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1.
BMC Cardiovasc Disord ; 24(1): 191, 2024 Apr 03.
Article in English | MEDLINE | ID: mdl-38570824

ABSTRACT

AIM: To examine the prognostic value of superoxide dismutase (SOD) activity for monitoring reduced left ventricular ejection fraction(LVEF)in the patients with type 2 diabetes and acute coronary syndrome (ACS). METHODS: The population of this cross-sectional study included 2377 inpatients with type 2 diabetes who had an ACS admitted to the Shandong Provincial Hospital Affiliated to Shandong First Medical University from January 2016 to January 2021. RESULTS: Diabetic patients with ACS were divided into 2 subgroups based on LVEF. The mean SOD activity was significantly lower in patients with an LVEF ≤ 45% than in those with an LVEF > 45% (149.1 (146.4, 151.9) versus 161.9 (160.8, 163.0)). Using ROC statistic, a cut-off value of 148.8 U/ml indicated an LVEF ≤ 45% with a sensitivity of 51.6% and a specificity of 73.7%. SODs activity were found to be correlated with the levels of NT-proBNP, hs-cTnT, the inflammatory marker CRP and fibrinogen. Despite taking the lowest quartile as a reference (OR 0.368, 95% CI 0.493-0.825, P = 0.001) or examining 1 normalized unit increase (OR 0.651, 95% CI 0.482-0.880, P = 0.005), SOD activity was found to be a stronger predictor of reduced LVEF than CRP and fibrinogen, independent of confounding factors. CONCLUSIONS: Our cross-sectional study suggests that SOD activity might be a valuable and easily accessible tool for assessing and monitoring reduced LVEF in the diabetic patients with ACS.


Subject(s)
Acute Coronary Syndrome , Diabetes Mellitus, Type 2 , Ventricular Dysfunction, Left , Humans , Acute Coronary Syndrome/diagnosis , Stroke Volume , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/diagnosis , Biomarkers , Cross-Sectional Studies , Ventricular Function, Left , Ventricular Dysfunction, Left/epidemiology , Prognosis , Superoxide Dismutase , Fibrinogen
2.
Eur J Med Chem ; 227: 113871, 2022 Jan 05.
Article in English | MEDLINE | ID: mdl-34638033

ABSTRACT

The ubiquitination of the hypoxia-inducible factor-1α (HIF-1α) is mediated by interacting with the von Hippel-Lindau protein (VHL), and is associated with cancer, chronic anemia, and ischemia. VHL, an E3 ligase, has been reported to degrade HIF-1 for decades, however, there are few successful inhibitors currently. Poor understanding of the binding pocket and a lack of in-depth exploration of the interactions between two proteins are the main reasons. Hence, we developed an effective strategy to identify and design new inhibitors for protein-protein interaction targets. The hydroxyproline (Hyp564) of HIF-1α contributed the key interaction between HIF-1α and VHL. In this study, detailed information of the binding pocket were explored by alanine scanning, site-directed mutagenesis and molecular dynamics simulations. Interestingly, we found the interaction(s) between Y565 and H110 played a key role in the binding of VHL/HIF-1α. Based on the interactions, 8 derivates of VH032, 16a-h, were synthesized by introducing various groups bounded to H110. Further assay on protein and cellular level exhibited that 16a-h accessed higher binding affinity to VHL and markable or modest improvement in stabilization of HIF-1α or HIF-1α-OH in HeLa cells. Our work provides a new orientation for the modification or design of VHL/HIF-1α protein-protein interaction inhibitors.


Subject(s)
Drug Design , Hydroxyproline/pharmacology , Hypoxia-Inducible Factor 1, alpha Subunit/antagonists & inhibitors , Von Hippel-Lindau Tumor Suppressor Protein/antagonists & inhibitors , Cell Survival/drug effects , Dose-Response Relationship, Drug , HeLa Cells , Humans , Hydroxyproline/chemical synthesis , Hydroxyproline/chemistry , Hypoxia-Inducible Factor 1, alpha Subunit/metabolism , Molecular Dynamics Simulation , Molecular Structure , Protein Binding/drug effects , Structure-Activity Relationship , Von Hippel-Lindau Tumor Suppressor Protein/metabolism
3.
Ibrain ; 8(1): 15-22, 2022.
Article in English | MEDLINE | ID: mdl-37786417

ABSTRACT

Encephalitis is one of the common diseases in neurology. Early diagnosis and appropriate treatments are essential. Autoimmune encephalitis (AE) generally refers to a type of encephalitis mediated by autoimmune mechanisms. It is gradually considered to be an important cause of reversible encephalitis caused by noninfectious factors. It can occur in children, adolescents, and adults, and is clinically characterized by multifocal or diffuse brain damage such as personality changes, seizures, and cognitive impairment, with an overall good effect of immunotherapy. According to the clinical features of the patients, blood and cerebrospinal fluid tests, neuroelectrophysiology, cranial imaging, treatment and prognosis, AEs can be broadly divided into specific antigen (antibody)-related AEs and nonspecific antigen (or antibody) -related AEs. With the development of AEs research, more and more anti-neuron antibodies have been found, which provides an important reference for the diagnosis and treatment of AEs. Understanding the knowledge about AEs is important to discover new diseases and deepen the understanding of the immunopathological mechanisms of existing central nervous system diseases. Anti-γ-aminobutyric acid B (GABA-B) receptor encephalitis is a type of AE, but this disease is rare in AE, often develop to the clinical manifestations of marginal encephalitis, accompanied by obvious seizures or status epilepticus, Some patients had tumors, mainly small-cell carcinoma, prompt diagnosis, early immunotherapy and, if necessary, tumor treatment resulted in complete or partial neurological improvement in most patients.

