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1.
Molecules ; 29(8)2024 Apr 16.
Artículo en Inglés | MEDLINE | ID: mdl-38675627

RESUMEN

The abietane diterpenoid 7α-acetoxy-6ß-hydroxyroyleanone (Roy) isolated from Plectranthus grandidentatus demonstrates cytotoxicity across numerous cancer cell lines. To potentiate anticancer attributes, a series of semi-synthetic Roy derivatives were generated and examined computationally. ADMET predictions were used to evaluate drug-likeness and toxicity risks. The antineoplastic potential was quantified by PASS. The DFT models were used to assess their reactivity and stability. Molecular docking determined cancer-related protein binding. MS simulations examined ligand-protein stability. Additionally, network pharmacology was used to identify potential targets and signaling pathways. Favorable ADME attributes and acceptable toxicity profiles were determined for all compounds. Strong anticancer potential was shown across derivatives (Pa 0.819-0.879). Strategic modifications altered HOMO-LUMO gaps (3.39-3.79 eV) and global reactivity indices. Favorable binding was revealed against cyclin-dependent kinases, BCL-2, caspases, receptor tyrosine kinases, and p53. The ligand exhibited a stable binding pose in MD simulations. Network analysis revealed involvement in cancer-related pathways. In silico evaluations predicted Roy and derivatives as effective molecules with anticancer properties. Experimental progress is warranted to realize their chemotherapeutic potential.


Asunto(s)
Abietanos , Diterpenos , Simulación del Acoplamiento Molecular , Plectranthus , Humanos , Abietanos/química , Abietanos/farmacología , Plectranthus/química , Simulación por Computador , Antineoplásicos/farmacología , Antineoplásicos/química , Línea Celular Tumoral , Antineoplásicos Fitogénicos/farmacología , Antineoplásicos Fitogénicos/química , Simulación de Dinámica Molecular , Estructura Molecular
2.
J Cell Mol Med ; 27(13): 1867-1879, 2023 07.
Artículo en Inglés | MEDLINE | ID: mdl-37259630

RESUMEN

Fibrosis is an important phenomenon as it can occur early in the pathogenesis of asthma; it may be associated with disease severity and resistance to therapy. There is a strong evidence that infection caused by human rhinovirus (HRV) contributes to remodelling process, but there is lack of studies clearly explaining this pathway. Synthetic peroxisome proliferator-activated receptor (PPAR) γ presents immunomodulatory and anti-inflammatory features. In this study, we examined immunomodulatory properties of ciglitazone - PPAR-γ agonist, in development and modulation of airway remodelling. Epithelial cells (NHBE) and two lines of fibroblasts (WI-38, HFL1) were stimulated with ciglitazone and rhinovirus. The expression of genes related to airway remodelling process were analysed in the cells; moreover NF-κB, c-Myc and STAT3 were silenced in order to estimate potential pathways involved. Ciglitazone decreased mRNA expression of MMP-9 and TGF-ß. It also modified the expression of α-SMA and collagen after rhinovirus infection. Transcription factors knockdown altered the levels of expression. The results suggest possible anti-fibrotic activity of PPAR-γ agonist in human airway cells. Ciglitazone has been shown to be dependent on NF-κB- and STAT3-related pathways, thus, the PPAR-γ agonist may have therapeutic potential for the treatment of airway remodelling in asthma.


Asunto(s)
Asma , Tiazolidinedionas , Humanos , FN-kappa B/metabolismo , Rhinovirus/metabolismo , Remodelación de las Vías Aéreas (Respiratorias) , Frecuencia Cardíaca , Tiazolidinedionas/farmacología , Asma/tratamiento farmacológico , Asma/patología , Fibrosis , PPAR gamma/metabolismo
3.
Int J Mol Sci ; 24(6)2023 Mar 21.
Artículo en Inglés | MEDLINE | ID: mdl-36982980

