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Burkitt's lymphoma (BL) is a rare and highly aggressive B-cell non-Hodgkin lymphoma. Although the outcomes of patients with BL have greatly improved, options for patients with relapsed and refractory BL are limited. Therefore, there is an urgent need to improve BL therapeutics and to develop novel drugs with reduced toxicity. In this study, we demonstrated that enolase 1 (ENO1) is a potential novel drug target for BL treatment. We determined that ENO1 was aberrantly upregulated in BL, which was closely related to its invasiveness and poor clinical outcomes. Furthermore, using RNA interference, we demonstrated that ENO1 depletion significantly inhibited cell proliferation and invasion both in vitro and in vivo. Mechanistically, we established that ENO1 knockdown suppressed the PI3K-AKT and epithelial-mesenchymal transition (EMT) signaling pathways by reducing plasminogen (PLG) recruitment, plasmin (PL) generation, and TGF-ß1 activation. Addition of activated TGF-ß1 protein to the culture medium of shENO1 cells reversed the inhibitory effects on cell proliferation and invasion, as well as those on the PI3K-AKT and EMT signaling pathways. Notably, our research led to the discovery of a novel ENO1-PLG interaction inhibitor, Ciwujianoside E (L-06). L-06 effectively disrupts the interaction between ENO1 and PLG, consequently reducing PL generation and suppressing TGF-ß1 activation. In both in vitro and in vivo experiments, L-06 exerted impressive antitumor effects. In summary, our study elucidated the critical role of ENO1 in BL cell proliferation and invasion and introduced a novel ENO1 inhibitor, which holds promise for improving the treatment of patients with BL in the future.
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Linfoma de Burkitt , Proliferação de Células , Proteínas de Ligação a DNA , Transição Epitelial-Mesenquimal , Invasividade Neoplásica , Fosfopiruvato Hidratase , Plasminogênio , Fator de Crescimento Transformador beta1 , Proteínas Supressoras de Tumor , Fosfopiruvato Hidratase/metabolismo , Humanos , Proliferação de Células/efeitos dos fármacos , Linhagem Celular Tumoral , Animais , Linfoma de Burkitt/tratamento farmacológico , Linfoma de Burkitt/patologia , Linfoma de Burkitt/metabolismo , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Proteínas de Ligação a DNA/metabolismo , Fator de Crescimento Transformador beta1/metabolismo , Proteínas Supressoras de Tumor/metabolismo , Plasminogênio/metabolismo , Transdução de Sinais/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Masculino , Camundongos Nus , Feminino , Fosfatidilinositol 3-Quinases/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Movimento Celular/efeitos dos fármacos , Ensaios Antitumorais Modelo de Xenoenxerto , Biomarcadores TumoraisRESUMO
In recent years, the ethylene-mediated ripening and softening of non-climacteric fruits have been widely mentioned. In this paper, recent research into the ethylene-mediated ripening and softening of non-climacteric fruits is summarized, including the involvement of ethylene biosynthesis and signal transduction. In addition, detailed studies on how ethylene interacts with other hormones to regulate the ripening and softening of non-climacteric fruits are also reviewed. These findings reveal that many regulators of ethylene biosynthesis and signal transduction are linked with the ripening and softening of non-climacteric fruits. Meanwhile, the perspectives of future research on the regulation of ethylene in non-climacteric fruit are also proposed. The overview of the progress of ethylene on the ripening and softening of non-climacteric fruit will aid in the identification and characterization of key genes associated with ethylene perception and signal transduction during non-climacteric fruit ripening and softening.
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ATP citrate lyase (ACLY) is a key enzyme in glucolipid metabolism, and abnormally high expression of ACLY occurs in many diseases, including cancers, dyslipidemia and cardiovascular diseases. ACLY inhibitors are prospective treatments for these diseases. However, the scaffolds of ACLY inhibitors are insufficient with weak activity. The discovery of inhibitors with structural novelty and high activity continues to be a research hotpot. Acanthopanax senticosus (Rupr. & Maxim.) Harms is used for cardiovascular disease treatment, from which no ACLY inhibitors have ever been found. In this work, we discovered three novel ACLY inhibitors, and the most potent one was isochlorogenic acid C (ICC) with an IC50 value of 0.14 ± 0.04 µM. We found dicaffeoylquinic acids with ortho-dihydroxyphenyl groups were important features for inhibition by studying ten phenolic acids. We further investigated interactions between the highly active compound ICC and ACLY. Thermal shift assay revealed that ICC could directly bind to ACLY and improve its stability in the heating process. Enzymatic kinetic studies indicated ICC was a noncompetitive inhibitor of ACLY. Our work discovered novel ACLY inhibitors, provided valuable structure-activity patterns and deepened knowledge on the interactions between this targe tand its inhibitors.
