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cell and molecular and development

Pieterjan Merckx, Lynn De Backer, Lien Van Hoecke, Roberta Guagliardo, Mercedes Echaide, Pieter Baatsen, Bárbara Olmeda, Xavier Saelens, Jésus Pérez-Gil, Stefaan C De Smedt, Koen Raemdonck
Despite the many advantages of small interfering RNA (siRNA) inhalation therapy and a growing prevalence for respiratory pathologies, its clinical translation is severely hampered by inefficient intracellular delivery. To this end, we previously developed hybrid nanoparticles consisting of an siRNA-loaded nanosized hydrogel core (nanogel) coated with Curosurf® , a clinically used pulmonary surfactant (PS). Interestingly, the PS shell was shown to markedly improve particle stability as well as intracellular siRNA delivery in vitro and in vivo...
August 14, 2018: Acta Biomaterialia
Hongzhi Du, Yue Huang, Xiaoying Hou, Xingping Quan, Jingwei Jiang, Xiaohui Wei, Yang Liu, Hongyang Li, Puhai Wang, Meixiao Zhan, Xun Ai, Ligong Lu, Shengtao Yuan, Li Sun
At present, chemotherapy is still to be the preferred and most significant therapeutic strategy for cancer patients in clinical practice. Although Camptothecin (CPT) has been discovered for over half century, a series of CPT derivatives such as Topotecan (TPT) and irinotecan (CPT-11) have been approved and are still to be the first-line medicines for clinical application. Up to now, the topoisomerase 1 inhibitor continues to be a significant drug development research field. Based on previous study of the structure-activity relationship, we consider that the introduction of lipophilic group at C7 position can prolong the retention time and the hydroxyl esterification at C20 can eliminate the hydrogen bond interaction, stabilize the E-lactone form and promote the anti-cancer effect...
August 14, 2018: European Journal of Pharmaceutical Sciences
Xiao Tan, Zhongqiang Zhang, Hongliang Yao, Liangfang Shen
T-cell immunoglobulin domain and mucin domain-4 (Tim-4) is overexpressed in several tumors and is correlated with enhanced tumor development and metastasis. In this study, we investigated the physiological alterations and molecular events related to Tim-4 overexpression in a mouse model of colorectal cancer (CRC). In the current study, we observed that Tim-4 is upregulated in CRC tissues compared with neighboring normal tissues. In addition, statistical analysis revealed that elevated Tim-4 expression was strongly linked to distant metastasis, TNM stage and reduced overall survival duration in CRC patients...
August 14, 2018: Cancer Letters
Aravind T Reddy, Sowmya P Lakshmi, Asoka Banno, Raju C Reddy
Cigarette smoke, a source of numerous oxidants, produces oxidative stress and exaggerated inflammatory responses that lead to irreversible lung tissue damage. It is the single, most significant risk factor for chronic obstructive pulmonary disease (COPD). Although an intrinsic defense system that includes both enzymatic and non-enzymatic players exists to protect lung tissues against oxidative stress, impairment of these protective mechanisms has been demonstrated in smokers and COPD patients. The antioxidant enzyme GSH peroxidase (GPx) is an important part of this intrinsic defense system...
August 14, 2018: Free Radical Biology & Medicine
Nebras Alattar, Hasbullah Daud, Rasoul Al-Majmaie, Domonic Zeulla, Mohameed Al-Rubeai, James H Rice
Raman-spectroscopy-based methods, such as surface-enhanced Raman spectroscopy, are a well-evolved method to molecular fingerprint cell types. Here we demonstrate that surface-enhanced Raman spectroscopy can enable us to distinguish cell development stages of bone marrow hematopoietic stem cells towards red blood cells through the identification of specific surface-enhanced Raman spectroscopy biomarkers. The approach taken here is to allow cells to take in gold nanoparticles as Raman enhancement platforms for kinetic structural observations presented here through the view of the multidimensional parameter contribution, thereby enabling profiling of bone marrow hematopoietic stem cells acquired from proliferation (stage one), differentiation (stage two), and mature red blood cells (stage three)...
August 1, 2018: Applied Optics
Lutz Schmitz, Claus Oster-Schmidt, Eggert Stockfleth
Actinic keratoses (AKs) are defined as intraepithelial proliferation of atypical keratinocytes. Given their potential for progression to invasive squamous cell carcinoma, they may eventually evolve into a life-threatening disease. In recent decades, there has been a significant increase in the incidence of AKs, primarily due to changes in recreational activities and demographic trends in industrialized countries. As it is currently impossible to predict if and when a given AK might progress to invasive carcinoma, rigorous treatment of field cancerization is a key component in preventing potential progression...
