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BACKGROUND: Calculus bovis (CB), used in traditional Chinese medicine, exhibits anti-tumor effects in various cancer models. It also constitutes an integral component of a compound formulation known as Pien Tze Huang, which is indicated for the treatment of liver cancer. However, its impact on the liver cancer tumor microenvironment, particularly on tumor-associated macrophages (TAMs), is not well understood. AIM: To elucidate the anti-liver cancer effect of CB by inhibiting M2-TAM polarization via Wnt/ß-catenin pathway modulation. METHODS: This study identified the active components of CB using UPLC-Q-TOF-MS, evaluated its anti-neoplastic effects in a nude mouse model, and elucidated the underlying mechanisms via network pharmacology, transcriptomics, and molecular docking. In vitro assays were used to investigate the effects of CB-containing serum on HepG2 cells and M2-TAMs, and Wnt pathway modulation was validated by real-time reverse transcriptase-polymerase chain reaction and Western blot analysis. RESULTS: This study identified 22 active components in CB, 11 of which were detected in the bloodstream. Preclinical investigations have demonstrated the ability of CB to effectively inhibit liver tumor growth. An integrated approach employing network pharmacology, transcriptomics, and molecular docking implicated the Wnt signaling pathway as a target of the antineoplastic activity of CB by suppressing M2-TAM polarization. In vitro and in vivo experiments further confirmed that CB significantly hinders M2-TAM polarization and suppresses Wnt/ß-catenin pathway activation. The inhibitory effect of CB on M2-TAMs was reversed when treated with the Wnt agonist SKL2001, confirming its pathway specificity. CONCLUSION: This study demonstrated that CB mediates inhibition of M2-TAM polarization through the Wnt/ß-catenin pathway, contributing to the suppression of liver cancer growth.
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Neoplasias Hepáticas , Camundongos Nus , Simulação de Acoplamento Molecular , Microambiente Tumoral , Macrófagos Associados a Tumor , Via de Sinalização Wnt , Via de Sinalização Wnt/efeitos dos fármacos , Animais , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/metabolismo , Humanos , Camundongos , Células Hep G2 , Macrófagos Associados a Tumor/metabolismo , Macrófagos Associados a Tumor/efeitos dos fármacos , Macrófagos Associados a Tumor/imunologia , Microambiente Tumoral/efeitos dos fármacos , Ensaios Antitumorais Modelo de Xenoenxerto , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/metabolismo , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico , Proliferação de Células/efeitos dos fármacos , Camundongos Endogâmicos BALB C , Masculino , Farmacologia em Rede , beta Catenina/metabolismo , Medicina Tradicional Chinesa/métodosRESUMO
Hyperuricemia, characterized by elevated uric acid levels and subsequent crystal deposition, contributing to conditions such as gout, cardiovascular events, and kidney injury, poses a significant health threat, particularly in developed countries. Current drug options for treatment are limited, with safety concerns, leading to suboptimal therapeutic outcomes in symptomatic hyperuricemia patients and a lack of pharmaceutical interventions for asymptomatic cases. Distinguishing from the previous drug design strategies, we directly target uric acid, the pathological molecule of hyperuricemia, resulting in a pyrimidine derivative capable of increasing the solubility and excretion of uric acid by forming a complex with it. Its prodrug showed an anti-hyperuricemia activity comparable to benzbromarone and a favorable safety profile in vivo. Our finding provides a strategy purely based on organic chemistry to address the largely unmet therapeutic needs on novel anti-hyperuricemia drugs.
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Human pluripotent stem cell (hPSC)-derived kidney organoids share similarities with the fetal kidney. However, the current hPSC-derived kidney organoids have some limitations, including the inability to perform nephrogenesis and lack of a corticomedullary definition, uniform vascular system, and coordinated exit pathway for urinary filtrate. Therefore, further studies are required to produce hPSC-derived kidney organoids that accurately mimic human kidneys to facilitate research on kidney development, regeneration, disease modeling, and drug screening. In this review, we discussed recent advances in the generation of hPSC-derived kidney organoids, how these organoids contribute to the understanding of human kidney development and research in disease modeling. Additionally, the limitations, future research focus, and applications of hPSC-derived kidney organoids were highlighted.