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ATP Citrato (pro-S)-Liase , Eleutherococcus , Eleutherococcus/química , Estrutura Molecular , ATP Citrato (pro-S)-Liase/antagonistas & inibidores , Inibidores Enzimáticos/farmacologia , Inibidores Enzimáticos/isolamento & purificação , Inibidores Enzimáticos/química , Ácido Clorogênico/farmacologia , Ácido Clorogênico/isolamento & purificação , Ácido Clorogênico/química , Compostos Fitoquímicos/farmacologia , Compostos Fitoquímicos/isolamento & purificação , Compostos Fitoquímicos/química , Ácido Quínico/análogos & derivados , Ácido Quínico/farmacologia , Ácido Quínico/isolamento & purificação , Ácido Quínico/química , Hidroxibenzoatos/farmacologia , Hidroxibenzoatos/isolamento & purificação , Hidroxibenzoatos/química , Relação Estrutura-AtividadeRESUMO
This study aimed to determine the effects of the nitrogen (N) application period and level on the fate of fertilizer N and the contribution of N absorption and translocation to apple organ N. Two N application periods (labeled by the 15N tracer technique in spring and summer, represented by SP and SU, respectively) and three N levels (N0, MN, and HN) were used to determine the physiological indexes and aboveground, root, and soil 15N content of 4-year-old dwarf ('Red Fuji'/M9T337) and arborized ('Red Fuji'/Malus hupehensis Rehd.) apple trees. The results showed that HN led to shoot overgrowth, which was not conducive to the growth of the apple root system (root length, root tips, root surface area, and root volume) or the improvement of root activity. The contribution of soil N to apple organ N accounted for more than 50%, and the contribution of N application in summer to fruit N was higher than that in spring. Under HN treatment, the proportion of soil N absorbed by trees decreased, while that of fertilizer N increased; however, the highest proportion was still less than 50%, so apple trees were highly dependent on soil N. Under MN treatment, fertilizer N residue was similar to soil N consumption, and soil N fertility maintained a basic balance. Under HN treatment, fertilizer N residue was significantly higher than soil N consumption, indicating that excessive N application increased fertilizer N residue in the soil. Overall, the 15N utilization rate of arborized trees (17.33-22.38%) was higher than that of dwarf trees (12.89-16.91%). A total of 12.89-22.38% of fertilizer 15N was absorbed by trees, 30.37-35.41% of fertilizer 15N remained in the soil, and 44.65-54.46% of fertilizer 15N was lost. The 15N utilization rate and 15N residual rate of summer N application were higher than those of spring N application, and the 15N loss rate was lower than that of spring N application. High microbial biomass N (MBN) may be one of the reasons for the high N utilization rate and the low loss rate of N application in summer.
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Objectives: This study aimed to conduct a non-targeted metabolomic analysis of plasma from patients with spinal tuberculosis (STB) to systematically elucidate the metabolomic alterations associated with STB, and explore potential diagnostic biomarkers for STB. Methods: From January 2020 to January 2022, 30 patients with spinal tuberculosis (STBs) clinically diagnosed at the General Hospital of Ningxia Medical University and 30 age- and sex-matched healthy controls (HCs) were selected for this study. Using ultra-high performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-QTOF/MS) based metabolomics, we analyzed the metabolic profiles of 60 plasma samples. Statistical analyses, pathway enrichment, and receiver operating characteristic (ROC) analyses were performed to screen and evaluate potential diagnostic biomarkers. Results: Metabolomic profiling revealed distinct alterations between the STBs and HCs cohorts. A total of 1635 differential metabolites were screened, functionally clustered, and annotated. The results showed that the differential metabolites were enriched in sphingolipid metabolism, tuberculosis, cutin, suberine and wax biosynthesis, beta-alanine metabolism, methane metabolism, and other pathways. Through the random forest algorithm, LysoPE (18:1(11Z)/0:0), 8-Demethyl-8-formylriboflavin 5'-phosphate, Glutaminyl-Gamma-glutamate, (2R)-O-Phospho-3-sulfolactate, and LysoPE (P-16:0/0:0) were determined to have high independent diagnostic value. Conclusions: STBs exhibited significantly altered metabolite profiles compared with HCs. Here, we provide a global metabolomic profile and identify potential diagnostic biomarkers of STB. Five potential independent diagnostic biomarkers with high diagnostic value were screened. This study provides novel insights into the pathogenesis, diagnosis, and treatment strategies of STB.
