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1.
Mol Cell Biochem ; 479(4): 975-991, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-37266747

RESUMEN

Parkinson's disease (PD) is a common neurodegenerative disease developed due to the degeneration of dopaminergic neurons in the substantia nigra. There is no single effective treatment in the management of PD. Therefore, repurposing effective and approved drugs like metformin could be an effective strategy for managing PD. However, the mechanistic role of metformin in PD neuropathology was not fully elucidated. Metformin is an insulin-sensitizing agent used as a first-line therapy in the management of type 2 diabetes mellitus (T2DM) and has the ability to reduce insulin resistance (IR). Metformin may have a beneficial effect on PD neuropathology. The neuroprotective effect of metformin is mainly mediated by activating adenosine monophosphate protein kinase (AMPK), which reduces mitochondrial dysfunction, oxidative stress, and α-synuclein aggregation. As well, metformin mitigates brain IR a hallmark of PD and other neurodegenerative diseases. However, metformin may harm PD neuropathology by inducing hyperhomocysteinemia and deficiency of folate and B12. Therefore, this review aimed to find the potential role of metformin regarding its protective and detrimental effects on the pathogenesis of PD. The mechanistic role of metformin in PD neuropathology was not fully elucidated. Most studies regarding metformin and its effectiveness in PD neuropathology were observed in preclinical studies, which are not fully translated into clinical settings. In addition, metformin effect on PD neuropathology was previously clarified in T2DM, potentially linked to an increasing PD risk. These limitations hinder the conclusion concerning the therapeutic efficacy of metformin and its beneficial and detrimental role in PD. Therefore, as metformin does not cause hypoglycemia and is a safe drug, it should be evaluated in non-diabetic patients concerning PD risk.


Asunto(s)
Diabetes Mellitus Tipo 2 , Metformina , Enfermedades Neurodegenerativas , Enfermedad de Parkinson , Humanos , Enfermedad de Parkinson/metabolismo , Metformina/farmacología , Metformina/uso terapéutico , Enfermedades Neurodegenerativas/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Neuronas Dopaminérgicas
2.
Diabetes Obes Metab ; 26(8): 3031-3044, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38802993

RESUMEN

Depression is a mood disorder that may increase risk for the development of insulin resistance (IR) and type 2 diabetes (T2D), and vice versa. However, the mechanistic pathway linking depression and T2D is not fully elucidated. The aim of this narrative review, therefore, was to discuss the possible link between depression and T2D. The coexistence of T2D and depression is twice as great compared to the occurrence of either condition independently. Hyperglycaemia and dyslipidaemia promote the incidence of depression by enhancing inflammation and reducing brain serotonin (5-hydroxytryptamine [5HT]). Dysregulation of insulin signalling in T2D impairs brain 5HT signalling, leading to the development of depression. Furthermore, depression is associated with the development of hyperglycaemia and poor glycaemic control. Psychological stress and depression promote the development of T2D. In conclusion, T2D could be a potential risk factor for the development of depression through the induction of inflammatory reactions and oxidative stress that affect brain neurotransmission. In addition, chronic stress in depression may induce the development of T2D through dysregulation of the hypothalamic-pituitary-adrenal axis and increase circulating cortisol levels, which triggers IR and T2D.


Asunto(s)
Depresión , Diabetes Mellitus Tipo 2 , Resistencia a la Insulina , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/metabolismo , Humanos , Depresión/etiología , Estrés Psicológico/complicaciones , Estrés Psicológico/fisiopatología , Sistema Hipotálamo-Hipofisario/metabolismo , Sistema Hipotálamo-Hipofisario/fisiopatología , Encéfalo/metabolismo , Estrés Oxidativo/fisiología , Factores de Riesgo , Hiperglucemia/metabolismo , Sistema Hipófiso-Suprarrenal/fisiopatología , Sistema Hipófiso-Suprarrenal/metabolismo , Trastorno Depresivo/etiología , Serotonina/metabolismo
3.
Phys Chem Chem Phys ; 26(4): 3229-3239, 2024 Jan 24.
Artículo en Inglés | MEDLINE | ID: mdl-38193862

