RESUMO
OBJECTIVE: To investigate the effectiveness and clinical efficacy of tension-free vaginal tape (TVT) surgery in treating female recurrent stress urinary incontinence (rSUI). METHODS: A retrospective analysis was conducted on 24 patients who experienced recurrence of mid-urethral sling failure and were treated with TVT surgery at Beijing Chao-Yang Hospital from January 2016 to June 2020. Basic patient information was collected. The International Consultation on Incontinence questionnaire-short form (ICI-Q-SF) was used to record urinary incontinence symptom scores preoperatively, 1-year postoperatively, and more than three years postoperatively. The changes in various ICI-Q-SF scores and total scores were compared. Additionally, clinical symptom severity of urinary incontinence was recorded and compared preoperatively and more than three years postoperatively. RESULTS: Among the 24 patients included in the follow-up, one patient was lost to follow-up due to death from a cerebrovascular accident one year postoperatively, leaving 23 patients with a follow-up period ranging from 3.9 to 7.3 years, with an ave-rage follow-up time of (5.2±1.1) years. Preoperatively, the median ICI-Q-SF total score was 20.0 (16.0, 21.0); at the 1-year follow-up, the median ICI-Q-SF total score was 5.0 (1.5, 7.8) (P < 0.001); at an average follow-up of five years, the median ICI-Q-SF total score was 6.0 (3.0, 9.0), still showing a statistically significant difference compared with preoperative scores (P < 0.001). The individual ICI-Q-SF scores were significantly lower at the 1-year and average five-year follow-ups compared with preoperative scores (P < 0.001). Regarding the severity of urinary incontinence, all the patients had moderate to severe urinary incontinence preoperatively; Five years postoperatively, 87.0% (20/23) of the patients had no or only mild urinary incontinence, and 13.0% (3/23) had recurrent moderate to severe urinary incontinence (P < 0.001). CONCLUSION: TVT surgery is effective in treating female recurrent stress urinary incontinence, with an average 5-year cure and improvement rate of 87.0%.
Assuntos
Recidiva , Slings Suburetrais , Incontinência Urinária por Estresse , Humanos , Feminino , Incontinência Urinária por Estresse/cirurgia , Estudos Retrospectivos , Resultado do Tratamento , Inquéritos e Questionários , Pessoa de Meia-Idade , SeguimentosRESUMO
OBJECTIVE: To investigate the potential clinical benefits of mid-urethral sling (MUS) and urethral dilatation (UD) operations for the treatment of stress urinary incontinence (SUI) combined with urethral stricture. STUDY DESIGN: Descriptive study. Place and Duration of the Study: Department of Urology, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China, from January 2017 to 2022. METHODOLOGY: Patients with Qmax <15ml/s or PVR >50ml, and video urodynamic study (VUDS) capable of confirming the presence and position of urethral stricture were included. The clinical efficacy was evaluated by International Consultation on Incontinence Questionnaire-Short Form (ICIQ-SF) questionnaire, maximum flow rate (Qmax), and postvoid residual (PVR) urine. ICIQ-SF, Qmax, and PVR were measured presurgery, on postoperative 2-week, and 1-month postsurgery. RESULTS: There were total 19 patients with an average age of 61.37 ± 11.28 years (range 39-84) with SUI and urethral stricture. ICIQ-SF scores were decreased significantly at one month postoperatively compared with the preoperative [5.0 (0.0, 7.0) vs. 14.0 (13.0, 15.0), p <0.001]. Qmax was increased dramatically compared with the preoperative [21.3 (14.0, 28.4) vs. 13.0 (8.7,18.0), p <0.001], and PVR was decreased remarkably than the preoperative [0.0 (0.0,0.0) vs. 0.0 (0.0,60.0), p = 0.018]. Of 19 patients primarily managed with MUS and UD, two patients experienced recurrence requiring repetitive dilation till sling excision surgery was conducted, and improvement was evident in one patient after repeating UD. CONCLUSION: The overall incidence of SUI combined with urethral stricture in women is low. With a success rate of 89.5%, MUS and UD were effective therapies for the co-existence of SUI with urethral stricture, and repeated UD can be performed safely if necessary in long-term follow-up. KEY WORDS: Stress urinary incontinence, Urethral stricture, Mid-urethral sling, Urethral dilatation.
