Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 2.769
Filtrar
1.
Org Lett ; 2023 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-36637443

RESUMO

Herein, a mild and convenient defluorinative reductive cross coupling of gem-difluoroalkenes with aliphatic aldehydes has been developed to afford diverse silyl-protected ß-fluorinated allylic alcohols. The reaction is operationally simple and shows good functional group tolerance with moderate to excellent yields. The utility of this method is demonstrated by converting the products into various bioactive fluorinated compounds, showing its potential applications in drug discovery and biochemistry.

2.
World J Surg ; 2023 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-36624311

RESUMO

BACKGROUND: To evaluate the value of ultrasound-guided vacuum-assisted excision (US-guided VAE) in the treatment of intraductal papillomas, including intraductal papillomas with atypical ductal hyperplasia (ADH), and to evaluate the lesion characteristic features affecting the local recurrence rate. MATERIALS AND METHODS: Between August 2011 and December 2020, 91 lesions of 91 patients underwent US-guided VAE and were diagnosed with intraductal papilloma with or without ADH. The recurrence rate of intraductal papilloma was evaluated on follow-up US. The lesion characteristic features were analyzed to identify the factors affecting the local recurrence rate. RESULTS: The local recurrence rate of intraductal papillomas removed by US-guided VAE was 7.7% (7/91), with the follow-up duration 12-92 months (37.4 ± 23.9 months). Of the 91 patients, five cases diagnosed as intraductal papilloma with ADH did not recur, with the follow-up time 12-47 months (26.4 ± 14.4 months). There were no malignant transformation in all 91 cases during the follow-up period. All 7 patients recurred 7-58 months (22.8 ± 19.2 months) after US-guided VAE. There were no significant differences between the non-recurrence and recurrence groups in terms of age, side, distance from nipple, lesion size, BI-RADS category, with ADH, or history of excision (p > 0.05). CONCLUSIONS: US-guided VAE is an effective method for the treatment of intraductal papilloma, including intraductal papilloma with ADH. It avoids invasive surgical excision, but regular follow-up is recommended to prevent recurrence or new onset due to multifocality. Any suspicious lesions during the follow-up should be actively treated.

3.
ACS Omega ; 8(2): 2752-2759, 2023 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-36687054

RESUMO

With the further development of the concept of green chemistry, the new generation of energetic materials tends to exhibit detonation properties such as higher insensitivity, higher density, and higher energy. Therefore, the precise molecular design and green and efficient synthesis of energetic materials will be one of the serious challenges. For the purpose of accurate prediction of detonation performance of energetic materials, an ensemble modeling strategy based on the combination of Monte Carlo (MC) and variable importance measurement (VIM) improved random forest (RF) and quantitative structure-property relationship (QSPR) is proposed, which was successfully used for density prediction of energetic materials. First, the structure of 162 energetic compounds was optimized by Gaussian software, and the molecular descriptor data were calculated by CODESSA software based on the optimized molecular structure. Then, the MCVIMRF_Med ensemble model was constructed on the basis of the above molecular descriptor data and the corresponding energetic compound density index. The joint X-Y distance algorithm (SPXY) is used to partition the data set. And then, MC is used to further divide the calibration set data into multiple subsets for the construction of the ensemble model. The subset size and the number of iterations of the MCVIMRF_Med ensemble model were optimized through MC cross validation. The final output strategy of the ensemble model is optimized based on the optimized parameters, and an output optimization method based on median screening is proposed and successfully applied for the prediction performance optimization of the MCVIMRF_Med ensemble model. To further investigate the performance of the MCVIMRF_Med ensemble model, the performance of it was compared with partial least squares, RF, VIMRF, and MCVIMRF calibration models. It shows that the MCVIMRF_Med ensemble model can achieve a better prediction result for the density of energetic materials, with R 2 CV of 0.9596, RMSECV of 0.0437 g/cm3, R 2 P of 0.9768, RMSEP of 0.0578 g/cm3, and relative analysis deviation of prediction set of 3.951. Therefore, the MCVIMRF_Med ensemble modeling strategy combined with QSPR is an effective approach for the density prediction of energetic materials. This work is expected to provide new research ideas and technical support for accurate prediction of detonation performance of energetic materials.