RESUMEN

Perovskites composed of inorganic cesium (Cs) halide provide a route to thermally resistant solar cells. Nevertheless, the use of hole-transporting layers (HTLs) with hydrophobic additives is constrained by moisture-induced phase deterioration. Due to significant electrical loss, dopant-free HTLs are unable to produce practical solar cells. In this article, we designed a two-dimensional 1,3,6,8-tetrakis[5-(N,N-di(p-(methylthio)phenyl)amino-p-phenyl)-thiophen-2-yl]pyrene (termed SMe-TATPyr) molecule as a new HTL to regulate electrical loss in lead-free perovskite solar cells (PSCs). We optimized the power conversion efficiency (PCE) of PSCs based on mixed tin (Sn)/germanium (Ge) halide perovskite (CsSn0.5Ge0.5I3) by exploring different factors, such as the deep and shallow levels of defects, density of states at the valence band (NV), thickness of the perovskite film, p-type doping concentration (NA) of HTL, the series and shunt resistances, and so on. We carried out comparative research by employing the 1D-SCAPS (a solar cell capacitance simulator) analysis tool. Through optimization of the PSC, we obtained the highest parameters in the simulated solar cell structure of fluorine tin oxide (FTO)/titanium dioxide (TiO2)/CsSn0.5Ge0.5I3/SMe-TATPyr/gold (Au), and the PCE reached up to 20% with a fill factor (FF) of 81.89%.

4.
J Cell Mol Med ; 27(13): 1775-1789, 2023 07.
Artículo en Inglés | MEDLINE | ID: mdl-37210624

RESUMEN

Parkinson's disease (PD) is the second most common neurodegenerative disease after Alzheimer's disease (AD). Genetic predisposition and immune dysfunction are involved in the pathogenesis of PD. Notably, peripheral inflammatory disorders and neuroinflammation are associated with PD neuropathology. Type 2 diabetes mellitus (T2DM) is associated with inflammatory disorders due to hyperglycaemia-induced oxidative stress and the release of pro-inflammatory cytokines. Particularly, insulin resistance (IR) in T2DM promotes the degeneration of dopaminergic neurons in the substantia nigra (SN). Thus, T2DM-induced inflammatory disorders predispose to the development and progression of PD, and their targeting may reduce PD risk in T2DM. Therefore, this narrative review aims to find the potential link between T2DM and PD by investigating the role of inflammatory signalling pathways, mainly the nuclear factor kappa B (NF-κB) and the nod-like receptor pyrin 3 (NLRP3) inflammasome. NF-κB is implicated in the pathogenesis of T2DM, and activation of NF-κB with induction of neuronal apoptosis was also confirmed in PD patients. Systemic activation of NLRP3 inflammasome promotes the accumulation of α-synuclein and degeneration of dopaminergic neurons in the SN. Increasing α-synuclein in PD patients enhances NLRP3 inflammasome activation and the release of interleukin (IL)-1ß followed by the development of systemic inflammation and neuroinflammation. In conclusion, activation of the NF-κB/NLRP3 inflammasome axis in T2DM patients could be the causal pathway in the development of PD. The inflammatory mechanisms triggered by activated NLRP3 inflammasome lead to pancreatic ß-cell dysfunction and the development of T2DM. Therefore, attenuation of inflammatory changes by inhibiting the NF-κB/NLRP3 inflammasome axis in the early T2DM may reduce future PD risk.


Asunto(s)
Diabetes Mellitus Tipo 2 , Enfermedades Neurodegenerativas , Enfermedad de Parkinson , Humanos , Inflamasomas/metabolismo , FN-kappa B/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , alfa-Sinucleína , Enfermedad de Parkinson/metabolismo , Pirina , Proteínas NLR , Enfermedades Neuroinflamatorias , Diabetes Mellitus Tipo 2/complicaciones
5.
Molecules ; 28(6)2023 Mar 09.
Artículo en Inglés | MEDLINE | ID: mdl-36985473

RESUMEN

The goal of the current work was to create an antibacterial agent by using polycaprolactone/chitosan (PCL/CH) nanofibers loaded with Cordia myxa fruit extract (CMFE) as an antimicrobial agent for wound dressing. Several characteristics, including morphological, physicomechanical, and mechanical characteristics, surface wettability, antibacterial activity, cell viability, and in vitro drug release, were investigated. The inclusion of CMFE in PCL/CH led to increased swelling capability and maximum weight loss. The SEM images of the PCL/CH/CMFE mat showed a uniform topology free of beads and an average fiber diameter of 195.378 nm. Excellent antimicrobial activity was shown towards Escherichia coli (31.34 ± 0.42 mm), Salmonella enterica (30.27 ± 0.57 mm), Staphylococcus aureus (21.31 ± 0.17 mm), Bacillus subtilis (27.53 ± 1.53 mm), and Pseudomonas aeruginosa (22.17 ± 0.12 mm) based on the inhibition zone assay. The sample containing 5 wt% CMFE had a lower water contact angle (47 ± 3.7°), high porosity, and high swelling compared to the neat mat. The release of the 5% CMFE-loaded mat was proven to be based on anomalous non-Fickian diffusion using the Korsmeyer-Peppas model. Compared to the pure PCL membrane, the PCL-CH/CMFE membrane exhibited suitable cytocompatibility on L929 cells. In conclusion, the fabricated antimicrobial nanofibrous films demonstrated high bioavailability, with suitable properties that can be used in wound dressings.


