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Endometrial polyps commonly contribute to female infertility, and hysteroscopic resection is the established surgical approach for their treatment. Numerous resection methods are available, with the most used and cost-effective options being cold resection employing micro-scissors or hot resection using an electric loop. However, both methods involve sharp resection, posing a challenge in achieving complete polyp removal while avoiding damage to the uterine endometrium. To address this issue, this study proposes an innovative approach: the combined use of the 6 Fr micro-scissors and forceps under hysteroscopy. The method entails utilizing 6 Fr micro-scissors to initially remove large polyps, followed by using 6 Fr micro-forceps to extract the remaining polyp tissue expeditiously and bluntly near the basal layer of the endometrium. This approach not only prevents surgical damage to the basal layer of the endometrium but also mitigates the risk of residual polyps resulting from incomplete resection. This method is particularly suitable for women with fertility requirements, offering additional considerations for the selection of treatment options for endometrial polyp resection.
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Histeroscopia , Pólipos , Feminino , Histeroscopia/métodos , Histeroscopia/instrumentação , Pólipos/cirurgia , Humanos , Doenças Uterinas/cirurgia , Instrumentos Cirúrgicos , Endométrio/cirurgia , Endométrio/patologiaRESUMO
Ageing is defined as the degeneration of physiological functions in numerous tissues and organs of an organism, which occurs with age. As we age, the gut undergoes a series of changes and weaknesses that may contribute to overall ageing. Emerging evidence suggests that ß-nicotinamide mononucleotide (NMN) plays a role in regulating intestinal function, but there is still a lack of literature on its role in maintaining the colon health of ageing mice. In our research, Zmpste24-/- mice proved that NMN prolonged their life span and delayed senescence. This study was designed to investigate the effects of long-term intervention on regulating colon function in ageing mice. Our results indicated that NMN improved the pathology of intestinal epithelial cells and intestinal permeability by upregulating the expression of intestinal tight junction proteins and the number of goblet cells, increasing the release of anti-inflammatory factors, and increasing beneficial intestinal bacteria. NMN increased the expression of the proteins SIRT1, NMNAT2, and NMNAT3 and decreased the expression of the protein P53. It also regulated the activity of ISCs by increasing Wnt/ß-catenin and Lgr5. Our findings also revealed that NMN caused a significant increase in the relative abundance of Akkermansia muciniphila and Bifidobacterium pseudolongum and notable differences in metabolic pathways related to choline metabolism in cancer. In summary, NMN supplementation can delay frailty in old age, aid healthy ageing, and delay gut ageing.
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Longevidade , Mononucleotídeo de Nicotinamida , Camundongos , Animais , Mononucleotídeo de Nicotinamida/metabolismo , Mononucleotídeo de Nicotinamida/farmacologia , Envelhecimento , Suplementos Nutricionais , Colo/metabolismoRESUMO
Akt1, as an important member of the Akt family, plays a controlled role in cancer cell growth and survival. Inhibition of Akt1 activity can promote cancer cell apoptosis and inhibit tumor growth. Therefore, in this investigation, a multilayer virtual screening approach, including receptor-ligand interaction-based pharmacophore, 3D-QSAR, molecular docking, and deep learning methods, was utilized to construct a virtual screening platform for Akt1 inhibitors. 17 representative compounds with different scaffolds were identified as potential Akt1 inhibitors from three databases. Among these 17 compounds, the Hit9 exhibited the best inhibitory activity against Akt1 with inhibition rate of 33.08% at concentration of 1 µM. The molecular dynamics simulations revealed that Hit9 and Akt1 could form a compact and stable complex. Moreover, Hit9 interacted with some key residues by hydrophobic, electrostatic, and hydrogen bonding interactions and induced substantial conformation changes in the hinge region of the Akt1 active site. The average binding free energies for the Akt1-CQU, Akt1-Ipatasertib, and Akt1-Hit9 systems were - 34.44, - 63.37, and - 39.14 kJ mol-1, respectively. In summary, the results obtained in this investigation suggested that Hit9 with novel scaffold may be a promising lead compound for developing new Akt1 inhibitor for treatment of various cancers with Akt1 overexpressed.
