Basic cell penetrating peptides induce plasma membrane positive curvature, lipid domain separation and protein redistribution.

Basic cell penetrating peptides are tools for molecular cellular internalization of nonmembrane permeable molecules. Their uptake mechanisms involve energy-dependent and energy-independent pathways such as endocytosis, direct translocation or physical endocytosis. These mechanisms are ruled by both, the peptides physicochemical properties and structure and by the membrane lipids characteristics and organization.

Trophoblasts and decidual stromal cells regulate decidual NK cell functions via interaction between collagen and LAIR-1.

Problem: To determine the effect of collagen from maternal-fetal interface on decidual natural killer cell (dNK) function.

Method Of Study: Decidual and villous samples were collected from normal pregnancy and miscarriage. The phenotype and cytokine production were analyzed, respectively, by flow cytometry and enzyme-linked immunosorbent assay (ELISA).

α-catenin acts as a tumour suppressor in E-cadherin-negative basal-like breast cancer by inhibiting NF-κB signalling.

Basal-like breast cancer is a highly aggressive tumour subtype associated with poor prognosis. Aberrant activation of NF-κB signalling is frequently found in triple-negative basal-like breast cancer cells, but the cause of this activation has remained elusive.Here we report that α-catenin functions as a tumour suppressor in E-cadherin-negative basal-like breast cancer cells by inhibiting NF-κB signalling.

Treatment-related secondary cancer in malignant meningiomas: a population-based study.

Purpose: To evaluate the risk of secondary cancer especially treatment-related secondary cancer in patients with malignant meningiomas by using data from surveillance, epidemiology and end results (SEER) database.

Patients And Methods: All patients diagnosed as malignant meningiomas were identified from SEER database (1973-2007). Standardized incidence ratios (SIRs) and excess absolute risks of those with secondary cancers were analyzed.

Synthesis and evaluation of the antimicrobial activities of 3-((5-phenyl-1,3,4-oxadiazol-2-yl)methyl)-2-thioxothiazolidin-4-one derivatives.

Two novel series of 3-((5-phenyl-1,3,4-oxadiazol-2-yl)methyl)-2-thioxothiazolidin-4-one derivatives were designed and synthesized, and their anti-bacterial activities evaluated. These compounds showed broad-spectrum inhibitory activities against both Gram-positive and Gram-negative bacteria with minimum inhibitory concentration (MIC) values in the range of 1-64 μg/mL. The activity of compound 6c was the more potent with MIC values of 1 μg/mL against the MRSA (3167 and 3506) strains than those of gatifloxacin, oxacillin, and norfloxacin.

Increasing newly diagnosed rate and changing risk factors of HCV in Yanbian Prefecture, a high endemic area in China.

Background: The newly diagnosed rate of HCV infection is increasing in China. However, the risk factors have not been fully identified. Here, a survey was performed in Yanbian Prefecture, a high-endemic area in China.

Elafin drives poor outcome in high-grade serous ovarian cancers and basal-like breast tumors.

High-grade serous ovarian carcinoma (HGSOC) and basal-like breast cancer (BLBC) share many features including TP53 mutations, genomic instability and poor prognosis. We recently reported that Elafin is overexpressed by HGSOC and is associated with poor overall survival. Here, we confirm that Elafin overexpression is associated with shorter survival in 1000 HGSOC patients.

Conditioned medium of human adipose-derived mesenchymal stem cells mediates protection in neurons following glutamate excitotoxicity by regulating energy metabolism and GAP-43 expression.

Glutamate excitotoxicity has been implicated as one of the pathological mechanisms contributing to neuronal cell death and is involved in many neurological disorders. Stem cell transplantation is a promising approach for the treatment of nervous system damage or diseases. Previous studies have shown that mesenchymal stem cells (MSCs) have important therapeutic effects in experimental animal and preclinical disease model of central nervous system pathology.

Embryonic trophoblasts induce decidual regulatory T cell differentiation and maternal-fetal tolerance through thymic stromal lymphopoietin instructing dendritic cells.

Physiological pregnancy requires the maternal immune system to recognize and tolerate embryonic Ags. Although multiple mechanisms have been proposed, it is not yet clear how the fetus evades the maternal immune system. In this article, we demonstrate that trophoblast-derived thymic stromal lymphopoietin (TSLP) instructs decidual CD11c(+) dendritic cells (dDCs)with increased costimulatory molecules; MHC class II; and Th2/3-type, but not Th1-type, cytokines.

FoxO transcription factors promote AKT Ser473 phosphorylation and renal tumor growth in response to pharmacologic inhibition of the PI3K-AKT pathway.

