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International Journal of Molecular Sciences

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https://www.readbyqxmd.com/read/29789517/fluorescent-proteins-for-investigating-biological-events-in-acidic-environments
#1
REVIEW
Hajime Shinoda, Michael Shannon, Takeharu Nagai
The interior lumen of acidic organelles (e.g., endosomes, secretory granules, lysosomes and plant vacuoles) is an important platform for modification, transport and degradation of biomolecules as well as signal transduction, which remains challenging to investigate using conventional fluorescent proteins (FPs). Due to the highly acidic luminal environment (pH ~ 4.5⁻6.0), most FPs and related sensors are apt to lose their fluorescence. To address the need to image in acidic environments, several research groups have developed acid-tolerant FPs in a wide color range...
May 23, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29789508/dual-effects-of-metformin-on-adipogenic-differentiation-of-3t3-l1-preadipocyte-in-ampk-dependent-and-independent-manners
#2
Dian Chen, Ying Wang, Kaikai Wu, Xingya Wang
Metformin has been reported to have body weight lowering effects while treating type 2 diabetes. However, limited studies examined the effects of metformin on adipogenesis in vitro, and available data are inconclusive and contradictory. In this study, we examined the effects of a variety of concentrations of metformin on adipocyte differentiation of 3T3-L1 preadipocytes and found metformin exhibits a dual effect on adipogenesis. Metformin at lower concentrations (1.25⁻2.5 mM) significantly induced adipogenesis while at higher concentrations (5⁻10 mM) metformin significantly inhibited adipogenesis in 3T3-L1 cells...
May 23, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29789502/detection-of-dystrophin-dp71-in-human-skeletal-muscle-using-an-automated-capillary-western-assay-system
#3
Tatsuya Kawaguchi, Emma Tabe Eko Niba, Abdul Qawee Mahyoob Rani, Yoshiyuki Onishi, Makoto Koizumi, Hiroyuki Awano, Masaaki Matsumoto, Masashi Nagai, Shinobu Yoshida, Sachiko Sakakibara, Naoyuki Maeda, Osamu Sato, Hisahide Nishio, Masafumi Matsuo
BACKGROUND: Dystrophin Dp71 is one of the isoforms produced by the DMD gene which is mutated in patients with Duchenne muscular dystrophy (DMD). Although Dp71 is expressed ubiquitously, it has not been detected in normal skeletal muscle. This study was performed to assess the expression of Dp71 in human skeletal muscle. METHODS: Human skeletal muscle RNA and tissues were obtained commercially. Mouse skeletal muscle was obtained from normal and DMDmdx mice. Dp71 mRNA and protein were determined by reverse-transcription PCR and an automated capillary Western assay system, the Simple Western, respectively...
May 23, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29789480/alterations-in-cellular-iron-metabolism-provide-more-therapeutic-opportunities-for-cancer
#4
REVIEW
Liangfu Zhou, Bin Zhao, Lixiu Zhang, Shenghang Wang, Dandan Dong, Huanhuan Lv, Peng Shang
Iron is an essential element for the growth and proliferation of cells. Cellular iron uptake, storage, utilization and export are tightly regulated to maintain iron homeostasis. However, cellular iron metabolism pathways are disturbed in most cancer cells. To maintain rapid growth and proliferation, cancer cells acquire large amounts of iron by altering expression of iron metabolism- related proteins. In this paper, normal cellular iron metabolism and the alterations of iron metabolic pathways in cancer cells were summarized...
May 22, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29789464/role-of-mtor-complexes-in-neurogenesis
#5
REVIEW
Francesca LiCausi, Nathaniel W Hartman
Dysregulation of neural stem cells (NSCs) is associated with several neurodevelopmental disorders, including epilepsy and autism spectrum disorder. The mammalian target of rapamycin (mTOR) integrates the intracellular signals to control cell growth, nutrient metabolism, and protein translation. mTOR regulates many functions in the development of the brain, such as proliferation, differentiation, migration, and dendrite formation. In addition, mTOR is important in synaptic formation and plasticity. Abnormalities in mTOR activity is linked with severe deficits in nervous system development, including tumors, autism, and seizures...
