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BACKGROUND: The heightened risk of cardiovascular and cerebrovascular events is associated with the increased instability of atherosclerotic plaques. However, the lack of effective diagnostic biomarkers has impeded the assessment of plaque instability currently. This study was aimed to investigate and identify hub genes associated with unstable plaques through the integration of various bioinformatics tools, providing novel insights into the detection and treatment of this condition. METHODS: Weighted Gene Co-expression Network Analysis (WGCNA) combined with two machine learning methods were used to identify hub genes strongly associated with plaque instability. The cell-type identification by estimating relative subsets of RNA transcripts (CIBERSORT) method was utilized to assess immune cell infiltration patterns in atherosclerosis patients. Additionally, Gene Set Variation Analysis (GSVA) was conducted to investigate the potential biological functions, pathways, and mechanisms of hub genes associated with unstable plaques. To further validate the diagnostic efficiency and expression of the hub genes, immunohistochemistry (IHC), quantitative real-time polymerase chain reaction (RT-qPCR), and enzyme-linked immunosorbent assay (ELISA) were performed on collected human carotid plaque and blood samples. Immunofluorescence co-staining was also utilized to confirm the association between hub genes and immune cells, as well as their colocalization with mitochondria. RESULTS: The CIBERSORT analysis demonstrated a significant decrease in the infiltration of CD8 T cells and an obvious increase in the infiltration of M0 macrophages in patients with atherosclerosis. Subsequently, two highly relevant modules (blue and green) strongly associated with atherosclerotic plaque instability were identified. Through intersection with mitochondria-related genes, 50 crucial genes were identified. Further analysis employing least absolute shrinkage and selection operator (LASSO) logistic regression and support vector machine recursive feature elimination (SVM-RFE) algorithms revealed six hub genes significantly associated with plaque instability. Among them, NT5DC3, ACADL, SLC25A4, ALDH1B1, and MAOB exhibited positive correlations with CD8 T cells and negative correlations with M0 macrophages, while kynurenine 3-monooxygenas (KMO) demonstrated a positive correlation with M0 macrophages and a negative correlation with CD8 T cells. IHC and RT-qPCR analyses of human carotid plaque samples, as well as ELISA analyses of blood samples, revealed significant upregulation of KMO and MAOB expression, along with decreased ALDH1B1 expression, in both stable and unstable samples compared to the control samples. However, among the three key genes mentioned above, only KMO showed a significant increase in expression in unstable plaque samples compared to stable plaque samples. Furthermore, the expression patterns of KMO in human carotid unstable plaque tissues and cultured mouse macrophage cell lines were assessed using immunofluorescence co-staining techniques. Finally, lentivirus-mediated KMO silencing was successfully transduced into the aortas of high-fat-fed ApoE-/- mice, with results indicating that KMO silencing attenuated plaque formation and promoted plaque stability in ApoE-/- mice. CONCLUSIONS: The results suggest that KMO, a mitochondria-targeted gene associated with macrophage cells, holds promise as a valuable diagnostic biomarker for assessing the instability of atherosclerotic plaques.
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Placa Aterosclerótica , Femenino , Humanos , Masculino , Persona de Mediana Edad , Biología Computacional/métodos , Perfilación de la Expresión Génica , Redes Reguladoras de Genes , Genes Mitocondriales/genética , Macrófagos/metabolismo , Macrófagos/patología , Mitocondrias/metabolismo , Placa Aterosclerótica/genética , Placa Aterosclerótica/patología , Reproducibilidad de los Resultados , Quinurenina 3-Monooxigenasa/genética , Quinurenina 3-Monooxigenasa/metabolismoRESUMEN
Natural products (NPs) play an irreplaceable role in the intervention of various diseases and have been considered a critical source of drug development. Many new pharmacodynamic compounds with potential clinical applications have recently been derived from NPs. These compounds range from small molecules to polysaccharides, polypeptides, proteins, self-assembled nanoparticles, and extracellular vesicles. This review summarizes various active substances found in NPs. The investigation of active substances in NPs can potentiate new drug development and promote the in-depth comprehension of the mechanism of action of NPs that can be beneficial in the prevention and treatment of human diseases.