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Developing effective near-infrared (NIR) photosensitizers (PSs) has been an attractive goal of photodynamic therapy (PDT) for cancer treatment. In this study, we synthesized N, N-diethylaminomethylphenyl-containing Aza-BODIPY photosensitizers and comprehensively investigated their photophysical/photochemical properties, as well as cell-based and animal-based anti-tumor studies. Among them, BDP 1 has strong NIR absorption at 680 nm and higher singlet oxygen yield in PBS which showed favorable pH-activatable and lysosome-targeting ability. BDP 1 could be easily taken up by tumor cells and showed negligible dark activity (IC50 > 50 µM), however strong phototoxicity upon exposure to light irradiation. The acceptable fluorescence emission from BDP 1 allowed convenient in vivo fluorescence imaging for organ distribution studies in mice. After PDT treatment with upon single time PDT treatment at the beginning using relatively low light dose (54 J/ cm2), BDP 1 (2 mg/kg, 0.1 mL) was found to have strong efficacy to inhibit tumor growth and even to ablate off tumor without causing body weight loss. Therefore, pH-activatable and lysosome-targeted PS may become an effective way to develop potent PDT agent.
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Neoplasias , Fotoquimioterapia , Camundongos , Animais , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/uso terapêutico , Fármacos Fotossensibilizantes/química , Fotoquimioterapia/métodos , Compostos de Boro/farmacologia , Compostos de Boro/uso terapêutico , Compostos de Boro/química , Neoplasias/tratamento farmacológico , LisossomosRESUMO
Six pyrazolopyrimidine rhodium(III) or palladium(II) complexes, [Rh(L1)(H2O)Cl3] (1), [Rh(L2)(CH3OH)Cl3] (2), [Rh(L3)(H2O)Cl3] (3), [Rh2(L4)Cl6]·CH3OH (4), [Rh(L5)(CH3CN)Cl3]·0.5CH3CN (5), and [Pd(L5)Cl2] (6), were synthesized and characterized. These complexes showed high cytotoxicity against six tested cancer cell lines. Most of the complexes showed higher cytotoxicity to T-24 cells in vitro than cisplatin. Mechanism studies indicated that complexes 5 and 6 induced G2/M phase cell cycle arrest through DNA damage, and induced apoptosis via endoplasmic reticulum stress response. In addition, complex 5 also induced cell apoptosis via mitochondrial dysfunction. Complexes 5 and 6 showed low in vivo toxicity and high tumor growth inhibitory activity in mouse tumor models. The inhibitory effect of rhodium complex 5 on tumor growth in vivo was more pronounced than that of palladium complex 6.
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Antineoplásicos , Complexos de Coordenação , Neoplasias , Ródio , Animais , Camundongos , Antineoplásicos/farmacologia , Antineoplásicos/metabolismo , Ródio/farmacologia , Paládio/farmacologia , Linhagem Celular , Neoplasias/tratamento farmacológico , Apoptose , Complexos de Coordenação/farmacologia , Linhagem Celular TumoralRESUMO
Recent studies have suggested that ubiquitin-conjugating enzyme E2D1 (UBE2D1) is involved in tumor progression. In this study, we found that UBE2D1 expression was upregulated in breast cancer (BC) and was related to the prognosis of BC patients. Through in vitro and in vivo experiments, we demonstrated the aberrant expression of UBE2D1 promoted the proliferation and migration of BC cells, and the IGF2BP2-mediated N6-methyladenosine (m6A) modification increased the stability of UBE2D1 mRNA. Mechanistically, UBE2D1 expression regulated the activity of TGF-ß signaling through modulating the expression and the phosphorylation level of Smad2/3. Furthermore, UBE2D1 directly bound to Smad2/3 and affected the subsequent binding of Smad2 and Smad3, which is a necessary step for TGF-ß signaling activation. Thus, our study reveals a pro-oncogenic role of UBE2D1 in the progression of BC and may provide novel strategies for BC treatment.
