Design of magnetic nanoparticles for hepatocellular carcinoma treatment using the control mechanisms of the cell internal nucleus and external membrane

2015 ◽  
Vol 3 (20) ◽  
pp. 4191-4204 ◽  
Author(s):  
Xiuyu Zhan ◽  
Yan-Qing Guan
Keyword(s):  
Hepatocellular Carcinoma ◽  
Magnetic Nanoparticles ◽  
Outer Membrane ◽  
Control Mechanisms ◽  
Molecular Control

This work is helpful for developing nanoparticle drugs that assure the molecular control of both the cell inner nucleus and outer membrane.

scholarly journals RhoA/ROCK pathway is the major molecular determinant of basal tone in intact human internal anal sphincter

2012 ◽  
Vol 302 (7) ◽  
pp. G664-G675 ◽  
Author(s):  
Satish Rattan ◽  
Jagmohan Singh
Keyword(s):  
Anal Sphincter ◽  
Internal Anal Sphincter ◽  
Control Mechanisms ◽  
Rock Inhibitor ◽  
Critical Determinant ◽  
Molecular Control ◽  
Motility Disorders ◽  
Basal Tone ◽  
Before And After ◽  
Rational Therapy

The knowledge of molecular control mechanisms underlying the basal tone in the intact human internal anal sphincter (IAS) is critical for the pathophysiology and rational therapy for a number of debilitating rectoanal motility disorders. We determined the role of RhoA/ROCK and PKC pathways by comparing the effects of ROCK- and PKC-selective inhibitors Y 27632 and Gö 6850 (10−8to 10−4M), respectively, on the basal tone in the IAS vs. the rectal smooth muscle (RSM). Western blot studies were performed to determine the levels of RhoA/ROCK II, PKC-α, MYPT1, CPI-17, and MLC20in the unphosphorylated and phosphorylated forms, in the IAS vs. RSM. Confocal microscopic studies validated the membrane distribution of ROCK II. Finally, to confirm a direct relationship, we examined the enzymatic activities and changes in the basal IAS tone and p-MYPT1, p-CPI-17, and p-MLC20, before and after Y 27632 and Gö 6850. Data show higher levels of RhoA/ROCK II and related downstream signal transduction proteins in the IAS vs. RSM. In addition, data show a significant correlation between the active RhoA/ROCK levels, ROCK enzymatic activity, downstream proteins, and basal IAS tone, before and after ROCK inhibitor. From these data we conclude 1) RhoA/ROCK and downstream signaling are constitutively active in the IAS, and this pathway (in contrast with PKC) is the critical determinant of the basal tone in intact human IAS; and 2) RhoA and ROCK are potential therapeutic targets for a number of rectoanal motility disorders for which currently there is no satisfactory treatment.

scholarly journals In Vivo Screening of Hepatocellular Carcinoma Using AC Susceptibility of Anti-Alpha Fetoprotein-Activated Magnetic Nanoparticles

PLoS ONE ◽  
2012 ◽  
Vol 7 (10) ◽  
pp. e46756 ◽  
Author(s):  
Jen-Jie Chieh ◽  
Kai-Wen Huang ◽  
Yang-De Lee ◽  
Herng-Er Horng ◽  
Hong-Chang Yang ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Magnetic Nanoparticles ◽  
Ac Susceptibility ◽  
Alpha Fetoprotein ◽  
In Vivo Screening

scholarly journals Role of SM22 in the differential regulation of phasic vs. tonic smooth muscle

2015 ◽  
Vol 308 (7) ◽  
pp. G605-G612 ◽  
Author(s):  
Satish Rattan ◽  
Mehboob Ali
Keyword(s):  
Smooth Muscle ◽  
Kinase Inhibitor ◽  
Smooth Muscles ◽  
Rho Kinase ◽  
Actin Binding ◽  
Control Mechanisms ◽  
Molecular Control ◽  
Tonic Smooth Muscle ◽  
Before And After ◽  
Protein Kinase C Inhibitor

Preliminary proteomics studies between tonic vs. phasic smooth muscles identified three distinct protein spots identified to be those of transgelin (SM22). The latter was found to be distinctly downregulated in the internal anal sphincter (IAS) vs. rectal smooth muscle (RSM) SMC. The major focus of the present studies was to examine the differential molecular control mechanisms by SM22 in the functionality of truly tonic smooth muscle of the IAS vs. the adjoining phasic smooth muscle of the RSM. We monitored SMC lengths before and after incubation with pFLAG-SM22 (for SM22 overexpression), and SM22 small-interfering RNA. pFLAG-SM22 caused concentration-dependent and significantly greater relaxation in the IAS vs. the RSM SMCs. Conversely, temporary silencing of SM22 caused contraction in both types of the SMCs. Further studies revealed a significant reverse relationship between the levels of SM22 phosphorylation and the amount of SM22-actin binding in the IAS and RSM SMC. Data showed higher phospho-SM22 levels and decreased SM22-actin binding in the IAS, and reverse to be the case in the RSM SMCs. Experiments determining the mechanism for SM22 phosphorylation in these smooth muscles revealed that Y-27632 (Rho kinase inhibitor) but not Gö-6850 (protein kinase C inhibitor) caused concentration-dependent decreased phosphorylation of SM22. We speculate that SM22 plays an important role in the regulation of basal tone via Rho kinase-induced phosphorylation of SM22.

