scholarly journals Harmine and Harmaline Downregulate TCDD-Induced Cyp1a1 in the Livers and Lungs of C57BL/6 Mice

2013 ◽  
Vol 2013 ◽  
pp. 1-9 ◽  
Author(s):  
Mohamed A. M. El Gendy ◽  
Ayman O. S. El-Kadi
Keyword(s):  
Activity Levels ◽  
Male Mice ◽  
Peganum Harmala ◽  
Promising Candidate ◽  
Active Constituents ◽  
The Third ◽  
Extrahepatic Tissues ◽  
Cyp1a1 Mrna

We previously demonstrated thatPeganum harmalaL. extract and its main active constituents, harmine and harmaline inhibit the 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-mediated induction of the carcinogen-activating enzyme, Cyp1a1,in vitro. However, the effect of both alkaloids on Cyp1a1in vivohas not been investigated. Therefore, the aim of this study is to examine the effect of harmine and harmaline on TCDD-mediated induction of Cyp1a1 in mice livers and lungs. C57BL/6 male mice were distributed into four groups (n=6). First group received vehicle, while the second group received TCDD (i.p.). The third and fourth groups received either harmine or harmaline (i.p.) × 3 times along with TCDD one time with the mid dose of harmine and harmaline. All mice were sacrificed after 14 h from TCDD injection, and livers and lungs were isolated. The effect of harmine and harmaline on TCDD-mediated induction of Cyp1a1 mRNA, protein, and activity levels was determined using real-time PCR, Western blot analysis, and 7-ethoxyresurofin as a substrate, respectively. Our results showed that harmine and harmaline significantly decreased the TCDD-mediated induction of Cyp1a1 in both the livers and lungs. We concluded that harmine and harmaline are promising candidate to inhibit TCDD-mediated induction of Cyp1a1 in mice hepatic and extrahepatic tissues.

scholarly journals Identification of the Active Ingredient and Beneficial Effects of Vitex rotundifolia Fruits on Menopausal Symptoms in Ovariectomized Rats

Biomolecules ◽  
2021 ◽  
Vol 11 (7) ◽  
pp. 1033
Author(s):  
Ji Hwan Lee ◽  
Sullim Lee ◽  
Quynh Nhu Nguyen ◽  
Hung Manh Phung ◽  
Myoung-Sook Shin ◽  
...  
Keyword(s):  
Weight Gain ◽  
Body Weight Gain ◽  
Animal Experiments ◽  
Ovariectomized Rats ◽  
Biological Functions ◽  
Menopausal Syndrome ◽  
Active Constituents ◽  
Mcf 7

Estrogen replacement therapy is a treatment to relieve the symptoms of menopause. Many studies suggest that natural bioactive ingredients from plants resemble estrogen in structure and biological functions and can relieve symptoms of menopause. The fruit of V. rotundifolia, called “Man HyungJa” in Korean, is a traditional medicine used to treat headache, migraine, eye pain, neuralgia, and premenstrual syndrome in Korea and China. The aim of the present study was to confirm that V. rotundifolia fruit extract (VFE) exerts biological functions similar to those of estrogen in menopausal syndrome. We investigated its in vitro effects on MCF-7 cells and in vivo estrogen-like effects on weight gain and uterine contraction in ovariectomized rats. Using the polar extract, the active constituents of VFE (artemetin, vitexicarpin, hesperidin, luteolin, vitexin, and vanillic acid) with estrogen-like activity were identified in MCF-7 cells. In animal experiments, the efficacy of VFE in ameliorating body weight gain was similar to that of estrogen, as evidenced from improvements in uterine atrophy. Vitexin and vitexicarpin are suggested as the active constituents of V. rotundifolia fruits.

scholarly journals Bone marrow mesenchymal stem cells promote prostate cancer cell stemness via cell–cell contact to activate the Jagged1/Notch1 pathway

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Ji-wen Cheng ◽  
Li-xia Duan ◽  
Yang Yu ◽  
Pu Wang ◽  
Jia-le Feng ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Western Blot ◽  
Cell Contact ◽  
Activity Levels ◽  
Tumor Resistance ◽  
Cell Cell

