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Freeform off-axis reflective systems are significantly more difficult to align and assemble owing to their asymmetric surface shapes and system structures. In this study, a freeform surface system design method with low coupling position error sensitivity (FCPESM) was proposed. First, we established a mathematical model of a reflective system when it was perturbed by coupling position errors and used the clustering-microelement method to establish the coupling error sensitivity evaluation function. The evaluation function was then applied to the design process of a freeform surface off-axis three-mirror optical system. The results showed that the FCPESM optical design method can significantly relax the assembly tolerance requirements of optical systems on the basis of ensuring image performance. In this study, the reflective system was perturbed by tilt and decenter simultaneously, and the disturbance mechanism of position errors on optical systems was further improved. Through this research, freeform surface systems with both image performance and error sensitivity can be obtained, which makes freeform off-axis reflective systems with better engineering realizability.
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Antieméticos , Cirurgia Bariátrica , Dexametasona , Dexmedetomidina , Obesidade Mórbida , Náusea e Vômito Pós-Operatórios , Humanos , Dexmedetomidina/uso terapêutico , Dexametasona/uso terapêutico , Dexametasona/administração & dosagem , Náusea e Vômito Pós-Operatórios/prevenção & controle , Antieméticos/uso terapêutico , Antieméticos/administração & dosagem , Obesidade Mórbida/cirurgia , Sinergismo FarmacológicoRESUMO
Epimedium is a Chinese herbal medicine commonly used in clinical practice to reinforce yang. Previous studies have shown that Epimedium fried with suet oil based has the best effect on warming kidney and promoting yang. Evidence suggests a relationship between kidney yang deficiency syndrome (KYDS) and metabolic disorders of the intestinal microflora. However, the specific interaction between KYDS and the intestinal microbiome, as well as the internal regulatory mechanism of the KYDS intestinal microbiome regulated by Epimedium fried with suet oil, remain unclear. The purpose of this study was to investigate the regulatory effects of different processed products of Epimedium on intestinal microflora and metabolites in rats with kidney yang deficiency, and to reveal the processing mechanism of Epimedium fried with suet oil warming kidney and helping yang. 16 S rRNA and LC-MS/MS technology were used to detect fecal samples. Combined with multivariate statistical analysis, differential intestinal flora and metabolites were screened. Then the content of differential bacteria was then quantified using quantitative real-time fluorescence PCR. Furthermore, the correlation between differential bacterial flora and metabolites was analyzed using Spearman's method. The study found that the composition of intestinal flora in rats with kidney yang deficiency changed compared to healthy rats. Epimedium fried with suet oil could increase the levels of beneficial bacteria, while significantly reducing the levels of harmful bacteria. Real-time quantitative PCR results were consistent with 16 S rRNA gene sequencing analysis. Fecal metabolomics revealed that KYDS was associated with 30 different metabolites, involving metabolic pathways steroid hormone biosynthesis etc. Moreover, differential bacteria were closely correlated with potential biomarkers. Epimedium could improve metabolic disorders associated with KYDS by acting on the intestinal flora, with Epimedium fried with suet oil demonstrating the most effective regulatory effect. Its potential mechanism may involve the regulation of abnormal metabolism and the impact on the diversity and structure of the intestinal flora.
