BACKGROUND: So far there's no tumor maker applied in diagnosis and treatment of thymic epithelial tumors. This study is to assess the correlation between serum cytokine 19 fragment (Cyfra 21-1) and clinicopathological features and prognosis of thymic epithelial tumors (TETs). METHODS: The clinical data of 159 patients with TETs in Shanghai Chest Hospital was retrospectively analysed. Patients were divided into groups according to different tumor stages and histotypes. Serum Cyfra 21-1 was thus compared. In addition, the possible relationship between perioperative serum Cyfra 21-1 level and the recurrent status was carrid out. RESULTS: Preoperative Cyfra 21-1 serum concentrations in patiants with advanced stage (T4) and thymic carcinomas were significantly higher than that in others (P<0.001, P<0.001, respectively). When the preoperative serum level exceeds the out-off of 1.66 ng/mL, it possibly indicates the recurrence during follow up. Furthermore, the sensitivity, specificity, and positive as well as negative predictive value (PPV and NPV) of postoperative Cyfra 21-1 to predict tumor recurrence were evaluated. At a cut-off of Cyfra 21-1 of 2.66 ng/mL, the sensitivity was 0.7, the specificity was 0.925, the PPV was 0.5 and the NPV was 0.966. CONCLUSIONS The elevated level of preoperative serum Cyfra 21-1 indicates an advanced stage of tumor or a more malignant histotype (thymic carcinoma). It also probably suggests a higher risk of tumor recurrence. During the oncological follow up, in addition to regular imaging examinations, the blood test of serum Cyfra 21-1 is also suggested to improve the diagnosis of tumor recurrence in order to improve the prognosis.
Biomarkers, Tumor ; blood ; Female ; Follow-Up Studies ; Humans ; Keratin-19 ; blood ; chemistry ; Male ; Middle Aged ; Neoplasms, Glandular and Epithelial ; blood ; diagnosis ; pathology ; Peptide Fragments ; blood ; Prognosis ; ROC Curve ; Retrospective Studies ; Thymus Neoplasms ; blood ; diagnosis ; pathology

Naodesheng (NDS) formula, which consists of Rhizoma Chuanxiong, Lobed Kudzuvine, Carthamus tinctorius, Radix Notoginseng, and Crataegus pinnatifida, is widely applied for the treatment of cardio/cerebrovascular ischemic diseases, ischemic stroke, and sequelae of cerebral hemorrhage, etc. At present, the studies on NDS formula for Alzheimer's disease (AD) only focus on single component of this prescription, and there is no report about the synergistic mechanism of the constituents in NDS formula for the potential treatment of dementia. Therefore, the present study aimed to predict the potential targets and uncover the mechanisms of NDS formula for the treatment of AD. Firstly, we collected the constituents in NDS formula and key targets toward AD. Then, drug-likeness, oral bioavailability, and blood-brain barrier permeability were evaluated to find drug-like and lead-like constituents for treatment of central nervous system diseases. By combining the advantages of machine learning, molecular docking, and pharmacophore mapping, we attempted to predict the targets of constituents and find potential multi-target compounds from NDS formula. Finally, we built constituent-target network, constituent-target-target network and target-biological pathway network to study the network pharmacology of the constituents in NDS formula. To the best of our knowledge, this represented the first to study the mechanism of NDS formula for potential efficacy for AD treatment by means of the virtual screening and network pharmacology methods.
Alzheimer Disease ; drug therapy ; pathology ; physiopathology ; Autoanalysis ; Biological Availability ; Biomarkers ; Biomarkers, Pharmacological ; Databases, Chemical ; Drug Combinations ; Drug Discovery ; methods ; Drugs, Chinese Herbal ; chemistry ; pharmacology ; therapeutic use ; Humans ; Machine Learning ; Molecular Docking Simulation ; Neural Networks, Computer ; Peptide Fragments ; chemistry ; Permeability

