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1.
Plants (Basel) ; 13(3)2024 Jan 26.
Artigo em Inglês | MEDLINE | ID: mdl-38337906

RESUMO

The brown planthopper (BPH), Nilaparvata lugens (Stål), a rice-specific pest, has risen to the top of the list of significant pathogens and insects in recent years. Host plant-mediated resistance is an efficient strategy for BPH control. Nonetheless, BPH resistance in rice cultivars has succumbed to the emergence of distinct virulent BPH populations. Circular RNAs (circRNAs) play a pivotal role in regulating plant-environment interactions; however, the mechanisms underlying their insect-resistant functions remain largely unexplored. In this study, we conducted an extensive genome-wide analysis using high-throughput sequencing to explore the response of rice circRNAs to BPH infestations. We identified a total of 186 circRNAs in IR56 rice across two distinct virulence groups: IR-IR56-BPH (referring to IR rice infested by IR56-BPH) and IR-TN1-BPH, along with a control group (IR-CK) without BPH infestation. Among them, 39 circRNAs were upregulated, and 43 circRNAs were downregulated in the comparison between IR-IR56-BPH and IR-CK. Furthermore, in comparison with IR-CK, 42 circRNAs exhibited upregulation in IR-TN1-BPH, while 42 circRNAs showed downregulation. The Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis revealed that the targets of differentially expressed circRNAs were considerably enriched in a multitude of biological processes closely linked to the response to BPH infestations. Furthermore, we assessed a total of 20 randomly selected circRNAs along with their corresponding expression levels. Moreover, we validated the regulatory impact of circRNAs on miRNAs and mRNAs. These findings have led us to construct a conceptual model that circRNA is associated with the defense regulatory network in rice, which is likely facilitated by the mediation of their parental genes and competing endogenous RNA (ceRNA) networks. This model contributes to the understanding of several extensively studied processes in rice-BPH interactions.

2.
Eur J Pharmacol ; 944: 175592, 2023 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-36804835

RESUMO

Abnormal tumor vasculature blocks the extravasation of T lymphocytes into the tumor, thereby suppressing anti-tumor immunity. Recently, metformin has been shown to affect tumor vasculature and enhance T lymphocyte anti-tumor immunity. However, whether or how metformin affects T lymphocyte anti-tumor immunity via a vascular mechanism remains poorly understood. Herein, we show that a large number of CD8+ lymphocytes gathered in the peri-tumoral region, while very few infiltrated the tumor. Metformin administration increased the expression of anti-tumor immunity-associated genes and the number of tumor-infiltrating CD8+ lymphocytes. Injection of CD8 but not CD4 neutralization antibody into tumor-bearing mice significantly abrogated the anti-tumor effect of metformin. Critically, CD8+ lymphocytes were found to pass through the wall of perfused vessel. Further results of immunofluorescent staining showed that metformin greatly elevated tumor perfusion, which was accompanied by increased vascular maturity in the intratumoral region (ITR) but not peritumoral region (PTR). These findings provide evidence for the vascular mechanism involved in metformin-induced enhancement of T lymphocyte anti-tumor immunity. By remodeling the abnormal tumor vasculature, also called vessel normalization metformin increases vascular maturity and tumor perfusion, thus allowing more CD8+ lymphocytes to infiltrate the tumor.


Assuntos
Metformina , Neoplasias , Camundongos , Animais , Linfócitos T CD8-Positivos , Metformina/farmacologia , Linfócitos do Interstício Tumoral , Neoplasias/patologia , Linfócitos T CD4-Positivos
3.
Comb Chem High Throughput Screen ; 26(8): 1571-1577, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36683371

RESUMO

BACKGROUND AND OBJECTIVE: Dizziness is a common complication of gastrointestinal endoscopy under general anesthesia. Dizziness is primarily caused by a lack of energy and blood volume following fasting and water deprivation. Hypertonic glucose solution (HGS) is an intravenous energy replenishment, that increases blood volume due to its hyperosmotic characteristics and can be directly absorbed from blood circulation. This study aimed to HGS can prevent dizziness after gastrointestinal endoscopy. METHODS: This was a double-blind, randomized, controlled study. Eligible patients were randomly allocated into two groups based on the intravenous agent administered before gastrointestinal endoscopy: Group A, saline (0.9%; 20 mL); and group B, HGS (50%; 20 mL). Overall, 840 patients were included in the statistical analysis. The scores and incidence of dizziness were assessed. RESULTS: The dizziness score were higher in group A than in group B (1.92 ± 0.08 vs. 0.92 ± 0.06; p < 0.01). The incidence of mild dizziness and moderate-to-severe dizziness was significantly lower in group B than in group A (40.10% vs. 51.78% and 3.10% vs. 19.72%, respectively; p < 0.01). The incidence and score of dizziness were significantly lower in males than in females (30.81% vs. 51.82% and 0.64 ± 0.08 vs. 1.12 ± 0.08, respectively; p < 0.01) after pretreatment with HGS. CONCLUSION: Pretreatment with HGS effectively prevents dizziness after gastrointestinal endoscopy under general anesthesia. The mechanism of action is unclear but might be related to body energy replacement and an increase in blood volume following HGS administration.


