Clinical outcomes of -mutant non-small cell lung cancer under untargeted therapeutic regimes in the real world: a retrospective observational study.

Background: Kirsten rat sarcoma viral oncogene homolog () mutation seemingly suffered less effective therapeutic regimens in the absence of widely-accepted targeted drugs compared with other mutation types in non-small cell lung cancer (NSCLC). However, whether these non-selective therapy schedules for mutation matters is still under debate. Correspondingly, we aimed to compare the long term expectancy of indicated therapeutic regimes and further explore the optimal schemes of mutated NSCLC in the absence of targeted drugs in this retrospective study cohort.

Short and long-term outcomes between laparoscopic and open total gastrectomy for advanced gastric cancer after neoadjuvant chemotherapy.

Background: Neoadjuvant chemotherapy (NACT) combined with surgery is regarded as an effective treatment for advanced gastric cancer (AGC). Laparoscopic surgery represents the mainstream of minimally invasive surgery. Currently, surgeons focus more on surgical safety and oncological outcomes of laparoscopic gastrectomy after NACT.

Serum miR-632 is a potential marker for the diagnosis and prognosis in laryngeal squamous cell carcinoma.

It has been demonstrated that miRNAs play critical roles in the tumorigenesis and progression of various tumors. The purpose of this research was to determine the serum miR-632 levels in patients with laryngeal squamous cell carcinoma (LSCC) and to investigate its diagnostic and prognostic value. We detected serum miR-632 levels in 162 LSCC patients and 42 healthy volunteers.

Notch signaling pathway regulates the growth and the expression of inflammatory cytokines in mouse basophils.

Basophils (BAs) are the least common granulocytes of all leukocytes, but they play an important role in orchestrating of chronic allergic inflammation. The Notch signaling pathway is a highly conserved pathway that influences cell lineage decisions and differentiation during various stages of development. However, the relationship between Notch signaling and BA remains to be elucidate.

Catalysis of Extracellular Deamination by a FAD-Linked Oxidoreductase after Prodrug Maturation in the Biosynthesis of Saframycin A.

The biosynthesis of antibiotics in bacteria is usually believed to be an intracellular process, at the end of which the matured compounds are exported outside the cells. The biosynthesis of saframycin A (SFM-A), an antitumor antibiotic, requires a cryptic fatty acyl chain to guide the construction of a pentacyclic tetrahydroisoquinoline scaffold; however, the follow-up deacylation and deamination steps remain unknown. Herein we demonstrate that SfmE, a membrane-bound peptidase, hydrolyzes the fatty acyl chain to release the amino group; and SfmCy2, a secreted oxidoreductase covalently associated with FAD, subsequently performs an oxidative deamination extracellularly.

Reverse screening approach to identify potential anti-cancer targets of dipyridamole.

Dipyridamole (DIP) inhibits thrombus formation when given chronically, and causes vasodilation over a short time. To date, DIP can increase the anticancer drugs (5-fluorouracil, methotrexate, piperidine, vincristine) concentration in cancer cells and hence enhance the efficacy of treatment cancer. The inhibition of DIP may result in increased 5-fluorouracil efficacy and diminish the drug side effects.

Biosynthesis of Tetrahydroisoquinoline Antibiotics.

The tetrahydroisoquinoline (THIQ) alkaloids are naturally occurring antibiotics isolated from a variety of microorganisms and marine invertebrates. This family of natural products exhibit broad spectrum antimicrobial and strong antitumor activities, and the potency of clinical application has been validated by the marketing of ecteinascidin 743 (ET-743) as anticancer drug. In the past 20 years, the biosynthetic gene cluster of six THIQ antibiotics has been characterized including saframycin Mx1 from Myxococcus xanthus, safracin-B from Pseudomonas fluorescens, saframycin A, naphthyridinomycin, and quinocarcin from Streptomyces, as well as ET-743 from Ecteinascidia turbinata.

The impact of intermittent and repetitive cold stress exposure on endoplasmic reticulum stress and instability of atherosclerotic plaques.

Background: The incidence of acute coronary syndrome caused by the rupture of atherosclerotic plaque and subsequent arterial thrombosis increases as the weather gets colder. However, the association between cold stress and atherosclerotic plaque rupture is currently unknown.

Methods: An atherosclerotic plaque model was established in rabbits by balloon injury and a high-fat diet with or without cold stress (4 °C, 1 hour per day, 20 weeks) at the onset of modeling.

Combined effects of CYP1A1 MspI and GSTM1 genetic polymorphisms on risk of lung cancer: an updated meta-analysis.

Genetic polymorphisms of cytochrome P450 1A1 (CYP1A1) and glutathione S-transferase M1 (GSTM1) genes might contribute to the variability in individual susceptibility to lung cancer, but the reported results from individual studies are not always consistent. We therefore conducted a meta-analysis to systematically estimate the associations between polymorphisms of these two genes and risk of lung cancer. Twenty-one studies with 8,926 subjects were finally enrolled into this study.

CYP2C19 polymorphisms and coronary heart disease risk factors synergistically impact clopidogrel response variety after percutaneous coronary intervention.

Background: Platelet inhibition by clopidogrel is highly variable and the elevated platelet activity will increase the risk of major adverse cardiovascular events after percutaneous coronary intervention (PCI). CYP2C19 loss-of-function (LOF) alleles and risk factors of coronary heart disease (CAD) were reported to be associated with the low response of clopidogrel.