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Medicamentos de Ervas Chinesas , Epimedium , Microbioma Gastrointestinal , Doenças Metabólicas , Ratos , Animais , Deficiência da Energia Yang/tratamento farmacológico , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico , Medicamentos de Ervas Chinesas/química , Epimedium/química , Cromatografia Líquida , Espectrometria de Massas em Tandem , Metabolômica , Rim/metabolismoRESUMO
Circular RNAs (circRNAs) are linked to cancer, but it's still not clear what role they play in prostatic cancer. Through high-throughput sequencing, the goal of this study was to compare how circRNAs are expressed at different stages of prostate cancer. 12 patients attending the Department of Urology at the Second Affiliated Hospital of Nanchang University between June 2020 and October 2021 were used for RNA sequencing, and 14 patients were used for real-time fluorescent quantitative PCR (qRT-PCR). The expression profiles of prostate cancer circRNAs were constructed by sequencing with the help of next-generation high-throughput sequencing technology, and the differentially expressed circRNAs were analyzed by targeting microRNA (miRNA) loci and Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis of the genes from which circRNAs originated. Finally, the expression of target circRNAs in two prostate tissues was verified by qRT-PCR. Following high-throughput sequencing, 13,047 circRNAs were identified, and 605 circRNAs with significant differential expression were identified, of which 361 circRNAs were up-regulated, and 244 circRNAs were down-regulated. Analysis of circRNA-originated genes using GO and the KEGG enrichment analysis showed that circRNA host genes can regulate and influence multiple signaling pathways in prostate cancer with important biological functions. And the circRNA-miRNA network was constructed. The highest number of differentially expressed circRNA-binding miRNAs were: hsa_circ_000 7582 (52), hsa_circ_000 6198 (37), hsa_circ_000 6759 (28), hsa_circ_000 5675 (25), and hsa_circ_000 2172 (22). Moreover, we further screened out the circRNA (hsa_circ_0005692) that was significantly differentially expressed and common to all groups and verified by qRT-PCR that the expression of the target circRNA (hsa_circ_0005692) was significantly downregulated in prostate cancer compared with benign prostatic hyperplasia (BPH) tissues.
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MicroRNAs , Neoplasias da Próstata , Masculino , Humanos , RNA Circular/genética , MicroRNAs/genética , Sequência de Bases , Neoplasias da Próstata/genética , Análise de Sequência de RNARESUMO
The monocentric camera based on fiber relay imaging offers benefits of light weight, compact size envelope, vast field of view, and high resolution, which can fully fulfill the index requirements of space-based surveillance systems. However, the fiber optic plate's (FOP) defects will result in the loss of imaging data, and the FOP's discrete structural features will exacerbate the imaging's non-uniformity. A global defect detection approach based on manual threshold segmentation of saturated frames is suggested to detect FOP defect features. The suggested method's efficacy and accuracy are confirmed when compared to the classical Otsu algorithm. Additionally, through tests, the relative imaging response coefficients of each pixel are identified, the response non-uniformity of the pixels is corrected, and the whole image non-uniformity drops from 10.01% to 0.78%. The study in this paper expedites the use of fiber relay imaging-based monocentric cameras in the field of space-based surveillance, and the technique described in this paper is also appropriate for large-array optical fiber coupled relay image transmission systems.
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Conventional therapy for kidney renal clear cell carcinoma (KIRC) is unpromising. The tumor microenvironment (TME) is intimately linked to the invasiveness of a variety of tumor forms, including KIRC. The purpose of this research is to establish the prognostic and immune-related significance of dihydrolipoamide branched chain transacylase E2 (DBT) in individuals with KIRC. In this investigation, we discovered that DBT expression was down-regulated in a range of human malignancies, and low DBT expression in KIRC was linked to higher-level clinicopathological characteristics as well as a poor prognosis for KIRC patients. Based on the findings of univariate and multivariate Cox regression analyses, DBT might be employed as an independent prognostic factor in KIRC patients. Furthermore, we developed a nomogram to better investigate DBT's predictive usefulness. To confirm DBT expression, we examined KIRC cell lines using RT-qPCR and Western blotting. We also examined the role of DBT in KIRC using colony formation, CCK-8, EdU, transwell, and wound healing assays. We discovered that plasmid-mediated overexpression of DBT in KIRC cells slowed cell proliferation and decreased migration and invasion. Multiple enrichment analyses revealed that DBT may be involved in processes and pathways related to immunotherapy and drug metabolism. We computed the immune infiltration score and discovered that the immunological score and the ESTIMATE score were both greater in the DBT low expression group. According to the CIBERSORT algorithm, DBT seems to promote anti-cancer immune responses in KIRC by activating M1 macrophages, mast cells, and dendritic cells while inhibiting regulatory T cells. Finally, in KIRC, DBT expression was found to be highly linked to immunological checkpoints, targeted medicines, and immunotherapeutic agents. Our findings suggest that DBT is a distinct predictive biomarker for KIRC patients, playing a significant role in the TME of KIRC and serving as a reference for the selection of targeted treatment and immunotherapy.