Assuntos
Tontura , Solução Hipertônica de Glucose , Masculino , Feminino , Humanos , Administração Intravenosa , Endoscopia Gastrointestinal , Anestesia Geral/efeitos adversos
4.
Chin J Integr Med ; 28(11): 983-991, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-35997859

RESUMO

OBJECTIVE: To examine the effect of Shenmai Injection (SMJ) on ferroptosis during myocardial ischemia reperfusion (I/R) injury in rats and the underlying mechanism. METHODS: A total of 120 SPF-grade adult male SD rats, weighing 220-250 g were randomly divided into different groups according to a random number table. Myocardial I/R model was established by occluding the left anterior descending artery for 30 min followed by 120 min of reperfusion. SMJ was injected intraperitoneally at the onset of 120 min of reperfusion, and erastin (an agonist of ferroptosis), ferrostatin-1 (Fer-1, an inhibitor of ferroptosis) and ML385 (an inhibitor of nuclear factor erythroid-2 related factor 2 (Nrf2)) were administered intraperitoneally separately 30 min before myocardial ischemia as different pretreatments. Cardiac function before ischemia, after ischemia and after reperfusion was analysed. Pathological changes in the myocardium and the ultrastructure of cardiomyocytes were observed, and the myocardial infarction area was measured. Additionally, the concentration of Fe2+ in heart tissues and the levels of creatine kinase-MB (CK-MB), troponin I (cTnl), malondialdehyde (MDA) and superoxide dismutase (SOD) in serum were measured using assay kits, and the expressions of Nrf2, glutathione peroxidase 4 (GPX4) and acyl-CoA synthetase long-chain family member 4 (ACSL4) were examined by Western blot. RESULTS: Compared with the sham group, I/R significantly injured heart tissues, as evidenced by the disordered, ruptured and oedematous myocardial fibres; the increases in infarct size, serum CK-MB, cTnI and MDA levels, and myocardial Fe2+ concentrations; and the decreases in SOD activity (P<0.05). These results were accompanied by ultrastructural alterations to the mitochondria, increased expression of ACSL4 and inhibited the activation of Nrf2/GPX4 signalling (P<0.05). Compared with I/R group, pretreatment with 9 mL/kg SMJ and 2 mg/kg Fer-1 significantly reduced myocardial I/R injury, Fe2+ concentrations and ACSL4 expression and attenuated mitochondrial impairment, while 14 mg/kg erastin exacerbated myocardial I/R injury (P<0.05). In addition, cardioprotection provided by 9 mL/kg SMJ was completely reversed by ML385, as evidenced by the increased myocardial infarct size, CK-MB, cTnI, MDA and Fe2+ concentrations, and the decreased SOD activity (P<0.05). CONCLUSIONS: Ferroptosis is involved in myocardial I/R injury. Pretreatment with SMJ alleviated myocardial I/R injury by activating Nrf2/GPX4 signalling-mediated ferroptosis, thereby providing a strategy for the prevention and treatment of ischemic heart diseases.


Assuntos
Ferroptose , Infarto do Miocárdio , Isquemia Miocárdica , Traumatismo por Reperfusão Miocárdica , Animais , Masculino , Ratos , Coenzima A , Creatina Quinase , Ligases , Malondialdeído , Infarto do Miocárdio/tratamento farmacológico , Isquemia Miocárdica/tratamento farmacológico , Traumatismo por Reperfusão Miocárdica/tratamento farmacológico , Traumatismo por Reperfusão Miocárdica/patologia , Miócitos Cardíacos/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Fosfolipídeo Hidroperóxido Glutationa Peroxidase , Ratos Sprague-Dawley , Superóxido Dismutase/metabolismo , Troponina I
5.
Ann Transl Med ; 10(12): 670, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35845517

RESUMO

Background: The development of personalized and high-precision dental treatment is inseparable from the accurate measurement and analysis of the model. Compared with traditional plaster models, digital models allow dentists to obtain richer and more detailed inspection results. However, the measurement of digital models in clinical practice usually ignores the influence of the overall three-dimensional (3D) structure of teeth and tooth arrangement on the measurement results. The purpose of this study was to evaluate the effect of calibrated tooth axis and tooth arrangement on tooth width and arch length. Methods: A total of 110 digital models from 80 participants were used to measure teeth width and dental arch length using the following methods: Method A, simple positioning of the proximal and distal of teeth; Method B: calibration of the clinical crown axis; and Method C: calibration of the overall 3D axis of the teeth. The Measurand model included pre- and post-orthodontic models of the same patients to assess the impact of tooth alignment on outcomes. Results: In the aligned dentition, whether the tooth axis was calibrated had no effect on the measurement results. On unaligned dentitions, calibrating the pinion allowed for more accurate measurements, with Method C the closest to the true size. Furthermore, the arrangement of teeth affected the measurement, but there was no continuous linear correlation with arch length discrepancy (ALD). Conclusions: Clinicians should choose appropriate measurement methods according to actual needs when performing model measurement, and should pay attention to the influence of tooth axis, tooth shape, and arrangement on the measurement results.

