). Anthropometric parameters (BMI SDS: 0.92±1.8 to 0.25±1.47, p=0.003; weight SDS: 0.20±1.6 to -0.11±1.3, p=0.01; and height SDS: -0.93±1.88 to -0.45±1.54, p=0.04) as well as obesity (38% to 20%, p=0.003) and short stature (11% to 3%, p=0.02) improved. Results remained significant even when analysis was restricted to children ≤12 years (n=88), (BMI SDS: 0.97±1.98 to 0.25±1.5, p=0.001; weight SDS: 0.33±1.6 to 0.02±1.2, p=0.01; and height SDS: -0.67±1.84 to -0.186±1.42, p=0.001). CONCLUSIONS: Use of rituximab resulted in significant steroid sparing effect with an improvement in both growth and obesity parameters.


Assuntos
Transtornos do Crescimento/induzido quimicamente , Fatores Imunológicos/farmacologia , Síndrome Nefrótica/tratamento farmacológico , Rituximab/farmacologia , Esteroides/efeitos adversos , Antropometria , Estatura/efeitos dos fármacos , Índice de Massa Corporal , Peso Corporal/efeitos dos fármacos , Criança , Pré-Escolar , Feminino , Seguimentos , Transtornos do Crescimento/epidemiologia , Humanos , Fatores Imunológicos/administração & dosagem , Infusões Intravenosas , Masculino , Síndrome Nefrótica/fisiopatologia , Obesidade/induzido quimicamente , Obesidade/epidemiologia , Estudos Retrospectivos , Rituximab/administração & dosagem , Esteroides/uso terapêutico
9.
Ecotoxicol Environ Saf ; 182: 109450, 2019 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-31349104

RESUMO

The major sources for release of hydrocarbons into the environment include the effluents generated from chemical processing industries and ports. The introduction of such hazardous compounds into natural water bodies creates considerable disturbances in aquatic life and causes a threat to humans. Thus, it is essential to detect and quantify pollutants at various stages of the wastewater generation and treatment before they reach natural aquatic environments and contaminate them. This study reports the development of "biosensing strains" by cloning hydrocarbon recognizing promoter-operator and a reporter gene in bacterial strains for sensing the presence of pollutants at their lowest possible concentration. So far, various biosensing strains have been constructed with a fused promoter-operator region of the hydrocarbon degrading operons, but most of them use luxAB as a reporter gene. A novel approach in the present study aimed at constructing strains harboring two different fluorescent protein (FP)-based reporter genes for the quantification of multiple pollutants at a time. Two vectors were designed with a fusion of tbuT-gfp and phnR-cfp for the quantification of mono- and poly-aromatic hydrocarbons, respectively. The designed vectors were transformed into E. coli DH5α, and these strains were designated as E. coli DH5α 2296-gfp (containing pPROBE-Tbut-RBS-gfp-npt) and E. coli DH5α 2301-cfp (containing pPROBE-phn-RBS-cfp-npt). Both the developed recombinant strains were capable of successfully detecting mono- and poly-aromatic hydrocarbons in the range of 1-100 µM. The sensing capacity of recombinant strains was successfully validated with actual wastewater samples against available physico-chemical analytical techniques. The development of such recombinant microbial strains indicates the future for online contaminant detection, treatment quality monitoring and protection of aquatic flora and fauna.


Assuntos
Técnicas Biossensoriais/métodos , Escherichia coli/genética , Hidrocarbonetos Aromáticos/análise , Poluentes Químicos da Água/análise , Genes Reporter , Proteínas de Fluorescência Verde/genética , Humanos , Regiões Promotoras Genéticas , Águas Residuárias/química , Purificação da Água
10.
Regul Toxicol Pharmacol ; 105: 77-85, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30991075

RESUMO

Citrus sinensis contains glycoside hesperetin-7-rhamnoglucoside (hesperidin) which harbor an array of therapeutic potentials including antioxidant, anticancer, and anti-inflammatory. However, a systematic examination of safety is needed before its utilization. Hence, the present investigation is aimed to evaluate acute and sub-chronic toxicity of hesperidin isolated from the citrus fruit. Hesperidin (73%) was isolated from a methanolic extract of dried peel of the citrus fruit, characterized using FTIR, and standardized by HPLC. Its acute oral toxicity (AOT) and sub-chronic toxicity studies were carried out in Sprague-Dawley rats. Hesperidin (5000 mg/kg) showed 10% mortality in AOT. In sub-chronic toxicity study, hesperidin (250 and 500 mg/kg) did not induce any abnormalities in body weight, food consumption, clinical signs, ophthalmological and neurological observations, urine analysis, hematology, clinical chemistry, organ weights, and gross pathology. However, hesperidin (1000 mg/kg) showed significant (p < 0.05) alterations in body and organ weights, hematology, clinical chemistry, and tissue histopathology. To conclude, hesperidin has median lethal dose (LD50) of 4837.5 mg/kg, and Low Observed Adverse Effect Level (LOAEL) at 1000 mg/kg for both male and female Sprague-Dawley rats. Thus, hesperidin isolated from citrus fruit showed a good safety profile in animal study.