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Carcinoma de Células Renais , Neoplasias Renais , Humanos , Algoritmos , Bioensaio , Carcinoma de Células Renais/genética , Carcinoma de Células Renais/terapia , Imunoterapia , Neoplasias Renais/genética , Microambiente TumoralRESUMO
PURPOSE: Applying eHealth interventions via social media is common in modern medicine. LINE® is a popular communication app in Taiwan that can deliver messages 24 h a day. In addition to being free of charge, it also allows bariatric nurses (BNs) and patients to enjoy bidirectional communication via telecommunication services instead of direct, face-to-face contact for patients undergoing bariatric-metabolic surgery (BMS). We conducted this retrospective study to determine the frequency and reasons for early post-discharge of LINE® messages/calls and investigate the relationship between this frequency and contents of these messages and postoperative outcomes after BMS. MATERIALS AND METHODS: A retrospective review of prospectively collected data was conducted in an Asian weight management center. The study period ran from August 2016 to December 2021, and a total of 143 native patients with severe obesity were enrolled. All patients were informed of the necessity of a postoperative dietitian consultation before bariatric surgery. The patterns of LINE® communication with the BN and associated actions to resolve patients' needs within 180 days after index BMS were analyzed. RESULTS: Among the 143 enrolled patients, 100 underwent laparoscopic sleeve gastrectomy and 43 underwent laparoscopic Roux-en-Y gastric bypass. A total of 1205 messages/calls were analyzed concomitantly; most LINE® communications focused on diet problems (47.97%; n = 578), weight problems (11.54%; n = 139), and medications (9.21%; n = 111). Most problems could be resolved by LINE® communications directly, and only a small portion (5.6%) was directed to local clinics or emergency departments. During the COVID-19 pandemic, the usage of LINE® communications significantly increased (12.2 ± 10.4 vs. 6.4 ± 4.9; p < 0.01); nonetheless, a higher frequency of LINE® communications would not hinder the regular clinic visits (r = 0.359; p = 0.01). CONCLUSION: Based on our limited experience, the LINE® consultation service operated by the BN could effectively address patients' problems. Moreover, it might reduce the need for emergency department visits or unexpected clinic appointments for patients after BMS.
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Cirurgia Bariátrica , COVID-19 , Derivação Gástrica , Laparoscopia , Obesidade Mórbida , Mídias Sociais , Telemedicina , Humanos , Obesidade Mórbida/cirurgia , Estudos Retrospectivos , Cuidados Pós-Operatórios , Assistência ao Convalescente , Pandemias , Redução de Peso , Alta do Paciente , COVID-19/epidemiologia , Gastrectomia , Complicações Pós-Operatórias/cirurgiaRESUMO
Bladder cancer (BC) is the most common malignant tumour of the urinary system and one of the leading causes of cancer-related death. Cuproptosis is a novel form of programmed cell death, and its mechanism in tumours remains unclear. This study aimed to establish the prognostic signatures of cuproptosis-related lncRNAs and determine their clinical prognostic value. RNA sequencing data from The Cancer Genome Atlas were used to detect the expression levels of cuproptosis-related genes in BC. Cuproptosis-related lncRNAs linked to survival were identified using co-expression and univariate Cox regression. Furthermore, consensus cluster analysis divided the lncRNAs into two subtypes. Subsequently, we established a signature model consisting of seven cuproptosis-related lncRNAs (AC073534.2, AC021321.1, HYI-AS1, PPP1R26-AS1, AC010328.1, AC012568.1 and MIR4435-2Hg) using least absolute shrinkage and selection operator regression. Survival analysis based on risk score showed that the overall survival and progression-free survival of patients in the high-risk group were worse than those in the low-risk group. Multivariate Cox analysis demonstrated the independent prognostic potential of this signature model for patients with BC. Moreover, age and clinical stage were also significantly correlated with prognosis. The constructed nomogram plots revealed good predictive power for the prognosis of patients with BC and were validated using calibration plots. Additionally, enrichment analysis, Single sample gene set enrichment analysis and immune infiltration abundance analysis revealed significant differences in immune infiltration between the two risk groups, with high levels of immune cell subset infiltrations observed in the high-risk group accompanied by various immune pathway activation. Moreover, almost all the immune checkpoint genes showed high expression levels in the high-risk group. Moreover, TIDE analysis suggested that the high-risk group was more responsive to immunotherapy. Finally, eight drugs with low IC50 values were screened, which may prove to be beneficial for patients in the high-risk group.
