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Tauopathies, a group of neurodegenerative disorders, are characterized by disrupted homeostasis of the microtubule binding protein tau. Nogo-A mainly hinders axonal growth and development in neurons, but the underlying mechanism of tau vulnerability has not been determined. Here, to gain more comprehensive insights into the impact of Nogo-A on tau protein expression, we showed that Nogo-A induces tau hyperphosphorylation, synapse loss and cognitive dysfunction. Consistent with the biological function of tau hyperphosphorylation, Nogo-A-induced tau hyperphosphorylation altered microtubule stability, which causes synaptic dysfunction. Mechanistically, Nogo-A-induced tau hyperphosphorylation was abolished by the Nogo-A antagonist NEP1-40 in primary neurons. Surprisingly, downregulation of Nogo-A in the hippocampus of AD mice (hTau. P301S) inhibited tau hyperphosphorylation at the AT8, Thr181, The231 and Ser404 sites and rescued synaptic loss and cognitive impairment in AD mice. Our findings exhibit a strong degree of consistency with Nogo-A-induced tauopathy vulnerability, reinforcing the coherence and reliability of our research. Furthermore, in mice, Nogo-A increases tauopathy vulnerability to exacerbate AD progression via ROCK/AKT/GSK3ß signaling. Together, our findings provide new insight into the function of Nogo-A in regulating tau hyperphosphorylation and reveal an effective treatment strategy for tauopathies.
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Proton pump inhibitors (PPIs) are currently routinely used for the treatment of reflux esophagitis (RE); however, with frequent symptom recurrence after discontinuation and limited clinical improvement in accompanying gastrointestinal symptoms. This study aims to explore the adjuvant therapeutic effect of Bifidobacterium supplement for RE patients. A total of 110 eligible RE patients were recruited and randomly assigned to the placebo and probiotic groups. All patients were treated with rabeprazole tablets and simultaneously received either Bifidobacterium animalis subsp. lactis MH-02 or placebo for 8 weeks. Patients who achieved clinical remission then entered the next 12 weeks of follow-up. RDQ, GSRS scores, and endoscopy were performed to assess clinical improvement, and changes in intestinal microbiota were analyzed with high-throughput sequencing. Our results revealed that MH-02 combined therapy demonstrated an earlier time to symptom resolution (50.98% vs. 30.61%, p = 0.044), a significant reduction in the GSRS score (p = 0.0007), and a longer mean time to relapse (p = 0.0013). In addition, high-throughput analyses showed that MH-02 combined therapy increased the α (p = 0.001) diversity of gut microbiota and altered microbial composition by beta diversity analysis, accompanied with significantly altered gut microbiota taxa at the genus level, where the abundance of some microbial genera including Bifidobacterium, Clostridium, and Blautia were increased, while the relative abundance of Streptococcus and Rothia were decreased (p < 0.05). Collectively, these results support the beneficial effects of MH-02 as a novel complementary strategy in RE routine treatment.
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Bifidobacterium animalis , Esofagite Péptica , Probióticos , Humanos , Bifidobacterium , Inibidores da Bomba de Prótons/uso terapêutico , Método Duplo-CegoRESUMO
Mounting evidence has proposed the importance of the Wnt/ß-catenin pathway and tripartite motif 31 (TRIM31) in certain malignancies. Our research aimed to clarify the correlation between aberrant TRIM31 expression and the Wnt/ß-catenin pathway during gastric cancer (GC) oncogenesis and development. TRIM31 was drastically elevated in GC tissues and was closely associated with aggressive clinical outcomes and poor prognosis. Moreover, TRIM31 downregulation attenuated GC cell proliferation and invasion in vitro. Mechanistically, TRIM31 could bind and ubiquitinate Axin1 protein, thereby facilitating the activation of the Wnt/ß-catenin pathway. Additionally, Axin1 knockdown partially abrogated the inhibitory effects on the proliferative, invasive and migratory abilities of GC cells induced by TRIM31 silencing. Furthermore, TRIM31 was negatively correlated with Axin1 protein expression in GC tissues. In summary, we revealed a new TRIM31-Axin1-Wnt/ß-catenin axis that contributed greatly to the progression of GC, and targeting this regulatory axis may represent an effective treatment for GC patients.