4.
Biomed Pharmacother ; 159: 114259, 2023 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-36652737

RESUMO

A common eye disorder known as age-related macular degeneration (AMD) eventually results in blindness and vision loss. AMD has a complicated and poorly understood aetiology. The main pathological processes associated with AMD include oxidative damage, inflammation, and neovascularization. Flavonoids are naturally occurring bioactive substances with extensive distribution and antioxidant, anti-inflammatory, and neovascularization inhibitory properties. Several in vitro and in vivo AMD-related models pertinent to vision and this ocular ailment have been used to assess the mechanisms of action of various flavonoids. This article will discuss the research progress of flavonoids in AMD, especially the characteristics and mechanism of flavonoids in treating AMD.

5.
Life Sci Alliance ; 6(4)2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36690443

RESUMO

Store-operated Ca2+ entry (SOCE) is a universal Ca2+ influx pathway that is important for the function of many cell types. SOCE is controlled by the interaction of the ER Ca2+ sensor STIM1 with the plasma membrane Ca2+ channel Orai1. S417 is located in the third coiled-coil (CC3) domain of the C-terminus of STIM1. We found that single-point mutation of this residue (S417G) abolished STIM1 C-terminus interactions with Orai1. Mutation of S417 also abolished CAD-Orai1 binding and Orai1 channel activation, eliminated STIM1 puncta formation, and co-localization with Orai1 and SOCE. 2-APB was found to restore the binding of the STIM1 C-terminus mutant (S417G) to Orai1 and dose-dependently activate Orai1 channel. Both CBD and NBD of Orai1 are required for 2-APB-induced coupling between the Orai1 and STIM1 C-terminus mutant (S417G) and CRAC channel activation. We also demonstrated that 2-APB led to delayed activation of Orai1-K85E channel, although Orai1-K85E obviously impairs 2-APB-induced STIM1 C-terminus mutant (S417G)-Orai1 coupling. Our results suggest S417 in the CC3 domain of STIM1 is essential for STIM1-Orai1 binding and CRAC channel activation.


Assuntos
Canais de Cálcio , Canais de Cálcio Ativados pela Liberação de Cálcio , Canais de Cálcio/genética , Proteínas de Membrana/metabolismo , Proteína ORAI1 , Membrana Celular/metabolismo
6.
J Environ Radioact ; 259-260: 107108, 2023 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-36638725

RESUMO

Radium (Ra) isotopes are extensively used as geochemical tracers for studying water mass mixing and submarine groundwater discharge in marginal and coastal seas. However, river-borne particles and seafloor sediments are an important source of Ra in marine systems due to Ra desorption. Therefore, it is necessary to study the desorption behaviors of Ra isotopes in river sediment or suspended particles. Here, the desorption behaviors of four Ra isotopes (223Ra, 224Ra, 226Ra, and 228Ra) in the Zhangjiang River sediments were investigated by a series of designed variable-controlling experiments in the laboratory. Within the designed salinity range, desorption amounts of Ra isotopes increased with increasing salinity, and when the salinity was greater than 15 ppt, Ra desorption reached an equilibrium state. Overall, desorption of Ra isotopes increased with the decrease of particle grain size, however, the desorption fractions of 224Ra and 228Ra decreased with decreasing particle size due to the increase of original Ra activities in smaller sediment particles. In the experiments, we found that two sediment samples with similar mean grain size (3.8 µm and 3.3 µm) and similar grain size distributions had significantly different Ra desorption under the same conditions. The results of mineral composition analysis based on X-ray diffraction showed that these two samples had different percentages of kaolinite, quartz, and plagioclase, which indicated that the mineral composition of particles had an important effect on Ra isotope desorption. In conclusion, salinity, particle grain size, and mineral composition all had significant effects on Ra desorption behaviors of sediment particles. Based on the above desorption experiments, the desorbed fluxes of four Ra isotopes from river-borne sediments to the Dongshan Bay were estimated to be (5.95 ± 1.47) × 107 Bq yr-1 for 223Ra, (1.95 ± 0.27) × 109 Bq yr-1 for 224Ra, (2.73 ± 0.47) × 108 Bq yr-1 for 226Ra, and (1.26 ± 0.20) × 109 Bq yr-1 for 228Ra, respectively.