RESUMEN

Asthma is an inflammatory disease whose etiology remains unclear. Its characteristics encompass a wide range of clinical symptoms, inflammatory processes, and reactions to standard therapies. Plants produce a range of constitutive products and secondary metabolites that may have therapeutic abilities. The aim of this study was to determine the effects of Senna obtusifolia transgenic hairy root extracts on virus-induced airway remodeling conditions. Three cell lines were incubated with extracts from transformed (SOA4) and transgenic (SOPSS2, with overexpression of the gene encoding squalene synthase 1) hairy roots of Senna obtusifolia in cell lines undergoing human rhinovirus-16 (HRV-16) infection. The effects of the extracts on the inflammatory process were determined based on the expression of inflammatory cytokines (IL-8, TNF-α, IL-1α and IFN-γ) and total thiol content. The transgenic Senna obtusifolia root extract reduced virus-induced expression of TNF, IL-8 and IL-1 in WI-38 and NHBE cells. The SOPSS2 extract reduced IL-1 expression only in lung epithelial cells. Both tested extracts significantly increased the concentration of thiol groups in epithelial lung cells. In addition, the SOPPS2 hairy root extract yielded a positive result in the scratch test. SOA4 and SOPPS2 Senna obtusifolia hairy root extracts demonstrated anti-inflammatory effects or wound healing activity. The SOPSS2 extract had stronger biological properties, which may result from a higher content of bioactive secondary metabolites.


Asunto(s)
Interleucina-8 , Senna , Humanos , Interleucina-8/metabolismo , Senna/genética , Cicatrización de Heridas , Extractos Vegetales/uso terapéutico , Antiinflamatorios/farmacología , Antiinflamatorios/metabolismo , Interleucina-1/metabolismo , Raíces de Plantas/genética
4.
J Cell Mol Med ; 26(3): 736-749, 2022 02.
Artículo en Inglés | MEDLINE | ID: mdl-34939316

RESUMEN

Bronchial epithelial cells and fibroblasts play an essential role in airway remodelling, due to their protective and secretory functions. There are many studies proving that infection caused by human rhinovirus may contribute to the process of airway remodelling. The beneficial properties of curcumin, the basic ingredient of turmeric, have been proved in many studies. Therefore, the aim of this study was the evaluation of curcumin immunomodulatory properties in development of airway remodelling. Fibroblasts (WI-38 and HFL1) and epithelial cells (NHBE) were incubated with curcumin. Additionally, remodelling conditions were induced with rhinovirus (HRV). Airway remodelling genes were determined by qPCR and immunoblotting. Moreover, NF-κB, c-Myc and STAT3 were silenced to analyse the pathways involved in airway remodelling. Curcumin reduced the expression of the genes analysed, especially MMP-9, TGF-ß and collagen I. Moreover, curcumin inhibited the HRV-induced expression of MMP-9, TGF-ß, collagen I and LTC4S (p < 0.05). NF-κB, c-Myc and STAT3 changed their course of expression. Concluding, our study shows that curcumin significantly downregulated gene expression related to the remodelling process, which is dependent on NF-κB and, partially, on c-Myc and STAT3. The results suggest that the remodelling process may be limited and possibly prevented, however this issue requires further research.


Asunto(s)
Remodelación de las Vías Aéreas (Respiratorias) , Curcumina , Curcumina/farmacología , Células Epiteliales/metabolismo , Fibroblastos/metabolismo , Humanos , FN-kappa B/genética , FN-kappa B/metabolismo
5.
Int J Mol Sci ; 23(15)2022 Jul 29.
Artículo en Inglés | MEDLINE | ID: mdl-35955554

RESUMEN

Fibrosis is one of the parameters of lung tissue remodeling in asthma. Relaxin has emerged as a natural suppressor of fibrosis, showing efficacy in the prevention of a multiple models of fibrosis. Therefore, the aim of this study was to analyze the aptitudes of relaxin, in the context of its immunomodulatory properties, in the development of airway remodeling. WI-38 and HFL1 fibroblasts, as well as epithelial cells (NHBE), were incubated with relaxin. Additionally, remodeling conditions were induced with two serotypes of rhinovirus (HRV). The expression of the genes contributing to airway remodeling were determined. Moreover, NF-κB, c-Myc, and STAT3 were knocked down to analyze the pathways involved in airway remodeling. Relaxin decreased the mRNA expression of collagen I and TGF-ß and increased the expression of MMP-9 (p < 0.05). Relaxin also decreased HRV-induced expression of collagen I and α-SMA (p < 0.05). Moreover, all the analyzed transcription factors­NF-κB, c-Myc, and STAT3­have shown its influence on the pathways connected with relaxin action. Though relaxin requires further study, our results suggest that this natural compound offers great potential for inhibition of the development, or even reversing, of factors related to airway remodeling. The presented contribution of the investigated transcription factors in this process additionally increases its potential possibilities through a variety of its activity pathways.