Assuntos
Antioxidantes/toxicidade , Citrus sinensis/química , Hesperidina/toxicidade , Extratos Vegetais/toxicidade , Administração Oral , Animais , Antioxidantes/administração & dosagem , Antioxidantes/isolamento & purificação , Relação Dose-Resposta a Droga , Feminino , Hesperidina/administração & dosagem , Hesperidina/isolamento & purificação , Dose Letal Mediana , Masculino , Metanol/química , Extratos Vegetais/administração & dosagem , Extratos Vegetais/química , Ratos , Ratos Sprague-Dawley , Testes de Toxicidade Aguda/métodos , Testes de Toxicidade Subcrônica/métodos
11.
Curr Mol Pharmacol ; 12(2): 122-138, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30605067

RESUMO

BACKGROUND: Allergic asthma is a chronic immune-inflammatory disorder, characterized by airway inflammation and airway hyperresponsiveness (AHR). Morin is a natural flavonoid reported to exhibit inhibitory action against IgE-mediated allergic response. AIM: To determine the efficacy of murine model of ovalbumin (OVA)-induced AHR inhibition by morin and decipher the molecular mechanism involved. MATERIALS AND METHODS: Sprague-Dawley rats were sensitized and challenged with OVA to induce AHR. Rats received treatment with morin (10, 30 and 100 mg/kg, p.o.) for the next 28 days. RESULTS: Morin (30 and 100 mg/kg) significantly and dose-dependently attenuated (p < 0.01 and p < 0.001) OVA-induced alterations in pulse oxy and lung function test, increased bronchoalveolar lavage fluid cell counts, elevated total protein and albumin levels in serum, BALF, and lungs, increased serum total and OVA-specific IgE levels and, elevated oxidative stress levels in the lung. RT-PCR analysis revealed that morin treatment (30 and 100 mg/kg) significantly (p < 0.001) up-regulated SUMF2 mRNA expression in lungs whereas mRNA expressions of BLT2, NF-κB, and Th2-cytokine (TNF-α, IL-1ß, IL-4, IL-6, and IL-13) were down-regulated significantly and dose-dependently (p < 0.01 and p < 0.001). Also, histologic and ultrastructural studies showed that morin significantly inhibited (p < 0.001) OVAinduced perivascular and peribranchial inflammatory infiltration and interstitial fibrosis. CONCLUSION: Morin exhibited inhibitory effect against OVA-induced allergic asthma by activation of SUMF2 which impeded IL-13 expression and in turn attenuated Th2-cytokines, BLT2, NF-κB, and IgE levels to ameliorate AHR. Thus, our findings suggested that morin could be considered as a potential alternative therapeutic agent for the management of allergic asthma.


Assuntos
Asma/tratamento farmacológico , Flavonoides/uso terapêutico , Interleucina-13/metabolismo , NF-kappa B/metabolismo , Receptores do Leucotrieno B4/metabolismo , Sulfatases/metabolismo , Animais , Asma/etiologia , Asma/metabolismo , Líquido da Lavagem Broncoalveolar/química , Flavonoides/farmacologia , Hemodinâmica/efeitos dos fármacos , Imunoglobulina E/sangue , Interleucina-13/genética , Pulmão/metabolismo , Pulmão/patologia , Pulmão/ultraestrutura , Masculino , NF-kappa B/genética , Ovalbumina/imunologia , Oxigênio/metabolismo , Ratos , Ratos Sprague-Dawley , Receptores do Leucotrieno B4/genética , Transdução de Sinais/efeitos dos fármacos , Sulfatases/genética , Superóxido Dismutase/metabolismo
12.
EXCLI J ; 17: 399-419, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29805347