Animals ; Cell Respiration ; Electron Transport Complex III ; metabolism ; Humans ; Iron-Sulfur Proteins ; chemistry ; metabolism ; Mitochondria ; metabolism ; Peptide Fragments ; chemistry ; metabolism ; Protein Multimerization ; Protein Structure, Quaternary ; Protein Subunits ; chemistry

Alzheimer's disease (AD) is one of the major neurodegenerative disorders of the elderly, which is characterized by the accumulation and deposition of amyloid-beta (Aβ) peptide in human brains. Oxidative stress and neuroinflammation induced by Aβ in brain are increasingly considered to be responsible for the pathogenesis of AD. The present study aimed to determine the protective effects of walnut peptides against the neurotoxicity induced by Aβ25-35 in vivo. Briefly, the AD model was induced by injecting Aβ25-35 into bilateral hippocampi of mice. The animals were treated with distilled water or walnut peptides (200, 400 and 800 mg/kg, p.o.) for five consecutive weeks. Spatial learning and memory abilities of mice were investigated by Morris water maze test and step-down avoidance test. To further explore the underlying mechanisms of the neuroprotectivity of walnut peptides, the activities of superoxide dismutase (SOD), glutathione (GSH), acetylcholine esterase (AChE), and the content of malondialdehyde (MDA) as well as the level of nitric oxide (NO) in the hippocampus of mice were measured by spectrophotometric method. In addition, the levels of 8-hydroxy-2'-deoxyguanosine (8-OHdG), tumor necrosis factor-α (TNF-α), interleukin 1β (IL-1β) and IL-6 in the samples were determined using ELISA. The hippocampal expressions of inducible nitric oxide synthase (iNOS) and nuclear factor κB (NF-κB) were evaluated by Western blot analysis. The results showed that walnut peptides supplementation effectively ameliorated the cognitive deficits and memory impairment of mice. Meanwhile, our study also revealed effective restoration of levels of antioxidant enzymes as well as inflammatory mediators with supplementation of walnut peptides (400 or 800 mg/kg). All the above findings suggested that walnut peptides may have a protective effect on AD by reducing inflammatory responses and modulating antioxidant system.
Acetylcholinesterase ; metabolism ; Alzheimer Disease ; drug therapy ; etiology ; Amyloid beta-Peptides ; toxicity ; Animals ; Female ; Glutathione ; metabolism ; Hippocampus ; drug effects ; metabolism ; Interleukins ; metabolism ; Juglans ; chemistry ; Male ; Malondialdehyde ; metabolism ; Maze Learning ; Memory Disorders ; drug therapy ; etiology ; Mice ; NF-kappa B ; metabolism ; Neuroprotective Agents ; pharmacology ; therapeutic use ; Nitric Oxide ; metabolism ; Peptide Fragments ; toxicity ; Peptides ; pharmacology ; therapeutic use ; Plant Extracts ; pharmacology ; therapeutic use ; Superoxide Dismutase ; metabolism ; Tumor Necrosis Factor-alpha ; metabolism