The PI3K-AKT pathway is hyperactivated in many human cancers, and several drugs to inhibit this pathway, including the PI3K/mTOR dual inhibitor NVP-BEZ235, are currently being tested in various preclinical and clinical trials. It has been shown that pharmacologic inhibition of the PI3K-AKT pathway results in feedback activation of other oncogenic signaling pathways, which likely will limit the clinical utilization of these inhibitors in cancer treatment. However, the underlying mechanisms of such feedback regulation remain incompletely understood.

Human adipose-derived mesenchymal stem cells: a better cell source for nervous system regeneration.

Background: In order to suggest an ideal source of adult stem cells for the treatment of nervous system diseases, MSCs from human adipose tissue and bone marrow were isolated and studied to explore the differences with regard to cell morphology, surface markers, neuronal differentiation capacity, especially the synapse structure formation and the secretion of neurotrophic factors.

Methods: The neuronal differentiation capacity of human mesenchymal stem cells from adipose tissue (hADSCs) and bone marrow (hBMSCs) was determined based on nissl body and synapse structure formation, and neural factor secretion function. hADSCs and hBMSCs were isolated and differentiated into neuron-like cells with rat brain-conditioned medium, a potentially rich source of neuronal differentiation promoting signals.

The 3rd international conference on reproductive immunology in Shanghai: September 27-29, 2013. Shanghai, China.

Problem: After the first and second international conferences on reproductive immunology held by Dr. DaJin Li in Shanghai, the related investigators all over the world hope to get together to share their latest findings with each other.

Method Of Study: Drs.

Deubiquitylation and stabilization of PTEN by USP13.

The tumour suppressor PTEN is frequently lost in human cancers. In addition to gene mutations and deletions, recent studies have revealed the importance of post-translational modifications, such as ubiquitylation, in the regulation of PTEN stability, activity and localization. However, the deubiquitylase that regulates PTEN polyubiquitylation and protein stability remains unknown.

Long non-coding RNA HOTAIR in carcinogenesis and metastasis.

Long non-coding RNAs (lncRNAs) have gained massive attention in recent years as a potentially new and crucial layer of gene regulation. LncRNAs are prevalently transcribed in the genome, but their roles in gene regulation and disease development are largely unknown. HOX antisense intergenic RNA (HOTAIR), a lncRNA located in the HOXC locus, has been shown to repress HOXD gene expression and promote breast cancer metastasis.

Cyclosporin A promotes proliferating cell nuclear antigen expression and migration of human cytotrophoblast cells via the mitgen-activated protein kinase-3/1-mediated nuclear factor-κB signaling pathways.

Our previous studies have demonstrated that cyclosporin A (CsA) promotes the proliferation and migration of human trophoblasts via the mitgen-activated protein kinase-3/1 (MAPK3/1) pathway. In the present study, we further investigated the role of nuclear factor (NF)-κB in the CsA-induced trophoblast proliferating cell nuclear antigen (PCNA) expression and migration, and its relationship to MAPK3/1 signal. Flow cytometry was used to analyze the expression of PCNA in trophoblasts.

25-Methoxylprotopanaxadiol derivatives and their anti-proliferative activities.

(20R)-25-Methoxyl-dammarane-3β,12β,20-triol (25-OCH₃-PPD) is a dammarane-type sapogenin showing anti-proliferative potential. In our study, two series of analogs substituted at the C-3 or C-3 and C-12 positions with fatty acids were prepared conveniently. The cytotoxic activity of these compounds was evaluated using four different human tumor cell lines (A549, Hela, HT-29 and MCF-7) and a normal cell line (IOSE144).

Synthesis and biological evaluation of (E)-1-(substituted)-3-phenylprop-2-en-1-ones bearing rhodanines as potent anti-microbial agents.

Herein, we report the design, syntheses and in vitro anti-microbial activity of two series of rhodanines with chalcone moiety. Anti-microbial tests showed that some of the synthesized compounds exhibited good inhibition (MIC = 1-8 µg/mL) against multi-drug-resistant Gram-positive organisms, including methicillin resistant and quinolone-resistant Staphylococcus aureus, in which the compound 4g was found to be the most potent with minimum inhibitory concentration (MIC) value of 1 µg/mL against two methicillin-resistant S. aureus.

Hyaluronan-CD44 interaction promotes growth of decidual stromal cells in human first-trimester pregnancy.

Hyaluronan (HA) and its receptor CD44 are expressed at the maternal-fetal interface, but its role in early pregnancy remains unclear. Here, we found that primary decidual stromal cells (DSCs) continuously secreted HA and expressed its receptor CD44. Pregnancy-associated hormones up-regulated HA synthetase (HAS) 2 transcription and HA release from DSCs.

