scholarly journals Designation of a Novel DKK1 Multiepitope DNA Vaccine and Inhibition of Bone Loss in Collagen-Induced Arthritic Mice

2015 ◽  
Vol 2015 ◽  
pp. 1-9 ◽  
Author(s):  
Xiaoqing Zhang ◽  
Sibo Liu ◽  
Shentao Li ◽  
Yuxuan Du ◽  
Yunpeng Dou ◽  
...  
Keyword(s):  
Bone Loss ◽  
Dna Vaccine ◽  
Bone Erosion ◽  
Critical Role ◽  
Serum Levels ◽  
Positive Control ◽  
Protective Effects ◽  
High Level

Dickkopf-1 (DKK1), a secretory inhibitor of canonical Wnt signaling, plays a critical role in certain bone loss diseases. Studies have shown that serum levels of DKK1 are significantly higher in rheumatoid arthritis (RA) patients and are correlated with the severity of the disease, which indicates the possibility that bone erosion in RA may be inhibited by neutralizing the biological activity of DKK1. In this study, we selected a panel of twelve peptides using the software DNASTAR 7.1 and screened high affinity and immunogenicity epitopesin vitroandin vivoassays. Furthermore, we optimized four B cell epitopes to design a novel DKK1 multiepitope DNA vaccine and evaluated its bone protective effects in collagen-induced arthritis (CIA), a mouse model of RA. High level expression of the designed vaccine was measured in supernatant of COS7 cells. In addition, intramuscular immunization of BALB/c mice with this vaccine was also highly expressed and sufficient to induce the production of long-term IgG, which neutralized natural DKK1in vivo. Importantly, this vaccine significantly attenuated bone erosion in CIA mice compared with positive control mice. These results provide evidence for the development of a DNA vaccine targeted against DKK1 to attenuate bone erosion.

scholarly journals IN-VITRO ANTIOXIDANT AND IN-VIVO HEPATO PROTECTIVE ACTIVITY OF ETHANOL EXTRACTS FROM THE BARK OF SHOREA ROBUSTA (DIPTEROCARPACEAE) AGAINST CARBON TETRA CHLORIDE INDUCED LIVER TOXICITY IN RATS

2016 ◽  
Vol 9 (6) ◽  
pp. 225
Author(s):  
Diptanu Biswas
Keyword(s):  
Liver Toxicity ◽  
Hepatoprotective Activity ◽  
Positive Control ◽  
Protective Effects ◽  
Shorea Robusta ◽  
Carbon Tetra ◽  
Anti Oxidant ◽  
Ethanol Extracts

ABSTRACT: The study is designed for the evaluation of in-vivo Hepato protective and in-vitro Anti oxidant activity of ethanol extracts from the bark of Shorea robusta (Dipterocarpaceae) by CCl4 induced hepatotoxicity in rats. Ethanol extracts from the bark Shorea robusta (EESR) was evaluated for hepatoprotective activity in rats by inducing liver damage by CCl4. The anti oxidant activity of EESR was assayed by various in-vitro antioxidant methods and activities were compared to standard ascorbic acid. Ethanol extracts at an oral dose 200mg/kg and 400mg/kg exhibited a significant (*p<0.005) protective effects by lowering the level of SGOT, SGPT, ALP, Serum bilirubin, total cholesterol and increasing the level of total proteins as compared to Silymarin (50mg/kg) used as positive control. The extracts exhibit significant anti oxidant activity in various in vitro anti oxidant models.  From these studies we are concluding that, the ethanolic extracts of S.robusta have potent hepatoprotective effects and have anti oxidant properties, hence can be used as a natural product against liver damage.KEY WORDS: Anti oxidant, Carbon tetra chloride,  Hepatoprotective,  Shorea robusta

scholarly journals Fucoidan Prevents RANKL-Stimulated Osteoclastogenesis and LPS-Induced Inflammatory Bone Loss via Regulation of Akt/GSK3β/PTEN/NFATc1 Signaling Pathway and Calcineurin Activity

Marine Drugs ◽  
2019 ◽  
Vol 17 (6) ◽  
pp. 345 ◽  
Author(s):  
Sheng-Hua Lu ◽  
Yi-Jan Hsia ◽  
Kuang-Chung Shih ◽  
Tz-Chong Chou
Keyword(s):  
Bone Loss ◽  
Molecular Mechanisms ◽  
Bone Erosion ◽  
Osteoclast Differentiation ◽  
Bone Diseases ◽  
Nuclear Factor ◽  
Activated T Cells ◽  
Calcineurin Activity