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Two new quinoline alkaloids with an α, ß-unsaturated amide side chain, xylarinines A and B (1 and 2), were isolated from the ethyl acetate extracts of Xylaria longipes solid fermentation. The structures of these were primarily determined though NMR and HRESIMS data analysis. The absolute configuration of compound 1 was assigned using experimental and calculated ECD data. The neuroprotective effects of compounds 1 and 2 against glutamate-induced damage in PC12 cells were evaluated in vitro bioassay. The results demonstrated that both compounds significantly improved cell viability, inhibited apoptosis, decreased malondialdehyde (MDA) levels, increased superoxide dismutase (SOD) and glutathione (GSH) levels, and reduced intracellular reactive oxygen species (ROS) accumulation. These findings suggested that these mechanisms contribute to the neuroprotective effects of the compounds.
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Alcaloides , Apoptose , Fármacos Neuroprotetores , Quinolinas , Espécies Reativas de Oxigênio , Xylariales , Células PC12 , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/isolamento & purificação , Animais , Ratos , Quinolinas/farmacologia , Quinolinas/isolamento & purificação , Estrutura Molecular , Alcaloides/farmacologia , Alcaloides/isolamento & purificação , Espécies Reativas de Oxigênio/metabolismo , Xylariales/química , Apoptose/efeitos dos fármacos , Superóxido Dismutase/metabolismo , Compostos Fitoquímicos/farmacologia , Compostos Fitoquímicos/isolamento & purificação , Malondialdeído/metabolismo , Glutationa/metabolismo , Sobrevivência Celular/efeitos dos fármacos , China , Ácido GlutâmicoRESUMO
A pair of new chromone derivative enantiomers, (+)-xylarichromone A (1a) and (-)-xylarichromone A (1b), were isolated from the solid fermentation of Xylaria nigripes. The planar structure of 1 was determined by extensive NMR spectroscopic data, and its absolute configuration was assigned by comparison the ECD spectra with the known chromone derivatives. Compound 1 was the first chromone derivative reported from this medicinal fungus. The neuroprotective effects of 1 against oxygen and glucose deprivation (OGD) induced pheochromocytoma-12 cells (PC12) injury was investigated.
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Ascomicetos , Cromonas , Cromonas/farmacologia , Cromonas/química , Estrutura Molecular , Espectroscopia de Ressonância MagnéticaRESUMO
Circadian (24-h) rhythms in the suprachiasmatic nucleus (SCN) are established in utero in rodents, but rhythmicity of peripheral circadian clocks appears later in postnatal development. Since peripheral oscillators can be influenced by maternal feeding and behavior, we investigated whether exposure to the adverse environmental conditions of limited bedding (LB) during postnatal life would alter rhythmicity in the SCN, adrenal gland and liver in neonatal (postnatal day PND10), juvenile (PND28) and adult rats. We also examined locomotor activity in adults. Limited bedding increased nursing time and slightly increased fragmentation of maternal behavior. Exposure to LB reduced the amplitude of Per2 in the SCN on PND10. Adrenal clock gene expression (Bmal1, Per2, Cry1, Rev-erbα, Dbp) and corticosterone secretion were rhythmic at all ages in NB offspring, whereas rhythmicity of Bmal1, Cry1 and corticosterone was abolished in neonatal LB pups. Circadian gene expression in the adrenal and liver was well established by PND28. In adults, liver expression of several circadian genes was increased at specific daytimes by LB and the microstructure of locomotor behavior was altered. Thus, changes in maternal care and behavior might provide important signals to the maturing peripheral oscillators and modify, in particular their output functions in the long-term.
