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Increasing evidence highlights the role of bacteria in promoting tumorigenesis. The underlying mechanisms may be diverse and remain poorly understood. Here, we report that Salmonella infection leads to extensive de/acetylation changes in host cell proteins. The acetylation of mammalian cell division cycle 42 (CDC42), a member of the Rho family of GTPases involved in many crucial signaling pathways in cancer cells, is drastically reduced after bacterial infection. CDC42 is deacetylated by SIRT2 and acetylated by p300/CBP. Non-acetylated CDC42 at lysine 153 shows an impaired binding of its downstream effector PAK4 and an attenuated phosphorylation of p38 and JNK, consequently reduces cell apoptosis. The reduction in K153 acetylation also enhances the migration and invasion ability of colon cancer cells. The low level of K153 acetylation in patients with colorectal cancer (CRC) predicts a poor prognosis. Taken together, our findings suggest a new mechanism of bacterial infection-induced promotion of colorectal tumorigenesis by modulation of the CDC42-PAK axis through manipulation of CDC42 acetylation.
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Neoplasias Colorretais , Infecções por Salmonella , Proteína cdc42 de Ligação ao GTP , Humanos , Acetilação , Carcinogênese , Proteína cdc42 de Ligação ao GTP/metabolismo , Transformação Celular Neoplásica , Quinases Ativadas por p21/metabolismo , Transdução de SinaisRESUMO
Background: In patients with chronic aortic regurgitation (AR), the left ventricle (LV) develops compensatory mechanisms to sustain its function. LV global longitudinal strain (GLS) is a key means to detect subclinical LV dysfunction, even when LV ejection fraction (LVEF) remains within the normal range. Compared to GLS, Tissue motion annular displacement (TMAD) is a simpler strain-based method to assess LV systolic function. This study investigated the correlation among TMAD parameters, LVEF, and GLS, and determined the diagnostic value and threshold of TMAD parameters for left ventricular systolic dysfunction. Methods: A prospective study was conducted at a single center. The case and control groups consisted of patients with chronic severe AR and healthy volunteers, respectively. Speckle-tracking echocardiography (STE) was used to assess the GLS and TMAD parameters in the apical 4-chamber and apical 2-chamber. Subsets of participants were analyzed for inter- and intra-observer variability and analysis time. A correlation analysis was performed among the TMAD parameters, LVEF, and GLS. Receiver operating characteristic curves and the area under the curves (AUCs) were used to evaluate the predictive value of the TMAD parameters for LVEF <50% and GLS > -18%. Results: This study involved 96 patients with severe chronic AR and 45 healthy volunteers. Compared to GLS, TMAD demonstrated superior intra- and inter-observer consistency and shorter average analysis time. Biplane global Midpt% showed the highest correlation with GLS and LVEF among all the TMAD parameters, with r values of 0.81 and 0.74, respectively. Furthermore, global Midpt% had AUCs of 0.89 and 0.92 for predicting LVEF< 50% and GLS > -18%, respectively. Conclusion: The TMAD global Midpt% has the potential to replace GLS in clinical practice and find wide applications.
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AIM: Ibuprofen is the most commonly used analgesic. CYP polymorphisms are mainly responsible for the differences in drug metabolism among individuals. Variations in the ability of populations to metabolize ibuprofen can lead to drug exposure events. The aim of this study was to evaluate the effects of CYP2C19 and CYP3A4 polymorphisms on ibuprofen metabolism in a Chinese population. METHODS: First, 31 CYP2C19 and 12 CYP3A4 microsomal enzymes were identified using an insect expression system. Then, variants were evaluated using a mature incubation system. Moreover, ibuprofen metabolite content was determined via ultra-performance liquid chromatography-tandem mass spectrometry analysis. Finally, kinetic parameters of CYP2C19 and CYP3A4 genotypes were determined via Michaelis-Menten curve fitting. RESULTS: Most variants exhibited significantly altered intrinsic clearance compared to the wild type. In the CYP2C19 metabolic pathway, seven variants exhibited no significant alterations in intrinsic clearance (CLint), six variants exhibited significantly high CLint (121-291%), and the remaining 15 variants exhibited substantially reduced CLint (1-71%). In the CYP3A4 metabolic pathway, CYP3A4*30 was not detected in the metabolite content due to the absence of activity, and 10 variants exhibited significantly reduced CLint. CONCLUSION: To the best of our knowledge, this is the first study to assess the kinetic characteristics of 31 CYP2C19 and 12 CYP3A4 genotypes on ibuprofen metabolism. However, further studies are needed on poor metabolizers as they are more susceptible to drug exposure. Our findings suggest that the kinetic characteristics in combination with artificial intelligence to predict the toxicity of ibuprofen and reduce any adverse drug reactions.
