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1.
Ultrasonics ; 118: 106561, 2022 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-34500338

RESUMEN

Angiogenesis involves the activation of endothelial cells (ECs). Low-intensity pulsed ultrasound (LIPUS), which delivers ultrasound waves at a low intensity, can induce the angiogenic potential of ECs. However, the underlying cellular mechanisms remain to be elucidated. In this study, the LIPUS parameters were 1.5 MHz pulsed frequency, 200 us pulse duration, 1.0 kHz repetition rate, and 30 mW/cm2 energy intensity. First, we evaluated the effects of LIPUS on the proliferation and angiogenic differentiation of the EC line EA.hy926. The results showed that LIPUS could induce cell proliferation, promote migration, and increase mRNA level inKDR and CD144.Also, the mRNA level and secretion of VEGF were enhanced. We then investigated the role of the AKT signaling pathway in this process. We observed that the expression of p-AKT was upregulated which means that the AKT signaling pathway could be activated by LIPUS, while inhibitor LY294002 of the AKT signaling pathway effectively blocked LIPUS-induced angiogenesis. Finally,we applied confocal Raman microscopy to track biomolecular changes in cells after LIPUS treatment. Spectral analysis showed DNA methylation changes. An Infinium Methylation assay suggested that399 sites were significantly different. After KEGG enrichment analysis, we found seven genes (IRS1, GNG7, COL4A1, FOXO3, COL4A2, CDK4 and EGF) which were closely related to AKT signaling pathway. We verified that AKT signaling pathway inhibition partially blocked LIPUS-induced DNA methylation changes. Ourstudy demonstrated that LIPUS couldpromote the proliferation and angiogenic differentiation of ECs via the AKT signaling pathway. LIPUS could also alter DNA methylation of ECs via the activation of AKT signal.


Asunto(s)
Metilación de ADN , Células Endoteliales de la Vena Umbilical Humana/metabolismo , Neovascularización Fisiológica , Proteínas Proto-Oncogénicas c-akt/metabolismo , Ondas Ultrasónicas , Movimiento Celular , Proliferación Celular , Supervivencia Celular , Células Cultivadas , Humanos , Microscopía Confocal , Transducción de Señal
2.
J Colloid Interface Sci ; 605: 500-512, 2022 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-34343730

RESUMEN

Herein, we report for the first time a facile strategy for the highly efficient (NH4)xCs1-xPbBr3 quantum dots (QDs). By modulating the amount of ammonium, (NH4)xCs1-xPbBr3 QDs with different photoluminescence (PL) quantum yields (QY) were synthesized. The results of X-ray diffraction and X-ray photoelectron spectroscopy showed that the crystal structure of (NH4)xCs1-xPbBr3 was altered by incorporation of NH4+ cations into the CsPbBr3 lattice. The (NH4)xCs1-xPbBr3 QDs showed enhanced PL QY, higher photostability, and long-term storage stability compared to CsPbBr3 QDs. Furthermore, (NH4)xCs1-xPbBr3 QDs could be conjugated with a photothermal dye (IR780) via a one-pot reaction using poly(styrene-co-maleic anhydride) and IR780-MPTS. To the best of our knowledge, the present work is the first attempt integrating perovskite QDs and phototherapeutic molecules into one system (abbreviated as PQD-IR780), demonstrating good water dispersibility and high photothermal conversion efficiency of 57.85%. In vitro experiments performed to examine subcellular uptake showed high fluorescence brightness was observed in HeLa, B16F1, and HepG2 cancer cells cultured with PQD-IR780. The results indicate that the internalization mechanism for uptaking of PQD-IR780 inside HeLa cells is energy-dependent and caveolin-mediated endocytosis. The in vitro cell viability assays and photothermal therapy revealed that PQD-IR780 showed good biocompatibility and can induce hyperthermia upon laser irradiation.


Asunto(s)
Puntos Cuánticos , Supervivencia Celular , Células HeLa , Humanos , Luminiscencia , Terapia Fototérmica
3.
J Ethnopharmacol ; 283: 114701, 2022 Jan 30.
Artículo en Inglés | MEDLINE | ID: mdl-34606948

RESUMEN

ETHNOPHARMACOLOGICAL RELEVANCE: Xuanfei Baidu Decoction (XFBD), one of the "three medicines and three prescriptions" for the clinically effective treatment of COVID-19 in China, plays an important role in the treatment of mild and/or common patients with dampness-toxin obstructing lung syndrome. AIM OF THE STUDY: The present work aims to elucidate the protective effects and the possible mechanism of XFBD against the acute inflammation and pulmonary fibrosis. METHODS: We use TGF-ß1 induced fibroblast activation model and LPS/IL-4 induced macrophage inflammation model as in vitro cell models. The mice model of lung fibrosis was induced by BLM via endotracheal drip, and then XFBD (4.6 g/kg, 9.2 g/kg) were administered orally respectively. The efficacy and molecular mechanisms in the presence or absence of XFBD were investigated. RESULTS: The results proved that XFBD can effectively inhibit fibroblast collagen deposition, down-regulate the level of α-SMA and inhibit the migration of fibroblasts. IL-4 induced macrophage polarization was also inhibited and the secretions of the inflammatory factors including IL6, iNOS were down-regulated. In vivo experiments, the results proved that XFBD improved the weight loss and survival rate of the mice. The XFBD high-dose administration group had a significant effect in inhibiting collagen deposition and the expression of α-SMA in the lungs of mice. XFBD can reduce bleomycin-induced pulmonary fibrosis by inhibiting IL-6/STAT3 activation and related macrophage infiltration. CONCLUSIONS: Xuanfei Baidu Decoction protects against macrophages induced inflammation and pulmonary fibrosis via inhibiting IL-6/STAT3 signaling pathway.


