A redox-activated theranostic nanoagent: toward multi-mode imaging guided chemo-photothermal therapy.

Development of tumor microenvironment responsive and modulating theranostic nano-systems is of great importance for specific and efficient cancer therapy. Herein, we report a redox-sensitive nanoagent combining manganese dioxide (MnO) and gold nanoshell coated silicon nanoparticles for synergistic chemo-photothermal therapy of hypoxia solid tumors. In highly reducing tumor tissues, the outer MnO nanosheet with the loaded drug would be dissociated by intracellular glutathione (GSH), resulting in on-demand drug release, as well as generating Mn ions which provided high contrast magnetic resonance imaging (MRI), and fluorescence imaging (FI) and .

Rapidly progressive non-alcoholic fatty liver disease due to hypopituitarism. Report of 5 cases.

Background: A few reports had revealed the clinical associations between hypopituitarism and non-alcoholic fatty liver disease (NAFLD). Further evidences were needed.

Objectives: To report 5 cases of young patients with rapidly progressive NAFLD in conjunction with hypopituitarism, aiming to detect the associations.

Evaluation of IL-17A, IL-17F, IL-23R, VDR, CCL2, CCL5, CCR2, and CCR5 gene polymorphisms and expression in Chinese individuals with syphilis.

Syphilis is a sexually transmitted disease caused by the infection of Treponema pallidum subspecies pallidum. T-helper type 17-related genes, vitamin D receptor (VDR) gene, and chemokine/chemokine receptor genes are crucial in microbial infection. A total of 16 single-nucleotide polymorphisms (SNPs) in eight genes (interleukin [IL]-17A, IL-17F, IL-23R, VDR, C-C motif chemokine ligand [CCL] 2, CCL5, C-C chemokine receptor [CCR] 2, and CCR5) were analyzed in 188 patients with syphilis and 216 healthy controls.

Network-based drug repositioning: A novel strategy for discovering potential antidepressants and their mode of action.

Current target-oriented paradigm for novel antidepressant discovery has been difficult to succeed and the failures always bring huge economic losses. Although abundant ledge of disease related genes and drug action targets has been accumulated, the successful application of the knowledge for new drug discovery is limited. Here, we predicted and validated potential antidepressants and molecular targets from DrugBank recorded drugs using a novel network-based drug repositioning approach.

Magnetic beads-based neuraminidase enzyme microreactor as a drug discovery tool for screening inhibitors from compound libraries and fishing ligands from natural products.

Neuraminidase (NA) is a glycoside hydrolase that has been proposed as a potential therapeutic target for influenza. Thus, the identification of compounds that modulate NA activity could be of great therapeutic importance. The aim of this study is to develop a drug discovery tool for the identification of novel modulators of NA from both compound libraries and natural plant extracts.

[Preliminary study on the clinical application of temporary treatment denture in difficult edentulous cases before complete denture restoration].

Objective: To explore the clinical effects of treatment denture on difficult edentulous cases before complete denture restoration.

Methods: Thirty-six patients who experienced unsuccessful restoration of conventional complete dentures were included in this study. Treatment dentures were fabricated to solve issues such as abnormal occlusion, tissue surface problems, and neuromuscular dysfunction of the stomatognathic system caused by systemic diseases.

[Distribution Characteristics of Drugs of Abuse and Their Metabolites in Aqueous Environment of Beijing, China].

This work investigated the occurrence and distribution of six drugs of abuse and their metabolites, i.e. methamphetamine(METH), amphetamine(AMP), ketamine(KET), ephedrine(EPH), methcathinone(MC) and hydroxylimine(HY) in the surface water and groundwater in Beijing, China.

A Systems Biology-Based Approach to Uncovering Molecular Mechanisms Underlying Effects of Traditional Chinese Medicine Qingdai in Chronic Myelogenous Leukemia, Involving Integration of Network Pharmacology and Molecular Docking Technology.

BACKGROUND The method of multiple targets overall control is increasingly used to predict the main active ingredient and potential target group of Chinese traditional medicines and to determine the mechanisms involved in their curative effects. Qingdai is the main traditional Chinese medicine used in the treatment of chronic myelogenous leukemia (CML), but the complex active ingredients and antitumor targets in treatment of CML have not been clearly defined in previous studies. MATERIAL AND METHODS We constructed a protein-protein interaction network diagram of CML with 638 nodes (proteins) and 1830 edges, based on the biological function of chronic myelocytic leukemia by use of Cytoscape, and we determined 19 key gene nodes in the CML molecule by network topological properties analysis in a data bank.