4.
Med Sci Monit ; 27: e930421, 2021 Aug 20.
Article in English | MEDLINE | ID: mdl-34415897

ABSTRACT

BACKGROUND In a previous study, we reported that pro-brain-derived neurotrophic factor (proBDNF) was involved in the pathology of alcohol dependence, and the single-nucleotide polymorphism (SNP) Val66Met was located at the prodomain of the brain-derived neurotrophic factor gene (BDNF). This polymorphism has been reported to affect intracellular trafficking and activity-dependent secretion of BDNF. Our present research investigated the relationships between the BDNF Val66Met polymorphism and the plasma levels of proBDNF and mature brain-derived neurotrophic factor (mBDNF) in patients with alcohol dependence. MATERIAL AND METHODS The BDNF gene Val66Met polymorphism was genotyped in 59 alcohol-dependent patients and 37 age- and sex-matched controls, and the plasma levels of proBDNF and mBDNF were assessed by enzyme-linked immunosorbent assay in all participants. RESULTS No association was found between the BDNF gene Val66Met polymorphism and alcohol dependence (P>0.05). In comparison with the control group, the level of plasma proBDNF in the alcohol-dependence group was notably increased (Z=-2.228, P=0.026), while the level of mBDNF was remarkedly decreased (Z=-2.014, P=0.044). In the alcohol-dependence group, significant associations were not found between the Val66Met polymorphisms and proBDNF and mBDNF plasma levels (P>0.05). The plasma level of proBDNF was positively correlated with the average daily alcohol consumption in the last month (r=0.344, P=0.008) and drinking history (r=0.317, P=0.014), while the plasma level of mBDNF had negative effects (r=-0.361, P=0.005, with the average daily alcohol consumption; r=-0.427, P=0.001, with drinking history). CONCLUSIONS The BDNF gene Val66Met polymorphism does not appear to affect the secretion of proBDNF and mBDNF in Chinese patients with alcohol dependence. Furthermore, this study reconfirmed that the plasma levels of proBDNF and mBDNF were correlated with the average daily alcohol consumption in the last month and with drinking history.


Subject(s)
Alcoholism/blood , Alcoholism/genetics , Amino Acid Substitution , Brain-Derived Neurotrophic Factor/blood , Brain-Derived Neurotrophic Factor/genetics , Polymorphism, Single Nucleotide , Protein Precursors/blood , Adult , Alcoholism/diagnosis , Alleles , Biomarkers , Case-Control Studies , Disease Susceptibility , Enzyme-Linked Immunosorbent Assay , Genotype , Humans , Linkage Disequilibrium , Male , Middle Aged , Protein Precursors/genetics , Young Adult
5.
Ibrain ; 7(3): 200-210, 2021 Sep.
Article in English | MEDLINE | ID: mdl-37786793

ABSTRACT

Epilepsy is a common neurological disease with various seizure types, complicated etiologies, and unclear mechanisms. Its diagnosis mainly relies on clinical history, but an electroencephalogram is also a crucial auxiliary examination. Recently, brain imaging technology has gained increasing attention in the diagnosis of epilepsy, and conventional magnetic resonance imaging can detect epileptic foci in some patients with epilepsy. However, the results of brain magnetic resonance imaging are normal in some patients. New molecular imaging has gradually developed in recent years and has been applied in the diagnosis of epilepsy, leading to enhanced lesion detection rates. However, the application of these technologies in epilepsy patients with negative brain magnetic resonance must be clarified. Thus, we reviewed the relevant literature and summarized the information to improve the understanding of the molecular imaging application value of epilepsy.

6.
Metab Syndr Relat Disord ; 17(4): 217-222, 2019 05.
Article in English | MEDLINE | ID: mdl-30741593

ABSTRACT

Background: Given its high incidence, thyroid nodule (TN) warrants public attention. Thyroid volume (TV) has also been associated with multiple factors, such as iodine deficiency and supply and body mass index. It is well known that metabolic syndrome (MetS) comprises many metabolic disturbances, with insulin resistance being its major component. Materials and Methods: The aim of this study was to investigate the relationship between TN and TV and MetS and its components in an iodine-adequate area in Asia. All participants were asked to complete a questionnaire. After excluding 938 individuals based on the exclusion criteria, we reviewed data from 927 of 1865 participants. Adopting MetS diagnostic criteria, we found 437 subjects to be MetS positive [MetS(+)] and 490 subjects to be MetS negative [MetS(-)], respectively. Multivariate linear regression was used to assess the relationship between TNs and MetS. Moreover, univariate binary logistic regression analyses were used to calculate odds ratios (ORs), and 95% confidence intervals (CIs) were used to estimate the associations between different variables and TNs. Results: A total of 232 females and 205 males were MetS(+), as diagnosed using the International Diabetes Federation criteria. However, there were 330 females and 160 males in the group of MetS(-) individuals. The prevalence of TNs was 38.29% in the MetS(+) group and 17.79% in the MetS(-) group. After adjusting for systolic blood pressure, diastolic blood pressure, and gender, only high-density lipoprotein, waist circumference (WC), and age were related to TNs (OR = 0.45, 95% CI 0.27-0.75, P = 0.0023; OR = 1.04, 95% CI 1.02-1.06, P = 0.0036). The TV of all participants was 13.98 (11.24, 17.01) mL; 13.26 (10.62, 16.17) mL for females and 14.96 (11.83, 18.01) mL for males. It was found that only WC was related to TV, after controlling for sex and age (P = 0.02). Conclusions: The morbidity among TN patients in the MetS(+) group was higher than that among the MetS(-) group. High-density lipoprotein cholesterol emerged as a protective factor, and WC was a risk factor for TN. Moreover, TV was related to MetS, and WC was an independent risk factor for TV.