6.
Zhongguo Zhen Jiu ; 40(7): 721-5, 2020 Jul 12.
Artigo em Chinês | MEDLINE | ID: mdl-32648395

RESUMO

OBJECTIVE: To observe the therapeutic effect of herb-separated moxibustion combined with budesonide nasal spray (rhinocort) on moderate to severe persistent allergic rhinitis (AR) of kidney-yang deficiency type, and to explore the correlation between nasal temperature and condition of allergic rhinitis. METHODS: A total of 70 patients with moderate to severe persistent AR were randomized into an observation group (35 cases) and a control group (35 cases, 3 cases dropped off). Both groups were treated with rhinocort, one spray on each side of the nostril (approximately 64 µg each spray), once in the morning and once in the evening, for 4 weeks. On the basis of the above treatment, the observation group was treated with herb-separated moxibustion at Shenshu (BL 23), Feishu (BL 13), Zhiyang (GV 9), Dazhui (GV 14), 3 moxibustions per acupoint, a single treatment lasting about 30 min. This treatment was given once every other day, 3 times every week, and totally continuous 4 weeks. The changes of AR symptom visual analogue scale (VAS) scores were observed before and after treatment and at 3 months follow-up after treatment. The heat variation (temperature, range) on projection areas of the nose, lungs, large intestine and kidneys of the two groups' patients before and after treatment were detected by the infrared thermal imaging diagnostic system, and the correlation between the VAS scores and nasal temperature before and after treatment was analyzed. The clinical effects of both groups were evaluated according to the VAS score. RESULTS: The total effective rate in the observation group after treatment was 85.7% (30/35), which was higher than 71.9% in the control group (23/32, P<0.05). After treatment and at follow-up, the VAS scores of both groups were lower than those before treatment (P<0.05), and the VAS score of the observation group was lower than that of the control group at follow-up (P<0.05). After treatment, the nasal temperature, pulmonary range, large intestinal range and renal range of the observation group were all lower than those before treatment (P<0.05), the nasal temperature and nasal range of the control group were lower than before treatment (P<0.05), and the reduction of nasal temperature, nasal range and renal range in the observation group was greater than that of the control group (P<0.05). Before and after treatment, there was a correlation between VAS score and nasal temperature (P<0.05). CONCLUSION: The herb-separated moxibustion combining western medication has a better effect and long-term effect than western medication alone for moderate to severe persistent AR, which can improve heat variation on projected areas of the nose, lung, large intestine and kidney of patients. In addition, nasal temperature can reflect the severity of the symptoms of patients with moderate to severe persistent AR, or it can be used as a secondary indicator to evaluate condition of AR.


Assuntos
Terapia por Acupuntura , Moxibustão , Rinite Alérgica/terapia , Pontos de Acupuntura , Budesonida/uso terapêutico , Humanos , Deficiência da Energia Yang
7.
Clin Chim Acta ; 508: 161-169, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32417211

RESUMO

BACKGROUND: Obstructive sleep apnea (OSA) is the most common type of sleep breathing disorder and is characterized by chronic intermittent hypoxia, which could cause inflammation and nuclear factor kappa B (NF-KB)-dependent inflammatory pathways activation. Circulating APRIL (a proliferation-inducing ligand) play an important role in promoting inflammation and NF-KB-dependent inflammatory pathways activation. We explored the role of APRIL as a potential mechanism of inflammation in OSA patients. METHODS: After detailed sleep evaluated, venous blood and demographic data were collected from 155 subjects with varying severity of OSA and 52 control subjects. Plasma levels of APRIL were measured by human Magnetic Luminex assay. RESULTS: Plasma APRIL levels were significantly higher in OSA subjects compared with control subjects. Categorization of the OSA subjects into mild, moderate, and severe OSA subgroups found that plasma levels of APRIL increased with the severity of OSA. After adjusting confounding factors, found that increased plasma APRIL levels were conferred a higher odds ratio of OSA. Moreover, plasma APRIL levels were positively associated with the apnea-hypopnea index, which represents the severity of OSA. Furthermore, plasma APRIL showed higher discriminatory accuracy in predicting the presence of OSA. CONCLUSIONS: Plasma APRIL levels were significantly associated with the occurrence of OSA and its severity. APRIL could be a plasma biomarker with a positive diagnostic value for inflammation and NF-KB-dependent inflammatory pathways activation in subjects with OSA. TRIAL REGISTRATION: The project was approved by the Chinese Clinical Trial Registry (No. ChiCTRROC-17011027).