RESUMO

Background: Delayed wound healing is a diverse, multifactorial, complex and inter-related complication of diabetes resulting in significant clinical morbidity. Hesperidin possesses potent antidiabetic and wound healing activity. Aim: To evaluate the potential of hesperidin against experimentally induced diabetes foot ulcers. Methods: Diabetes was induced experimentally by streptozotocin (STZ, 55 mg/kg, i.p.) in Sprague Dawley rats (180-220 g) and wounds were created on the dorsal surface of the hind paw of rats. Hesperidin (25, 50 and 100 mg/kg, p.o.) was administered for 21 days after wound stabilization. Various biochemical, molecular and histopathological parameters were evaluated in wound tissue. Results: STZ-induced decrease in body weight and increase in blood glucose, food, and water intake was significantly (p < 0.05) inhibited by hesperidin (50 and 100 mg/kg) treatment. It showed a significant increase (p < 0.05) in percent wound closure and serum insulin level. The STZ-induced decrease in SOD and GSH level, as well as elevated MDA and NO levels, were significantly (p < 0.05) attenuated by hesperidin (50 and 100 mg/kg) treatment. Intraperitoneal administration of STZ caused significant down-regulation in VEGF-c, Ang-1, Tie-2, TGF-ß and Smad 2/3 mRNA expression in wound tissues whereas hesperidin (50 and 100 mg/kg) treatment showed significant up-regulation in these mRNA expressions. STZ-induced alteration in would architecture was also attenuated by hesperidin (50 and 100 mg/kg) treatment. Conclusion: Together, treatment with hesperidin accelerate angiogenesis and vasculogenesis via up-regulation of VEGF-c, Ang-1/Tie-2, TGF-ß and Smad-2/3 mRNA expression to enhance wound healing in chronic diabetic foot ulcers.

13.
Ren Fail ; 40(1): 107-118, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-29363392

RESUMO

BACKGROUND: Hemolytic uraemic syndrome (HUS) is progressive renal failure disease and determination of their quality of life (QoL) on the basis of patient-reported outcomes (PROs) are becoming increasingly important in the economic evaluations for its treatment with eculizumab (ECU). AIM: To perform the systematic evaluation of QoL in HUS patients treated with ECU on the basis of Evaluating Measures of Patient Reported Outcomes (EMPRO) tool. MATERIALS AND METHODS: A systematic review was conducted in PubMed, EMBASE, the Cochrane Library, CINAHL and Google Scholar till September 2016 by two independent researchers. Each identified instrument was evaluated for its quality of performance by using the EMPRO tool for its overall score and seven attribute specific scores (range 0-100, worst to best). RESULTS: Five different PROs instruments were identified from 10 articles (n = 112) which showed eculizumab significantly improves health-related quality of life (HRQOL) in atypical HUS (aHUS) patients. Amongst five instruments viz. EuroQol five dimensions questionnaire (EQ-5 D), Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F), Headache Impact Test-6 (HIT-6), 36-Item Short Form Health Survey (SF-36) and Visual Analogue Scale (VAS), the overall EMPRO score was higher for VAS (73.83) and EQ-5 D (73.81). Whereas, FACIT-F and HIT- 6 were just able to meet the minimal threshold of EMPRO scoring (50.24 and 59.09, respectively). CONCLUSIONS: Evidence from present investigation support that eculizumab significantly improves HRQoL in patients with aHUS furthermore, EQ-5 D and VAS instrument should be recommended for assessing HRQoL in them. However, selection of PRO instrument for determination of QoL in HUS entirely depend upon the study requirements.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Síndrome Hemolítico-Urêmica Atípica/tratamento farmacológico , Medidas de Resultados Relatados pelo Paciente , Qualidade de Vida , Síndrome Hemolítico-Urêmica Atípica/psicologia , Estudos de Viabilidade , Humanos , Psicometria
14.
Curr Neuropharmacol ; 16(7): 1086-1097, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29189163