Metformin reduces TRIB3 expression and restores autophagy flux: an alternative antitumor action.

Deregulation of metabolism during melanoma progression is tightly associated with the genetic and epigenetic alterations of metabolic regulators. Metformin, a macroautophagy/autophagy inducer, has beneficial effects of preventing and treating multiple cancers with an unclear mechanism. Enhanced pseudokinase TRIB3 was reported to link metabolic stressors to melanoma promotion by inhibiting autophagy and ubiquitin-proteasome degradation systems.

[Electrophysiological identification of human induced pluripotent stem cell-derived cardiomyocytes].

The present study was aimed to characterize the electrophysiology of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs). IMR90-4 cells were induced to differentiate into cardiomyocytes by temporal modulation of regulators of canonical Wnt signaling. The protein expression of cardiac troponin T (cTnT) was detected by immunofluorescence staining and flow cytometry, and the differentiation rate of hiPSC-CMs was calculated.

NRG1 regulates redox homeostasis via NRF2 in papillary thyroid cancer.

Thyroid cancer is a common endocrine cancer, of which papillary thyroid cancer (PTC) is the most common type. Neuregulin 1 (NRG1), a glycoprotein mediating cell‑cell signaling, plays vital roles in cellular activities; however, its role in PTC progression remains poorly understood. In this study, we performed immunohistochemistry in 196 samples from patients and found that NRG1, a potential prognostic marker is highly expressed in PTC compared with adjacent normal tissues.

Ammoxetine attenuates diabetic neuropathic pain through inhibiting microglial activation and neuroinflammation in the spinal cord.

Background: Diabetic neuropathic pain (DNP) is a common and distressing complication in patients with diabetes, and the underlying mechanism remains unclear. Tricyclic antidepressants (TCAs) and serotonin and norepinephrine reuptake inhibitors (SNRIs) are recommended as first-line drugs for DNP. Ammoxetine is a novel and potent SNRI that exhibited a strong analgesic effect on models of neuropathic pain, fibromyalgia-related pain, and inflammatory pain in our primary study.

Antiproliferative Phenothiazine Hybrids as Novel Apoptosis Inducers against MCF-7 Breast Cancer.

We designed a series of novel phenothiazine-1,2,3-triazole hybrids by the molecular hybridization strategy and evaluated their antiproliferative activity against three cancer cell lines (MDA-MB-231, MDA-MB-468 and MCF-7). For the structure-activity relationships, the importance of 1,2,3-triazole and substituents on phenyl ring was explored. Among these phenothiazine-1,2,3-triazole hybrids, compound showed the most potent inhibitory effect against MCF-7 cells, with an IC value of 0.

Renal inhibition of miR-181a ameliorates 5-fluorouracil-induced mesangial cell apoptosis and nephrotoxicity.

The development of nephrotoxicity largely limits the clinical use of chemotherapy. MiRNAs are able to target various genes and involved in the regulation of diverse cellular processes, including cell apoptosis and death. Our study showed that miR-181a expression was significantly increased after 5-fluorouracil (5-FU) treatment in renal mesangial cells and kidney tissue, which was associated with decreased baculoviral inhibition of apoptosis protein repeat-containing 6 (BIRC6) expression and increased apoptotic rate.

An exploration of nucleic acid liquid biopsy using a glucose meter.

The development of non-invasive techniques for the diagnosis of cancer, characterization of mutation and monitoring treatment response could greatly reduce the morbidity and mortality caused by cancer. Nevertheless, the extremely low amount of cell free nucleic acids makes liquid biopsy a very challenging task. Herein, taking advantage of the pocket size, reliable quantitative results and simple operation of the pocket-sized personal glucose meter (PGM), we report an approach of circulating microRNA-21 (miR-21) detection with high precision and low cost.

Surgical Treatment and Long-Term Outcome of Cerebral Cavernous Malformations-Related Epilepsy in Pediatric Patients.

Cerebral cavernous malformations (CMs) are vascular malformations affecting any part of the central nervous system. Clinical data and surgical outcomes for 27 pediatric patients with CM-related epilepsy were retrospectively reviewed. The mean age of onset was 12.

A Temporal Transcriptional Switch Governs Stem Cell Division, Neuronal Numbers, and Maintenance of Differentiation.