Asunto(s)
COVID-19/tratamiento farmacológico , Medicamentos Herbarios Chinos , Inflamación/tratamiento farmacológico , Macrófagos/efectos de los fármacos , SARS-CoV-2 , Transducción de Señal/efectos de los fármacos , Animales , Supervivencia Celular/efectos de los fármacos , Medicamentos Herbarios Chinos/farmacología , Medicamentos Herbarios Chinos/uso terapéutico , Fibroblastos/efectos de los fármacos , Regulación de la Expresión Génica/efectos de los fármacos , Redes Reguladoras de Genes , Humanos , Interleucina-6/antagonistas & inhibidores , Interleucina-6/genética , Interleucina-6/metabolismo , Masculino , Ratones , Ratones Endogámicos C57BL , Células 3T3 NIH , Fitoterapia , Fibrosis Pulmonar/patología , Fibrosis Pulmonar/prevención & control , Células RAW 264.7 , Factor de Transcripción STAT3/antagonistas & inhibidores , Factor de Transcripción STAT3/genética , Factor de Transcripción STAT3/metabolismo
4.
Front Biosci (Landmark Ed) ; 26(10): 789-798, 2021 10 30.
Artículo en Inglés | MEDLINE | ID: mdl-34719206

RESUMEN

Background: The coronavirus disease 2019 pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has infected more than 210 million individuals globally and resulted in over 4 million deaths since the first report in December 2019. The early use of traditional Chinese medicine (TCM) for light and ordinary patients, can rapidly improve symptoms, shorten hospitalization days and reduce severe cases transformed from light and normal. Many TCM formulas and products have a wide application in treating infectious and non-infectious diseases. Polygonum cuspidatum Sieb. et Zucc. (P. cuspidatum), is an important Traditional Chinese Medicine with actions of clearing away heat and eliminating dampness, draining the gallbladder to relieve jaundice, removing blood stasis to alleviate pain, resolving phlegm and arrest cough. In the search for anti-SARS-CoV-2, P. cuspidatum was recommended as as a therapeutic drug of COVID-19 pneumonia.In this study, we aimed to identifies P. cuspidatum is the potential broad-spectrum inhibitor for the treatment of coronaviruses infections. Methods: In the present study , we infected human malignant embryonal rhabdomyoma (RD) cells with the OC43 strain of the coronavirus, which represent an alternative model for SARS-CoV-2 and then employed the cell viability assay kit for the antiviral activity. We combined computer aided virtual screening to predicte the binding site and employed Surface plasmon resonance analysis (SPR) to comfirm the interaction between drugs and coronavirus. We employed fluorescence resonance energy transfer technology to identify drug's inhibition in the proteolytic activity of 3CLpro and Plpro. Results: Based on our results, polydatin and resveratrol derived from P. cuspidatum significantly suppressed HCoV-OC43 replication. 50% inhibitory concentration (IC50) values of polydatin inhibited SARS-CoV-2 Mpro and Plpro, MERS Mpro and Plpro were 18.66, 125, 14.6 and 25.42 µm, respectively. IC50 values of resveratrol inhibited SARS-CoV-2 Mpro and Plpro, MERS Mpro and Plpro were 29.81 ,60.86, 16.35 and19.04 µM, respectively. Finally, SPR assay confirmed that polydatin and resveratrol had high affinity to SARS-CoV-2, SARS-CoV 3Clpro, MERS-CoV 3Clpro and PLpro protein. Conclusions: we identified the antiviral activity of flavonoids polydatin and resveratrol on RD cells. Polydatin and resveratrol were found to be specific and selective inhibitors for SARS-CoV-2, 3CLpro and PLpro, viral cysteine proteases. In summary, this study identifies P. cuspidatum as the potential broad-spectrum inhibitor for the treatment of coronaviruses infections.


Asunto(s)
Medicamentos Herbarios Chinos/química , Fallopia japonica/química , Glucósidos/farmacología , Resveratrol/farmacología , SARS-CoV-2/efectos de los fármacos , Estilbenos/farmacología , Replicación Viral/efectos de los fármacos , Antivirales/farmacología , COVID-19/epidemiología , COVID-19/prevención & control , COVID-19/virología , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Glucósidos/metabolismo , Células HEK293 , Interacciones Huésped-Patógeno/efectos de los fármacos , Humanos , Medicina China Tradicional/métodos , Pandemias , Unión Proteica , Resveratrol/metabolismo , SARS-CoV-2/metabolismo , SARS-CoV-2/fisiología , Estilbenos/metabolismo , Resonancia por Plasmón de Superficie/métodos , Proteínas Virales/metabolismo
5.
Anticancer Res ; 41(11): 5415-5423, 2021 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-34732410

RESUMEN

BACKGROUND/AIM: Antimicrobial peptides are part of the innate immune response, regulate inflammation and initiate acquired immunity. This study focused on theta-defensins that have been shown to have anticancer properties. MATERIALS AND METHODS: RTD-2 analogs were synthesized on a peptide synthesizer. Cell viability was estimated using the MTT test. Immunoprecipitation assay was conducted to determine the molecular partner of the [Ser3,7,12,16]-RTD-2 analog. RESULTS: Here, we present the biologically active [Ser3,7,12,16]-RTD-2 analog that selectively targets various types of breast cancer cells. Immunoprecipitation protein-protein interaction studies showed eleven proteins common to MDA-MB-231 and T47D cell lines. Taking into account their cellular location, it can be concluded that the synthesized peptide interacts mainly with nuclear proteins, which correlates with the obtained microscopic image. CONCLUSION: Proteins that interact strongly with the [Ser3,7,12,16]-RTD-2 analog are closely related to the proteasomal protein degradation pathway. As the activity of the ubiquitin-proteasome system is markedly increased in patients with breast cancer, it is likely that selective modulation of this system may be a useful method for breast cancer treatment.