Assuntos
Dilatação , Slings Suburetrais , Estreitamento Uretral , Incontinência Urinária por Estresse , Humanos , Incontinência Urinária por Estresse/cirurgia , Feminino , Pessoa de Meia-Idade , Dilatação/métodos , Estreitamento Uretral/cirurgia , Estreitamento Uretral/terapia , Resultado do Tratamento , Idoso , Adulto , Urodinâmica , Idoso de 80 Anos ou mais , Uretra/cirurgia , China/epidemiologia , Procedimentos Cirúrgicos Urológicos/métodos , Inquéritos e QuestionáriosRESUMO
The aims of this study were to investigate whether the ferroptosis is involved in intestinal Behçet's syndrome (IBS), and to identify if miR-141-3p could attenuate RAS-selective lethal 3 (RSL3)-induced ferroptosis and intestinal epithelial to mesenchymal transition (EMT) via directly inhabits zinc fnger E-box binding homeobox 1 (ZEB1). The expressions of ferroptosis-related proteins in the intestinal tissues of patients with IBS were investigated by immunohistochemistry and quantitative real-time PCR (qRT-PCR). Malondialdehyde (MDA) contents of the intestinal tissues and cells were detected. Serum from IBS patients and RSL3 were co-cultured with intestinal epithelial cells in vitro. In order to investigate whether RSL3-induced ferroptosis can be ameliorated by miR-141-3p, the intestinal epithelial cells were firstly stimulated with RSL3 and then incubated with miR-141-3p mimics. Western blot was used to measure the expression of EMT and ferroptosis-related proteins. Expression of GPX4 (22.51% ± 2.05%, 51.75% ± 3.47%, t = - 7.77, p = 0.000) and xCT (17.49% ± 1.57%, 28.73% ± 1.75%, t = - 4.38, p = 0.003) were significantly lower in intestinal mucosal tissues of patients with IBS compared with HC group. Compared with the HC samples, the IBS specimens had significantly higher MDA (t = 4.32, p = 0.01). Moreover, the relative mRNA levels of ferritin light chain (FTL) (t = 4.07, p = 0.02) and ferritin heavy chain (FTH) (t = 8.82, p = 0.001) in the intestinal tissues were significant higher in IBS patients than in HC group. Serum from IBS patients could induce intestinal epithelial cell ferroptosis in vitro. Moreover, miR-141-3p could attenuate intestinal epithelial cell ferroptosis-induced by RSL3 and intestinal EMT via targeting ZEB1 in vitro. Ferroptosis were induced in patients with IBS. Moreover, the serum from IBS patients could induce ferroptosis in vitro. miR-141-3p could attenuate intestinal epithelial cell ferroptosis and intestinal EMT via targeting ZEB1. Therefore, miR-141-3p may open new avenues for the treatment of IBS in the future. Key Points ⢠Ferroptosis in IBS is first reported in this study. ⢠In this study, we explored that the serum from IBS patients could induce ferroptosis in vitro and miR-141-3p could attenuate intestinal epithelial cell ferroptosis and intestinal EMT via targeting ZEB1.
Assuntos
Síndrome de Behçet , Transição Epitelial-Mesenquimal , Ferroptose , MicroRNAs , Homeobox 1 de Ligação a E-box em Dedo de Zinco , Humanos , MicroRNAs/metabolismo , Masculino , Homeobox 1 de Ligação a E-box em Dedo de Zinco/metabolismo , Feminino , Adulto , Síndrome de Behçet/metabolismo , Mucosa Intestinal/metabolismo , Mucosa Intestinal/patologia , Pessoa de Meia-IdadeRESUMO
This study aims to evaluate the role of the peri-coronary Fat Attenuation Index (FAI) and High-Risk Plaque Characteristics (HRPC) in the assessment of coronary heart disease risk. By conducting coronary CT angiography and coronary angiography on 217 patients with newly developed chest pain (excluding acute myocardial infarction), their degree of vascular stenosis, FAI, and the presence and quantity of HRPC were assessed. The study results demonstrate a correlation between FAI and HRPC, and the combined use of FAI and HRPC can more accurately predict the risk of major adverse cardiovascular events (MACE). Additionally, the study found that patients with high FAI were more prone to exhibit high-risk plaque characteristics, severe stenosis, and multiple vessel disease. After adjustment, the combination of FAI and HRPC improved the ability to identify and reclassify MACE. Furthermore, the study identified high FAI as an independent predictor of MACE in patients undergoing revascularization, while HRPC served as an independent predictor of MACE in patients not undergoing revascularization. These findings suggest the potential clinical value of FAI and HRPC in the assessment of coronary heart disease risk, particularly in patients with newly developed chest pain excluding acute myocardial infarction.
