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1.
Nucleic Acids Res ; 52(6): 2808-2820, 2024 Apr 12.
Artículo en Inglés | MEDLINE | ID: mdl-38426933

RESUMEN

Chemical modifications in RNAs play crucial roles in diversifying their structures and regulating numerous biochemical processes. Since the 1990s, several hydrophobic prenyl-modifications have been discovered in various RNAs. Prenyl groups serve as precursors for terpenes and many other biological molecules. The processes of prenylation in different macromolecules have been extensively studied. We introduce here a novel chemical biology toolkit that not only labels i6A, a prenyl-modified RNA residue, by leveraging the unique reactivity of the prenyl group, but also provides a general strategy to incorporate fluorescence functionalities into RNAs for molecular tracking purposes. Our findings revealed that iodine-mediated cyclization reactions of the prenyl group occur rapidly, transforming i6A from a hydrogen-bond acceptor to a donor. Based on this reactivity, we developed an Iodine-Mediated Cyclization and Reverse Transcription (IMCRT) tRNA-seq method, which can profile all nine endogenous tRNAs containing i6A residues in Saccharomyces cerevisiae with single-base resolution. Furthermore, under stress conditions, we observed a decline in i6A levels in budding yeast, accompanied by significant decrease of mutation rate at A37 position. Thus, the IMCRT tRNA-seq method not only permits semi-quantification of i6A levels in tRNAs but also holds potential for transcriptome-wide detection and analysis of various RNA species containing i6A modifications.


Asunto(s)
Isopenteniladenosina , Procesamiento Postranscripcional del ARN , ARN de Transferencia , Yodo , Neopreno , ARN de Transferencia/metabolismo , Saccharomyces cerevisiae , Análisis de Secuencia de ARN
2.
Cytokine ; 161: 156058, 2023 01.
Artículo en Inglés | MEDLINE | ID: mdl-36209650

RESUMEN

Understanding the crosstalk between endothelial cells (ECs) and bone-marrow mesenchymal stem cells (BMSCs) in response to hypoxic environments and deciphering of the underlying mechanisms are of great relevance for better application of BMSCs in tissue engineering. Here, we demonstrated that hypoxia promoted BMSCs proliferation, colony formation, osteogenic markers expression, mineralization, and extracellular signal-regulated protein kinase (ERK) phosphorylation, and that PD98059 (ERK inhibitor) blocked hypoxia-induced osteogenic differentiation. Hypoxia enhanced ECs migration, cyclooxygenase 2 (COX-2) and integrin αvß3 expression, and prostaglandin E2 (PGE2), vascular endothelial growth factor (VEGF) secretion. NS398 (selective COX-2 inhibitor) and LM609 (integrin αvß3 specific inhibitor) impaired the ECs response to hypoxia, and exogenous PGE2 partially reversed the effects of NS398. BMSCs: ECs co-culture under hypoxia upregulated BMSCs osteogenesis and ERK phosphorylation, as well as ECs migration, integrin αvß3 expression, and PGE2 and VEGF secretion. NS398 (pretreated ECs) lessened PGE2, VEGF concentrations of the co-culture system. NS398-treated ECs and AH6809 (combined EP1/2 antagonist)/L-798106 (selective EP3 antagonist)/L-161982 (selective EP4 antagonist)/SU5416 [VEGF receptor (VEGFR) inhibitor]-treated BMSCs impaired the co-cultured ECs-induced enhancement of BMSCs osteogenic differentiation. In conclusion, hypoxia enhances BMSCs proliferation and ERK-mediated osteogenic differentiation, and augments the COX-2-dependent PGE2 and VEGF release, integrin αvß3 expression, and migration of ECs. COX-2/PGE2/VEGF signaling is involved in intercellular BMSCs: ECs communication under hypoxia.