Asunto(s)
Remodelación de las Vías Aéreas (Respiratorias) , Relaxina , Remodelación de las Vías Aéreas (Respiratorias)/genética , Colágeno/metabolismo , Fibrosis , Humanos , FN-kappa B/genética , FN-kappa B/metabolismo , Relaxina/genética , Relaxina/metabolismo , Relaxina/farmacología , Transducción de Señal
6.
Molecules ; 27(3)2022 Jan 25.
Artículo en Inglés | MEDLINE | ID: mdl-35164060

RESUMEN

In recent years, there has been a considerable increase in interest in the use of transgenic plants as sources of valuable secondary metabolites or recombinant proteins. This has been facilitated by the advent of genetic engineering technology with the possibility for direct modification of the expression of genes related to the biosynthesis of biologically active compounds. A wide range of research projects have yielded a number of efficient plant systems that produce specific secondary metabolites or recombinant proteins. Furthermore, the use of bioreactors allows production to be increased to industrial scales, which can quickly and cheaply deliver large amounts of material in a short time. The resulting plant production systems can function as small factories, and many of them that are targeted at a specific operation have been patented. This review paper summarizes the key research in the last ten years regarding the use of transgenic plants as small, green biofactories for the bioreactor-based production of secondary metabolites and recombinant proteins; it simultaneously examines the production of metabolites and recombinant proteins on an industrial scale and presents the current state of available patents in the field.


Asunto(s)
Reactores Biológicos , Biotecnología , Industrias , Plantas Modificadas Genéticamente/metabolismo , Técnicas de Cultivo de Célula/métodos , Proteínas Recombinantes/metabolismo
7.
Int Arch Allergy Immunol ; 181(1): 56-70, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-31707382

RESUMEN

INTRODUCTION: Phospholipases are enzymes that occur in many types of human cells, including mast cells, and play an important role in the molecular background of asthma pathogenesis, and the development of inflammation NF-κB activities that affect numerous biological processes has been reported in many inflammatory diseases including asthma. Vitamin D is a widely studied factor that affects many diseases, including asthma. The aim of this study is to assess the influence of 1,25-(OH)2D3 on regulation of chosen phospholipase-A2 (PLA2) expression-selected inflammation mediators. METHODS: LUVA mast cells were stimulated with 1,25(OH)2D3, and inhibitors of NF-κB p65 and ubiquitination. Expression analysis of phospholipases (PLA2G5, PLA2G10, PLA2G12, PLA2G15, PLA2G4A, PLA2G4B, PLA2G4C, PLAA, NF-κB p65, and UBC) was done utilizing real-time PCR and Western blot. Eicosanoid (LTC4, LXA4, 15[S]-HETE, and PGE2) levels and sPLA2 were also measured. RESULTS: We found that 1,25(OH)2D3 decreased the expression of PLA2G5, PLA2G15, PLA2G5,UBC, and NF-κB p65 but increased expression of PLAA and PLA2G4C (p < 0.05). Moreover, the expression of PLA2G5 and PLA2G15 decreased after inhibition of NF-κB p65 and UBC. Increased levels of released LXA4 and 15(S)-HETE, decreased levels of LTC4, and sPLA2s enzymatic activity in response to 1,25(OH)2D3 were also observed. Additionally, NF-κB p65 inhibition led to an increase in the LXA4 concentration. CONCLUSION: Future investigations will be needed to further clarify the role of 1,25(OH)2D3 in the context of asthma and the inflammatory process; however, these results confirm a variety of effects which can be caused by this vitamin. 1,25(OH)2D3-mediated action may result in the development of new therapeutic strategies for asthma treatment.


Asunto(s)
Asma/metabolismo , Colecalciferol/metabolismo , Inflamación/metabolismo , Mastocitos/metabolismo , FN-kappa B/metabolismo , Fosfolipasas A2/metabolismo , Asma/genética , Línea Celular Transformada , Regulación de la Expresión Génica , Humanos , Inflamación/genética , Lipoxinas/metabolismo , FN-kappa B/genética , Fosfolipasas A2/genética , Transducción de Señal , Ubiquitinación
8.
Int J Mol Sci ; 21(14)2020 Jul 19.
Artículo en Inglés | MEDLINE | ID: mdl-32707732

RESUMEN

The skin is an important organ that acts as a physical barrier to the outer environment. It is rich in immune cells such as keratinocytes, Langerhans cells, mast cells, and T cells, which provide the first line of defense mechanisms against numerous pathogens by activating both the innate and adaptive response. Cutaneous immunological processes may be stimulated or suppressed by numerous plant extracts via their immunomodulatory properties. Several plants are rich in bioactive molecules; many of these exert antimicrobial, antiviral, and antifungal effects. The present study describes the impact of plant extracts on the modulation of skin immunity, and their antimicrobial effects against selected skin invaders. Plant products remain valuable counterparts to modern pharmaceuticals and may be used to alleviate numerous skin disorders, including infected wounds, herpes, and tineas.