7.
Immunol Cell Biol ; 2023 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-36630591

RESUMO

There is growing evidence that programmed death ligand-1 (PD-L1) has exciting therapeutic efficacy in hematological malignancy and partial solid tumors. However, many patients still face failure with the treatment of immune checkpoint blockade because of PD-L1 expression regulation during transcription and post-transcription processes, including N6-methyladenosine (m6A). Similar to the epigenetic regulation in DNA and histones, recent research has revealed the essential regulation of m6A modification in RNA nuclear export, metabolism and translation. Recent studies have shown that m6A-induced PD-L1 expression emerges as one of the main reasons for the immunological alteration in this process and contributes to the failure of T cell-induced anti-tumor immunity. The results of preclinical studies demonstrate the potential of m6A-targeted therapy in combination with immune checkpoint blockade. Meanwhile, the comprehensive expression of m6A-related genes has provided the possibility to indicate the prognosis and optimize the treatment for patients of various cancer types. In this review, we focus on the m6A modification in PD-L1 mRNA as well as the regulation of PD-L1 expression in cancer cells and summarize its clinical value in anti-PD-L1 cancer immune therapy.

8.
Signal Transduct Target Ther ; 8(1): 36, 2023 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-36646687

RESUMO

Clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) gene-editing technology is the ideal tool of the future for treating diseases by permanently correcting deleterious base mutations or disrupting disease-causing genes with great precision and efficiency. A variety of efficient Cas9 variants and derivatives have been developed to cope with the complex genomic changes that occur during diseases. However, strategies to effectively deliver the CRISPR system to diseased cells in vivo are currently lacking, and nonviral vectors with target recognition functions may be the focus of future research. Pathological and physiological changes resulting from disease onset are expected to serve as identifying factors for targeted delivery or targets for gene editing. Diseases are both varied and complex, and the choice of appropriate gene-editing methods and delivery vectors for different diseases is important. Meanwhile, there are still many potential challenges identified when targeting delivery of CRISPR/Cas9 technology for disease treatment. This paper reviews the current developments in three aspects, namely, gene-editing type, delivery vector, and disease characteristics. Additionally, this paper summarizes successful examples of clinical trials and finally describes possible problems associated with current CRISPR applications.


Assuntos
Sistemas CRISPR-Cas , Edição de Genes , Sistemas CRISPR-Cas/genética , Terapia Genética/métodos
9.
Opt Express ; 31(1): 459-468, 2023 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-36606980

RESUMO

Polarization imaging techniques have more prominent advantages for imaging in strongly scattered media. Previous de-scattering methods of polarization imaging usually require the priori information of the background region, and rarely consider the effect of non-uniformity of the optical field on image recovery, which not only reduces the processing speed of imaging but also introduces errors in image recovery, especially for moving targets in complex scattering environments. In this paper, we propose a turbid underwater moving image recovery method based on the global estimation of the intensity and the degree of polarization (DOP) of the backscattered light, combined with polarization-relation histogram processing techniques. The full spatial distribution of the intensity and the DOP of the backscattered light are obtained by using frequency domain analysis and filtering. Besides, a threshold factor is set in the frequency domain low-pass filter, which is used to adjust the execution region of the filter, which effectively reduces the error in image recovery caused by estimating the DOP of the backscattered light as a constant in traditional methods with non-uniform illumination. Meanwhile, our method requires no human-computer interaction, which effectively solves the drawbacks that the moving target is difficult to be recovered by traditional methods. Experimental studies were conducted on static and moving targets under turbid water, and satisfactory image recovery quality is achieved.


