Induction of Accommodation Model by Combined RNA Interference Targeting 1,3-Galactosyltransferase Gene and Low-Dose GS-IB4 Lectin In Vitro

2006 ◽  
Vol 38 (10) ◽  
pp. 3193-3195 ◽  
Author(s):  
M. Zhu ◽  
G. Chen ◽  
D. Chen ◽  
H.G. Qi ◽  
Z.X. Xia ◽  
...  
Keyword(s):  
Rna Interference ◽  
Low Dose

Ciamexon in low-dose streptozotocin induced diabetes mellitus. In vivo and in vitro studies

1986 ◽  
Vol 113 (1_Suppl) ◽  
pp. S120-S121
Author(s):  
TH. LINN ◽  
H. GERMANN ◽  
B. HERING ◽  
R. BRETZEL ◽  
K. FEDERLIN
Keyword(s):  
Diabetes Mellitus ◽  
Low Dose ◽  
In Vitro Studies ◽  
Streptozotocin Induced Diabetes

RNA interference and its clinical applications

2007 ◽  
Vol 148 (47) ◽  
pp. 2235-2240 ◽  
Author(s):  
Gyöngyi Munkácsy ◽  
Zsolt Tulassay ◽  
Balázs Győrffy
Keyword(s):  
Rna Interference ◽  
Clinical Applications

Az RNS-interferencia a poszttranszkripciós génelcsendesítés olyan formája, amelynek során rövid, specifikusan RNS-molekulák elnyomják a gének kifejeződésében kulcsszerepet játszó hírvivő RNS-ek működését. A sejtbe juttatott dupla szálú vagy rövid interferáló RNS-molekulák aktiválják az RNS-indukált elcsendesítő komplexet, amely a célgén hírvivő RNS-ét lebontja. A sejtek saját szabályozó mikro-RNS-molekulákkal is rendelkeznek, amelyeknek hírvivő RNS-e képes önmagával hajtűt képezni, amit a sejt dupla szálú RNS-ként értelmez. Az RNS-interferencia élettani működései közé tartozik a vírusok és a transzpozonok elleni védekezés, valamint a génkifejeződés szabályozása. Az RNS-interferencia nemcsak in vitro alkalmazható az egyes gének működésének vizsgálatára, hanem klinikai alkalmazásainak lehetőségei is megjelentek. Eddig vírusfertőzésekben, az időskori makuladegeneráció gátlására, a vér koleszterinszint-csökkentésére, daganatellenes és neurodegeneratív betegségek kezelésében alkalmazták. Az RNS-interferencia alkalmazását azonban nehezíti, hogy a megfelelő rövid interferáló RNS-molekulák tervezéséhez szükséges bioinformatikai algoritmusok nem tökéletesek; a szervezet szöveteibe való bejuttatásuk nehéz; illetve csak olyan esetekben alkalmazható, amelyekben átmeneti antagonista génelcsendesítő hatás és nem hosszú távú kezelés szükséges. Az alkalmazás legnagyobb előnye a jelentős specificitás, ami miatt mellékhatása is kevés. Az RNS-interferencia alapú kezelések megjelenése már a közeli jövőben várható.

Bioactive Peptides Sensitize Cells to Anticancer Effects of Oxaliplatin in Human Colorectal Cancer Xenografts in Nude Mice

2019 ◽  
Vol 26 (7) ◽  
pp. 512-522
Author(s):  
Xian Li ◽  
Long Xia ◽  
Xiaohui Ouyang ◽  
Qimuge Suyila ◽  
Liya Su ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Colorectal Cancer ◽  
Nude Mice ◽  
Low Dose ◽  
Bioactive Peptides ◽  
Human Colorectal Cancer ◽  
Short Term ◽  
Hct 116

<P>Background: Despite new agent development and short-term benefits in patients with Colorectal Cancer (CRC), metastatic CRC cure rates have not improved due to high rates of oxaliplatin resistance and toxicity. There is an urgent need for effective tools to prevent and treat CRC and reduce morbidity and mortality of CRC patients. Exploring the effects of bioactive peptides on the antitumor to CRC was of vital importance to the clinical application. </P><P> Objective: This study aimed to investigate the therapeutic impact of Anticancer Bioactive Peptides (ACBP) on anticancer effect of oxaliplatin (LOHP) in human colorectal cancer xenografts models in nude mice. </P><P> Methods: HCT-116 cells were cultured in vitro via CCK-8 assays and the absorbance was measured at 450 nm. Apoptosis and cell cycle were assessed by Flow Cytometry (FCM) in vitro. HCT-116 human colorectal cancer cells inoculated subcutaneously in nude mice of treatment with PBS (GG), ACBP, LOHP, ACBP+LOHP (A+L) in vivo. The quality of life was assessed by dietary amount of nude mice, the weight of nude mice, inhibition rates, tumor weight and tumor volume. Immunohistochemistry and RT-qPCR method was conducted to determine the levels of apoptosisregulating proteins/genes in transplanted tumors. </P><P> Results: ACBP induced substantial reductions in viable cell numbers and apoptosis of HCT116 cells in combined with LOHP in vitro. Compared with the control GG group, ACBP combined low dose oxaliplatin (U) group demonstrated significantly different tumor volume, the rate of apoptosis, the expression levels of Cyt-C, caspase-3,8,9 proteins and corresponding RNAs (P<0.05). The expression of pro-apoptotic proteins in the cytoplasm around the nucleus was significantly enhanced by ACBP. Short term intermittent use of ACBP alone indicted a certain inhibitory effect on tumor growth, and improve the quality of life of tumor bearing nude mice. </P><P> Conclusion: ACBP significantly increased the anti-cancer responses of low dose oxaliplatin (L-LOHP), thus, significantly improving the quality of life of tumor-bearing nude mice.</P>