RESUMO

BACKGROUND: There is a growing body of evidence in animal and cell based models of Parkinson's disease (PD) to suggest that overexpression and / or abnormal accumulation and aggregation of α-synuclein can trigger neuronal death. This important role of α-synuclein in PD pathogenesis is supported by the fact that duplication, triplication and mutations of α-synuclein gene cause familial forms of PD. METHODS: A review of literature was performed by searching PubMed and Google Scholar for relevant articles highlighting the pathogenic role of α-synuclein and the potential therapeutic implications of targeting various pathways related to this protein. RESULTS: The overexpression and accumulation of α-synuclein within neurons may involve both transcriptional and post-transcriptional mechanisms including a decreased degradation of the protein through proteasomal or autophagic processes. The mechanisms of monomeric α-synuclein aggregating to oligomers and fibrils have been investigated intensively, but it is still not certain which form of this natively unfolded protein is responsible for toxicity. Likewise the proteotoxic pathways induced by α- synuclein leading to neuronal death are not elucidated completely but mitochondrial dysfunction, endoplasmic reticulum (ER) stress and altered ER-golgi transport may play crucial roles in this process. At the molecular level, the ability of α-synuclein to form pores in biomembranes or to interact with specific proteins of the cell organelles and the cytosol could be determining factors in the toxicity of this protein. CONCLUSION: Despite many limitations in our present knowledge of physiological and pathological functions of α-synuclein, it appears that this protein may be a target for the development of neuroprotective drugs against PD. This review has discussed many such potential drugs which prevent the expression, accumulation and aggregation of α-synuclein or its interactions with mitochondria or ER and thereby effectively abolish α-synuclein mediated toxicity in different experimental models.


Assuntos
Antiparkinsonianos/uso terapêutico , Fármacos Neuroprotetores/uso terapêutico , Doença de Parkinson/tratamento farmacológico , Doença de Parkinson/metabolismo , Animais , Antiparkinsonianos/farmacologia , Humanos , Fármacos Neuroprotetores/farmacologia , alfa-Sinucleína/metabolismo
15.
Chem Biol Interact ; 278: 212-221, 2017 Dec 25.
Artigo em Inglês | MEDLINE | ID: mdl-29108777

RESUMO

BACKGROUND: Diabetic nephropathy (DN) is one of the leading causes of morbidity and mortality amongst the diabetes mellitus patients. Oxidative stress played a major role in the pathogenesis of DN. Many studies reported that therapies with antioxidant potential have a beneficial effect on DN but there is conflicting evidence amongst them. OBJECTIVE: To elucidate the association between antioxidant and DN and to develop a robust evidence for clinical decisions by conducting systematic reviews and meta-analysis. PATIENT AND METHODS: A comprehensive systematic literature search was conducted in PubMed, EMBASE, Cochrane Library, CPCI-S, ICTRP, and Google Scholar till February 2017 by two independent researchers. Various outcomes were included and statistical analyses were performed using RevMan V.5.3. RESULTS: There were total 1461 participants identified from twelve studies, of which 882 (60.37%) were monitored on antioxidant treatment. Results indicated that antioxidant treatment was associated with significantly change in Blood Urea Nitrogen (SMD = 1.11, 95% CI: 0.38 to 1.85, p = 0.003), urinary Transforming Growth Factor-ß (SMD = 2.16, 95% CI: -0.01 to 4.33; p = 0.05) and estimated Glomerular filtration Rate (SMD = 0.30, 95% CI: 0.06 to 0.55; p = 0.02) than control group. There was no association of change in urine albumin-to-creatinine ratio, serum creatinine, adverse events and rate of death with antioxidant treatment. CONCLUSION: The findings of this investigation indicate that antioxidant treatment is effective clinically for DN treatment in T2DM patient. However, there is a need of high degree of caution for interpreting the outcomes of the studies with a short duration of antioxidant treatment.


Assuntos
Antioxidantes/uso terapêutico , Nefropatias Diabéticas/tratamento farmacológico , Albuminas/análise , Nitrogênio da Ureia Sanguínea , Creatinina/sangue , Creatinina/urina , Bases de Dados Factuais , Nefropatias Diabéticas/metabolismo , Nefropatias Diabéticas/patologia , Taxa de Filtração Glomerular , Humanos , Fator de Crescimento Transformador beta/urina
16.
Environ Toxicol Pharmacol ; 56: 172-185, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28942082