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Neoplasias Gástricas , Humanos , Neoplasias Gástricas/patologia , beta Catenina/metabolismo , Linhagem Celular Tumoral , Via de Sinalização Wnt , Proliferação de Células , Estabilidade Proteica , Regulação Neoplásica da Expressão Gênica , Proteína Axina/genética , Proteína Axina/metabolismo , Movimento Celular , Proteínas com Motivo Tripartido/metabolismo , Ubiquitina-Proteína Ligases/genética , Ubiquitina-Proteína Ligases/metabolismoRESUMO
A bidynamical all-optical reservoir computing (RC) system for parallel task processing is proposed based on a unidirectional semiconductor optical amplifier optical fiber loop. The polarization dynamics and intensity dynamics are excited by the input signals injected into the reservoir via phase modulation and intensity modulation, respectively. Simultaneous computation of two independent tasks is implemented based on the dynamical responses in polarization and intensity of the optical fiber loop. To our knowledge, this is the first time that two kinds of dynamical responses of an all-optical RC system are used as independent task processing channels to implement parallel task processing. The proposed RC system can achieve good parallel task processing performance with low system cost.
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OBJECTIVE: Human adipose-derived mesenchymal stem cell exosomes (ADSC-Exos) are active constituents for treating liver fibrosis. This paper attempted to preliminarily explain the functional mechanism of ADSC-Exos in liver fibrosis through the p38 MAPK/NF-κB pathway. METHODS: The cell models of hepatic fibrosis were established by inducing LX-2 cells with TGF-ß1. Mouse models of liver fibrosis were established by treating mice with CCl4. The in vivo and in vitro models of liver fibrosis were treated with ADSC-Exos. ADSCs were identified by flow cytometry/Alizarin red/oil red O/alcian blue staining. ADSC-Exos were identified by transmission electron microscopy, nanoparticle tracking analysis, and Western blot. LX-2 cell proliferation/viability were evaluated by MTT/BrdU assays. Exosomes were tracked in vivo and body weight changes in mice were monitored. Hepatic pathological changes were observed by HE/Masson staining. α-SMA/collagen I levels in liver tissues were assessed by immunohistochemistry. HA/PIIINP concentrations were measured using the magnetic particle chemiluminescence method. Liver function was assessed using an automatic analyzer. miR-20a-5p level was measured by RT-qPCR. The mRNA levels of fibrosis markers were determined by RT-qPCR, and their protein levels and levels of MAPK/NF-κB pathway-related proteins, as well as TGFBR2 protein level were measured by Western blot. The P65 nuclear expression in mouse liver tissues was quantified by immunofluorescence. RESULTS: ADSC-Exos suppressed TGF-ß1-induced LX-2 cell proliferation and fibrosis and reduced mRNA and protein levels of fibrosis markers in vitro. ADSC-Exos ameliorated liver fibrosis by inhibiting the p38 MAPK/NF-κB pathway activation. ADSC-Exos inhibited activation of the p38 MAPK/NF-κB pathway via regulating the miR-20a-5p/TGFBR2 axis. The in vivo experiment asserted that ADSC-Exos were mainly distributed in the liver, and ADSC-Exos relieved liver fibrosis in mice, which was evidenced by alleviating decreased body weight, reducing collagen and enhancing liver function, and repressed the activation of the p38 MAPK/NF-κB pathway via the miR-20a-5p/TGFBR2 axis. CONCLUSION: ADSC-Exos attenuated liver fibrosis by suppressing the activation of the p38 MAPK/NF-κB pathway via the miR-20a-5p/TGFBR2 axis.