Abstract Background Mesenchymal stem cells (MSCs) play a crucial role in cancer development and tumor resistance to therapy in prostate cancer, but the influence of MSCs on the stemness potential of PCa cells by cell–cell contact remains unclear. In this study, we investigated the effect of direct contact of PCa cells with MSCs on the stemness of PCa and its mechanisms. Methods First, the flow cytometry, colony formation, and sphere formation were performed to determine the stemness of PCaMSCs, and the expression of stemness-related molecules (Sox2, Oct4, and Nanog) was investigated by western blot analysis. Then, we used western blot and qPCR to determine the activity levels of two candidate pathways and their downstream stemness-associated pathway. Finally, we verified the role of the significantly changed pathway by assessing the key factors in this pathway via in vitro and in vivo experiments. Results We established that MSCs promoted the stemness of PCa cells by cell–cell contact. We here established that the enhanced stemness of PCaMSCs was independent of the CCL5/CCR5 pathway. We also found that PCaMSCs up-regulated the expression of Notch signaling-related genes, and inhibition of Jagged1-Notch1 signaling in PCaMSCs cells significantly inhibited MSCs-induced stemness and tumorigenesis in vitro and in vivo. Conclusions Our results reveal a novel interaction between MSCs and PCa cells in promoting tumorigenesis through activation of the Jagged1/Notch1 pathway, providing a new therapeutic target for the treatment of PCa.

IgG modulation in male mice with reproductive failure after prenatal inflammation

Reproduction ◽  
2021 ◽  
Author(s):  
Marina Izvolskaia ◽  
Vasilina Ignatiuk ◽  
Ayshat Ismailova ◽  
Viktoria Sharova ◽  
Liudmila Zakharova
Keyword(s):  
Positive Impact ◽  
Brain Structures ◽  
Peritoneal Macrophages ◽  
The Body ◽  
Male Rats ◽  
Male Mice ◽  
Prenatal Inflammation ◽  
Exposure In Vivo

Sexual performance in adult male rats is highly sensitive to prenatal stress which can affect the functionality of the reproductive system and various brain structures involved in modulating sexual behavior. The immunomodulatory effect of mouse IgG on reproductive maturity in male offspring after LPS exposure in vivo and in vitro was studied. Prenatal IgG injection (20 µg / mouse) had a positive impact on the puberty of male mice whose mothers were exposed to LPS (100 µg / kg) on the 12th day of pregnancy. The number of Sertoli cells were increased, whereas the body weight and the number of symplastic spermatids were decreased in offspring as compared to LPS-treated animals. Besides, IgG had a positive effect on altered hormone levels: reduced estradiol level on the 5th and 14th postnatal days and increased testosterone level on the 30th postnatal day in blood that led to an increased number of mounting attempts in sexually mature males. The cAMP-dependent pathway may be involved in the regulation of the LPS-induced inflammation. IgG reduced the increased level of cAMP in mouse peritoneal macrophages activated by LPS in vitro. IgG is able to modulate inflammation processes, but its exposure time is important.

scholarly journals Preclinical Pharmacokinetics of C118P, a Novel Prodrug of Microtubules Inhibitor and Its Metabolite C118 in Mice, Rats, and Dogs

Molecules ◽  
2018 ◽  
Vol 23 (11) ◽  
pp. 2883 ◽  
Author(s):  
Cang Zhang ◽  
Xiaolan Zhang ◽  
Guangji Wang ◽  
Ying Peng ◽  
Xueyuan Zhang ◽  
...  
Keyword(s):  
Clinical Development ◽  
High Dose ◽  
Protein Inhibitor ◽  
Promising Candidate ◽  
Preclinical Pharmacokinetics ◽  
Tumor Bearing ◽  
Microtubule Protein ◽  
Further Development

C118P, a phosphate prodrug of C118, which is a novel microtubule protein inhibitor, is currently under Phase I clinical development in China for treating ovarian cancer and lung cancer. The preclinical pharmacokinetics of prodrug C118P and its metabolite C118 were extensively characterized in vivo in mice, rats, and dogs and in vitro to support the further development of C118P. The preclinical tissue distribution and excretion were investigated in rats. Plasma protein binding in mice, rat, and human, and hepatic microsomal metabolic stability in mice, rat, dog, monkey, and human, were also evaluated. The (AUC0-inf) and C30s of C118P at 50 mg/kg in rats and 6 mg/kg in dogs, and the C2min of C118 at 6 mg/kg in dogs increased less than the dosage increase, suggested nonlinear pharmacokinetic occurred at high dose. As a prodrug, C118P can be quickly hydrolyzed into C118 after an intravenous administration. The unbound C118 in plasma is slightly higher than C118P. C118P can hardly penetrate the tissue, while C118 can distribute widely into tissues. In tumor-bearing nude mice, the concentration of C118 is high in lung, ovary, and tumor, with an extended half-life in tumor. C118P is a promising candidate prodrug for further clinical development.