Assuntos
Apneia Obstrutiva do Sono , Membro 13 da Superfamília de Ligantes de Fatores de Necrose Tumoral , Adulto , Biomarcadores , China , Humanos
8.
Zhen Ci Yan Jiu ; 45(1): 46-50, 2020 Jan 25.
Artigo em Chinês | MEDLINE | ID: mdl-32144908

RESUMO

OBJECTIVE: To observe the clinical effect of herbal cake-partitioned moxibustion combined with Rhinocort spray in the treatment of symptoms, sleep quality and daily life quality of patients with moderate-severe allergic rhinitis(AR).. METHODS: A total of 67 patients with persistent moderate-severe AR were recruited in the present study and randomized into a treatment group (n=35) and a control group (n=32). The patients in the treatment group were treated by herbal cake-partitioned moxibustion (applied to Dazhui [GV14], and bilateral Feishu [BL13], Shenshu [BL23] and Zhiyang [GV9], 3 moxa-cones/time, once every other day) plus Rhinocort spray (once in the morning and evening separately, 256 µg/d), and patients in the control group treated by Rhinocort spray alone (the same to that mentioned above). All the treatments were given for 4 weeks. The therapeutic effect was evaluated with reference to the "Principles and Recommended Schemes for Diagnosis and Treatment of AR" formulated by Otolaryngology Branch of Chinese Medical Association before and after the treatment. The severity of symptoms of AR was assessed by using visual analogue scale (VAS), the life quality of nasal conjunctivitis assessed using "Rhino-conjunctivitis Quality of Life Questionnaire (RQLQ)", and the sleep quality assessed using "Pittsburgh Sleep Quality Index (PSQI)" before and after the treatment, followed by 3 months' follow-up survey. RESULTS: After the treatment, the VAS and RQLQ scores in both groups and PSQI of the treatment group were significantly decreased in comparison with their own base-line levels of pre-treatment in each group (P<0.05). The RQLQ and PSQI in the treatment group were substantially lower than those in the control group (P<0.05). No marked difference was found between the two groups in VAS(P>0.05). Follow-up survey showed that the VAS and RQLQ scores in both groups and PSQI of the treatment group were still significantly lower than those of pre-treatment in each group(P<0.05), and the VAS, RQLQ and PSQI scores of the treatment group were significantly lower than those of the control group(P<0.05). After 4 weeks' treatment, of the 32 and 35 AR patients in the control and treatment groups, 7 and 16 experienced marked improvement, 16 and 14 were effective, and 9 and 5 failed, with the effective rate being 71.9% and 85.7%, respectively. The effective rate of the treatment group was significantly superior to that of the control group (P<0.05). CONCLUSION: Herbal cake-partitioned moxibustion combined with Rhinocort spray has a good therapeutic effect in improving symptoms, sleep and quality of life in patients with persistent moderate-severe AR, which is obviously superior to that of Rhinocort spray alone in improving sleep and quality of life.


Assuntos
Moxibustão , Rinite Alérgica , Pontos de Acupuntura , Budesonida , Humanos , Qualidade de Vida , Rinite Alérgica/terapia
9.
Trials ; 20(1): 372, 2019 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-31221225

RESUMO

BACKGROUND: Patients with moderate and severe persistent allergic rhinitis (AR) have long-term physical and mental stress, leading to dysfunction of the hypothalamus-pituitary-adrenal (HPA) axis, which results in recurrence of AR. Previous research has proved acupuncture can regulate the function of the neuron-endocrine-immune system and contribute to improving the quality of life of patients with AR. This research aims to investigate the mechanism of acupuncture on the HPA axis in patients with moderate or severe persistent AR. METHODS/DESIGN: This randomized controlled trial aims to study the impact of acupuncture on the HPA axis of patients with moderate and severe AR. This research also aims to compare the curative effects of different treatments in three groups of patients: those receiving western medicine, western medicine and conventional acupuncture, or western medicine and mind-regulating acupuncture. We will study the therapeutic effect of acupuncture and the correlation between the changes of therapeutic indexes and experimental indexes after the treatments. Therapeutic indexes include the Visual Analog Scale (VAS) of nasal symptoms and the Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) for AR patients; experimental indexes include corticotropin releasing hormone (CRH), adreno-corticotropic hormone (ACTH), cortisol (CORT), interleukin 4 (IL-4), and interferon-γ (IFN-γ). DISCUSSION: The results of this trial will provide evidence for the influence of chronic, long-term, repeated stimulation in patients with moderate and severe persistent AR and the impact of acupuncture on the HPA axis of these patients. TRIAL REGISTRATION: Acupuncture-Moxibustion Clinical Trial Registry, AMCTR-IOR-16000009 . Registered on 22 August 2016.


Assuntos
Terapia por Acupuntura , Sistema Hipotálamo-Hipofisário/fisiologia , Sistema Hipófise-Suprarrenal/fisiologia , Ensaios Clínicos Controlados Aleatórios como Assunto , Rinite Alérgica/terapia , Terapia por Acupuntura/efeitos adversos , Adolescente , Hormônio Adrenocorticotrópico/sangue , Adulto , Humanos , Interferon gama/sangue , Pessoa de Meia-Idade , Qualidade de Vida , Projetos de Pesquisa , Rinite Alérgica/psicologia , Adulto Jovem
10.
Rev. bras. anestesiol ; 69(2): 160-167, Mar.-Apr. 2019. graf
Artigo em Inglês | LILACS | ID: biblio-1003397