Assuntos
Dor no Peito , Angiografia por Tomografia Computadorizada , Angiografia Coronária , Placa Aterosclerótica , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Angiografia por Tomografia Computadorizada/métodos , Dor no Peito/diagnóstico por imagem , Placa Aterosclerótica/diagnóstico por imagem , Placa Aterosclerótica/complicações , Angiografia Coronária/métodos , Idoso , Infarto do Miocárdio/diagnóstico por imagem , Infarto do Miocárdio/complicações , Medição de Risco , Tecido Adiposo/diagnóstico por imagem , Tecido Adiposo/patologia , Doença da Artéria Coronariana/diagnóstico por imagem , Doença da Artéria Coronariana/complicações , Fatores de Risco , Vasos Coronários/diagnóstico por imagem , Vasos Coronários/patologiaRESUMO
Seagrass beds can trap large amounts of marine debris leading to areas of accumulation, known as 'sinks', of anthropogenic particles. While the presence of vegetation can enhance accumulation, less is known about how the trapping effect changes from vegetated to less vegetated patches. To test this, vegetation and sediment were sampled along a vegetation percent cover gradient from the centre of seagrass beds to nearby less vegetated patches. To determine whether trapped particles can lead to increased accumulation in associated fauna, gastropods were also collected from the transects laid across this gradient. Extracted anthropogenic particles were counted and characterised. Particles were detected in all sample types and reached quantifiable limits in at least 50% of sediment and gastropod samples. There was no significant difference in the distribution of particles found in seagrass beds compared to less vegetated patches, suggesting other factors contribute to the trapping efficiency of biogenic habitats besides simply the presence or absence of vegetation.
Assuntos
Microplásticos , Plásticos , EcossistemaRESUMO
Following the publication of this paper, the authors realized that they had made an error in assembling the data shown in Fig. 6B on p. 2455, and requested the publication of a corrigendum to rectify this error. However, following an independent investigation of the data published in this paper made by the Editorial Office, it was noted that one set of the immunofluorescence assay images shown in Fig. 4A appeared to be strikingly similar to data appearing in different form in a paper published previously in the journal BMC Medicine by different authors at different research institutes [Jing YY, Han ZP, Sun K, Zhang SS, Hou J, Liu Y, Li R, Gao L, Zhao X, Zhao QD et al: Tanshinone IIA reduces SW837 colorectal cancer cell viability via the promotion of mitochondrial fission by activating JNKMff signaling pathways. BMC Medicine 10: 98, 2012]. Owing to the fact that the abovementioned data in Fig. 4A had already been published prior to its submission to International Journal of Molecular Medicine, the Editor has chosen to decline the authors' request to publish a corrigendum, and decided that this paper should be retracted from the Journal instead. After having been in contact with the authors, they accepted the decision to retract the paper. The Editor apologizes to the readership for any inconvenience caused. [International Journal of Molecular Medicine 42: 24472458, 2018; DOI: 10.3892/ijmm.2018.3860].