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Apoptose , RNA Longo não Codificante , Neoplasias da Bexiga Urinária , Humanos , Imunoterapia , Prognóstico , Fatores de Risco , RNA Longo não Codificante/genética , Neoplasias da Bexiga Urinária/genética , Neoplasias da Bexiga Urinária/terapia , CobreRESUMO
Aflatoxin B1 (AFB1) has strong carcinogenicity and toxicity, so it is necessary to develop a highly sensitive detection method. In this paper, a novel nitrogen-doped carbon supported palladium (C-N-Pd) material was synthesized and firstly used as the energy receptor for fluorescent aptasensor. Using C-N-Pd as a novel quenching material and exonuclease â ¢ (Exo III) as assisted signal amplification, a fluorescent aptasensor for AFB1 detection was constructed. Compared with the sensor without enzyme, the fluorescence intensity obtained by the sensor with Exo III increased by 74.7%. The fabricated fluorescent aptasensor exhibited a good selectivity toward AFB1 with a limit of detection (LOD) as low as 9 pg mL-1. Moreover, the designed aptasensor was successfully utilized to detect AFB1 in spiked corn, peanut and wine samples, and the LOD is 15 pg mL-1, 13 pg mL-1 and 18 pg mL-1, respectively. In addition, the aptasensor was also compared with HPLC method, and the good agreement was found between them.
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Aptâmeros de Nucleotídeos , Técnicas Biossensoriais , Nanopartículas Metálicas , Aflatoxina B1/análise , Técnicas Biossensoriais/métodos , Carbono , Exodesoxirribonucleases , Ouro , Limite de Detecção , Nitrogênio , PaládioRESUMO
Objective: The aim of this study was to investigate gender differences after renal ischemia-reperfusion injury in mice and the effects of androgen receptor (AR) and microRNA-21 (miR-21) on apoptosis in renal ischemia-reperfusion injury. Methods: Renal ischemia-reperfusion injury model was induced by 45 min of bilateral renal artery ischemia and reperfusion. BALB/c mice were randomly divided into groups according to different experimental protocols. The levels of renal function were evaluated by serum creatinine and blood urea nitrogen. TUNEL staining was used to analyze the pathological changes and apoptosis levels of renal tissue, and western blotting and qPCR were used to detect the expressions of miR-21, AR, PDCD4 and caspase3. Results: After renal ischemia-reperfusion injury in mice with different genders, the levels of plasma urea nitrogen and creatinine in female and male mice increased, the histopathological score increased, and TUNEL staining in renal tissue indicated increased apoptosis. The expressions of miR-21, PDCD4, and active caspase-3 protein were up-regulated. The above trend was more pronounced in male mice, and a significant decrease in AR mRNA expression was detected. Silencing the expression of AR aggravated the decline of renal function and renal tubular injury after renal ischemia in mice. The expression of PDCD4 and active caspase-3 increased, while the level of miR-21 was correspondingly decreased. Up-regulation of miR-21 expression by pre-miR-21 could negatively regulate PDCD4, reduce the expression level of active caspase3, and yet induce AR expression accordingly. MiR-21 alleviated renal ischemia-reperfusion injury by inhibiting renal tubular epithelial cell apoptosis. The effect of antagomiR-21 was the opposite, which aggravated renal ischemia-reperfusion injury. Conclusion: There are gender differences in renal ischemia-reperfusion injury. Male mice are more susceptible to renal ischemia-reperfusion injury than female. Silencing AR expression or down-regulating the level of miR-21 can promote the expression of PDCD4 and apoptosis protein caspase3, thereby aggravating ischemia-reperfusion injury in mice. The protective effect of AR and miR-21 in renal ischemia-reperfusion injury has a certain synergy.