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The Mamyshev oscillator (MO) can generate high-performance pulses. However, due to their non-resonant cavities, they usually are not self-starting, and there is almost no effort to reveal the pulse buildup dynamics of the MO. This paper investigates the dynamic of single pulse (SP) and multi-pulse formation in a self-starting MO. It indicated that both SP self-starting and multi-pulse self-starting can be obtained by adjusting the oscillator parameters. More importantly, increasing pump power could only result in bound state pulses (BSPs) if SP self-starting was formed. With the increase of the pump power, the pulse number in BSPs would increase. However, multiple pulses could not be formed only by increasing the pump power, and the BSPs obtained here underwent SP generated from noise, amplified, and then bounded, which is different from conventional passive mode-locked fiber lasers (CPMLFLs). On the other hand, if multiple pulses were self-initiated, BSPs, pulse bunch, and harmonic mode-locked pulses (HMLPs) could be obtained by adjusting the polarization state and pump power in the cavity. Furthermore, once any of the above states are formed, if the oscillator polarization state and filter interval are unchanged, only increasing the pump power from zero, the original state can still be obtained, which is consistent with the characteristics of the CPMLFLs. These findings will provide new insights into the pulse dynamics of self-starting MO, which will be significant for studying ultrafast laser technology and nonlinear optics.
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Fuke Qianjin capsules (FKQJ) exhibit obvious advantages and characteristics in the treatment of pelvic inflammatory disease. At present, information regarding the in vivo process of FKQJ is lacking, which has become a bottleneck in further determining the therapeutic effect of this traditional Chinese medicine. In the present study, a sensitive, simple and reliable method was developed and validated for the simultaneous quantification of 12 main components (4 flavonoids, 4 alkaloids, 2 phthalides and 2 diterpene lactones) in plasma and seven tissues of rats to study the pharmacokinetic and distribution characteristics of these components in vivo by using ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) for the first time. Plasma and tissue were prepared by protein precipitation with acetonitrile and methanol, followed by its separation on a Waters Acquity UPLC BEH C18 column. The quantification was performed via multiple reaction monitoring (MRM) by a triple quadrupole mass spectrometer under positive electrospray ionization (ESI) mode. The method was validated to demonstrate its selectivity, linearity, accuracy, precision, recovery, matrix effect and stability. For 12 analytes, the low limit of quantification (LLOQs) reached 0.005-2.44â¯ng/mL, and all calibration curves showed good linearity (r2 ≥ 0.990) in linear ranges. The intra-day and inter-day precision (relative standard deviation) for all analytes was less than 14.96%, and the accuracies were in the range of 85.29%-114.97%. Extraction recoveries and matrix effects of analytes were acceptable. The pharmacokinetic results showed that the main components could be absorbed quickly, had a short residence time, and were eliminated quickly in vivo. At different time points, the 12 components were widely distributed with uneven characteristics in the body, which tended to be distributed in the liver, kidney and lung and to a lesser extent in the uterus, brain and heart. The pharmacokinetic process and tissue distribution characteristics of FKQJ were expounded in this study, which can provide a scientific theory for in-depth development of FKQJ and guide FKQJ use in the clinic.
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Medicamentos de Ervas Chinesas , Feminino , Ratos , Animais , Cromatografia Líquida/métodos , Cromatografia Líquida de Alta Pressão/métodos , Medicamentos de Ervas Chinesas/análise , Espectrometria de Massas em Tandem/métodos , Distribuição Tecidual , Reprodutibilidade dos TestesRESUMO
Dactylicapnos scandens (D. scandens) is an ethnic medicine commonly used for the treatment of analgesia. In this study, an integrated strategy was proposed for the quality evaluation of D. scandens based on "phytochemistry-network pharmacology-effectiveness-specificity" to discover and determine the quality marker (Q-marker) related to analgesia. First, phytochemical analysis was conducted using UPLC-Q-TOF-MS/MS and a self-built compound library, and 19 components were identified in D. scandens extracts. Next, the "compounds-targets" network was constructed to predict the relevant targets and compounds related to analgesia. Then, the analgesic activity of related compounds was verified through dynamic mass redistribution (DMR) assays on D2 and Mu receptors, and 5 components showed D2 antagonistic activity with IC50 values of 39.2 ± 14.7 µM, 5.46 ± 0.37 µM, 17.5 ± 1.61 µM, 7.89 ± 0.79 µM and 3.29 ± 0.73 µM, respectively. Subsequently, nine ingredients were selected as Q-markers in consideration of specificity, effectiveness and measurability, and their content was measured in 12 batches of D. scandens. Furthermore, the hierarchical cluster analysis and heatmap results indicated that the selected Q-marker could be used to discriminate D. scandens and that the content of Q-marker varied greatly in different batches. Our study shows that this strategy provides a useful method to discover the potential Q-markers of traditional Chinese medicine and offers a practical workflow for exploring the quality consistency of medicinal materials.