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Citocromo P-450 CYP3A , Ibuprofeno , Humanos , Citocromo P-450 CYP3A/genética , Citocromo P-450 CYP3A/metabolismo , Citocromo P-450 CYP2C19/genética , Inteligência Artificial , Polimorfismo GenéticoRESUMO
Background: Chronic aortic regurgitation (AR) is a common valvular disease characterized by an overload of left ventricular volume and pressure. Accurate assessment of the heart from all angles is crucial for effective clinical management and prognostic evaluation of AR patients. As an advanced imaging technique, cardiac magnetic resonance (CMR) has become the gold standard for assessing cardiac volume and function. Accordingly, this study aimed to evaluate the prognostic value of CMR in chronic AR. Methods: EMBASE, Cochrane Library, PubMed, and Web of Science were searched for clinical studies published between inception and July 19, 2022. Only studies that used CMR to assess patients with chronic isolated AR and provided prognostic data were included. Results: For our analysis, 11 studies, which involved 1702 subjects and follow-up periods of 0.6-9.7 years, were eligible. We identified 13 CMR-related parameters associated with AR prognosis. With aortic valve surgery as the outcome, we estimated the pooled hazard ratios (HRs) for four of these parameters: aortic regurgitation fraction (ARF), aortic regurgitation volume (ARV), left ventricle end-diastolic volume (LVEDV), and LV end-systolic volume (LVESV). The pooled HR for ARF was found to be 4.31 (95% confidence interval [CI]: 1.12-16.59, p = 0.034), while that for ARV was 3.88 (95% CI: 0.71-21.04, p = 0.116). Additionally, the combined HRs of LVEDV and LVESV were estimated to be 2.20 (95% CI: 1.04-4.67, p = 0.039) and 3.14 (95% CI: 1.22-8.07, p = 0.018), respectively. Conclusions: The assessment of ARF, LVEDV, and LVESV via CMR has significant prognostic value in predicting the prognosis of AR patients with aortic valve surgery as an endpoint. It is recommended to consider using multi-parameter CMR in the clinical management of AR patients for timely interventions and effective prognostic evaluation.
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BACKGROUND: Preclinical studies showed that HC-1119, a deuterated version of enzalutamide, could competitively inhibit androgen binding to androgen receptor by blocking the transmission of androgen receptor signaling pathway as enzalutamide, inducing apoptosis of prostate cancer cells and reducing the proliferation of prostate cancer cells. Animal pharmacokinetic studies also show that deuterization of enzalutamide as HC-1119 could retain the basic properties of mother drug, increases the stability of compounds to metabolic enzymes and the drug exposure in vivo, prolong the half-life and reduce the production of metabolites, which may lead to a better efficacy and safety of HC-1119 compared with enzalutamide. METHODS: To evaluate the pharmacokinetics and safety of HC-1119 and the effects of food on pharmacokinetics in healthy adult Chinese men after single-dose administration of HC-1119. A total of 47 Chinese healthy adult male subjects received HC-1119 soft capsule at a single oral dose of 40, 80, or 160 mg followed on fasting or 160 mg after high-fat meal respectively. HC-1119 prototype and its metabolites M1 and M2 in plasma were collected individually in a total 23 time points. Pharmacokinetics were determined by sensitive LC/MS/MS for dose-proportionality study. RESULTS: In subjects taking HC-1119 soft capsules on fasting, Cmax of HC-1119 prototype increased dose-dependently. Either Cmax and AUC0-∞ of M1 or Cmax of M2 showed statistically significant difference. Dose-proportionality evaluation showed linear pharmacokinetic characteristics in Cmax of HC-1119 prototype, Cmax and AUC0-∞ of M2 in dose range of 40-160 mg. Cmax of HC-1119 was significantly different between the two groups as 160 mg HC-1119 on fasting or after a high-fat diet respectively, while the other parameter were not. HC-1119 and its metabolites M1 and M2 showed a linear dynamic trend. CONCLUSIONS: HC-1119 is expected to have lower clinical dose than the similar drug enzalutamide. The absorption of HC-1119 and the main pharmacokinetic parameters of HC-1119 and its metabolites M1 and M2 were not affected by high-fat diet. The clinical application of HC-1119 soft capsule in the later stage can be recommended for both fasting and postprandial. The safety and tolerance were good in this population.