RESUMO
Purpose: Ocular pathology may be reduced by slowing myopia progression. The purpose of this study was to evaluate the potential of a novel custom-designed rigid gas permeable (RGP) contact lens to control high myopia by comparing the efficacy of multifocal RGP lenses and single-vision spectacles for high myopia control. Methods: The medical records of children fitted with spectacles or multifocal rigid gas-permeable lenses between January 2018 and May 2020 were retrospectively reviewed. Children (5-17 years) with non-cycloplegic spherical equivalent refraction of ≤ -6.00 D or spherical equivalent refraction > - 6.00 D with baseline axial length ≥ 26.5 mm, and astigmatism of ≥ -2.00 D were included. Axial length and refraction were measured at baseline, before fitting the participants with multifocal rigid gas-permeable lenses or spectacles, and at 1- and 2-year follow-up visits. Changes in axial length were compared between the groups. Results: Among the 77 children with 1-year follow-up data, the mean axial elongation was 0.20 ± 0.17 mm and 0.21 ± 0.14 mm in the multifocal rigid gas-permeable and control groups, respectively, without significant differences between groups (F = 0.004, p = 0.835). Among the 41 patients who completed 2 years of follow-up, the mean axial elongation values in the multifocal rigid gas-permeable and control groups were 0.21 ± 0.15 mm and 0.24 ± 0.13 mm, respectively, at the 1-year follow-up, and 0.37 ± 0.27 mm and 0.43 ± 0.23 mm, respectively, at the 2-year follow-up, without significant between-group differences at either time point (p = 0.224). Conclusion: Axial length increased at a similar rate in both the control (spectacles) and multifocal rigid gas-permeable lens groups, suggesting that multifocal rigid gas-permeable lenses have no significant impact on controlling high myopia progression compared with spectacles.
RESUMO
The intracellular protozoan parasite Babesia gibsoni infects canine erythrocytes and causes babesiosis. The hazards to animal health have increased due to the rise of B. gibsoni infections and medication resistance. However, the lack of high-quality full-genome sequencing sets has expanded the obstacles to the development of pathogeneses, drugs, and vaccines. In this study, the whole genome of B. gibsoni was sequenced, assembled, and annotated. The genomic size of B. gibsoni was 7.94 Mbp in total. Four chromosomes with the size of 0.69 Mb, 2.10 Mb, 2.77 Mb, and 2.38 Mb, respectively, 1 apicoplast (28.4 Kb), and 1 mitochondrion (5.9 Kb) were confirmed. KEGG analysis revealed 2,641 putative proteins enriched on 316 pathways, and GO analysis showed 7,571 annotations of the nuclear genome in total. Synteny analysis showed a high correlation between B. gibsoni and B. bovis. A new divergent point of B. gibsoni occurred around 297.7 million years ago, which was earlier than that of B. bovis, B. ovata, and B. bigemina. Orthology analysis revealed 22 and 32 unique genes compared to several Babesia spp. and apicomplexan species. The metabolic pathways of B.gibsoni were characterized, pointing to a minimal size of the genome. A species-specific secretory protein SA1 and 19 homologous genes were identified. Selected specific proteins, including apetala 2 (AP2) factor, invasion-related proteins BgAMA-1 and BgRON2, and rhoptry function proteins BgWH_04g00700 were predicted, visualized, and modeled. Overall, whole-genome sequencing provided molecular-level support for the diagnosis, prevention, clinical treatment, and further research of B. gibsoni. IMPORTANCE The whole genome of B. gibsoni was first sequenced, annotated, and disclosed. The key part of genome composition, four chromosomes, was comparatively analyzed for the first time. A full-scale phylogeny evolution analysis based on the whole-genome-wide data of B. gibsoni was performed, and a new divergent point on the evolutionary path was revealed. In previous reports, molecular studies were often limited by incomplete genomic data, especially in key areas like life cycle regulation, metabolism, and host-pathogen interaction. With the whole-genome sequencing of B. gibsoni, we provide useful genetic data to encourage the exploration of new terrain and make it feasible to resolve the theoretical and practical problems of babesiosis.
Assuntos
Babesia , Babesiose , Doenças do Cão , Animais , Cães , Babesia/genética , Babesiose/parasitologia , Sequenciamento Completo do Genoma , Genômica , GenomaRESUMO
The megajansky radio burst, FRB 20200428, and other bright radio bursts detected from the Galactic source SGR J1935+2154 suggest that magnetars can make fast radio bursts (FRBs), but the emission site and mechanism of FRB-like bursts are still unidentified. Here, we report the emergence of a radio pulsar phase of the magnetar 5 months after FRB 20200428. Pulses were detected in 16.5 hours over 13 days using the Five-hundred-meter Aperture Spherical radio Telescope, with luminosities of about eight decades fainter than FRB 20200428. The pulses were emitted in a narrow phase window anti-aligned with the x-ray pulsation profile observed using the x-ray telescopes. The bursts, conversely, appear in random phases. This dichotomy suggests that radio pulses originate from a fixed region within the magnetosphere, but bursts occur in random locations and are possibly associated with explosive events in a dynamically evolving magnetosphere. This picture reconciles the lack of periodicity in cosmological repeating FRBs within the magnetar engine model.