Purpose: This study was carried out to analyze the contributions of CYP2C19 polymorphisms and risk factors to the various clopidogrel responses in Chinese patients with stable CAD after PCI.

Naphthyridinomycin biosynthesis revealing the use of leader peptide to guide nonribosomal peptide assembly.

Analysis of naphthyridinomycin gene cluster revealed that this antibiotic is generated by nonribosomal peptide synthetase (NRPS) machinery. However, four modules encoded by two genes do not correspond with the structural units in the final product. Genetic and biochemical characterization of the gene cluster suggested that the leader peptide mechanism for the NRPS assembly line was involved in biosynthesis of this tetrahydroisoquinoline alkaloid.

Low strength static magnetic field inhibits the proliferation, migration, and adhesion of human vascular smooth muscle cells in a restenosis model through mediating integrins β1-FAK, Ca2+ signaling pathway.

The proliferation, migration, and adhesion of vascular smooth muscle cells (VSMCs) and their interactions with extracellular matrix are key features of atherosclerosis and restenosis. Recently, there has been evidence that magnetic fields exert multiple effects on the biological performance of cells and may aid in the treatment of vascular disease. However, the effect of a static magnetic field (SMF) on human VSMCs still remains unknown.

Hijacking a hydroxyethyl unit from a central metabolic ketose into a nonribosomal peptide assembly line.

Nonribosomal peptide synthetases (NRPSs) usually catalyze the biosynthesis of peptide natural products by sequential selection, activation, and condensation of amino acid precursors. It was reported that some fatty acids, α-ketoacids, and α-hydroxyacids originating from amino acid metabolism as well as polyketide-derived units can also be used by NRPS assembly lines as an alternative to amino acids. Ecteinascidin 743 (ET-743), naphthyridinomycin (NDM), and quinocarcin (QNC) are three important antitumor natural products belonging to the tetrahydroisoquinoline family.

Curcumin reverses cis-platin resistance and promotes human lung adenocarcinoma A549/DDP cell apoptosis through HIF-1α and caspase-3 mechanisms.

Curcumin, a yellow pigment derived from Curcuma longa Linn, has been favored by the Eastern as dietary ingredients for centuries. During the past decade, extensive investigations have revealed curcumin sensitized various chemotherapeutic agents in human breast, colon, pancreas, gastric, liver, brain and hematological malignant disorders in vivo and in vitro. Several pathways and specific targets including NF-κB, STAT3, COX-2, Akt and multidrug resistant protein have been identified to facilitate curcumin as a chemosensitizer.

Notch signaling regulates the FOXP3 promoter through RBP-J- and Hes1-dependent mechanisms.

Evidence has shown that Notch signaling modulates CD4(+)CD25(+) regulatory T-cells (Tregs). As transcription factor Foxp3 acts as a master molecule governing the development and function of Tregs, we investigated whether Notch signaling might directly regulate Foxp3 expression. Here, we provide evidence that Notch signaling can modulate the FOXP3 promoter through RBP-J- and Hes1-dependent mechanisms.

[Achievement of the noninvasive measurement for human blood glucose with NIR diffusion reflectance spectrum method].

The noninvasive measurement of human blood glucose was achieved with NIR diffusion reflectance spectrum method. The thumb fingertip NIR diffusion reflectance spectra of six different age healthy volunteers were collected using Nexus-870 and its NIR fiber port smart accessory. The test was implemented with changing the blood glucose concentration for the limosis and satiation of every volunteer.

[Exploration of serum endothelin-1 as a marker of early radiation lung injury].

Aim: To explore the possibility of endothelin-1(ET-1) as a serological marker of early diagnosis and progression of radiation induced lung injury.

Methods: One hundred and ninety female rats were randomly divided into control group (group C) and experimental groups, namely, radiation group (group R), fluvastatin treatment group (group Flu), retinoic acid treatment group (group Ra) and dexemethasone treatment group (group Dex). The chests of rats in experimental groups were exposed to radiation by linear accelerator after anesthesia.

[Cloning and expression of the extracellular domain of calcium-activated chloride channel in mouse airway goblet cells].

Aim: To clone and express the extracellular domain of murine calcium-activated chloride channel (mCLCA3) in airway goblet cell of mouse.

Methods: According to the gene sequence of mCLCA3 the PCR primers for N-terminal, middle and C-terminal extracellular domains were designed. Using recombinant plasmid pcDNA3.

[Inhibitive effect on airway mucus overproduction with DNA vaccine based on xenogeneic homologous calcium-activated chloride channel in asthmatic mice].

Objective: To observe the inhibitive effect on airway mucus overproduction with DNA vaccine based on human calcium-activated chloride channel 1 (hCLCA1) in asthmatic mice, who own mCLCA3 being xenogeneic homology of hCLCA1 in airway goblet cell.

Methods: The DNA vaccine was made with hCLCA1 gene inserted into pSecTag2B, and then BALB/c mice were vaccinated by i.m.

[The inhibiting effect of niflumic acid on airway hyperresponsiveness in asthmatic mice].

Objective: To evaluate the inhibiting effect of niflumic acid (NFA), an inhibitor of calcium-activated chloride channel (ClCa) on airway epithelium, on the airway hyperresponsiveness in asthmatic mice.

Methods: BALB/c mice were randomly divided into an asthma group (A group), a NFA prevention asthmatic group (B group) and a sham-challenged group (C group). The airway pressure time index (APTI) and the content of ET-1 and NO in bronchoalveolar lavage fluid (BALF) in all groups were measured.