August 2018: Journal der Deutschen Dermatologischen Gesellschaft, Journal of the German Society of Dermatology: JDDG
Sevinci Pop, Ana-Maria Enciu, Laura G Necula, Cristiana Tanase
Glioma biology is a major focus in tumour research, primarily due to the aggressiveness and high mortality rate of its most aggressive form, glioblastoma. Progress in understanding the molecular mechanisms behind poor prognosis of glioblastoma, regardless of treatment approaches, has changed the classification of brain tumours after nearly 100 years of relying on anatomopathological criteria. Expanding knowledge in genetic, epigenetic and translational medicine is also beginning to contribute to further elucidating molecular dysregulation in glioma...
August 17, 2018: Journal of Cellular and Molecular Medicine
Kumar Bhaskar Pal, Mukul Mahanti, Xiaoli Huang, Stella Persson, Anders P Sundin, Fredrik R Zetterberg, Stina Oredsson, Hakon Leffler, Ulf J Nilsson
Quinolines, indolizines, and coumarins are well known structural elements in many biologically active molecules. In this report, we have developed straightforward methods to incorporate quinoline, indolizine, and coumarin structures into galactoside derivatives under robust reaction conditions for the discovery of glycomimetic inhibitors of the galectin family of proteins that are involved in immunological and tumor-promoting biological processes. Evaluation of the quinoline, indolizine and coumarin-derivatised galactosides as inhibitors of the human galectin-1, 2, 3, 4N (N-terminal domain), 4C (C-terminal domain), 7, 8N, 8C, 9N, and 9C revealed quinoline derivatives that selectively bound galectin-8N, a galectin with key roles in lymphangiogenesis, tumor progression, and autophagy, with up to nearly 60-fold affinity improvements relative to methyl β-d-galactopyranoside...
August 17, 2018: Organic & Biomolecular Chemistry
Vanessa D'Urbano, Elisa De Crignis, Maria Carla Re
Mammalian cells have evolved several mechanisms to prevent or block lentiviral infection and spread. Among the innate immune mechanisms, the signaling cascade triggered by type I interferon (IFN) plays a pivotal role in limiting the burden of HIV-1. In presence of IFN, human cells upregulate the expression of a number of genes, referred to as IFN-stimulated genes (ISGs), many of them acting as antiviral restriction factors (RFs). RFs are dominant proteins that target different essential steps of the viral cycle, thereby providing an early line of defense against the virus...
August 16, 2018: Current HIV Research
Eiichi Sasaki, Daisuke Nishikawa, Nobuhiro Hanai, Yasuhisa Hasegawa, Yasushi Yatabe
AIMS: Molecular targeted therapy against EGFR kinase domain mutations has been successfully established for lung cancer. These mutations now have also been reported in head and neck tumours, particularly in inverted sinonasal papillomas (ISPs). The aim of this study was to clarify the spectrum of EGFR mutations in head and neck squamous cell carcinomas and papillomas. METHODS AND RESULTS: We examined EGFR mutations in 288 head and neck squamous cell carcinomas and 58 head and neck papillomas or polyps...
August 17, 2018: Histopathology
Daya V Pavitrakar, Rekha G Damle, Anuradha S Tripathy, Pratip Shil
Chandipura virus (CHPV), associated with an encephalitic illness in humans, has caused multiple outbreaks with high mortality in central and western India in recent years. The present study compares surface glycoprotein (G-protein) from prototype and recent outbreak strains using in silico tools and in vitro experiments. In silico epitope predictions (B-cell and T-helper cell) for the sequences, 3D structure prediction and comparison of the G-proteins of the strains: I653514 (Year 1965), CIN0327 (Year 2003) and 148974 (Year 2014) revealed that the CHPV G-protein is stable and antigenic determinants are conserved...
August 16, 2018: Archives of Virology
R S Kalinin, A V Petukhov, V D Knorre, M A Maschan, A V Stepanov, A G Gabibov
Chimeric antigen receptor-modified T-cell therapy (CAR-T therapy) is one of the fastest developing areas of immuno-oncology. Over the past decade, it has revolutionized the cell therapy modality and expedited its pace of development, from optimization of the structure of chimeric antigen receptors and animal model experiments to successful clinical application. The initial designs of the CAR configuration focused on increasing T-cell activation, cytotoxicity, and persistence. However, the first attempts to treat patients with CAR T cells have demonstrated the need for increased safety and controlled activation of genetically modified T cells...
April 2018: Acta Naturae
Marta Lemieszewska, Antoni Polanowski, Tadeusz Wilusz, Agata Sokołowska, Aleksandra Zambrowicz, Katarzyna Mikołajewicz, Józefa Macała, Joanna Rymaszewska, Agnieszka Zabłocka
Colostrum and milk are the initial mammalian nourishment and rich reservoir of essential nutrients for newborn development. Bioactive peptides isolated from natural sources, such as colostrum, serve as endogenous regulators and can be used as alternative therapeutic agents in the treatment of neurodegenerative diseases. One example is the previously unknown NP-POL nonapeptide isolated from Colostrinin. In the present study, we investigated a method of NP-POL nonapeptide isolation using Bio-Gel P2 molecular sieve chromatography...