The progress towards the development of DHQO derivatives and related analogues with inotropic effects.

During the course of the past two decades, our group has worked towards the development of increasingly potent inotropic agents by making structural modifications to compounds derived from 3,4-dihydro-2(1H)-quinolinone (DHQO) and related analogues. Herein, we describe the design and synthesis of a new series of DHQO derivatives and the subsequent evaluation of their positive inotropic activity towards left atrium stroke volume in isolated rabbit-heart preparations. Some of these derivatives presented favorable in vitro activities compared with the reference drug, milrinone, and compound 10a, in particular is currently being investigated as a preclinical drug candidate.

9-Phenanthrol, a TRPM4 inhibitor, protects isolated rat hearts from ischemia-reperfusion injury.

Despite efforts to elucidate its pathophysiology, ischemia-reperfusion injury lacks an effective preventative intervention. Because transient receptor potential cation channel subfamily M member 4 (TRPM4) is functionally expressed by many cell types in the cardiovascular system and is involved in the pathogenesis of various cardiovascular diseases, we decided to assess its suitability as a target of therapy. Thus, the aim of this study was to examine the possible cardioprotective effect of 9-phenanthrol, a specific inhibitor of TRPM4.

Affinity-matured recombinant immunotoxin targeting gangliosides 3'-isoLM1 and 3',6'-isoLD1 on malignant gliomas.

About 60 percent of glioblastomas highly express the gangliosides 3'-isoLM1 and 3',6'-isoLD1 on the cell surface, providing ideal targets for brain tumor immunotherapy. A novel recombinant immunotoxin, DmAb14m-(scFv)-PE38KDEL (DmAb14m-IT), specific for the gangliosides 3'-isoLM1 and 3',6'-isoLD1, was constructed with improved affinity and increased cytotoxicity for immunotherapeutic targeting of glioblastoma. We isolated an scFv parental clone from a previously established murine hybridoma, DmAb14, that is specific to both 3'-isoLM1 and 3',6'-isoLD1.

Novel arylhydrazone derivatives bearing a rhodanine moiety: synthesis and evaluation of their antibacterial activities.

A series of arylhydrazone derivatives bearing a rhodanine moiety have been synthesized, characterized, and evaluated as antibacterial agents. Some of these compounds showed potent antibacterial activities against several different strains of Gram-positive bacteria, including multidrug-resistant clinical isolates. Of the compounds tested, IIk and IIIk were identified as the most effective, with minimum inhibitory concentration values of 2-4 μg/mL against multidrug-resistant Gram-positive organisms, including methicillin-resistant and quinolone-resistant Staphylococcus aureus.

The genus Gnaphalium L. (Compositae): phytochemical and pharmacological characteristics.

The genus Gnaphalium, a herb distributed worldwide, comprises approximately 200 species of the Compositae (Asteraceae) family that belongs to the tribe Gnaphalieae. Some species are traditionally used as wild vegetables and in folk medicine. This review focuses on the phytochemical investigations and biological studies of plants from the genus Gnaphalium over the past few decades.

Construction of an immunotoxin, D2C7-(scdsFv)-PE38KDEL, targeting EGFRwt and EGFRvIII for brain tumor therapy.

Purpose: The EGF receptor gene (EGFR) is most frequently amplified and overexpressed, along with its deletion mutant, EGFRvIII, in glioblastoma. We tested the preclinical efficacy of the recombinant immunotoxin, D2C7-(scdsFv)-PE38KDEL, which is reactive with a 55-amino acid (AA) region present in the extracellular domain of both EGFRwt (583-637 AAs) and EGFRvIII (292-346 AAs) proteins.

Experimental Design: The binding affinity and specificity of D2C7-(scdsFv)-PE38KDEL for EGFRwt and EGFRvIII were measured by surface-plasmon resonance and flow cytometry.

Hyaluronan up-regulates growth and invasion of trophoblasts in an autocrine manner via PI3K/AKT and MAPK/ERK1/2 pathways in early human pregnancy.

Introduction: As one of the key molecules in the extracellular matrix in human conceptus, hyaluronan (HA) has been receiving particular attention. Here, we have investigated the expression and regulation of different molecular weight HA on the biological behaviors of primary human trophoblasts during the first trimester of pregnancy.

Methods: The expression of HA and HA synthetase (HAS) by human first trimester trophoblasts was analyzed in placentae from normal pregnancy or miscarriage by immunochemistry and real-time RT-PCR, respectively.