Development and differentiation in vitro of Drosophila imaginal disc cells from dissociated early embryos

Development ◽  
1975 ◽  
Vol 33 (2) ◽  
pp. 487-498
Author(s):  
Andreas Dübendorfer ◽  
Glen Shields ◽  
James H. Sang
Keyword(s):  
Imaginal Disc ◽  
Larval Instar ◽  
Cell Types ◽  
The Third ◽  
Early Embryos ◽  
Disc Cells ◽  
Development And Differentiation ◽  
Pattern Specification

Embryos of Drosophila melanogaster, 6–8 h after oviposition, were dissociated and the cells cultured in vitro. Besides larval cell types, imaginal disc cells, assembled and growing in bloated monolayered vesicles, were obtained. The cells of these vesicles become competent to differentiate adult structures when treated with α-ecdysone or ecdysterone in vitro. Recognizable patterns of the adult fly are not formed though. If metamorphosis of imaginal cell vesicles from in vitro-cultures is induced in vivo by transplantation into host larvae of various ages within the third larval instar, recognizable patterns can differentiate provided the host larva does not metamorphose prior to 2 days after transplantation. The frequency of specific patterns in the implants can be increased by providing 9 days of culture in vivo (adult host flies) before metamorphosis. Passage through the third larval instar is not essential for these cells to produce identifiable patterns since culture in adult flies alone can achieve this. The quality of the differentiated pattern is not correlated with the extent of cell proliferation in the cultured tissues. The problem of pattern specification in vitro and in vivo is discussed.

Glutathione-responsive PLGA nanocomplex for dual delivery of doxorubicin and curcumin to overcome tumor multidrug resistance

Nanomedicine ◽  
2021 ◽  
Author(s):  
Xuandi Lai ◽  
Xinran Geng ◽  
Mengqing Li ◽  
Mengxiong Tang ◽  
Qiong Liu ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Multidrug Resistance ◽  
Blood Circulation ◽  
Release Profile ◽  
Drug Release Profile ◽  
Promising Candidate ◽  
Nano Drug Delivery ◽  
Mdr Reversal

Aim: This work aims to develop an injectable nano-drug delivery system to overcome tumor multidrug resistance (MDR). Methods: A drug delivery nanoplatform based on PEGylated PLGA with glutathione (GSH) responsivity was constructed for dual delivery of doxorubicin and curcumin (termed DCNP), and its MDR reversal efficiency was studied in vitro and in vivo. Results: The DCNPs exhibited a rapid drug release profile under high GSH concentration and could enhance the cellular uptake and cytotoxicity of doxorubicin to MDR cancer cells. Moreover, the DCNPs showed better biocompatibility, longer blood circulation and enhanced antitumor efficiency compared with free drugs. Conclusion: The GSH-responsive nanocarrier is believed to be a promising candidate for overcoming tumor MDR.

scholarly journals Sevoflurane Promotes Bactericidal Properties of Macrophages through Enhanced Inducible Nitric Oxide Synthase Expression in Male Mice

2019 ◽  
Vol 131 (6) ◽  
pp. 1301-1315 ◽  
Author(s):  
Thomas J. Gerber ◽  
Valérie C. O. Fehr ◽  
Suellen D. S. Oliveira ◽  
Guochang Hu ◽  
Randal Dull ◽  
...  
Keyword(s):  
Early Stage ◽  
No Synthase ◽  
Control Group ◽  
Male Mice ◽  
Proinflammatory Response ◽  
E Coli ◽  
Inducible No Synthase ◽  
Bactericidal Properties