Excessive osteoclast differentiation and/or function plays a pivotal role in the pathogenesis of bone diseases such as osteoporosis and rheumatoid arthritis. Here, we examined whether fucoidan, a sulfated polysaccharide present in brown algae, attenuates receptor activator of nuclear factor-κB ligand (RANKL)-stimulated osteoclastogenesis in vitro and lipopolysaccharide (LPS)-induced bone resorption in vivo, and investigated the molecular mechanisms involved. Our results indicated that fucoidan significantly inhibited osteoclast differentiation in RANKL-stimulated macrophages and the bone resorbing activity of osteoclasts. The effects of fucoidan may be mediated by regulation of Akt/GSK3β/PTEN signaling and suppression of the increase in intracellular Ca2+ level and calcineurin activity, thereby inhibiting the translocation of nuclear factor-activated T cells c1 (NFATc1) into the nucleus. However, fucoidan-mediated NFATc1 inactivation was greatly reversed by kenpaullone, a GSK3β inhibitor. In addition, using microcomputer tomography (micro-CT) scanning and bone histomorphometry, we found that fucoidan treatment markedly prevented LPS-induced bone erosion in mice. Collectively, we demonstrated that fucoidan was capable of inhibiting osteoclast differentiation and inflammatory bone loss, which may be modulated by regulation of Akt/GSK3β/PTEN/NFATc1 and Ca2+/calcineurin signaling cascades. These findings suggest that fucoidan may be a potential agent for the treatment of osteoclast-related bone diseases.

scholarly journals An Explanation of the Underlying Mechanisms for the In Vitro and In Vivo Antiurolithic Activity of Glechoma longituba

2016 ◽  
Vol 2016 ◽  
pp. 1-11 ◽  
Author(s):  
Qiang Liang ◽  
Xiaoran Li ◽  
Wangning Zhou ◽  
Yu Su ◽  
Shenbao He ◽  
...  
Keyword(s):  
Kidney Injury ◽  
Positive Control ◽  
Potassium Citrate ◽  
Positive Control Group ◽  
Control Group ◽  
Protective Effects ◽  
In Vivo Models ◽  
Glechoma Longituba

Purpose. To use in vitro and in vivo models to evaluate Glechoma longituba extract to provide scientific evidence for this extract’s antiurolithic activity. Materials and Methods. Potassium citrate was used as a positive control group. Oxidative stress (OS) markers and the expression of osteopontin (OPN) and kidney injury molecule-1 (KIM-1) were measured to assess the protective effects of Glechoma longituba. Multiple urolithiasis-related biochemical parameters were evaluated in urine and serum. Kidneys were harvested for histological examination and the assessment of crystal deposits. Results. In vitro and in vivo experiments demonstrated that treatment with Glechoma longituba extract significantly decreased calcium oxalate- (CaOx-) induced OPN expression, KIM-1 expression, and OS compared with the positive control group (P<0.05). Additionally, in vivo rats that received Glechoma longituba extract exhibited significantly decreased CaOx deposits and pathological alterations (P<0.05) compared with urolithic rats. Significantly lower levels of oxalate, creatinine, and urea and increased citrate levels were observed among rats that received Glechoma longituba (P<0.05) compared with urolithic rats. Conclusion. Glechoma longituba has antiurolithic effects due to its possible combined effects of increasing antioxidant levels, decreasing urinary stone-forming constituents and urolithiasis-related protein expression, and elevating urinary citrate levels.

scholarly journals Functional inhibition of osteoblastic cells in an in vivo mouse model of myeloid leukemia

Blood ◽  
2012 ◽  
Vol 119 (2) ◽  
pp. 540-550 ◽  
Author(s):  
Benjamin J. Frisch ◽  
John M. Ashton ◽  
Lianping Xing ◽  
Michael W. Becker ◽  
Craig T. Jordan ◽  
...  
Keyword(s):  
Bone Loss ◽  
Myeloid Leukemia ◽  
Serum Levels ◽  
Osteoblastic Cells ◽  
Novel Approach ◽  
Vitro Data ◽  
In Vitro Data ◽  
Marrow Cells