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Benzamidas , Proliferação de Células/efeitos dos fármacos , Estabilidade de Medicamentos , Interações Alimento-Droga , Nitrilas , Feniltioidantoína , Neoplasias da Próstata , Receptores Androgênicos/metabolismo , Administração Oral , Adulto , Antineoplásicos/administração & dosagem , Antineoplásicos/efeitos adversos , Antineoplásicos/farmacocinética , Benzamidas/administração & dosagem , Benzamidas/efeitos adversos , Benzamidas/farmacocinética , Biomarcadores Farmacológicos/análise , Cápsulas , China , Relação Dose-Resposta a Droga , Meia-Vida , Voluntários Saudáveis , Humanos , Masculino , Nitrilas/administração & dosagem , Nitrilas/efeitos adversos , Nitrilas/farmacocinética , Feniltioidantoína/administração & dosagem , Feniltioidantoína/efeitos adversos , Feniltioidantoína/farmacocinética , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/patologia , Transdução de Sinais/efeitos dos fármacosRESUMO
Pulmonary fibrosis is a progressive interstitial lung disease with poor prognosis. Anemarrhenae Rhizoma is a traditional Chinese herbal medicine and has been applied in clinical practice for a long history. Recently, components of Anemarrhenae Rhizoma were reported to possess anti-inflammatory and immunomodulatory features; however, the effect of them on pulmonary fibrosis remains unknown. In this study, we explored the therapeutic effect of total extract of Anemarrhenae Rhizoma (TEAR) on bleomycin-induced pulmonary fibrosis. Pulmonary fibrosis rat model was established by a single intratracheal instillation of bleomycin, three doses of TEAR were intragastrically administered for consecutive 28 days. Subsequent to sacrificing of rats, pulmonary fibrosis was observed in rats treated with bleomycin, but administration of TEAR attenuated lung fibrosis, as evidenced by the improved lung histopathological damage and decreased weight loss and lung index. Moreover, TEAR treatment inhibited the inflammatory response in lung fibrosis, which was shown by the reduced nitrogen oxide level and myeloperoxidase activity. Furthermore, TEAR modulated the redox balance in lung tissue by alleviated lipid peroxidation and enhanced enzymatic antioxidants activity. Meanwhile, TEAR protected the rats from fibrosis in a dose-dependent manner, and the anti-fibrotic activity of TEAR may be related to the modulation of TGF-ß1/Smad signaling pathway. Collectively, TEAR alleviates bleomycin-induced pulmonary fibrosis, indicating perspectives for development of a potential agent for lung fibrosis therapy.
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Anemarrhena/química , Medicamentos de Ervas Chinesas/uso terapêutico , Flavonoides/uso terapêutico , Fibrose Pulmonar/tratamento farmacológico , Rizoma/química , Saponinas/uso terapêutico , Animais , Bleomicina , Relação Dose-Resposta a Droga , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/isolamento & purificação , Flavonoides/química , Flavonoides/isolamento & purificação , Masculino , Medicina Tradicional Chinesa , Estrutura Molecular , Fibrose Pulmonar/induzido quimicamente , Fibrose Pulmonar/patologia , Ratos , Ratos Sprague-Dawley , Saponinas/química , Saponinas/isolamento & purificação , Relação Estrutura-AtividadeRESUMO
Long non-coding RNAs (lncRNAs) play crucial roles in diverse biological processes and human complex diseases. Distinguishing lncRNAs from protein-coding transcripts is a fundamental step for analyzing the lncRNA functional mechanism. However, the experimental identification of lncRNAs is expensive and time-consuming. In this study, we presented an alignment-free multimodal deep learning framework (namely lncRNA_Mdeep) to distinguish lncRNAs from protein-coding transcripts. LncRNA_Mdeep incorporated three different input modalities, then a multimodal deep learning framework was built for learning the high-level abstract representations and predicting the probability whether a transcript was lncRNA or not. LncRNA_Mdeep achieved 98.73% prediction accuracy in a 10-fold cross-validation test on humans. Compared with other eight state-of-the-art methods, lncRNA_Mdeep showed 93.12% prediction accuracy independent test on humans, which was 0.94%~15.41% higher than that of other eight methods. In addition, the results on 11 cross-species datasets showed that lncRNA_Mdeep was a powerful predictor for predicting lncRNAs.