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During investigations of invertebrate-associated fungi in Yunnan Province of China, a new species, Sporodiniella sinensis sp. nov., was collected. Morphologically, S. sinensis is similar to Sporodiniella umbellata; however, it is distinguished from S. umbellata by its greater number of sporangiophore branches, longer sporangiophores, larger sporangiospores, and columellae. The novel species exhibits similarities of 91.62â% for internal transcribed spacer (ITS), 98.66-99.10â% for ribosomal small subunit (nrSSU), and 96.36-98.22â% for ribosomal large subunit (nrLSU) sequences, respectively, compared to S. umbellata. Furthermore, phylogenetic analyses based on combined sequences of ITS, nrLSU and nrSSU show that it forms a separate clade in Sporodiniella, and clusters closely with S. umbellata with high statistical support. The phylogenetic and morphological evidence support S. sinensis as a distinct species. Here, it is formally described and illustrated, and compared with other relatives.
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Ácidos Grasos , Mucorales , Animales , Filogenia , China , Análisis de Secuencia de ADN , Composición de Base , ARN Ribosómico 16S/genética , ADN Bacteriano/genética , Técnicas de Tipificación Bacteriana , Ácidos Grasos/química , InvertebradosRESUMEN
A non-invasive condensation collection-ion chromatography method was established for the determination of organic acids and anions including lactic acid, formic acid, acetic acid, pyruvic acid, chloride, nitrate, nitrite, and sulfate in the exhaled breath of humans. The breath exhaled was condensed and collected using a home-made exhaled breath condensation equipment. This equipment included a disposable mouthpiece as a blow-off port, one-way valve and flow meter, cold trap, disposable condensate collection tube placed in the cold trap, and gas outlet. A standard sampling procedure was used. Before collection, the collection temperature and sampling volume were set on the instrument control panel, and sampling was started when the cold-trap temperature dropped to the set value, while maintaining the balance. Subjects were required to gargle with pure water before sampling. During the sampling process, the subjects were required to inhale deeply until the lungs were full of gas and then exhale evenly through the air outlet. When the set volume was collected, the instrument made a prompt sound; then, the collection was immediately ended, the expiration time was recorded, and the average collection flow was calculated according to the expiration time and sampling volume. After collection, the disposable condensation collection tube was immediately taken out, sealed, and stored in the refrigerator at -20 â away from light, and immediately used for further testing. The organic acids and anions in exhaled breath condensation (EBC) were filtered through a 0.22 µm membrane filter before injection and detected by ion chromatography with conductivity detection. Factors such as collection temperature and collection flow rate during condensation collection were optimized. The optimal cooling temperature was set at -15 â, and the optimal exhaled breath flow rate was set at 15 L/min. The mobile phase consisted of a mixture of sodium carbonate (1.5 mmol/L) and sodium bicarbonate (3 mmol/L). The flow rate was 0.8 mL/min, and the injection volume was 100 µL. An IC-SA3 column (250 mm×4.0 mm) was used, and the temperature was set at 45 â. An ICDS-40A electrodialysis suppressor was used, and the current was set at 150 mA. The linear ranges of the eight organic acids and anions were 0.1-10.0 mg/L; their correlation coefficients (r) were ≥0.9993. The limits of detection (LODs) for the eight organic acids and anions were 0.0017-0.0150 mg/L based on a signal-to-noise ratio of 3, and the limits of quantification (LOQs) were 0.0057-0.0500 mg/L based on a signal-to-noise ratio of 10. The intra-day precisions were 5.06%-6.33% (n=5), and the inter-day precisions were 5.37%-7.50% (n=5). This method was used to detect organic acids and anions in the exhaled breath of five healthy subjects. The contents of organic acids and anions in the exhaled breath were calculated. The content of lactic acid was relatively high, at 1.13-42.3 ng/L, and the contents of other seven organic acids and anions were 0.18-11.0 ng/L. During a 10 km-long run, the majority of organic acids and anions in the exhaled breath of five subjects first increased and then decreased. However, due to abnormal metabolism, the content changes of lactic acid, acetic acid, pyruvic acid and chloride in one subject were obviously different from others during exercise, showing a continuous rise. This method has the advantages of involving a simple sampling process and exhibiting good precision, few side effects, and no obvious discomfort or risk to the subjects. This study provides experimental ideas and a theoretical basis for future research on human metabolites.