Asunto(s)
Antineoplásicos/farmacología , Neoplasias de la Mama/tratamiento farmacológico , Defensinas/farmacología , Diseño de Fármacos , Péptidos Cíclicos/farmacología , Complejo de la Endopetidasa Proteasomal/metabolismo , Secuencia de Aminoácidos , Antineoplásicos/química , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/patología , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Defensinas/química , Femenino , Humanos , Péptidos Cíclicos/química , Proteolisis , Relación Estructura-Actividad
6.
Pestic Biochem Physiol ; 179: 104979, 2021 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-34802529

RESUMEN

Rotenone, a plant-derived pesticide belonging to genera Derris and Lonchorcarpus, is an inhibitor of NADH dehydrogenase complex. Studies have shown that rotenone was applied as a neurotoxic agent in various neuronal models. Hydroxytyrosol [2-(3,4-dihydroxyphenyl)-ethanol] is a natural phenolic compound found in the olive (Olea europaea L.). Studies of hydroxytyrosol have dramatically increased because this compound may contribute to the prevention of neurodegenerative diseases. Although hydroxytyrosol has received increasing attention due to its multiple pharmacological activities, it is not explored whether hydroxytyrosol inhibited rotenone-induced cytotoxicity in the neuronal cell model. The aim of this study was to explore whether hydroxytyrosol prevented rotenone-induced Ca2+ signaling, cytotoxicity and oxidative stress in HCN-2 neuronal cell line. In HCN-2 cells, rotenone (5-30 µM) concentration-dependently induced cytosolic Ca2+ concentrations ([Ca2+]i) rises and cytotoxicity. Treatment with hydroxytyrosol (30 µM) reversed rotenone (20 µM)-induced cytotoxic responses. In Ca2+-containing medium, rotenone-induced Ca2+ entry was inhibited by 2-APB (a store-operated Ca2+ channel modulator) or hydroxytyrosol. In Ca2+-free medium, treatment with thapsigargin (an endoplasmic reticulum Ca2+ pump inhibitor) or hydroxytyrosol significantly inhibited rotenone-induced [Ca2+]i rises. Furthermore, treatment with hydroxytyrosol reversed ROS levels, cytotoxic responses, and antioxidant enzyme activities (SOD, GPX and CAT) in rotenone-treated cells. Together, in HCN-2 cells, rotenone induced Ca2+ influx via store-operated Ca2+ entry and Ca2+ release from the endoplasmic reticulum and caused oxidative stress. Moreover, hydroxytyrosol ameliorated Ca2+ or ROS-associated cytotoxicity. It suggests that hydroxytyrosol might have a protective effect on rotenone-induced neurotoxicity in human neuronal cells.


Asunto(s)
Plaguicidas , Rotenona , Calcio/metabolismo , Supervivencia Celular , Estrés Oxidativo , Alcohol Feniletílico/análogos & derivados , Rotenona/toxicidad
8.
DNA Cell Biol ; 40(11): 1418-1427, 2021 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-34767735

RESUMEN

In this study, we examined the regulatory role of CCDC34 in the sorafenib sensitivity of hepatocellular carcinoma (HCC) and its functional partners. Wide-type Huh7 and Hep3B and induced sorafenib-resistant (SR) Huh7/SR and Hep3B/SR cells were used as in vitro cell models. Immunofluorescent staining and coimmunoprecipitation were performed to check protein-protein interaction. Cell Counting Kit-8 (CCK-8), terminal deoxynucleotidyl transferase-mediated nick end labeling (TUNEL), PI/Annexin V staining, and western blot analysis were performed to assess cell response to sorafenib. The results showed that CCDC34 upregulation in HCC was associated with poor survival. Huh7/SR and Hep3B/SR cells had significantly higher CCDC34 expression than the parental cell lines. RABL2A expression was significantly upregulated in SR HCC cells and interacted with CCDC34 in its GTP-bound state in Huh7/SR and Hep3B/SR cells. RABL2A depletion sensitized Huh7/SR and Hep3B/SR cells to sorafenib. RABL2A Q80L mutant (GTP-bound state locked), but not S35N mutant (GDP-bound state locked) overexpression increased sorafenib IC50 of Huh7 and Hep3B cells. CCDC34 depletion nearly abrogated the protective effects of RABL2A Q80L overexpression both in vitro and in vivo. RABL2A Q80L overexpression significantly increased the expression of p-p38 and p-JNK, the effects of which were significantly attenuated by CCDC34 depletion. In summary, we infer that the RABL2A-CCDC34 axis plays an important role in mediating p38/MAPK and JNK/MAPK signaling, thereby contributing to acquired sorafenib resistance in HCC.