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OBJECTIVE: To compare the therapeutic effect on bronchial asthma between presence of skin reaction and the absence of skin reaction after acupoint application. METHODS: Sixty-one patients with bronchial asthma were treated with acupoint application during the hottest periods of summer ("dog days"). The acupoints included Dingchuan (EX-B 1), Feishu (BL 13), Xinshu (BL 15), Pishu (BL 20) and Shenshu (BL 23). The treatment was given once every 7 days, with the herbal plaster remained for 6 h each time, and 4 treatments were required totally. According to the local skin reaction after acupoint application, a skin reaction group (30 cases, 2 cases dropped off) and a non-skin reaction group (31 cases) were divided. Separately, before treatment and 1 year after treatment, using chronic disease management platform of asthma, the number of asthma attacks, the score of asthma control test (ACT) and the score of asthma quality of life questionnaire (AQLQ) were recorded online. Besides, the therapeutic effect was observed in the two groups 1 year after treatment. RESULTS: One year after treatment, the number of asthma attacks was reduced as compared with that before treatment in the patients of either group (P<0.001), the score of ACT and each domain in AQLQ, i.e. activity limitation, asthma symptoms, psychological state, reactions to stimuli and self-health care as well as the total scores of AQLQ were all increased as compared with those before treatment (P<0.001). The number of asthma attacks in the skin reaction group was less than the non-skin reaction group (P<0.05), the score of ACT and each domain of AQLQ and the total scores of AQLQ were all higher than the non-skin reaction group successively (P<0.05, P<0.01). The total effective rate was 82.1% (23/28) in the skin reaction group, better than 67.7% (21/31) in the non-skin reaction group (P<0.05). CONCLUSION: In treatment of acupoint application for bronchial asthma, the clinical therapeutic effect is better in the patients with local skin reaction after acupoint application. The chronic disease management platform of asthma is convenient for online evaluation.
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Terapia por Acupuntura , Asma , Pontos de Acupuntura , Asma/etiologia , Asma/terapia , Gerenciamento Clínico , Humanos , Qualidade de VidaRESUMO
The function of androgen receptor (AR)/microRNA-21 (miR-21) axis in tumor development was well investigated. However, the roles of the axis performed in hypoxia/reoxygenation (H/R)-induced apoptosis of mouse renal tubular epithelial cells (RTECs) is not known. In this study, H/R-induced apoptosis of RTECs was established to evaluate the role of miR-21-AR axis. The protocol of 8-h hypoxia and 24-h reoxygenation were selected to produce H/R injury. Our data showed that H/R increased miR-21 and caspase-3 expression, reduced the expression AR and programmed cell death protein 4 (PDCD4). By contrast, AR-siRNA increased H/R-induced apoptosis, and promoted caspase-3 expression, but reduced PDCD4 expression (vs. H/R group). pre-miR-21 reduced, while antagomiR-21 promoted apoptosis and PDCD4 expression in H/R-induced RTECs. Moreover, pre-miR-21 promoted, while antagomiR-21 reduced caspase-3 expression in H/R-induced RTECs. Together, H/R increased miRNA-21 and reduced AR expression, then regulating PDCD4- and caspase-3-dependent apoptosis. AR/miR-21 axis could be a potential therapeutic target for the kidney ischemia injury.
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Pioglitazone (Pio), a peroxisome proliferators-activated receptor-γ (PPAR-γ) agonist, may protect against renal ischemia/reperfusion injury (IRI). Recent studies have shown that autophagy plays a protective role in IRI. We aimed to evaluate whether autophagy was involved in pioglitazone-induced protection during tubular cell hypoxia/reoxygenation (H/R). Normal rat kidney proximal tubular cells NRK-52E were subjected to H/R injury, and they were divided into 6 groups: control, control + Pio, H/R, H/R + Pio, H/R + MA, H/R + MA + Pio. Autophagy-related proteins were primarily assessed by Western blot and TUNEL was performed to assess cell apoptosis. Our results showed pioglitazone pretreatment had a cytoprotective effect against H/R injury. The H/R + Pio group had an increased ratio of LC3-II to LC3-I and increased Beclin-1, decreased p62. Pioglitazone also reduced apoptosis and enhanced cell survival while inducing autophagy. Correspondingly, autophagy inhibition with 3-MA alleviated this protective effect. Furthermore, pioglitazone-induced enhancement of autophagy could be related to increased AMP-activated protein kinase (AMPK) phosphorylation and decreased Mammalian target of rapamycin (mTOR) phosphorylation. Thus, pioglitazone pretreatment protects against H/R injury by enhancting autophagy through the AMPK-mTOR signaling pathway.