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Cloruros , Ácido Pirúvico , Humanos , Aniones , Ácido Láctico/análisis , Cromatografía , Acetatos/análisisRESUMEN
In this study, seventeen isobavachalcone (IBC) derivatives (1-17) were synthesised, and evaluated for their cytotoxic activity against three human lung cancer cell lines. Among these derivatives, compound 16 displayed the most potent cytotoxic activity against H1975 and A549 cells, with IC50 values of 4.35 and 14.21 µM, respectively. Compared with IBC, compound 16 exhibited up to 4.11-fold enhancement of cytotoxic activity on human non-small cell lung cancer H1975 cells. In addition, we found that compound 16 suppressed H1975 cells via inducing apoptosis and necroptosis. The initial mechanism of compound 16 induced cell death in H1975 cells involves the increasing of Bax/Bcl-2 ratio and Cyt C protein level, down-regulating of Akt protein level, and cleaving caspase-9 and -3 induced apoptosis; the up-regulation of RIP3, p-RIP3, MLKL, and p-MLKL levels induced necroptosis. Moreover, compound 16 also caused mitochondrial dysfunction, thereby decreasing cellular ATP levels, and resulting in excessive reactive oxygen species (ROS) accumulation.
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Antineoplásicos , Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Humanos , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/metabolismo , Necroptosis , Apoptosis , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Especies Reactivas de Oxígeno/metabolismoRESUMEN
Xanthohumol (Xn) is a chalcone compound isolated from Humulus lupulus Linn., that has various biological activities. In this study, eight Xn derivatives were synthesized by Williamson, Mannich, Reimer-Tiemann, and Schiff base reactions, and evaluated for their in vitro cytotoxic activity against five human cancer cell lines (MDA-MB-231, MCF-7, CNE-2Z, SMMC-7721, and H1975). Among these compounds, 2-((E)-2,4-dihydroxy-5-((E)-3-(4-hydroxyphenyl)acryloyl)-6-methoxy-3-(3- methylbut-2-en-1-yl)benzylidene)hydrazine-1-carboximidamide (8) exhibited the most potent cytotoxic activity against the five cancer cells, with IC50 values ranging from 4.87 to 14.35 µM. Wound-healing and transwell assays showed that compound 8 inhibited the migration and invasion of MDA-MB-231 cells by down-regulation HIF-1α, MMP-2 and MMP-9 protein expression. We further demonstrated that compound 8 induced apoptosis of MDA-MB-231 cells by increasing of Bax/Bcl-2 ratio and down-regulation of Akt protein expression.
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Four new magnolol derivatives were synthesized and evaluated for their in vitro anti-cancer properties. Among these, compound 3 showed the most potent cytotoxic activity against the SMMC-7721, SUN-449, and HepG2 human hepatocellular carcinoma cell lines, with IC50 values of 3.39, 4.11, and 6.88 µM, respectively. Compound 3 also induced apoptosis of SMMC-7721 cells by down-regulating Bcl-2 and Akt protein levels, up-regulating of Bax protein level, and cleaving caspase-9 and -3. In addition, transwell assays showed that compound 3 significantly suppressed the migration and invasion of SMMC-7721 cells, which was confirmed based on the down-regulation of hypoxia inducible factor-1α (HIF-1α), matrix metalloproteinase-2 and -9 (MMP-2, and MMP-9) protein levels.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/tratamiento farmacológico , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patología , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patología , Metaloproteinasa 2 de la Matriz/metabolismo , Línea Celular Tumoral , Movimiento Celular , Invasividad Neoplásica , Apoptosis , Proliferación CelularRESUMEN
In this study, 21 new honokiol derivatives were synthesised, and their anti-cancer properties were investigated. Among these, compound 1g exhibited the most potent cytotoxic activity against human nasopharyngeal carcinoma CNE-2Z cells, human gastric cancer SGC7901 cells, human breast cancer MCF-7 cells, and mouse leydig testicular cancer I-10 lines with IC50 values of 6.04, 7.17, 6.83, and 5.30 µM, respectively. Compared to the parental compound, 1g displayed up to 5.18-fold enhancement of the cytotoxic effect on CNE-2Z cells. We further demonstrated that 1g inhibited cell growth, suppressed migration and invasion, and induced apoptosis of CNE-2Z cells by down-regulating HIF-1α, MMP-2, MMP-9, Bcl-2, Akt and up-regulating Bax protein levels. Transfection of CNE-2Z cells with HIF-1α siRNA reduced cell migration and invasion. In addition, in vivo experiments confirmed that 1g inhibited tumour growth in CNE-2Z cell-xenografted nude mice with low toxicity. Thus, our data suggested that 1g was a potent and safe lead compound for nasopharyngeal carcinoma therapy.