The chronic effects of carboxyl-terminal polypeptide of Cardiotrophin-1 (CT-1-CP) on ventricular electrical remodeling were investigated. CT-1-CP, which contains 16 amino acids in sequence of the C-terminal of Cardiotrophin-1, was selected and synthesized, and then administered to Kunming mice (aged 5 weeks) by intraperitoneal injection (500 ng·g⁻¹·day⁻¹) (4 groups, n=10 and female: male=1:1 in each group) for 1, 2, 3 and 4 weeks, respectively. The control group (n=10, female: male=1:1) was injected by physiological saline for 4 weeks. The epicardial monophasic action potential (MAP) was recorded by using a contact-type MAP electrode placed vertically on the left ventricular (LV) epicardium surface, and the electrocardiogram (ECG) signal in lead II was monitored synchronously. ECG intervals (RR, PR, QRS and QT) and the amplitude of MAP (Am), the maximum upstroke velocity (Vmax), as well as action potential durations (APDs) at different repolarization levels (APD30, APD50, APD70, and APD90) of MAP were determined and analyzed in detail. There were no significant differences in RR and P intervals between CT-1-CP-treated groups and control group, but the PR segment and the QRS complex were greater in the former than in the latter (F=2.681 and 5.462 respectively, P<0.05). Though QT interval and the corrected QT interval (QTc) were shorter in CT-1-CP-treated groups than in control group, the QT dispersion (QTd) of them was greater in the latter than in the former (F=3.090, P<0.05) and increased with the time. The ECG monitoring synchronously with the MAP showed that the compression of MAP electrode on the left ventricular epicardium induced performance similar to myocardium ischemia. As compared with those before chest-opening, the PR segment and QT intervals remained basically unchanged in control group, but prolonged significantly in all CT-1-CP-treated groups and the prolongation of QT intervals increased gradually along with the time of exposure to CT-1-CP. The QRS complex had no significant change in control group, one-week and three-week CT-1-CP-treated groups, but prolonged significantly in two-week and four-week CT-1-CP-treated groups. Interestingly, the QTd after chest-opening was significantly greater than that before chest-opening in control group (t=5.242, P<0.01), but decreased along with the time in CT-1-CP-treated groups. The mean MAP amplitude, Vmax and APD were greater in CT-1-CP-treated groups than those in control group, and became more obvious along with the time. The APD in four CT-1-CP-treat groups was prolonged mainly in middle to final repolarization phase. The difference among these groups became significant in middle phase (APD50) (F=6.076, P<0.01) and increased furthermore in late and final phases (APD70: F=10.054; APD90: F=18.691, P<0.01) along with the time of injection of CT-1-CP. The chronic action of CT-1-CP might induce the adapting alteration in cardiac conductivity and ventricular repolarization. The amplitude and the Vmax of the anterior LV epicardial MAP increased obviously, and the APD prolonged mainly in late and final phase of repolarization.
Animals ; Cytokines ; chemistry ; physiology ; Electrocardiography ; Heart Ventricles ; metabolism ; Mice ; Peptide Fragments ; physiology ; Ventricular Function

Analysis of the T-cell receptor (TCR) repertoire of innate CD4+ T cells selected by major histocompatibility complex (MHC) class II-dependent thymocyte-thymocyte (T-T) interaction (T-T CD4+ T cells) is essential for predicting the characteristics of the antigens that bind to these T cells and for distinguishing T-T CD4+ T cells from other types of innate T cells. Using the TCRmini Tg mouse model, we show that the repertoire of TCRalpha chains in T-T CD4+ T cells was extremely diverse, in contrast to the repertoires previously described for other types of innate T cells. The TCRalpha chain sequences significantly overlapped between T-T CD4+ T cells and conventional CD4+ T cells in the thymus and spleen. However, the diversity of the TCRalpha repertoire of T-T CD4+ T cells seemed to be restricted compared with that of conventional CD4+ T cells. Interestingly, the frequency of the parental OT-II TCRalpha chains was significantly reduced in the process of T-T interaction. This diverse and shifted repertoire in T-T CD4+ T cells has biological relevance in terms of defense against diverse pathogens and a possible regulatory role during peripheral T-T interaction.
Amino Acid Sequence ; Animals ; Antigens, Surface/metabolism ; CD4-Positive T-Lymphocytes/cytology/*immunology/*metabolism ; Cell Communication ; Cell Differentiation/genetics/immunology ; Clonal Evolution ; Histocompatibility Antigens Class II/*immunology ; *Immunity, Innate ; Immunophenotyping ; Lymphocyte Count ; Mice ; Mice, Knockout ; Mice, Transgenic ; Peptide Fragments/chemistry ; Phenotype ; Receptors, Antigen, T-Cell/chemistry/*genetics/metabolism ; Receptors, Antigen, T-Cell, alpha-beta/chemistry/genetics ; Spleen/cytology ; Thymocytes/cytology/immunology/metabolism