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Proteínas Quinases Ativadas por AMP/metabolismo , Autofagia/efeitos dos fármacos , Túbulos Renais/citologia , Oxigênio/metabolismo , Pioglitazona/farmacologia , Transdução de Sinais/efeitos dos fármacos , Serina-Treonina Quinases TOR/metabolismo , Animais , Hipóxia Celular/efeitos dos fármacos , Linhagem Celular , Citoproteção/efeitos dos fármacos , Túbulos Renais/efeitos dos fármacos , Túbulos Renais/metabolismo , RatosRESUMO
An amorphous S-doping TiO2 catalyst [S-TiO2 (300)] with visible light catalytic activity was successfully prepared via a sol-gel method with low-temperature calcination (300⯰C) using thiourea as the sulfur source. The S-TiO2 (300) catalyst showed great performance in degrading the recalcitrant pharmaceutical, diclofenac (DCF). 93% of the target pollutant DCF degraded in 4â¯h under visible light irradiation. Both the amorphous form of the catalyst and cationic S-doping (with a coordinated structure) contributed to narrowing the band gap. As a result, the photocatalytic activity of S-TiO2 (300) was significantly enhanced under visible light irradiation. In addition, oxidative species such as photogenic cavitation (h+), OH and O2- were proved to participate in the photodegradation process, attacking COOH group and NH bond, degraded DCF into low molecule organic gradually.
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This study was designed to detecting the influences of lncRNA MEG3 in prostate cancer. Aberrant lncRNAs expression profiles of prostate cancer were screened by microarray analysis. The qRT-PCR and Western blot were employed to investigating the expression levels of lncRNA MEG3, miR-9-5p and QKI-5. The luciferase reporter assay was utilized to testifying the interactions relationship among these molecules. Applying CCK-8 assay, wound healing assay, transwell assay and flow cytometry in turn, the cell proliferation, migration and invasion abilities as well as apoptosis were measured respectively. LncRNA MEG3 was a down-regulated lncRNA in prostate cancer tissues and cells and could inhibit the expression of miR-9-5p, whereas miR-9-5p down-regulated QKI-5 expression. Overexpressed MEG3 and QKI-5 could decrease the abilities of proliferation, migration and invasion in prostate cancer cells effectively and increased the apoptosis rate. On the contrary, miR-9-5p mimics presented an opposite tendency in prostate cancer cells. Furthermore, MEG3 inhibited tumour growth and up-regulated expression of QKI-5 in vivo. LncRNA MEG3 was a down-regulated lncRNA in prostate cancer and impacted the abilities of cell proliferation, migration and invasion, and cell apoptosis rate, this regulation relied on regulating miR-9-5p and its targeting gene QKI-5.
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Regulação Neoplásica da Expressão Gênica , MicroRNAs/genética , Neoplasias da Próstata/genética , RNA Longo não Codificante/genética , Proteínas de Ligação a RNA/genética , Animais , Apoptose/genética , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Progressão da Doença , Perfilação da Expressão Gênica/métodos , Humanos , Masculino , Camundongos Endogâmicos BALB C , Camundongos Nus , Células PC-3 , Neoplasias da Próstata/patologia , Neoplasias da Próstata/terapia , Proteínas de Ligação a RNA/metabolismo , Carga Tumoral/genética , Ensaios Antitumorais Modelo de Xenoenxerto/métodosRESUMO
Renal ischemia-reperfusion injury (IRI) is a major cause of acute renal failure. Our previous studies have shown that pioglitazone, a peroxisome proliferators-activated receptor (PPAR)-γ agonist used in type 2 diabetes, protects against renal IRI; however, the molecular mechanism underlying the renoprotective effects of pioglitazone is still unclear. In this study, we investigated the role of AMP-activated protein kinase (AMPK)-regulated autophagy in renoprotection by pioglitazone in IRI. To investigate whether pioglitazone protects renal cells from IRI, an in vivo renal IRI model was used. Cell apoptosis in the kidneys was determined by TUNEL staining. Western blotting was used to determine the expression of AMPK, autophagy-related proteins, and caspase-3/8 proteins in the kidneys. In a rat model of IRI, pioglitazone decreased the increased serum creatinine and urea nitrogen, improved renal histological score, and decreased the cell injury. Pioglitazone also increased AMPK phosphorylation, inhibited p62 and cleaved caspase-3/8 proteins, and activated autophagy-related proteins LC3 II and Beclin-1 in the kidneys of IRI rats. Moreover, GW9662, as a selective inhibitor of PPAR-γ, inhibited the protective effects of pioglitazone. These results suggest that pioglitazone exerts its protective effects in renal IRI via activation of an AMPK-regulated autophagy signaling pathway.