Assuntos
Diagnóstico por Imagem , Iluminação , Nefelometria e Turbidimetria , Espalhamento de Radiação , Refração Ocular
10.
BMC Med Imaging ; 23(1): 10, 2023 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-36631781

RESUMO

OBJECTIVE: The conventional breast Diffusion-weighted imaging (DWI) was subtly influenced by microcirculation owing to the insufficient selection of the b values. However, the multiparameter derived from multiple b-value exhibits more reliable image quality and maximize the diagnostic accuracy. We aim to evaluate the diagnostic performance of stand-alone parameter or in combination with multiparameter derived from multiple b-value DWI in differentiating malignant from benign breast lesions. METHODS: A total of forty-one patients diagnosed with benign breast tumor and thirty-eight patients with malignant breast tumor underwent DWI using thirteen b values and other MRI functional sequence at 3.0 T magnetic resonance. Data were accepted mono-exponential, bi-exponential, stretched-exponential, aquaporins (AQP) model analysis. A receiver operating characteristic curve (ROC) was used to evaluate the diagnostic performance of quantitative parameter or multiparametric combination. The Youden index, sensitivity and specificity were used to assess the optimal diagnostic model. T-test, logistic regression analysis, and Z-test were used. P value < 0.05 was considered statistically significant. RESULT: The ADCavg, ADCmax, f, and α value of the malignant group were lower than the benign group, while the ADCfast value was higher instead. The ADCmin, ADCslow, DDC and ADCAQP showed no statistical significance. The combination (ADCavg-ADCfast) yielded the largest area under curve (AUC = 0.807) with sensitivity (68.42%), specificity (87.8%) and highest Youden index, indicating that multiparametric combination (ADCavg-ADCfast) was validated to be a useful model in differentiating the benign from breast malignant lesion. CONCLUSION: The current study based on the multiple b-value diffusion model demonstrated quantitatively multiparametric combination (ADCavg-ADCfast) exhibited the optimal diagnostic efficacy to differentiate malignant from benign breast lesions, suggesting that multiparameter would be a promising non-invasiveness to diagnose breast lesions.


Assuntos
Neoplasias da Mama , Imagem de Difusão por Ressonância Magnética , Humanos , Feminino , Reprodutibilidade dos Testes , Imagem de Difusão por Ressonância Magnética/métodos , Mama/diagnóstico por imagem , Mama/patologia , Imageamento por Ressonância Magnética/métodos , Neoplasias da Mama/patologia , Sensibilidade e Especificidade , Curva ROC
11.
Public Health Nutr ; : 1-18, 2023 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-36691746

RESUMO

OBJECTIVES: As the world's population is ageing, improving the physical performance of the older population is becoming important. Although diets are fundamental to maintaining and improving physical performance, few studies have addressed the role of these factors in adults aged ≥85 years, and none have been conducted in Asia. This study aimed to determine the dietary patterns and examine their relationship with physical performance in this population. DESIGN: This cross-sectional study (Kawasaki Aging and Wellbeing Project) estimated food consumption using a brief-type self-administered diet history questionnaire. The results were adjusted for energy after aggregating into 33 groups, excluding possible over- or underestimation. Principal component analysis was used to identify dietary patterns, and outcomes included hand grip strength, timed up-and-go test, and usual walking speed. SETTING: This study was set throughout several hospitals in Kawasaki city. PARTICIPANTS: In total, 1,026 community-dwelling older adults (85-89 years) were enrolled. RESULTS: Data of 1,000 participants (median age: 86.9 years, men: 49.9 %) were included in the analysis. Three major dietary patterns (DP1: various foods, DP2: red meats and coffee, DP3: bread and processed meats) were identified. The results of multiple regression analysis showed that the score of DP2 was negatively associated with hand grip strength (B, 95% confidence interval: -0.35, -0.64 to -0.06). CONCLUSIONS: This study suggests a negative association between hand grip strength and dietary patterns characterised by red meats and coffee in older adults aged ≥85 years in Japan.