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PURPOSE: Heart failure (HF) remains a major cause of late morbidity and mortality after myocardial infarction (MI). To date, no clinically established 18F-labeled sympathetic nerve PET tracers for monitoring myocardial infarction are available. Therefore, in this study, we synthesized a series of 18F-labeled benzyl guanidine analogs and evaluated their efficacy as cardiac neuronal norepinephrine transporter (NET) tracers for myocardial imaging. We also investigated the preliminary diagnostic capabilities of these tracers in myocardial infarction animal models, as well as the structure-activity relationship of these tracers. PROCEDURES: Three benzyl guanidine-NET tracers, including [18F]1, [18F]2, and [18F]3, were synthesized and evaluated in vivo as PET tracers in a myocardial infarction mouse model. [18F]LMI1195 was used as a positive control for the tracers. H&E staining of the isolated myocardial infarction heart tissue sections was performed to verify the efficacy of the selected PET tracer. RESULTS: Our data show that [18F]3 had a moderate decay corrected labeling yield (~10%) and high radiochemical purity (>95%) compared to other tracers. The uptake of [18F]3 in normal mouse hearts was 1.7±0.1%ID/cc at 1 h post-injection (p. i.), while it was 2.4±0.1, 2.6±0.9, and 2.1±0.4%ID/cc in the MI mouse hearts at 1, 2, and 3 days after surgery, respectively. Compared with [18F]LMI1195, [18F]3 had a better myocardial imaging effect in terms of the contrast between normal and MI hearts. The area of myocardial infarction shown by PET imaging corresponded well with the infarcted tissue demonstrated by H&E staining. CONCLUSIONS: With an obvious cardiac uptake contrast between normal mice and the myocardial infarction mouse model, [18F]3 appears to be a potential tool in the diagnosis of myocardial infarction. Therefore, it is necessary to conduct further structural modification studies on the chemical structure of [18F]3 to improve its in vivo stability and diagnostic detection ability to achieve reliable and practical imaging effects.
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Infarto do Miocárdio , Proteínas da Membrana Plasmática de Transporte de Norepinefrina , Camundongos , Animais , Infarto do Miocárdio/diagnóstico por imagem , Guanidinas , Tomografia por Emissão de Pósitrons/métodos , Modelos Animais de Doenças , Radioisótopos de Flúor/químicaRESUMO
FAM50A encodes a nuclear protein involved in mRNA processing; however, its role in cancer development remains unclear. Herein, we conducted an integrative pan-cancer analysis using The Cancer Genome Atlas, Genotype-Tissue Expression, and the Clinical Proteomic Tumor Analysis Consortium databases. Based on the gene expression data from TCGA and GTEx databases, we compared FAM50A mRNA levels in 33 types of human cancer tissues to those in corresponding normal tissues and found that FAM50A mRNA level was upregulated in 20 of the 33 types of common cancer tissues. Then, we compared the DNA methylation status of the FAM50A promoter in tumor tissues to that in corresponding normal tissues. FAM50A upregulation was accompanied by promoter hypomethylation in 8 of the 20 types of tumor tissues, suggesting that promoter hypomethylation contributes to the upregulation of FAM50A in these cancer tissues. Elevated FAM50A expression in 10 types of cancer tissues was associated with poor prognosis in patients with cancer. FAM50A expression was positively correlated with CD4+ T-lymphocyte and dendritic cell infiltration in cancer tissues but was negatively correlated with CD8+ T-cell infiltration in cancer tissues. FAM50A knockdown caused DNA damage, induced interferon beta and interleukin-6 expression, and repressed the proliferation, invasion, and migration of cancer cells. Our findings indicate that FAM50A might be useful in cancer detection, reveal insights into its role in cancer development, and may contribute to the development of cancer diagnostics and treatments.