Asunto(s)
Antígenos de Neoplasias/metabolismo , Carcinoma Hepatocelular/metabolismo , Proteínas de Neoplasias/metabolismo , Sorafenib/metabolismo , Antígenos de Neoplasias/fisiología , Antineoplásicos/farmacología , Carcinoma Hepatocelular/tratamiento farmacológico , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , China , Resistencia a Antineoplásicos/fisiología , Expresión Génica/efectos de los fármacos , Expresión Génica/genética , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Humanos , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/metabolismo , Proteínas de Neoplasias/fisiología , Transducción de Señal/efectos de los fármacos , Sorafenib/farmacología , Proteínas de Unión al GTP rab/metabolismo , Proteínas de Unión al GTP rab/fisiología
9.
Sci Rep ; 11(1): 21462, 2021 11 02.
Artículo en Inglés | MEDLINE | ID: mdl-34728736

RESUMEN

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the coronavirus disease-19 (COVID-19). More than 143 million cases of COVID-19 have been reported to date, with the global death rate at 2.13%. Currently, there are no licensed therapeutics for controlling SARS-CoV-2 infection. The antiviral effects of heme oxygenase-1 (HO-1), a cytoprotective enzyme that inhibits the inflammatory response and reduces oxidative stress, have been investigated in several viral infections. To confirm whether HO-1 suppresses SARS-CoV-2 infection, we assessed the antiviral activity of hemin, an effective and safe HO-1 inducer, in SARS-CoV-2 infection. We found that treatment with hemin efficiently suppressed SARS-CoV-2 replication (selectivity index: 249.7012). Besides, the transient expression of HO-1 using an expression vector also suppressed the growth of the virus in cells. Free iron and biliverdin, which are metabolic byproducts of heme catalysis by HO-1, also suppressed the viral infection. Additionally, hemin indirectly increased the expression of interferon-stimulated proteins known to restrict SARS-CoV-2 replication. Overall, the findings suggested that HO-1, induced by hemin, effectively suppressed SARS-CoV-2 in vitro. Therefore, HO-1 could be potential therapeutic candidate for COVID-19.


Asunto(s)
Antivirales/uso terapéutico , COVID-19/tratamiento farmacológico , Hemo-Oxigenasa 1/metabolismo , Hemina/uso terapéutico , Animales , Antivirales/química , Antivirales/farmacología , COVID-19/virología , Supervivencia Celular/efectos de los fármacos , Chlorocebus aethiops , Hemo-Oxigenasa 1/antagonistas & inhibidores , Hemo-Oxigenasa 1/genética , Hemina/química , Hemina/farmacología , Humanos , Interferencia de ARN , ARN Interferente Pequeño/metabolismo , ARN Viral/metabolismo , SARS-CoV-2/genética , SARS-CoV-2/aislamiento & purificación , SARS-CoV-2/fisiología , Regulación hacia Arriba/efectos de los fármacos , Células Vero , Replicación Viral/efectos de los fármacos
10.
Comput Math Methods Med ; 2021: 6021763, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34754326

RESUMEN

Background: Oxidative stress, inflammation, and nucleus pulposus cells (NPCs) apoptosis are involved in pathogenesis of intervertebral disc (IVD) degeneration (IVDD). Dimethyl fumarate (DMF) has been found to effectively depress oxidative stress and inflammation via the Nrf2 pathway. Hence, this project was designed to explore the underlying mechanisms of how DMF protects NPCs from damage by LPS challenge. Methods and Results: CCK8 assay and flow cytometry of apoptosis indicated that DMF treatment attenuated LPS-induced NPC damage. Western blot analysis demonstrated that DMF enhanced the expressions of nuclear factor-erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) in LPS-challenged NPCs. DMF treatment significantly decreased the accumulation of ROS, downregulated inflammatory cytokines (p-NF-κB, IL-1ß, and TNF-α), and ER stress-associated apoptosis proteins (Bip, calpain-1, caspase-12, caspase-3, and Bax) in LPS-challenged NPCs. The level of antiapoptotic protein Bcl-2 was promoted by DMF treatment in LPS-challenged NPCs. Glutathione (GSH) assay showed that DMF treatment improved reduced to oxidized glutathione ratio in LPS-challenged NPCs. Furthermore, the results of western blot analysis indicated that in LPS-challenged NPCs, DMF treatment ameliorated the elevated levels of matrix degradation enzymes (MMP-13, aggrecanase 1) and type I collagen and the reduced levels of matrix composition (type II collagen and ACAN). However, Nrf2 knockdown abolished these protective effects of DMF. Conclusion: Our data suggested that treatment with DMF mitigated LPS-induced oxidative stress, inflammation, and ER stress-associated apoptosis in NPCs via the Nrf2/HO-1 signaling pathway, thus reliving LPS-induced dysfunction of NPCs, which offered a novel potential pharmacological treatment strategy for IVDD.


Asunto(s)
Dimetilfumarato/farmacología , Hemo-Oxigenasa 1/metabolismo , Degeneración del Disco Intervertebral/tratamiento farmacológico , Degeneración del Disco Intervertebral/metabolismo , Factor 2 Relacionado con NF-E2/agonistas , Núcleo Pulposo/efectos de los fármacos , Núcleo Pulposo/metabolismo , Antioxidantes/farmacología , Apoptosis/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Células Cultivadas , Biología Computacional , Citocinas/metabolismo , Citoprotección/efectos de los fármacos , Estrés del Retículo Endoplásmico/efectos de los fármacos , Humanos , Inflamación/tratamiento farmacológico , Degeneración del Disco Intervertebral/patología , Lipopolisacáridos/toxicidad , Núcleo Pulposo/patología , Estrés Oxidativo/efectos de los fármacos , Transducción de Señal/efectos de los fármacos
11.
J Wound Care ; 30(Sup9a): IIIi-IIIix, 2021 Sep 02.
Artículo en Inglés | MEDLINE | ID: mdl-34597164