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Antineoplásicos , Carcinoma , Neoplasias Nasofaríngeas , Neoplasias Testiculares , Masculino , Humanos , Animales , Ratones , Carcinoma Nasofaríngeo/tratamiento farmacológico , Carcinoma/tratamiento farmacológico , Neoplasias Nasofaríngeas/tratamiento farmacológico , Neoplasias Nasofaríngeas/genética , Neoplasias Nasofaríngeas/patología , Ratones Desnudos , Línea Celular Tumoral , Proliferación Celular , Apoptosis , Antineoplásicos/farmacología , Antineoplásicos/uso terapéuticoRESUMEN
In patients with breast cancer, lower bone mineral density increases the risk of bone metastasis. Although the relationship between bone-matrix mineralization and tumour-cell phenotype in breast cancer is not well understood, mineralization-induced rigidity is thought to drive metastatic progression via increased cell-adhesion forces. Here, by using collagen-based matrices with adjustable intrafibrillar mineralization, we show that, unexpectedly, matrix mineralization dampens integrin-mediated mechanosignalling and induces a less proliferative stem-cell-like phenotype in breast cancer cells. In mice with xenografted decellularized physiological bone matrices seeded with human breast tumour cells, the presence of bone mineral reduced tumour growth and upregulated a gene-expression signature that is associated with longer metastasis-free survival in patients with breast cancer. Our findings suggest that bone-matrix changes in osteogenic niches regulate metastatic progression in breast cancer and that in vitro models of bone metastasis should integrate organic and inorganic matrix components to mimic physiological and pathologic mineralization.
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Neoplasias de la Mama , Calcinosis , Neoplasias Mamarias Animales , Humanos , Ratones , Animales , Femenino , Matriz Ósea/patología , Integrinas , Neoplasias de la Mama/patología , Calcificación Fisiológica/fisiología , ColágenoRESUMEN
A plant can be thought of as a colony comprising numerous growth buds, each developing to its own rhythm. Such lack of synchrony impedes efforts to describe core principles of plant morphogenesis, dissect the underlying mechanisms, and identify regulators. Here, we use the minimalist known angiosperm to overcome this challenge and provide a model system for plant morphogenesis. We present a detailed morphological description of the monocot Wolffia australiana, as well as high-quality genome information. Further, we developed the plant-on-chip culture system and demonstrate the application of advanced technologies such as single-nucleus RNA-sequencing, protein structure prediction, and gene editing. We provide proof-of-concept examples that illustrate how W. australiana can decipher the core regulatory mechanisms of plant morphogenesis.
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Li3YX6 (X = Cl, Br) materials are Li-ion conductors that can be used as solid electrolytes in all solid-state batteries. Solid electrolytes ideally have high ionic conductivity and (electro)chemical compatibility with the electrodes. It was proven that introducing Br to Li3YCl6 increases ionic conductivity but, according to thermodynamic calculations, should also reduce oxidative stability. In this paper, the trade-off between ionic conductivity and electrochemical stability in Li3YBr x Cl6-x halogen-substituted compounds is investigated. The compositions of Li3YBr1.5Cl4.5 and Li3YBr4.5Cl1.5 are reported for the first time, along with a consistent analysis of the whole Li3YBr x Cl6-x (x = 0-6) tie-line. The results show that, while Br-rich materials are more conductive (5.36 × 10-3 S/cm at 30 °C for x = 4.5), the oxidative stability is lower (â¼3 V compared to â¼3.5 V). Small Br content (x = 1.5) does not affect oxidative stability but substantially increases ionic conductivity compared to pristine Li3YCl6 (2.1 compared to 0.049 × 10-3 S/cm at 30 °C). This work highlights that optimization of substitutions in the anion framework provide prolific and rational avenues for tailoring the properties of solid electrolytes.