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Relógios Circadianos , Ritmo Circadiano , Feminino , Ratos , Animais , Ritmo Circadiano/genética , Corticosterona/metabolismo , Fatores de Transcrição ARNTL/metabolismo , Relógios Circadianos/genética , Núcleo Supraquiasmático/metabolismoRESUMO
BACKGROUND: Obesity usually causes diabetes mellitus (DM) and is a serious danger to human health. Type 2 DM (T2DM) mostly occurs along with obesity. Foodborne obesity-induced DM is caused by an excessive long-term diet and surplus energy. Bariatric surgery can improve the symptoms of T2DM in some obese patients. But different types of bariatric surgery may have different effects. AIM: To investigate the effect of bariatric surgery on glucose and lipid metabolism and liver and kidney function in rats. METHODS: Male Sprague-Dawley rats aged 6-8 wk underwent Roux-en-Y gastric bypass surgery (RYGB), sleeve gastrectomy (SG), or gastric banding (GB). Glucose and insulin tolerance tests, analyses of biochemical parameters, histological examination, western blot, and quantitative real-time polymerase chain reaction were conducted. RESULTS: In comparison to the sham operation group, the RYGB, SG, and GB groups had decreased body weight and food intake, reduced glucose intolerance and insulin insensitivity, downregulated biochemical parameters, alleviated morphological changes in the liver and kidneys, and decreased levels of protein kinase C ß/ P66shc. The effect in the RYGB group was better than that in the SG and GB groups. CONCLUSION: These results suggest that RYGB, SG and GB may be helpful for the treatment of foodborne obesity-induced DM.
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Wellcomia compar (Spirurina: Oxyuridae) is a pinworm that infects wild and captive porcupines. Despite clear records of its morphological structure, its genetics, systematics, and biology are poorly understood. This study aimed to determine the complete mitochondrial (mt) genome of W. compar and reconstruct its phylogenetic relationship with other nematodes. We sequenced the complete mt genome of W. comparand conducted phylogenetic analyses using concatenated coding sequences of 12 protein-coding genes (PCGs) by maximum likelihood and Bayesian inference. The complete mt genome is 14,373 bp in size and comprises 36 genes, including 12 protein-coding, two rRNA and 22 tRNA genes. Apart from 28 intergenic regions, one non-coding region and one overlapping region also occur. A comparison of the gene arrangements of Oxyuridomorpha revealed relatively similar features in W. compar and Wellcomia siamensis. Phylogenetic analysis also showed that W. compar and W. siamensis formed a sister group. In Oxyuridomorpha the genetic distance between W. compar and W. siamensis was 0.0805. This study reports, for the first time, the complete W. compar mt genome sequence obtained from Chinese porcupines. It provides genetic markers for investigating the taxonomy, population genetics, and phylogenetics of pinworms from different hosts and has implications for the diagnosis, prevention, and control of parasitic diseases in porcupines and other animals.
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Genoma Mitocondrial , Oxyuroidea , Spirurina , Animais , Filogenia , Teorema de BayesRESUMO
The Xifeng Hot Spring is one of the eight largest hot springs in China, which is rich in radon gas and sulphur in karst scenery. Little is known about the microbiota structure in the spring. The water was collected from three sites containing the outlet of spring water discharge site (OWD), spring pool for tourist (SPT) and sewage effluent pool (SEP) in the Xifeng Hot Spring and further analyzed by culture-independent technique and culture-dependent method. A total of 57 phyla were identified from the water samples. The dominate phyla at OWD was Bacteroidetes (46.93%), while it was Proteobacteria in both sites of SEP and SPT with relative richness of 61.9% and 94.9%, respectively. Two bacteria, Deinococcus and Hymenobacter, that confirmed to be radiation-resistant, seven sulphur bacteria and three thermophilic bacteria were detected from Xifeng Hot Spring. Furthermore, it was found that genus Flavobacterium was susceptible to environmental change with abundance of 11 ~ 2825 times higher in OWD than the other two groups. Compared bacteria from the OWD group with that from 14 hot springs in six countries, total 94 unique genera bacteria were found out from the Xifeng Hot Spring including four thiometabolism-related bacteria (Propionispira, Desulforegula, Desulfobacter and Desulfococcus) and the thermophilic bacterium (Symbiobacterium). Using microbial culturing and isolation technology, sixteen strains were isolated from the water samples of three sites. The diversity of microbiota was abundant and variable along with the niche changed in conditions and surroundings. It indicated that numbers of valuable bacteria resources could be explored from the special surroundings of Xifeng Hot Spring.
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Fontes Termais , Bactérias/genética , China , Esgotos , Enxofre , ÁguaRESUMO
Two pairs of new isobenzofuranone derivative enantiomers, (±)-penicifurans E (1) and (±)-penicifurans F (2), together with four know compounds (3-6) were isolated from the solid fermentation of Penicillium canescens DWS225. The structures of these enantiomers were elucidated by extensive NMR spectroscopic data, and their absolute configurations were assigned by the experimental and calculated ECD data. The neuroprotective effects of all the isolates against oxygen-glucose deprivation/reperfusion injury in pheochromocytoma-12 cells (PC12) were investigated.