Asunto(s)
Células Madre Mesenquimatosas , Osteogénesis , Diferenciación Celular , Células Cultivadas , Ciclooxigenasa 2/metabolismo , Dinoprostona/metabolismo , Células Endoteliales/metabolismo , Quinasas MAP Reguladas por Señal Extracelular/metabolismo , Hipoxia/metabolismo , Integrinas , Células Madre Mesenquimatosas/metabolismo , Factor A de Crecimiento Endotelial Vascular/metabolismo
3.
J Org Chem ; 88(3): 1762-1771, 2023 02 03.
Artículo en Inglés | MEDLINE | ID: mdl-36691112

RESUMEN

Prenyl functionalities have been widely discovered in natural products, nucleic acids, and proteins with significant biological roles in both healthy and diseased cells. In this work, we develop a series of new nitroso-based probes for the labeling, enrichment, and regulation of prenylated RAS protein, which is highly associated with ∼20% of human cancers and used to be regarded as an "undruggable" target via a sequential ene-ligation and oxime condensation (SELOC) process. We found that these nitroso species can rapidly react with prenyl-containing molecules through ene-ligation and install a molecular tag for functional applications under physiological conditions. We first investigated this ligation process on two peptide models and demonstrated its labeling efficiency on various proteins such as myoglobin, lysozyme, RNase A, BSA, and HSP40. We further coupled this reactive platform with proteolysis-targeting chimera technology targeting to increase its efficiency and accuracy, as well as to expand its application range. Using the prenylated RAS protein as the model, we demonstrated that RAS could be efficiently decorated with our nitroso probes, which further condensate with oxime and rapidly react with a pomalidomide-containing hydroxylamine probe for protein degradation. As a result, the RAS protein in both HeLa and A549 cell lines has been determined to be efficiently degraded both in vitro and in vivo. This is the first case targeting post-translational modification other than ligand-protein interaction to degrade and regulate RAS proteins. We envision that our SELOC strategy will have great potential in studying the fundamental structures and functions of prenylated biomolecules and developing new drugs based on these unique cellular pathways.


Asunto(s)
Neoplasias , Oximas , Humanos , Oximas/química , Proteínas ras/metabolismo , Proteínas/química , Células HeLa
4.
Org Biomol Chem ; 21(9): 1895-1902, 2023 03 01.
Artículo en Inglés | MEDLINE | ID: mdl-36752060

RESUMEN

Five new uncommon 20-nor-isopimarane diterpenoids, aspewentins N-R (1-5), and three related known congeners (6-8), along with an isopimarane diterpenoid, sphaeropsidin C (9), were isolated from a Coptis chinensis Franch. rhizosphere soil-derived fungal strain, Aspergillus sp. WT03. The structures of compounds 1-9 were characterized based on the comprehensive analysis of the spectroscopic data, and their absolute configurations were elucidated by single crystal X-ray diffraction and time-dependent density functional theory (TDDFT)-ECD calculations. Compounds 1-5 represent rare examples of 20-nor-isopimarane analogues featuring a 1,2,3,4-tetrahydronaphthalene and 3,4-dihydronaphthalen-1(2H)-one moiety. The biosynthetic pathway of these diterpenoids was also proposed. Additionally, compounds 1, 3 and 4 showed moderate cytotoxic activity against MCF-7, A549 and HT-29 cell lines.


Asunto(s)
Antineoplásicos , Diterpenos , Abietanos , Estructura Molecular , Diterpenos/química , Aspergillus/química
5.
Cell Biol Toxicol ; 39(5): 2421-2429, 2023 10.
Artículo en Inglés | MEDLINE | ID: mdl-35644856

RESUMEN

We report development of a controllable gene editing tool that boronated gRNA, simply generated in situ, could regulate binding of gRNA molecules with either Cas9 endonuclease or target genes, thus serving as a modulator that can control CRISPR-Cas9 gene editing. Subsequent treatment with H2O2 facilitates the restoration of gene editing ability of the boronated gRNA to the level of using untreated gRNA. This is one of the few cases using small molecule to regulate CRISPR-Cas9 gene editing, which is a complement to the light approach, displaying great application potential. We develop a controllable gene editing tools based on the CRISPR-Cas9 gene editing system. This tool can be regulated by oxidative small molecule, i.e., H2O2. Compared with the light method, the application scope of our CRISPR-Cas9 systems have been widened with the small-molecule-triggered approaches, preventing the potential damage of cells or organism caused by UV light. In addition, the gain-of-function tools are expanding the gene code expansion for mechanistic studies of target enzymes since it provides a positive route to evaluate the activity of a given enzyme in dynamic and inversible regulation of targeting cellular processes.