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AbstactA total of 16 fungal strains were isolated from fresh leaves and flowers of Magnolia grandiflora and the EtOAc extracts of them were assayed for antitumor activities. Among these, the fungus Dothideomycetes sp. BMC-101 with broad spectrum inhibition was selected for further study. Four alkaloids (1-4) including two new compounds (2-(hydroxyimino)-3-phenylpropanoyl)-L-phenylalanine (1) and 8-Acetyl-bisdethiobis(methylsulfanyl)apoaranotin (4)) were isolated from Dothideomycetes sp. BMC-101. The structure of 1 was characterized with an oxime moiety formed by the condensation of two phenylalanines. To our knowledge, this is the first report on a fungal phenylalanine derivative with an oxime moiety.
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Environmental parameters have a significant impact on the spread of respiratory viral diseases (temperature (T), relative humidity (RH), and air saturation state). T and RH are strongly correlated with viral inactivation in the air, whereas supersaturated air can promote droplet deposition in the respiratory tract. This study introduces a new concept, the dynamic virus deposition ratio (α), that reflects the dynamic changes in viral inactivation and droplet deposition under varying ambient environments. A non-steady-state-modified Wells-Riley model is established to predict the infection risk of shared air space and highlight the high-risk environmental conditions. Findings reveal that a rise in T would significantly reduce the transmission of COVID-19 in the cold season, while the effect is not significant in the hot season. The infection risk under low-T and high-RH conditions, such as the frozen seafood market, is substantially underestimated, which should be taken seriously. The study encourages selected containment measures against high-risk environmental conditions and cross-discipline management in the public health crisis based on meteorology, government, and medical research.
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COVID-19 , Humanos , Temperatura , Humedad , Frío , Inactivación de VirusRESUMEN
OBJECTIVE@#To explore the manifestations of jingjin (sinews/fascia) lesions and summarize their distribution rules in the patients with neck-type cervical spondylosis so as to provide the evidences for the development of clinical diagnosis and treatment scheme of acupuncture for cervical spondylosis.@*METHODS@#A total of 120 patients with neck-type cervical spondylosis were collected. The meridian diagnostic method was used to examine the upper back of each patient, the manifestation category of jingjin lesions, locations and the affected muscle regions of twelve meridians were recorded.@*RESULTS@#(1) The punctate lesions of jingjin were detected in 15 regions, and the highest frequency of lesion occurred in the region from the inner upper corner of the scapula to Quyuan (SI 13) (113 cases, 94.2% of lesion frequency). The lesion frequency of 10 regions was ≥50.0%. The punctate lesions were mainly distributed in the muscle regions of hand-shaoyang (349 cases) and foot-taiyang (333 cases). (2) The linear lesions of jingjin were detected in 10 regions, and the highest frequency of lesion occurred in the region from the inner upper corner of the scapula to Quyuan (SI 13) (77 cases, 64.2% of lesion frequency). The lesion frequency of 2 regions was ≥50.0%. The linear lesions occurred mainly in the muscle region of foot-taiyang (251 cases). (3) Eight regions were examined to be the planar lesions of jingjin, and the highest frequency of lesion was found in the site of Jianjing (GB 21) (84 cases, 70.0% of lesion frequency). The lesion frequency of 3 regions was ≥50.0%. The muscle region of foot-taiyang (260 cases) was predominated in the planar lesions. (4) The distribution of all of the punctate, linear and planar lesions of jingjin was analyzed statistically. It was found that 25 regions were involved and those with the high lesion frequency were distributed in the area from the inner upper corner of the scapula to Quyuan (SI 13), the sites of Jianjing (GB 21) and Dazhui (GV 14), transverse processes of C3 to C5 and the area from the lateral border of the scapula to the teres minor, separately. The muscle regions of foot-taiyang, hand-shaoyang and hand-yangming were involved in various kinds of jingjin lesions.@*CONCLUSION@#Jingjin lesions in patients with neck-type cervical spondylosis can be divided into three categories, namely, punctate, linear and planar lesions; of which, the punctate lesions are dominated. A majority of jingjin lesions is related to the muscle region of foot-taiyang, and the lesion frequency is higher compared with the lesions to the muscle regions of hand-shaoyang and hand-yangming. Jingjin lesions are commonly distributed in the area from the inner upper corner of the scapula to Quyuan (SI 13).