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Purpose: We aim to present effective and computer aided diagnostics in the field of ophthalmology and improve eye health. This study aims to create an automated deep learning based system for categorizing fundus images into three classes: normal, macular degeneration and tessellated fundus for the timely recognition and treatment of diabetic retinopathy and other diseases. Methods: A total of 1,032 fundus images were collected from 516 patients using fundus camera from Health Management Center, Shenzhen University General Hospital Shenzhen University, Shenzhen 518055, Guangdong, China. Then, Inception V3 and ResNet-50 deep learning models are used to classify fundus images into three classes, Normal, Macular degeneration and tessellated fundus for the timely recognition and treatment of fundus diseases. Results: The experimental results show that the effect of model recognition is the best when the Adam is used as optimizer method, the number of iterations is 150, and 0.00 as the learning rate. According to our proposed approach we, achieved the highest accuracy of 93.81% and 91.76% by using ResNet-50 and Inception V3 after fine-tuned and adjusted hyper parameters according to our classification problem. Conclusion: Our research provides a reference to the clinical diagnosis or screening for diabetic retinopathy and other eye diseases. Our suggested computer aided diagnostics framework will prevent incorrect diagnoses caused by the low image quality and individual experience, and other factors. In future implementations, the ophthalmologists can implement more advanced learning algorithms to improve the accuracy of diagnosis.
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OBJECTIVES: Sarcopenia is associated with significantly higher mortality risk, and earlier detection of sarcopenia has remarkable public health benefits. However, the model that predicts sarcopenia in the community has yet to be well identified. The study aimed to develop a nomogram for predicting the risk of sarcopenia and compare the performance with 3 sarcopenia screen models in community-dwelling older adults in China. DESIGN: Cross-sectional study. SETTING AND PARTICIPANTS: A total of 966 community-dwelling older adults. METHODS: A total of 966 community-dwelling older adults were enrolled in the study, with 678 participants grouped into the Training Set and 288 participants grouped into the Validation Set according to a 7:3 randomization. Predictors were identified in the Training Set by univariate and multivariate logistic regression and then combined into a nomogram to predict the risk of sarcopenia. The performance of this nomogram was assessed by calibration, discrimination, and clinical utility. RESULTS: Age, body mass index, calf circumference, congestive heart failure, and chronic obstructive pulmonary disease were demonstrated to be predictors for sarcopenia. The nomogram (named as AB3C model) that was constructed based on these predictors showed excellent calibration and discrimination in the Training Set with an area under the receiver operating characteristic curve (AUC) of 0.930. The nomogram also showed perfect calibration and discrimination in the Validation Set with an AUC of 0.897. The clinical utility of the nomogram was supported by decision curve analysis. Comparing the performance with 3 sarcopenia screen models (SARC-F, Ishii, and Calf circumference), the AB3C model outperformed the other models regarding sensitivity and AUC. CONCLUSIONS AND IMPLICATIONS: AB3C model, an easy-to-apply and cost-effective nomogram, was developed to predict the risk of sarcopenia, which may contribute to optimizing sarcopenia screening in community settings.
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Sarcopenia , Humanos , Idoso , Sarcopenia/diagnóstico , Vida Independente , Estudos Transversais , Nomogramas , Programas de Rastreamento , Avaliação GeriátricaRESUMO
INTRODUCTION: The etiology of Parkinson's disease (PD) is still unknown. Until now, oxidative stress and neuroinflammation play a crucial role in the pathogenesis of PD. However, the specific synergistic role of oxidative stress and neuroinflammation in the occurrence and development of PD remains unclear. METHODS: The changes in motor behavior, dopamine (DA) neurons quantification and their mitochondrial respiratory chain, glial cells activation and secreted cytokines, Nrf2 signaling pathway, and redox balance in the brain of rats were evaluated. RESULTS: Lipopolysaccharide (LPS)-induced neuroinflammation and rotenone (ROT)-induced oxidative stress synergistically aggravated motor dysfunction, DA neuron damage, activation of glial cells, and release of related mediators, activation of Nrf2 signaling and destruction of oxidative balance. In addition, further studies indicated that after ROT-induced oxidative stress caused direct damage to DA neurons, LPS-induced inflammatory effects had stronger promoting neurotoxic effects on the above aspects. CONCLUSIONS: Neuroinflammation and oxidative stress synergistically aggravated DA neuronal loss. Furtherly, oxidative stress followed by neuroinflammation caused more DA neuronal loss than neuroinflammation followed by oxidative stress.