Asunto(s)
Quitosano , Cordia , Nanofibras , Frutas , Antibacterianos/farmacología , Poliésteres/farmacología , Vendajes
6.
J Food Sci Technol ; 60(1): 200-210, 2023 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-36618031

RESUMEN

Development of fermented flavour during storage reduces acceptability of Shughri pear. Therefore, the current study was designed to investigate the combined effect of 1-Methylcyclopropene (1-MCP) and hypobaric treatment on stability of Shughri pear during 120 days of storage. Fruit were treated individually or combinedly with 25, 50, and 75 kilo pascal hypobaric treatments for 4 h and 1-MCP (0.3 µLL-1 and 0.6 µLL-1) for 24 h, whereas control received no treatment. The pears were stored for 120 days at (0 ± 1 °C, 85 ± 5% RH), and were evaluated after every 30 days. After cold storage, pears were shifted to simulated retail conditions (20 ± 3 °C, 65 ± 5% RH). The combination of 25 kPa + 0.6 µLL-1 1-MCP significantly (P ≤ 0.05) delayed fruit ripening, reduced Alcohol dehydrogenase (ADH), and Pyruvate decarboxylase (PDC) activities, maintained the quality, and led to higher consumers' acceptability of the pear followed by 50 kPa + 0.6 µLL-1 and 25 kPa + 0.3 µLL-1. The control fruit were marketable for a week after storage with relatively less acceptability due to fermented flavour compared to treated fruit, marketable for more than two weeks. Among all the treatments, the synergy of 1-MCP and hypobaric treatment 25 kPa + 0.6 µLL-1 1-MCP improved the postharvest storage life and quality parameters, preventing development of fermented flavour in the pears. The experiment was conducted on pilot scale, for commercial application, the results of this study should be validated on large scale.

7.
Mov Disord ; 37(4): 826-841, 2022 04.
Artículo en Inglés | MEDLINE | ID: mdl-35218056

RESUMEN

BACKGROUND: The Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) has become the gold standard for evaluating different domains in Parkinson's disease (PD), and it is commonly used in clinical practice, research, and clinical trials. OBJECTIVES: The objectives are to validate the Arabic-translated version of the MDS-UPDRS and to assess its factor structure compared with the English version. METHODS: The study was carried out in three phases: first, the English version of the MDS-UPDRS was translated into Arabic and subsequently back-translated into English by independent translation team; second, cognitive pretesting of selected items was performed; third, the Arabic version was tested in over 400 native Arabic-speaking PD patients. The psychometric properties of the translated version were analyzed using confirmatory factor analysis (CFA) as well as exploratory factor analysis (EFA). RESULTS: The factor structure of the Arabic version was consistent with that of the English version based on the high CFIs for all four parts of the MDS-UPDRS in the CFA (CFI ≥0.90), confirming its suitability for use in Arabic. CONCLUSIONS: The Arabic version of the MDS-UPDRS has good construct validity in Arabic-speaking patients with PD and has been thereby designated as an official MDS-UPDRS version. The data collection methodology among Arabic-speaking countries across two continents of Asia and Africa provides a roadmap for validating additional MDS rating scale initiatives and is strong evidence that underserved regions can be energically mobilized to promote efforts that apply to better clinical care, education, and research for PD. © 2022 International Parkinson and Movement Disorder Society.


Asunto(s)
Enfermedad de Parkinson , Análisis Factorial , Humanos , Pruebas de Estado Mental y Demencia , Enfermedad de Parkinson/diagnóstico , Enfermedad de Parkinson/psicología , Índice de Severidad de la Enfermedad , Sociedades Médicas
8.
Molecules ; 27(14)2022 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-35889394