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Exossomos , Células-Tronco Mesenquimais , MicroRNAs , Camundongos , Humanos , Animais , NF-kappa B/metabolismo , Fator de Crescimento Transformador beta1 , Receptor do Fator de Crescimento Transformador beta Tipo II/genética , Exossomos/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno , Cirrose Hepática/genética , Cirrose Hepática/terapia , Células-Tronco Mesenquimais/metabolismo , Fibrose , Colágeno , MicroRNAs/genética , RNA Mensageiro , Peso CorporalRESUMO
BACKGROUND: The incidence and mortality rates of gastric cancer in China are the second-highest in the world, and most patients with gastric cancer lose their chance of surgery by the time of their diagnosis. AIM: To explore the predictive potential of serum basic fibroblast growth factor and interleukin-1ß levels for the effect of first-line chemotherapy in patients with advanced gastric cancer. METHODS: From the gastric cancer patients admitted to our hospital from May 2019 to April 2023, 84 patients were selected and randomly and equally assigned to the experimental or control group. The FLOT group received the FLOT chemotherapy regimen (composed of oxaliplatin + calcium folinate + fluorouracil + paclitaxel), while the SOX group received the SOX chemotherapy regimen (composed of oxaliplatin + tiga capsules). The clinical efficacy, tumor marker levels, adverse reactions, and survival rates of the two groups were compared 7 days after the end of the relevant treatments. RESULTS: The target effective rate of the FLOT group was 54.76%, which was much higher than that of the SOX group (33.33%; P < 0.05). After treatment, both the groups demonstrated lower levels of cancer antigen (CEA), carbohydrate antigen 199 (CA199), and peptide tissue antigen (TPS). For several patients before treatment (P < 0.05). Third and fourth grades. In terms of adverse reactions, the level of white blood cells in both the groups was lower. Moreover, the incidence of hand-foot skin reactions in these two study groups was lower (P < 0.05), while those of peripheral neuritis, vomiting, diarrhea, and abnormal liver function were significant (P < 0.05). No statistically significant difference was noted between the two groups (P < 0.05). The 1-year survival rate was higher in the FLOT group (P < 0.05). CONCLUSION: The FLOT regimen was effective in reducing the serum CEA, CA199, and TPS levels as well as in improving the 1-year survival rate of patients with good tolerability, making it worthy of clinical promotion and application.
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Background: Endoscopic sclerotherapy is a widely used minimally invasive procedure for internal hemorrhoids, yet postoperative symptoms remain a concern. The purpose of this study is to investigate the postoperative adjuvant efficacy of Lactiplantibacillus plantarum. Method: In this study, patients (≥18 years) with internal hemorrhoids that conformed to Goligher's classification of grade I-III received administration of L. plantarum MH-301 for 4 weeks following endoscopic sclerotherapy. The primary clinical endpoint in this study was the improvement rate, which was defined as the percentage of patients whose n-HDSS score decreased to 0 following the procedure. Stools were collected for high-throughput sequencing analysis post operation. Result: A total of 103 participants (51 in the LP group and 52 in the C group) were recruited, with 96 completing the entire trial (49 in the LP group and 47 in the C group). The primary clinical endpoint showed a higher improvement rate in the LP group (87.8% vs. 70.2%, P = 0.045). High-throughput sequencing analysis demonstrated that the LP group had a greater diversity of intestinal microbiota and a higher relative abundance of beneficial bacteria such as Bifidobacterium, Megamonas, and Lactobacillus. No significant difference in postoperative complications and adverse events was found. Conclusion: This paper concludes that the administration of L. plantarum MH-301 after endoscopic sclerotherapy can further increase the efficacy of the procedure and improve bowel movements. Regulation of intestinal microbiota may be the potential mechanism for the efficacy of L. plantarum MH-301.