Subject(s)
Iodine/pharmacology , Metabolic Syndrome/pathology , Thyroid Gland/pathology , Thyroid Nodule/pathology , Adult , Anthropometry , Blood Glucose/metabolism , Blood Pressure , Body Mass Index , Female , Humans , Insulin Resistance , Logistic Models , Male , Metabolic Syndrome/complications , Metabolic Syndrome/diagnostic imaging , Middle Aged , Multivariate Analysis , Obesity/complications , Organ Size , Prevalence , Risk Factors , Sex Factors , Thyroid Gland/diagnostic imaging , Thyroid Nodule/complications , Thyroid Nodule/diagnostic imaging , Time Factors , Waist Circumference
7.
Molecules ; 23(12)2018 Dec 01.
Article in English | MEDLINE | ID: mdl-30513790

ABSTRACT

: The judicious application of ligand or binding efficiency (LE) metrics, which quantify the molecular properties required to obtain binding affinity for a drug target, is gaining traction in the selection and optimization of fragments, hits and leads. Here we report for the first time the use of LE based metric, fit quality (FQ), in virtual screening (VS) of MDM2/p53 protein-protein interaction inhibitors (PPIIs). Firstly, a Receptor-Ligand pharmacophore model was constructed on multiple MDM2/ligand complex structures to screen the library. The enrichment factor (EF) for screening was calculated based on a decoy set to define the screening threshold. Finally, 1% of the library, 335 compounds, were screened and re-filtered with the FQ metric. According to the statistical results of FQ vs activity of 156 MDM2/p53 PPIIs extracted from literatures, the cut-off was defined as FQ = 0.8. After the second round of VS, six compounds with the FQ > 0.8 were picked out for assessing their antitumor activity. At the cellular level, the six hits exhibited a good selectivity (larger than 3) against HepG2 (wt-p53) vs Hep3B (p53 null) cell lines. On the further study, the six hits exhibited an acceptable affinity (range of Ki from 10² to 10³ nM) to MDM2 when comparing to Nutlin-3a. Based on our work, FQ based VS strategy could be applied to discover other PPIIs.


Subject(s)
Drug Discovery , Protein Binding/drug effects , Proto-Oncogene Proteins c-mdm2/chemistry , Quantitative Structure-Activity Relationship , Tumor Suppressor Protein p53/chemistry , Cell Line, Tumor , Drug Discovery/methods , Drug Screening Assays, Antitumor , Humans , Ligands , Molecular Docking Simulation , Molecular Dynamics Simulation , Molecular Structure , Proto-Oncogene Proteins c-mdm2/metabolism , Reproducibility of Results , Small Molecule Libraries , Structure-Activity Relationship , Tumor Suppressor Protein p53/metabolism
8.
Curr Vasc Pharmacol ; 16(6): 589-595, 2018.
Article in English | MEDLINE | ID: mdl-29299987

ABSTRACT

OBJECTIVE: To investigate the characteristics of body fat distribution and the relationship between body fat index and Atherogenic Index of Plasma (AIP) in Type 2 Diabetes Mellitus (T2DM) patients. METHODS: A total of 316 participants were divided into a T2DM group and a non-diabetes group (controls). According to the Visceral Fat Area (VFA), all participants were further divided into VFA ≥100 cm2 and VFA <100 cm2 groups. To compare the differences of blood lipid, blood glucose, body fat index and AIP between the 2 groups, single factor correlation analysis was used to determine the correlation between the indexes and AIP, and multiple linear regression was used to analyse the correlation between the related factors and AIP. RESULTS: The body fat index (including body fat content, Percentage of Body Fat (PBF), Waist to Hip Fat Ratio (WHR) and VFA), Triglyceride (TG), Fasting Insulin (FINS), Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) and AIP in T2DM group were significantly higher than in the control group, while High Density Lipoprotein Cholesterol (HDL-C) level was significantly higher in the control group. In the VFA≥100 cm2 group, TG, Low Density Lipoprotein Cholesterol (LDL-C), FINS, HOMAIR and AIP were all higher than that in the VFA <100 cm2 group. There was a positive correlation between AIP and VFA, body fat content, percentage of body fat, and WHR, respectively. There was also a negative correlation between AIP and HDL-C, which was not related to age, sex, Fasting Glucose (FPG), glycosylated haemoglobin (HbA1c), Total Cholesterol (TC), LDL-C and course of disease. Compared with the VFA <100 cm2 group, the VFA ≥100 cm2 group had higher blood Uric Acid (UA) levels and UA was positively correlated with VFA. After correcting the effect of UA on AIP, VFA was still an independent related factor of AIP, and VFA increased the risk of atherosclerosis by increased UA. CONCLUSION: T2DM patients have the abnormal distribution of body fat and a high VFA, which was associated with AIP.