RESUMEN

The purpose of this study was to evaluate the potential of a newly modified cyclodextrin derivative, water-soluble ß-cyclodextrin-epichlorohydrin (ß-CD), as an effective drug carrier to enhance the poor solubility and bioavailability of galangin (GAL), a poorly water-soluble model drug. In this regard, inclusion complexes of GAL/ß-CDP were prepared. UV-VIS spectrophotometry, Fourier-transform infrared spectroscopy (FTIR), X-ray crystallography (XRD), zeta potential analysis, particle size analysis, field emission scanning electron microscopy (FESEM), and transmission electron microscopy (TEM) were applied to characterize the synthesized GAL/ß-CD. Michigan Cancer Foundation-7 (MCF-7; human breast cancer cells) and rat embryo fibroblast (REF; normal cells) were employed to examine the in vitro cytotoxic effects of GAL/ß-CD using various parameters. The dye-based tests of MTT and crystal violet clearly exhibited that GAL/ß-CD-treated cells had a reduced proliferation rate, an influence that was not found in the normal cell line. The cells' death was found to follow apoptotic mechanisms, as revealed by the dye-based test of acridine orange/ethidium bromide (AO/EtBr), with the involvement of the mitochondria via caspase-3-mediated events, as manifested by the Rh 123 test. We also included a mouse model to examine possible in vivo toxic effects of GAL/ß-CD. It appears that the inclusion complex does not have a significant influence on normal cells, as indicated by serum levels of kidney and liver enzymatic markers, as well as thymic and splenic mass indices. A similar conclusion was reached on the histological level, as manifested by the absence of pathological alterations in the liver, kidney, thymus, spleen, heart, and lung.


Asunto(s)
Neoplasias de la Mama , beta-Ciclodextrinas , Animales , Neoplasias de la Mama/tratamiento farmacológico , Rastreo Diferencial de Calorimetría , Portadores de Fármacos , Femenino , Flavonoides , Humanos , Ratones , Ratas , Solubilidad , Espectroscopía Infrarroja por Transformada de Fourier , Agua/química , Difracción de Rayos X , beta-Ciclodextrinas/química
9.
J Food Sci Technol ; 59(11): 4221-4229, 2022 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-36193482

RESUMEN

This research aimed to extend the postharvest shelf life of Royal Gala apple during cold storage and maintain its market value in simulated retail conditions. Apples were treated with hypobaric pressure (50 kPa for 4 h) followed by 1-MCP (0.5 µL L-1, 0.7 µL L-1, and 1.0 µL L-1) treatment for 24 h individually and in combinations, stored at (1 ± 1 °C, 85 ± 3% RH) for 120 d and analyzed for different quality parameters (Peel color, firmness, weight loss, TSS, acidity, ethylene production rate, and respiration rate) at each 30 d interval, followed by a 20 d simulated retail condition at 20 ± 3 °C with 4 d interval. Results indicated that all 1-MCP concentrations were more effective in retaining quality compared to individual hypobaric treatment. However, a synergistic effect was observed by combining 1-MCP with hypobaric treatment. Among the combined treatments, 1.0 µL L-11-MCP + 50 kPa more effectively and significantly retained quality during cold storage. Furthermore, the apples were more juicy, tasty, and attractive in color than others in simulated conditions. Addition of hypobaric treatment to 1-MCP might reduce endogenous ethylene in fruit by outward diffusion and blocking further ethylene synthesis by the action of 1-MCP. However, in-depth study is required for further understanding the phenomena.

10.
Molecules ; 26(11)2021 May 21.
Artículo en Inglés | MEDLINE | ID: mdl-34063773

RESUMEN

Flaky graphene oxide (GO) nanoparticles (NPs) were synthesized using Hummer's method and then capped with polyethylene glycol (PEG) by an esterification reaction, then loaded with Nigella sativa (N. sativa) seed extract. Aiming to investigate their potential use as a smart drug delivery system against Staphylococcus aureus and Escherichia coli, the spectral and structural characteristics of GO-PEG NPs were comprehensively analyzed by XRD, AFM, TEM, FTIR, and UV- Vis. XRD patterns revealed that GO-PEG had different crystalline structures and defects, as well as a higher interlayer spacing. AFM results showed GONPs with the main grain size of 24.41 nm, while GONPs-PEG revealed graphene oxide aggregation with the main grain size of 287.04 nm after loading N. sativa seed extract, which was verified by TEM examination. A strong OH bond appeared in FTIR spectra. Furthermore, UV- Vis absorbance peaks at (275, 284, 324, and 327) nm seemed to be correlated with GONPs, GO-PEG, N. sativa seed extract, and GO -PEG- N. sativa extract. The drug delivery system was observed to destroy the bacteria by permeating the bacterial nucleic acid and cytoplasmic membrane, resulting in the loss of cell wall integrity, nucleic acid damage, and increased cell-wall permeability.