Asunto(s)
Sistemas CRISPR-Cas , Edición Génica , Edición Génica/métodos , Sistemas CRISPR-Cas/genética , Peróxido de Hidrógeno/farmacología , Proteína 9 Asociada a CRISPR/genética
6.
J Org Chem ; 87(13): 8648-8655, 2022 07 01.
Artículo en Inglés | MEDLINE | ID: mdl-35708493

RESUMEN

Here, we first report a rapid and highly selective biocompatible ligation that proceeds via a strain-promoted prenyl-involved [2, 3]-Ene rearrangement process. We demonstrate the usefulness of naturally occurring strain-promoted ß-caryophyllene with triazoline (PTAD)/Selectfluor in the study of tagging molecule-of-interest. Experiments in peptide (Histone H3 (1-21) and Myhc (614-629)) and protein (BSA, ßLG, and HSP40) models exemplified the utility of the Ene-ligation for in vivo imaging and tracking.


Asunto(s)
Compuestos de Diazonio , Neopreno , Sesquiterpenos Policíclicos
7.
Pediatr Dermatol ; 39(3): 372-375, 2022 May.
Artículo en Inglés | MEDLINE | ID: mdl-35194837

RESUMEN

The clinicopathological features of 32 patients (17 females and 15 males) with a median age of 8 years (range, 1.5-21 years) from Southwestern China diagnosed with hydroa vacciniforme-like lymphoproliferative disorder (HVLPD) were reviewed. At presentation, 6 patients showed only skin lesions, while 26 patients showed both skin lesions and systemic symptoms, including fever, lymphadenopathy and hepatosplenomegaly. As the disease progressed, systemic symptoms occurred in all patients. Follow-up data of 29 patients showed that 14 patients were still alive with disease with a median follow-up time of 22 months (range 3.6-71 months), and 15 patients died within a median follow-up of 6 months (range 0-60 months).


Asunto(s)
Infecciones por Virus de Epstein-Barr , Hidroa Vacciniforme , Trastornos Linfoproliferativos , Adolescente , Adulto , Niño , Preescolar , Infecciones por Virus de Epstein-Barr/complicaciones , Infecciones por Virus de Epstein-Barr/diagnóstico , Infecciones por Virus de Epstein-Barr/patología , Femenino , Herpesvirus Humano 4 , Humanos , Hidroa Vacciniforme/diagnóstico , Hidroa Vacciniforme/patología , Lactante , Trastornos Linfoproliferativos/diagnóstico , Trastornos Linfoproliferativos/patología , Masculino , Estudios Retrospectivos , Adulto Joven
8.
Am J Orthod Dentofacial Orthop ; 161(1): e12-e19, 2022 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-34376339

RESUMEN

INTRODUCTION: This retrospective study aimed to quantify the impact of coronavirus disease 2019 (COVID-19) on the orthodontic appointment and make an analysis of orthodontic emergencies (OEs) that occurred during the pandemic. METHODS: A total of 628 patients were randomly sampled from 3489 subjects who were undergoing active orthodontic treatment with fixed appliances, and the medical records were reviewed. OE occurrence was analyzed from 617 patients who had explicit return-visit records after the COVID-19 outbreak. Wilcoxon signed rank tests, chi-square tests, and a binary logistic regression were performed. RESULTS: The return-visit of 98.6% of the patients was delayed significantly with an increase over 8.98 ± 4.76 weeks (P <0.001). In general, 32.3% of the patients suffered from various OEs while waiting for their first return-visit, and bracket or band debonding was the most frequently reported category. Most OEs did not receive timely treatments because of the lockdown. The incidence was nearly 2 times higher than that of the normal appointment times. No correlation was found between OE occurrence and different demographic and clinical characteristics of patients. The therapeutic progress of patients, especially those in stage 3, was postponed because of the occurrence of OEs. CONCLUSIONS: Regardless of the limitations, our study suggested that it is highly possible that the COVID-19 pandemic has delayed appointments of fixed orthodontic patients. OEs did bother a minority of patients and could not be settled in time during the lockdown, which had a negative impact on the near-term treatment progress and should have been prevented. Further studies are required to investigate the long-dated influence of COVID-19 on orthodontic practices.


Asunto(s)
COVID-19 , Control de Enfermedades Transmisibles , Humanos , Pandemias , Estudios Retrospectivos , SARS-CoV-2
9.
Bioorg Chem ; 107: 104624, 2021 02.
Artículo en Inglés | MEDLINE | ID: mdl-33465669

RESUMEN

Two novel monoterpenoid indole alkaloids (MIAs), gelsechizines A-B (1-2), along with four known ones (3-6) were isolated from the fruits of Gelsemium elegans. Compound 1 features a new carbon skeleton with two additional carbon atoms forming a 4-methylpyridine unit. Their structures with absolute configurations were elucidated by NMR, MS, X-ray diffraction and electronic circular dichroism (ECD) calculations. Compounds 1-3 showed significant anti-inflammatory effects in vivo and in vitro, which may be related to the inhibition of the trecruitment of neutrophils and macrophages as well as the secretion of TNF-α and IL-6. Preliminary structure-activity relationship analysis revealed that the ß-N-acrylate moiety plays an important role in the anti-inflammatory effect.