Subject(s)
Adiposity , Atherosclerosis/etiology , Diabetes Mellitus, Type 2/blood , Diabetes Mellitus, Type 2/physiopathology , Intra-Abdominal Fat/physiopathology , Lipids/blood , Aged , Atherosclerosis/blood , Atherosclerosis/diagnosis , Atherosclerosis/physiopathology , Biomarkers/blood , Blood Glucose/metabolism , Case-Control Studies , Cross-Sectional Studies , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/diagnosis , Female , Humans , Insulin/blood , Insulin Resistance , Male , Middle Aged , Prognosis , Risk Assessment , Risk Factors , Waist-Hip Ratio
9.
Biomed Environ Sci ; 30(6): 418-425, 2017 Jun.
Article in English | MEDLINE | ID: mdl-28705265

ABSTRACT

OBJECTIVE: The influence of anti-tuberculosis (TB) treatment history on tuberculous lymphadenitis (TBLN) diagnosis is unclear. Therefore, this study aims to evaluate the diagnostic methods, including histology, microbiology, and molecular tests, used for TBLN. METHODS: In this study, suspected patients with TBLN and having different anti-TB treatment background were enrolled. All the samples were tested simultaneously by histology, Ziehl-Neelsen (ZN) staining, mycobacterial culture (culture), Xpert MTB/RIF (xpert), real-time PCR, and high-resolution melting curve PCR (HRM). Thereafter, the performance of these methods on samples with different anti-TB treatment background was assessed. RESULTS: In our study, 89 patients were prospectively included 82 patients with TBLN and 7 with other diseases. The overall sensitivities of Xpert, real-time PCR, histology, ZN staining, and culture were 86.6%, 69.5%, 58.5%, 43.9%, and 22.0%, respectively. The anti-TB treatment history revealed dramatic influences on the sensitivity of culture (P < 0.0001). In fact, the treatment that lasted over 3 months also influenced the sensitivity of Xpert (P < 0.05). However, the treatment history did not affect the performance of remaining tests (P > 0.05). For rifampicin drug susceptibility test (DST), the anti-TB treatment showed only significant influence on the success rate of culture DST (P = 0.001), but not on those of Xpert and HRM tests (P > 0.05). CONCLUSION: Other tests as well as culture should be considered for patients with TBLN having retreatment history or over 1-month treatment to avoid false negative results.


Subject(s)
Antitubercular Agents/therapeutic use , Tuberculosis, Lymph Node/diagnosis , Tuberculosis, Lymph Node/drug therapy , Adolescent , Adult , Aged , Bacteriological Techniques , Drug Resistance, Bacterial , Female , Humans , Male , Middle Aged , Tuberculosis, Lymph Node/microbiology , Young Adult
10.
Endocr Pract ; 22(8): 935-40, 2016 Aug.
Article in English | MEDLINE | ID: mdl-27042744

ABSTRACT

OBJECTIVE: Natural killer (NK) cells serve as primary immune surveillance and are partially regulated by combinations of killer immunoglobulin-like receptors (KIR) and their human leukocyte antigen-C (HLA-C) ligands. Alterations in NK cell activity have been associated with Hashimoto thyroiditis (HT). The aim of this study was to determine whether certain KIR/HLA-C genotype combinations play a role in HT pathogenesis. METHODS: The present study enrolled 107 unrelated HT patients and 108 random healthy individuals in a case-control study. Blood was collected for DNA extraction; typing of KIR genes and HLA-C alleles was performed by polymerase chain reaction with sequence specific primers (PCR-SSP), followed by electrophoresis on agarose gels. RESULTS: Among a panel of KIR2D/HLA-C genotype combinations, the frequency of KIR2DS2/HLA-C1 was significantly increased in HT patients compared to controls (33.64% vs. 12.96%, P<.001). To further analyze the precise genotype, we investigated inhibitory or activating KIR/HLA-C gene pairs when their corresponding activating or inhibitory KIR genes were absent in the 2 groups. Only the frequency of KIR2DS2(-)2DL2/3(+)HLA-C1(+) was significantly decreased in HT patients compared to controls (48.60% vs. 70.37%, P = .001). CONCLUSION: Our data suggest that KIR2DS2/HLA-C1 may correlate with HT pathogenesis. On the contrary, the predominance of KIR2DL2/3/HLA-C1 in the absence of KIR2DS2 suggests a potential inhibitory role in HT pathogenesis. In conclusion, our findings may further elucidate the mechanisms underlying the pathogenesis of HT and other autoimmune diseases. ABBREVIATIONS: HLA-C = human leukocyte antigen-C HT = Hashimoto thyroiditis KIR = killer immunoglobulin-like receptor NK = natural killer PCR = polymerase chain reaction.