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Doença de Parkinson , Rotenona , Ratos , Animais , Rotenona/toxicidade , Rotenona/metabolismo , Lipopolissacarídeos/toxicidade , Dopamina/metabolismo , Doenças Neuroinflamatórias , Fator 2 Relacionado a NF-E2/metabolismo , Doença de Parkinson/metabolismo , Estresse Oxidativo , Neurônios Dopaminérgicos/metabolismoRESUMO
Three undescribed methylsuccinic acid derivatives, xylaril acids A-C, and two undescribed enoic acid derivatives, xylaril acids D-E, were isolated from the fungus Xylaria longipes. The structures of the undescribed compounds were deduced by spectroscopic means, including HRESIMS and 1D/2D NMR spectroscopy, as well as ECD calculations. The absolute configuration of xylaril acids A was further determined by single-crystal X-ray diffraction experiments. All the isolated compounds displayed neuroprotective activities against oxygen-glucose deprivation/reperfusion injury in PC12 cells by enhancing cell viability and inhibiting cell apoptosis.
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Ascomicetos , Xylariales , Ratos , Animais , Xylariales/química , Espectroscopia de Ressonância Magnética , Estrutura MolecularRESUMO
The possible mechanism by which the active components of Anhua fuzhuan tea act on FAM in NAFLD lesions was investigated. 83 components of Anhua fuzhuan tea were analysed by UPLC-Q-TOF/MS. Luteolin-7-rutinoside and other compounds were first discovered in fuzhuan tea. According to the TCMSP database and the Molinspiration website tool to predict and review the literature reports, 78 compounds were identified in fuzhuan tea with possible biological activities. The PharmMapper, Swiss target prediction, and SuperPred databases were used to predict the action targets of biologically active compounds. The GeneCards, CTD, and OMIM databases were mined for NAFLD and FAM genes. Then, a fuzhuan Tea-NAFLD-FAM Venn diagram was constructed. Using the STRING database and CytoHubba program of Cytoscape software, protein interaction analysis was performed, and 16 key genes, including PPARG, were screened. GO function and KEGG enrichment analyses of the screened key genes showed that Anhua fuzhuan tea may regulate FAM in the process of NAFLD through the AMPK signalling pathway, nonalcoholic fatty liver disease pathway, etc. After constructing an active ingredient-key target-pathway map with Cytoscape software, combined with literature reports and BioGPS database analysis, we believe that among the 16 key genes, SREBF1, FASN, ACADM, HMGCR, and FABP1 have potential in the treatment of NAFLD. Animal experiments confirmed the effect of Anhua fuzhuan tea in improving NAFLD and confirmed that this tea can interfere with the gene expression of the above five targets by the AMPK/PPAR pathway, providing support for Anhua fuzhuan tea interfering with FAM in NAFLD lesions.