RESUMO
To evaluate the changes in testicular stiffness and microcirculation caused by spermatic vein ligation in patients with varicocele, we conducted a case-controlled study. A total of 27 grade III left varicocele cases were enrolled. Testicular stiffness and perfusion were evaluated by shear wave elastography and contrast-enhanced ultrasound during subinguinal microscopic varicocelectomy. The external and the internal parenchyma of bilateral testes were selected to compare the shear wave velocity of bilateral testes during the spermatic vein ligation. We mapped and compared the intensity-time curves following bolus contrast injection three times in the same region of interest. Initially, the shear wave velocity of the left internal parenchyma was higher than the right side (1.10 ± 0.06 m/s vs. 1.00 ± 0.03 m/s). It decreased (1.09 ± 0.06 m/s) (p < 0.05) after ligation. Meanwhile, the left epididymis had the higher agent peak intensity (0.90 × 10E-5 AU), the largest area under the curve (80.20 × 10E-5 AU s), and the longest washout area (54.35 × 10E-5 AU s). In addition, the left internal parenchyma presented a sharper slope (0.18 × 10E-5 AU/s) (p < 0.05). In conclusion, the spermatic vein ligation improved the perfusion of the internal testicular parenchyma, but it could temporally deteriorate the stasis of the epididymis. These changes caused softer testicular parenchyma.
Assuntos
Técnicas de Imagem por Elasticidade , Varicocele , Masculino , Humanos , Varicocele/diagnóstico por imagem , Varicocele/cirurgia , Veias/diagnóstico por imagem , Procedimentos Cirúrgicos Vasculares , Testículo/diagnóstico por imagem , Testículo/cirurgia , Testículo/irrigação sanguíneaRESUMO
BACKGROUND: Venous hemangioma is a benign and non-invasive type of tumor, which is rarely identified due to the absence of clinical manifestations. A retroperitoneal benign tumor is comparatively rare, and hemangioma is exceptional. Because of the different types and locations of hemangioma, presentations are varied; thus, establishing an accurate diagnosis before surgery is challenging. CASE SUMMARY: A 45-year-old female patient visited our hospital with the complaint of a retroperitoneal mass without symptoms discovered during a medical examination. An abdominal and pelvic computed tomography (CT) revealed a giant hypodense mass that extended from the lower edge of the liver down to the right groin and showed no marked enhancement in the arterial phase of the enhanced CT. On magnetic resonance imaging, the retroperitoneal mass was hyperintense on the T2-weighted image and hypointense on the T1-weighted image. The mass was completely resected and confirmed as a venous hemangioma by pathology. CONCLUSION: Venous hemangioma is rare in adults, and an accurate diagnosis before surgery is challenging. Surgery is the curative treatment for venous hemangioma, and the definitive diagnosis relies on pathology.
RESUMO
Camellia oleifera Abel. is an important woody oil plant, and its pollination success is essential for oil production. We conducted this study to select the best pollinator candidates for C. oleifera using principal component analysis and multi-attribute decision-making. Field observations of the flower-visiting characteristics of candidate pollinators were conducted at three sites. The insect species that visited flowers did not considerably differ between regions or time periods. However, the proportion of each species recorded did vary. We recorded eleven main candidates from two orders and six families at the three sites. The pollen amount carried by Apis mellifera was significantly higher than that of other insects. However, the visit frequency and body length of Apis mellifera were smaller than those of Vespa velutina. Statistical analysis showed that A. mellifera is the best candidate pollinator; Eristaliscerealis is a good candidate pollinator; Phytomia zonata, A. cerana, and V. velutina were ordinary candidate pollinators; and four fly species, Episyrphus balteatus, and Eristalinus arvorum were classified as inefficient candidate pollinators. Our study shows that flies and hoverflies play an important role in the pollination system. Given the global decline in bee populations, the role of flies should also be considered in C. oleifera seed production.