Subject(s)
HLA-C Antigens/genetics , Hashimoto Disease/genetics , Receptors, KIR/genetics , Adult , Asian People/genetics , Case-Control Studies , China , Female , Gene Frequency , Genetic Predisposition to Disease , Hashimoto Disease/immunology , Humans , Ligands , Male , Middle Aged
11.
Acta Pharmacol Sin ; 37(5): 656-63, 2016 May.
Article in English | MEDLINE | ID: mdl-26997566

ABSTRACT

AIM: The eicosanoids derived from phospholipids play key roles in inflammation. However, the profiles of serum eicosanoids in subclinical hypothyroidism (SH) patients and the effects of thyroxine replacement therapy (TRT) on these eicosanoids remain unclear. Many studies show that TSH regulates lipid metabolism. As eicosanoids derived from phospholipids play key roles in oxidative stress and immune function and inflammatory process, it was necessary to explore the profiles of serum eicosanoids in SH patients and the effects of thyroxine replacement therapy (TRT) on the eicosanoids. METHODS: A total of 50 Chinese SH patients and 22 healthy volunteers were recruited. SH patients received TRT (L-T4, 25 and 50 mcg/d for patients with TSH≤10.0 mIU/L and TSH>10.0 mIU/L, respectively) for 3 months. Serum levels of major eicosanoids and cPLA2 were analyzed using LC-MS and clinical biochemical assays. RESULTS: The serum levels of cPLA2, eicosanoids (8-isoPGF2a, 11-dehydroTXB2 and 12-HETE) and 11-dehydroTXB2/6-Keto-PGF1a were significantly elevated in SH patients. The serum TSH levels were significantly correlated with the levels of cPLA2 (r=+0.65), 11-dehydroTXB2 (r=+0.32) and 11-dehydroTXB2/6-Keto-PGF1a (r=+0.37). After 3-month TRT, the serum levels of TSH, cPLA2 and the above-mentioned eicosanoids in SH patients were significantly decreased. CONCLUSION: The metabolism of eicosanoids is significantly altered in Chinese SH patients, and TRT can ameliorate the abnormalities of serum eicosanoid levels.


Subject(s)
Eicosanoids/blood , Hormone Replacement Therapy , Hypothyroidism/drug therapy , Thyroxine/therapeutic use , Asian People , Female , Humans , Hypothyroidism/blood , Hypothyroidism/ethnology , Male , Phospholipases A2/blood
12.
Immunol Lett ; 166(1): 13-8, 2015 Jul.
Article in English | MEDLINE | ID: mdl-25952624

ABSTRACT

Toll-like receptor (TLR) 9, recognizing different ligands, confers distinct features of plasmacytoid dendritic cells (pDCs). Our previous study demonstrated a role for TLR9 in the mechanism of experimental autoimmune neuritis (EAN). In this study, we explored whether suppressive oligodeoxynucleotides (sODN) could induce tolerogenic pDCs via TLR9 and thus promote the recovery of EAN. Effects of different TLR9 ligands, CpG ODN and sODN on P0 180-199 peptide-stimulated pDCs were measured by detecting the expression of co-stimulatory molecules, indoleamine 2,3-dioxygenase (IDO), secretion of Th1- and Th2-type cytokines and the TLR9 signaling pathway. CpG ODN- or sODN-treated pDCs were intravenously injected into the EAN mice and their effects were compared. Our data showed that P0180-199 peptides significantly promoted mRNA expression of co-stimulatory molecules (CD40, CD80 and CD86) in pDCs and induced secretion of Th1-type cytokines. Treatment of CpG ODN aggravated the effects of P0 180-199 peptides on pDCs; however, sODN had the opposite effects and significantly upregulated the IDO expression in pDCs. Further analysis showed that MYD88 is necessary for sODN to modulate the TLR9/NF-κB signaling in pDCs. Finally, the sODN-treated pDCs significantly promoted recovery of the EAN mice. Taken together, sODN could induce tolerogenic pDCs and thus ameliorate the EAN.


Subject(s)
Dendritic Cells/immunology , Immune Tolerance/immunology , Neuritis, Autoimmune, Experimental/immunology , Oligodeoxyribonucleotides/pharmacology , Peptides/pharmacology , Animals , B7-1 Antigen/genetics , B7-2 Antigen/genetics , CD40 Antigens/genetics , Cells, Cultured , CpG Islands/genetics , Cytokines/biosynthesis , Cytokines/metabolism , Indoleamine-Pyrrole 2,3,-Dioxygenase/biosynthesis , Indoleamine-Pyrrole 2,3,-Dioxygenase/genetics , Male , Mice , Mice, Inbred C57BL , Myeloid Differentiation Factor 88/metabolism , Neuritis, Autoimmune, Experimental/therapy , RNA, Messenger/genetics , Th1 Cells/immunology , Th2 Cells/immunology , Toll-Like Receptor 9/immunology , Transcription Factor RelA/metabolism
13.
Biomed Rep ; 2(6): 898-904, 2014 Nov.
Article in English | MEDLINE | ID: mdl-25279166

ABSTRACT

Endostatin, as the most potential antiangiogenic factor, is a naturally occurring fragment of collagen XVIII in bloodstream capable of inhibiting tumor growth and metastasis. This study was conducted to explore the clinical value of endostatin in serum and tumor tissue in patients with operable non-small cell lung cancer (NSCLC). ELISA and immunohistochemistry were applied to detect the expression of endostatin in serum and tumor tissue in 105 patient-matched operable NSCLC patients. The serum level of endostatin was significantly higher in NSCLC patients than healthy individuals (P=0.0018). Cases with poorer differentiation showed a higher endostatin serum level (P=0.008). There was no significant correlation between tumor tissue expression and clinical parameters, such as TNM stage, differentiation degree, histological type and lymph node invasion status. A stronger expression of endostain in tumor tissue was associated with a higher serum level (r=0.223). The univariate and multivariate analyses with Cox proportional hazards model for overall survival showed that tumor stage and node status were independent prognostic factors, whereas neither endostatin levels in serum nor in tumor tissue showed potential in predicting the long-term survival of operable NSCLC patients. In conclusion, the results observed in the present study did not support the prediction of overall survival in operable NSCLC based on the expression levels of endostatin in serum and tumor tissue.