12.
Hortic Res ; 10(1): uhac241, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36643737

RESUMO

The genus Rhododendron (Ericaceae), with more than 1000 species highly diverse in flower color, is providing distinct ornamental values and a model system for flower color studies. Here, we investigated the divergence between two parental species with different flower color widely used for azalea breeding. Gapless genome assembly was generated for the yellow-flowered azalea, Rhododendron molle. Comparative genomics found recent proliferation of long terminal repeat retrotransposons (LTR-RTs), especially Gypsy, has resulted in a 125 Mb (19%) genome size increase in species-specific regions, and a significant amount of dispersed gene duplicates (13 402) and pseudogenes (17 437). Metabolomic assessment revealed that yellow flower coloration is attributed to the dynamic changes of carotenoids/flavonols biosynthesis and chlorophyll degradation. Time-ordered gene co-expression networks (TO-GCNs) and the comparison confirmed the metabolome and uncovered the specific gene regulatory changes underpinning the distinct flower pigmentation. B3 and ERF TFs were found dominating the gene regulation of carotenoids/flavonols characterized pigmentation in R. molle, while WRKY, ERF, WD40, C2H2, and NAC TFs collectively regulated the anthocyanins characterized pigmentation in the red-flowered R simsii. This study employed a multi-omics strategy in disentangling the complex divergence between two important azaleas and provided references for further functional genetics and molecular breeding.

13.
J Ginseng Res ; 47(1): 1-8, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36644389

RESUMO

The herbal medication Panax ginseng Meyer has widespread use in China, Korea, and other parts of the world. The main constituents of ginseng are ginsenosides, which include over 30 different triterpene saponins. It has been found that ginsenosides and their metabolites including Rg1, compound K, Rb1, Re, Rg3, and Rg5 exert anti-inflammatory activities by binding to the glucocorticoid receptor, modulating inflammation-related signaling, including NF-κB and MAPK signaling, and reducing levels of pro-inflammatory cytokines. Here, we review the recent literature on the molecular actions of ginsenosides in sepsis, suggesting ways in which they may be used to prevent and treat the disease.

15.
J Affect Disord ; 325: 480-486, 2023 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-36621675

RESUMO

BACKGROUND: Cognitive reserve (CR) is closely associated with cognitive and functional outcome, disease severity, progression and prognosis in psychiatric patients; however, it has not been extensively tested in mood disorders. This study examined the psychometric properties of the Cognitive Reserve Assessment Scale in Health (CRASH) in mood disorder patients. METHODS: Altogether 166 subjects were recruited, 44 with major depressive disorder (MDD), 64 with bipolar disorder (BD), and 58 healthy controls. CR was assessed using the CRASH and the Cognitive Reserve Questionnaire (CRQ). RESULTS: Internal consistency (Cronbach's alpha) was 0.779 for the CRASH. The Receiver Operating Characteristic (ROC) curve analysis revealed an area under the ROC curve (AUC) value of 0.73 (95 % CI: 0.647-0.809). The optimal cut-off score of 51 generated the best combination of sensitivity (0.78) and specificity (0.43) for discriminating between patients with mood disorders and healthy controls. The CRASH score was highly correlated with the CRQ score in both mood disorder patients (rs = 0.586, P < 0.001) and healthy controls (rs = 0.627, P < 0.001), indicating acceptable convergent validity for the CRASH. Within the mood disorder sample, the CRASH score was associated with functional outcomes (FAST: rs = -0.243, P = 0.011). CONCLUSIONS: The CRASH is a useful tool to measure CR in mood disorder with acceptable psychometric properties and could be used in both research and clinical practice.

