scholarly journals Dendrobium officinale Polysaccharides Inhibit 1-Methyl-2-Nitro-1-Nitrosoguanidine Induced Precancerous Lesions of Gastric Cancer in Rats through Regulating Wnt/β-Catenin Pathway and Altering Serum Endogenous Metabolites

Molecules ◽  
2019 ◽  
Vol 24 (14) ◽  
pp. 2660 ◽  
Author(s):  
Yi Zhao ◽  
Bingtao Li ◽  
Gaoyu Wang ◽  
Shuchao Ge ◽  
Ximing Lan ◽  
...  

Dendrobium officinale is a herb in traditional Chinese medicine where D. officinale polysaccharides (DOP) are the main active ingredient. This study aimed at evaluating DOP efficiency at inhibiting 1-Methyl-2-nitro-1-nitrosoguanidine (MNNG) induced precancerous lesions of gastric cancer (PLGC) in rats through the Wnt/b-catenin pathway and analyzing the variations of serum endogenous metabolites. PLGC was established in male Sprague-Dawley (SD) rats by administering 150 μg/mL MNNG in drinking water for 7 months and giving 0.1 mL of 10% NaCl once weekly during the initial 20 weeks. Treatment with DOP inhibited the progress of PLGC through decreasing the expression of β-catenin by immunohistochemical analysis. The futher study indicated DOP downregulated gene expression of Wnt2β, Gsk3β, PCNA, CyclinD1, and β-catenin, as well as protein expression of Wnt2β, PCNA, and β-catenin. On the other hand, there were nine endogenous metabolites identified after the DOP treatment. Among these, the most significant one is betaine because of its strong antioxidant activity, leading to an anti-tumor effect. DOP can inhibit MNNG-induced PLGC models via regulating Wnt/β-catenin pathway and by changing endogenous metabolites.

2020 ◽  
Vol 4 (Supplement_2) ◽  
pp. 1244-1244
Author(s):  
Amanda Bries ◽  
Joe Webb ◽  
Brooke Vogel ◽  
Claudia Carrillo ◽  
Aileen Keating ◽  
...  

Abstract Objectives Polycystic ovary syndrome (PCOS) is an endocrine disorder that affects 10% of reproductive age women and leads to hyperandrogenism, abnormal menstrual cycles, and polycystic ovaries. Moreover, PCOS has been associated with elevated serum homocysteine; however, the characterization of one-carbon metabolism (OCM) in PCOS remains incomplete. The aim of our research was to examine OCM in a genetic and chemically-induced rodent model of PCOS: 1) viable yellow Agouti (Avy) mice; and 2) letrozole (Let)-induced Sprague Dawley (SD) rats. Methods Five wk old female Avy mice (N = 18), their lean controls (N = 18), and SD rats (N = 36) were acclimated for one wk. Following acclimation, the animals were placed on a modified standard AIN93G diet (energy, %: 50.4, carbohydrate; 17.3, protein; and 32.3, fat). Rats were randomly assigned to Let (1 g/kg BW) treatment or vehicle (carboxymethylcellulose) control that was administered via a subcutaneously implanted slow-release pellet every 30-d. For both models, 12 animals were randomly assigned to be euthanized during proestrus at one of the following ages: 8, 16 or 24 wk. Bodyweight and estrous cycles were measured daily. Ovaries were collected to assess gene expression of OCM. These data were analyzed using linear mixed models to determine the main effects of age and treatment at a significance level of P < 0.05. Results Letrozole significantly reduced the occurrence of proestrus and estrus stages (P = 0.0001 and P = 0.006, respectively). Additionally, Let-induced rats had increased BW compared to control rats, across all age groups (P < 0.0001). In contrast, Avy mice weighed less than their controls by 24 wk of age (P < 0.0001). Cystathionine-β synthase (CBS) mRNA expression was downregulated in the Let-induced vs. control rats at 16 (59%; P < 0.05) and 24 (77%; P < 0.01) wk of age. As expected, Cyp19A1, aromatase mRNA was downregulated in the Let-induced rats (P = 0.02). Interestingly, betaine-homocysteine s-methyltransferase (BHMT) mRNA increased as a function of age in Let-induced rats (P = 0.03). Conclusions These data demonstrate that Letrozole-induced PCOS temporally decreases ovarian CBS mRNA expression; whereas, BHMT mRNA is upregulated as a function of age. Funding Sources This work was supported by the National Institute of Child Health and Human Development.


2015 ◽  
Vol 2015 ◽  
pp. 1-9 ◽  
Author(s):  
Yanqing Chen ◽  
Liyan Miao ◽  
Yusheng Yao ◽  
Weilan Wu ◽  
Xiaodan Wu ◽  
...  