Asunto(s)
Antiinfecciosos/administración & dosificación , Extractos Vegetales/administración & dosificación , Enfermedades Cutáneas Infecciosas/tratamiento farmacológico , Enfermedades Cutáneas Infecciosas/microbiología , Dermatomicosis/tratamiento farmacológico , Dermatomicosis/inmunología , Dermatomicosis/microbiología , Sinergismo Farmacológico , Humanos , Factores Inmunológicos/administración & dosificación , Plantas Medicinales/química , Piel/efectos de los fármacos , Piel/inmunología , Piel/microbiología , Enfermedades Cutáneas Bacterianas/tratamiento farmacológico , Enfermedades Cutáneas Bacterianas/inmunología , Enfermedades Cutáneas Bacterianas/microbiología , Enfermedades Cutáneas Infecciosas/inmunología , Virosis/tratamiento farmacológico , Virosis/inmunología , Virosis/virología
9.
Neurochem Res ; 43(7): 1363-1370, 2018 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-29786770

RESUMEN

The aim of this study was to determine the anticancer potential of Leonurus sibiricus extract derived from in vitro transgenic roots transformed by Agrobacetrium rhizogenes with AtPAP1 transcriptional factor, and that of transformed roots without construct, on grade IV human glioma cells and the U87MG cell line, and attempt to characterize the mechanism involved in this process. The anticancer effect induced by the tested extracts was associated with DNA damage, PARP cleavage/increased H2A.X histone levels and UHRF-1/DNMT1 down-regulation of mRNA levels. Additionally, we demonstrated differences in the content of compounds in the tested extracts by HPLC analysis with ATPAP1 construct and without. Both the tested extracts showed anticancer properties and the better results were observed for AtPAP1 with transcriptional factor root extract; this effect could be ascribed to the presence of higher condensed phenolic acids such as neochlorogenic acid, chlorogenic acids, ferulic acid, caffeic acid and p-coumaric acid. Further studies with AtPAP1 (with the transcriptional factor from Arabidopisi thaliana) root extract which showed better activities in combination with anticancer drugs are needed.


Asunto(s)
Proteínas de Arabidopsis/toxicidad , Daño del ADN/efectos de los fármacos , Epigénesis Genética/efectos de los fármacos , Leonurus , Extractos Vegetales/toxicidad , Raíces de Plantas , Factores de Transcripción/toxicidad , Apoptosis/efectos de los fármacos , Apoptosis/fisiología , Proteínas de Arabidopsis/aislamiento & purificación , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Supervivencia Celular/fisiología , Daño del ADN/fisiología , Relación Dosis-Respuesta a Droga , Regulación hacia Abajo/efectos de los fármacos , Regulación hacia Abajo/fisiología , Epigénesis Genética/fisiología , Humanos , Extractos Vegetales/aislamiento & purificación , Factores de Transcripción/aislamiento & purificación
10.
Mol Cell Biochem ; 445(1-2): 89-97, 2018 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-29238899

RESUMEN

The present study is the first investigation of the inhibitory effect of Rhaponticum carthamoides transformed roots (TR) extract on the proliferation of grade II and III human glioma cells. TR extract showed the cytotoxic effect and inhibited the colony formation of both glioma cell lines in dose-dependent manner. The root extract induced apoptosis by increasing of the reactive oxygen species (about threefold compared to the control cells) leading to a disruption of mitochondrial membrane potential. Additionally, the mRNA levels of the apoptotic factors such as Bax, Tp53, caspase-3, and caspase-9 were observed to increase. These results indicate that the TR extract possesses anticancer activity by inhibiting glioma cell proliferation and inducing apoptotic cell death, and may be used as a promising anticancer agent.


Asunto(s)
Neoplasias Encefálicas/patología , Caspasa 3/metabolismo , Caspasa 9/metabolismo , Glioma/patología , Leuzea/química , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Extractos Vegetales/farmacología , Raíces de Plantas/química , Especies Reactivas de Oxígeno/metabolismo , Antineoplásicos Fitogénicos/farmacología , Neoplasias Encefálicas/enzimología , Neoplasias Encefálicas/metabolismo , Caspasa 3/genética , Caspasa 9/genética , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Activación Enzimática , Glioma/enzimología , Glioma/metabolismo , Humanos , Leuzea/crecimiento & desarrollo , Leuzea/metabolismo , Persona de Mediana Edad , Raíces de Plantas/crecimiento & desarrollo , Raíces de Plantas/metabolismo , Proteína p53 Supresora de Tumor/efectos de los fármacos , Proteína X Asociada a bcl-2/genética
11.
Respir Res ; 16: 147, 2015 Dec 09.
Artículo en Inglés | MEDLINE | ID: mdl-26646719

