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https://www.readbyqxmd.com/read/29777999/targeted-delivery-of-cd44s-sirna-by-scfv-overcomes-de-novo-resistance-to-cetuximab-in-triple-negative-breast-cancer
#1
Wenyan Fu, Hefen Sun, Yang Zhao, Mengting Chen, Lipeng Yang, Xueli Yang, Wei Jin
The overexpression of EGFR often occurs in TNBC, and the anti-EGFR receptor antibody cetuximab is used widely to treat metastatic cancer in the clinic. However, EGFR-targeted therapies have been developed for TNBC without clinical success. In this study, we show that impaired EGFR degradation is crucial for resistance to cetuximab, which depends on the cell surface molecule CD44. To further investigate the role of CD44 in EGFR signaling and its treatment potential, we developed a targeting fusion protein composed of an anti-EGFR scFv generated from cetuximab and truncated protamine, called Ce-tP...
May 16, 2018: Molecular Immunology
https://www.readbyqxmd.com/read/29777958/sssupramolecular-poly-acrylic-acid-f127-hydrogel-with-hydration-controlled-nitric-oxide-release-for-enhancing-wound-healing
#2
Mathilde Champeau, Valéria Póvoa, Lucas Militão, Flávia Cabrini, Guilherme F Picheth, Florian Meneau, Carlos P Jara, Eliana P de Araujo, Marcelo G de Oliveira
Topical nitric oxide (NO) delivery has been shown to accelerate wound healing. However, delivering NO to wounds at appropriate rates and doses requires new biomaterial-based strategies. Here, we describe the development of supramolecular interpolymer complex hydrogels comprising PEO-PPO-PEO (F127) micelles embedded in a poly(acrylic acid) (PAA) matrix, with S-nitrosoglutathione (GSNO) molecules dissolved in the hydrophilic domain. We show that PAA:F127/GSNO hydrogels start releasing NO upon hydration at rates controlled by their rates of water absorption...
May 16, 2018: Acta Biomaterialia
https://www.readbyqxmd.com/read/29777919/brain-to-bone-what-is-the-contribution-of-the-brain-to-skeletal-homeostasis
#3
REVIEW
Anna Idelevich, Roland Baron
The brain, which governs most, if not all, physiological functions in the body, from the complexities of cognition, learning and memory, to the regulation of basal body temperature, heart rate and breathing, has long been known to affect skeletal health. In particular, the hypothalamus - located at the base of the brain in close proximity to the medial eminence, where the blood-brain-barrier is not as tight as in other regions of the brain but rather "leaky", due to fenestrated capillaries - is exposed to a variety of circulating body cues, such as nutrients (glucose, fatty acids, amino acids), and hormones (insulin, glucagon, leptin, adiponectin) [1-3]...
May 16, 2018: Bone
https://www.readbyqxmd.com/read/29777795/sirna-in-ovarian-cancer-delivery-strategies-and-targets-for-therapy
#4
REVIEW
Dirk van den Brand, Vicky Mertens, Leon F A G Massuger, Roland Brock
Epithelial ovarian cancer (EOC) is the most lethal gynecological malignancy, and the sixth leading cause of cancer related death in women overall. Despite improved surgical techniques and advances in chemotherapy, mortality hardly decreased over the last twenty years. The major problem is that (micro)metastases persevere in the abdominal cavity, causing incurable tumor recurrence. Therefore, there is an imminent need for new therapeutic strategies. Oligonucleotide (ON) based therapies such as RNA interference (RNAi) provide the possibility to specifically address disease-related pathways...
May 16, 2018: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/29777712/speckle-type-poz-protein-suppresses-hepatocellular-carcinoma-cell-migration-and-invasion-via-ubiquitin-dependent-proteolysis-of-sumo1-sentrin-specific-peptidase-7
#5
Piyou Ji, Shaohua Liang, Pengtao Li, Chengrong Xie, Jie Li, Kang Zhang, Xuqing Zheng, Min Feng, Qiu Li, Hui Jiao, Xiaoqin Chi, Wenxiu Zhao, Sheng Zhang, Xiaomin Wang
Hepatocellular carcinoma (HCC) is associated with high metastatic potential and high mortality. Accumulating evidence has demonstrated that speckle-type POZ protein (SPOP) is a key adaptor molecule of ubiquitination. However, the molecular mechanism of SPOP-mediated ubiquitination in HCC metastasis remains obscure. In the present study, our results indicated that SPOP expression was significantly downregulated in HCC and was associated with tumor size, differentiation and metastasis. Cox regression model showed that low SPOP expression was a risk factor related to the prognosis of HCC patients...