RESUMO

Abstract Background and objectives: Dexmedetomidine has demonstrated protective effects against lung injury in vitro. Here, we investigated whether dexmedetomidine preconditioning protected against lung injury in hemorrhagic shock rats. Methods: Male Sprague-Dawley rats were randomly divided into four groups (n = 8): control group, hemorrhagic shock group, 5 ug.kg-1 dexmedetomidine (DEX1) group, and 10 ug.kg-1 dexmedetomidine (DEX2) group. Saline or dexmedetomidine were administered over 20 min. 30 min after injection, hemorrhage was initiated in the hemorrhagic shock, DEX1 and DEX2 group. Four hours after resuscitation, protein and cellular content in bronchoalveolar lavage fluid, and the lung histopathology were measured. The malondialdehyde, superoxide dismutase, Bcl-2, Bax and caspase-3 were also tested in the lung tissue. Results: Compare with hemorrhagic shock group, 5 ug.kg-1 dexmedetomidine pretreatment reduced the apoptosis (2.25 ± 0.24 vs. 4.12 ± 0.42%, p < 0.05), histological score (1.06 ± 0.12 vs. 1.68 ± 0.15, p < 0.05) and protein (1.92 ± 0.38 vs. 3.95 ± 0.42 mg.mL-1, p < 0.05) and WBC (0.42 ± 0.11 vs. 0.92 ± 0.13 × 109/L, p < 0.05) in bronchoalveolar lavage fluid. Which is correlated with increased superoxide dismutase activity (8.35 ± 0.68 vs. 4.73 ± 0.44 U.mg-1 protein, p < 0.05) and decreased malondialdehyde (2.18 ± 0.19 vs. 3.28 ± 0.27 nmoL.mg-1 protein, p < 0.05). Dexmedetomidine preconditioning also increased the Bcl-2 level (0.55 ± 0.04 vs. 0.34 ± 0.05, p < 0.05) and decreased the level of Bax (0.46 ± 0.03 vs. 0.68 ± 0.04, p < 0.05), caspase-3 (0.49 ± 0.03 vs. 0.69 ± 0.04, p < 0.05). However, we did not observe any difference between the DEX1 and DEX2 groups for these (p > 0.05). Conclusion: Dexmedetomidine preconditioning has a protective effect against lung injury caused by hemorrhagic shock in rats. The potential mechanisms involved are the inhibition of cell death and improvement of antioxidation. But did not show a dose-dependent effect.


Resumo Justificativa e objetivos: Dexmedetomidina demonstrou efeitos protetores contra a lesão pulmonar in vitro. Neste estudo, investigamos se o pré-condicionamento com dexmedetomidina protege contra a lesão pulmonar em ratos com choque hemorrágico. Métodos: Ratos machos, Sprague-Dawley, foram aleatoriamente divididos em quatro grupos (n = 8): grupo controle, grupo com choque hemorrágico, grupo com 5 µg.kg-1 de dexmedetomidina (DEX1) e grupo com 10 µg.kg-1 de dexmedetomidina (DEX2). Solução salina ou dexmedetomidina foi administrada durante 20 minutos. Trinta minutos após a injeção, a hemorragia foi iniciada nos grupos choque hemorrágico, DEX1 e DEX2. Quatro horas após a ressuscitação, a proteína e o conteúdo celular no lavado broncoalveolar e a histopatologia pulmonar foram medidos. Malondialdeído, superóxido dismutase, Bcl-2, Bax e caspase-3 também foram testados no tecido pulmonar. Resultados: Na comparação com o grupo choque hemorrágico, o pré-tratamento com 5 ug.kg-1 de dexmedetomidina reduziu a apoptose (2,25 ± 0,24 vs. 4,12 ± 0,42%, p < 0,05), escore histológico (1,06 ± 0,12 vs. 1,68 ± 0,15, p < 0,05) e proteína (1,92 ± 0,38 vs. 3,95 ± 0,42 mg.mL-1, p < 0,05) e leucócitos (0,42 ± 0,11 vs. 0,92 ± 0,13 × 109/L, p < 0,05) no lavado broncoalveolar; o que está correlacionado com o aumento da atividade da superóxido dismutase (8,35 ± 0,68 vs. 4,73 ± 0,44 U.mg-1 de proteína, p < 0,05) e diminuição do malondialdeído (2,18 ± 0,19 vs. 3,28 ± 0,27 nmoL.mg-1 de proteína, p < 0,05). O pré-condicionamento com dexmedetomidina também aumentou o nível de Bcl-2 (0,55 ± 0,04 vs. 0,34 ± 0,05, p < 0,05) e diminuiu o nível de Bax (0,46 ± 0,03 vs. 0,68 ± 0,04, p < 0,05), caspase-3 (0,49 ± 0,03 vs. 0,69 ± 0,04, p < 0,05). No entanto, não houve diferença entre os grupos DEX1 e DEX2 para essas proteínas (p > 0,05). Conclusão: O pré-condicionamento com dexmedetomidina tem um efeito protetor contra a lesão pulmonar causada por choque hemorrágico em ratos. Os potenciais mecanismos envolvidos são a inibição da morte celular e a melhora da antioxidação. Porém, não mostrou um efeito dose-dependente.