RESUMEN

BACKGROUND: Up to 30% of adults with severe asthma are hypersensitive to aspirin and no unambiguous theory exists which provides a satisfactory explanation for the occurrence of aspirin-induced asthma (AIA) in some asthmatic patients. Therefore, the aim of this study was to compare the AIA expression profile against aspirin tolerant asthma (ATA) and healthy volunteers (HV) profile in peripheral blood mononuclear cells (PBMCs) after in vitro aspirin challenge in Caucasian population. METHODS: PBMCs were separated from blood of three groups of subjects--11 AIA, 7 ATA and 15 HV and then stimulated by either 2 µM lysine aspirin or 20 µM lysine as a control. Subsequently, RNA was isolated, transcribed into cDNA and subjected to microarray and qPCR studies. Simultaneously, protein was extracted from PBMCs and used in further immunoblotting analysis. RESULTS: The validation of results at mRNA level has shown only three genes, whose expression was significantly altered between comprising groups. mRNA expression of CNPY3 in PBMCs in AIA was significantly lower (-0.41 ± 2.67) than in HV (1.04 ± 2.69), (p = 0.02); mRNA expression of FOSL1 in PBMCs in AIA was also significantly decreased (-0.66 ± 2.97) as opposed to HV (0.31 ± 4.83), (p = 0.02). While mRNA expression of ERAS in PBMCs was increased (1.15 ± 0.23) in AIA in comparison to HV (-1.32 ± 0.41), (p = 0.03). At protein level the changed expression of one protein was confirmed. Protein expression of FOSL1 in PBMCs in AIA was both significantly lower (-0.86 ± 0.08) than in ATA (0.39 ± 0.42), (p = 0.046) and in HV (0.9 ± 0.27), (p = 0.007). CONCLUSIONS: This pilot study implies a positive association between CNPY3, ERAS, FOSL1 and aspirin-intolerant asthma, suggesting that these findings would be useful for further investigations of NSAIDs mechanism.


Asunto(s)
Antiinflamatorios no Esteroideos/farmacología , Aspirina/farmacología , Asma Inducida por Aspirina/genética , Leucocitos Mononucleares/metabolismo , Adulto , Anciano , ADN Complementario/biosíntesis , ADN Complementario/genética , Femenino , Regulación de la Expresión Génica/efectos de los fármacos , Humanos , Leucocitos Mononucleares/efectos de los fármacos , Masculino , Análisis por Micromatrices , Persona de Mediana Edad , Proteína Oncogénica p21(ras)/genética , Proyectos Piloto , Proteínas Proto-Oncogénicas c-fos/genética , ARN/biosíntesis , ARN/genética , Reproducibilidad de los Resultados , Adulto Joven
12.
Mediators Inflamm ; 2015: 870428, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-27057091

RESUMEN

Dermatitis herpetiformis (DH) and bullous pemphigoid (BP) are skin diseases associated with eosinophilic and neutrophilic infiltrations. Although chemokines are critical for the selective accumulation and activation of various leukocyte subsets in the inflammatory process, there are few findings concerning inflammatory cells and production of coagulation factors in blistering diseases. Skin biopsies were taken from 14 patients with DH, 27 with BP, and 20 control subjects. The localization and expression of tissue factor (TF) in skin lesions and perilesional skin were studied by immunohistochemistry and confirmed by Western Blot. Moreover the plasma concentrations of TF were measured by immunoassays. D dimers, fibrinogen, and selected coagulation parameters were measured by routine methods. Expression of TF in the epidermis and in inflammatory influxed cells in dermis was detected in skin biopsies from BP patients. Examined TF expression was detected in perilesional skin of all BP patients too. The expression of TF was not observed in biopsies from healthy people and DH patients. The findings of the study show an increased expression of tissue factor in the lesional and perilesional skin of patients with bullous pemphigoid. The difference in chemokine pattern expression and variations in the cellular infiltration in BP and DH cause variable expression of TF.