May 16, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29777694/gapdh-targeted-therapy-a-new-approach-for-secondary-damage-after-traumatic-brain-injury-on-rats
#6
Vladimir F Lazarev, Elizaveta A Dutysheva, Elena Y Komarova, Elena R Mikhaylova, Irina V Guzhova, Boris A Margulis
Massive neuronal death caused by a neurodegenerative pathology or damage due to ischaemia or traumatic brain injury leads to the appearance of cytosolic proteins in the extracellular space. We found that one of the most abundant cellular polypeptides, glyceraldehyde-3-phosphate dehydrogenase (GAPDH), appearing in the medium of dying cells or body fluids is able to form aggregates that are cytotoxic to adjacent cells. Since we previously showed that the hydrocortisone derivative RX624 can inhibit the ability of GAPDH to transport the enzyme complex with polyglutamine and reduce the cytotoxicity of the complex, we explored the effects of GAPDH on SH-SY5Y neuroblastoma cells...
May 16, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29777359/regulatory-mechanisms-of-thiol-based-redox-sensors-lessons-learned-from-structural-studies-on-prokaryotic-redox-sensors
#7
REVIEW
Sang Jae Lee, Dong-Gyun Kim, Kyu-Yeon Lee, Ji Sung Koo, Bong-Jin Lee
Oxidative stresses, such as reactive oxygen species, reactive electrophilic species, reactive nitrogen species, and reactive chlorine species, can damage cellular components, leading to cellular malfunction and death. In response to oxidative stress, bacteria have evolved redox-responsive sensors that enable them to simultaneously monitor and eradicate potential oxidative stress. Specifically, redox-sensing transcription regulators react to oxidative stress by means of modifying the thiol groups of cysteine residues, functioning as part of an efficient survival mechanism for many bacteria...
May 17, 2018: Archives of Pharmacal Research
https://www.readbyqxmd.com/read/29777138/shining-light-on-molecular-mechanism-for-odor-selectivity-of-cnt-immobilized-olfactory-receptor
#8
Liyun Zhang, Yuan Yuan, Tian Ren, Yanzhi Guo, Chuan Li, Xuemei Pu
Olfactory receptor (OR)-based bioelectronic nose is a new type of bio-affinity sensor applied for detecting numerous odorant molecules. In order to elucidate the effect of the adsorption of nanomaterial carriers on the receptor structure and its selectivity to odors, we used a systematic computation-scheme to study two OR models immobilized onto carbon nanotube. Our result indicates that there is a multistep OR-adsorption process driven by hydrophobic interaction. Many allosteric communication pathways exist between the absorbed residues and the pocket ones, leading to a significant shrinkage of the pocket...
May 18, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29775932/bond-length-equalization-with-molecular-aromaticity-a-new-measurement-of-aromaticity
#9
Chen-Fei Shen, Zi-Zhong Liu, Hong-Xia Liu, Hui-Qing Zhang
A new method to measure the amount of aromaticity is presented through the process of Bond Length Equalization (BLE). Degree of Aromaticity (DOA), a two-dimensional intensive quantity including geometric and energetic factors, as a new measurement of aromaticity is proposed. The unique characteristic of DOA and the formation of DOA will be displayed. The calculation of the geometrical optimization, DOA, Nucleus Independent Chemical Shifts (NICS) and Ring Stretching Vibration Raman Spectroscopy Frequency (RSVRSF) for the aromatic ring molecules - Gn Hn m (G = C, Si, Ge, n = 3, 5-8, m = +1, -1, 0, +1, +2) were calculated using the method of Density Functional Theory (DFT)...
May 8, 2018: Spectrochimica Acta. Part A, Molecular and Biomolecular Spectroscopy
https://www.readbyqxmd.com/read/29775896/dysregulated-network-of-mirnas-involved-in-the-pathogenesis-of-multiple-sclerosis
#10
REVIEW
Sanam Dolati, Faroogh Marofi, Zohreh Babaloo, Leili Aghebati-Maleki, Leila Roshangar, Majid Ahmadi, Reza Rikhtegar, Mehdi Yousefi
Multiple sclerosis (MS) is a chronic and organ-specific autoimmune disease in which immune cells act against the myelin sheath, resulting in central nervous system (CNS) damage. It has been revealed that miRNAs can play significant role in the pathogenesis of MS. These regulatory molecules lead to the activation of different signaling pathways, regulation of several transcriptional factors, influencing the differentiation of Th17 cells, development of Tregs and alteration from Th2 to Th1 response in MS. New studies have discovered that dysregulation of miRNAs may trigger abnormal immune responses leading consequently in the emergence of autoimmunity...