Assuntos
Animais , Masculino , Ratos , Choque Hemorrágico/tratamento farmacológico , Substâncias Protetoras/administração & dosagem , Dexmedetomidina/administração & dosagem , Lesão Pulmonar/prevenção & controle , Ratos , Choque Hemorrágico/complicações , Líquido da Lavagem Broncoalveolar , Ratos Sprague-Dawley , Apoptose/efeitos dos fármacos , Substâncias Protetoras/farmacologia , Dexmedetomidina/farmacologia , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Lesão Pulmonar/etiologia
11.
Cell Death Differ ; 26(11): 2300-2313, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30778200

RESUMO

The transcription factor nuclear factor (erythroid-derived 2)-like 2 (NRF2) is one of the master regulators that control hundreds of genes containing antioxidant response elements (AREs). The NRF2-ARE pathway plays a complex role in colorectal cancer (CRC). NRF2 activity is known to be regulated by KEAP1-CUL3 E3 ligase-mediated ubiquitination, indicating the importance of deubiquitination regulation. However, the deubiquitinase (DUB) of NRF2 remains unknown. Here, by screening a DUB library, we identified DUB3 as a DUB that remarkably stabilized NRF2. Further experiments demonstrated that DUB3 promoted NRF2 stability and transcriptional activity by decreasing the K48-linked ubiquitination of NRF2. Coimmunoprecipitation studies revealed interactions between NRF2 and DUB3, as well as between KEAP1 and DUB3, indicating that NRF2, DUB3, and KEAP1 formed a large functional complex. Importantly, ectopic expression of DUB3 caused NRF2-dependent chemotherapy resistance in colon cancer cell lines. Thus, to the best of our knowledge, our findings are the first to identify DUB3 as a NRF2 DUB and may provide a new strategy against chemotherapy resistance in CRC and other NRF2-related diseases.


Assuntos
Neoplasias Colorretais/patologia , Enzimas Desubiquitinantes/metabolismo , Resistencia a Medicamentos Antineoplásicos/fisiologia , Endopeptidases/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Antineoplásicos Fitogênicos/uso terapêutico , Apoptose/fisiologia , Sistemas CRISPR-Cas/genética , Proliferação de Células/fisiologia , Neoplasias Colorretais/tratamento farmacológico , Células HCT116 , Células HEK293 , Células HT29 , Humanos , Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , Fator 2 Relacionado a NF-E2/genética , Paclitaxel/uso terapêutico , Ativação Transcricional/genética , Ubiquitinação/fisiologia
12.
J Coll Physicians Surg Pak ; 29(1): 4-7, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30630559

RESUMO

OBJECTIVE: To analyse the impact of dezocine-remifentanil intravenous anaesthesia on perioperative signs, serum tumour necrosis factor-α (TNF-α), and interleukin-6 (IL-6) in liver cancer patients undergoing radiofrequency ablation (RFA). STUDY DESIGN: An experimental study. PLACE AND DURATION OF STUDY: Renmin Hospital of Wuhan University, Wuhan, China, from January 2017 to February 2018. METHODOLOGY: Eighty patients with small hepatocellular carcinoma (SHCC) were selected as the research object. They were divided into Group A and Group B with the random number table method, with 40 cases in each group. Group A were given dezocine-remifentanil intravenous anaesthesia and Group B were given midazolam-remifentanil intravenous anaesthesia. Patients' situations in the surgery were compared between the two groups. Changes in heart rate (HR), mean arterial pressure (MAP) and blood oxygen saturation (SpO2) were recorded before the surgery (T0), at 5 minutes after the RFA (T1) and at the end of the RFA (T2). Levels of tumour necrosis factor-α (TNF-α) and interleukin-6 (IL-6) on the 12 day after the RFA were compared between the two groups. RESULTS: The wake-up time in Group A was shorter than Group B (p<0.001), and the VAS pain score in Group A was lower than Group B (p<0.001). At T1, the MAP in Group A was higher than Group B (p<0.001). There was no significant difference in MAP between the two groups at T0 and T2 (p=0.881, 0.696, respectively). At T1 and T2, the HR in Group A was lower than Group B (all p<0.001). There was no significant difference in HR between the two groups at T0 (p=0.684). There was no significant difference in SpO2 between the two groups at T0, T1 and T2 (p=0.654, 0.884 and 0.798, respectively). On the 1st day after the RFA, the level of TNF-α, IL-6 in Group A were lower than those of Group B (all p<0.001). There was no significant difference in the incidence of intraoperative complications between the two groups (p=0.644). CONCLUSION: Compared with midazolam-remifentanil intravenous anaesthesia, the dezocine-remifentanil method has a better analgesic effect, shorter wake-up time, and can effectively regulate the expression of inflammatory cytokines TNF-α and IL-6. However, the effect of remifentanil on the respiratory function is dose-dependent. Therefore, respiratory cycle monitoring and management should be strengthened during the surgery.