Asunto(s)
Coagulación Sanguínea/inmunología , Dermatitis Herpetiforme/sangre , Dermatitis Herpetiforme/inmunología , Penfigoide Ampolloso/sangre , Penfigoide Ampolloso/inmunología , Tromboplastina/metabolismo , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Estudios de Casos y Controles , Dermatitis Herpetiforme/patología , Femenino , Productos de Degradación de Fibrina-Fibrinógeno/metabolismo , Fibrinógeno/metabolismo , Humanos , Inmunohistoquímica , Masculino , Persona de Mediana Edad , Penfigoide Ampolloso/patología , Piel/inmunología , Piel/patología , Adulto Joven
13.
Artículo en Inglés | MEDLINE | ID: mdl-36981614

RESUMEN

Inflammation is closely related to asthma and its defining feature: airway remodeling. The aim of this study was to determine the effects of extracts of normal (NR) and transformed (TR) Leonotis nepetifolia roots on respiratory cells and against the gingival epithelium. Extracts from NR and TR roots were added to lung fibroblast, bronchial epithelial and gingival fibroblast cell lines, in the presence of HRV-16 infection, to determine their impact on inflammation. The expression of inflammatory cytokines (IL-6, IL-1ß, GM-CSF and MCAF) as well as total thiol contents were assessed. The TR extract inhibited rhinovirus-induced IL-6 and IL-1ß expression in all tested airway cells (p < 0.05). Additionally, the extract decreased GM-CSF expression in bronchial epithelial cells. The tested extracts had positive effects on total thiol content in all tested cell lines. The TR root extract demonstrated wound healing potential. While both tested extracts exhibited anti-inflammatory and antioxidative effects, they were stronger for the TR extract, possibly due to higher concentrations of beneficial metabolites such as phenols and flavonoids. Additionally, wound healing activity was demonstrated for the TR root extract. These results suggest that TR root extract may become a promising therapeutic agent in the future.


Asunto(s)
Citocinas , Lamiaceae , Humanos , Citocinas/metabolismo , Factor Estimulante de Colonias de Granulocitos y Macrófagos , Interleucina-6 , Extractos Vegetales/farmacología , Extractos Vegetales/uso terapéutico , Lamiaceae/metabolismo , Inflamación/tratamiento farmacológico
14.
Oxid Med Cell Longev ; 2022: 5589089, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35281470

RESUMEN

The COVID-19 pandemic caused relatively high mortality in patients, especially in those with concomitant diseases (i.e., diabetes, hypertension, and chronic obstructive pulmonary disease (COPD)). In most of aforementioned comorbidities, the oxidative stress appears to be an important player in their pathogenesis. The direct cause of death in critically ill patients with COVID-19 is still far from being elucidated. Although some preliminary data suggests that the lung vasculature injury and the loss of the functioning part of pulmonary alveolar population are crucial, the precise mechanism is still unclear. On the other hand, at least two classes of medications used with some clinical benefits in COVID-19 treatment seem to have a major influence on ROS (reactive oxygen species) and RNS (reactive nitrogen species) production. However, oxidative stress is one of the important mechanisms in the antiviral immune response and innate immunity. Therefore, it would be of interest to summarize the data regarding the oxidative stress in severe COVID-19. In this review, we discuss the role of oxidative and antioxidant mechanisms in severe COVID-19 based on available studies. We also present the role of ROS and RNS in other viral infections in humans and in animal models. Although reactive oxygen and nitrogen species play an important role in the innate antiviral immune response, in some situations, they might have a deleterious effect, e.g., in some coronaviral infections. The understanding of the redox mechanisms in severe COVID-19 disease may have an impact on its treatment.


Asunto(s)
COVID-19/inmunología , Estrés Oxidativo/inmunología , Antioxidantes/farmacología , Antioxidantes/uso terapéutico , Antivirales/inmunología , Antivirales/farmacología , Antivirales/uso terapéutico , COVID-19/metabolismo , Infecciones por Coronavirus/tratamiento farmacológico , Infecciones por Coronavirus/inmunología , Infecciones por Coronavirus/metabolismo , Humanos , Inmunidad Innata , Estrés Oxidativo/efectos de los fármacos , Especies de Nitrógeno Reactivo/inmunología , Especies de Nitrógeno Reactivo/metabolismo , Especies Reactivas de Oxígeno/inmunología , Especies Reactivas de Oxígeno/metabolismo , SARS-CoV-2/patogenicidad , Tratamiento Farmacológico de COVID-19
15.
Int J Immunopathol Pharmacol ; 35: 2058738421990952, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33626953