RESUMO
The hydrochemical characterization and irrigation suitability assessment of the Ganges-Brahmaputra River System (GBRS) has immense importance for the livelihoods of people and ecosystem sustainability in the region. This study aims to assess the hydrochemical characteristics and evaluate the irrigation suitability of water in the GBRS by reviewing published literature of the major tributaries. The studied rivers were categorized into two groups namely Group-1 and Group-2 considering the similarities of climatic patterns, hydrochemical attributes, and drainage characteristics. The hydrochemistry of the river water was characterized by the Piper diagram, Gibbs plot, mixing plots, and ionic ratios. Furthermore, irrigation water qualities were evaluated by electrical conductivity (EC), sodium percentage (Na%), sodium adsorption ratio (SAR), magnesium hazard (MH), and Wilcox diagram. The results indicated that the hydrochemistry of the GBRS was slightly alkaline to alkaline (7.42-8.78) in nature. The average concentrations of most of the chemical attributes showed higher in Group-1, whereas the average concentrations of K+ and NO3 - were found higher in Group-2. The average concentration of the major ions followed the dominancy order Ca2+ > Mg2+ > Na+ > K+ for cations and HCO3 - >SO4 2- > Cl- > NO3 - for anions in both groups. Gibbs plot and mixing plot indicated that carbonate rock weathering dominates the hydrochemical process, which was further confirmed by the Piper diagram and the ionic ratios. From the analyses of irrigational water quality, almost all the rivers (except Gomti River in terms of MH and Rangit River in terms of Na%) in the GBRS were found to be suitable based on EC, SAR, Na%, MH, and Wilcox diagram. Finally, the majority of river systems in the GBRS were characterized by carbonate dominated lithology and irrigational water quality is mostly suitable for utilization. This study could be useful for water quality management in the glacial-fed Himalayan river under the context of global climate change.
RESUMO
BACKGROUND: This study introduces the results of laparoscopic radical cystectomy with modified intracorporeal ileal conduit (mICIC), which was accompanied by enhanced recovery after surgery (ERAS) protocols. METHODS: From March 2014 to June 2020, 48 patients underwent mICIC. Patients were divided into ERAS (n=17) and non-ERAS groups (n=31). Baseline and perioperative variables were analyzed. The primary outcome was 90-day complications. Secondary outcomes were operative time, length of stay, two-year overall survival, cancer-specific survival, and disease-free survival. RESULTS: Forty-eight patients underwent intracorporeal ileal conduit with no transition to open surgery. Twenty-five patients (52.1%) experienced at least one complication, including 22 minor cases (45.8%) and three major cases (6.2%). The median operative time, urinary diversion time, estimated blood loss, and length of stay were 320 min, 135 min, 200 mL, and 10.5 days, respectively. The median time to flatus and normal diet were two days and three days, respectively. A comparison between ERAS and non-ERAS groups indicated that ERAS implementation was associated with less complications (29.4% vs. 64.5%, P=0.018), faster time to flatus (2 vs. 3 days, P=0.016) and liquid diet (2 vs. 4 days, P<0.001). The results of hydronephrosis and compromised renal function showed no difference between the preoperative period and six months after surgery. The mean follow-up time was 25.4 months, and the two-year overall survival, cancer-specific survival, and disease-free survival rates were 61.3%, 73.2%, and 58.4%, respectively. CONCLUSIONS: The complication rate and operative time of the mICIC were acceptable. Clinical outcomes can be optimized with ERAS pathway.
RESUMO
Hippocampal lesions are recognized as the earliest pathological changes in Alzheimer's disease (AD). Recent researches have shown that the co-activation of growth hormone secretagogue receptor 1α (GHSR1α) and dopamine receptor D1 (DRD1) could recover the function of hippocampal synaptic and cognition. We combined traditional virtual screening technology with artificial intelligence models to screen multi-target agonists for target proteins from TCM database and a novel boost Generalized Regression Neural Network (GRNN) model was proposed in this article to improve the poor adjustability of GRNN. R-square was chosen to evaluate the accuracy of these artificial intelligent models. For the GHSR1α agonist dataset, Adaptive Boosting (AdaBoost), Linear Ridge Regression (LRR), Support Vector Machine (SVM), and boost GRNN achieved good results; the R-square of the test set of these models reached 0.900, 0.813, 0.708, and 0.802, respectively. For the DRD1 agonist dataset, Gradient Boosting (GB), Random Forest (RF), SVM, and boost GRNN achieved good results; the R-square of the test set of these models reached 0.839, 0.781, 0.763, and 0.815, respectively. According to these values of R-square, it is obvious that boost GRNN and SVM have better adaptability for different data sets and boost GRNN is more accurate than SVM. To evaluate the reliability of screening results, molecular dynamics (MD) simulation experiments were performed to make sure that candidates were docked well in the protein binding site. By analyzing the results of these artificial intelligent models and MD experiments, we suggest that 2007_17103 and 2007_13380 are the possible dual-target drugs for Alzheimer's disease (AD).