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Humanos , Meridianos , Terapia por Acupuntura , Puntos de Acupuntura , Espondilosis/terapia , AcupunturaRESUMEN
Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease worldwide. Fat accumulation "sensitizes" the liver to insult and leads to nonalcoholic steatohepatitis (NASH). G protein-coupled receptor 35 (GPR35) is involved in metabolic stresses, but its role in NAFLD is unknown. We report that hepatocyte GPR35 mitigates NASH by regulating hepatic cholesterol homeostasis. Specifically, we found that GPR35 overexpression in hepatocytes protected against high-fat/cholesterol/fructose (HFCF) diet-induced steatohepatitis, whereas loss of GPR35 had the opposite effect. Administration of the GPR35 agonist kynurenic acid (Kyna) suppressed HFCF diet-induced steatohepatitis in mice. Kyna/GPR35 induced expression of StAR-related lipid transfer protein 4 (STARD4) through the ERK1/2 signaling pathway, ultimately resulting in hepatic cholesterol esterification and bile acid synthesis (BAS). The overexpression of STARD4 increased the expression of the BAS rate-limiting enzymes cytochrome P450 family 7 subfamily A member 1 (CYP7A1) and CYP8B1, promoting the conversion of cholesterol to bile acid. The protective effect induced by GPR35 overexpression in hepatocytes disappeared in hepatocyte STARD4-knockdown mice. STARD4 overexpression in hepatocytes reversed the aggravation of HFCF diet-induced steatohepatitis caused by the loss of GPR35 expression in hepatocytes in mice. Our findings indicate that the GPR35-STARD4 axis is a promising therapeutic target for NAFLD.
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Standardized treatment guidelines and effective drugs are not available for human triple-negative breast cancer (TNBC). Many efforts have recently been exerted to investigate the efficacy of natural compounds as anticancer agents owing to their low toxicity. However, no study has examined the effects of isobavachalcone (IBC) on the programmed cell death (PCD) of human triple-negative breast MDA-MB-231 cancer cells. In this study, IBC substantially inhibited the proliferation of MDA-MB-231 cells in concentration- and time-dependent manners. In addition, we found that IBC induced multiple cell death processes, such as apoptosis, necroptosis, and autophagy in MDA-MB-231 cells. The initial mechanism of IBC-mediated cell death in MDA-MB-231 cells involves the downregulation of Akt and p-Akt-473, an increase in the Bax/Bcl-2 ratio, and cleaved caspases-3 induced apoptosis; the upregulation of RIP3, p-RIP3 and MLKL induced necroptosis; as well as a simultaneous increase in LC3-II/I ratio induced autophagy. In addition, we observed that IBC induced mitochondrial dysfunction, thereby decreasing cellular ATP levels and increasing reactive oxygen species accumulation to induce PCD. These results suggest that IBC is a promising lead compound with anti-TNBC activity.
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Antineoplásicos , Neoplasias de la Mama Triple Negativas , Humanos , Neoplasias de la Mama Triple Negativas/tratamiento farmacológico , Neoplasias de la Mama Triple Negativas/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Línea Celular Tumoral , Proteína X Asociada a bcl-2 , Apoptosis , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Adenosina Trifosfato/farmacología , Proliferación CelularRESUMEN
OBJECTIVE: To investigate the prognostic value of interim 18F-FDG PET/CT in patients with diffuse large B-cell lymphoma (DLBCL). METHODS: A total of 97 patients with pathologically diagnosed DLBCL at Sichuan Cancer Hospital and Institute from March 2015 to June 2020 were enrolled in this retrospective study. Receiver operating characteristic analysis (ROC) was used to calculate the optimum maximum standard uptake value reduction ratio (â³SUVmax%) cut-off value. The prognostic value of â³SUVmax% and Deauville five-point scale (5-PS) in patients with DLBCL was compared, and the determined prognostic factors were analyzed. RESULTS: ROC curve indicated that the optimum â³SUV max% cut-off value was 74.9%. Patients with â³SUVmax%≥74.9% had a lower rate of progression or recurrence than those with â³SUVmax% < 74.9% (both P<0.001). Meanwhile, patients with 5-PS score < 4 also had a lower rate of progression or recurrence than those with 5-PS score≥4 (both P<0.001). â³SUVmax% and 5-PS had high specificity (83.7% vs 83.7%) and negative predictive value (87.3% vs 84.9%), while low sensitivity (56.0% vs 52.2%) and positive predictive value (53.8% vs 50.0%). â³SUVmax% was more sensitive than 5-PS for the corresponding parameters (78.3% vs 76.2%). Univariate analysis showed that Ann Arbor stage, international prognostic index of National Comprehensive Cancer Network (NCCN-IPI), â³SUVmax% and 5-PS were associated with TTP and PFS (all P<0.001). Multivariate analysis showed that â³SUVmax% was an independent predictor of TTP and PFS (P=0.031, P=0.023). CONCLUSION: Both 5-PS and â³SUVmax% can be used to evaluate the prognosis of DLBCL patients, but the predictive value of â³SUVmax% is superior to that of 5-PS.