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Neoplasias , Proteômica , Humanos , Regulação para Cima , Ativação Transcricional , Neoplasias/genética , Linfócitos T CD4-Positivos , Proteínas de Ligação a DNA , Proteínas de Ligação a RNARESUMO
As a continuation of our endeavors in discovering metal-based drugs with cytotoxic and antimetastatic activities, herein, we reported the syntheses of 11 new rhodium(III)-picolinamide complexes and the exploration of their potential anticancer activities. These Rh(III) complexes showed high antiproliferative activity against the tested cancer cell lines in vitro. The mechanism study indicated that Rh1 ([Rh(3a)(CH3CN)Cl2]) and Rh2 ([Rh(3b)(CH3CN)Cl2]) inhibited cell proliferation by multiple modes of action via cell cycle arrest, apoptosis, and autophagy and inhibited cell metastasis via FAK-regulated integrin ß1-mediated suppression of EGFR expression. Furthermore, Rh1 and Rh2 significantly inhibited bladder cancer growth and breast cancer metastasis in a xenograft model. These rhodium(III) complexes could be developed as potential anticancer agents with antitumor growth and antimetastasis activity.
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Antineoplásicos , Neoplasias da Mama , Complexos de Coordenação , Ródio , Humanos , Feminino , Ródio/farmacologia , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Apoptose , Proliferação de Células , Autofagia , Linhagem Celular Tumoral , Complexos de Coordenação/farmacologia , Complexos de Coordenação/uso terapêuticoRESUMO
BACKGROUND: Whether smoking is a risk factor for ischemic stroke (IS) recurrence in IS survivors is still uncovered, and evidences are sparse. Meanwhile, an add-on effect of clopidogrel was observed in myocardial infarction patients who smoked, but whether the paradox exists in IS patients is still unsolved. The objectives of this study are to explore the association between smoking behavior after index stroke and IS recurrence and to explore whether the paradox exists. METHODS: A prospective cohort of first-ever IS patients was conducted between 2010 and 2019. The prognosis and smoking features of enrolled patients were obtained via telephone follow-up every 3 months. Fine-gray model with interaction terms was applied to measure the relationships between stroke recurrence and smoking behaviors after index stroke and to explore the add-on effect of clopidogrel in smoking patients. RESULTS: There were 171 (24.26%) recurrences and 129 (18.30%) deaths during follow-up in 705 enrolled IS patients. One hundred forty-six (20.71%) patients smoked after index stroke. The hazard ratios (HRs) and 95% confidence intervals (CIs) of interaction terms between antiplatelet drug and follow-up smoking (smoking status and daily smoking amount) were 1.092 (95% CI: 0.524, 2.276) and 0.985 (95% CI: 0.941, 1.031), respectively. A significantly higher risk of recurrence was observed in patients with a higher daily smoking amount during follow-up (per cigarette), with HR being 1.027 (95% CI: 1.003, 1.052). CONCLUSIONS: Smoking could elevate the risk of IS recurrence, and IS survivor should be advised to quit or smoke less. Add-on effect of clopidogrel may not exist in smoking strokers taking clopidogrel.