14.
Biomed Rep ; 2(4): 481-489, 2014 Jul.
Article in English | MEDLINE | ID: mdl-24944792

ABSTRACT

Non-small-cell lung cancer (NSCLC) is the most common cause of cancer-related mortality. Adenocarcinoma (AC) is the predominant histological type of NSCLC; however, AC consists of several subtypes. It has not yet been determined whether there is a correlation of CRKL and AXL expression with epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) gene status in lung AC. We assayed exons 18 through 21 of the EGFR gene by direct sequencing; ALK rearrangement and the expression of CRKL and AXL were detected by immunostaining. A total of 212 cases of AC were included in this study, diagnosed using the novel classification system established by the International Association for the Study of Lung Cancer, the American Thoracic Society and the European Respiratory Society in 2011, including 69 acinar ACs, 17 lepidic predominant ACs (LPAs), 63 papillary, 14 mucinous, 17 micropapillary and 32 solid ACs. Of the 212 cases, 101 harbored EGFR mutations. The most common subtypes carrying delK745-S753 were papillary and acinar ACs. ALK rearrangement was found in 23 cases (11%) of lung ACs. Acinar and solid ACs were the most frequent subtypes with ALK aberrance, particularly in acinar ACs with cribriform structure (4/5 cases, 80%). The expression of CRKL was significantly different among the AC subtypes (P=0.01), with the highest and lowest expression levels of CRKL protein in papillary ACs and LPAs, respectively (P<0.05). AXL expression was also significantly different among the AC subtypes (P=0.002) and was correlated with lymph node infiltration in acinar ACs. ACs with EGFR mutations exhibited high levels of AXL protein expression compared to those without mutations (P<0.001). Acinar AC with cribriform structure is a distinct subtype that frequently harbors ALK rearrangement. The activation of AXL may be one of the factors contributing to the invasion of acinar and micropapillary ACs.

15.
Int J Clin Exp Med ; 7(4): 1014-21, 2014.
Article in English | MEDLINE | ID: mdl-24955175

ABSTRACT

UNLABELLED: The present study aimed to investigate the feasibility of quantitative analysis of liver fibrosis using real-time tissue elastography (RTE) and its pathological and molecule biological basis. METHODS: Fifty-four New Zealand rabbits were subcutaneously injected with thioacetamide (TAA) to induce liver fibrosis as the model group, and another eight New Zealand rabbits served as the normal control group. Four rabbits were randomly taken every two weeks for real-time tissue elastography (RTE) and quantitative analysis of tissue diffusion. The obtained twelve characteristic quantities included relative mean value (MEAN), standard deviation (SD), blue area % (% AREA), complexity (COMP), kurtosis (KURT), skewness (SKEW), contrast (CONT), entropy (ENT), inverse different moment (IDM), angular secon moment (ASM), correlation (CORR) and liver fibrosis index (LF Index). Rabbits were executed and liver tissues were taken for pathological staging of liver fibrosis (grouped by pathological stage into S0 group, S1 group, S2 group, S3 group and S4 group). In addition, the collagen I (Col I) and collagen III (Col III) expression levels in liver tissue were detected by Western blot. RESULTS: Except for KURT, there were significant differences among the other eleven characteristic quantities (P < 0.05). LF Index, Col I and Col III expression levels showed a rising trend with increased pathological staging of liver fibrosis, presenting a positive correlation with the pathological staging of liver fibrosis (r = 0.718, r = 0.693, r = 0.611, P < 0.05). CONCLUSION: RTE quantitative analysis is expected for noninvasive evaluation of the pathological staging of liver fibrosis.

16.
PLoS One ; 9(6): e99564, 2014.
Article in English | MEDLINE | ID: mdl-24932524

ABSTRACT

Leaf-color is an effective marker to identify the hybridization of rice. Leaf-color related genes function in chloroplast development and the photosynthetic pigment biosynthesis of higher plants. The ygl7 (yellow-green leaf 7) is a mutant with spontaneous yellow-green leaf phenotype across the whole lifespan but with no change to its yield traits. We cloned gene Ygl7 (Os03g59640) which encodes a magnesium-chelatase ChlD protein. Expression of ygl7 turns green-leaves to yellow, whereas RNAi-mediated silence of Ygl7 causes a lethal phenotype of the transgenic plants. This indicates the importance of the gene for rice plant. On the other hand, it corroborates that ygl7 is a non-null mutants. The content of photosynthetic pigment is lower in Ygl7 than the wild type, but its light efficiency was comparatively high. All these results indicated that the mutational YGL7 protein does not cause a complete loss of original function but instead acts as a new protein performing a new function. This new function partially includes its preceding function and possesses an additional feature to promote photosynthesis. Chl1, Ygl98, and Ygl3 are three alleles of the OsChlD gene that have been documented previously. However, mutational sites of OsChlD mutant gene and their encoded protein products were different in the three mutants. The three mutants have suppressed grain output. In our experiment, plant materials of three mutants (ygl7, chl1, and ygl98) all exhibited mutational leaf-color during the whole growth period. This result was somewhat different from previous studies. We used ygl7 as female crossed with chl1 and ygl98, respectively. Both the F1 and F2 generation display yellow-green leaf phenotype with their chlorophyll and carotenoid content falling between the values of their parents. Moreover, we noted an important phenomenon: ygl7-NIL's leaf-color is yellow, not yellowy-green, and this is also true of all back-crossed offspring with ygl7.