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Hemorroidas , Humanos , Hemorroidas/cirurgia , Escleroterapia , Lactobacillus , Adjuvantes Imunológicos , BifidobacteriumRESUMO
A novel multi-wavelength Brillouin random fiber laser with the channel space of triple Brillouin frequency shift and high polarization orthogonality between adjacent wavelengths (TOP-MWBRFL), to the best of our knowledge, is experimentally demonstrated. The TOP-MWBRFL is structured in a ring form by cascading two Brillouin random cavities of single-mode fiber (SMF) and one Brillouin random cavity of polarization-maintaining fiber (PMF). Based on polarization pulling properties of stimulated Brillouin scattering in long-distance SMFs and PMFs, the states of polarization (SOPs) of lasing light from SMF random cavities are linearly bounded to the SOPs of local pump light, whereas the SOP of lasing light from the PMF random cavity is strictly clamped on one of the principal axes of the PMF. Thus, the TOP-MWBRFL can stably emit multi-wavelength light with high polarization extinction ratio (>35d B) between adjacent wavelengths without precise polarization feedback. In addition, the TOP-MWBRFL can also work in one polarization mode to stably lase multi-wavelength light with SOP uniformity as high as 37 dB.
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Ressecção Endoscópica de Mucosa , Tumores Neuroendócrinos , Neoplasias Retais , Neoplasias Gástricas , Humanos , Tumores Neuroendócrinos/cirurgia , Tumores Neuroendócrinos/patologia , Tração , Dispositivos para o Cuidado Bucal Domiciliar , Neoplasias Gástricas/patologia , Resultado do Tratamento , Neoplasias Retais/cirurgia , Neoplasias Retais/patologiaRESUMO
Multi-modal medical image fusion can reduce information redundancy, increase the understandability of images and provide medical staff with more detailed pathological information. However, most of traditional methods usually treat the channels of multi-modal medical images as three independent grayscale images which ignore the correlation between the color channels and lead to color distortion, attenuation and other bad effects in the reconstructed image. In this paper, we propose a multi-modal medical image fusion algorithm with geometric algebra based sparse representation (GA-SR). Firstly, the multi-modal medical image is represented as a multi-vector, and the GA-SR model is introduced for multi-modal medical image fusion to avoid losing the correlation of channels. Secondly, the orthogonal matching pursuit algorithm based on geometric algebra (GAOMP) is introduced to obtain the sparse coefficient matrix. The K-means clustering singular value decomposition algorithm based on geometric algebra (K-GASVD) is introduced to obtain the geometric algebra dictionary, and update the sparse coefficient matrix and dictionary. Finally, we obtain the fused image by linear combination of the geometric algebra dictionary and the coefficient matrix. The experimental results demonstrate that the proposed algorithm outperforms existing methods in subjective and objective quality evaluation, and shows its effectiveness for multi-modal medical image fusion.
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Background: Postoperative symptoms, bowel dysfunction and recurrence are common problems after resection of colorectal polyps. We aimed to evaluate the efficacy of Bifidobacterium in the postoperative patients. Methods: In this single-center, randomized, double-blind, placebo-controlled trial, adults (≥ 18 years) undergoing endoscopic resection of colorectal polyps were treated with probiotics (Bifidobacterium animalis subsp. lactis MH-02, 2 × 109 colony-forming units per packet) or placebo once daily for 7 days. The primary clinical endpoint was a reduction in the mean total postoperative symptoms score within 7 days postoperatively. Secondary clinical endpoints were the single symptom scores, time to recovery of bowel function, and changes in the intestinal microbiota. This study is registered with the number ChiCTR2100046687. Results: A total of 100 individuals were included (48 in probiotic group and 52 in placebo group). No difference was seen in the mean scores between the two groups (0.29 vs. 0.43, P = 0.246). Colorectal polyps size (P = 0.008) and preoperative symptoms (P = 0.032) were influential factors for the primary endpoint. Besides, MH-02 alleviated difficult defecation (P = 0.045), and reduced the time to recovery of bowel function (P = 0.032). High-throughput analysis showed that MH-02 can help restore the diversity of intestinal microbiota, and increased the relative abundance of Bifidobacterium, Roseburia, Gemmiger, Blautia and Ruminococcus, while reduced the relative abundance of Clostridium at genus level (P < 0.05). Conclusion: In this prospective trial, MH-02 showed efficacy in patients with resection of colorectal polyps, particularly in the recovery of bowel function, and the changes in the intestinal microbiota may provide evidence for further exploration of the therapeutic mechanisms.