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Medicamentos de Ervas Chinesas , Hepatopatia Gordurosa não Alcoólica , Animais , Proteínas Quinases Ativadas por AMP/genética , Farmacologia em Rede , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Hepatopatia Gordurosa não Alcoólica/genética , Bases de Dados Factuais , Chá , Medicamentos de Ervas Chinesas/farmacologia , Simulação de Acoplamento MolecularRESUMO
Prostate cancer (PCa) is one of the most fundamental causes of cancerrelated mortality and morbidity among males. However, the underlying mechanisms have not yet been fully clarified. The present study aimed to investigate the effects of plasmacytoma variant translocation 1 (PVT1) on the malignant behaviors of PCa cells and to explore the possible molecular mechanisms involved. The expression levels of PVT1 and microRNA (miRNA/miR)27b3p in PCa tissues and cell lines were measured using reversetranscritpionquantitative polymerase chain reaction. Methyltransferase 3 (METTL3)mediated PVT1 N6methyladenosine (m6A) modifications were detected using RNA immunoprecipitation (RIP) and RNA pulldown assays. Bioinformatics analysis was used to predict the interactions of miR27b3p with PVT1 and bloom syndrome protein (BLM), and these interactions were validated using RIP, dualluciferase reporter and biotin pulldown assays. The functional importance of miR27b3p, PVT1 and BLM within PCa cells was assessed through the in vitro utilization of Cell Counting Kit8, Transwell, wound healing and colony formation assays, and the in vivo use of a mouse xenograft model. The results revealed the high expression level of PVT1 in PCa tissues and cells, and epigenetic analyses revealed the upregulation of PVT1 expression following METTL3mediated m6A modification. PVT1 overexpression induced PCa cells to become more proliferative, migratory and invasive, whereas PVT1 knockdown led to the opposite phenotype. Furthermore, miR27b3p was found to target both PVT1 and BLM, and PVT1 functioned to sequester miR27b3p within cells, thereby indirectly promoting the BLM expression level. BLM overexpression reversed the adverse effects of PVT1 knockdown on the migratory, proliferative and invasive capabilities of PCa cells in vitro and in vivo. The overexpression of PVT1 contributed to the aggressive phenotype of PCa cells by regulating the miR27b3p/BLM axis. On the whole, the findings of the present study may provide novel potential targets for the treatment of PCa.
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MicroRNAs , Neoplasias da Próstata , RNA Longo não Codificante , Humanos , Camundongos , Animais , Masculino , RNA Longo não Codificante/genética , Neoplasias da Próstata/genética , MicroRNAs/genética , MetiltransferasesRESUMO
This study aimed to establish a nomogram model based on the clinicopathological factors affecting the prognosis of patients with primary splenic lymphoma (PSL) to predict the overall survival (OS) and cancer-specific survival (CSS) of patients. A total of 4074 patients diagnosed with PSL were included in this study. Among them, 4052 cases from the SEER (Surveillance, Epidemiology, and End Results) database were randomized into a training set and an internal validation set in a 7:3 ratio. Another 22 patients from the First Affiliated Hospital of Xi'an Jiaotong University were used as an external validation set. The prognostic factors affecting the OS and CSS of patients were analyzed using univariate and multivariate Cox regression models. Survival analysis was performed using Kaplan-Meier (KM) method and compared by Log-rank test. Then, a nomogram model was established to predict OS and CSS. Finally, the model was validated both internally and externally using the concordance index (C-index), receiver operating characteristic curve (ROC), and calibration curve to evaluate its predictive value, and the decision curve analysis (DCA) was conducted to assess its clinical utility. Our results showed that the model displayed a good prediction ability. In the training set, the OS rates at 1, 3, and 5 years were 85.9%, 75.8% and 70.1%, respectively, while the CSS rates at 1, 3, and 5 years were 91.9%, 86.2% and 82.3%, respectively. Predictors in the prediction model of OS included age, sex, marital status, Ann Arbor stage, histology, surgery, chemotherapy and year at diagnosis. On the other hand, predictors in the model of CSS included age, Ann Arbor stage, histology, chemotherapy, and year at diagnosis. Internal and external validation of the nomogram model showed that the C-index for predicting OS was 0.678 (0.662, 0.694) in the training set, 0.672 (0.648, 0.696) in the internal validation set, and 0.704 (0.565, 0.843) in the external validation set; the C-index for predicting CSS was 0.685 (0.661, 0.709) in the training set, 0.683 (0.650, 0.716) in the internal validation set, and 0.676 (0.488, 0.864) in the external validation set. The calibration curves for several groups showed good consistency, and DCA suggested its clinical usability. In conclusion, the nomogram constructed in this study has a good predictive value for the survival of patients with PSL, and can be a clinically applicable and practical prediction tool, facilitating rapid and accurate individualized predictions of the patient survival.