The aim was to verify that dexmedetomidine (DEX) can attenuate CLP-induced intestinal injury via inhibition of inflammation. Male Sprague-Dawley (SD) rats were randomly allocated into Sham group and the other three CLP model groups, in terms of different treatments: placebo, DEX, and yohimbine plus DEX (DEX + YOH) groups. Pathology examination was conducted with HE stain. To identify differences among groups, the levels of DAO, and D-lactate in serum were measured by spectrophotometry, and the levels of TNF-α, IL-1β, and IL-6 in serum and organ were measured by ELISA. The expressions of occludin and TLR4 in tissue were detected by Western blot. The survival rate of an additional group of animals within 7 d was recorded. In DEX group, mortality was lower, histology change was minor, DAO, and D-lactate levels were reduced, and occludin expression was increased; the expressions of TNF-α, IL-1β, IL-6, and TLR4 were also decreased in DEX group. These results indicated that acute intestinal injury induced by CLP was mitigated by DEX treatment. However, these effects of DEX were significantly attenuated by yohimbine in DEX + YOH group. Our study indicated the protective effects of DEX on CLP-induced injury, which may be associated with the inhibition of inflammation via modulating TLR4 pathway and can be blocked by yohimbine.


Author(s):  
Stephanie M. Himmler ◽  
Brett T. Himmler ◽  
Rafał Stryjek ◽  
Klaudia Modlińska ◽  
Wojciech Pisula ◽  
...  

During play fighting, rats attack and defend the nape and during the course of this competitive interaction, they may adopt a configuration in which one animal stands over its supine partner (i.e., pin). Because the pin configuration is typically frequent and relatively easy to identify, it has been widely used as a marker to detect the effects of experimental treatments. In the present study, the frequency of pinning during standardized, 10min trials in three strains of rats, Long Evans hooded (LE), Sprague-Dawley (SD) and wild (WWCPS), was compared. LE and SD had higher rates than WWCPS rats (#/min: 6.5, 5.5, 1.5, respectively). When adjusted for strain differences in the frequency of attacks, SD as well as WWCPS rats had lower rates of pinning compared to LE rats. Both SD and WWCPS rats were less likely to use tactics of defense that promote pinning. Moreover, while the majority of the pins achieved in LE rats arose from the defender actively rolling over onto its back, the majority of pins in WWCPS rats arose because one partner pushed the other onto its back. SD rats were intermediate in this regard. Finally, once they do adopt the pin configuration, SD rats are less likely to remain supine than LE and WWCPS rats. That is, both SD and WWCPS rats have significantly fewer pins than LE rats, but a different combination of factors account for this. These data highlight the need to use a battery of measures for ascertaining the effects of experimental manipulations on play. Some suggested guidelines are provided.


1997 ◽  
Vol 272 (3) ◽  
pp. L521-L532 ◽  
Author(s):  
U. P. Kodavanti ◽  
R. H. Jaskot ◽  
W. Y. Su ◽  
D. L. Costa ◽  
A. J. Ghio ◽  
...  

Occupational exposure to anthropogenic particles is associated with lung injury in humans. We hypothesized that residual oil fly ash (ROFA), an emission source particulate, may induce acute lung injury and fibrosis in sensitive rat strains and that fibronectin (Fn) gene expression will correspond to the development of fibrosis. Male Sprague-Dawley (SD), Wistar (WIS), and Fischer 344 (F-344) rats (60 days old) were exposed to saline or ROFA (8.3 mg/kg) by intratracheal instillation and examined for up to 12 wk. Histology indicated focal areas of lung damage showing inflammatory cell infiltration as well as alveolar, airway, and interstitial thickening in all three rat strains during 1-7 days postexposure. Trichrome staining of the lung sections indicated a sporadic incidence of focal alveolar fibrosis at 1, 3, and 12 wk in SD rats, whereas WIS and F-344 rats showed only a modest increase in trichrome staining in the septal areas. Of all Fn mRNA isoforms examined by polymerase chain reaction, only EIIIA(+) was upregulated during 6 h-1 wk in ROFA-exposed SD and WIS rats but not in F-344 rats. In situ hybridization analysis in SD rats revealed Fn mRNA expression by macrophage and alveolar and airway epithelium and within fibrotic areas. Immunohistochemical analysis revealed increased presence of Fn EIIIA(+) protein in the areas of fibrotic injury and basally to the airway epithelium. In summary, Fn EIIIA(+) increases early in the course of particle-induced lung injury and remodeling, which may or may not result in discernible alveolar fibrosis. There is a rat strain variation in ROFA-induced fibrosis and associated Fn EIIIA(+) expression.