May 22, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29789460/frizzled-receptors-as-potential-therapeutic-targets-in-human-cancers
#6
REVIEW
Chui-Mian Zeng, Zhe Chen, Li Fu
Frizzled receptors (FZDs) are a family of seven-span transmembrane receptors with hallmarks of G protein-coupled receptors (GPCRs) that serve as receptors for secreted Wingless-type (WNT) ligands in the WNT signaling pathway. Functionally, FZDs play crucial roles in regulating cell polarity, embryonic development, cell proliferation, formation of neural synapses, and many other processes in developing and adult organisms. In this review, we will introduce the basic structural features and review the biological function and mechanism of FZDs in the progression of human cancers, followed by an analysis of clinical relevance and therapeutic potential of FZDs...
May 22, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29786669/protein-tyrosine-phosphatase-1b-inhibition-and-glucose-uptake-potentials-of-mulberrofuran-g-albanol-b-and-kuwanon-g-from-root-bark-of-morus-alba-l-in-insulin-resistant-hepg2-cells-an-in-vitro-and-in-silico-study
#7
Pradeep Paudel, Ting Yu, Su Hui Seong, Eun Bi Kuk, Hyun Ah Jung, Jae Sue Choi
Type II diabetes mellitus (T2DM) is the most common form of diabetes and has become a major health problem across the world. The root bark of Morus alba L. is widely used in Traditional Chinese Medicine for treatment and management of diabetes. The aim of the present study was to evaluate the enzyme inhibitory potentials of three principle components, mulberrofuran G ( 1 ), albanol B ( 2 ), and kuwanon G ( 3 ) in M. alba root bark against diabetes, establish their enzyme kinetics, carry out a molecular docking simulation, and demonstrate the glucose uptake activity in insulin-resistant HepG2 cells...
May 22, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29786668/scf-c-kit-signaling-increased-mucin2-production-by-maintaining-atoh1-expression-in-mucinous-colorectal-adenocarcinoma
#8
Ping Shen, Shu Yang, Haimei Sun, Guilan Li, Bo Wu, Fengqing Ji, Tingyi Sun, Deshan Zhou
Mucinous colorectal adenocarcinoma (MCA) patients often a show high risk of malignant potential and a poorer survival rate. Given that the pathological feature and oncobiological characteristics of MCA are correlated with its abundant extracellular mucin2 (MUC2), we paid interest toward investigating the key factor that promotes MUC2 production exposure to highly-activated stem cell factor (SCF)/c-KIT signaling, which we believed to contribute to MCA formation. Long-term azoxymethane and dextran sodium sulfate treatment successfully induced MCA only in wild-type (WT) mice at week 37 and 43, while all c-kit loss-of-function mutant mice (Wadsm/m ) developed non-MCA...
May 22, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29786666/dopamine-receptor-subtypes-differentially-regulate-autophagy
#9
Dongmei Wang, Xinmiao Ji, Juanjuan Liu, Zhiyuan Li, Xin Zhang
Some dopamine receptor subtypes were reported to participate in autophagy regulation, but their exact functions and mechanisms are still unclear. Here we found that dopamine receptors D2 and D3 (D2-like family) are positive regulators of autophagy, while dopamine receptors D1 and D5 (D1-like family) are negative regulators. Furthermore, dopamine and ammonia, the two reported endogenous ligands of dopamine receptors, both can induce dopamine receptor internalization and degradation. In addition, we found that AKT (protein kinase B)-mTOR (mechanistic target of rapamycin) and AMPK (AMP-activated protein kinase) pathways are involved in DRD3 (dopamine receptor D3) regulated autophagy...
May 22, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29786658/melatonin-as-a-therapy-for-traumatic-brain-injury-a-review-of-published-evidence
#10
REVIEW
Nicole Osier, Emily McGreevy, Lan Pham, Ava Puccio, Dianxu Ren, Yvette P Conley, Sheila Alexander, C Edward Dixon
Melatonin (MEL) is a hormone that is produced in the brain and is known to bind to MEL-specific receptors on neuronal membranes in several brain regions. MEL's documented neuroprotective properties, low toxicity, and ability to cross the blood-brain-barrier have led to its evaluation for patients with traumatic brain injury (TBI), a condition for which there are currently no Food and Drug Administration (FDA)-approved therapies. The purpose of this manuscript is to summarize the evidence surrounding the use of melatonin after TBI, as well as identify existing gaps and future directions...