Asunto(s)
Antibacterianos/farmacología , Sistemas de Liberación de Medicamentos , Grafito/química , Nanopartículas/química , Nigella sativa/química , Extractos Vegetales/farmacología , Polietilenglicoles/química , Antibacterianos/administración & dosificación , Escherichia coli/efectos de los fármacos , Pruebas de Sensibilidad Microbiana , Microscopía Electrónica de Transmisión , Extractos Vegetales/administración & dosificación , Análisis Espectral/métodos , Staphylococcus aureus/efectos de los fármacos , Difracción de Rayos X
11.
J Sci Food Agric ; 101(1): 179-184, 2021 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-32613605

RESUMEN

BACKGROUND: Information about the nutritive value, dry matter (DM) digestibility, and methane (CH4 ) emission potential of grass species is required for their optimal utilization in ruminant rations. The present study was designed: (i) to quantify the nutrient profile, mineral composition and in vitro dry matter digestibility (IVDMD) of winter grass species commonly available in northern Pakistan; and (ii) to measure the in vitro gas production (IVGP) and CH4 emission of the grass species during 72 h in vitro ruminal fermentation. Seven grass species, namely, Cenchrus ciliaris, Setaria anceps, Panicum antidotale, P. maximum, Pennisetum purpureum, Pennisetum orientale, and Atriplex lentiformis were assessed. RESULTS: A high level of variability (P < 0.001) was observed among grass species for the content of all measured nutrients, IVDMD, IVGP, and CH4 -production. Notably, the content (g kg-1 DM) of crude protein varied from 59.8 to 143.3, neutral detergent fiber from 560.3 to 717.9, IVDMD from 375.1 to 576.2, and 72 h cumulative IVGP from 97.6 to 227.4 mL g-1 organic matter (OM) and CH4 from 48 to 67 mL g-1 OM. Among the grasses, P. antidotale had greater content (g kg-1 DM) of crude protein (CP) (143.3), IVDMD (576.2), and 72 h cumulative IVGP (227.4 mL g-1 OM), and produced the smallest amount of total CH4 (48 mL g-1 OM) during 72 h fermentation. In contrast, A. lentiformis had the lowest content (g kg-1 DM) of CP (59.8), IVDMD (375.1), 72 h cumulative IVGP (97.6 mL g-1 OM), and produced a greater amount of total CH4 (67 mL g-1 OM) during 72 h fermentation. CONCLUSION: The findings of the current study highlight that it is possible to select and further develop grass species with high nutritional value and lower CH4 -production, which can improve livestock productivity, farm profitability, and long-term environment sustainability. © 2020 Society of Chemical Industry.


Asunto(s)
Alimentación Animal/análisis , Bovinos/metabolismo , Metano/metabolismo , Poaceae/química , Poaceae/metabolismo , Rumen/metabolismo , Animales , Digestión , Fermentación , Cinética , Metano/química , Valor Nutritivo , Pakistán , Rumen/química , Estaciones del Año
12.
Int J Sport Nutr Exerc Metab ; 30(6): 427-434, 2020 Nov 01.
Artículo en Inglés | MEDLINE | ID: mdl-32932231

RESUMEN

This study aimed to identify the acute effects of caffeinated chewing gum (CAF) on bicycle motocross (BMX) time-trial (TT) performance. In a randomized, placebo-controlled, double-blind cross-over design, 14 male BMX riders (age = 20.0 ± 3.3 years; height = 1.78 ± 0.04 m; body mass = 72 ± 4 kg), consumed either (300 mg; 4.2 ± 0.2 mg/kg) caffeinated (300 mg caffeine, 6 g sugars) or a placebo (0 mg caffeine, 0 g sugars) gum, and undertook three BMX TTs. Repeated-measure analysis revealed that CAF has a large ergogenic effect on TT time, F(1, 14) = 33.570, p = .001, ηp2=.71; -1.5% ± 0.4 compared with the placebo. Peak power and maximal power to weight ratio also increased significantly compared with the placebo condition, F(1, 14) = 54.666, p = .001, ηp2=.79; +3.5% ± 0.6, and F(1, 14) = 57.399, p = .001, ηp2=.80; +3% ± 0.3, respectively. Rating of perceived exertion was significantly lower F(1, 14) = 25.020, p = .001, ηp2=.64 in CAF (6.6 ± 1.3) compared with the placebo (7.2 ± 1.7). Administering a moderate dose (300 mg) of CAF could improve TT time by enhancing power and reducing the perception of exertion. BMX coaches and riders may consider consuming CAF before a BMX race to improve performance and reduce rating of perceived exertion.

13.
Philos Trans A Math Phys Eng Sci ; 376(2118)2018 Apr 28.
Artículo en Inglés | MEDLINE | ID: mdl-29555804

RESUMEN

We consider Hilbert's problem of the axioms of physics at a qualitative or conceptual level. This is more pressing than ever as we seek to understand how both general relativity and quantum theory could emerge from some deeper theory of quantum gravity, and in this regard I have previously proposed a principle of self-duality or quantum Born reciprocity as a key structure. Here, I outline some of my recent work around the idea of quantum space-time as motivated by this non-standard philosophy, including a new toy model of gravity on a space-time consisting of four points forming a square.This article is part of the theme issue 'Hilbert's sixth problem'.