Subject(s)
Genes, Plant , Lyases/genetics , Mutation, Missense , Oryza/genetics , Photosynthesis/genetics , Plant Leaves/metabolism , Plant Proteins/genetics , Point Mutation , Amino Acid Substitution , Carotenoids/analysis , Chlorophyll/analysis , Chlorophyll/biosynthesis , Chromosome Mapping , Chromosomes, Plant/genetics , Color , Crosses, Genetic , Exons/genetics , Gene Knockdown Techniques , Genes, Lethal , Genes, Recessive , Genetic Complementation Test , Inbreeding , Lyases/chemistry , Lyases/deficiency , Lyases/physiology , Oryza/metabolism , Plant Proteins/physiology , Plants, Genetically Modified , Protein Structure, Tertiary , Protein Subunits , RNA, Small Interfering/pharmacology , Sequence Alignment
17.
Int J Infect Dis ; 25: 82-7, 2014 Aug.
Article in English | MEDLINE | ID: mdl-24858903

ABSTRACT

BACKGROUND: A Mycobacterium parascrofulaceum strain was isolated from a pneumonia patient-the first such reported case from China. The bacteriological characteristics of the strain were determined. METHODS: Species identification was performed by homologue gene sequence comparison, then a series of biochemical tests was conducted to elucidate the bacteriological characteristics. Drug susceptibility and pathogenicity to mice of the strain were tested. RESULTS: The clinical M. parascrofulaceum strain presented a very similar phenotypic profile to that of Mycobacterium scrofulaceum. The M. parascrofulaceum strain was sensitive to rifabutin, rifapentine, clarithromycin, azithromycin, cefoxitin, and moxifloxacin in vitro. At week 2 post-infection, the lung tissues of mice demonstrated a local inflammatory response denoted by peri-bronchiolar inflammatory infiltrates. At weeks 4 and 8, the lung tissues showed peri-bronchiolar inflammatory infiltrates with large aggregates of lymphocytes and part of the tissue showed granulomatous lesions; there was no appreciable necrosis. The colony-forming units (CFU) count of infected lung and spleen increased gradually during the 8 weeks of the experiment. CONCLUSIONS: The M. parascrofulaceum strain isolated in China was sensitive to rifabutin, rifapentine, clarithromycin, azithromycin, cefoxitin, and moxifloxacin. The mycobacteria were capable of proliferating in mice and could lead to pathological changes in the lungs of the mice.


Subject(s)
Mycobacterium Infections, Nontuberculous/microbiology , Nontuberculous Mycobacteria/classification , Pneumonia, Bacterial/microbiology , Animals , Anti-Bacterial Agents/pharmacology , Bacterial Load , Bacterial Typing Techniques , China/epidemiology , DNA, Ribosomal Spacer/genetics , Disease Models, Animal , Humans , Male , Mice , Microbial Sensitivity Tests , Middle Aged , Molecular Sequence Data , Mycobacterium Infections, Nontuberculous/epidemiology , Mycobacterium Infections, Nontuberculous/pathology , Nontuberculous Mycobacteria/drug effects , Nontuberculous Mycobacteria/genetics , Nontuberculous Mycobacteria/isolation & purification , Phenotype , Pneumonia, Bacterial/epidemiology , Pneumonia, Bacterial/pathology
18.
Acta Pharmacol Sin ; 35(1): 65-73, 2014 Jan.
Article in English | MEDLINE | ID: mdl-24241350

ABSTRACT

AIM: To investigate the effects of diosgenin (Dio), a naturally occurring steroid saponin, on goiter formation in a mouse model of Graves' disease (GD) and the underlying mechanisms. METHODS: Female BALB/c mice were injected with adenovirus expressing the A subunit of thyrotropin receptor to induce GD. The mice were treated with Dio (20, 100 mg·kg(-1)·d(-1), ip) for 12 or 24 d. The serum levels of TT4 and TRAb were examined using radioimmunoassay and electrochemiluminescence. The size and morphology of thyroid glands were examined. Thyrocyte proliferation was determined using BrdU incorporation assay. The expression of proliferation-associated proteins IGF-1, NF-κB, cyclin D1, and PCNA in thyroids was analyzed using immunohistochemistry and real-time PCR. RESULTS: The GD mice showed significantly high serum levels of TRAb and TT4 compared to the normal mice. Treatment of the GD mice with Dio for 24 d dose-dependently reduced the TT4 level and thyroid size, but did not affect the abnormal level of TRAb. Furthermore, Dio treatment dose-dependently reversed the morphological changes and reduced excessive thyrocyte proliferation in thyroids of the GD mice. Dio treatment also dose-dependently reduced the mRNA and protein levels of IGF-1, NF-κB, cyclin D1, and PCNA in thyroids of the GD mice. CONCLUSION: Dio relieves goiter in a mouse model of GD through the inhibition of thyrocyte proliferation. The mechanisms involve the suppression of IGF-1, NF-κB, cyclin D1, and PCNA expression.