Asunto(s)
Antiinflamatorios/farmacología , Gelsemium/química , Macrófagos/efectos de los fármacos , Alcaloides de Triptamina Secologanina/química , Animales , Animales Modificados Genéticamente/crecimiento & desarrollo , Animales Modificados Genéticamente/metabolismo , Antiinflamatorios/química , Antiinflamatorios/aislamiento & purificación , Frutas/química , Frutas/metabolismo , Gelsemium/metabolismo , Interleucina-6/metabolismo , Larva/efectos de los fármacos , Larva/crecimiento & desarrollo , Larva/metabolismo , Lipopolisacáridos/farmacología , Macrófagos/citología , Macrófagos/metabolismo , Espectroscopía de Resonancia Magnética , Ratones , Conformación Molecular , Neutrófilos/citología , Neutrófilos/patología , Células RAW 264.7 , Alcaloides de Triptamina Secologanina/aislamiento & purificación , Alcaloides de Triptamina Secologanina/farmacología , Relación Estructura-Actividad , Factor de Necrosis Tumoral alfa/metabolismo , Pez Cebra/crecimiento & desarrollo , Pez Cebra/metabolismo
10.
Med Sci Monit ; 27: e932328, 2021 Mar 25.
Artículo en Inglés | MEDLINE | ID: mdl-33762562

RESUMEN

An editorial decision has been made to retract this manuscript due to breach of publishing guidelines, following the identification of non-original and manipulated figures. Reference: Peng Li, Zhiqiang Zhang, Feng Zhang, Hongling Zhou, Bei Sun: Effects of 3-Tetrazolyl Methyl-3-Hydroxy-Oxindole Hybrid (THOH) on Cell Proliferation, Apoptosis, and G2/M Cell Cycle Arrest Occurs by Targeting Platelet-Derived Growth Factor D (PDGF-D) and the MEK/ERK Signaling Pathway in Human Lung Cell Lines SK-LU-1, A549, and A-427. Med Sci Monit 2018; 24: 4547-4554. 10.12659/MSM.909125.

11.
Toxicol Appl Pharmacol ; 407: 115252, 2020 11 15.
Artículo en Inglés | MEDLINE | ID: mdl-32987027

RESUMEN

Acute lung injury (ALI) is a severe disease for which effective drugs are still lacking at present. Forsythia suspensa is a traditional Chinese medicine commonly used to relieve respiratory symptoms in China, but its functional mechanisms remain unclear. Therefore, forsythoside A (FA), the active constituent of F. suspensa, was studied in the present study. Inflammation models of type II alveolar epithelial MLE-12 cells and BALB/c mice stimulated by lipopolysaccharide (LPS) were established to explore the effects of FA on ALI and the underlying mechanisms. We found that FA inhibited the production of monocyte chemoattractant protein-1 (MCP-1/CCL2) in LPS-stimulated MLE-12 cells in a dose-dependent manner. Moreover, FA decreased the adhesion and migration of monocytes to MLE-12 cells. Furthermore, miR-124 expression was upregulated after FA treatment. The luciferase report assay showed that miR-124 mimic reduced the activity of CCL2 in MLE-12 cells. However, the inhibitory effects of FA on CCL2 expression and monocyte adhesion and migration to MLE-12 cells were counteracted by treatment with a miR-124 inhibitor. Critically, FA ameliorated LPS-induced pathological damage, decreased the serum levels of tumor necrosis factor-α and interleukin-6, and inhibited CCL2 secretion and macrophage infiltration in lungs in ALI mice. Meanwhile, administration of miR-124 inhibitor attenuated the protective effects of FA. The present study suggests that FA attenuates LPS-induced adhesion and migration of monocytes to type II alveolar epithelial cells though upregulating miR-124, thereby inhibiting the expression of CCL2. These findings indicate that the potential application of FA is promising and that miR-124 mimics could also be used in the treatment of ALI.