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Bases de Dados de Ácidos Nucleicos , Aprendizado Profundo , RNA Longo não Codificante/genética , Software , Animais , Humanos , CamundongosRESUMO
BACKGROUND: The association of high-sensitivity C-reactive protein (hsCRP) with mortality is controversial. We aimed to investigate the associations of hsCRP concentrations with the risks of all-cause and cause-specific mortality and identify potential modifying factors affecting these associations among middle-aged and elderly individuals. METHODS: This community-based prospective cohort study included 14,220 participants aged 50+ years (mean age: 64.9 years) from the Health and Retirement Study. Cox proportional hazard models were employed to estimate the associations between the hsCRP concentrations and the risk of all-cause and cause-specific mortality with adjustment for sociodemographic and lifestyle factors, self-reported medical history, and other potential confounders. RESULTS: In total, 1730 all-cause deaths were recorded, including 725 cardiovascular- and 417 cancer-related deaths, after an 80,572 person-year follow-up (median: 6.4 years; range: 3.6-8.1 years). The comparisons of the groups with the highest (quartile 4) and lowest (quartile 1) hsCRP concentrations revealed that the adjusted hazard ratios and 95% confidence intervals were 1.50 (1.31-1.72) for all-cause mortality, 1.44 (1.13-1.82) for cardiovascular mortality, and 1.67 (1.23-2.26) for cancer mortality. The associations between high hsCRP concentrations and the risks of all-cause, cardiovascular, and cancer mortality were similar in the men and women (P for interaction > 0.05). CONCLUSIONS: Among middle-aged and older individuals, elevated hsCRP concentration could increase the risk of all-cause, cardiovascular, and cancer mortality in men and women.
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Long microchannels with thin walls, small width, and nanoholes or irregular shaped microgaps, which are similar to capillaries or cancerous vessels, are urgently needed to simulate the physiological activities in human body. However, the fabrication of such channels remains challenging. Here, microchannels with designable holes are manufactured by combining laser printing with line-contact capillary-force assembly. Two microwalls are first printed by femtosecond laser direct-writing, and subsequently driven to collapse into a channel by the capillary force that arises in the evaporation of developer. The channel can remain stable in solvent due to the enhanced Van der Waals' force caused by the line-contact of microwalls. Microchannels with controllable nanoholes and almost arbitrary patterns can be fabricated without any bonding or multistep processes. As-prepared microchannels, with wall thicknesses less than 1 µm, widths less than 3 µm, lengths more than 1 mm, are comparable with human capillaries. In addition, the prepared channels also exhibit the ability to steer the flow of liquid without any external pump.
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PURPOSE: Obstructive sleep apnea hypopnea syndrome (OSAHS) is an independent risk factor for development of hypertension. Epidemiological surveys have found that risk of cardiovascular diseases increased in postmenopausal women. However, it is not well known about the profiles of hypertension of women with OSAHS in their different reproductive stages. This study aimed to investigate the difference of blood pressure profile between pre and postmenopausal women with OSAHS. METHODS: Women who were tested by polysomnography (PSG) (n = 207) in Ruijin Hospital were recruited in the study. The subjects were divided into two groups of premenopausal women (24 with and 30 without OSAHS), and two groups of postmenopausal women (116 with and 37 without OSAHS). Among the groups, the differences of demographic and PSG variables were compared. The factors influencing blood pressure were further studied. RESULTS: The prevalence of hypertension (56.9 %) in postmenopausal OSAHS patients was higher than the other three groups. Among OSAHS patients, both average systolic blood pressure (SBP) and diastolic blood pressure (DBP) of postmenopausal women were higher than those of premenopausal ones [(129.9 ± 16.16 mmHg vs. 123.7 ± 18.89), (84.96 ± 9.88 mmHg vs. 78.81 ± 10.34), P = 0.05, P < 0.01, respectively], with the elevation of DBP being more pronounced. For premenopausal women, body mass index (BMI) was the only factor affecting blood pressure (p < 0.05); in postmenopausal women, BMI was a factor affecting SBP, while BMI and apnea hypopnea index (AHI) affecting DBP (P < 0.05). CONCLUSION: Blood pressure profile of postmenopausal women with OSAHS was affected by both BMI and AHI. But those of premenopausal ones were predominantly related to BMI.