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Medicamentos de Ervas Chinesas , Espectrometria de Massas em Tandem , Farmacologia em Rede , Medicina Tradicional Chinesa , Medicamentos de Ervas Chinesas/química , Compostos Fitoquímicos/farmacologiaRESUMO
Background: Post-transplant lymphoproliferative disorder (PTLD) is a significant complication after liver transplantation. Research on the diagnostic value of the Fluorine-18 fluorodeoxyglucose positron emission tomography/computerized tomography (18F-FDG PET/CT) metabolic parameters of PTLD in pediatric liver transplantation (pLT) recipients is limited. This study sought to evaluate the diagnostic efficacy of 18F-FDG PET/CT in differentiating between PTLD and non-PTLD lymphadenopathy in pLT recipients. Methods: This retrospective study collected the 18F-FDG PET/CT scans with clinical and pathological information of all consecutive children who were clinically suspected of PTLD from November 2016 to September 2022 at the Beijing Friendship Hospital. The 18F-FDG PET/CT metabolic parameters of the two groups were analyzed. We then established a diagnostic model composed of the clinical characteristics and metabolic parameters. Results: In total, 57 eligible patients were enrolled in this study, of whom 40 had PTLD and 17 had non-PTLD lymphadenopathy. Of the metabolic parameters examined in this study, total lesion glycolysis (TLG) had the highest area under the curve (AUC) value [0.757, 95% confidence interval (CI): 0.632-0.883, P=0.002]. The AUCs of the other metabolic parameters were all less than the AUC of TLG, including the maximum standardized uptake value (SUVmax) (AUC: 0.725, 95% CI: 0.597-0.853, P=0.008), mean standardized uptake value (SUVmean) (AUC: 0.701, 95% CI: 0.568-0.834, P=0.017), metabolic tumor volume total (MTVtotal) (AUC: 0.688, 95% CI: 0.549-0.827, P=0.040), TLG total (AUC: 0.674, 95% CI: 0.536-0.812, P=0.026). The diagnostic model, which was composed of clinical characteristics (digestive symptoms), the SUVmax, TLG, and the MTVtotal, showed excellent performance in the differential diagnosis (sensitivity: 0.675, 95% CI: 0.508-0.809; specificity: 0.941, 95% CI: 0.692-0.997; positive predictive value: 0.964, 95% CI: 0.798-0.998; and negative predictive value: 0.552, 95% CI: 0.360-0.730). Conclusions: The 18F-FDG PET/CT metabolic parameters can be used to distinguishing between PTLD and non-PTLD lymphadenopathy in pLT recipients.
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Due to the complexity of the automobile manufacturing process, some flexible and delicate assembly work relies on manual operations. However, high-frequency and high-load repetitive operations make assembly workers prone to physical fatigue. This study proposes a method for evaluating human physical fatigue for the manual assembly of automobiles with methods: NIOSH (National Institute for Occupational Safety and Health), OWAS (Ovako Working Posture Analysis System) and RULA (Rapid Upper Limb Assessment). The cerebral oxygenation signal is selected as an objective physiological index reflecting the human fatigue level to verify the proposed physical fatigue evaluation method. Taking auto seat assembly and automobile manual assembly as an example, 18 group experiments were carried out with the ARE platform (Augmented Reality-based Ergonomic Platform). Furthermore, predictions of metabolic energy expenditure were performed for experiments in Tecnomatix Jack. Finally, it is concluded that the proposed physical fatigue evaluation method can reflect the human physical fatigue level and is more accurate than the evaluation of metabolic energy consumption in Tecnomatix Jack because of the immersion that comes with the AR devices and the precision that comes with motion capture devices.
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Doenças Profissionais , Saúde Ocupacional , Estados Unidos , Humanos , Ergonomia/métodos , Postura/fisiologia , Postura Sentada , Extremidade Superior , Doenças Profissionais/etiologiaRESUMO
Prostate cancer remains the second most common malignancy in men worldwide, is a global health issue, and poses a huge health burden. Precision medicine provides more treatment options for prostate cancer patients, but its popularity, drug resistance, and adverse reactions still need to be focused on. Chinese herbal medicines (CHMs) have been widely accepted as an alternative therapy for cancer, with the advantages of multiple targets, multiple pathways, and low toxicity. We searched the experimental research and clinical practice of CHMs for prostate cancer treatment published in PubMed, Embase, and Web of Science in the last five years. We found five CHM formulas and six single CHM extracts as well as 12 CHM-derived compounds, which showed induction of apoptosis, autophagy, and cell cycle arrest, suppression of angiogenesis, proliferation, and migration of prostate cancer cells, reversal of drug resistance, and enhancement of anti-tumor immunity. The mechanisms of action include the PI3K/Akt/mTOR, AR, EGFR and Wnt/ß-catenin signaling pathways, which are commonly implicated in the development of prostate cancer. We also summarized the advantages of CHMs in patients with hormone-sensitive and castration-resistant prostate cancer and provided ideas for their further experimental design and application.