16.
Langenbecks Arch Surg ; 408(1): 25, 2023 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-36637531

RESUMO

BACKGROUND: Laparoscopic liver resection (LLR) is now widely adopted for the treatment of liver tumors due to its minimally invasive advantages. However, multicenter, large-sample population-based laparoscopic right posterior sectionectomy (LRPS) has rarely been reported. We aimed to assess the advantages and drawbacks of right posterior sectionectomy compared with laparoscopic and open surgery by meta-analysis. METHODS: Relevant literature was searched using the PubMed, Embase, Cochrane, Ovid Medline, and Web of Science databases up to September 12, 2021. Quality assessment was performed based on a modified version of the Newcastle-Ottawa Scale (NOS). The data were analyzed by Review Manager 5.3. The data were calculated by odds ratio (OR) or mean difference (MD) with 95% confidence intervals (CI) for fixed-effects and random-effects models. RESULTS: The meta-analysis included seven studies involving 739 patients. Compared with open right posterior sectionectomy (ORPS), the LRPS group had lower intraoperative blood loss (MD - 135.45; 95%CI - 170.61 to - 100.30; P < 0.00001) and shorter postoperative hospital stays (MD - 2.17; 95% CI - 3.03 to - 1.31; P < 0.00001). However, there were no statistically significant differences between LRPS and ORPS regarding operative time (MD 44.97; P = 0.11), pedicle clamping (OR 0.65; P = 0.44), clamping time (MD 2.72; P = 0.31), transfusion rate (OR 1.95; P = 0.25), tumor size (MD - 0.16; P = 0.13), resection margin (MD 0.08; P = 0.63), R0 resection (OR 1.49; P = 0.35), recurrence rate (OR 2.06; P = 0.20), 5-year overall survival (OR 1.44; P = 0.45), and 5-year disease-free survival (OR 1.07; P = 0.88). Furthermore, no significant difference was observed in terms of postoperative complications (P = 0.08), bile leakage (P = 0.60), ascites (P = 0.08), incisional infection (P = 0.09), postoperative bleeding (P = 0.56), and pleural effusion (P = 0.77). CONCLUSIONS: LRPS has an advantage in the length of hospital stay and blood loss. LRPS is a very useful technology and feasible choice in patients with the right posterior hepatic lobe tumor.


Assuntos
Laparoscopia , Neoplasias Hepáticas , Humanos , Neoplasias Hepáticas/cirurgia , Hepatectomia , Intervalo Livre de Doença , Laparoscopia/efeitos adversos , Tempo de Internação , Estudos Multicêntricos como Assunto
17.
Prev Med ; 166: 107379, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36495926

RESUMO

Violence against women is rampant in China. Even though meaningful strides have been made in the country, it remains disturbingly common for men to assault women-verbally or physically, who may or may not be their partners-in broad daylight in China. To make the situation worse, COVID-19, along with its restrictions, has both undermined women's ability to escape from abuse or violence and society's ability to provide timely help to victims. In light of the rising violence against women post-COVID, in this paper, we discuss the policy imperatives for countries like China to establish effective guardrails and support systems to protect women from the dehumanizing and destabilizing crime that is violence against women-a social malaise that not only harms and undermines the safety of society's daughters, mothers, and grandmothers, but also the integrity of local communities and social contract, let along shared humanity and global solidarity at large.


Assuntos
COVID-19 , Violência Doméstica , Feminino , Humanos , Pandemias/prevenção & controle , COVID-19/prevenção & controle , Violência , Crime , Políticas , Violência Doméstica/prevenção & controle
18.
Eur J Med Chem ; 245(Pt 1): 114911, 2023 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-36379106

RESUMO

Systemic inflammatory responses often result in sepsis and inhibition of inflammation is one strategy for sepsis treatment. In this study, we designed and synthesized 32 novel hederagenin (HD) derivatives with modifications at the A-ring, C-28, and C-23 positions and screened their anti-inflammatory activities in vitro, finding multiple compounds with potential anti-inflammatory activity. Of these, compound 1 was the most effective and was used for subsequent investigations into its mechanism of action and in vivo activity. In vivo assessments of anti-inflammatory activity showed that compound 1 reduced inflammation in a mouse model of sepsis with acute liver injury caused by lipopolysaccharide (LPS). Compound 1 also inhibited STING, p-IRF3, p-TBK1, p-p65, and p-IκB proteins in cGAS-STING-associated signaling. These findings indicated that compound 1 reduced inflammation through inhibition of STING expression and hence reducing activation of STING and nuclear factor-κB (NF-κB) signaling. Our work demonstrated that compound 1 is a promising lead compound for designing and developing anti-sepsis drugs.