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Pressão Sanguínea/fisiologia , Pós-Menopausa/fisiologia , Pré-Menopausa/fisiologia , Apneia Obstrutiva do Sono/fisiopatologia , Adulto , Índice de Massa Corporal , Estudos Transversais , Feminino , Humanos , Hipertensão/diagnóstico , Hipertensão/epidemiologia , Hipertensão/fisiopatologia , Pessoa de Meia-Idade , Polissonografia , Fatores de Risco , Apneia Obstrutiva do Sono/diagnóstico , Apneia Obstrutiva do Sono/epidemiologia , Estatística como AssuntoRESUMO
BACKGROUND: Intranasal dexmedetomidine has been used for sedation in children undergoing nonpainful procedures. OBJECTIVE: The aim of this study was to determine the success rate of intranasal dexmedetomidine sedation for children undergoing transthoracic echocardiography examination. METHODS: This was a prospective observational study of 115 children under the age of 3 years undergoing echocardiography examination under sedation with intranasal dexmedetomidine at 3 mcg·kg(-1). RESULTS: Of the 115 children, 100 (87%) had satisfactory sedation with intranasal dexmedetomidine. The mean onset time was 16.7 ± 7 min (range 5-50 min). The mean wake up time was 44.3 ± 15.1 min (range 12-123 min). The wake up time was significantly correlated with duration of procedure with R = 0.540 (P < 0.001). Aside from one patient who required oxygen supplementation, all children in this investigation had an acceptable heart rate and blood pressure and required no medical intervention. CONCLUSION: Sedation by intranasal dexmedetomidine at 3 mcg·kg(-1) is associated with acceptable success rate in children undergoing echocardiography with no adverse events in this cohort.
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Dexmedetomidina/administração & dosagem , Ecocardiografia , Hipnóticos e Sedativos/administração & dosagem , Administração Intranasal , Período de Recuperação da Anestesia , Pressão Sanguínea/efeitos dos fármacos , Pré-Escolar , Feminino , Frequência Cardíaca/efeitos dos fármacos , Humanos , Lactente , Masculino , Estudos Prospectivos , Fatores de TempoRESUMO
OBJECTIVE: To develop a rapid analytical method for the determination of genome size of Atractylodes lancea by flow cytometry (FCM), and to estimate genome size of five typical plant types of cultivated Atractylodes lancea. METHODS: The fresh young leaves of Atractylodes lancea were used for the preparation of nuclear suspension with two-step protocol. After staining with propidium iodide, the mixture was analyzed by flow cytometry. Zea mays 'CE-777' or Vicafaba 'Inorce' was used for DNA reference standard. RESULTS: The flow cytometric method was developed after screening internal standard, optimizing sample preparation and FCM setups. The narrow leaf type of Atractylodes lancea got the biggest genome size, whereas the smallest one was fasciated stem type. It was suggested that parted leaf might be caused by genome size decrease. CONCLUSION: The methodology presented in this study is suitable for measuring the genome size of Atractylodes lancea. This study also provides useful information on population variation, evaluation of germplasm resources, and breeding of Atractylodes lancea.
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Atractylodes/genética , Citometria de Fluxo , Tamanho do Genoma , DNA de Plantas , Folhas de Planta , Coloração e RotulagemRESUMO
Recent studies showed that hydrogen can be used as an effective radioprotective agent through scavenging free radicals. This study was undertaken to evaluate the radioprotective effects of hydrogen on immune system in mice. H(2) was dissolved in physiological saline using an apparatus produced by our department. Spleen index and histological analysis were used to evaluate the splenic structural damage. Spleen superoxide dismutase, GSH, MDA were measured to appraise the antioxidant capacity and a DCF assay for the measurement of radical oxygen species. Cell apoptosis was evaluated by an Annexin V-FITC and propidium iodide staining method as well as the apoptotic proteins such as Bcl-2, Bax, caspase-3 and c-caspase-3. CD4+ and CD8+ T cells subtypes were detected by flow cytometry with FITC-labelled antimouse CD4 and PE antimouse CD8 staining. Real-time PCR was utilized to determine the CD4+ T cell subtypes and related cytokines. Our study demonstrated that pre-treatment with H(2) could increase the spleen index and attenuate the radiation damage on splenic structure. Radical oxygen species level was also reduced by H(2) treatment. H(2) also inhibited radiation-induced apoptosis in splenocytes and down-regulated pro-apoptotic proteins in living mice. Radiation-induced imbalance of T cells was attenuated by H(2). Finally, we found that H(2) could regulate the polarization of CD4+ T cells and the level of related cytokines. This study suggests H(2) as an effective radioprotective agent on immune system by scavenging reactive oxygen species.