RESUMO
The aim of the present study was to use the clustered regularly interspaced short palindromic repeats (CRISPR) and CRISPRassociated (Cas) 9mediated gene knockout technology for the rapid classification of the differential function of micro (mi)RNAs screened using miRNA expression profiling by microarray. The rational design of single guide RNAs for the CRISPR/Cas9 system was verified to function in human LNCaP cells with rapid and efficient target gene editing. miRNA (miR)205, miR221, miR222, miR30c, miR224, miR4553p, miR23b and miR505 were downregulated in patients with prostate cancer (PCa) and were experimentally validated to function as tumor suppressors in prostate cancer cells, affecting tumor proliferation, invasion and aerobic glycolysis. In addition, the data of the present study suggested that miR663a and mfiR12255p were upregulated in prostate cancer tissues and cell proliferation of miR663a and miR12255p knockout PCa cells was significantly lower compared with miRNC cells. Furthermore, knockout of miR12255p and miR663a significantly decreased the lactate production in LNCaP cells in vitro. In conclusion, the present study offered a simple and efficient method for rapidly classifying miRNA function by applying CRISPR/Cas9 in LNCaP cells. The present study suggested, for the first time to the best of the authors' knowledge, that the aberrant expression of miR663a and miR12255p may be involved with the progression of prostate cancer, implying their potential as candidate markers for this type of cancer. However, the precise role of miR663a and miR12255p in accelerating the development of prostate cancer and promoting tumor progression remains to be elucidated.
Assuntos
Técnicas de Inativação de Genes/métodos , MicroRNAs/genética , Neoplasias da Próstata/genética , Sistemas CRISPR-Cas , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Progressão da Doença , Regulação Neoplásica da Expressão Gênica , Glicólise , Humanos , MasculinoRESUMO
PURPOSE: To investigate the anticancer properties of a well-known naturally occurring sesquiterpene lactone - artemisinin - against cisplatin resistant human breast carcinoma cells along with examining its effects on apoptosis, autophagy as well as cell cycle phase distribution. METHODS: MTT assay was used to study cytotoxic effects of artemisinin while clonogenic assay analysed its effects on cancer cell colony formation. Fluorescence microscopy using DAPI staining was employed to study apoptotic effects of artemisinin which was followed by annexin V/propidium iodide (PI) assay which quantified the apoptotic effects of artemisinin in cancer cells. Apoptotic effects of artemisinin were finally confirmed by western blot assay by analysing its effects on Bcl-2 and Bax protein expressions. Effects of artemisinin on autophagy were determined by transmission electron microscopy (TEM). Effects on cell cycle were analysed by flow cytometry and western blot. RESULTS: The results indicated that artemisinin led to considerable and dose-dependent antiproliferative effects on MDA-MB-231 cisplatin-resistant breast cancer cells with less toxicity in normal cell line, thus exhibiting selectivity. The colony formation decreased significantly as artemisinin dose increased. DAPI and comet assays revealed that artemisinin induced powerful apoptotic effects, triggering significant dose-dependent DNA damage. TEM indicated that artemisinin induced autophagy in MDA-MB-231 cisplatin-resistant human breast cancer cells by creating autophagosomes and autophagic vacuoles. The molecule also targeted G2/M phase cell cycle along with targeting some key cell cycle related proteins including cyclin-B1, cyclin D1 and cyclin E. CONCLUSION: The results show that artemisinin showed strong anticancer effects in MDA-MB-231 cisplatin-resistant cancer cells by triggering apoptosis and autophagy and G2/M phase arrest.