Assuntos
Anti-Inflamatórios , Falência Hepática Aguda , NF-kappa B , Sepse , Animais , Camundongos , Anti-Inflamatórios/síntese química , Anti-Inflamatórios/química , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Inflamação/tratamento farmacológico , Lipopolissacarídeos , Fígado/efeitos dos fármacos , Fígado/metabolismo , NF-kappa B/metabolismo , Sepse/complicações , Sepse/tratamento farmacológico , Falência Hepática Aguda/microbiologia , Falência Hepática Aguda/prevenção & controle
19.
Anticancer Drugs ; 34(1): 155-165, 2023 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-36539368

RESUMO

Circular RNAs (circRNAs) exert pivotal functions in many malignancies. However, the roles of circ-ABCC4 in prostate cancer (PCa) radioresistance and progression remain largely unclear. Cell viability, proliferation, apoptosis, invasion, and radioresistance were evaluated by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide, 5-ethynyl-2'-deoxyuridine, flow cytometry, transwell invasion, and colony formation assays. Tumor xenograft experiment was conducted to assess circ-ABCC4 role in xenograft growth in vivo. Dual-luciferase reporter assay was implemented to test the target relation of microRNA-1253 (miR-1253) and circ-ABCC4 or SRY-box transcription factor 4 (SOX4). Circ-ABCC4 enrichment was prominently raised in PCa tissue specimens and cells. Circ-ABCC4 depletion blocked PCa cell viability, proliferation, invasion, and radioresistance and triggered apoptosis. Circ-ABCC4 silencing aggravated irradiation-induced inhibitory effect on xenografts growth. miR-1253 was a downstream molecule of circ-ABCC4, and circ-ABCC4 depletion-mediated anti-cancer impacts in PCa cells were partly counteracted by decreasing miR-1253 abundance. miR-1253 targeted SOX4 mRNA, and miR-1253 blocked PCa cell malignant phenotypes partly by targeting SOX4. Circ-ABCC4 could enhance SOX4 abundance by absorbing miR-1253. Circ-ABCC4 exerted a pro-tumor activity by facilitating PCa cell viability, proliferation, invasion, and radioresistance and suppressing apoptosis.


Assuntos
MicroRNAs , Neoplasias da Próstata , Humanos , Masculino , Neoplasias da Próstata/genética , Neoplasias da Próstata/radioterapia , Apoptose , Sobrevivência Celular , Citometria de Fluxo , MicroRNAs/genética , Proliferação de Células , Linhagem Celular Tumoral , Fatores de Transcrição SOXC/genética , Proteínas Associadas à Resistência a Múltiplos Medicamentos
20.
Oncol Rep ; 49(1)2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36453240

RESUMO

Microcystin­leucine arginine (MC­LR) is an environmental toxin produced by cyanobacteria and is considered to be a potent carcinogen. However, to the best of our knowledge, the effect of MC­LR on colorectal cancer (CRC) cell proliferation has never been studied. The aim of the present study was to investigate the effect of MC­LR on CRC cell proliferation and the underlying mechanisms. Firstly, a Cell Counting Kit­8 (CCK­8) assay was conducted to determine cell viability at different concentrations, and 50 nM MC­LR was chosen for further study. Subsequently, a longer CCK­8 assay and a cell colony formation assay showed that MC­LR promoted SW620 and HT29 cell proliferation. Furthermore, western blotting analysis showed that MC­LR significantly upregulated protein expression of PI3K, p­Akt (Ser473), p­GSK3ß (Ser9), ß­catenin, c­myc and cyclin D1, suggesting that MC­LR activated the PI3K/Akt and Wnt/ß­catenin pathways in SW620 and HT29 cells. Finally, the pathway inhibitors LY294002 and ICG001 were used to validate the role of the PI3K/Akt and Wnt/ß­catenin pathways in MC­LR­accelerated cell proliferation. The results revealed that MC­LR activated Wnt/ß­catenin through the PI3K/Akt pathway to promote cell proliferation. Taken together, these data showed that MC­LR promoted CRC cell proliferation by activating the PI3K/Akt/Wnt/ß­catenin pathway. The present study provided a novel insight into the toxicological mechanism of MC­LR.


Assuntos
Neoplasias Colorretais , beta Catenina , Humanos , Leucina/farmacologia , Fosfatidilinositol 3-Quinases , Proteínas Proto-Oncogênicas c-akt , Microcistinas/toxicidade , Arginina , Sincalida , Proliferação de Células , Receptores Proteína Tirosina Quinases
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...