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AVC Isquêmico , Acidente Vascular Cerebral , Humanos , Clopidogrel/uso terapêutico , AVC Isquêmico/complicações , Estudos Prospectivos , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/etiologia , Inibidores da Agregação Plaquetária/uso terapêutico , Fumar/efeitos adversos , Fumar/epidemiologia , Sobreviventes , Recidiva , Resultado do TratamentoRESUMO
Cholangiocarcinoma (CCA) is a type of epithelial cancer with poor outcomes and late diagnosis. Accumulating evidence has demonstrated the promoting role of plasminogen activator, urokinase (PLAU) in several tumor types, while its function in CCA is largely unknown. The expression of PLAU in CCA was determined by data from Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) database and further confirmed in human tissues using immunohistochemical (IHC) staining. Moreover, PLAU-silencing CCA cell models were constructed for subsequent functional assays in vitro and in vivo. PLAU expression in CCA was significantly higher than that in normal tissues. High PLAU expression was positively correlated with poor patients' survival. PLAU knockdown remarkably suppressed proliferation and migration of CCA cells, whereas enhanced apoptosis. Consistently, tumor growth in mice injected with PLAU-silencing CCA cells was also impaired. Furthermore, we revealed that the activation of NF-κB signaling was required for PLAU-induced malignant phenotypes of CCA cells. Inhibiting the high expression of PLAU in CCA may be a potential entry point for targeted therapy in CCA patient.
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Neoplasias dos Ductos Biliares , Colangiocarcinoma , Humanos , Animais , Camundongos , NF-kappa B/metabolismo , Ativador de Plasminogênio Tipo Uroquinase/metabolismo , Ativadores de Plasminogênio/metabolismo , Transdução de Sinais , Colangiocarcinoma/genética , Colangiocarcinoma/metabolismo , Colangiocarcinoma/patologia , Ductos Biliares Intra-Hepáticos/metabolismo , Ductos Biliares Intra-Hepáticos/patologia , Neoplasias dos Ductos Biliares/metabolismo , Neoplasias dos Ductos Biliares/patologia , Proliferação de Células/genética , Linhagem Celular Tumoral , Movimento Celular/genéticaRESUMO
Ribosomal protein S6 kinase beta-1 (S6K1) is considered a potential target for the treatment of various diseases, such as obesity, type II diabetes, and cancer. Development of novel S6K1 inhibitors is an urgent and important task for the medicinal chemists. In this research, an effective ensemble-based virtual screening method, including common feature pharmacophore model, 3D-QSAR pharmacophore model, naïve Bayes classifier model, and molecular docking, was applied to discover potential S6K1 inhibitors from BioDiversity database with 29,158 compounds. Finally, 7 hits displayed considerable properties and considered as potential inhibitors against S6K1. Further, carefully analyzing the interactions between these 7 hits and key residues in the S6K1 active site, and comparing them with the reference compound PF-4708671, it was found that 2 hits exhibited better binding patterns. In order to further investigate the mechanism of the interactions between 2 hits and S6K1 at simulated physiological conditions, the molecular dynamics simulation was performed. The ΔGbind energies for S6K1-Hit1 and S6K1-Hit2 were - 111.47 ± 1.29 and - 54.29 ± 1.19 kJ mol-1, respectively. Furthermore, deep analysis of these results revealed that Hit1 was the most stable complex, which can stably bind to S6K1 active site, interact with all of the key residues, and induce H1, H2, and M-loop regions changes. Therefore, the identified Hit1 may be a promising lead compound for developing new S6K1 inhibitor for various metabolic diseases treatment.
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Simulação de Dinâmica Molecular , Proteínas Quinases S6 Ribossômicas 70-kDa , Humanos , Teorema de Bayes , Simulação de Acoplamento Molecular , Relação Quantitativa Estrutura-Atividade , Proteínas Quinases S6 Ribossômicas 70-kDa/antagonistas & inibidoresRESUMO
Background: Focal atrial tachycardia (AT) originating from the right atrial appendage (RAA), often persistent and refractory, is clinically rare in pregnant woman, and the therapy is much more challenging. We report that a pregnant woman presented with hypotension due to persistent and refractory atrial tachycardia and was successfully cured by a multidisciplinary treatment (MDT) approach, consisting of a combination of zero-fluoroscopy mapping and thoracoscopic atrial appendectomy. We also carried out a literature review of this topic. Methods and Results: A 26-year-old woman in pregnancy at 21 weeks presented with severe palpitation and hypotension due to persistent rapid supraventricular tachycardia (SVT). Since adenosine triphosphate could not terminate the tachycardia, a catheter ablation procedure was planned and finally canceled when the zero-fluoroscopy mapping using Carto 3TM system revealed an atrial tachycardia originating from the RAA. Thoracoscopic RAA ectomy was recommended after multidisciplinary consultation and successfully performed without fluoroscopy. EnsiteTM velocity mapping system was used for accurately locating the origin of the arrhythmia during ectomy. The woman finally produced a healthy baby during follow-up. Conclusions: Focal AT originating from appendage in pregnant patients can be persistent, refractory, and life-threatening; traditional strategies, such as medicine or catheter ablation, are limited in this situation. MDT measures, using a thoracoscopic ectomy and zero-fluoroscopy three-dimensional electroanatomical mapping technique, is minimally invasive and a promising strategy.