Asunto(s)
Lesión Pulmonar Aguda/prevención & control , Adhesión Celular/efectos de los fármacos , Movimiento Celular/efectos de los fármacos , Células Epiteliales/efectos de los fármacos , Glicósidos/farmacología , MicroARNs/biosíntesis , Monocitos/efectos de los fármacos , Alveolos Pulmonares/citología , Lesión Pulmonar Aguda/inducido químicamente , Lesión Pulmonar Aguda/patología , Animales , Quimiocina CCL2/antagonistas & inhibidores , Quimiocina CCL2/biosíntesis , Relación Dosis-Respuesta a Droga , Glicósidos/uso terapéutico , Lipopolisacáridos , Ratones , Ratones Endogámicos BALB C , MicroARNs/genética , Alveolos Pulmonares/efectos de los fármacos , Regulación hacia Arriba/efectos de los fármacos
12.
Clin Sci (Lond) ; 134(19): 2549-2563, 2020 10 16.
Artículo en Inglés | MEDLINE | ID: mdl-32975280

RESUMEN

Acute lung injury (ALI) is a life-threatening disease without effective pharmacotherapies, so far. Forsythia suspensa is frequently used in the treatment of lung infection in traditional Chinese medicine. In search for natural anti-inflammatory components, the activity and the underlying mechanism of Forsythoside A (FA) from Forsythia suspensa were explored. In the present paper, BALB/c mice and murine RAW 264.7 cells were stimulated by LPS to establish inflammation models. Data showed that FA inhibited the production of TNF-α and IL-6 and the activation of STAT3 in LPS-stimulated RAW 264.7 cells. Additionally, FA increased the expression level of microRNA-124 (miR-124). Furthermore, the inhibitory effect of FA on STAT3 was counteracted by the treatment of miR-124 inhibitor. Critically, FA ameliorated LPS-induced ALI pathological damage, the increase in lung water content and inflammatory cytokine, cells infiltration and activation of the STAT3 signaling pathway in BALB/c mice. Meanwhile, FA up-regulated the expression of miR-124 in lungs, while administration with miR-124 inhibitor attenuated the protective effects of FA. Our results indicated that FA alleviates LPS-induced inflammation through up-regulating miR-124 in vitro and in vivo. These findings indicate the potential of FA and miR-124 in the treatment of ALI.


Asunto(s)
Lesión Pulmonar Aguda/inducido químicamente , Lesión Pulmonar Aguda/genética , Glicósidos/farmacología , MicroARNs/genética , Sustancias Protectoras/farmacología , Regulación hacia Arriba/genética , Animales , Glicósidos/química , Inflamación/genética , Inflamación/patología , Interleucina-6/metabolismo , Lipopolisacáridos , Macrófagos/efectos de los fármacos , Macrófagos/metabolismo , Masculino , Ratones , Ratones Endogámicos BALB C , MicroARNs/metabolismo , Modelos Biológicos , Sustancias Protectoras/química , Células RAW 264.7 , Factor de Transcripción STAT3/metabolismo , Transducción de Señal/efectos de los fármacos , Factor de Necrosis Tumoral alfa/metabolismo , Regulación hacia Arriba/efectos de los fármacos
13.
BMC Anesthesiol ; 20(1): 234, 2020 09 15.
Artículo en Inglés | MEDLINE | ID: mdl-32933470

RESUMEN

BACKGROUND: The peri-operative effectiveness of ultrasound-guided great auricular nerve block (GANB) in patients, especially in adult patients undergoing middle ear microsurgery remains unclear. We hypothesized that ultrasound-guided GANB would decrease the hemodynamic responsiveness to incision and opioid consumption in middle ear microsurgery as well as the post-operative analgesia requirement. METHODS: Sixty patients undergoing middle ear microsurgery were randomized into two equal groups to receive either a GANB with 2 ml of 0.25% ropivacaine under ultrasound guidance (GANB group) or to receive a blank control intervention (without any performed injection) before general anesthesia inductions. The primary outcomes were hemodynamic changes of MAP (mean artery pressure) and HR (heart rate) to skin incision. The secondary endpoints were to determine the consumptions of propofol and remifentanil during the operation and the incidence of remedial analgesia 48 h post-operation to maintain VAS ≤ 3. RESULTS: The MAP post incision in GANB group was significantly lower than that in control group (GANB group 93.83 ± 11.72 mmHg vs. control group 100.87 ± 12.65 mmHg, P = 0.029). The increases for MAP and HR post incision were also lower in GANB group (∆MAP GANB group 11.90 ± 8.32 mmHg vs. control group 19.83 ± 10.37 mmHg, P = 0.002; ∆HR GANB group 3.67 ± 5.30 beat min- 1 vs. control group 8.23 ± 8.56 beat min- 1, P = 0.016). Remifentanil consumption was significantly decreased in GANB group (GANB group 401.55 ± 100.51 µg h- 1 vs. control group 697.34 ± 215.45 µg h- 1, P = 0.000). The incidence of remedial analgesia post-operation in GANB group (5/30) was significantly lower than that in control group (20/30, P = 0.000). CONCLUSION: Ultrasound-guided GANB decreases the hemodynamic responsiveness to incision and remifentanil consumption in middle ear microsurgery as well as the post-operative analgesia requirement. TRIAL REGISTRATION: This trial was retrospectively registered at http://www.chictr.org.cn with the registration number of ChiCTR1800014333 on 6 January, 2018.