Pancytopenia is a major cause of morbidity in acute myeloid leukemia (AML), yet its cause is unclear. Normal osteoblastic cells have been shown to support hematopoiesis. To define the effects of leukemia on osteoblastic cells, we used an immunocompetent murine model of AML. Leukemic mice had inhibition of osteoblastic cells, with decreased serum levels of the bone formation marker osteocalcin. Osteoprogenitor cells and endosteal-lining osteopontin+ cells were reduced, and osteocalcin mRNA in CD45− marrow cells was diminished. This resulted in severe loss of mineralized bone. Osteoclasts were only transiently increased without significant increases in bone resorption, and their inhibition only partially rescued leukemia-induced bone loss. In vitro data suggested that a leukemia-derived secreted factor inhibited osteoblastic cells. Because the chemokine CCL-3 was recently reported to inhibit osteoblastic function in myeloma, we tested its expression in our model and in AML patients. Consistent with its potential novel role in leukemic-dependent bone loss, CCL-3 mRNA was significantly increased in malignant marrow cells from leukemic mice and from samples from AML patients. Based on these results, we propose that therapeutic mitigation of leukemia-induced uncoupling of osteoblastic and osteoclastic cells may represent a novel approach to promote normal hematopoiesis in patients with myeloid neoplasms.

scholarly journals In Vitro and In Vivo Protective Effects of Lentil (Lens culinaris) Extract against Oxidative Stress-Induced Hepatotoxicity

Molecules ◽  
2021 ◽  
Vol 27 (1) ◽  
pp. 59
Author(s):  
Yeon-Seop Jung ◽  
So-Hee Lee ◽  
So Young Chun ◽  
Dae Hwan Kim ◽  
Byung Ik Jang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Serum Levels ◽  
Liver Cells ◽  
Dependent Manner ◽  
Protective Effects ◽  
H2o2 Treatment ◽  
Antioxidant Genes ◽  
Hepatic Diseases

Excessive oxidative stress plays a role in hepatotoxicity and the pathogenesis of hepatic diseases. In our previous study, the phenolic extract of beluga lentil (BLE) showed the most potent in vitro antioxidant activity among extracts of four common varieties of lentils; thus, we hypothesized that BLE might protect liver cells against oxidative stress-induced cytotoxicity. BLE was evaluated for its protective effects against oxidative stress-induced hepatotoxicity in AML12 mouse hepatocytes and BALB/c mice. H2O2 treatment caused a marked decrease in cell viability; however, pretreatment with BLE (25–100 μg/mL) for 24 h significantly preserved the viability of H2O2-treated cells up to about 50% at 100 μg/mL. As expected, BLE dramatically reduced intracellular reactive oxygen species (ROS) levels in a dose-dependent manner in H2O2-treated cells. Further mechanistic studies demonstrated that BLE reduced cellular ROS levels, partly by increasing expression of antioxidant genes. Furthermore, pretreatment with BLE (400 mg/kg) for 2 weeks significantly reduced serum levels of alanine transaminase and triglyceride by about 49% and 40%, respectively, and increased the expression and activity of glutathione peroxidase in CCl4-treated BALB/c mice. These results suggest that BLE protects liver cells against oxidative stress, partly by inducing cellular antioxidant system; thus, it represents a potential source of nutraceuticals with hepatoprotective effects.

scholarly journals Pristimerin Suppresses RANKL-Induced Osteoclastogenesis and Ameliorates Ovariectomy-Induced Bone Loss

2021 ◽  
Vol 11 ◽  
Author(s):  
Dahu Qi ◽  
Hui Liu ◽  
Xuying Sun ◽  
Danni Luo ◽  
Meipeng Zhu ◽  
...  
Keyword(s):  
Bone Loss ◽  
Osteoclast Differentiation ◽  
Cathepsin K ◽  
Serum Levels ◽  
Mapk Signaling ◽  
Heme Oxygenase 1 ◽  
Related Factor ◽  
Treatment Of Osteoporosis

Osteoporosis is characterized by bone loss and destruction of trabecular architecture, which greatly increases the burden on the healthcare system. Excessive activation of osteoclasts is an important cause of osteoporosis, and suppression of osteoclastogenesis is helpful for the treatment of osteoporosis. Pristimerin, a natural compound, possesses numerous pharmacological effects via inactivating the NF-κB and MAPK pathways, which are closely related to osteoclastogenesis process. However, the relationship between Pristimerin and osteoclastogenesis requires further investigation. In this research, we examined the effect of Pristimerin on osteoclastogenesis and investigated the related mechanisms. Our results showed Pristimerin inhibited RANKL-induced osteoclast differentiation and osteoclastic bone resorption in vitro, with decreased expression of osteoclastogenesis-related markers including c-Fos, NFATc1, TRAP, Cathepsin K, and MMP-9 at both mRNA and protein levels. Furthermore, Pristimerin suppressed NF-κB and MAPK signaling pathways, reduced reactive oxygen species (ROS) production and activated the nuclear factor erythroid 2-related factor 2/heme oxygenase 1 (Nrf2/HO-1) signaling during osteoclastogenesis. Our in vivo experiments showed that Pristimerin remarkably ameliorated ovariectomy-induced bone loss, reduced serum levels of TNF-α, IL-1β, IL-6, and RANKL, and increased serum level of osteoprotegerin (OPG). Therefore, our research indicated that Pristimerin is a potential chemical for the treatment of osteoporosis.