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Ablação por Cateter , Taquicardia Supraventricular , Humanos , Feminino , Gravidez , Adulto , Gestantes , Resultado do Tratamento , Taquicardia Supraventricular/cirurgia , Taquicardia/cirurgia , Arritmias Cardíacas , Fluoroscopia/métodos , Ablação por Cateter/métodosRESUMO
Background: Non-alcoholic steatohepatitis (NASH) is a progressive form of non-alcoholic fatty liver disease (NAFLD). The diagnostic gold standard for detecting NASH still relies upon an invasive pathological biopsy. There is, therefore, a need to identify non-invasive diagnostic markers. Oxidative stress mediates fatty liver progression to NASH. Imbalanced iron metabolism produces many reactive oxygen species (ROS). Ceruloplasmin is associated with oxidase and iron metabolism-related activities. The current study aimed to determine whether there was a correlation between ceruloplasmin levels and NASH and whether such a relationship may be associated with altered iron metabolism in NASH patients. Methods: A total of 135 NAFLD patients were enrolled in this study. A pathological biopsy confirmed that 60 of those patients had NAFLD activity scores (NAS) 5, while the remaining 75 had NAS<5. Results: Receiver operating characteristic (ROC) curves confirmed that serum ceruloplasmin and ferritin levels were predictors of NAS 5 and NAS<5, with area under the curve (AUC) values of 0.80 and 0.81, respectively. The serum ceruloplasmin levels in NAS 5 patients were significantly lower than those in NAS<5 patients (p< 0.001). Serum ceruloplasmin levels were also negatively correlated with ferritin levels. Lower serum ceruloplasmin levels were associated with more severe histopathological findings. Conclusions: Low serum ceruloplasmin and high serum ferritin are correlated with NASH. A high concentration of serum ferritin is a viable clinical biomarker of NASH, and low serum ceruloplasmin may participate in the occurrence of NASH by regulating iron load, which can be used as a non-invasive diagnostic marker of NASH.
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Tubulin γ-1 (TUBG1) is a highly conserved component of the centrosome and its deregulation is involved in the development of several types of cancer. However, the role of TUBG1 in hepatocellular carcinoma (HCC) remains unclear. In this study, we found that TUBG1 was upregulated in human HCC cells and tissues and that TUBG1 upregulation was associated with promoter hypomethylation in HCC tissues. TUBG1 knockdown suppressed the proliferation, invasion, and migration of HCC cells. While TUBG1 expression was positively correlated with CD4 + memory T lymphocyte infiltration, it was negatively correlated with CD4 + regulatory T-cell infiltration in human HCC tissues. Furthermore, TUBG1 expression was positively correlated with the expression of genes involved in cell division. Noticeably, high expression of TUBG1 was associated with poor prognosis in patients with HCC. Overall, our findings revealed that TUBG1 promotes hepatocarcinogenesis by increasing proliferation, invasion, and migration of HCC cells and may regulate T lymphocyte infiltration. The current findings provide important insights into TUBG1 regulation in HCC, which could provide new therapeutic targets for hepatocarcinoma which has a very high incidence and mortality rate worldwide.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/patologia , Regulação para Cima , Tubulina (Proteína)/genética , Proliferação de Células/genética , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica , Movimento Celular/genéticaRESUMO