Asunto(s)
Oído Medio/cirugía , Hemodinámica/fisiología , Microcirugia/métodos , Bloqueo Nervioso/métodos , Ultrasonografía Intervencional/métodos , Adulto , Anestesia General , Anestésicos Locales , Beijing , Oído Medio/diagnóstico por imagen , Oído Medio/inervación , Femenino , Hemodinámica/efectos de los fármacos , Humanos , Masculino , Estudios Prospectivos , Ropivacaína
14.
Med Sci Monit ; 24: 4547-4554, 2018 07 02.
Artículo en Inglés | MEDLINE | ID: mdl-29961751

RESUMEN

BACKGROUND The aim of this study was to evaluate the effects of 3-tetrazolyl methyl-3-hydroxy-oxindole hybrid (THOH) on cell proliferation, apoptosis, and the cell cycle in human lung cancer cell lines SK-LU-1, A549, and A-427, and the normal lung fibroblast cell line, MRC-5, in vitro. MATERIAL AND METHODS Human lung adenocarcinoma cells SK-LU-1, A549, and A-427, and the normal lung fibroblast cells, MRC-5 were cultured and treated with increasing concentrations of 10 mM of a stock solution of THOH in dimethyl sulfoxide (DMSO). An MTT cell proliferation assay was used. Cell apoptosis and the cell cycle were studied using fluorescence-activated cell sorting (FACs) with fluorescein isothiocyanate (FITC), Annexin-V, propidium iodide (PI), and nuclear staining with 4',6-diamidino-2-phenylindole (DAPI). DNA damage was measured using the comet (single-cell gel electrophoresis) assay. Cell migration was evaluated using a wound healing assay, and Western blotting was used to measure protein expression levels. RESULTS Treatment of SK-LU-1 cells with THOH inhibited cell migration. Treatment of lung cancer cells, SK-LU-1, A549, and A-427, with THOH inhibited cell proliferation, with the most marked inhibition found in the SK-LU-1 lung cancer cells (IC50, 12 µM). Treatment of lung cancer cells, SK-LU-1, A549, and A-427, with THOH increased cell apoptosis, resulted in G2/M cell cycle arrest, and inhibited both the platelet-derived growth factor D (PDGF-D) and MEK/ERK signaling pathways. CONCLUSIONS Treatment of adenocarcinoma cells, SK-LU-1, A549, and A-427, with THOH inhibited cell proliferation, apoptosis, and resulted in G2/M cell cycle arrest by targeting PDGF-D and the MEK/ERK signaling pathway.


Asunto(s)
Indoles/farmacología , Linfocinas/efectos de los fármacos , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Factor de Crecimiento Derivado de Plaquetas/efectos de los fármacos , Tetrazoles/farmacología , Células A549/efectos de los fármacos , Apoptosis/efectos de los fármacos , Ciclo Celular/efectos de los fármacos , Puntos de Control del Ciclo Celular/efectos de los fármacos , Línea Celular Tumoral , Movimiento Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Humanos , Indoles/metabolismo , Neoplasias Pulmonares/patología , Oxindoles , Transducción de Señal , Tetrazoles/metabolismo
15.
Phytother Res ; 32(9): 1770-1783, 2018 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-29876982