14.
J Allergy Clin Immunol ; 134(6): 1422-1432.e11, 2014 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-24985397

RESUMEN

BACKGROUND: The initiation and regulation of pulmonary fibrosis are not well understood. IL-33, an important cytokine for respiratory diseases, is overexpressed in the lungs of patients with idiopathic pulmonary fibrosis. OBJECTIVES: We aimed to determine the effects and mechanism of IL-33 on the development and severity of pulmonary fibrosis in murine bleomycin-induced fibrosis. METHODS: Lung fibrosis was induced by bleomycin in wild-type or Il33r (St2)(-/-) C57BL/6 mice treated with the recombinant mature form of IL-33 or anti-IL-33 antibody or transferred with type 2 innate lymphoid cells (ILC2s). The development and severity of fibrosis was evaluated based on lung histology, collagen levels, and lavage cytology. Cytokine and chemokine levels were quantified by using quantitative PCR, ELISA, and cytometry. RESULTS: IL-33 is constitutively expressed in lung epithelial cells but is induced in macrophages by bleomycin. Bleomycin enhanced the production of the mature but reduced full-length form of IL-33 in lung tissue. ST2 deficiency, anti-IL-33 antibody treatment, or alveolar macrophage depletion attenuated and exogenous IL-33 or adoptive transfer of ILC2s enhanced bleomycin-induced lung inflammation and fibrosis. These pathologic changes were accompanied, respectively, by reduced or increased IL-33, IL-13, TGF-ß1, and inflammatory chemokine production in the lung. Furthermore, IL-33 polarized M2 macrophages to produce IL-13 and TGF-ß1 and induced the expansion of ILC2s to produce IL-13 in vitro and in vivo. CONCLUSIONS: IL-33 is a novel profibrogenic cytokine that signals through ST2 to promote the initiation and progression of pulmonary fibrosis by recruiting and directing inflammatory cell function and enhancing profibrogenic cytokine production in an ST2- and macrophage-dependent manner.


Asunto(s)
Interleucinas/inmunología , Pulmón/inmunología , Pulmón/patología , Macrófagos Alveolares/inmunología , Receptores de Interleucina/inmunología , Animales , Fibrosis , Proteína 1 Similar al Receptor de Interleucina-1 , Interleucina-13/genética , Interleucina-13/inmunología , Interleucina-33 , Interleucinas/genética , Linfocitos/inmunología , Ratones Endogámicos C57BL , Ratones Noqueados , Receptores de Interleucina/genética , Factor de Crecimiento Transformador beta1/genética , Factor de Crecimiento Transformador beta1/inmunología
15.
Am J Physiol Lung Cell Mol Physiol ; 307(3): L205-18, 2014 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-24879054

RESUMEN

Cigarette smoking (CS) can impact the immune system and induce pulmonary disorders such as chronic obstructive pulmonary disease (COPD), which is currently the fourth leading cause of chronic morbidity and mortality worldwide. Accordingly, the most significant risk factor associated with COPD is exposure to cigarette smoke. The purpose of the present study is to provide an updated overview of the literature regarding the effect of CS on the immune system and lungs, the mechanism of CS-induced COPD and oxidative stress, as well as the available and potential treatment options for CS-induced COPD. An extensive literature search was conducted on the PubMed/Medline databases to review current COPD treatment research, available in the English language, dating from 1976 to 2014. Studies have investigated the mechanism by which CS elicits detrimental effects on the immune system and pulmonary function through the use of human and animal subjects. A strong relationship among continued tobacco use, oxidative stress, and exacerbation of COPD symptoms is frequently observed in COPD subjects. In addition, therapeutic approaches emphasizing smoking cessation have been developed, incorporating counseling and nicotine replacement therapy. However, the inability to reverse COPD progression establishes the need for improved preventative and therapeutic strategies, such as a combination of intensive smoking cessation treatment and pharmaceutical therapy, focusing on immune homeostasis and redox balance. CS initiates a complex interplay between oxidative stress and the immune response in COPD. Therefore, multiple approaches such as smoking cessation, counseling, and pharmaceutical therapies targeting inflammation and oxidative stress are recommended for COPD treatment.


