Objective To analyze the predictive value of N-terminal B-type natriuretic peptide precursor(NT-proBNP) on auricular thrombosis in patients of coronary heart disease (CHD) combined with atrial fibrillation (AF).Methods The clinical data of 124 patients of CHD combined with AF were analyzed retrospectively.All patients were divided into research group (60 cases,compliance with auricular thrombosis) and control group (64 cases,non-compliance with auricular thrombosis),according to the occurrence of auricular thrombosis.The values of NT-proBNP,fasting plasma glucose (FPG),postprandial plasma glucose(2 h PG),total cholesterol (TC),high density lipoprotein cholesterol (HDL-C),oxidized low density lipoprotein (ox-LDL),high sensitivity C reactive protein (hs-CRP) and left ventricular ejection fraction (LVEF),left ventricular end diastolic diameter (LVEDd) and left atrial diameter (LAD) were detected and compared between two groups.The relative factors to the occurrence of auricular thrombosis were confirmed by multivariate Logistic analysis.The best cutoff point of NT-proBNP was confirmed by the areas under the receiver operating characteristic curve (ROC).Results The values of NT-proBNP,ox-LDL,hs-CRP,LVEDd and LAD in research group were higher than those in control group [(4 312.6 ± 209.1) pmol/L vs.(3 421.6 ± 156.8) pmol/L,(4.0 ± 0.9) mmol/L vs.(3.4 ± 0.8) mmol/L,(7.4 ± 1.3)mg/L vs.(5.8 ± 1.0) mg/L,(74.3 ± 6.8) mm vs.(58.1 ± 5.5) mm,(39.6 ± 4.3) mm vs.(32.5 ± 3.8) mm],LVEF and HDL-C were lower than those in control group [(48.2 ± 3.1)％ vs.(57.3 ± 3.8)％,(0.72 ± 0.16)mmol/L vs.(1.08 ±0.27) mmol/L],and there were significant differences (P ＜0.05).There were no significant differences in the values of FPG,2 h PG and TC between two groups (P ＞ 0.05).Multivariate Logistic analysis showed that NT-proBNP and LAD were independent factors to the occurrence of auricular thrombosis (P =0.009,0.028).There was significant difference in the occurrence of auricular thrombosis between patients with NT-proBNP ＞ 4 250 pmol/L and patients with NT-proBNP≤4 250 pmol/L (P =0.028).Conclusion NT-proBNP is an independent predictor for the occurrence of auricular thrombosis to patients of CHD combined with AF.

Hypoxia occurs in chronic and acute vascular diseases and tumor formation. The ability of tumor cells to maintain a balance between an adaptation to hypoxia and cell death is regulated by a family of transcription factors called hypoxia-inducible factor 1 (HIF-1). Tumor hypoxia mediated by HIF-1 would facilitate the likelihood of resistance to chemotherapy and radiotherapy, proliferation, metastasis and the invasive potential; all of which culminate in a decrease in patient survival. And HIF-1 alpha subunit decides the activity of HIF-1, which is regulated by oxygen. So understanding the role of HIF in signal pathway, drug resistance mechanism and its feature is crucial for developing novel anticancer therapies. In recent years, more attentions have focused on HIF-1 alpha inhibitors. It is expected that development of more potent and selective HIF inhibitors will provide an effective treatment of cancer and other HIF-related diseases. So we will focus on the biological characteristics and mechanism of HIF-1 to review currently studied HIF-1 inhibitors.
Cell Death ; Humans ; Hypoxia-Inducible Factor 1 ; antagonists & inhibitors ; metabolism ; Hypoxia-Inducible Factor 1, alpha Subunit ; antagonists & inhibitors ; metabolism ; Neoplasms ; drug therapy ; Oxygen ; metabolism ; Signal Transduction

Hypoxia-inducible factor-1 (HIF-1) is a key transcription factor on hypoxia responses in mammalian tissues. HIF-1 plays as a positive factor in solid tumor and leads to hypoxia-driven responses that enhance its downstream gene expression for tumor growth and survival. LXY6099 was obtained by the structural modification and optimization of manassantin A (MA) as a high potent HIF-1 inhibitor. Antitumor activity of LXY6099 was observed in this study. LXY6099 with an IC50 value of 2.46 x 10(-10) mol x L(-1) showed more sensitive inhibition activity to HIF-1 than that of MA detected by reporter gene assay (> 100 folds). It showed strong inhibition on the growth of human solid tumor cell lines. Furthermore, LXY6099 exhibited significant antitumor activity against established human tumor xenografts in nu/nu mice with treatment of MX-1 breast cancer. Thus, LXY6099 as a novel HIF-1 inhibitor could be further developed into anti-cancer agents.
Animals ; Antineoplastic Agents ; pharmacology ; Breast Neoplasms ; metabolism ; Cell Line, Tumor ; Gene Expression Regulation, Neoplastic ; Heterografts ; Humans ; Hypoxia-Inducible Factor 1 ; metabolism ; Lignans ; pharmacology ; Mice, Nude