RESUMEN

Casticin, a compound purified from the Chinese herb Viticis Fructus, has been proven effective in preventing tumor progression in previous studies. Ulcerative colitis (UC) is a common inflammatory bowel disease that affects millions of people worldwide, but no effective and safe drugs are available. In this study, we aimed to study how did casticin affect UC by evaluating its effects on dextran sulfate sodium (DSS)-induced colitis in mice. Our data suggested that casticin attenuated body weight loss, colon length shortening, and pathological damage in the colon of DSS-treated mice. Casticin decreased reactive oxygen species level and chemocytokines (IL-1ß, IL-6, TNF-α) productions in colon tissue. The decreased reactive oxygen species level and suppressed proinflammatory cytokines productions were also confirmed in casticin-treated LPS-stimulated RAW264.7 cells and hydrogen peroxide-treated CACO-2 cells in vitro. Mechanistically, casticin treatment prevented the profound activation of AKT signaling caused by DSS administration. And casticin inhibited the productions of proinflammatory chemocytokines through downregulating AKT/NF-κB pathway in macrophages. Meanwhile, data revealed that casticin increased expressions of endogenous antioxidants peroxiredoxin 3 and MnSOD were through activation in FOXO3α signaling by downregulating AKT signaling in colon epithelium cells. Our findings demonstrated that casticin alleviated DSS-induced UC by increasing the antioxidant enzyme peroxiredoxin 3 and MnSOD expressions, and decreasing the production of proinflammatory chemocytokines through inhibition of AKT signaling.


Asunto(s)
Colitis Ulcerosa/tratamiento farmacológico , Flavonoides/farmacología , Especies Reactivas de Oxígeno/metabolismo , Animales , Células CACO-2 , Colitis Ulcerosa/inducido químicamente , Sulfato de Dextran , Modelos Animales de Enfermedad , Humanos , Interleucina-1beta/metabolismo , Interleucina-6/metabolismo , Macrófagos/efectos de los fármacos , Masculino , Ratones , FN-kappa B/metabolismo , Peroxiredoxina III/metabolismo , Células RAW 264.7 , Transducción de Señal/efectos de los fármacos , Superóxido Dismutasa/metabolismo , Factor de Necrosis Tumoral alfa/metabolismo
17.
Zhonghua Xin Xue Guan Bing Za Zhi ; 42(6): 504-9, 2014 Jun.
Artículo en Zh | MEDLINE | ID: mdl-25164226

RESUMEN

OBJECTIVE: To explore the incidence of sudden cardiac death (SCD) of urban residents in Beijing. METHODS: A community based epidemiology survey was performed on the residents of 4 communities in the Xicheng and Haidian districts in Beijing from October 2008 to September 2009. Data on the total population, age, gender and vital status were monitored, and incidence of SCD as well as related information were collected from the household administrative workers, the family members of the deceased, the hospital personnel and the witnesses. RESULTS: 479 521 subjects (244 000 men and 235 521 women) were monitored, a total of 1 285 (642 men and 643 women) all cause death occurred during the study period and 184 (86 men and 98 women) deaths were identified as SCD. The incidence of SCD was 35.2 (95%CI 27.8-42.7) per 100 000 per year for men and 41.6 (95%CI 33.4-49.8) per 100 000 per year for women. SCD accounted for 13.4% mortality in men and 15.2% mortality in women. There were 171 (91.0%) SCD cases in residents over 55 years of age. The incidence of SCD for the age group 0-24, 25-34, 35-44, 45-54, 55-64, 65-74 and 75 years and over was 5.6, 4.6, 3.0, 9.8, 78.4, 88.4, and 272.8 per 100 000 per year for men, and 1.6, 0, 3.2, 0, 21.1, 84.2 and 470.0 per 100 000 per year for women, respectively. The proportion of the cases that have at least one cardiovascular disease history was 57.0% (49/86) for men and 60.2% (59/98) for women. The cases that occurred at home, on the way to hospital, in the hospital emergency room, in the hospital ward and other places account for 53.3% (98 cases), 12.2% (22 cases), 9.2% (17 cases), 12.5% (23 cases) and 13.0% (24 cases) of the 184 SCD cases, respectively. CONCLUSION: SCD is a great threat to the urban residents in Beijing. Most SCD cases occurred at home on residents over 55 years of age. More than half SCD residents have at least one cardiovascular disease. It is important to take preventive measures in the urban residents over 55 years old and with history of cardiovascular disease.