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Hidrogênio/farmacologia , Substâncias Protetoras/uso terapêutico , Lesões por Radiação/tratamento farmacológico , Lesões por Radiação/imunologia , Cloreto de Sódio/uso terapêutico , Animais , Antioxidantes/farmacologia , Apoptose/efeitos dos fármacos , Citocinas/genética , Citocinas/metabolismo , Raios gama , Masculino , Camundongos Endogâmicos C57BL , Estresse Oxidativo/efeitos dos fármacos , Estresse Oxidativo/efeitos da radiação , Substâncias Protetoras/farmacologia , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Lesões por Radiação/fisiopatologia , Reação em Cadeia da Polimerase em Tempo Real , Cloreto de Sódio/farmacologia , Baço/efeitos dos fármacos , Baço/patologia , Baço/efeitos da radiação , Linfócitos T/efeitos dos fármacos , Linfócitos T/efeitos da radiaçãoRESUMO
Radiation-induced lung injury (RILI) is a potentially fatal and dose-limiting complication of thoracic radiotherapy. This study was to investigate the protective effects of grape seed pro-anthocyanidins (GSPs), an efficient antioxidant and anti-carcinogenic agent, on RILI. In our study, it was demonstrated that acute and late RILI was ameliorated after GSPs treatment possibly through suppressing TGF-ß1/Smad3/Snail signalling pathway and modulating the levels of cytokines (interferon-γ, IL-4 and IL-13) derived from Th1/Th2 cells. In addition, a sustained high level of PGE2 was also maintained by GSPs treatment to limited fibroblast functions. As shown by electron spin resonance spectrometry, GSPs could scavenge hydroxyl radical (â¢OH) in a dose-dependent manner, which might account for the mitigation of lipid peroxidation and consequent apoptosis of lung cells. In vitro, GSPs radiosensitized lung cancer cell A549 while mitigating radiation injury on normal alveolar epithelial cell RLE-6TN. In conclusion, the results showed that GSPs protects mice from RILI through scavenging free radicals and modulating RILI-associated cytokines, suggesting GSPs as a novel protective agent in RILI.
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Raios gama/efeitos adversos , Lesão Pulmonar/etiologia , Lesão Pulmonar/prevenção & controle , Extratos Vegetais/farmacologia , Lesões Experimentais por Radiação/prevenção & controle , Protetores contra Radiação/farmacologia , Vitis/química , Animais , Western Blotting , Citocinas/genética , Citocinas/metabolismo , Espectroscopia de Ressonância de Spin Eletrônica , Feminino , Humanos , Técnicas Imunoenzimáticas , Lesão Pulmonar/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , RNA Mensageiro/genética , Lesões Experimentais por Radiação/etiologia , Lesões Experimentais por Radiação/metabolismo , Reação em Cadeia da Polimerase em Tempo Real , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Sementes/químicaRESUMO
BACKGROUND/AIMS: CpG-oligodeoxynucleotides (ODNs) are synthetic DNA sequences containing unmethylated cytosine-guanine motifs with potent immunomodulatory effects. Previous reports showed a powerful protective effect of CpG-ODN against the damage induced by low-LET γ-rays. In this study, we explored whether CpG-ODN also protects against the damage induced by high-LET irradiation. Parallel experiments were performed with low-LET irradiation. METHODS: RAW264.7 cells were incubated with 1 µM of CpG-ODN after γ-ray or carbon-beam irradiation. Cell death was then measured by PI/DAPI double staining, cell survival was assessed by colony-formation assays, DNA damage was evaluated by comet assays, cell cycle was monitored by flow cytometry, and the levels of apoptosis-related proteins were detected by western blots. RESULTS: When irradiated cells were treated with the CpG-ODN, cell viability decreased, cell survival increased, DNA damage and G2/M-phase arrest were ameliorated, and apoptosis was inhibited. CONCLUSIONS: The CpG-ODN showed protective effects against low-LET γ-ray and high-LET carbon-beam irradiation. These effects might be associated with the repair of DNA damage and inhibition of apoptosis.