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The most common subtype of lung cancer is non-small cell lung cancer (NSCLC), which has a poor prognosis and seriously threatens the health of human beings. The multidisciplinary comprehensive treatment model has gradually become the mainstream of NSCLC treatment. Traditional Chinese medicine (TCM) can be used effectively either as an adjunctive therapy or alone throughout the NSCLC therapy, which has a significant impact on survival, quality of life, and reduction of toxicity. Therefore, this paper reviewed the theoretical basis, the latest clinical application, and combined treatment mechanisms in order to explore the advantage stage of TCM treatment and the synergistic therapeutic mechanisms.
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Insomnia is a common and refractory disease. Since more than 2000 years ago, people have been using Ziziphi Spinosae Semen (ZSS). However, there are lack of molecular mechanisms of sleep promotion effects of ZSS. The purpose of this study is to clarify the active ingredients in ZSS that are used to treat insomnia. Using a method called cellular label-free integrative pharmacology (CLIP), we established five insomnia-related target models, including serotonin (5HT2A and 5HT1A), melatonin (MT1), dopamine (D2) and epinephrine (ß2) receptors. The one-dimensional (1D) fractions of ZSS extract were prepared on a RZC18 column and assayed on five models. Subsequently, the active fraction was further analyzed, fractionated and quantified using a two-dimensional (2D) liquid phase method coupled with a charged aerosol detector (CAD), This CAD-coupled 2D-LC method requires micro-fractions from the 1D separation and thus it greatly saves sample amounts and corresponding preparation time, and quickly conduct activity screening. The composition of the active 2D fractions was then determined using three-dimensional (3D) HPLC-MS, and molecular docking was separately carried out for the described compounds on the targets for activity prediction. Seven compounds were predicted to be active on 5HT2A, and two compounds on D2. We experimentally verified the prediction and found that vitexin exhibited D2 agonistic activity, and nuciferine exhibited 5HT2A antagonistic activity. This study revealed the effective components and their targets of ZSS in the treatment of insomnia, also highlighted the potential of the CLIP technique and bioactivity guided multi-dimensional HPLC-MS in molecular mechanism elucidation for traditional Chinese medicines.
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Distúrbios do Início e da Manutenção do Sono , Humanos , Distúrbios do Início e da Manutenção do Sono/tratamento farmacológico , Simulação de Acoplamento Molecular , Estrutura Molecular , Sementes , Medicina Tradicional ChinesaRESUMO
BACKGROUND: Probiotic fermentation is a promising strategy for improving the nutritional and functional properties of traditional Chinese medicines (TCMs). Ganoderma lucidum and Raphani Semen are famous TCMs that have been shown to help alleviate immune system disorders. However, few studies have experimentally investigated the effects of probiotic-fermented G.lucidum and Raphani Semen on the immune system. PURPOSE: We established the in vitro fermentation of G. lucidum and Raphani Semen with a probiotic mixture (Bifidobacterium longum, Lactobacillus acidophilus, and l. fermentum) (GRFB), investigated its ameliorating effect against cyclophosphamide (CTX)-induced immunosuppression, and explored its possible mechanisms. METHODS: First, the different components in GRFB were identified by high-performance liquid chromatography. Second, its immune-stimulatory activities were evaluated in CTX-treated mice. Lastly, its possible in vitro and in vivo mechanisms were studied. RESULTS: Probiotic fermentation of G. lucidum and Raphani Semen altered some of its chemical constituents, potentially helping improve the ability of GRFB to alleviate immunosuppression. As expected, GRFB effectively ameliorated CTX-induced immunosuppression by increasing the number of splenic lymphocytes and regulating the secretion of serum and ileum cytokines. GRFB supplementation also effectively improved intestinal integrity in CTX-treated mice by upregulating tight junction proteins. It also protects against CTX-induced intestinal dysbiosis by increasing the abundance of beneficial bacteria and reducing the abundance of harmful bacteria. GRFB could directly promote intestinal immunity but not systemic immunity in vitro, suggesting a microbiota-dependent regulation of GRFB. Interestingly, cohousing CTX-induced immunosuppressed mice with GRFB-treated mice promoted their symptoms recovery. Enhanced CTX-induced immunosuppression by GRFB in vitro depended on the gut microbiota. Remarkably, a Kyoto Encyclopedia of Genes and Genomes analysis showed that the GRFB-reprogrammed microbiota was significantly enriched in DNA damage repair pathways, which contribute to repairing the intestinal mucosal barrier. CONCLUSION: This is the first study to suggest that compare with unfermented G. lucidum and Raphani Semen, GRFB can more effectively promote intestinal immunity and manipulate the gut microbiota to promote immunostimulatory activity and repair immunosuppression-induced intestinal barrier damage by biotransforming G.lucidum and Raphani Semen components.