scholarly journals The Ethanol Extract of Avocado (Persea americana Mill. (Lauraceae)) Seeds Successfully Induces Implant Regression and Restores Ovarian Dynamic in a Rat Model of Endometriosis

2020 ◽  
Vol 2020 ◽  
pp. 1-10
Author(s):  
Stéphane Minko Essono ◽  
Marie Alfrede Mvondo ◽  
Esther Ngadjui ◽  
François Xavier Kemka Nguimatio ◽  
Pierre Watcho
Keyword(s):  
Ethanol Extract ◽  
Serum Levels ◽  
Positive Control ◽  
Negative Control ◽  
Persea Americana ◽  
Corpora Lutea ◽  
Serum Samples ◽  
Female Wistar Rats

Endometriosis is an estrogen-dependent disease with conventional therapies which do not have desirable effectiveness and possess many side effects. Scientific evidences suggest that medicinal plants with antioxidant, anti-inflammatory, and/or antiproliferative properties are potential alternatives for the treatment of endometriosis. The ethanol extract of Persea americana Mill. (Lauraceae) seeds was found exhibiting antiproliferative properties in vitro and in vivo. This study therefore is aimed at investigating the effects of such an extract on an experimental model of endometriosis. Endometriosis was induced by grafting uterine fragments onto the peritoneum of female Wistar rats. After checking the success of the transplantation surgery, animals with endometriosis were orally treated with the ethanol extract of P. americana seeds at the doses of 12.5, 25, and 50 mg/kg. The positive control was treated with letrozole (10 mg/kg) while the negative control received the vehicle. Treatments lasted 7 days and animals were sacrificed thereafter. Endometrial implant volume was determined. Estradiol and progesterone levels were measured in serum samples and endometriosis lesions. The oxidative status of endometriosis lesions was evaluated. Histological analysis of endometriosis lesions, uterus, and ovaries was also performed. Results showed that the ethanol extract of P. americana seeds decreased endometrial implant volume (p<0.001) and serum levels of estradiol and progesterone (p<0.01). The levels of estradiol also decreased in endometriosis lesions at doses of 12.5 and 50 mg/kg (p<0.001). Both malondialdehyde and glutathione levels increased in endometriosis lesions (p<0.001). The ectopic endometrium height decreased and the number of antral follicles and corpora lutea (p<0.05) increased while that of luteinized unruptured follicles decreased (p<0.001). In conclusion, the ethanol extract of P. americana seeds displayed an antiendometriosis effect suggesting that it could be a potential alternative for the treatment of endometriosis.

Polyphenols: Anti-Platelet Nutraceutical?

2018 ◽  
Vol 24 (2) ◽  
pp. 146-157 ◽  
Author(s):  
Valeria Ludovici ◽  
Jens Barthelmes ◽  
Matthias P. Nagele ◽  
Andreas J. Flammer ◽  
Isabella Sudano
Keyword(s):  
Platelet Aggregation ◽  
Platelet Activation ◽  
Therapeutic Potential ◽  
Critical Role ◽  
Organ Damage ◽  
Low Grade ◽  
Protective Effects ◽  
Dietary Polyphenols

Background: Coronary artery disease (CAD) is a disease progressing over many years. Genetic factors, as well as the exposure to risk factors, are continuously leading to endothelial dysfunction, vascular alterations and, eventually, organ damage, major cardiovascular events and deaths. Oxidative stress, platelet hyperactivity and low-grade inflammation are important modulators in this context, contributing to plaque formation. Since platelet activation plays a critical role in the development and progression of atherothrombotic events, the inhibition of platelet hyperactivity may contribute to decreased atherothrombotic risk. The consumption of bioactive foods, and plant-derived polyphenols in particular, might impart anti-thrombotic and cardiovascular protective effects. Methods: Aim of this work is to focus on the potential of dietary derived polyphenols to reduce platelet hyperactivity or hypercoagulability in addition to discussing their possible complementary anti-platelet therapeutic potential. All the relevant publications on this topic were systematically reviewed. Results: Various studies demonstrated that polyphenol supplementation affects platelet aggregation and function in vitro and in vivo, mainly neutralizing free radicals, inhibiting platelet activation and related signal transduction pathways, blocking thromboxane A2 receptors and enhancing nitric oxide production. Experimental data concerning the effect of dietary polyphenols on platelet aggregation in vivo are poor, and results are often conflicting. Only flavanols clearly mirrored in vivo showed the efficacy in vitro in modulating platelet function. Conclusion: Dietary polyphenols, and above all flavanols contained in cocoa and berries, reduce platelet activation and aggregation via multiple pathways. However, more controlled interventional studies are required to establish which doses are required as well as what circulating concentrations are sufficient to induce functional antiplatelet effects.