Hypoxia is a general characteristic of most solid malignancies and intimately related to cancer progression. Homeostatic response to hypoxia is primarily mediated by hypoxia inducible factor-1alpha (HIF-1alpha) that elicits transcriptional activity through recruitment P300 coactivator. Targeting the interaction of HIF- alpha and P300 would thus constitute a novel approach for cancer treatment by suppressing tumor angiogenesis and metastasis. Here, a screening assay was developed for inhibitors targeting the interaction between HIF-1alpha and P300. The nucleotide sequence of human HIF-1alpha and P300 were cloned into pBIND and pACT vectors, named pBIND-HIF1alpha and pACT-P300. The interaction of HIF-1alpha and P300 was identified in HEK293 cell using mammalian two-hybrid system. And compound chetomin decreased their interaction in this mammalian two-hybrid system. We further verified HIF-1 inhibition effect of chetomin in U251-HRE cells. Therefore, we established a screening assay combined HIF-1alpha and P300 mammalian two-hybrid system and U251-HRE reporter assay for HIF-1 selective inhibitors.
Cell Hypoxia ; Disulfides ; pharmacology ; Drug Screening Assays, Antitumor ; E1A-Associated p300 Protein ; antagonists & inhibitors ; HEK293 Cells ; Humans ; Hypoxia-Inducible Factor 1, alpha Subunit ; antagonists & inhibitors ; Indole Alkaloids ; pharmacology ; Two-Hybrid System Techniques

The whole developing history of the in-flight bladder relief device for US fighter pilots from the first generation to the third generation was introduced.The optimized design of the third-generation product was described in terms of male use and female use.It's pointed out the US Air Force developed the in-flight bladder relief device with the mode of integration and innovation,the idea closely following the troops'needs and the key technology upgrading thought introducing the newest achievements,and references were provided for the technical improvement of this type of device for the PLA.[Chinese Medical Equipment Journal,2024,45(6):71-76]

AIMTo study the mechanism of evodiamine-induced growth inhibition of HeLa cells.

METHODSHeLa cells viability and the effect of caspase inhibitors on evodiamine-induced apoptosis were measured by crystal violet assay. Changes in cellular morphology were observed by phase-contrast microscopy. Apoptosis-specific nucleosomal DNA fragmentation was assayed by agarose gel electrophoresis.

RESULTSEvodiamine was found to inhibit HeLa cell growth in dose- and time-dependent manners. Caspase-3 inhibitor, z-Asp-Glu-Val-Asp-fmk (z-DEVD-fmk) was shown to partially inhibit evodiamine-induced apoptosis. However, caspase-1 inhibitor, Ac-Tyr-Val-Ala-Asp-chloromethyl-ketone (Ac-YVAD-cmk), did not antagonize evodiamine induced cell death.

CONCLUSIONEvodiamine suppresses the growth of HeLa cells in vitro by apoptosis. Evodiamine-induced apoptosis is partially dependent on caspase-3 pathway in HeLa cells. Other apoptotic pathways might be also related to the induction of apoptosis by evodiamine.

Antineoplastic Agents, Phytogenic ; pharmacology ; Apoptosis ; Caspase 3 ; Caspases ; metabolism ; Evodia ; chemistry ; Fruit ; chemistry ; HeLa Cells ; Humans ; Plant Extracts ; isolation & purification ; pharmacology ; Plants, Medicinal ; chemistry ; Quinazolines ; isolation & purification ; pharmacology ; Signal Transduction ; drug effects

Objective To obtain a novel tool-enzyme for genetic engineering with good solubility,strong specificity of enzyme digestion and maintaining the enzyme activity at low temperature by using E.coli expression system to express self-processed re-combinant MBP-HRV 3C fusion protease.Methods The cDNA encoding HRV 3C protease was cloned into pRSF-Duet vector.The recombinant plasmid was transferred into E.coli BL21 (DE3)for expression.HRV 3C protease was obtained through Nichol col-umn affinity purification.The cleavage activity of HRV 3C protease was determined by in vivo experiment.Results HRV 3C prote-ase was highly expressed in E.coli expression system,and the obtained HRV 3C protease could recognize and digest HRV 3C site. Conclusion A novel tool-enzyme for genetic engineering is obtained.