May 22, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29786656/temperature-effects-on-force-and-actin%C3%A2-myosin-interaction-in-muscle-a-look-back-on-some-experimental-findings
#11
REVIEW
K W Ranatunga
Observations made in temperature studies on mammalian muscle during force development, shortening, and lengthening, are re-examined. The isometric force in active muscle goes up substantially on warming from less than 10 °C to temperatures closer to physiological (>30 °C), and the sigmoidal temperature dependence of this force has a half-maximum at ~10 °C. During steady shortening, when force is decreased to a steady level, the sigmoidal curve is more pronounced and shifted to higher temperatures, whereas, in lengthening muscle, the curve is shifted to lower temperatures, and there is a less marked increase with temperature...
May 22, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29786653/role-for-cystathionine-%C3%AE-lyase-cse-in-an-ethanol-e-induced-lesion-in-fetal-brain-gsh-homeostasis
#12
Dhyanesh Patel, Marylatha Rathinam, Courtney Jarvis, Lenin Mahimainathan, George Henderson, Madhusudhanan Narasimhan
Earlier, we reported that gestational ethanol (E) can dysregulate neuron glutathione (GSH) homeostasis partially via impairing the EAAC1-mediated inward transport of Cysteine (Cys) and this can affect fetal brain development. In this study, we investigated if there is a role for the transulfuration pathway (TSP), a critical bio-synthetic point to supply Cys in E-induced dysregulation of GSH homeostasis. These studies utilized an in utero E binge model where the pregnant Sprague⁻Dawley (SD) rat dams received five doses of E at 3...
May 22, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29786649/kudzu-leaf-extract-suppresses-the-production-of-inducible-nitric-oxide-synthase-cyclooxygenase-2-tumor-necrosis-factor-alpha-and-interleukin-6-via-inhibition-of-jnk-tbk1-and-stat1-in-inflammatory-macrophages
#13
Seok Hyun Eom, So-Jung Jin, Hee-Yeong Jeong, Youngju Song, You Jin Lim, Jong-In Kim, Youn-Hyung Lee, Hee Kang
Kudzu ( Pueraria montana var. lobata (Willd.) Sanjappa & Pradeep) is a perennial leguminous vine, and its root and flower have been used for herbal medicine in Asia for a long time. Most dietary flavonoids are reported to be concentrated in its root, not in its aerial parts including leaves. In this study, we investigated whether kudzu leaf and its major constituent, robinin (kaempferol-3- O -robinoside-7- O -rhanmoside) possessed anti-inflammatory activity. To test this hypothesis, we used peritoneal macrophages isolated from BALB/c mice and stimulated the cells with lipopolysaccharide (LPS) or LPS plus interferon (IFN)-γ...
May 22, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29786646/metabolic-reprogramming-by-3-iodothyronamine-t1am-a-new-perspective-to-reverse-obesity-through-co-regulation-of-sirtuin-4-and-6-expression
#14
Fariba M Assadi-Porter, Hannah Reiland, Martina Sabatini, Leonardo Lorenzini, Vittoria Carnicelli, Micheal Rogowski, Ebru S Selen Alpergin, Marco Tonelli, Sandra Ghelardoni, Alessandro Saba, Riccardo Zucchi, Grazia Chiellini
Obesity is a complex disease associated with environmental and genetic factors. 3-Iodothyronamine (T1AM) has revealed great potential as an effective weight loss drug. We used metabolomics and associated transcriptional gene and protein expression analysis to investigate the tissue specific metabolic reprogramming effects of subchronic T1AM treatment at two pharmacological daily doses (10 and 25 mg/kg) on targeted metabolic pathways. Multi-analytical results indicated that T1AM at 25 mg/kg can act as a novel master regulator of both glucose and lipid metabolism in mice through sirtuin-mediated pathways...
May 22, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29786645/skeletal-muscle-micrornas-as-key-players-in-the-pathogenesis-of-amyotrophic-lateral-sclerosis
#15
REVIEW
Lorena Di Pietro, Wanda Lattanzi, Camilla Bernardini
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder, for which, to date, no effective treatment to ameliorate the clinical manifestations is available. The long-standing view of ALS as affecting only motor neurons has been challenged by the finding that the skeletal muscle plays an active role in the disease pathogenesis and can be a valuable target for therapeutic strategies. In recent years, non-coding RNAs, including microRNAs, have emerged as important molecules that play key roles in several cellular mechanisms involved in the pathogenic mechanisms underlying various human conditions...