Asunto(s)
Pulmón/inmunología , Estrés Oxidativo/inmunología , Enfermedad Pulmonar Obstructiva Crónica/tratamiento farmacológico , Enfermedad Pulmonar Obstructiva Crónica/etiología , Enfermedad Pulmonar Obstructiva Crónica/inmunología , Fumar/inmunología , Animales , Humanos , Pulmón/efectos de los fármacos , Cese del Hábito de Fumar/métodos
16.
Br J Dermatol ; 171(2): 234-41, 2014 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-24665835

RESUMEN

Melanoma is one of the most aggressive and deadly skin cancers, and, in its advanced stages, accounts for > 80% mortality. The incidence of melanoma is increasing worldwide; however, beyond surgical removal of the tumour, there is currently no curative therapy available, especially for its advanced stages. This may, in part, be owing to incomplete understanding of the molecular mechanisms that regulate the initiation and/or progression of melanoma to metastasis. The molecular mechanisms leading to the development and progression of melanoma are the focus of intense investigation, and many genetic/epigenetic alterations affecting melanoma progression and development have been identified. microRNAs (miRNAs) are emerging as important causal modulators in the development and progression of melanoma. The understanding of miRNA-mediated regulation of tumours has grown immensely over the last few years, as it has been understood to regulate most biological processes. Here, we review the currently available data on miRNAs associated with melanoma, highlighting those deregulated miRNAs that target important genes and pathways involved in the progression of melanocytes to primary and metastatic melanoma. We also review their potential clinical utility as biomarkers and potential use in targeted therapy.


Asunto(s)
Melanoma/etiología , MicroARNs/fisiología , Neoplasias Cutáneas/etiología , Biomarcadores de Tumor/metabolismo , Transformación Celular Neoplásica/patología , Regulación hacia Abajo/fisiología , Detección Precoz del Cáncer , Epigénesis Genética/fisiología , Genes Supresores de Tumor/fisiología , Humanos , Melanoma/diagnóstico , Factor de Transcripción Asociado a Microftalmía/fisiología , Invasividad Neoplásica , Metástasis de la Neoplasia , Pronóstico , Neoplasias Cutáneas/diagnóstico , Proteína p53 Supresora de Tumor/metabolismo , Regulación hacia Arriba/fisiología
17.
Ann Allergy Asthma Immunol ; 112(1): 18-22, 2014 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-24331388

RESUMEN

OBJECTIVE: To investigate the molecular mechanism of reactive nitrogen species (RNS) in the pathogenesis of asthma and examine the use of fractional exhaled nitric oxide (FENO) measurements in close conjunction with standard clinical assessments of asthma. DATA SOURCES: Through PubMed, Google Scholar, and Medline databases, a broad medical literature review was performed in the following areas of asthma pathobiology and management: allergic asthma, RNS, nitric oxide (NO), airway inflammation, and FENO. STUDY SELECTIONS: Studies were selected based on the physiologic and pathophysiologic roles of RNS in relation to allergic asthma. Current evaluations on clinical applications of FENO in asthma treatment also were selected. RESULTS: At the onset of an asthma attack, an enhanced production of NO strongly correlates with increase inducible NO synthase (NOS) activity, whereas endothelial NOS and neuronal NOS regulate primarily normal metabolic functions in the central and peripheral airways. During allergic inflammatory responses, NO and superoxide form peroxynitrite, which has deleterious effects in the respiratory tract. RNS directly accentuates airway inflammation and cytotoxicity through nitrosative stress. Moreover, the use of FENO to monitor eosinophilic-mediated airway inflammation is a potentially valuable assessment that supplements standard procedures to monitor the progression of asthma. CONCLUSION: This review examines recent evidence implicating the molecular mechanisms of NO and NO-derived RNS in the pathobiology of asthma and suggests that monitoring FENO may markedly contribute to asthma diagnosis.


Asunto(s)
Asma/metabolismo , Óxido Nítrico/metabolismo , Especies de Nitrógeno Reactivo/metabolismo , Humanos , Inflamación/inmunología , Óxido Nítrico Sintasa de Tipo I/metabolismo , Óxido Nítrico Sintasa de Tipo II/biosíntesis , Óxido Nítrico Sintasa de Tipo II/metabolismo , Óxido Nítrico Sintasa de Tipo III/metabolismo , Ácido Peroxinitroso/biosíntesis , Ácido Peroxinitroso/metabolismo , Sistema Respiratorio/patología
18.
Lipids Health Dis ; 13: 95, 2014 Jun 09.
Artículo en Inglés | MEDLINE | ID: mdl-24912476