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Microbioma Gastrointestinal , Probióticos , Reishi , Animais , Camundongos , Fermentação , Probióticos/farmacologia , Probióticos/uso terapêutico , Ciclofosfamida/efeitos adversos , Imunidade , Terapia de Imunossupressão , SementesRESUMO
BACKGROUND: Among the common malignant tumors in men worldwide, the incidence of prostate cancer ranks second to lung cancer. This disease will bring an economic burden to patients and their families and can reduce the quality of life of patients. Researchers have conducted numerous clinical trials on the efficacy and safety of different interventions in the treatment of prostate cancer with traditional Chinese medicine (TCM) combined with standard treatment regimens. However, the currently published clinical trials exhibit inconsistent and irregular reporting of outcome measures. OBJECTIVE: The objective of this paper is to emphasize the need for a core outcome set (COS) to facilitate future prostate cancer research, aiming to improve the quality of trials and generate high-quality evidence. METHODS: This mixed methods project has three phases, as follows: (1) a scoping review of the literature to identify outcomes that have been reported in clinical trials and systematic reviews of interventions involving TCM for the treatment of prostate cancer as well as a qualitative component using interviews to obtain the views of patients with prostate cancer, their families, and their caregivers who have a history of TCM treatment; (2) a Delphi survey among stakeholders to prioritize the core outcomes-Participants will include traditional Chinese and Western medicine clinicians in prostate cancer-related directions, nurses, and methodology experts who will participate in 2 rounds of the Delphi method expert consultation to score each outcome in the list of outcome indicators; and (3) a face-to-face consensus meeting to discuss and agree on the final COS for the application of TCM in the treatment of prostate cancer. RESULTS: The protocol has been registered in PROSPERO (CRD42022356184) before the start of the review process, and we will initiate the review on August 1, 2023; results should be expected by September 1, 2023. The Delphi survey among stakeholders is expected to start in October 2023. CONCLUSIONS: The development of a core outcome set for assessing clinical safety outcomes of prostate cancer in clinical trials of TCM will provide a significant first step to assist Chinese doctors, researchers, and policy makers. TRIAL REGISTRATION: PROSPERO CRD42022356184; https://tinyurl.com/ysakz74r. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/46794.
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OBJECTIVE: To compare and analyze the clinical effects of bilateral natural pressure drainage and negative pressure drainage after posterior lumbar interbody fusion (PLIF) to provide a reference for selecting drainage methods after lumbar surgery. METHODS: A retrospective cohort study, 281 patients who underwent single-segment PLIF in our hospital from January 2017 to December 2020 and met the inclusion and exclusion criteria were included in the study, including 132 males and 149 females, aged 22-85 years, with an average of (53.62 ± 11.23) years. According to different postoperative incision drainage methods determined by the random number table method before surgery, they were divided into the natural pressure drainage group and negative pressure drainage group, both of which were bilateral drainage. The general observation indexes and perioperative-related indexes were recorded and analyzed. RESULTS: There were 143 cases in the natural pressure drainage group and 138 cases in the negative pressure drainage group. There was no significant difference in age, gender, body mass index, disease type, blood pressure on the day of surgery, preoperative albumin, hemoglobin, platelet, prothrombin time, and intraoperative bleeding between the two groups (P > 0.05). The albumin on the first postoperative day in the natural pressure drainage group was higher than that in the negative pressure drainage group [(33.24 ± 3.52) vs. (32.17 ± 5.03), P < 0.05]; The hemoglobin on the first postoperative day in the natural pressure drainage group was higher than that in the negative pressure drainage group [(126.01 ± 15.03) vs. (115.19 ± 16.25), P < 0.01]; The drainage volume on the first postoperative day in the natural pressure drainage group was lower than that in the negative pressure drainage group [(93.25 ± 63.58) ml vs. (119.46 ± 54.48) ml, P < 0.01]; The total postoperative drainage volume in the natural pressure drainage group was lower than that in the negative pressure drainage group [(355.60 ± 189.69) ml vs. (434.37 ± 149.12) ml, P < 0.01]; The indwelling time of drainage tube in the natural pressure drainage group was lower than that in the negative pressure drainage group [(3.29 ± 1.17) d vs. (3.45 ± 0.97) d, P < 0.05]. There was no significant difference in platelet count on the first postoperative day, postoperative hospital stays, and complications (incision infection and hematoma) between the two groups (P > 0.05). CONCLUSION: Bilateral natural pressure drainage and negative pressure drainage can achieve good drainage effects after PLIF, but patients with natural pressure drainage have less loss of albumin and hemoglobin, less drainage volume, and shorter drainage tube indwelling time, which is worthy of clinical application.