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Bifidobacterium animalis , Pólipos do Colo , Probióticos , Adulto , Bifidobacterium , Pólipos do Colo/cirurgia , Humanos , Probióticos/uso terapêutico , Estudos ProspectivosRESUMO
BACKGROUND: Gastric cancer is one of the most lethal malignancies worldwide with surgery as the only curative therapy. However, postoperative overall survival of gastric cancer is far from satisfactory although significant improvement has been made in adjuvant therapies. Gastric cancer is characterized as highly heterogeneous and illustrating the molecular mechanisms is invaluable for both identification of novel prognostic biomarkers and development of therapeutic drugs. Here we aimed to investigate the participation of Anoctamin 6 (ANO6) in gastric adenocarcinoma. METHODS: Immunohistochemical (IHC) staining was used to explore the expression pattern of ANO6 in tumor tissues from gastric adenocarcinoma patients (n=108). Clinicopathological data was subjected to Kaplan-Meier survival and Cox multivariate analyses to evaluate prognostic predictors. Overexpression and silencing procedures were performed on gastric cancer cell lines to investigate the functional mechanisms of ANO6 in regulating tumor development. RESULTS: Higher ANO6 expression showed a positive correlation with advanced tumor stage of gastric cancer. Univariate and multivariate analyses revealed that ANO6 was an independent prognostic factor for overall survival of gastric cancer. An in vitro study demonstrated that ANO6 can promote cell proliferation while silencing ANO6 significantly downregulated cell viability. CONCLUSION: High ANO6 expression in gastric cancer indicates poor clinical outcomes, and ANO6 may act as a potential target for novel therapy development targeting gastric cancer.
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Adenocarcinoma , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/patologia , Prognóstico , Adenocarcinoma/patologia , Proliferação de Células , Anoctaminas , Biomarcadores Tumorais/análise , Estimativa de Kaplan-MeierRESUMO
To improve the accuracy of signal recognition in optical fiber perimeter defense systems, a method based on Mel frequency cepstral coefficients (MFCCs) and a fast dynamic time warping (FastDTW) algorithm is proposed. Four kinds of sensing signals are acquired by employing an in-line Sagnac interferometer system. MFCC features of the signals are extracted. The FastDTW algorithm is utilized to calculate distances of the optimal warping paths between a test sample and all reference templates. According to the nearest neighbor criterion, signal recognition results are obtained. The average accuracy is over 96%. This proposed identification method is highly efficient and easy to implement.
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Algoritmos , Fibras ÓpticasRESUMO
ABSTRACT: Early determination of coronavirus disease 2019 (COVID-19) pneumonia from numerous suspected cases is critical for the early isolation and treatment of patients.The purpose of the study was to develop and validate a rapid screening model to predict early COVID-19 pneumonia from suspected cases using a random forest algorithm in China.A total of 914 initially suspected COVID-19 pneumonia in multiple centers were prospectively included. The computer-assisted embedding method was used to screen the variables. The random forest algorithm was adopted to build a rapid screening model based on the training set. The screening model was evaluated by the confusion matrix and receiver operating characteristic (ROC) analysis in the validation.The rapid screening model was set up based on 4 epidemiological features, 3 clinical manifestations, decreased white blood cell count and lymphocytes, and imaging changes on chest X-ray or computed tomography. The area under the ROC curve was 0.956, and the model had a sensitivity of 83.82% and a specificity of 89.57%. The confusion matrix revealed that the prospective screening model had an accuracy of 87.0% for predicting early COVID-19 pneumonia.Here, we developed and validated a rapid screening model that could predict early COVID-19 pneumonia with high sensitivity and specificity. The use of this model to screen for COVID-19 pneumonia have epidemiological and clinical significance.