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Sobrevivência Celular/efeitos dos fármacos , Dano ao DNA/efeitos dos fármacos , Raios gama/efeitos adversos , Oligodesoxirribonucleotídeos/farmacologia , Substâncias Protetoras/farmacologia , Animais , Apoptose/efeitos dos fármacos , Apoptose/efeitos da radiação , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Pontos de Checagem do Ciclo Celular/efeitos da radiação , Linhagem Celular , Sobrevivência Celular/genética , Sobrevivência Celular/efeitos da radiação , Dano ao DNA/efeitos da radiação , Pontos de Checagem da Fase G2 do Ciclo Celular/efeitos dos fármacos , Pontos de Checagem da Fase G2 do Ciclo Celular/efeitos da radiação , CamundongosRESUMO
Gene transformation is an important method for improvement of plants into elite varieties. However, the possibility of gene flow between genetically modified (GM) crops and similar species is a serious public issue that may potentially endanger ecological stability. Cleistogamy is expected to be an ideal genetic tool for preventing transgene propagation from GM crops. A rice mutant, cl7(t), was created by ethyl methanesulfonate mutagenesis. The mutant exhibited cleistogamy, and had closed spikelets, reduced plant height, and altered morphology of the leaves, panicle, and seeds. Anatomical investigations revealed that the cl7(t) mutant contained more vascular bundles and thicker stems than the wild type, which increased the mechanical strength of its internodes, and anti-lodging ability. Further studies demonstrated that the force required to open the lemma and palea was higher in the cl7(t) mutant, and there was weak swelling ability in the lodicules, which leads to cleistogamy. Allelic analyses and complementation tests indicated that cl7(t) was a novel allele of dep2, a mutant that was previously reported to have similar panicle morphology. Sequence analysis showed that cl7(t) had a single nucleotide substitution (C to A) in the third exon that leads to a Ser substitution with a stop codon, giving a truncated DEP2 protein. Quantitative RT-PCR and in situ hybridization tests demonstrated that there was lower CL7(t) expression level in the spikelets and weaker CL7(t) signals in the lodicules of the cl7(t) mutant compared with wild type, which implies that CL7(t) might participate in the development of lodicules. To improve the agronomic traits of cl7(t) to fit the needs of field production, the cl7(t) mutant was crossed with an intermediate-type rice variety named Guanghui102, which bears some important agronomic traits, including increased grain numbers and high rate of seed setting. Through multi-generational pedigree selection, cleistogamy lines with improved economic traits were obtained, which can be used for the selection of ecologically safe GM rice varieties.
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Oryza/genética , Fenótipo , Proteínas de Plantas/genética , Alelos , Clonagem Molecular , Teste de Complementação Genética , Oryza/anatomia & histologia , Oryza/metabolismo , Proteínas de Plantas/metabolismo , PolinizaçãoRESUMO
A Gram-stain-negative, facultatively anaerobic, non-motile and coccoid- to short-rod-shaped bacterium, designated strain Dys-CH1(T), was isolated from the hindgut of a fungus-growing termite Macrotermes barneyi. The optimal pH and cultivation temperature of strain Dys-CH1(T) were pH 7.2-7.6 and 35-37 °C, respectively. Sequence analysis of 16S rRNA gene showed that Dys-CH1(T) shared 94.6â% and 90.9â% similarity with Dysgonomonas capnocytophagoides JCM 16697(T) and Dysgonomonas gadei CCUG 42882(T), respectively. Strain Dys-CH1(T) was found to be different from other species of the genus Dysgonomonas with validly published names with respect to taxonomically important traits, including habitat, biochemical tests, DNA G+C content, bile resistance, fatty-acid composition and susceptibility to antimicrobial agents. On the basis of these characteristics, strain Dys-CH1(T) represents a novel species of the genus Dysgonomonas for which the name Dysgonomonas macrotermitis sp. nov. is proposed. The type strain is Dys-CH1(T) (â=âJCM 19375(T)â=âDSM 27370(T)).
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Bacteroidetes/classificação , Isópteros/microbiologia , Filogenia , Animais , Técnicas de Tipagem Bacteriana , Bacteroidetes/genética , Bacteroidetes/isolamento & purificação , Composição de Bases , DNA Bacteriano/genética , Sistema Digestório/microbiologia , Ácidos Graxos/química , Dados de Sequência Molecular , RNA Ribossômico 16S/genética , Análise de Sequência de DNARESUMO
A variety of distinct anisotropic exchange interactions commonly exist in one magnetic material due to complex crystal, magnetic and orbital symmetries. Here we investigate the effects of multiple anisotropic exchange interactions on topological magnon in a honeycomb ferromagnet, and find a chirality-selective topological magnon phase transition induced by a complicated interplay of Dzyaloshinsky-Moriya interaction and pseudo-dipolar interaction, accompanied by the bulk gap close and reopen with chiral inversion. Moreover, this novel topological phase transition involves band inversion at high symmetry pointsKandK', which can be regarded as a pseudo-orbital reversal, i.e. magnon valley degree of freedom, implying a new manipulation corresponding to a sign change of the magnon thermal Hall conductivity. Indeed, it can be realized in 4dor 5dcorrelated materials with both spin-orbit coupling and orbital localized states, such as iridates and ruthenates,etc.This novel regulation may have potential applications on magnon devices and topological magnonics.