The 1.23 kb DNA fragment encoding the early protein EP0 of pseudorabies virus (PRV) Ea strain was amplified by PCR technique and cloned into pBluescriptII sk+.Three sequencing plasmids containing the partial fragment of the EP0 gene were constructed and the sequences were obtained by Sanger's sequencing technique. Compared with PRV InFh strain, there were multipile site-mutations and a deleted-mutation in the EP0 gene of PRV strain Ea，and the diversity of amino acid residues also existed.Then, the EP0 gene was inserted into an expression vector, pET-28a, fused into the downstream of the 6ΧHis-Tag in frame, to yield the expression plasmid pETEP0. After induction by IPTG, a high expression of fusion protein was obtained, SDS-PAGE analysis and Western blotting showed that the fusion protein was 62kD and the protein was specific to antisera against PRV Ea strain. This indicated that the EP0 gene be expressed in BL21(DE3) and the expression products have immuno-genicity.

AlM:To explore treatment efficacy of the lower eyelid twitch muscle transposition surgery in senile entropion.METHODS:Fifty cases (86 eyes) of senile lower eyelid entropion patients underwent lower eyelid twitch muscle transposition correction surgery as the experimental group, and the other 42 cases (68 eyes) of senile lower eyelid entropion patients received orbicularis muscle shortening correction as controls group. The correction rate, double eyelid symmetry and overcorrection rate of patients were observed one week after surgery. The patients were followed up for 6~12mo to be observed the long-term recurrence rate, double eyelid symmetry and overcorrection rate.RESULTS: One week after operation, eyelid symmetry, overcorrection rate of experimental group and control group had significant difference (P<0. 05); After followed up for 6 ~12mo, eyelid symmetry, overcorrection rate of experimental group and control group had significant difference (P<0. 05). CONCLUSlON: Folding and orbicularis muscle shortening treatment of senile entropion was compared with the lower eyelid twitch muscle transposition surgery treatment of senile entropion, We can find that clinical results in double eyelid surgery symmetry and overcorrection rate are of obvious advantage.

PURPOSE: Hepatocellular carcinoma (HCC) is a common cancer worldwide. Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), a long noncoding RNA (lncRNA), has been reported to be aberrantly expressed in hypoxic cancer cells. MALAT1 plays a significant role in many malignancies, including HCC. The aim of this study was to explore the role of MALAT1 in hypoxic HCC cells and its underlying regulatory mechanism. MATERIALS AND METHODS: Quantitative reverse transcription PCR (qRT-PCR) assay was performed to detect the mRNA levels of MALAT1 and microRNA-200a (miR-200a) in HCC cells. Cell invasion and migration ability were evaluated by Transwell assay. Starbase v2.0 and luciferase reporter assay were employed to identify the association between MALAT1 and miR-200a. Cell proliferation and apoptosis were measured by MTT assay and flow cytometry, respectively. RESULTS: MALAT1 levels were significantly upregulated in HCC cells under hypoxia. Hypoxia promoted proliferation, migration, and invasion, and blocked apoptosis in Hep3B cells, which were weakened by knockdown of MALAT1. Starbase v2.0 showed that MALAT1 and miR-200a have a complementarity region, and luciferase reporter assay verified that MALAT1 interacted with miR-200a in Hep3B cells. Moreover, MALAT1 negatively regulated the expression of miR-200a. miR-200a levels were dramatically downregulated in HCC cells under hypoxia. Upregulation of miR-200a inhibited proliferation, migration, and invasion, and induced apoptosis in Hep3B cells under hypoxia. Interestingly, downregulation of miR-200a partially reversed the tumor-suppressive effect of knockdown of MALAT1 on Hep3B cells in hypoxic condition. CONCLUSION: LncRNA MALAT1 was involved in proliferation, migration, invasion, and apoptosis by interacting with miR-200a in hypoxic Hep3B cells, revealing a new mechanism of MALAT1 involved in hypoxic HCC progression.
Adenocarcinoma ; Anoxia ; Apoptosis ; Carcinoma, Hepatocellular ; Cell Proliferation ; Down-Regulation ; Flow Cytometry ; Luciferases ; Lung ; Polymerase Chain Reaction ; Reverse Transcription ; RNA, Long Noncoding ; RNA, Messenger ; Up-Regulation