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Xiaoer Fupi Granules, a refined version of the classical prescription Shenling Baizhu Powder, has the effect of invigora-ting spleen, replenishing Qi, harmonizing stomach and resolving accumulation and is commonly used to treat Qi deficiency in spleen and stomach, disordered transportation and transformation, and indigestion of children. However, its medicinal constituents and mechanism remain unclear. We studied the main active constituents and action mechanism of Xiaoer Fupi Granules by integrating network pharmacology and prototype constituent analysis in vivo. This study will help to increase the reliability of database analysis results and lay a foundation for precise medication and mining of quality control markers. On the basis of Bioinformatics Analysis Tool for Molecular mechanism of Traditional Chinese Medicine(BATMAN-TCM), the "key chemical constituents-target" network was constructed. Ultra-performance liquid chromatography coupled with linear ion trap-orbitrap mass spectrometry(UPLC-LTQ-Orbitrap-MS) was employed to analyze the absorbed constituents in rat urine and plasma, so as to validate the network. Further, we used BATMAN-TCM to construct the "absorbed constituents-target-pathway" network and explore the functioning mechanism of Xiaoer Fupi Granules. A total of 86 chemical constituents of Xiaoer Fupi Granules were predicted via BATMAN-TCM, among which only 18.6% were detected in rat plasma and urine. Accor-ding to the "absorbed constituents-target-pathway" network, 8 chemical constituents such as stearic acid and caprylic acid capable of regulating gastric acid and insulin secretion may be the critical constituents of Xiaoer Fupi Granules in invigorating spleen and harmonizing stomach. This study identified the critical active constituents and predicted the action mechanism of Xiaoer Fupi Granules, providing the reference for the research on the material basis of Xiaoer Fupi Granules.
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Medicamentos de Ervas Chinesas , Ratos , Animais , Medicamentos de Ervas Chinesas/química , Reprodutibilidade dos Testes , Farmacologia em Rede , Medicina Tradicional Chinesa , Cromatografia LíquidaRESUMO
Two new C21 steroidal glycosides, brapreguanes A and B (1-2) were isolated from 75 % aqueous ethanol extract of Selaginella braunii Baker. Their structures were established by spectroscopic analyses (1D/2D NMR spectra and HR-ESI-MS). The absolute configurations of sugar were elucidated by enzymatic hydrolysis and GCMS analysis. In addition, all compounds were evaluated for the anti-proliferative activities against various human cancer cells inâ vitro. Compounds exhibited no inhibition to various human cancer cells.
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Selaginellaceae , Humanos , Selaginellaceae/química , Estrutura Molecular , Glicosídeos/farmacologia , Glicosídeos/química , Açúcares , Etanol , Extratos VegetaisRESUMO
BACKGROUND: Abnormal expanded GGC repeats within the NOTCH2HLC gene has been confirmed as the genetic mechanism for most Asian patients with neuronal intranuclear inclusion disease (NIID). This cross-sectional observational study aimed to characterise the clinical features of NOTCH2NLC-related NIID in China. METHODS: Patients with NOTCH2NLC-related NIID underwent an evaluation of clinical symptoms, a neuropsychological assessment, electrophysiological examination, MRI and skin biopsy. RESULTS: In the 247 patients with NOTCH2NLC-related NIID, 149 cases were sporadic, while 98 had a positive family history. The most common manifestations were paroxysmal symptoms (66.8%), autonomic dysfunction (64.0%), movement disorders (50.2%), cognitive impairment (49.4%) and muscle weakness (30.8%). Based on the initial presentation and main symptomology, NIID was divided into four subgroups: dementia dominant (n=94), movement disorder dominant (n=63), paroxysmal symptom dominant (n=61) and muscle weakness dominant (n=29). Clinical (42.7%) and subclinical (49.1%) peripheral neuropathies were common in all types. Typical diffusion-weighted imaging subcortical lace signs were more frequent in patients with dementia (93.9%) and paroxysmal symptoms types (94.9%) than in those with muscle weakness (50.0%) and movement disorders types (86.4%). GGC repeat sizes were negatively correlated with age of onset (r=-0.196, p<0.05), and in the muscle weakness-dominant type (median 155.00), the number of repeats was much higher than in the other three groups (p<0.05). In NIID pedigrees, significant genetic anticipation was observed (p<0.05) without repeat instability (p=0.454) during transmission. CONCLUSIONS: NIID is not rare; however, it is usually misdiagnosed as other diseases. Our results help to extend the known clinical spectrum of NOTCH2NLC-related NIID.