scholarly journals Newly Developed Recombinant Antithrombin Protects the Endothelial Glycocalyx in an Endotoxin-Induced Rat Model of Sepsis

2020 ◽  
Vol 22 (1) ◽  
pp. 176
Author(s):  
Toshiaki Iba ◽  
Jerrold H. Levy ◽  
Koichiro Aihara ◽  
Katsuhiko Kadota ◽  
Hiroshi Tanaka ◽  
...  
Keyword(s):  
Dose Group ◽  
Low Dose ◽  
Leukocyte Adhesion ◽  
Endothelial Glycocalyx ◽  
High Dose Group ◽  
Control Group ◽  
High Dose ◽  
Protective Effects ◽  
Circulating Levels

(1) Background: The endothelial glycocalyx is a primary target during the early phase of sepsis. We previously reported a newly developed recombinant non-fucosylated antithrombin has protective effects in vitro. We further evaluated the effects of this recombinant antithrombin on the glycocalyx damage in an animal model of sepsis. (2) Methods: Following endotoxin injection, in Wistar rats, circulating levels of hyaluronan, syndecan-1 and other biomarkers were evaluated in low-dose or high-dose recombinant antithrombin-treated animals and a control group (n = 7 per group). Leukocyte adhesion and blood flow were evaluated with intravital microscopy. The glycocalyx was also examined using side-stream dark-field imaging. (3) Results: The activation of coagulation was inhibited by recombinant antithrombin, leukocyte adhesion was significantly decreased, and flow was better maintained in the high-dose group (both p < 0.05). Circulating levels of syndecan-1 (p < 0.01, high-dose group) and hyaluronan (p < 0.05, low-dose group; p < 0.01, high-dose group) were significantly reduced by recombinant antithrombin treatment. Increases in lactate and decreases in albumin levels were significantly attenuated in the high-dose group (p < 0.05, respectively). The glycocalyx thickness was reduced over time in control animals, but the derangement was attenuated and microvascular perfusion was better maintained in the high-dose group recombinant antithrombin group (p < 0.05). (4) Conclusions: Recombinant antithrombin maintained vascular integrity and the microcirculation by preserving the glycocalyx in this sepsis model, effects that were more prominent with high-dose therapy.

Effect of hypothalamic neuropeptides on corticotrophin release from quarters of rat anterior pituitary gland in vitro

1984 ◽  
Vol 100 (2) ◽  
pp. 219-226 ◽  
Author(s):  
S. A. Nicholson ◽  
T. E. Adrian ◽  
B. Gillham ◽  
M. T. Jones ◽  
S. R. Bloom
Keyword(s):  
Pituitary Gland ◽  
Anterior Pituitary ◽  
Low Dose ◽  
Physiological Role ◽  
Anterior Pituitary Gland ◽  
High Concentration ◽  
Response Curves ◽  
Corticotrophin Releasing Factor ◽  
Basal Release

ABSTRACT The effect of six hypothalamic peptides on the basal release of ACTH and that induced by arginine vasopressin (AVP) or by ovine corticotrophin releasing factor (oCRF) from fragments of the rat anterior pituitary gland incubated in vitro was investigated. Dose–response curves to AVP and to oCRF were obtained, and the response to a low dose of oCRF was potentiated by a low dose of AVP. Basal release of ACTH was not affected by any of the peptides in concentrations in the range 10−12 to 10−6 mol/l, and only substance P (SP) and somatostatin (SRIF) inhibited significantly the response to oCRF in a dose-related manner. The responses to a range of doses of oCRF or AVP were reduced by 10−8 and 10 − 6 mol SP or SRIF/1, and to a greater extent by the higher dose. Except in the case of 10−6 mol SRIF/1 on the response to AVP, the response was not further diminished by preincubation of the tissue with the peptide before the stimulating agent was added. The inhibition of the responses to AVP or oCRF by 10−9 mol SP/1 was not potentiated by its combination with either 5 × 10−10 or 10−8 mol SRIF/1; the inhibitory effects were merely additive. The results suggest that although SRIF and SP are able to modulate the release of ACTH from the anterior pituitary gland, they do so only at a high concentration. In the case of SRIF these concentrations are several orders of magnitude higher than those reported to be present in the hypophysial portal blood and therefore a physiological role for this peptide in the control of ACTH secretion is unlikely. J. Endocr. (1984) 100, 219–226

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