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Algoritmos , Teste para COVID-19/métodos , COVID-19/diagnóstico , Programas de Rastreamento/métodos , SARS-CoV-2/isolamento & purificação , Adulto , China , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Curva ROC , Sensibilidade e EspecificidadeRESUMO
OBJECTIVE: To investigate the establishment of a risk assessment system for peptic ulcer (PU) recurrence and implement an individualized intervention for PU patients with a moderate to high recurrence risk to reduce the recurrence of PU in patients with a moderate to high recurrence risk. METHODS: The factors for PU recurrence were collected through consulting the literature, and a risk prediction model for PU recurrence was established using the univariate binary and multivariate multinomial Logistic stepwise regression analysis. According to the model, a total of 235 PU patients were divided into patients with high, moderate and low recurrence risks. A total of 71 PU patients with moderate to high recurrence risks were selected as the study subjects, and further divided into the control group (n=35) and the experimental group (n=36). The control group was not treated with intervention, while the experimental group was treated with individualized intervention. The PU recurrence, adverse emotions and changes of pain degree were assessed in the two groups at 3, 6, 9 and 12 months after intervention. RESULTS: The univariate and multivariate Logistic regression analysis showed that drinking alcohol, smoking, chronic diseases, oral NSAIDS and depression were associated with the recurrence of PU. Individualized intervention improved the recurrence rate, anxiety, depression, pain degree and quality of life of patients with moderate to high PU recurrence risk. CONCLUSION: Drinking alcohol, smoking, chronic diseases, oral NSAIDS and depression were associated with the recurrence of PU. Individualized intervention can improve the quality of prognosis and the recurrence risk of PU in patients, which has positive clinical significance.
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BACKGROUND: The small proline-rich protein 2B (SPRR2B) was firstly reported as a member of the cross-linked envelope protein in keratinocytes. The effect of SPRR2B in gastric adenocarcinoma (GC) remains unclear. This study initially explored the clinical significance of SPRR2B in GC patients as well as its role in tumor progression. METHODS: Immunohistochemistry was performed to characterize the expression of SPRR2B in GC tissues and adjacent tissues. The relationship between SPRR2B expression and clinicopathological features of GC patients was analyzed by Chi-square test. Kaplan-Meier method and Cox regression analyses were utilized to identify the prognostic factors of GC. Overexpression and knockdown assays were conducted to investigate possible signaling pathways downstream of SPRR2B. Flow cytometry assays were performed to evaluate cell cycle and apoptosis. Xenograft experiments were performed to validate tumor-related role of SPRR2B in vivo. RESULTS: Both mRNA and protein levels of SPRR2B in cancerous tissue were significantly higher than those in non-cancerous tissues. Meanwhile, SPRR2B expression was significantly associated with tumor size and tumor stage. Survival analysis revealed SPRR2B as one of the independent prognosis factors for overall survival of GC patients. Cellular and xenografts data implicated that silencing SPRR2B blocked the cell cycle of GC cells perhaps through MDM2-p53/p21-CDK1 pathway, while overexpressing SPRR2B exhibited opposite effects. CONCLUSION: Our data suggest that SPRR2B may serve as a novel prognostic marker in GC, which functions at least partially by MDM2-p53/p21-CDK1 signaling pathway.