RESUMEN

Chronic inflammation in asthmatics is initiated/exacerbated by many environmental factors, such as bacterial lipopolysaccharide and allergens. Phospholipase A2 and histone acetyltransferase/deacetylases are enzymes involved in inflammatory process, particularly in lipid inflammatory mediators production and control of transcription of many inflammatory genes, respectively. The aim of the study was to identify differences in the inflammatory process in patients with severe and non-severe asthma, taking as a criterion expression of two groups of enzymes: phospholipases A2 and histone acetyltransferases/deacetylases. Thirty-two patients with severe, non-severe atopic to house dust mite asthmatics and 14 healthy volunteers were recruited. Peripheral blood mononuclear cells were stimulated with Dermatophagoides pteronyssinus allergen (nDer p1) and bacterial lipopolysaccharide (LPS). The expression of phospholipases A2 and histone acetyltransferases and deacetylases were assessed using TaqMan Low Density Array Cards. The protein expression was analyzed with immunoblot. Increased expression of phospholipase A2 Group IVC (PLA2G4C) and cytosolic phospholipase A2 gamma (cPLA2γ) protein was observed in peripheral blood mononuclear cells (PBMC) from severe asthmatics in response to LPS and nDer p1, compared to non-severe asthmatics. nDer p1-stimulated PBMC from severe asthmatics exhibit induced expression of HDAC1 and similar trend was observed in protein concentration. Decreased expression of EP300 occurred in PBMC of severe asthmatics. PBMC from non-severe asthmatics showed decreased expression of HDAC2 and PLA2G15 after LPS treatment. In conclusion, in response to LPS and dust mite allergen, PBMC from severe and non-severe asthmatics modulate expression of selected phospholipase A2, histone acetyltransferases and deacetylases, while increased expression of cPLA2γ characterizes PBMC response from severe asthmatics.


Asunto(s)
Asma , Fosfolipasas A2 Grupo IV/genética , Fosfolipasas A2 Grupo IV/inmunología , Leucocitos Mononucleares/inmunología , Adulto , Alérgenos/inmunología , Antígenos Dermatofagoides/inmunología , Asma/genética , Asma/inmunología , Asma/fisiopatología , Proteína p300 Asociada a E1A/genética , Femenino , Histona Desacetilasa 1/genética , Histona Desacetilasa 2/genética , Humanos , Lipopolisacáridos/inmunología , Masculino , Persona de Mediana Edad , ARN Mensajero , Índice de Severidad de la Enfermedad , Espirometría
16.
Curr Pharm Des ; 26(24): 2876-2884, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32250214

RESUMEN

Inflammation plays a major role in chronic airway diseases like asthma, COPD, and cystic fibrosis. Inflammation plays a crucial role in the worsening of the lung function resulting in worsening symptoms. The inflammatory process is very complexed, therefore the strategies for developing an effective treatment for inflammatory airway diseases would benefit from the use of natural substances. Plant products have demonstrated anti-inflammatory properties on various lung disease models and numerous natural plant agents have successfully been used to treat inflammation. Naturally occurring substances may exert some anti-inflammatory effects by modulating some of the inflammatory pathways. These agents have been used in different cultures for thousands of years and have proven to be relatively safe. Parthenolide, apocynin, proanthocyanidins, and boswellic acid present different mechanisms of actions - among others, through NF-kB or NADPH oxidase inhibition, therefore showing a wide range of applications in various inflammatory diseases. Moreover, some of them have also antioxidant properties. This review provides an overview of the anti-inflammatory effects of some of the natural agents and illustrates their great potential as sources of drugs to cover an extensive range of pharmacological effects.


Asunto(s)
Antiinflamatorios , Asma , Antiinflamatorios/farmacología , Antiinflamatorios/uso terapéutico , Asma/tratamiento farmacológico , Humanos , Inflamación/tratamiento farmacológico , Pulmón , Fitoquímicos/farmacología , Fitoquímicos/uso terapéutico
17.
Inflammation ; 43(3): 1173, 2020 06.
Artículo en Inglés | MEDLINE | ID: mdl-32048106

RESUMEN

The original version of this article contained mistakes concerning the affiliations of Ewa Skala and Tomasz Kowalczyk. Their correct affiliations are now presented on this proof.