Asunto(s)
Muerte Súbita Cardíaca/epidemiología , Adolescente , Adulto , Anciano , Niño , Preescolar , China/epidemiología , Femenino , Humanos , Incidencia , Lactante , Recién Nacido , Masculino , Persona de Mediana Edad , Adulto Joven
18.
Mol Cell Endocrinol ; 593: 112346, 2024 Nov 01.
Artículo en Inglés | MEDLINE | ID: mdl-39151653

RESUMEN

Insulin, a critical hormone in the human body, exerts its effects by binding to insulin receptors and regulating various cellular processes. While nitric oxide (NO) plays an important role in insulin secretion and acts as a mediator in the signal transduction pathway between upstream molecules and downstream effectors, holds a significant position in the downstream signal network of insulin. Researches have shown that the insulin-NO system exhibits a dual regulatory effect within the central nervous system, which is crucial in the regulation of diabetic encephalopathy (DE). Understanding this system holds immense practical importance in comprehending the targets of existing drugs and the development of potential therapeutic interventions. This review extensively examines the characterization of insulin, NO, Nitric oxide synthase (NOS), specific NO pathway, their interconnections, and the mechanisms underlying their regulatory effects in DE, providing a reference for new therapeutic targets of DE.


Asunto(s)
Insulina , Óxido Nítrico Sintasa , Óxido Nítrico , Transducción de Señal , Humanos , Insulina/metabolismo , Óxido Nítrico/metabolismo , Animales , Óxido Nítrico Sintasa/metabolismo , Encefalopatías Metabólicas/metabolismo , Complicaciones de la Diabetes/metabolismo
19.
Gigascience ; 132024 01 02.
Artículo en Inglés | MEDLINE | ID: mdl-38626722

RESUMEN

BACKGROUND: Most currently available reference genomes lack the sequence map of sex-limited (such as Y and W) chromosomes, which results in incomplete assemblies that hinder further research on sex chromosomes. Recent advancements in long-read sequencing and population sequencing have provided the opportunity to assemble sex-limited chromosomes without the traditional complicated experimental efforts. FINDINGS: We introduce the first computational method, Sorting long Reads of Y or other sex-limited chromosome (SRY), which achieves improved assembly results compared to flow sorting. Specifically, SRY outperforms in the heterochromatic region and demonstrates comparable performance in other regions. Furthermore, SRY enhances the capabilities of the hybrid assembly software, resulting in improved continuity and accuracy. CONCLUSIONS: Our method enables true complete genome assembly and facilitates downstream research of sex-limited chromosomes.


Asunto(s)
Genoma , Cromosomas Sexuales , Cromosomas Sexuales/genética , Análisis de Secuencia de ADN/métodos , Secuenciación de Nucleótidos de Alto Rendimiento/métodos
20.
Adv Healthc Mater ; 13(20): e2400148, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38780479

RESUMEN

Controlling bleeding by applying pressing cotton gauze is the most facile treatment in prehospital emergencies. However, the wettable nature of cotton fibers leads to unnecessary blood loss due to excessive blood absorption, inseparable adhesion-induced pain, and pliable to infection. Here, a kind of ultra-hydrophobic haemostatic anti-adhesive gauze whose surface is loaded with polydimethylsiloxane (PDMS) and hydrophobic-modified cellulose nanocrystals (CNCs), achieving a water contact angle of ≈160° is developed. It is demonstrated that the mechanism by which hydrophobic CNCs promote blood clotting is associated with their ability to activate coagulation factors, contributing to fibrin formation, and promoting platelet activation. The blood-restricting effect results from the low surface energy layer formed by PDMS and then the alkyl chains of hydrophobic CNCs are combined. The produced ultra-hydrophobic gauze resists blood flow and diffusion, decreases blood loss, is effortlessly peelable, and minimizes pathogen adhesion. Compared to the commercial cotton gauze, this gauze achieved effective haemostasis and antiadhesion by reducing blood loss by more than 90%, shortening haemostasis time by more than 75%, lowering peeling force by more than 90% and minifying bacterium attachment by more than 95%. This work presents promising applications in terms of prehospital first aid.


Asunto(s)
Celulosa , Dimetilpolisiloxanos , Hemostasis , Interacciones Hidrofóbicas e Hidrofílicas , Nanopartículas , Celulosa/química , Animales , Hemostasis/efectos de los fármacos , Nanopartículas/química , Dimetilpolisiloxanos/química , Vendajes , Humanos , Fibra de Algodón , Hemorragia , Coagulación Sanguínea/efectos de los fármacos , Coagulación Sanguínea/fisiología , Masculino , Hemostáticos/química , Hemostáticos/farmacología
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