Abstract Editor’s Perspective What We Already Know about This Topic What This Article Tells Us That Is New Background Sevoflurane with its antiinflammatory properties has shown to decrease mortality in animal models of sepsis. However, the underlying mechanism of its beneficial effect in this inflammatory scenario remains poorly understood. Macrophages play an important role in the early stage of sepsis as they are tasked with eliminating invading microbes and also attracting other immune cells by the release of proinflammatory cytokines such as interleukin-1β, interleukin-6, and tumor necrosis factor-α. Thus, the authors hypothesized that sevoflurane mitigates the proinflammatory response of macrophages, while maintaining their bactericidal properties. Methods Murine bone marrow–derived macrophages were stimulated in vitro with lipopolysaccharide in the presence and absence of 2% sevoflurane. Expression of cytokines and inducible NO synthase as well as uptake of fluorescently labeled Escherichia coli (E. coli) were measured. The in vivo endotoxemia model consisted of an intraperitoneal lipopolysaccharide injection after anesthesia with either ketamine and xylazine or 4% sevoflurane. Male mice (n = 6 per group) were observed for a total of 20 h. During the last 30 min fluorescently labeled E. coli were intraperitoneally injected. Peritoneal cells were extracted by peritoneal lavage and inducible NO synthase expression as well as E. coli uptake by peritoneal macrophages was determined using flow cytometry. Results In vitro, sevoflurane enhanced lipopolysaccharide-induced inducible NO synthase expression after 8 h by 466% and increased macrophage uptake of fluorescently labeled E. coli by 70% compared with vehicle-treated controls. Inhibiting inducible NO synthase expression pharmacologically abolished this increase in bacteria uptake. In vivo, inducible NO synthase expression was increased by 669% and phagocytosis of E. coli by 49% compared with the control group. Conclusions Sevoflurane enhances phagocytosis of bacteria by lipopolysaccharide-challenged macrophages in vitro and in vivo via an inducible NO synthase–dependent mechanism. Thus, sevoflurane potentiates bactericidal and antiinflammatory host-defense mechanisms in endotoxemia.

scholarly journals Mechanism of action of the third generation benzopyrans and evaluation of their broad anti-cancer activity in vitro and in vivo

2018 ◽  
Vol 8 (1) ◽  
Author(s):  
Alexander J. Stevenson ◽  
Eleanor I. Ager ◽  
Martina A. Proctor ◽  
Dubravka Škalamera ◽  
Andrew Heaton ◽  
...  
Keyword(s):  
Mechanism Of Action ◽  
Third Generation ◽  
The Third ◽  
Anti Cancer ◽  
Cancer Activity

scholarly journals In Vivo Ergogenic Properties of the Bifidobacterium longum OLP-01 Isolated from a Weightlifting Gold Medalist

Nutrients ◽  
2019 ◽  
Vol 11 (9) ◽  
pp. 2003 ◽  
Author(s):  
Mon-Chien Lee ◽  
Yi-Ju Hsu ◽  
Hsiao-Li Chuang ◽  
Pei-Shan Hsieh ◽  
Hsieh-Hsun Ho ◽  
...  
Keyword(s):  
Grip Strength ◽  
Animal Studies ◽  
Acute Exercise ◽  
Bifidobacterium Longum ◽  
Serum Lactate ◽  
Intestinal Microbiome ◽  
Activity Levels ◽  
Gold Medalist

In recent years, probiotics of human origin have shown superior results and performance compared to probiotics from plant or dairy sources, in both in vitro and animal studies. Towards this end, the current study was conducted to explore the ergogenic properties of Bifidobacterium longum subsp. longum OLP-01 isolated from the intestinal microbiome of the gold medalist from the 2008 Beijing Olympics women’s 48 kg weightlifting competition. Male Institute of Cancer Research (ICR) mice were divided into four groups (n = 10 per group) and orally administered OLP-01 for 4 weeks at 0 (vehicle), 2.05 × 109 (OLP-01-1X), 4.10 × 109 (OLP-01-2X), and 1.03 × 1010 (OLP-01-5X) CFU/kg/day. Physical performance tests including grip strength and endurance time were measured, with OLP-01 supplementation dose-dependently elevating grip strength and endurance. The anti-fatigue activity levels of serum lactate, ammonia, glucose, blood urea nitrogen (BUN), and creatine kinase (CK) were measured after an acute exercise challenge, and OLP-01 was found to significantly decrease lactate, ammonia, and CK levels. OLP-01 treatment was also found to significantly increase the resting levels of both hepatic and muscular glycogen, an indicator of energy storage. Supplementation by OLP-01 showed no subchronic toxic effects while supporting many health-promoting, performance-improving, and fatigue-ameliorating functions.

Sign in / Sign up

Export Citation Format

Share Document