The pericarp of Zanthoxylum bungeanum maxim (PZM) is a commonly used spice and herbal medicine in China. In the present study, the structural characteristics of PPZM were investigated by saccharide mapping after enzymatic digestion by using high-performance thin layer chromatography (HPTLC) and polysaccharide analysis by using carbohydrate gel electrophoresis (PACE). The mechanisms of protective effects of PPZM on Aß25-35-induced oxidative damage were explored in PC12 cells. The results showed that PPZM contained 1,4-α-D-galactosidic, 1,4-α-D-galactosiduronic, and (1â4)-ß-D-glucosidic linkages. Pretreatment with PPZM significantly increased the cell viability of Aß25-35-injured PC12 cells. Flow cytometry and Hoechst/PI staining indicated that PPZM gradually relieved the apoptosis of the Aß25-25-treated cells. PPZM markedly decreased the ROS level of PC12 cells and suppressed Aß25-35-induced oxidative stress by increasing the SOD level, and decreasing the level of MDA and LDH. The mRNA expressions of caspase-3 and Bax were significantly downregulated, and Bcl-2 expression was upregulated by treatment with PPZM. PPZM significantly increased the mRNA expression of Nrf2 and HO-1 in Aß25-35 treated cells. The results indicated that PPZM alleviated apoptosis and oxidative stress induced by Aß25-25 through the inhibition of mitochondrial dependent apoptosis and activation of Nrf2/HO-1 pathway. PPZM can be used as a potential protective agent against Aß25-25-induced neurotoxicity.
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Fármacos Neuroprotetores , Zanthoxylum , Animais , Ratos , Fármacos Neuroprotetores/farmacologia , Zanthoxylum/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Estresse Oxidativo , Apoptose , Polissacarídeos/química , Células PC12 , RNA Mensageiro/metabolismo , Peptídeos beta-Amiloides/metabolismo , Fragmentos de Peptídeos/metabolismoRESUMO
PURPOSE: [18F]FDG PET/CT to detect unknown primary lesions is essential for clinical management but still has limitations. [68Ga]Ga-FAPI is a tumor-stromal imaging agent that provides a promising alternative to [18F]FDG for the assessment of malignancies. We aimed to investigate whether [68Ga]Ga-FAPI PET/CT has an additional role in identifying unknown primary lesions with negative or equivocal [18F] FDG PET/CT results. METHODS: This single-center prospective clinical study was conducted between March 2020 and March 2022 at Southwest Medical University Hospital. Patients underwent [18F]FDG PET/CT for the identification of unknown primary lesions. They underwent repeat [68Ga]Ga-FAPI PET/CT when [18F]FDG PET/CT results were negative or equivocal. Histopathological examination, surgery, or clinical follow-up (at least 3 months) for FAPI-positive lesions. The diagnostic efficacy of [68Ga]Ga-FAPI in identifying unknown primary lesions was evaluated. RESULTS: A total of 44 participants (median age, 57 ± 12 [SD]; 22 [50%] men) were evaluated. Thirteen of the 44 patients had equivocal [18F]FDG PET/CT findings, while the diagnosis was clear on [68Ga]Ga-FAPI PET/CT. [68Ga]Ga-FAPI PET/CT also revealed primary lesions in additional 17 patients with negative [18F]FDG PET/CT findings. In fourteen of 44 patients, no primary lesion was detected by either tracer. On this basis, we analyzed 94 lymph node metastatic lesions. The mean SUVmax of lymph node metastases on [68Ga] Ga-FAPI PET/CT and [18F]FDG PET/CT were 9.2 ± 5.1, 7.9 ± 4.8 (p = 0.03) and the mean TBR were 9.1 ± 5.2, 4.9 ± 3.1 (p < 0.01), respectively. CONCLUSION: [68Ga]Ga-FAPI PET/CT showed great potential for identifying unknown primary lesions and has the potential to improve the detection rate of unknown primary lesions with negative or equivocal for [18F]FDG findings. TRIAL REGISTRATION: ClinicalTrial.gov. Identifier: ChiCTR2100044131.