Tongluo Xingnao effervescent tablet (TLXNET) is a patented prescription, which comes from modified Xionggui decoction and can improve cognitive function. However, its effect on the urine metabolites and anti-dementia mechanism in the dementia model rats induced by hippocampal injection with Aβ25-35 remains unclear. The experiment focused on the changes in trajectory and inter-relationship among the urinary metabolite of rats in the blank group, Aβ25-35 hippocampal injection dementia model group and the TLXNET intervention group, in order to determine theirs characteristic metabolic markers and explain the anti-dementia effect of TLX-NET base on the change of metabolic trajectory of these bio-markers. According to the experimental results, 5, 6-indolequinone, 4-hydroxyphenyl pyruvic acid (4-HPPA), cortisol and 3-thiosulfate lactic were preliminarily identified as the characteristic metabolic markers. They mainly participate in dopamine system, glucocorticoids and energy metabolic pathways. TLXNET can apparently downregulate the disturbances of metabolic trajectory of the four bio-markers. The experiment indicates that the dementia model induced by injecting Aβ25-3 into hippocampus has its characteristic endogenous metabolic markers in urine, and ELXNET can ameliorate dementia by down-regulating the disturbances of metabolic trajectory.
Amyloid beta-Peptides ; metabolism ; toxicity ; Animals ; Biomarkers ; urine ; Dementia ; drug therapy ; urine ; Drugs, Chinese Herbal ; administration & dosage ; Female ; Hippocampus ; drug effects ; metabolism ; Humans ; Male ; Metabolomics ; Peptide Fragments ; metabolism ; toxicity ; Rats ; Rats, Sprague-Dawley ; Tablets ; administration & dosage ; Urine ; chemistry

To study the expression of angiotensin converting enzyme 2 (ACE2) and angiotensin (Ang) 1-7 specific receptor Mas protain in renal blood vessels of metabolic syndrome ( MS) rats and its anti-oxidative effect. A total of 80 male SD rats were divided into four groups: the normal control group (NC, the same volume of normal saline), the MS group (high fat diet), the MS + Astragali Radix group (MS + HQ, 6 g x kg(-1) x d(-1) in gavage) and the MS + Valsartan group (MS + XST, 30 mg x kg(-1) x d(-1) in gavage). After four weeks of intervention, their general indexes, biochemical indexes and blood pressure were measured; plasma and renal tissue Ang II, malondialdehyde (MDA) and superoxide demutase (SOD) levels were measured with radioimmunoassay. The protein expressions of Mas receptor, AT1R, ACE and ACE2 were detected by western blot analysis. According to the result, compared with the NC group, the MS group and the MS + HQ group showed significant increases in systolic and diastolic pressures, body weight, fasting glucose, fasting insulin, triglycerides, free fatty acid and Ang II level of MS rats (P < 0.05). The MS + XST group showed notable decreases in systolic and diastolic pressures than that of the MS group. The MS group showed significant increases in the SOD activity and NO level and decrease in the MDA level after being intervened with Astragali Radix. ACE and AT1R protein expressions in renal tissues of the MS group were higher than that in the NC group, but with lower ACE2 and -Mas receptor expressions (all P < 0.05). Compared with the MS group, the MS + HQ group showed significant increase in Mas receptor expression in renal tissues, whereas the MS + XST group showed notable decrease in AT1R (all P < 0.05). In conclusion, Astragali Radix can increase the Mas receptor expressions in renal tissues, decrease ACE expression and change local Ang II, MDA, NO and SOD in kidneys, so as to protect early damages in renal tissues.
Angiotensin I ; metabolism ; Animals ; Astragalus Plant ; chemistry ; Blood Glucose ; metabolism ; Blood Pressure ; drug effects ; Drugs, Chinese Herbal ; administration & dosage ; Humans ; Kidney ; drug effects ; injuries ; metabolism ; Male ; Malondialdehyde ; metabolism ; Metabolic Syndrome ; drug therapy ; genetics ; metabolism ; physiopathology ; Peptide Fragments ; metabolism ; Peptidyl-Dipeptidase A ; genetics ; metabolism ; Proto-Oncogene Proteins ; genetics ; metabolism ; Rats ; Rats, Sprague-Dawley ; Receptors, G-Protein-Coupled ; genetics ; metabolism ; Signal Transduction ; drug effects