RESUMEN

AIMS: To analyse the effects of microcurrent on L929 fibroblast cell culture. METHODS: Cells were cultivated in six-well plates at densities of 5×104, 1×105, 3×105 and 5×105 cells/well to determine the best plating density. Subsequently, two methods of current application were tested: with a paper cone coupled to the electrode (M1) and with the electrode directly inside the well (M2). Then, streams of 60µA (G60), 100µA (G100), 500µA (G500) and 900µA (G900) were applied to the cells (n=3) once a day for three minutes, for a period of one (T1), two (T2) and three days (T3). The MTT assay method was used to evaluate cell proliferation. For the quantification of the inflammatory markers by flow cytometry, the group and time that presented the best results were selected. RESULTS: The ideal plating density was established as 1x105 cells/well and M2 as the best application method. An increase in cell viability was observed at all intensities from T1 to T2, but with no significant differences. From T2 to T3, there was a decrease in viability in all groups, with a significant difference only in G500 (p<0.05). Flow cytometry was performed in the GC and G900 groups at T2. It was possible to observe an increase of 0.56pg/ml in Interleukin (IL)-17 and a decrease of 5.45pg/ml in IL-2. CONCLUSION: This study showed that two applications of microcurrent increases cell proliferation and modulates the inflammatory response, aiding tissue regeneration and playing a key role in rehabilitation.


Asunto(s)
Citocinas , Fibroblastos , Animales , Línea Celular , Proliferación Celular , Supervivencia Celular , Fijación Interna de Fracturas , Ratones
12.
Gen Physiol Biophys ; 40(5): 409-417, 2021 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-34602454

RESUMEN

Astrocytes are greatly impacted by oxidative stress, which can also be related to neurodegenerative diseases. Therefore, preventing the production of reactive oxygen species (ROS) is crucial for maintaining healthy cells. Large conductance Ca2+-activated big potassium (BK) channel openers are effective in eliminating the effects of oxidative stress. The present study aims to determine if NS11021, a BK channel opener, protects the astrocytes from harmful effects of hydrogen peroxide (H2O2), which is an oxidative stress inducer. For this purpose, primary astrocyte cultures were incubated with H2O2, NS11021, and Iberiotoxin both separately and together. H2O2 decreased cell viability by approximately 50% and increased the number of ROS-positive astrocytes. However, NS11021, but not Iberiotoxin, reversed the deleterious effects of H2O2 on cell viability and decreased ROS production. Moreover, dysregulations in Cyclin D1/CDK6/p21 gene expressions under conditions of oxidative stress were regulated again by the opener. To the best of our knowledge, this study has been the first to reveal that NS11021 reversed the deleterious effects of H2O2 on cell viability by regulating ROS production in astrocytes. Its effect may also be related to the regulation of cell cycle at the transcriptional level. NS11021 may also be used as an agent for the treatment of oxidative-stress related dysfunction of astrocytes.


Asunto(s)
Astrocitos , Canales de Potasio de Gran Conductancia Activados por el Calcio , Supervivencia Celular , Peróxido de Hidrógeno/toxicidad , Canales de Potasio de Gran Conductancia Activados por el Calcio/metabolismo , Estrés Oxidativo , Oxígeno , Especies Reactivas de Oxígeno/metabolismo
13.
J Agric Food Chem ; 69(41): 12209-12218, 2021 Oct 20.
Artículo en Inglés | MEDLINE | ID: mdl-34610737

RESUMEN

Pterygium belongs to an ocular surface disease with triangular-shaped hyperplastic growth, characterized by conjunctivalization, inflammation, and connective tissue remodeling. We previously demonstrated neoplastic-like properties of pterygium cells. Green tea catechin, (-)-epigallocatechin gallate (EGCG), has been shown to possess antitumorigenic properties; herein, we aimed to determine the effects of green tea catechins on human primary pterygium cell survival and migration and compared to that on patients' conjunctival cells. Both human primary pterygium and conjunctival cells expressed EGCG receptor, the 67 kDa laminin receptor. Seven-day treatment of green tea extract (Theaphenon E; 16.25 µg/mL) and EGCG (25 µM) attenuated pterygium cell proliferation by 16.78% (p < 0.001) and 24.09% (p < 0.001) respectively, without significantly influencing conjunctival cells. Moreover, green tea extract (16.25 µg/mL) and EGCG (25 µM) treatments also hindered pterygium cell migration by 35.22% (p < 0.001) and 25.20% (p = 0.019), respectively, but not conjunctival cells. Yet, green tea extract and EGCG treatments did not significantly induce pterygium cell apoptosis. Furthermore, green tea extract and EGCG treatments significantly increased the phosphorylation of p38 protein but reduced the phosphorylation of p42/p44 protein in pterygium cells. In summary, this study revealed that green tea extract and EGCG attenuated human primary pterygium cell survival and migration in vitro without damaging conjunctival cells, suggesting a novel potential therapeutic approach for primary pterygium treatment.