RESUMEN

BACKGROUND: Major cardiovascular disorders are being recognized earlier in life. In this study we examined the effects of swimming and soccer training on male adolescent lipid-lipoprotein profiles relative to a maturity matched control group to determine the effects of these exercises on specific cardiovascular risk and anti-risk factors. METHODS: Forty five adolescent males (11.81 ± 1.38 yr) including swimmers (SW), soccer players (SO), and non-athlete, physically active individuals as controls (C), participated in this study. Training groups completed 12-wk exercise programs on three non-consecutive days per week. Plasma low-density lipoprotein (LDL), very low density lipoprotein (VLDL), high density lipoprotein (HDL), apolipoprotein A-I (apoA-I), apolipoprotein B (apoB), total cholesterol (TC), and triglyceride (TG) levels were measured in control, pre-training, during-training, and post-training. RESULTS: In response to the 12-wk training period, the SO group demonstrated a decrease in the mean LDL level compared to the SW and C (SW: 0.15%; SO: -9.51%; C: 19.59%; p < 0.001) groups. There was an increase in both the SW and SO groups vs. the control in mean HDL (SW: 5.66%; SO: 3.07%; C: -7.21%; p < 0.05) and apoA-I (SW: 3.86%; SO: 5.48%; C: -1.01%; p < 0.05). ApoB was considerably lower in the training groups vs. control (SW: -9.52%; SO: -13.87%; C: 21.09%; p < 0.05). ApoA-I/apoB ratio was significantly higher in training groups vs. control (SW: 16.74%; SO: 23.71%; C: -17.35%; p < 0.001). There were no significant differences between groups for other factors. CONCLUSIONS: The favorable alterations in LDL, HDL, apoA-I, and apoB observed in the training groups suggest that both regular swimming or soccer exercise can potentially mitigate cardiovascular risk in adolescent males.


Asunto(s)
Enfermedades Cardiovasculares/sangre , Enfermedades Cardiovasculares/prevención & control , Ejercicio Físico/fisiología , Adolescente , Apolipoproteína A-I/sangre , Apolipoproteínas B/sangre , Niño , HDL-Colesterol/sangre , LDL-Colesterol/sangre , Humanos , Lipoproteínas LDL/sangre , Masculino , Factores de Riesgo
19.
Int J Biol Macromol ; 274(Pt 1): 133383, 2024 Jun 22.
Artículo en Inglés | MEDLINE | ID: mdl-38914395

RESUMEN

In this report, we present a dual crosslinking hydrogel fiber made from polyamine saccharides chitosan (CS), synthesized through UV polymerization. This process utilizes Irgacure 2959 and N,N'-Methylenebisacrylamide (MBAA) as initiators, followed by immersion in an aluminum chloride (AlCl3) solution. The resulting hydrogel incorporates a dual crosslinking mechanism, quantitatively studied via Nuclear Magnetic Resonance (NMR) spectroscopy. This mechanism involves chemical crosslinking through radical graft polymerization of acrylamide and acrylic acid onto CS in the presence of MBAA, and physical crosslinking through hydrogen bonding interactions between P(AAm-co-AA) and a metal coordination bond. The mechanical properties of the hydrogel fiber enable it to withstand stresses up to 656 kPa and strains exceeding 300 %. Additionally, the hydrogel fiber exhibits conductivity at 1.96 Scm-1. Serving as a multifunctional material, it acts as a strain sensor and finds utility in optics. Remarkably, it demonstrates the capability to detect human motions such as finger bending and minor deformations like vibrations of the vocal cords. Furthermore, its ability to guide dynamic light makes it promising for optical applications. Consequently, this multifunctional hydrogel fiber emerges as a highly promising candidate for diverse applications in fields such as bioengineering and electronics.

20.
J Family Med Prim Care ; 13(3): 845-850, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38736827

RESUMEN

Introduction: Mental disorders are highly prevalent and affect people across all regions of the world. The State of Jammu and Kashmir has been witness to a conflict for about three decades. Little is known about the extent of mental disorders in Kashmir. There was a dire need to estimate the prevalence of mental disorders among the rural population of Kashmir. The study was undertaken to estimate the point prevalence of specific mental disorders in rural population of Kashmir, sociodemographic correlates of mental disorders and to assess the service utilization in individuals with mental disorders. Materials and Methods: Community-based survey carried out in rural districts of Kashmir using a mixed sampling technique. The survey was conducted in six blocks of two districts (Pulwama and Baramulla) of Kashmir. Mini-International Neuropsychiatric Interview (MINI) for psychiatric morbidity was used. Appropriate statistical methods were applied. Results: In total, 11.3% of adult population suffers from mental illness in the valley. As compared to males (8.4%), females had a higher prevalence (12.9%). Depressive disorders (8.4%) were the most common psychiatric disorders, followed by anxiety disorders (5.1%). Only 12.6% of patients suffering from mental disorders had sought treatment for their illnesses. Conclusion: The findings of this study have cleared many doubts and indicated the prevalence of 10 common mental health disorders in the general population as well as among different socioeconomic groups in Kashmir. This study has indicated low levels of treatment sought by people with mental illness.

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