2018: Oxidative Medicine and Cellular Longevity
Sergiu Chira, Lajos Raduly, Cornelia Braicu, Ancuta Jurj, Roxana Cojocneanu-Petric, Laura Pop, Valentina Pileczki, Calin Ionescu, Ioana Berindan-Neagoe
Cancer, and particularly colon cancer, is associated with an increasing number of cases resistant to chemotherapy. One approach to overcome this, and to improve the prognosis and outcome of patients, is the use of adjuvant therapy alongside the standard chemotherapy regiment. In the present study, the effect of deuterium-depleted water (DDW) as a potential modulator of adjuvant therapy on DLD-1 colorectal cancer models was assessed. A number of functionality assays were performed, including MTT, apoptosis and autophagy, and mitochondrial activity and senescence assays, in addition to assessing the capacity to modify the pattern of released miRNA via microarray technology...
August 2018: Experimental and Therapeutic Medicine
Dan Wang, Xinhao Jiang, Aiqing Lu, Min Tu, Wei Huang, Ping Huang
Bone marrow mesenchymal stem cells (BMSCs) are pluripotent cells, which have the capacity to differentiate into various types of mesenchymal cell phenotypes, including osteoblasts, chondroblasts, myoblasts and tendon fibroblasts (TFs). The molecular mechanism for tenogenic differentiation of BMSCs is still unknown. The present study investigated the effects of bone morphogenetic protein (BMP) 14 on BMSC differentiation in vitro . It was revealed that BMP14 significantly increased the expression of tendon markers (scleraxis and tenomodulin) at the mRNA and protein level, which led to the upregulation of sirtuin 1 (Sirt1) expression...
August 2018: Experimental and Therapeutic Medicine
Xueling Zou, Wenfeng Huang
A steroidal saponin named pennogenin 3-O-α-L-rhamnopyranosyl-(1→2) [α-L-rhamnopyranosyl-(1→4)]-β-D-glucoyranoside(TTB2) has been successfully separated from the n-BuOH extracts of Trillium tschonoskii Maxim and is able to induce cytotoxicity to some types cancer cells. The present study aimed to investigate how this novel saponinin duces cytotoxicity in malignant sarcoma cells and to clarify its molecular mechanisms of action. It was determined this steroidal saponin induced the apoptosis in Rh1 cells and activated caspase-3 and caspase-9...
August 2018: Experimental and Therapeutic Medicine
Heng Li, Guofeng Tian, Feipeng Tian, Lin Shao
Taurine upregulated gene 1 (TUG1), a long non-coding RNA (lncRNA), has recently been suggested to be associated with the development of osteosarcoma (OS), but the underlying molecular mechanism still remains largely unclear. In the present study, it was revealed that TUG1 was significantly upregulated whereas miR-212-3p was significantly downregulated in OS tissues and cell lines, when compared with adjacent non-tumor tissues and normal osteoblasts cell lines, respectively. An inverse association between the TUG1 and miR-212-3p expression was also observed in OS tissues...
August 2018: Experimental and Therapeutic Medicine
Ying He, Wen Yao, Meng Zhang, Ying Zhang, Dan Zhang, Zhuocheng Jiang, Tianyou Ma, Jian Sun, Mingming Shao, Jinghong Chen
The molecular mechanisms underlying osteoarthritis (OA) and Kashin-Beck disease (KBD) remain poorly understood. Hypertrophic chondrocytes serve an important role in the development of both OA and KBD, whereas oxidative stress can contribute to the pathological progression of cartilage damage. Therefore, the aim of the present study was to detect altered expression of osteogenesis-related genes in hypertrophic chondrocytes, following treatment with 3-morpholinosydnonimine (SIN-1). ATDC5 cells were induced to develop into hypertrophic chondrocytes via Insulin-Transferrin-Selenium...
August 2018: Experimental and Therapeutic Medicine
Stefania Arioli, Ranjan Koirala, Valentina Taverniti, Walter Fiore, Simone Guglielmetti
Probiotics are live microorganisms, and viability after transit through the gastrointestinal tract (GIT) is considered an inherent property of the health benefits of probiotics. The aim of the present study was to quantify the viable and total loads of Lactobacillus paracasei DG cells after passage through the GIT following the consumption of the probiotic product Enterolactis (L. casei DG®; L. paracasei CNCM I-1572; L. paracasei DG) from drinkable vials by healthy adults. We developed a novel method for discriminating and enumerating culturable L...
2018: Frontiers in Microbiology
Adhemar J Liquitaya-Montiel, Luis Mendoza
Many disease fighting strategies have focused on the generation of NK cells, since they constitute the main immune barrier against cancer and intracellular pathogens such as viruses. Therefore, a predictive model for the development of NK cells would constitute a useful tool to test several hypotheses regarding the production of these cells during both physiological and pathological conditions. Here, we present a boolean network model that reproduces experimental results reported on the literature regarding the progressive stages of the development of NK cells in wild-type and mutant backgrounds...
2018: Frontiers in Physiology
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