2020 ◽  
Vol 12 (45) ◽  
pp. 63-66
Author(s):  
Halim Nagem Filho ◽  
Reinaldo Francisco Maia ◽  
Reinaldo Missaka ◽  
Nasser Hussein Fares

The osseointegration is the stable and functional union between the bone and a titanium surface. A new bone can be found on the surface of the implant about 1 week after its installation; the bone remodeling begins between 6 and 12 weeks and continues throughout life. After the implant insertion, depending on the energy of the surface, the plasma fluid immediately adheres, in close contact with the surface, promoting the adsorption of proteins and inducing the indirect interaction of the cells with the material. Macrophages are cells found in the tissues and originated from bone marrow monocytes. The M1 macrophages orchestrate the phagocytic phase in the inflammatory region and also produce inflammatory cytokines involved with the chronic inflammation and the cleaning of the wound and damaged tissues from bacteria. On the other hand, alternative-activated macrophages (M2) are activated by IL-10, the immune complex. Its main function consists on regulating negatively the inflammation through the secretion of the immunosuppressant IL-10. The M2 macrophages present involvement with the immunosuppression, besides having a low capacity for presenting antigens and high production of cytokines; these can be further divided into M2a, M2b, and M2c, based on the gene expression profile.


2019 ◽  
Vol 44 (2) ◽  
pp. 77-87
Author(s):  
Koichi Ishida ◽  
Liyue Qin ◽  
Ting Wang ◽  
Ying Lei ◽  
Weiwei Hu ◽  
...  

Acupuncture manipulations are clinically important to traditional Chinese medicine, yet the biological mechanisms have not been fully understood. This study aimed to investigate continuous stimulation-induced gene expression changes at stimulated and non-stimulated adjacent acupoints in the same meridian. Catgut embedding into acupoint (CEP) was conducted at acupoint Yanglingquan (gall bladder meridian of foot-shaoyang 34, GB34) of Sprague Dawley rats once or continuously for eight weeks, and gene expression changes at GB34 were assessed by gene chip array analysis 72 h after the last CEP treatment. A total of 688 genes exhibited opposite changes in expression between the two treatments, and 1,336 genes were regulated only by the eight-week CEP treatment. Ingenuity Pathway Analysis revealed that among these differentially regulated genes by one-time and eight-week CEP treatment, insulin-like growth factor-1 pathway and integrin-linked kinase pathway, and Wnt/~ catenin signaling pathway match the observed gene changes to predicted up/down regulation patterns. Upstream analysis further predicted six molecules, namely, tumor necrosis factor, interleukin 1~, interleukin la, kallikrein-related peptidase 5, protein kinase Ca, and catenin ~1. On the other hand, continuous eight-week CEP stimulation at acupoint Xuanzhong (GB39) caused similar changes in the expression of 32 genes at acupoints GB34 and Fengshi (GB31) on the same meridian. Taken together, our results provide the first molecular evidence for the local acupoints' mechanisms for acupoint sensitization theory, and implicate the existence of signaling pathways, either direct or indirect, between acupoints within the meridian GB.


2020 ◽  
Vol 20 (3) ◽  
pp. 446-452
Author(s):  
Seyed S. Mortazavi-Jahromi ◽  
Shahab Alizadeh ◽  
Mohammad H. Javanbakht ◽  
Abbas Mirshafiey

Background: This study aimed to investigate the effects of guluronic acid (G2013) on blood sugar, insulin, and gene expression profile of oxLDL receptors (SR-A, CD36, LOX-1, and CD68) in the experimental model of diabetes. Methods: 18 Sprague Dawley rats were randomly assigned to three groups of healthy control, diabetic control, and G2013 group. Diabetes was induced through intraperitoneal (IP) injection of 60 mg/kg streptozotocin. The subjects were IP treated with 25 mg/kg of G2013 per day for 28 days. The body weight, food intake, fasting blood glucose and insulin were measured. In addition, the expression of mentioned genes was investigated through quantitative real-time PCR. Results: The data showed that the final weight increased significantly in the G2013-treated subjects compared to the diabetic control (p < 0.05). The results indicated that final food intake significantly reduced in the G2013-treated subjects compared to the diabetic control (p < 0.05). The study findings also suggested that the final fasting blood glucose significantly reduced in the G2013-treated group, whereas the final fasting serum insulin level significantly increased in this group compared to the diabetic control (p < 0.05). Moreover, the gene expression levels of SR-A, CD36, LOX-1, and CD68 in the G2013 group significantly reduced compared to the diabetic control (p < 0.05). Conclusion: This study showed that G2013, could reduce blood glucose and increase insulin levels and reduce the gene expression level of oxLDL receptors. In addition, it may probably play an important role in reducing the severity of diabetes-induced inflammatory symptoms.


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