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Fluorodesoxiglucosa F18 , Linfoma de Células B Grandes Difuso , Fluorodesoxiglucosa F18/uso terapéutico , Humanos , Linfoma de Células B Grandes Difuso/diagnóstico por imagen , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Tomografía Computarizada por Tomografía de Emisión de Positrones , Tomografía de Emisión de Positrones , Pronóstico , Estudios RetrospectivosRESUMEN
Glyphosate (GLY), an active ingredient of the most commonly used herbicide, when in crops and feed, is deleterious to male reproductive health. Trehalose (Tre), a naturally non-reducing disaccharide, is shown to counteract the adverse stresses due to its antioxidation effect. Thus, this study was designed to investigate whether Tre can improve GLY-induced testicular damage via suppressing oxidative stress. 60 healthy Hy-Line Brown breeder roosters were utilized to assess the protective effects of Tre supplementation against testicular oxidative damage caused by GLY. Data showed that Tre administration significantly alleviated GLY- induced reduction in testis weight, decreased GLY level in the testis tissues, and alleviated GLY-caused testicular pathological damage. Concurrently, GLY treatment significantly elevated serum malondialdehyde (MDA) and testicular reactive oxygen species (ROS) levels, decreased serum total anti-oxidation capacity (T-AOC), catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) levels, which were all notably reversed by Tre administration. Moreover, GLY- inhibited nuclear factor erythroid 2-related factor 2 (Nrf2) pathway in rooster testis, a master regulator of oxidative stress, was markedly recovered by Tre administration. In summary, these findings demonstrated that Tre can prevent GLY-induced testicular damage in roosters by ameliorating oxidative stress.
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Antioxidantes , Trehalosa , Masculino , Animales , Antioxidantes/farmacología , Trehalosa/metabolismo , Trehalosa/farmacología , Testículo/metabolismo , Pollos/metabolismo , Estrés Oxidativo , Superóxido Dismutasa/metabolismo , GlifosatoRESUMEN
INTRODUCTION: Surgical resection of medulloblastoma (MB) remains a challenge. At present, a variety of tracers have been used for intraoperative tumor visualization. However, there are few reports on the intraoperative visualization of MB. Hence, we reported our experience of applying fluorescein sodium (FS) in MB surgery. METHODS: We retrospectively analyzed the clinical information of patients with MB confirmed by surgery and pathology from January 2016 to December 2020 from Sun Yat-sen University Cancer Center. A total of 62 patients were enrolled, of which 27 received intraoperative FS and 35 did not. The intraoperative dose of FS was 3 mg/kg. RESULTS: Among the 62 patients, 42 were males, and twenty were females. The age of onset in the FS group was 9.588 ± 7.322, which in the non-fluorescein sodium group was 13.469 ± 10.968, p = 0.198. We did not find significant differences in tumor location, tumor size, tumor resection, tumor histology, and preoperative symptoms (hydrocephalus, headache, vomit, balance disorder) between the groups. There was no significant difference in the postoperative symptoms (hydrocephalus, headache, vomiting, balance disorder, and cerebellar mutism). However, patients in the FS group had a relatively low incidence of balance disorder and cerebellar mutism. There was definite fluorescence of tumor in all cases of the FS group, and even the tiny metastatic lesion was visible. No case had side effects related to the use of FS. CONCLUSIONS: FS is safe and effective in MB surgery. Whether the application of FS for surgery can reduce complications remains to be studied in the future.