Asunto(s)
Catequina , Pterigion , Catequina/farmacología , Proliferación Celular , Supervivencia Celular , Humanos , Pterigion/tratamiento farmacológico , Pterigion/genética ,
14.
BMC Cancer ; 21(1): 1087, 2021 Oct 08.
Artículo en Inglés | MEDLINE | ID: mdl-34625031

RESUMEN

BACKGROUND: Cancer remains one of the leading causes of death worldwide, despite the possibilities to detect early onset of the most common cancer types. The search for the optimal therapy is complicated by the cancer diversity within tumors and the unsynchronized development of cancerous cells. Therefore, it is necessary to characterize cancer cell populations after treatment has been applied, because cancer recurrence is not rare. In our research, we concentrated on small cancer cell subpopulation (microcells) that has a potential to be cancer resistance source. Previously made experiments has shown that these cells in small numbers form in specific circumstances after anticancer treatment. METHODS: In experiments described in this research, the anticancer agents' paclitaxel and doxorubicin were used to stimulate the induction of microcells in fibroblast, cervix adenocarcinoma, and melanoma cell lines. Mainly for the formation of microcells in melanoma cells. The drug-stimulated cells were then characterized in terms of their formation efficiency, morphology, and metabolic activity. RESULTS: We observed the development of cancer microcells and green fluorescent protein (GFP) transfection efficiency after stress. In the time-lapse experiment, we observed microcell formation through a renewal process and GFP expression in the microcells. Additionally, the microcells were viable after anticancer treatment, as indicated by the nicotinamide adenine dinucleotide hydrogen phosphate (NADPH) enzyme activity assay results. Taken together, these findings indicate that cancer microcells are viable and capable of resisting the stress induced by anticancer drugs, and these cells are prone to chemical substance uptake from the environment. CONCLUSION: Microcells are not only common to a specific cancer type, but can be found in any tumor type. This study could help to understand cancer emergence and recurrence. The appearance of microcells in the studied cancer cell population could be an indicator of the individual anticancer therapy effectiveness and patient survival.


Asunto(s)
Antineoplásicos/farmacología , Resistencia a Antineoplásicos , Neoplasias/tratamiento farmacológico , Neoplasias/patología , Adenocarcinoma/metabolismo , Adenocarcinoma/patología , Recuento de Células , Línea Celular Tumoral , Núcleo Celular/ultraestructura , Autorrenovación de las Células , Supervivencia Celular/efectos de los fármacos , Proteínas de Unión al ADN/metabolismo , Doxorrubicina/farmacología , Complejos de Clasificación Endosomal Requeridos para el Transporte/metabolismo , Femenino , Fibroblastos/efectos de los fármacos , Proteínas Fluorescentes Verdes/metabolismo , Células HeLa , Humanos , Indicadores y Reactivos/farmacocinética , Melanoma/metabolismo , Melanoma/patología , Microscopía Electrónica , NADP/metabolismo , Recurrencia Local de Neoplasia/metabolismo , Recurrencia Local de Neoplasia/patología , Neoplasias/metabolismo , Neoplasias/ultraestructura , Rojo Neutro/farmacocinética , Paclitaxel/farmacología , Estrés Fisiológico , Imagen de Lapso de Tiempo , Factores de Transcripción/metabolismo , Transfección , Neoplasias del Cuello Uterino/tratamiento farmacológico , Neoplasias del Cuello Uterino/metabolismo , Neoplasias del Cuello Uterino/patología
15.
Molecules ; 26(20)2021 Oct 14.
Artículo en Inglés | MEDLINE | ID: mdl-34684771

RESUMEN

Excessive host inflammation following infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is associated with severity and mortality in coronavirus disease 2019 (COVID-19). We recently reported that the SARS-CoV-2 spike protein S1 subunit (S1) induces pro-inflammatory responses by activating toll-like receptor 4 (TLR4) signaling in macrophages. A standardized extract of Asparagus officinalis stem (EAS) is a unique functional food that elicits anti-photoaging effects by suppressing pro-inflammatory signaling in hydrogen peroxide and ultraviolet B-exposed skin fibroblasts. To elucidate its potential in preventing excessive inflammation in COVID-19, we examined the effects of EAS on pro-inflammatory responses in S1-stimulated macrophages. Murine peritoneal exudate macrophages were co-treated with EAS and S1. Concentrations and mRNA levels of pro-inflammatory cytokines were assessed using enzyme-linked immunosorbent assay and reverse transcription and real-time polymerase chain reaction, respectively. Expression and phosphorylation levels of signaling proteins were analyzed using western blotting and fluorescence immunomicroscopy. EAS significantly attenuated S1-induced secretion of interleukin (IL)-6 in a concentration-dependent manner without reducing cell viability. EAS also markedly suppressed the S1-induced transcription of IL-6 and IL-1ß. However, among the TLR4 signaling proteins, EAS did not affect the degradation of inhibitor κBα, nuclear translocation of nuclear factor-κB p65 subunit, and phosphorylation of c-Jun N-terminal kinase p54 subunit after S1 exposure. In contrast, EAS significantly suppressed S1-induced phosphorylation of p44/42 mitogen-activated protein kinase (MAPK) and Akt. Attenuation of S1-induced transcription of IL-6 and IL-1ß by the MAPK kinase inhibitor U0126 was greater than that by the Akt inhibitor perifosine, and the effects were potentiated by simultaneous treatment with both inhibitors. These results suggest that EAS attenuates S1-induced IL-6 and IL-1ß production by suppressing p44/42 MAPK and Akt signaling in macrophages. Therefore, EAS may be beneficial in regulating excessive inflammation in patients with COVID-19.