RESUMO

BACKGROUND: Madhuca indica J. F. Gmel. (Sapotaceae) is widely used ethnobotanically as anti-diabetic, antipyretic, hepatoprotective, anti-inflammatory and analgesic. It was shown to possess potent anti-apoptotic property. THE AIM OF THE STUDY: To evaluate the possible mechanism of action of isolated phytoconstituent from Madhuca indica Leaves methanolic extract (MI-ALC) on arsenic-induced cardiotoxicity in rats. MATERIALS AND METHODS: The 3,5,7,3',4'-Pentahydroxy flavone (QTN) was isolated and characterized by using HPTLC, 1H NMR, and LC-MS from MI-ALC. QTN (5, 10 and 20mg/kg, p.o.) was administered in arsenic intoxicated rats (5mL/kg, p.o.) for 28days and evaluated for various behavioral, biochemical, molecular and ultra-histological changes. RESULTS: Treatment with QTN (10 and 20mg/kg, p.o.) significantly inhibited (p<0.05) arsenic-induced electrocardiographic, hemodynamic and left ventricular function alterations. Elevated levels of cardiac markers (LDH, CK-MB, AST, ALT, and ALP), altered lipid metabolism (total cholesterol, triglyceride, LDL, HDL, and VLDL) was significantly restored (p<0.05) by QTN. It also significantly inhibited (p<0.05) altered cardiac oxido-nitrosative stress, Na-K-ATPase level and mitochondrial enzymes (I-IV) activity after arsenite administration. QTN significantly increased (p<0.05) myocardial Nrf-2, PPAR-γ and significantly decreased (p<0.05) myocardial c-fos and c-jun mRNA expressions. Flow cytometric analysis showed that treatment with QTN (10 and 20mg/kg) significantly inhibited (p<0.05) arsenite-induce ROS and apoptosis. It also reduced ultra-histological aberrations induced by sodium arsenite. CONCLUSION: Administration of 3,5,7,3',4'- Pentahydroxy flavone (i.e. Quercetin (QTN)) isolated from MI-ALC showed significant protection against arsenic-induced oxido-nitrosative stress and myocardial injury via modulation of Nrf2, PPAR-γ, and apoptosis.


Assuntos
Arsênio/toxicidade , Cardiomiopatias/prevenção & controle , Flavonoides/farmacologia , Madhuca/química , Animais , Cardiomiopatias/induzido quimicamente , Cardiomiopatias/genética , Cardiomiopatias/fisiopatologia , Modelos Animais de Doenças , Flavonoides/isolamento & purificação , Regulação da Expressão Gênica/efeitos dos fármacos , Fator 2 Relacionado a NF-E2/genética , Estresse Nitrosativo/efeitos dos fármacos , PPAR gama/genética , Extratos Vegetais/isolamento & purificação , Extratos Vegetais/farmacologia , Folhas de Planta/química , Proteínas Proto-Oncogênicas c-fos/genética , Proteínas Proto-Oncogênicas c-jun/genética , Ratos , Simportadores de Cloreto de Sódio-Potássio/efeitos dos fármacos
17.
Biomed Pharmacother ; 94: 880-889, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28810518

RESUMO

INTRODUCTION: Asthma is a chronic, heterogeneous airway disorder characterized by airway inflammatory and remodeling. Artemisia pallens has been reported to possess antioxidant, anti-inflammatory and Anti-allergic potential. OBJECTIVE: To evaluate the anti-asthmatic effects of methanolic extract of Artemisia pallens (APME) against ovalbumin (OVA)-induced airway hyperresponsiveness (AHR) in rats. MATERIALS AND METHOD: AHR was induced in male Sprague-Dawley rats (180-200g) by intraperitoneal (i.p.) injection of OVA and boosted with an identical OVA solution (s.c.) on day 7. Rats were either treated orally with vehicle (10mg/kg), montelukast (10mg/kg) or APME (100, 200 and 400mg/kg) for next 28days. At the end treatments, various biochemical, molecular (RT-PCR and ELISA analysis) and histological parameters were evaluated. RESULTS: APME (200 and 400mg/kg) significantly attenuated (p<0.05) OVA-induced alteration in lung functions measured by Whole-body plethysmography. Increased Bronchoalveolar Lavage (BAL) fluid differential cell count, as well as total protein and albumin in BAL fluid and lungs, was significantly decreased (p<0.05) by APME. It also significantly attenuated (p<0.05) elevated lung oxido-nitrosative stress, myeloperoxidase, and serum IgE levels. OVA-induced down-regulation in lung Nrf2 and upregulation in TNF-α, IL-1ß, IL-4, IL-6, TGF-ß mRNA expression was significantly attenuated (p<0.05) by APME (200 and 400mg/kg) treatment. Histopathological analysis of lung tissue showed that APME treatment reduced OVA-induced inflammatory influx and fibrosis. CONCLUSION: Artemisia pallens simultaneously orchestrate plethora of mechanisms viz. modulations of IgE, TGF-ß, TNF-α, IL's and Nrf-2 levels to exhibit its anti-asthmatic potential in OVA-induced AHR in rats.