May 22, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29786644/impact-of-bone-fracture-on-ischemic-stroke-recovery
#16
REVIEW
Meng Wei, Haiyian Lyu, Kang Huo, Hua Su
Stroke is one of the most devastating complications of bone fracture, occurring in up to 4% of patients after surgical repair for hip fracture. Bone fracture and ischemic stroke have many common risk factors. The impact of bone fracture on stroke recovery has not drawn much attention in the research field. Bone fracture could occur in stroke patients at different times during the recovery phase, which steepens the trajectory of cognitive decline, greatly affects the quality of life, and causes a heavy burden on healthcare resources...
May 22, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29783779/hyperoxia-disrupts-extracellular-signal-regulated-kinases-1-2-induced-angiogenesis-in-the-developing-lungs
#17
Renuka T Menon, Amrit Kumar Shrestha, Roberto Barrios, Binoy Shivanna
Hyperoxia contributes to the pathogenesis of bronchopulmonary dysplasia (BPD), a chronic lung disease of infants that is characterized by interrupted alveologenesis. Disrupted angiogenesis inhibits alveologenesis, but the mechanisms of disrupted angiogenesis in the developing lungs are poorly understood. In pre-clinical BPD models, hyperoxia increases the expression of extracellular signal-regulated kinases (ERK) 1/2; however, its effects on the lung endothelial ERK1/2 signaling are unclear. Further, whether ERK1/2 activation promotes lung angiogenesis in infants is unknown...
May 20, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29783777/preferential-inhibition-of-wnt-%C3%AE-catenin-signaling-by-novel-benzimidazole-compounds-in-triple-negative-breast-cancer
#18
Abhishek Gangrade, Vibha Pathak, Corinne E Augelli-Szafran, Han-Xun Wei, Patsy Oliver, Mark Suto, Donald J Buchsbaum
Wnt/β-catenin signaling is upregulated in triple-negative breast cancer (TNBC) compared to other breast cancer subtypes and normal tissues. Current Wnt/β-catenin inhibitors, such as niclosamide, target the pathway nonspecifically and exhibit poor pharmacokinetics/pharmacodynamics in vivo. Niclosamide targets other pathways, including mTOR, STAT3 and Notch. Novel benzimidazoles have been developed to inhibit Wnt/β-catenin signaling with greater specificity. The compounds SRI33576 and SRI35889 were discovered to produce more cytotoxicity in TNBC cell lines than in noncancerous cells...
May 20, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29783748/neuronal-dysfunction-associated-with-cholesterol-deregulation
#19
Annalisa Marcuzzi, Claudia Loganes, Erica Valencic, Elisa Piscianz, Lorenzo Monasta, Sabrine Bilel, Roberta Bortul, Claudio Celeghini, Marina Zweyer, Alberto Tommasini
Cholesterol metabolism is crucial for cells and, in particular, its biosynthesis in the central nervous system occurs in situ, and its deregulation involves morphological changes that cause functional variations and trigger programmed cell death. The pathogenesis of rare diseases, such as Mevalonate Kinase Deficiency or Smith⁻Lemli⁻Opitz Syndrome, arises due to enzymatic defects in the cholesterol metabolic pathways, resulting in a shortage of downstream products. The most severe clinical manifestations of these diseases appear as neurological defects...
May 19, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29783744/interplay-between-er-ca-2-binding-proteins-stim1-and-stim2-is-required-for-store-operated-ca-2-entry
#20
Heather A Nelson, Colin A Leech, Richard F Kopp, Michael W Roe
Store-operated calcium entry (SOCE), a fundamentally important homeostatic and Ca2+ signaling pathway in many types of cells, is activated by the direct interaction of stromal interaction molecule 1 (STIM1), an endoplasmic reticulum (ER) Ca2+ -binding protein, with Ca2+ -selective Orai1 channels localized in the plasma membrane. While much is known about the regulation of SOCE by STIM1, the role of stromal interaction molecule 2 (STIM2) in SOCE remains incompletely understood. Here, using clustered regularly interspaced short palindromic repeats -CRISPR associated protein 9 (CRISPR-Cas9) genomic editing and molecular imaging, we investigated the function of STIM2 in NIH 3T3 fibroblast and αT3 cell SOCE...
May 19, 2018: International Journal of Molecular Sciences
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