18.
Curr Pharm Des ; 26(24): 2817-2842, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32048962

RESUMEN

BACKGROUND: For a long time, the researchers have been looking for new efficient methods to enhance production and obtain valuable plant secondary metabolites, which would contribute to the protection of the natural environment through the preservation of various plant species, often rare and endangered. These possibilities offer plant in vitro cultures which can be performed under strictly-controlled conditions, regardless of the season or climate and environmental factors. Biotechnological methods are promising strategies for obtaining the valuable plant secondary metabolites with various classes of chemical compounds including caffeoylquinic acids (CQAs) and their derivatives. CQAs have been found in many plant species which are components in the daily diet and exhibit a wide spectrum of biological activities, including antioxidant, immunomodulatory, antihypertensive, analgesic, anti-inflammatory, hepato- and neuroprotective, anti-hyperglycemic, anticancer, antiviral and antimicrobial activities. They have also been found to offer protection against Alzheimer's disease, and play a role in weight reduction and lipid metabolism control, as well as modulating the activity of glucose-6-phosphatase involved in glucose metabolism. METHODS: This work presents the review of the recent advances in use in vitro cultures of various plant species for the alternative system to the production of CQAs and their derivatives. Production of the secondary metabolites in in vitro culture is usually performed with cell suspension or organ cultures, such as shoots and adventitious or transformed roots. To achieve high production of valuable secondary metabolites in in vitro cultures, the optimization of the culture condition is necessary with respect to both biomass accumulation and metabolite content. The optimization of the culture conditions can be achieved by choosing the type of medium, growth regulators or growth conditions, selection of high-productivity lines or culture period, supplementation of the culture medium with precursors or elicitor treatments. Cultivation for large-scale in bioreactors and genetic engineering: Agrobacterium rhizogenes transformation and expression improvement of transcriptional factor or genes involved in the secondary metabolite production pathway are also efficient strategies for enhancement of the valuable secondary metabolites. RESULTS: Many studies have been reported to obtain highly productive plant in vitro cultures with respect to CQAs. Among these valuable secondary metabolites, the most abundant compound accumulated in in vitro cultures was 5-CQA (chlorogenic acid). Highly productive cultures with respect to this phenolic acid were Leonurus sibiricus AtPAP1 transgenic roots, Lonicera macranthoides and Eucomia ulmoides cell suspension cultures which accumulated above 20 mg g-1 DW 5-CQA. It is known that di- and triCQAs are less common in plants than monoCQAs, but it was also possible to obtain them by biotechnological methods. CONCLUSION: The results indicate that the various in vitro cultures of different plant species can be a profitable approach for the production of CQAs. In particular, an efficient production of these valuable compounds is possible by Lonicera macranthoides and Eucomia ulmoides cell suspension cultures, Leonurus sibiricus transformed roots and AtPAP1 transgenic roots, Echinacea angustifolia adventitious shoots, Rhaponticum carthamoides transformed plants, Lavandula viridis shoots, Sausera involucrata cell suspension and Cichorium intybus transformed roots.


Asunto(s)
Productos Biológicos , Echinacea , Agrobacterium , Humanos , Raíces de Plantas
19.
Plants (Basel) ; 9(2)2020 Jan 21.
Artículo en Inglés | MEDLINE | ID: mdl-31973076

RESUMEN

The plant kingdom abounds in countless species with potential medical uses. Many of them contain valuable secondary metabolites belonging to different classes and demonstrating anticancer, anti-inflammatory, antioxidant, antimicrobial or antidiabetic properties. Many of these metabolites, e.g., paclitaxel, vinblastine, betulinic acid, chlorogenic acid or ferrulic acid, have potential applications in medicine. Additionally, these compounds have many therapeutic and health-promoting properties. The growing demand for these plant secondary metabolites forces the use of new green biotechnology tools to create new, more productive in vitro transgenic plant cultures. These procedures have yielded many promising results, and transgenic cultures have been found to be safe, efficient and cost-effective sources of valuable secondary metabolites for medicine and industry. This review focuses on the use of various in vitro plant culture systems for the production of secondary metabolites.

20.
Curr Pharm Des ; 26(24): 2859-2875, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32303169

RESUMEN

Skin ailments present a major health burden in both developed and undeveloped countries. Maintaining healthy skin is important for a healthy body. Medicinal plants have long provided reliable therapy in the treatment of skin diseases in humans through a diverse range of bioactive molecules. Skin diseases may have a various basis, or may be genetically determined; together, they constitute approximately 34% of all occupational diseases encountered in people of all ages. Of these, melanoma is one of the most dangerous forms, with very poor prognosis for patients if it is diagnosed too late. This review of the literature over the past five years examines the role and utilities of plant extracts in treating various skin diseases such as atopic dermatitis, acne or melanoma with various potential mechanisms of action.


Asunto(s)
Dermatitis Atópica , Plantas Medicinales , Enfermedades de la Piel , Humanos , Extractos Vegetales/farmacología , Piel , Enfermedades de la Piel/tratamiento farmacológico
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