Molecular control mechanisms of fish spermatogenesis

2003 ◽  
Vol 28 (1-4) ◽  
pp. 181-186 ◽  
Author(s):  
Takeshi Miura ◽  
Chiemi I. Miura
Keyword(s):  
Control Mechanisms ◽  
Molecular Control

Differences in the somatotropic axis, in blood cortisol, insulin and thyroid hormone concentrations between two pig genotypes with markedly divergent growth rates and the effects of growth hormone treatment

2002 ◽  
Vol 74 (3) ◽  
pp. 423-430 ◽  
Author(s):  
F. Elsaesser ◽  
M. W. Pfaffl ◽  
H. H. D. Meyer ◽  
B. Serpek ◽  
H. Sauerwein
Keyword(s):  
Growth Hormone ◽  
Live Weight ◽  
Maximum Level ◽  
Pulse Amplitude ◽  
Hormone Treatment ◽  
Pulse Frequency ◽  
Growth Potential ◽  
Control Mechanisms ◽  
Somatotropic Axis ◽  
Molecular Control

AbstractThe intention of the current study was to gain more insight into the endocrine and molecular control mechanisms of growth in the pig. For this purpose various growth related parameters were determined in 4-month-old barrows of two extreme pig genotyes, the small, obese Göttingen Miniature (GM) and the large and lean German Landrace (DL). Mean growth hormone (GH) concentration, GH pulse frequency and GH pulse amplitude did not differ between breeds. Likewise, plasma IGF-1, thyroxine, tri-iodothyronine (T3) concentrations were similar in both breeds. However the plasma GH response (maximum level and area under curve) to a single i.v. injection of GHRH in DL was higher than in GM (P < 0·05). Furthermore, basal plasma insulin and in particular plasma cortisol concentrations were higher in GM compared with DL pigs (P 0·05 and 0·01 respectively). Analysis of cortisol during 4-h frequent blood sampling indicated higher cortisol amplitudes in GM compared with DL (P ≤ 0·01). Specific bGH-binding to hepatic membrane preparations was not different between breeds and IGF-1 m RNA concentrations determined by reverse transcription-polymerase chain reaction in liver, m. semimenbranosus and m. longissimus dorsi were similar in both breeds. I.m. treatment with recombinant porcine somatotropin (rpST; 70 µg/kg live weight) over an 8-day period in contemporary barrows increased without any breed difference, plasma IGF-1, T3 and insulin concentrations and hepatic specific bGH-binding, but did not affect thyroxine or cortisol concentrations in plasma. IGF-1 gene expression was also elevated in liver and muscle tissues in rpST-treated animals without obvious breed effects. The observations underline the complexity of the hormonal and molecular control of growth and support the notion that differences in growth potential are the consequence of differences at various levels of the somatotropic axis and apparently relate to differences in other control systems of energy metabolism such as the pituitary adrenal axis or the endocrine pancreas as well.

scholarly journals BMP signalling differentially regulates distinct haematopoietic stem cell types

2015 ◽  
Vol 6 (1) ◽  
Author(s):  
Mihaela Crisan ◽  
Parham Solaimani Kartalaei ◽  
Chris S. Vink ◽  
Tomoko Yamada-Inagawa ◽  
Karine Bollerot ◽  
...  
Keyword(s):  
Stem Cell ◽  
Developmental Stages ◽  
Fetal Liver ◽  
Cell Lineage ◽  
Cell Types ◽  
Haematopoietic Stem Cell ◽  
Control Mechanisms ◽  
Molecular Control ◽  
Bmp Signalling ◽  
Insight Into

Abstract Adult haematopoiesis is the outcome of distinct haematopoietic stem cell (HSC) subtypes with self-renewable repopulating ability, but with different haematopoietic cell lineage outputs. The molecular basis for this heterogeneity is largely unknown. BMP signalling regulates HSCs as they are first generated in the aorta-gonad-mesonephros region, but at later developmental stages, its role in HSCs is controversial. Here we show that HSCs in murine fetal liver and the bone marrow are of two types that can be prospectively isolated—BMP activated and non-BMP activated. Clonal transplantation demonstrates that they have distinct haematopoietic lineage outputs. Moreover, the two HSC types differ in intrinsic genetic programs, thus supporting a role for the BMP signalling axis in the regulation of HSC heterogeneity and lineage output. Our findings provide insight into the molecular control mechanisms that define HSC types and have important implications for reprogramming cells to HSC fate and treatments targeting distinct HSC types.

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