May 15, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29775788/complete-genome-sequence-of-achromobacter-spanius-type-strain-dsm-23806t-a-pathogen-isolated-from-human-blood
#11
Gengmi Li, Li Yang, Tao Zhang, Xiaojiao Guo, Jian Qin, Yingjiang Cao, Qianhua Yang, Shumei You, Guoliang Yuan, Xianqi Wan, Jing Luo, Zhaoxiang Li, Lei Gao, Ying Liu, Kaifeng Jiang, Jiakui Zheng
OBJECTIVES: Achromobacter spanius is a new described, non-fermenting Gram-negative and coccoid pathogen that isolated from patient blood. In order to investigate the pathogenesis of this strain in genomic level, whole genome sequencing was carried out on this strain. METHODS: In this study, complete genome of the type strain of this species DSM 23806T was sequenced using single-molecule real-time (SMRT) DNA sequencing. RESULTS: Complete genome of DSM 23806T consists of one circular DNA chromosome of 6,425,783bp with a GC content of 64...
May 15, 2018: Journal of Global Antimicrobial Resistance
https://www.readbyqxmd.com/read/29775613/suppression-of-nlrp3-inflammasome-attenuates-stress-induced-depression-like-behavior-in-nlgn3-deficient-mice
#12
Ze-Qun Li, Zhi-Yuan Yan, Bo-Jun Lan, Yi-Qun Dong, Ye Xiong
Depression, regulated by central nervous system (CNS), is a significant inflammatory disorder. Neuroligin3 (NLGN3) has been implicated in brain functions. In the study, a chronic unpredictable mild stress (CUMS) model in wild type (WT) or NLGN3-knockout (KO) mice was established to explore the role of NLGN3 in regulating depression and to reveal the underlying molecular mechanism. The results indicated that NLGN3-knockout markedly reversed the loss of body weight, the reduction of sucrose consumption, the decrease of immobile time in the forced swimming tests (FST) and tail suspension tests (TST) induced by CUMS paradigm...
May 15, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29775477/cryptococcus-neoformans-can-form-titan-like-cells-in-vitro-in-response-to-multiple-signals
#13
Nuria Trevijano-Contador, Haroldo Cesar de Oliveira, Rocío García-Rodas, Suélen Andreia Rossi, Irene Llorente, Ángel Zaballos, Guilhem Janbon, Joaquín Ariño, Óscar Zaragoza
Cryptococcus neoformans is an encapsulated pathogenic yeast that can change the size of the cells during infection. In particular, this process can occur by enlarging the size of the capsule without modifying the size of the cell body, or by increasing the diameter of the cell body, which is normally accompanied by an increase of the capsule too. This last process leads to the formation of cells of an abnormal enlarged size denominated titan cells. Previous works characterized titan cell formation during pulmonary infection but research on this topic has been hampered due to the difficulty to obtain them in vitro...
May 2018: PLoS Pathogens
https://www.readbyqxmd.com/read/29775295/noncovalent-grafting-of-a-dy-iii-2-single-molecule-magnet-onto-chemically-modified-multiwalled-carbon-nanotubes
#14
Vassilis Tangoulis, Nikolia Lalioti, John Parthenios, Nikos Boukos, Ondřej Malina, Jiří Tuček, Radek Zbořil
While synthetic methods for the grafting of nanoparticles or photoactive molecules onto carbon nanotubes (CNTs) have been developed in the last years, a very limited number of reports have appeared on the grafting of single-molecule magnets (SMMs) onto CNTs. There are many potential causes, mainly focused on the fact that the attachment of molecules on surfaces remains not trivial and their magnetic properties are significantly affected upon attachment. Nevertheless, implementation of this particular type of hybrid material in demanding fields such as spintronic devices makes of utmost importance the investigation of new synthetic protocols for effective grafting...
May 18, 2018: Inorganic Chemistry
https://www.readbyqxmd.com/read/29775273/the-role-of-clpp-protease-in-bacterial-pathogenesis-and-human-diseases
#15
Vaibhav Bhandari, Keith S Wong, Jin Lin Zhou, Mark F Mabanglo, Robert A Batey, Walid A Houry
In prokaryotic cells and eukaryotic organelles, the ClpP protease plays an important role in proteostasis. The disruption of ClpP function has been shown to influence the infectivity and virulence of a number of bacterial pathogens. More recently, ClpP has been found to be involved in various forms of carcinomas and in Perrault syndrome, which is an inherited condition characterized by hearing loss in males and females and by ovarian abnormalities in females. Hence, targeting ClpP is a potentially viable, attractive option for the treatment of different ailments...