Asunto(s)
Asparagus (Planta)/química , Interleucina-1beta/metabolismo , Interleucina-6/metabolismo , Macrófagos/efectos de los fármacos , Extractos Vegetales/farmacología , Transducción de Señal/efectos de los fármacos , Animales , Asparagus (Planta)/metabolismo , Butadienos/farmacología , Supervivencia Celular/efectos de los fármacos , Interleucina-1beta/genética , Interleucina-6/genética , Macrófagos/citología , Macrófagos/metabolismo , Masculino , Ratones , Ratones Endogámicos C57BL , Proteína Quinasa 1 Activada por Mitógenos/antagonistas & inhibidores , Proteína Quinasa 1 Activada por Mitógenos/metabolismo , Proteína Quinasa 3 Activada por Mitógenos/antagonistas & inhibidores , Proteína Quinasa 3 Activada por Mitógenos/metabolismo , Nitrilos/farmacología , Fosforilación/efectos de los fármacos , Extractos Vegetales/química , Tallos de la Planta/química , Tallos de la Planta/metabolismo , Proteínas Proto-Oncogénicas c-akt/antagonistas & inhibidores , Proteínas Proto-Oncogénicas c-akt/metabolismo , Glicoproteína de la Espiga del Coronavirus/farmacología , Receptor Toll-Like 4/metabolismo , Transcripción Genética/efectos de los fármacos
16.
J Phys Chem B ; 125(41): 11364-11373, 2021 10 21.
Artículo en Inglés | MEDLINE | ID: mdl-34613719

RESUMEN

In the present study, a dinuclear bis(µ-acetate) dicopper(II) complex [Cu2L2(µ1.1-CH3COO-)2] has been synthesized from a tridentate NNO Schiff Base ligand L (L = 2,4-dibromo-6-((3-(methylamino)propylimino)methyl)phenol) and characterized by elemental, ultraviolet-visible (UV-vis), Fourier transform infrared (FTIR), 1H NMR, and electrospray ionization-mass spectrometry (ESI-MS) spectroscopic studies. The single-crystal X-ray structure, different noncovalent interactions, Hirshfeld surface analysis, and density functional theory (DFT) studies of the dinuclear complex were determined by crystallographic computational studies. The structural study exposed that the complex consists of the penta-coordinated double µ1.1-acetato-bridged dinuclear units of Cu(II), and it is a centrosymmetric dimer in which the center of inversion lies at the midpoint of two Cu(II) ions. Hirshfeld surface and DFT studies pointed out the probable potentiality of the crystal in prospective binding with the protein. This was experimentally verified by carrying out the binding interaction studies against bovine serum albumin (BSA) protein using various spectroscopic methods. It was observed that the copper(II) complex could strongly bind to BSA and could quench the intrinsic fluorescence of BSA. Further, the studied complex was appraised for cell viability studies against SiHa cancer cells. It is observed that cell viability increases with time, demonstrating the biocompatible nature of the complex.


Asunto(s)
Complejos de Coordinación , Neoplasias , Animales , Bovinos , Línea Celular , Supervivencia Celular , Complejos de Coordinación/farmacología , Cobre , Cristalografía por Rayos X , ADN , Ligandos , Estudios Prospectivos , Bases de Schiff , Albúmina Sérica Bovina
17.
Arch Oral Biol ; 131: 105273, 2021 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-34600332

RESUMEN

OBJECTIVES: The present study aimed to assess the oxidative stress and the viability of dental pulp cells stimulated by lipopolysaccharide (LPS) and submitted to photobiomodulation (PBM) with infrared light-emitting diode (LED, 850 nm). DESIGN: Three healthy primary teeth (n = 3) were collected and seeded in 24-well plates with 10 µg/mL of LPS to induce inflammatory mediator formation. The cells were irradiated (850 nm, 40 mW/cm2 and 80 mW/cm2) at the proposed radiant exposures of 0 (control), 4, 15, and 30 J/cm2 shortly after LPS supplementation. The tests were performed 24 h after irradiation to assess mitochondrial activity (MTT assay), the number of viable cells (Trypan Blue), cell morphology (Scanning Electron Microscopy - SEM), and the quantification of Nitric Oxide (NO) and Reactive Oxygen Species (ROS). The data were analyzed using Kruskal-Wallis and Dunn's tests (p < 0.05). RESULTS: The irradiated groups showed larger viable cells number than the non-irradiated group with LPS (p < 0.0001). All irradiation parameters decreased ROS concentrations after LPS application compared to the non-irradiated group (p < 0.05). All irradiation parameters enhanced the NO values compared to those of the control group (p < 0.05). The SEM images showed cells with regular morphology that adhered to the substrate. CONCLUSIONS: According to the parameters used in this study, the radiant exposure of 15 J/cm2 and irradiance of 40 mW/cm2 were the most effective irradiation parameters to stimulate and modulate oxidative stress in the primary teeth-derived dental pulp cells.


Asunto(s)
Pulpa Dental , Rayos Infrarrojos , Supervivencia Celular , Estrés Oxidativo , Especies Reactivas de Oxígeno
18.
J Med Microbiol ; 70(10)2021 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-34612810

RESUMEN

Introduction. The emergence of multidrug-resistant Salmonella Typhimurium strains has increased the need for safe, alternative therapies from natural sources with antibacterial properties.Hypothesis/Gap Statement. There are no published data regarding the use of chitosan propolis nanocomposite (CPNP) either alone or in combination with antibiotics as antimicrobials against S. Typhimurium, especially in Egypt.Aim. This study evaluated the antibacterial activities of five antimicrobials [apramycin, propolis, chitosan nanoparticles (CNPs), chitosan propolis nanocomposite (CPNP) and CPNP +apramycin] against ten virulent and multidrug-resistant (MDR) S. Typhimurium field strains recovered from diarrheic rabbits through in vitro and in vivo study.Methodology. The expression levels of three virulence genes of S. Typhimurium strains were determined by quantitative reverse-transcription PCR (RT-qPCR) after exposure to sub-inhibitory concentrations of apramycin, propolis, CNPs, CPNP alone, and CPNP +apramycin. Additionally, 90 New Zealand rabbits were divided into control and experimentally S. Typhimurium-infected groups. The infected rabbits were orally administered saline solution (infected-untreated); 10 mg apramycin/kg (infected-apramycin-treated); 50 mg propolis/kg (infected-propolis-treated); 15 mg CPNP/kg (infected-CPNP-treated) and 15 mg CPNP +10 mg apramycin/kg (infected-CPNP +apramycin-treated) for 5 days.Results. The RT-qPCR analysis revealed different degrees of downregulation of all screened genes. Furthermore, the treatment of infected rabbits with CPNP or CPNP +apramycin significantly improved performance parameters, and total bacterial and Salmonella species counts, while also modulating both oxidative stress and altered liver and kidney parameters.Conclusion. This work demonstrates the use of CPNP alone or in combination with apramycin in the treatment of S. Typhimurium in rabbits.