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Albuminas , Drenagem , Feminino , Masculino , Humanos , Estudos Retrospectivos , Pressão Sanguínea , Índice de Massa CorporalRESUMO
Chronic stress can cause intestinal barrier damage. MAPK and NF-κB are closely related to it. Chlorogenic acid (CGA), a dietary polyphenol, has been shown to have intestinal protective effects, but whether by regulating MAPK and NF-κB is not known. Therefore, in this experiment, 24 Wistar rats were randomly divided into 4 groups (C group, CS group, CS + SB203580, and CS + CGA group). Rats in the CS group were restrained stress for 6 h per day for 21 days. Rats in the CS + SB203580 group were given SB203582 (0.5 mg/kg, intraperitoneal injection) 1 h before restraint stress every other day. Rats in the CS + CGA group were given CGA (100 mg/kg, gavage) 1 h before restraint stress. In chronic stress, intestinal barrier damage was evident, while being restored after CGA treatment. After chronic stress, the levels of p-P38 were increased (P < 0.01), while the levels of p-JNK and p-ERK were not changed. The levels of p-p38 were elevated after CGA treatment (P < 0.01). These results suggested that p38MAPK played an important role in chronic stress-induced intestinal injury, and CGA could inhibit p38MAPK activity. Therefore, we chose SB203582 (P38MAPK inhibitor) to elucidate the role of p38. After chronic stress, intestinal tight junction key proteins Occludin, ZO-1, and Claudin3 protein and gene expression were reduced (P < 0.01), while being elevated after CGA or SB203582 intervention (P < 0.05). After CGA treatment, the levels of p-IκB, p-p65, p-p38, and TNF-α were reduced (P < 0.01). SB203582 intervention reduced p-p65 and TNF-α levels significantly (P < 0.01). These results suggested that CGA could inhibit the NF-κB pathway by suppressing p38MAPK, thereby alleviating chronic stress-induced intestinal damage.
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Ácido Clorogênico , NF-kappa B , Ratos , Animais , NF-kappa B/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno/genética , Fator de Necrose Tumoral alfa , Ratos WistarRESUMO
Ziziphi spinosae semen has been widely used to treat insomnia and anxiety. To profile its chemical components, an online comprehensive two-dimensional liquid chromatography-mass spectrometry was developed. In this two-dimensional liquid chromatography system, a novel phthalic anhydride-bonded stationary phase column was combined with a C18 column. As a result, this new stationary phase exhibited remarkable differences in separation selectivity from C18, achieving a good orthogonality of 83.3%. Moreover, this new stationary phase with weaker hydrophobicity than C18 realized solvent compatibility in the online configuration. Coupled with tandem MS, 154 compounds were identified, including 51 unreported compounds. Compared with one-dimensional liquid chromatography-mass spectrometry, this online two-dimensional liquid chromatography-mass spectrometry system exhibited a much higher resolving power in isomer separation. This work provided an effective separation and characterization method for the material basis of Ziziphi spinosae semen. This strategy provides ideas for the material basis research of other traditional Chinese medicines.