RESUMO
Catalpol, a natural iridoid glycoside, has potential therapeutic benefits, including anti-inflammatory and neuroprotective effects. Investigating catalpol's role in angiogenesis is critical for understanding its potential therapeutic applications, particularly in diseases where modulating angiogenesis is beneficial. This study investigates catalpol's influence on angiogenesis and its mechanisms, combining network pharmacology and in vitro experiments. The target genes corresponding to the catalpol were analyzed by SwissTargetPrediction. Then angiogenesis-related targets were acquired from databases like GeneCards. Subsequently, the Database for Annotation, Visualization and Integrated Discovery was employed for Gene Ontology and pathway analysis, while Cytoscape visualized protein interactions. The effect of catalpol on viability and angiogenesis of HUVECs was further examined using Cell Counting Kit-8 and angiogenesis assays. RT-qPCR and western blot were applied to check the expression of angiogenesis-related proteins. Totally, 312 target genes of catalpol and 823 angiogenesis-related targets were obtained with 56 common targets leading to PPI network analysis, highlighting hub genes (AKT1, EGFR, STAT3, MAPK3, and CASP3). These hub genes were mainly enriched in lipid and atherosclerosis pathway and EGFR-related pathway. The in vitro experimental results showed that catalpol achieved a concentration-dependent increase in HUVECs viability. Catalpol also promoted the migration and angiogenesis of HUVECs and up-regulated the expression of EGFR. EGFR knockdown inhibited the effect of catalpol on HUVECs. Catalpol promotes angiogenesis in HUVECs by upregulating EGFR and angiogenesis-related proteins, indicating its potential therapeutic application in vascular-related diseases.
Assuntos
Células Endoteliais da Veia Umbilical Humana , Glucosídeos Iridoides , Farmacologia em Rede , Humanos , Glucosídeos Iridoides/farmacologia , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Células Endoteliais da Veia Umbilical Humana/metabolismo , Sobrevivência Celular/efeitos dos fármacos , Mapas de Interação de Proteínas/efeitos dos fármacos , Receptores ErbB/metabolismo , Receptores ErbB/genética , Transdução de Sinais/efeitos dos fármacos , Neovascularização Fisiológica/efeitos dos fármacos , Movimento Celular/efeitos dos fármacos , AngiogêneseRESUMO
BACKGROUND: Aplasitc anemia (AA) is a bone marrow failure syndrome characterized by an immune-mediated destruction of hematopoietic stem cells. Though clinical symptoms could be ameliorated by bone marrow transplantation and/or immunosuppressive therapy, frequent recurrence and especially evolution of clonal hematologic diseases remains problematic clinically. Cytokines such as interferon-γ (INF-γ), tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) secreted by autologous T cells are closely related with the development of AA. Hydrogen-rich solution was reported to inhibit the levels of cytokines including INF-γ, TNF-α and IL-6 in vivo in recent studies. This study was to investigate the potential therapeutic effects of hydrogen-rich solution on AA in vivo. METHODS: AA model was determined in vivo by mice and body weights of the mice were used as the basic physiological index. Peripheral blood cells were calculated to evaluate the hematologic recovery degree. Bone marrow nucleated cells (BMNCs), tissue histology, as well as CFU-S and CFU-GM forming units were used to evaluate the recovery of bone marrow microenvironment. The ratio of CD4(+) and CD8(+) cells were examined along with cytokine levels in serum to determine the efficacy of H2-rich solution on the affected immunological functions. RESULTS: Body weight and number of peripheral blood cells were significantly improved for mice in the H2-rich solution treated groups as compared with those with AA. The number of BMNCs and CFUs increased markedly and the bone marrow microenvironment was also improved significantly. The experimental group restrained the cell apoptosis, relieved hyperemia and accelerated tissue repair. The number of CD4(+) and CD8(+) cells as well as the ratio of CD4/CD8 increased to normal gradually, while the levels of TNF-α, IFN-γ, and IL-6 in serum decreased after H2-rich solution treatment. CONCLUSION: Our study firstly showed that hydrogen-rich solution accelerated the recovery of either hematological or immunological recovery on aplastic anemia mice. This finding suggests hydrogen-rich solution as a potential clinical therapeutic agent for AA.