The importance of producing the correct numbers of neurons during development is illustrated by both evolutionary enhancement of cognitive capacities in larger brains, and developmental disorders of brain size. In humans, increased neuronal numbers during development is speculated to partly derive from a unique subtype of neural stem cells (NSCs) that undergo a phase of expansion through symmetric self-amplifying divisions before generating neurons. Symmetric amplification also appears to underlie adult neural stem maintenance in the mouse.

Metformin suppresses melanoma progression by inhibiting KAT5-mediated SMAD3 acetylation, transcriptional activity and TRIB3 expression.

Metformin has beneficial effects of preventing and treating cancers on type 2 diabetic patients. However, the role of metformin in non-diabetic cancer patients and the precise molecular mechanisms against cancer have not yet been sufficiently elucidated. We recently reported that the pseudokinase protein TRIB3 acts as a stress sensor linking metabolic stressors to cancer promotion by inhibiting autophagy and ubiquitin-proteasomal degradation systems; genetically abrogating of TRIB3 expression reduces tumourigenesis and cancer progression.

Progress on the Studies of the Key Enzymes of Ginsenoside Biosynthesis.

As the main bioactive constituents of species, ginsenosides possess a wide range of notable medicinal effects such as anti-cancer, anti-oxidative, antiaging, anti-inflammatory, anti-apoptotic and neuroprotective activities. However, the increasing medical demand for ginsenosides cannot be met due to the limited resource of species and the low contents of ginsenosides. In recent years, biotechnological approaches have been utilized to increase the production of ginsenosides by regulating the key enzymes of ginsenoside biosynthesis, while synthetic biology strategies have been adopted to produce ginsenosides by introducing these genes into yeast.

Effects of nutrient restriction and arginine treatment on oxidative stress in the ovarian tissue of ewes during the luteal phase.

The aim of this study was to determine whether nutrient restriction and arginine treatment affect energy metabolism changes and oxidative stress through the mitochondrial pathway in the ovarian tissue of ewes during the luteal phase. On days 6-15 of the estrous cycle, 24 multiparous Hu sheep (BW = 43.56 ± 1.

Structural characteristics of natural chimeric genes and their implications for gene design.

The natural chimeric gene is a novel gene fused by two or more independent genes. Its discovery extends the classical gene concept that one gene resides in one chromosomal locus. During tumorigenesis, many chimeric genes lead to tumor-related diseases; therefore, it is one molecular marker for cancer diagnosis.

Dual Blockade of Interleukin-1 and Interleukin-17A Reduces Murine Arthritis Pathogenesis but Also Leads to Spontaneous Skin Infections in Nonhuman Primates.

Despite the efficacy of biologics for treatment of rheumatoid arthritis (RA), many patients show inadequate responses and likely require neutralization of multiple mediators. Neutralization of both interleukin (IL)-1 and IL-17A with monoclonal antibodies showed greater efficacy than either agent alone in a mouse arthritis model with cooperative inhibition of key inflammatory factors, IL-6, granulocyte colony-stimulating factor (G-CSF), and CXC chemokine ligand (CXCL)1. Given the potential clinical benefit in RA, we generated a human dual variable domain antibody Ig, ABBV-615, capable of simultaneous binding and neutralization of IL-1 and IL-17A.

Mediastinal Lymph Node Metastases in Thyroid Cancer: Characteristics, Predictive Factors, and Prognosis.

Background: Mediastinal lymph node metastases (MLNM) have not been extensively studied. The aim of this study is to investigate the characteristics, predictive factors, and prognosis of MLNM in thyroid cancer.

Methods: This is a retrospective study based on the thyroid cancer patients with MLNM at our institution from 2008 to 2015.

Inhibition of Orai1-mediated Ca entry limits endothelial cell inflammation by suppressing calcineurin-NFATc4 signaling pathway.

Orai1-dependent Ca entry plays an essential role in inflammatory response through regulating T cell and macrophage activation and neutrophil infiltration. However, whether Orai1 Ca entry contributes to endothelial activation, one of the early steps of vascular inflammation, remains elusive. In the present study, we observed that knockdown of Orai1 reduced, whereas overexpression of Orai1 potentiated, TNFα-induced expression of adhesion molecules such as ICAM-1 and VCAM-1 in HUVECs, and subsequently blocked adhesion of monocyte to HUVECs.