Bone sialoprotein-binding protein (Bbp), a MSCRAMMs (Microbial Surface Components Recognizing Adhesive Matrix Molecules) family protein expressed on the surface of Staphylococcus aureus (S. aureus), mediates adherence to fibrinogen α (Fg α), a component in the extracellular matrix of the host cell and is important for infection and pathogenesis. In this study, we solved the crystal structures of apo-Bbp(273-598) and Bbp(273-598)-Fg α(561-575) complex at a resolution of 2.03 Å and 1.45 Å, respectively. Apo-Bbp(273-598) contained the ligand binding region N2 and N3 domains, both of which followed a DE variant IgG fold characterized by an additional D1 strand in N2 domain and D1' and D2' strands in N3 domain. The peptide mapped to the Fg α(561-575) bond to Bbp(273-598) on the open groove between the N2 and N3 domains. Strikingly, the disordered C-terminus in the apo-form reorganized into a highly-ordered loop and a β-strand G'' covering the ligand upon ligand binding. Bbp(Ala298-Gly301) in the N2 domain of the Bbp(273-598)-Fg α(561-575) complex, which is a loop in the apo-form, formed a short α-helix to interact tightly with the peptide. In addition, Bbp(Ser547-Gln561) in the N3 domain moved toward the binding groove to make contact directly with the peptide, while Bbp(Asp338-Gly355) and Bbp(Thr365-Tyr387) in N2 domain shifted their configurations to stabilize the reorganized C-terminus mainly through strong hydrogen bonds. Altogether, our results revealed the molecular basis for Bbp-ligand interaction and advanced our understanding of S. aureus infection process.
Bacterial Proteins ; chemistry ; genetics ; metabolism ; Carrier Proteins ; chemistry ; genetics ; metabolism ; Crystallography, X-Ray ; Fibrinogen ; metabolism ; Ligands ; Models, Molecular ; Mutation ; Peptide Fragments ; chemistry ; metabolism ; Protein Binding ; Protein Structure, Tertiary ; Staphylococcus aureus

OBJECTIVETo investigate the effects of exogenous hydrogen sulfide (H2S) on β-site APP cleaving enzyme 1 (BACE-1) and β-amyloid peptide (Aβ) metabolism in primary culture of neurons under high-glucose condition.

METHODSThe cortical neurons in primary culture under normal and high glucose (60 mmol/L) conditions for 24 h were exposed to 25, 50 and 100 µmol/L NaHS. Aβ1-42 concentration in the cell culture was measured by ELISA, and BACE-1 mRNA and protein levels were detected by fluorescent quantitative real-time PCR and Western blotting, respectively.

RESULTSCompared with the neurons cultured in normal glucose, the neurons exposed to high glucose showed significantly increased Aβ1-42 concentration and BACE-1 mRNA and protein expressions (P<0.05). Exposure to 25, 50 and 100 µmol/L NaHS significantly decreased Aβ1-42 concentration and BACE-1 mRNA and protein expressions in the high-glucose cell culture (P<0.05).

CONCLUSIONNeurons exposed to high glucose exhibit increased Aβ1-42 levels and BACE-1 mRNA and protein expressions, which can be concentration-dependently decreased by NaHS.

Amyloid Precursor Protein Secretases ; metabolism ; Amyloid beta-Peptides ; metabolism ; Animals ; Aspartic Acid Endopeptidases ; metabolism ; Cells, Cultured ; Culture Media ; chemistry ; Glucose ; chemistry ; Hydrogen Sulfide ; pharmacology ; Neurons ; drug effects ; metabolism ; Peptide Fragments ; metabolism ; Rats ; Rats, Sprague-Dawley