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Neoplasias Primárias Desconhecidas , Quinolinas , Masculino , Humanos , Pessoa de Meia-Idade , Idoso , Feminino , Fluordesoxiglucose F18 , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Neoplasias Primárias Desconhecidas/diagnóstico por imagem , Estudos Prospectivos , Radioisótopos de GálioRESUMO
Prediction tools focused on cardiovascular and cerebrovascular events after noncardiac surgery are lacking, particularly for Chinese patients. We developed and validated what we believe is a new predictive tool for postoperative major cardiovascular and cerebrovascular events (MACCEs) in Chinese patients in this study. Overall, 401 variables derived from 598 patients who received noncardiac surgery at our center were retrospectively analyzed to develop and validate the new predictive model for MACCEs during hospitalization. The 7 strongest predictors for MACCEs in the development cohort were chronic heart failure, age, atrial fibrillation, general anesthesia, history of coronary heart disease, high-risk procedures, and lymphocyte count. The area under the receiver operating characteristic curve was 0.698 (95% confidence interval 0.616 to 0.780) for the new predictive tool with the validation cohort. Receiver operating characteristic curve analysis showed the new predictive tool had better performance than the Revised Cardiac Risk Index and the American College of Surgeons National Surgical Quality Improvement Program scores. This new predictive tool is effective for the prediction of postoperative MACCEs in patients who undergo noncardiac surgery.
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Hospitais , Complicações Pós-Operatórias , Humanos , Estudos Retrospectivos , Fatores de Risco , Medição de Risco , Complicações Pós-Operatórias/epidemiologia , China/epidemiologiaRESUMO
ABSTRACT: A patient with suspected malignant tumor underwent 18 F-FDG PET/CT. Based on the findings, the patient was suspected of having multiple myeloma. Then the patient underwent 68 Ga-pentixafor PET/CT, which showed similar results to 18 F-FDG PET/CT. Finally, the patient was eventually diagnosed with neuroendocrine carcinoma.
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Carcinoma Neuroendócrino , Complexos de Coordenação , Humanos , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Fluordesoxiglucose F18 , Carcinoma Neuroendócrino/diagnóstico por imagemRESUMO
INTRODUCTION: As one of the most important and frequently used molecular imaging techniques in the clinic, positron emission tomography (PET) features high sensitivity and specificity, which generally involves the use of PET contrast agents. Despite the exceptional promise, the availability of novel PET agents could limit its application and there is a clear need to develop new PET agents to improve our understanding of targets of interest and increase the diagnostic specificity. METHODS: Based on the fact that amino acid transport and protein anabolism are increased in tumor tissues, a series of 18F-labeled amino acid analog was labeled with 18F by using [18F]fluoro-4-(vinylsulfonyl)benzene as the radionuclide linker. The obtained probes were subjected to in vitro and in vivo evaluation, including stability, cell line transport channel specificity, PET/CT imaging on tumor and inflammation bearing mice, and biodistribution. RESULTS: Our data shows that [18F]2a had moderate decay corrected labeling yield (>42 %) and high radiochemical purity (>99 %). When tested in vivo, the uptake of [18F]2a was 1.5 ± 0.2%ID/g in NCI-H1975 tumors and 1.1 ± 0.2%ID/g in inflammatory tissues. In contrast, the values for [18F]FDG were 5.7 ± 0.2%ID/g and 4.8 ± 0.1%ID/g, respectively. The inflammatory lesion-to-muscle contrast is 2.4 for [18F]2a, which is 3.0 for [18F]FDG. CONCLUSION: Clearly, [18F]2a hold the great potential for cancer imaging. Its application in distinguishing tumor from inflammatory lesion would still need to be investigated further.