Assuntos
Anidridos Ftálicos , Sementes , Cromatografia Líquida de Alta Pressão/métodos , Cromatografia Líquida , Espectrometria de Massas/métodosRESUMO
Ciwujia injection is commonly used to treat cerebrovascular and central nervous system diseases in clinical practice. It can significantly improve blood lipid levels and endothelial cell function in patients with acute cerebral infarction and promote the proliferation of neural stem cells in cerebral ischemic brain tissues. The injection has also been reported to have good curative effects on cerebrovascular diseases, such as hypertension and cerebral infarction. At present, the material basis of Ciwujia injection remains incompletely understood, and only two studies have reported dozens of components, which were determined using high performance liquid chromatography-quadrupole time-of-flight mass spectrometry (HPLC-Q-TOF MS). Unfortunately, the lack of research on this injection restricts the in-depth study of its therapeutic mechanism.In the present study, a qualitative method based on ultra-high performance liquid chromatography-quadrupole-electrostatic field orbitrap high-resolution mass spectrometry (UHPLC-Q/Orbitrap HRMS) was developed to analyze the chemical components of Ciwujia injection. Separation was performed on a BEH Shield RP18 column (100 mm×2.1 mm, 1.7 µm) using 0.1% formic acid aqueous solution (A) and acetonitrile (B) as the mobile phases, and gradient elution was performed as follows: 0-2 min, 0%B; 2-4 min, 0%B-5%B; 4-15 min, 5%B-20%B; 15-15.1 min, 20%B-90%B; 15.1-17 min, 90%B. The flow rate and column temperature were set to 0.4 mL/min and 30 â respectively. MS1 and MS2 data were acquired in both positive- and negative-ion modes using a mass spectrometer equipped with an HESI source. For data post-processing, a self-built library including component names, molecular formulas, and chemical structures was established by collecting information on the isolated chemical compounds of Acanthopanax senticosus. The chemical components of the injection were identified by comparison with standard compounds or MS2 data in commercial databases or literature based on precise relative molecular mass and fragment ion information. The fragmentation patterns were also considered. For example, the MS2 data of 3-caffeoylquinic acid (chlorogenic acid), 4-caffeoylquinic acid (cryptochlorogenic acid), and 5-caffeoylquinic acid (neochlorogenic acid) were first analyzed. The results indicated that these compounds possessed similar fragmentation behaviors, yielding product ions at m/z 173 and m/z 179 simultaneously. However, the abundance of the product ion at m/z 173 was much higher in 4-caffeoylquinic acid than in 5-caffeoylquinic acid or 3-caffeoylquinic acid, and the fragment signal at m/z 179 was much stronger for 5-caffeoylquinic acid than for 3-caffeoylquinic acid. Four caffeoylquinic acids were identified using a combination of abundance information and retention times. MS2 data in commercial database and literature were also used to identify unknown constituents. For example, compound 88 was successfully identified as possessing a relative molecular mass and neutral losses similar to those of sinapaldehyde using the database, and compound 80 was identified as salvadoraside because its molecular and fragmentation behaviors were consistent with those reported in the literature. A total of 102 constituents, including 62 phenylpropanoids, 23 organic acids, 7 nucleosides, 1 iridoid, and 9 other compounds, were identified. The phenylpropanoids can be further classified as phenylpropionic acids, phenylpropanols, benzenepropanals, coumarins, and lignans. Among the detected compounds, 16 compounds were confirmed using reference compounds and 65 compounds were identified in Ciwujia injection for the first time. This study is the first to report the feasibility of using the UHPLC-Q/Orbitrap HRMS method to quickly and comprehensively analyze the chemical components of Ciwujia injection. The 27 newly discovered phenylpropanoids provide further material basis for the clinical treatment of neurological diseases and new research targets for the in-depth elucidation of the pharmacodynamic mechanism of Ciwujia injection and its related preparations.
Assuntos
Eleutherococcus , Humanos , Cromatografia Líquida de Alta Pressão , Ácido Clorogênico , Eletricidade EstáticaRESUMO
OBJECTIVES: To construct and validate a combined model based on axial skeleton radiomics of 18F-FDG PET/CT for predicting event-free survival in high-risk pediatric neuroblastoma patients. MATERIALS AND METHODS: Eighty-seven high-risk neuroblastoma patients were retrospectively enrolled in this study and randomized in a 7:3 ratio to the training and validation cohorts. The radiomics model was constructed using radiomics features that were extracted from the axial skeleton. A univariate Cox regression analysis was then performed to screen clinical risk factors associated with event-free survival for building clinical model. Radiomics features and clinical risk factors were incorporated to construct the combined model for predicting the event-free survival in high-risk neuroblastoma patients. The performance of the models was evaluated by the C-index. RESULTS: Eighteen radiomics features were selected to build the radiomics model. The radiomics model achieved better event-free survival prediction than the clinical model in the training cohort (C-index: 0.846 vs. 0.612) and validation cohort (C-index: 0.754 vs. 0.579). The combined model achieved the best prognostic prediction performance with a C-index of 0.863 and 0.799 in the training and validation cohorts, respectively. CONCLUSION: The combined model integrating radiomics features and clinical risk factors showed more accurate predictive performance for event-free survival in high-risk pediatric neuroblastoma patients, which helps to design individualized treatment strategies and regular follow-ups.