Assuntos
Analgésicos Opioides/uso terapêutico , Compostos Bicíclicos Heterocíclicos com Pontes/uso terapêutico , Carcinoma Hepatocelular/cirurgia , Frequência Cardíaca/efeitos dos fármacos , Interleucina-6/sangue , Neoplasias Hepáticas/cirurgia , Ablação por Radiofrequência , Remifentanil/uso terapêutico , Tetra-Hidronaftalenos/uso terapêutico , Fator de Necrose Tumoral alfa/sangue , Adulto , Idoso , Analgésicos Opioides/administração & dosagem , Anestesia Intravenosa/efeitos adversos , Anestesia Intravenosa/métodos , Compostos Bicíclicos Heterocíclicos com Pontes/administração & dosagem , Carcinoma Hepatocelular/sangue , Relação Dose-Resposta a Droga , Feminino , Humanos , Neoplasias Hepáticas/sangue , Masculino , Pessoa de Meia-Idade , Remifentanil/administração & dosagem , Tetra-Hidronaftalenos/administração & dosagem , Resultado do Tratamento
13.
Braz J Anesthesiol ; 69(2): 160-167, 2019.
Artigo em Português | MEDLINE | ID: mdl-30655009

RESUMO

BACKGROUND AND OBJECTIVES: Dexmedetomidine has demonstrated protective effects against lung injury in vitro. Here, we investigated whether dexmedetomidine preconditioning protected against lung injury in hemorrhagic shock rats. METHODS: Male Sprague-Dawley rats were randomly divided into four groups (n=8): control group, hemorrhagic shock group, 5ug.kg-1 dexmedetomidine (DEX1) group, and 10ug.kg-1 dexmedetomidine (DEX2) group. Saline or dexmedetomidine were administered over 20min. 30min after injection, hemorrhage was initiated in the hemorrhagic shock, DEX1 and DEX2 group. Four hours after resuscitation, protein and cellular content in bronchoalveolar lavage fluid, and the lung histopathology were measured. The malondialdehyde, superoxide dismutase, Bcl-2, Bax and caspase-3 were also tested in the lung tissue. RESULTS: Compare with hemorrhagic shock group, 5ug.kg-1 dexmedetomidine pretreatment reduced the apoptosis (2.25±0.24 vs. 4.12±0.42%, p<0.05), histological score (1.06±0.12 vs. 1.68±0.15, p<0.05) and protein (1.92±0.38 vs. 3.95±0.42mg.mL-1, p<0.05) and WBC (0.42±0.11 vs. 0.92±0.13×109/L, p<0.05) in bronchoalveolar lavage fluid. Which is correlated with increased superoxide dismutase activity (8.35±0.68 vs. 4.73±0.44U.mg-1 protein, p<0.05) and decreased malondialdehyde (2.18±0.19 vs. 3.28±0.27nmoL.mg-1 protein, p<0.05). Dexmedetomidine preconditioning also increased the Bcl-2 level (0.55±0.04 vs. 0.34±0.05, p<0.05) and decreased the level of Bax (0.46±0.03 vs. 0.68±0.04, p<0.05), caspase-3 (0.49±0.03 vs. 0.69±0.04, p<0.05). However, we did not observe any difference between the DEX1 and DEX2 groups for these (p>0.05). CONCLUSION: Dexmedetomidine preconditioning has a protective effect against lung injury caused by hemorrhagic shock in rats. The potential mechanisms involved are the inhibition of cell death and improvement of antioxidation. But did not show a dose-dependent effect.


Assuntos
Dexmedetomidina/administração & dosagem , Lesão Pulmonar/prevenção & controle , Substâncias Protetoras/administração & dosagem , Choque Hemorrágico/tratamento farmacológico , Animais , Apoptose/efeitos dos fármacos , Líquido da Lavagem Broncoalveolar , Dexmedetomidina/farmacologia , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Lesão Pulmonar/etiologia , Masculino , Substâncias Protetoras/farmacologia , Ratos , Ratos Sprague-Dawley , Choque Hemorrágico/complicações
14.
Clin Chim Acta ; 490: 39-45, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30562485

RESUMO

BACKGROUND: Obstructive sleep apnea (OSA) was characterized by chronic intermittent hypoxia, which was an independent risk factor for endothelial dysfunction. Circulating TNFRSF11B might play an important role in promoting endothelial cells dysfunction. We explored the role of plasma TNFRSF11B as a potential mechanism of endothelial dysfunction in OSA patients. METHODS: The study population consisted of 120 patients with varying severity of OSA and 40 control subjects. Plasma TNFRSF11B levels were measured using human Magnetic Luminex assay. RESULTS: Our data showed that plasma TNFRSF11B levels were significantly higher in patients with OSA. After adjusting confounding factors, plasma TNFRSF11B levels were independently associated with the presence of OSA (Beta:0.434, 95% CI: 664.096 to 1076.247; P < 0.001) and plasma TNFRSF11B levels were positively associated with the apnea-hypopnea index (Beta:0.486, 95% CI: 0.007 to 0.017; P < 0.001). Furthermore, plasma TNFRSF11B showed higher discriminatory accuracy in predicting the presence of OSA (AUC:0.964). CONCLUSIONS: Plasma TNFRSF11B levels were significantly associated with the presence of OSA and its severity. TNFRSF11B could be a plasma biomarker with a positive diagnostic value for premature vascular endothelial dysfunction in patients with OSA.