scholarly journals Anidulafungin in Treatment of Experimental Invasive Infection by Candida parapsilosis:In VitroActivity, (1→3)-β-d-Glucan and Mannan Serum Levels, Histopathological Findings, andIn VivoEfficacy

2011 ◽  
Vol 55 (11) ◽  
pp. 4985-4989 ◽  
Author(s):  
Valentina Salas ◽  
F. Javier Pastor ◽  
Enrique Calvo ◽  
Emilio Mayayo ◽  
Guillermo Quindós ◽  
...  
Keyword(s):  
Candida Parapsilosis ◽  
Serum Levels ◽  
Sensu Stricto ◽  
Invasive Infection ◽  
Content Type ◽  
Level Of Activity ◽  
High Level ◽  
Different Doses

ABSTRACTWe have evaluated thein vitroactivity of anidulafungin (AFG) against 31 strains ofCandida parapsilosissensu stricto by using broth microdilution, disk diffusion, and minimal fungicidal concentration (MFC) determination procedures. The two first methods showed a high level of activity of the drug, while MFCs were 1 to 5 dilutions higher than their corresponding MICs. To assess if MICs were predictive ofin vivooutcomes, six strains representing different AFG MICs (0.12 to 2 μg/ml) were tested in a murine model of disseminated infection treated with different doses of the drug (1, 5, or 10 mg/kg of body weight). AFG was able to prolong the survival of mice infected with all the strains tested but was able to reduce the tissue burden of those mice infected only with the strains that showed the lowest MIC (0.12 μg/ml).

scholarly journals Local Induction of B Cell Interleukin-10 Competency Alleviates Inflammation and Bone Loss in Ligature-Induced Experimental Periodontitis in Mice

2016 ◽  
Vol 85 (1) ◽  
Author(s):  
Pei Yu ◽  
Yang Hu ◽  
Zhiqiang Liu ◽  
Toshihisa Kawai ◽  
Martin A. Taubman ◽  
...  
Keyword(s):  
B Cells ◽  
Bone Loss ◽  
Critical Role ◽  
Cell Activity ◽  
Interleukin 10 ◽  
Tartrate Resistant Acid Phosphatase ◽  
Periodontal Inflammation ◽  
Experimental Periodontitis

ABSTRACT Interleukin-10 (IL-10)-producing B cells (B10 cells) play a critical role in the immune system balance by negatively regulating inflammatory responses. This study was conducted to determine the effect of local B10 cell induction on periodontal inflammation and bone loss in ligature-induced experimental periodontitis in vivo. Purified spleen B cells from C57BL/6J mice (8 to 10 weeks old) were cultured with CD40 ligand (CD40L) and the Toll-like receptor 9 (TLR9) agonist cytidine-phosphate-guanosine oligodeoxynucleotide (CpG) to determine effective IL-10 induction in vitro. Silk ligatures (size 7-0) were tied around the mouse maxillary second molars on day 0, followed by the injection of CD40L and CpG into the palatal gingiva on days 3, 6, and 9. All the mice were sacrificed, and samples were collected on day 14. CD40L and CpG significantly increased the level of IL-10 production by B cells in vitro, although the frequencies of CD1dhi CD5+ and IL-10-producing (IL-10+) CD45+ cells were decreased. IL-10 was predominantly produced by the CD1dhi CD5+ subpopulation of B cells. In vivo, both IL-10 mRNA expression and the number of IL-10+ CD45+ cells were significantly increased after gingival injection of CD40L and CpG. Periodontal bone loss was significantly decreased and the gingival expression of IL-1β, tumor necrosis factor alpha, and RANKL was significantly reduced. The number of multinucleated tartrate-resistant acid phosphatase-positive cells along the alveolar bone surface was significantly decreased after gingival injection of CD40L and CpG. This study indicates for the first time that the local induction of B10 cell activity could inhibit periodontal inflammation and bone loss.

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