Subject(s)
Cell Proliferation/drug effects , Diosgenin/therapeutic use , Disease Models, Animal , Graves Disease/drug therapy , Thyroid Gland/cytology , Thyroid Gland/drug effects , Animals , Diosgenin/pharmacology , Female , Goiter/drug therapy , Goiter/pathology , Graves Disease/pathology , HEK293 Cells , Humans , Mice , Mice, Inbred BALB C , Random Allocation
19.
Zhonghua Jie He He Hu Xi Za Zhi ; 36(7): 501-5, 2013 Jul.
Article in Chinese | MEDLINE | ID: mdl-24262085

ABSTRACT

OBJECTIVE: To study the clinicopathological features, diagnosis and prognosis of primary sinus histiocytosis (Rosai-Dorfman disease, RDD) of the trachea by case report and review of the literature. METHODS: A 63 year old man with a space-occupying lesion of the trachea firstly diagnosed as a malignant tumor was admitted to this hospital for further evaluation and treatment. The lesion was removed by surgery and the final diagnosis was primary RDD. The clinical data of the case was analyzed and the related literatures were reviewed. The literature review was carried out respectively with"Rosai-Dorfman disease" and "sinus histiocytosis"as the key words in Wanfang Med Online and with"Rosai-Dorfman disease","sinus histiocytosis","trachea or lung"as the key words in PubMed database by July 2012. RESULTS: The chest computerized tomography of the case showed that the mass was located at the right side of the trachea with heterogeneous density and contrast enhancement. Bronchoscopy revealed a neoplasma occluding the distal trachea. The lesion was excised by surgery. Microscopic histology showed that in the dark-staining area a large number of lymphocytes and plasma cells were noted while the light-staining area was formed by giant histiocytes. The pathological changes invaded the tracheal wall and eroded the cartilages. Intact lymphocytes and plasma cells were observed within the eosinophilic cytoplasm of the histiocytes. Immunohistochemistry showed that the giant histiocytes were strongly positive for S-100 protein and CD68 protein. Primary RDD of trachea was confirmed. The patient remained well without any other treatment or evidence of progression for 11 months. A total of 13 literatures and 26 cases were retrieved from Wanfang Med Online and Pubmed, including 21 cases of primary RDD of the upper respiratory tract and 4 cases of primary RDD of the lung. A total of 5 literatures and 5 cases of RDD affecting the trachea were retrieved from Wanfang Med Online and Pubmed. There was only one case of primary RDD of the trachea in Pubmed. A 39-year-old female patient with 1 month of dyspnea was misdiagnosed as having bronchial asthma and was unresponsive to empirical corticosteroid and bronchodilator therapy. The chest computerized tomography revealed an ill-defined irregular soft tissue in the trachea. A tracheal ring sleeve resection and reanastomosis was performed to prevent asphyxia. The mass was confirmed to be primary RDD of the trachea according to histopathology and immunohistochemistry. The patient was well without any treatment for 12 months. CONCLUSIONS: Primary RDD of the trachea is an extremely rare disease, with dyspnoea as a feature of the disease. When it is completely removed, the prognosis is good. Typical histopathology and immunohistochemistry are needed to make a definite diagnosis. The positive immunohistochemistry staining for S-100 and CD68 protein in giant histiocytes and lymphocyteemperipolesis are essential for the diagnosis. The differential diagnosis includes other benign or malignant space-occupying lesions of the trachea.


Subject(s)
Histiocytosis, Sinus/diagnosis , Trachea/pathology , Tracheal Diseases/diagnosis , Antigens, CD/metabolism , Antigens, Differentiation, Myelomonocytic/metabolism , Diagnosis, Differential , Dyspnea/etiology , Dyspnea/pathology , Histiocytosis, Sinus/complications , Histiocytosis, Sinus/metabolism , Histiocytosis, Sinus/surgery , Humans , Immunohistochemistry , Male , Middle Aged , Radiography, Thoracic , S100 Proteins/metabolism , Thorax/pathology , Tomography, X-Ray Computed , Trachea/diagnostic imaging , Trachea/surgery , Tracheal Diseases/complications , Tracheal Diseases/metabolism , Tracheal Diseases/surgery
20.
Biotechnol Lett ; 35(11): 1953-9, 2013 Nov.
Article in English | MEDLINE | ID: mdl-23881327

ABSTRACT

A drought stress-responsive Cys2/His2-type zinc finger protein gene DgZFP3 was previously isolated (Liu et al., Afr J Biotechnol 11:7781-7788, 2012b) from chrysanthemum. To assess roles of DgZFP3 in plant drought stress responses, we performed gain-of-function experiment. The DgZFP3-overexpression tobacco plants showed significant drought tolerance over the wild type (WT). The transgenic lines exhibited less accumulation of H2O2 under drought stress, more accumulation of proline and greater activities of peroxidase (POD) and superoxide dismutase than the WT under both control conditions and drought stress. In addition, there was greater up-regulation of the ROS-related enzyme genes (NtSOD and NtPOD) and stress-related genes (NtLEA5 and NtDREB) in transgenic lines under normal or drought conditons. Thus DgZFP3 probably plays a positive regulatory role in drought stress response and has the potential to be utilized in transgenic breeding to improve drought stress tolerance in plants.


Subject(s)
Chrysanthemum/physiology , DNA-Binding Proteins/metabolism , Desiccation , Nicotiana/physiology , Plant Proteins/metabolism , Stress, Physiological , Chrysanthemum/genetics , DNA-Binding Proteins/genetics , Droughts , Gene Expression , Hydrogen Peroxide/metabolism , Peroxidase/metabolism , Plant Proteins/genetics , Recombinant Proteins/genetics , Recombinant Proteins/metabolism , Superoxide Dismutase/metabolism , Nicotiana/genetics , Zinc Fingers
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