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Renal tubular epithelial-to-mesenchymal transition (EMT) and renal tubular interstitial fibrosis are the main pathological changes of diabetic nephropathy (DN), which is a common cause of end-stage renal disease. Previous studies have suggested that berberine (BBR) has antifibrotic effects in the kidney and can reduce apoptosis and inhibit the EMT of podocytes in DN. However, the effect of BBR on the renal tubular EMT in DN and its mechanisms of action are unknown. This study was performed to explore the effects of BBR on the renal tubular EMT and the molecular mechanisms of BBR in DN model KKAy mice and on the high glucose (HG)-induced EMT in mouse renal tubular epithelial cells. Our results showed that, relative to the model mice, the mice in the treatment group had an improved general state and reduced blood glucose and 24-h urinary protein levels. Degradation of renal function was ameliorated by BBR. We also observed the protective effects of BBR on renal structural changes, including normalization of an index of renal interstitial fibrosis and kidney weight/body weight. Moreover, BBR suppressed the activation of the Notch/snail pathway and upregulated the α-SMA and E-cadherin levels in DN model KKAy mice. BBR was further found to prevent HG-induced EMT events and to inhibit the HG-induced expression of Notch pathway members and snail1 in mouse renal tubular epithelial cells. Our findings indicate that BBR has a therapeutic effect on DN, including its inhibition of the renal tubular EMT and renal interstitial fibrosis. Furthermore, the BBR-mediated EMT inhibition occurs through Notch/snail pathway regulation.
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Berberina/farmacologia , Diabetes Mellitus Experimental/tratamento farmacológico , Nefropatias Diabéticas/tratamento farmacológico , Modelos Animais de Doenças , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Hipoglicemiantes/farmacologia , Animais , Células Cultivadas , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/patologia , Nefropatias Diabéticas/metabolismo , Nefropatias Diabéticas/patologia , Feminino , Glucose/antagonistas & inibidores , Glucose/farmacologia , Camundongos , Camundongos Endogâmicos C57BL , Receptores Notch/antagonistas & inibidores , Receptores Notch/metabolismo , Fatores de Transcrição da Família Snail/antagonistas & inibidores , Fatores de Transcrição da Família Snail/metabolismoRESUMO
Our previous studies have suggested a protective role for H. pylori infection in the prognosis of gastric cancer. Based on those findings, we hypothesized that H. pylori-positive and -negative gastric cancers may exhibit different growth patterns and pathobiological behaviors, indicating different mechanisms of cancer progression. By microarray analysis, we studied miRNAs expression profiles in 42 gastric cancer patients, comparing 21 H. pylori-positive and 21 H. pylori-negative groups. Luciferase reporter assay and western blot were used to examine the potential target genes of the interested miRNA. In the present study, 53 miRNAs were significantly differentially expressed in H. pylori-positive and -negative gastric cancer tissues. We investigated the expression and function of one candidate, miR-143-3p, which was the most significantly increased miRNA in H. pylori-positive gastric cancer tissues. We observed that miR-143-3p expression was significantly decreased in gastric cancer tissues and cells, which correlated with late stage and lymph node metastasis. Using gain- and loss-of-function experiments in vitro, we demonstrate that miR-143-3p negatively regulated cell growth, apoptosis, migration and invasion. We further characterized AKT2 as a novel direct target of miR-143-3p. Knockdown of AKT2 expression mimicked the effects of miR-143-3p restoration. In conclusion, our data suggest that miR-143-3p acts as a novel tumor suppressive miRNA by regulating tumor growth, migration and invasion through directly targeting AKT2 gene. Further investigation is warranted to characterize the mechanisms underlying gastric cancer progression and may eventually contribute to its therapy.