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Novel coronavirus pneumonia (NCP) has been widely spread in China and several other countries. Early finding of this pneumonia from huge numbers of suspects gives clinicians a big challenge. The aim of the study was to develop a rapid screening model for early predicting NCP in a Zhejiang population, as well as its utility in other areas. A total of 880 participants who were initially suspected of NCP from January 17 to February 19 were included. Potential predictors were selected via stepwise logistic regression analysis. The model was established based on epidemiological features, clinical manifestations, white blood cell count, and pulmonary imaging changes, with the area under receiver operating characteristic (AUROC) curve of 0.920. At a cut-off value of 1.0, the model could determine NCP with a sensitivity of 85% and a specificity of 82.3%. We further developed a simplified model by combining the geographical regions and rounding the coefficients, with the AUROC of 0.909, as well as a model without epidemiological factors with the AUROC of 0.859. The study demonstrated that the screening model was a helpful and cost-effective tool for early predicting NCP and had great clinical significance given the high activity of NCP.
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COVID-19/diagnóstico , COVID-19/epidemiologia , Programas de Rastreamento , Modelos Biológicos , Pneumonia/diagnóstico , SARS-CoV-2/fisiologia , Adulto , China/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Curva ROCRESUMO
The generation of ßamyloid protein (Aß) is considered a key step in the pathogenesis of Alzheimer's disease (AD) and the regulation of its production is an important therapeutic strategy. It was hypothesized in the present study that NogoA may be involved in AD and may regulate the generation of Aß. NogoA is known to act as a major inhibitor of neuron regeneration in the adult central nervous system. A recent study indicated that NogoA is associated with AD; however, the underlying effect and molecular mechanisms remain largely elusive. In the present study, the potential effects of NogoA on AD were investigated. ELISA was used to detect the levels of Aß, enzymatic activity detection kits were used to determine the activity of secretase enzymes in amyloid precursor protein (APP) metabolism, and western blot analysis was used to detect the expression levels of proteins associated with the APP processing and NogoA/Nogo66 receptor (NgR) signaling pathways. The results revealed that Nogo66, the major inhibitory region of NogoA, promoted neuronal Aß secretion by increasing the activity of ßsecretase 1 via the NgR/Rhoassociated coiledcoil containing kinases pathway in a dosedependent manner. The present data suggested that NogoA may facilitate the onset and development of AD by promoting Aß secretion, providing information on a potential novel target for AD therapy.
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Doença de Alzheimer/metabolismo , Secretases da Proteína Precursora do Amiloide/metabolismo , Peptídeos beta-Amiloides/metabolismo , Ácido Aspártico Endopeptidases/metabolismo , Proteínas Nogo/metabolismo , Receptor Nogo 1/metabolismo , Transdução de Sinais , Doença de Alzheimer/genética , Doença de Alzheimer/patologia , Secretases da Proteína Precursora do Amiloide/genética , Peptídeos beta-Amiloides/genética , Animais , Ácido Aspártico Endopeptidases/genética , Neurônios/metabolismo , Neurônios/patologia , Proteínas Nogo/genética , Receptor Nogo 1/genética , Ratos , Ratos Sprague-Dawley , Quinases Associadas a rho/genética , Quinases Associadas a rho/metabolismoRESUMO
Amyloid-ß (Aß) accumulation is a pathological hallmark of Alzheimer's disease (AD). The receptor for advanced glycation end products (RAGE) is involved in the production and accumulation of Aß. RP1, a peptide antagonist of RAGE, was screened by phage display technology in our previous studies, and its neuroprotective effects on an AD cell model have been confirmed. However, its efficacy in vivo remains unclear. Here, the intranasal delivery of RP1 to APPSwe/PS1dE9 (APP/PS1) mice significantly improved memory impairment and relieved the Aß burden by decreasing the expression of amyloid precursor protein and ß-secretase. RNA-sequencing (RNA-seq) was utilized to identify differentially expressed genes (DEGs) in APP/PS1 mice after RP1 administration. Several DEGs in RAGE downstream signalling pathways were downregulated. Some transcription factors (such as Fos) and the pathways enriched in the remarkable modules may also be related to the efficacy of RP1. In conclusion, RP1 significantly improves the AD symptoms of APP/PS1 mice, and the RNA-seq results provide new ideas for elucidating the possible mechanisms of RP1 treatment.