Assuntos
Antiasmáticos/farmacologia , Artemisia/química , Asma/tratamento farmacológico , Extratos Vegetais/farmacologia , Animais , Antialérgicos/administração & dosagem , Antialérgicos/isolamento & purificação , Antialérgicos/farmacologia , Antiasmáticos/administração & dosagem , Antiasmáticos/isolamento & purificação , Anti-Inflamatórios/administração & dosagem , Anti-Inflamatórios/isolamento & purificação , Anti-Inflamatórios/farmacologia , Asma/imunologia , Líquido da Lavagem Broncoalveolar , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Regulação para Baixo , Masculino , Ovalbumina/imunologia , Extratos Vegetais/administração & dosagem , Ratos , Ratos Sprague-Dawley , Testes de Função Respiratória , Hipersensibilidade Respiratória/tratamento farmacológico , Hipersensibilidade Respiratória/imunologia
18.
EXCLI J ; 16: 546-565, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28694757

RESUMO

Chronic neuropathic pain is a common and widely recognized pain syndrome for patients and difficult to manage for physicians. Azadirachta indica (AI) possesses analgesic, anti-inflammatory, and antioxidant properties. To evaluate the neuroprotective effect of AI standardized extract in an animal model of peripheral neuropathy induced by partial sciatic nerve ligation (PSNL). PSNL was induced in male Wistar rats (180-200 g) with tight ligation of the nerve. Rats received treatment with either vehicle i.e. distilled water (PSNL control), Pyridoxine (100 mg/kg, p.o.) or AI (100, 200 and 400 mg/kg, p.o.) for 28 days. Various behavioral parameters, biochemical, molecular and histological parameters were evaluated. PSNL resulted in a significant decrease (p < 0.05) in allodynia, hyperalgesia, motor coordination and motor nerve conduction velocity (MNCV) whereas chronic treatment with AI (200 and 400 mg/kg) significantly attenuated (p < 0.05) these behavioral changes. Enhanced activity of oxidative-nitrosative stress, inflammatory mediators (TNF-α, IL-1ß, and NF-κB) as well as mRNA expression of Bax, Caspase-3, and iNOs were significantly attenuated (p < 0.05) by AI treatment. It also significantly increased (p < 0.05) peripheral blood oxygen content and Bcl-2 mRNA expression. The flow cytometric analysis revealed that AI (200 and 400 mg/kg) treatment significantly attenuated neural apoptosis and reactive oxygen species levels. PSNL induced histological aberrations were also decreased by AI treatment. Azadirachta indica exerts its neuroprotection against PSNL induced neuropathic pain via inhibition of oxidative-nitrosative stress, the release of pro-inflammatory cytokines and apoptosis to improve MNCV (graphical abstract, Figure 1(Fig. 1)).

19.
Healthc Technol Lett ; 4(1): 13-19, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-28261491

RESUMO

Automated health monitoring and alert system development is a demanding research area today. Most of the currently available monitoring and controlling medical devices are wired which limits freeness of working environment. Wireless sensor network (WSN) is a better alternative in such an environment. Neonatal intensive care unit is used to take care of sick and premature neonates. Hypothermia is an independent risk factor for neonatal mortality and morbidity. To prevent it an automated monitoring system is required. In this Letter, an automated neonatal health monitoring system is designed using sensor mobile cloud computing (SMCC). SMCC is based on WSN and MCC. In the authors' system temperature sensor, acceleration sensor and heart rate measurement sensor are used to monitor body temperature, acceleration due to body movement and heart rate of neonates. The sensor data are stored inside the cloud. The health person continuously monitors and accesses these data through the mobile device using an Android Application for neonatal monitoring. When an abnormal situation arises, an alert is generated in the mobile device of the health person. By alerting health professional using such an automated system, early care is provided to the affected babies and the probability of recovery is increased.

20.
Nanotechnology ; 28(13): 135206, 2017 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-28186002

RESUMO

The nonlinear electrical characteristic of carbon nanodots (CNDs) has revealed important physical phenomena of charge trapping playing a dominant role in surface interactions. Functional groups on the surface of CNDs attract ambient water molecules which in turn act as charge traps and give rise to electrical hysteresis that plays a dominant role in understanding charge transport in CNDs on surface interactions. Hysteresis in the current-voltage response is further utilized to study the interaction of the CNDs with nitrogen dioxide gas as an external stimuli. The hysteresis area is observed to be dependent on the time of gas interaction with the CNDs, therefore revealing the interaction mechanism of the CNDs with the gas.

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