Asunto(s)
Antibacterianos/uso terapéutico , Quitosano/química , Farmacorresistencia Bacteriana Múltiple/efectos de los fármacos , Nanocompuestos/uso terapéutico , Própolis/química , Infecciones por Salmonella/tratamiento farmacológico , Salmonella typhimurium/efectos de los fármacos , Animales , Antibacterianos/química , Antibacterianos/farmacología , Antioxidantes/metabolismo , Carga Bacteriana/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Quitosano/farmacología , Quitosano/uso terapéutico , Chlorocebus aethiops , Farmacorresistencia Bacteriana Múltiple/genética , Regulación Bacteriana de la Expresión Génica/efectos de los fármacos , Pruebas de Sensibilidad Microbiana , Nanocompuestos/química , Nebramicina/análogos & derivados , Nebramicina/farmacología , Nebramicina/uso terapéutico , Própolis/farmacología , Própolis/uso terapéutico , Conejos , Infecciones por Salmonella/microbiología , Salmonella typhimurium/patogenicidad , Células Vero , Virulencia/genética
19.
Nat Commun ; 12(1): 5846, 2021 10 06.
Artículo en Inglés | MEDLINE | ID: mdl-34615868

RESUMEN

Inadequate oxygenation is a major challenge in cell encapsulation, a therapy which holds potential to treat many diseases including type I diabetes. In such systems, cellular oxygen (O2) delivery is limited to slow passive diffusion from transplantation sites through the poorly O2-soluble encapsulating matrix, usually a hydrogel. This constrains the maximum permitted distance between the encapsulated cells and host site to within a few hundred micrometers to ensure cellular function. Inspired by the natural gas-phase tracheal O2 delivery system of insects, we present herein the design of a biomimetic scaffold featuring internal continuous air channels endowed with 10,000-fold higher O2 diffusivity than hydrogels. We incorporate the scaffold into a bulk hydrogel containing cells, which facilitates rapid O2 transport through the whole system to cells several millimeters away from the device-host boundary. A computational model, validated by in vitro analysis, predicts that cells and islets maintain high viability even in a thick (6.6 mm) device. Finally, the therapeutic potential of the device is demonstrated through the correction of diabetes in immunocompetent mice using rat islets for over 6 months.


Asunto(s)
Oxígeno/química , Animales , Biomimética , Encapsulación Celular , Supervivencia Celular/genética , Supervivencia Celular/fisiología , Células Cultivadas , Espectroscopía de Resonancia por Spin del Electrón , Humanos , Hidrogeles/química , Masculino , Ratones , Ratones Endogámicos C57BL , Ratas Sprague-Dawley
20.
Int J Mol Sci ; 22(19)2021 Oct 03.
Artículo en Inglés | MEDLINE | ID: mdl-34639057

RESUMEN

Ferula penninervis Regel & Schmalh. is a perennial plant used in Kazakh traditional folk medicine to treat epilepsy, neurosis, rheumatism, gastroduodenal ulcers, dyspepsia, wounds, abscesses or tumors. The aim of this work was to isolate series of sesquiterpene lactones from a crude methanolic root extract and investigate their in vitro cytotoxic potential against androgen-dependent prostate cancer LNCaP and epithelial prostate PNT2 cells, as well as to evaluate their melanin production inhibitory effects in murine melanoma B16F10 cells stimulated with α-melanocyte-stimulating hormone (αMSH). Two new (penninervin P and penninervin Q) and five known (olgin, laferin, olgoferin, oferin and daucoguainolactone F) guaiane-type sesquiterpene lactones were isolated with the use of a simple and fast liquid-liquid chromatography method. Olgin and laferin showed the most promising cytotoxic effects in LNCaP cells (IC50 of 31.03 and 23.26 µg/mL, respectively). Additionally, olgin, laferin, olgoferin, and oferin (10 µg/mL) potently impaired melanin release (40.67-65.48% of αMSH + cells) without influencing the viability of B16F10 cells. In summary, our findings might indicate that guaiane-type sesquiterpene lactones from F. penninervis could be regarded as promising candidates for further research in discovering new therapeutic agents with anti-prostate cancer and skin depigmentation properties.


Asunto(s)
Cromatografía Liquida , Ferula/química , Lactonas/aislamiento & purificación , Lactonas/farmacología , Melaninas/antagonistas & inhibidores , Sesquiterpenos de Guayano/aislamiento & purificación , Sesquiterpenos de Guayano/farmacología , Animales , Antineoplásicos , Antineoplásicos Fitogénicos/química , Antineoplásicos Fitogénicos/aislamiento & purificación , Antineoplásicos Fitogénicos/farmacología , Supervivencia Celular/efectos de los fármacos , Cromatografía Liquida/métodos , Relación Dosis-Respuesta a Droga , Humanos , Lactonas/química , Melanoma Experimental , Ratones , Estructura Molecular , Extractos Vegetales/química , Raíces de Plantas/química , Sesquiterpenos de Guayano/química , Análisis Espectral
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