May 18, 2018: ACS Chemical Biology
https://www.readbyqxmd.com/read/29775183/improving-the-mesoscopic-modeling-of-dna-denaturation-dynamics
#16
Marta Marty-Roda, Oda Dahlen, Titus Sebastiaan van Erp, Santiago Cuesta-López
Although previously developed mesoscopic DNA models have successfully
 reproduced thermodynamic denaturation data, recent studies show that these
 overestimate the rate of denaturation by orders of magnitude. Using adapted PeyrardBishop-Dauxois (PBD) models, we calculated the denaturation rates of several DNA
 hairpins and made comparison with experimental data. We show that the addition of
 a barrier at the onsite potential of the PBD model gives a more accurate description
 of the unzipping dynamics of short DNA sequences...
May 18, 2018: Physical Biology
https://www.readbyqxmd.com/read/29774990/searching-for-a-mitochondrial-root-to-the-decline-in-muscle-function-with-ageing
#17
EDITORIAL
Marta Gonzalez-Freire, Fatemeh Adelnia, Ruin Moaddel, Luigi Ferrucci
Sarcopenia, the age-related loss of muscle mass and strength, is linked to a range of adverse outcomes, such as impaired physical performance, cognitive function, and mortality. Preventing sarcopenia may reduce the burden of functional decline with aging and its impact on physiological and economic well-being in older adults. Mitochondria in muscle cells lose their intrinsic efficiency and capacity to produce energy during aging, and it has been hypothesized that such a decline is the main driver of sarcopenia...
May 18, 2018: Journal of Cachexia, Sarcopenia and Muscle
https://www.readbyqxmd.com/read/29774965/pd-catalyzed-consecutive-c-h-arylation-triggered-cyclotrimerization-synthesis-of-star-shaped-benzotristhiazoles-and-benzotrisoxazoles
#18
Zhanqiang Xu, Kazuaki Oniwa, Hiromasa Kikuchi, Ming Bao, Yoshinori Yamamoto, Tienan Jin, Masahiro Terada
Star-shaped π-extended molecules comprising discotic aromatic cores and peripheral π-conjugated arms have attracted significant attention as diverse optoelectronic materials in terms of their large π-surface, tunable self-assembly, enhanced charge transport and fluorescence, and liquid crystallinity. Although many efforts have been made in construction of various aromatic discotic cores, a new class of C3-symmetric star-shaped discotic π-molecules consisting of electron-deficient benzotristhiazole and benzotrisoxazole cores remains unexplored owing to the unachievable synthetic approaches, which are expected to exhibit distinct optoelectronic properties...
May 18, 2018: Chemistry: a European Journal
https://www.readbyqxmd.com/read/29774912/late-stage-modifications-of-p-containing-ligands-using-transition-metal-catalysed-c-h-bond-functionalisation
#19
Zhuan Zhang, Pierre H Dixneuf, Jean-François Soulé
Phosphorus containing molecules have seen widespread applications in the development of innovative metal-ligand catalysts and materials. In recent years, the implementation of late-stage modifications of phosphorus derivatives via ortho-regioselective C-H bond functionalisation has led to faster and better ways for the synthesis of complex ligands by creating new reactions with low impact on the environment. This Feature article highlights transition-metal catalysed regioselective C-H bond functionalisation of phosphorus-containing molecules, in which the phosphorus containing unit plays the role of a directing group for C-H bond activation and the synthesis of new functional phosphorus derivatives...
May 18, 2018: Chemical Communications: Chem Comm
https://www.readbyqxmd.com/read/29774640/regulatory-roles-of-flavonoids-on-inflammasome-activation-during-inflammatory-responses
#20
REVIEW
Young-Su Yi
Inflammation is an innate immune response to noxious stimuli to protect the body from pathogens and dangers. Inflammatory responses consist of two main steps: priming and triggering. In priming, inflammatory cells increase expressions of inflammatory molecules, while in triggering, inflammasomes are activated, resulting in cell death and pro-inflammatory cytokine secretion. Inflammasomes are protein complexes comprising intracellular pattern recognition receptors (PRRs) (e.g. nucleotide-binding oligomerization domain-like receptors (NLRs), absent in melanoma 2 (AIM2), and caspases-4/5/11) and pro-caspase-1 with or without a bipartite adaptor molecule ASC...
May 17, 2018: Molecular Nutrition & Food Research
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