Assuntos
Osteoprotegerina/sangue , Apneia Obstrutiva do Sono/sangue , Apneia Obstrutiva do Sono/diagnóstico , Biomarcadores/sangue , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Proteínas de Neoplasias/sangue , Proteoglicanas/sangue
15.
Zhen Ci Yan Jiu ; 43(7): 450-5, 2018 Jul 25.
Artigo em Chinês | MEDLINE | ID: mdl-30094983

RESUMO

OBJECTIVE: To evaluate the clinical effect of herbal cake-partitioned moxibustion combined with medication in the treatment of moderate and severe persistent allergic rhinitis (PAR) patients of spleen deficiency pattern. METHODS: Sixty patients with moderate and severe PAR of spleen deficiency pattern were randomized into medication (Rhinocort) group and herbal cake-partitioned moxibustion combined with medication group (combination group, n=30 cases in each). Medicinal cake-partitioned moxibustion was applied to Yintang (GV 29, for about 20 min), Shenque(CV 8, about 50 min), bilateral Zusanli (ST 36, about 40 min)and Hegu(LI 4, about 40 min)once every other day for successive 8 weeks. All the patients received treatment with Rhinocort nasal spray, 2 jets/day for each nostril (64 µg/jet) for 8 weeks. The patients' conditions (symptoms of nasal sufferings, sleeping, sniffle, eye, emotion, etc.) were assessed by visual analogue scale (VAS) and rhino conjunctivitis quality of life questionnaire (RQLQ, 24 items of 7 aspects, 0-6 points/item), respectively. The spleen deficiency syndrome score was determined according to "Guiding Principles for Clinical Research of New Drugs of Chinese Materia Medica" (2002). The therapeutic effect was assessed by referring to "the Diagnostic and Therapeutic Principles and Recommended Schemes for Allergic Rhinitis" (2004). RESULTS: Following the treatment, the scores of VAS, RQLQ, spleen deficiency syndrome were significantly decreased on the 4thand the 8th week of treatment in both groups in comparison with those of their own individual pre-treatment (P<0.05, P<0.01). Four weeks' follow-up survey showed that the VAS score and RQLQ score of the combination group were obviously lower than those of the medication groups (P<0.05), suggesting a better post-effect of moxibustion. Of the two 30 cases in the medication and combination groups, 9 and 9 experienced marked improvement in their symptoms, 16 and 17 were effective, and 5 and 4 ineffective, with the effective rate being 83.3% and 86.7%, respectively. No significant differences were found between the two groups in the VAS and RQLQ scores on the 4th and 8th week during treatment and in the effective rate (P>0.05). CONCLUSION: Herbal cake-partitioned moxibustion combined with hormone (Rhinocort) nasal spray is effective in relieving symptoms of moderate and severe PAR patients of spleen deficiency syndrome, and has a better post-effect.


Assuntos
Moxibustão , Rinite Alérgica , Pontos de Acupuntura , Budesonida , Humanos , Sprays Nasais , Qualidade de Vida , Rinite Alérgica/terapia , Baço
16.
Sci Rep ; 6: 33204, 2016 09 14.
Artigo em Inglês | MEDLINE | ID: mdl-27625151

RESUMO

A series of novel harmine derivatives bearing a benzylindine substituent in position-1 of ß-carboline ring were synthesized and evaluated as antitumor agents. The N2-benzylated ß-carboline derivatives 3a-g represented the most interesting anticancer activities and compound 3c was found to be the most active agent to diverse cancer cell lines such as gastric carcinoma, melanoma and colorectal cancer. Notably, compound 3c showed low toxicity to normal cells. The treatment significantly induced cell apoptosis. Mechanistically, PI3K/AKT signaling pathway mediated compound 3c-induced apoptosis. Compound 3c inhibited phosphorylation of AKT and promoted the production of reactive oxygen species (ROS). The ROS scavenger, LNAC and GSH, could disturb the effect of compound 3c induced apoptosis and PI3K activity inhibitor LY294002 synergistically enhanced compound 3c efficacy. Moreover, the results from nude mice xenograft model showed that compound 3c treatment effectively inhibited tumor growth and decreased tumor weight. Collectively, our results demonstrated that compound 3c exerts apoptotic effect in cancer cells via suppression of phosphorylated AKT and evocation of ROS generation, which suggested that compound 3c might be served as a promising therapeutic agent for cancer treatment.


Assuntos
Antineoplásicos , Harmina , Neoplasias/tratamento farmacológico , Células A549 , Animais , Antineoplásicos/síntese química , Antineoplásicos/química , Antineoplásicos/farmacologia , Cromonas , Harmina/análogos & derivados , Harmina/síntese química , Harmina/química , Harmina/farmacologia , Células HeLa , Células Hep G2 , Humanos , Camundongos , Camundongos Nus , Morfolinas , Neoplasias/metabolismo , Neoplasias/patologia , Fosfatidilinositol 3-Quinases/metabolismo , Inibidores de Fosfoinositídeo-3 Quinase , Proteínas Proto-Oncogênicas c-akt/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto
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