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Today, 12 Ιουλίου 2016, 3:54:44 μμ
The Immunomodulatory Effects of Physical Activity
Today, 12 Ιουλίου 2016, 3:54:45 μμ
Background: An individual's level of physical activity is one of a set of lifestyle and behavioral factors that can affect immune function and health. Methods: The purpose of this review is to summarize the current knowledge in this research field and to review the recent developments in exercise immunology. Results: Most studies show that regular exercise training increases immune competence and reduces the risk of infection compared to a sedentary lifestyle. In contrast, acute prolonged bouts of exercise and periods of intensified training are followed by a temporary increase in the risk of infection. These observations have been attributed to differential exercise-induced changes of a series of humoral and cellular immune system parameters. Furthermore, regular exercise training is a countermeasure against a persistent systemic inflammatory state which is a typical feature of cardiovascular and metabolic diseases is by lowering levels of pro-inflammatory cytokines. It is supposed that these effects are mediated by a modification of metabolic signals and innate immune regulation, the release of anti-inflammatory cytokines from muscle, the release of stress hormones, and a process known as browning of adipose tissue. Conclusion: The effects of physical activity on the immune system strongly depend on the mode and intensity of exercise or training. Thereby, considerable knowledge has accumulated concerning the significance of exercise as an important lifestyle factor for prevention and therapy of major chronic diseases.
New Functions of the Inositol Polyphosphate 5-Phosphatases in Cancer
Today, 12 Ιουλίου 2016, 3:54:45 μμ
Inositol polyphosphate 5-phosphatases act on inositol phosphates and phosphoinositides as substrates. They are 10 different isoenzymes and several splice variants in the human genome that are involved in a series of human pathologies such as the Lowe syndrome, the Joubert and MORM syndromes, breast cancer, glioblastoma, gastric cancer and several other type of cancers. Inositol 5-phosphatases can be amplified in human cancer cells, whereas the 3- and 4- phosphatase tumor suppressor PTEN and INPP4B, repectively are often repressed or deleted. The inositol 5-phosphatases are critically involved in a complex network of higly regulated phosphoinositides, affecting the lipid content of PI(3, 4, 5)P<sub>3</sub>, PI(4, 5)P<sub>2</sub> and PI(3, 4)P<sub>2</sub>. This has an impact on the normal behavior of many intracellular target proteins e.g. protein kinase B (PKB/Akt) or actin binding proteins and final biological responses. The production of PI(3, 4P)<sub>2</sub> by dephosphorylation of the substrate PI(3, 4, 5)P<sub>3</sub> is particularly important as it produces a new signal messenger in the control of cell migration, invasion and endocytosis. New inhibitors/activators of inositol 5- phosphatases have recently been identified for the possible control of their activity in several human pathologies such as inflamation and cancer.
Lymphatic Delivery of Anti-HIV Drug Nanoparticles
Today, 12 Ιουλίου 2016, 3:54:45 μμ
Background: HIV infection persists for a longer time in AIDS patient compared to many other viral diseases. This is mainly because the HIV resides maximally in lymphatic system mainly the lymph nodes. Most of the present anti-HIV drugs have very poor bioavailability at lymphatic tissue. Hence, pharmaceutical scientists have made many efforts to formulate anti-HIV drugs for targeting lymphatic system. The exploration of nanoparticulate drug delivery systems have been popularly investigated for lymphatic targeting and for improving therapeutic efficacy. </p><p> Methods: An electronic search was undertaken to review the recent publications and patents from the available resources on nanoformulations of anti-HIV drugs for lymphatic delivery. </p><p> Results: Various carrier systems such as liposomes, polymeric nanoparticles, solid-lipid nanoparticles, nanostructured lipid carriers, polymeric micelles, dendrimers, and nanocrystals have been tried for lymphatic targeting. These nanoparticles are widely studied as passive targeting carriers for lymphatic systems. There is dearth of active targeting for anti-HIV drugs. The studies on surface modified nanoparticles have shown promising results for lymphatic targeting. </p><p> Conclusion: One of the reasons for low success rate in targeting the lymphatic tissue is poor-understanding of pharmacokinetic interactions of novel delivery systems in disease pathology. Apart from this, there are several hurdles in biological screening models and clinical trials. These issues should never be neglected in developing newer targeted delivery systems for treatment of AIDS. </p><p>
Ebola Virus Altered Innate and Adaptive Immune Response Signalling Pathways: Implications for Novel Therapeutic Approaches
Today, 12 Ιουλίου 2016, 3:54:45 μμ
Ebola virus (EBOV) arise attention for their impressive lethality by the poor immune response and high inflammatory reaction in the patients. It causes a severe hemorrhagic fever with case fatality rates of up to 90%. The mechanism underlying this lethal outcome is poorly understood. In 2014, a major outbreak of Ebola virus spread amongst several African countries, including Leone, Sierra, and Guinea. Although infections only occur frequently in Central Africa, but the virus has the potential to spread globally. Presently, there is no vaccine or treatment is available to counteract Ebola virus infections due to poor understanding of its interaction with the immune system. Accumulating evidence indicates that the virus actively alters both innate and adaptive immune responses and triggers harmful inflammatory responses. In the literature, some reports have shown that alteration of immune signaling pathways could be due to the ability of EBOV to interfere with dendritic cells (DCs), which link innate and adaptive immune responses. On the other hand, some reports have demonstrated that EBOV, VP35 proteins act as interferon antagonists. So, how the Ebola virus altered the innate and adaptive immune response signaling pathways is still an open question for the researcher to be explored. Thus, in this review, I try to summarize the mechanisms of the alteration of innate and adaptive immune response signaling pathways by Ebola virus which will be helpful for designing effective drugs or vaccines against this lethal infection. Further, potential targets, current treatment and novel therapeutic approaches have also been discussed.
The Gender Bender effect in Periodontal Immune Response
Today, 12 Ιουλίου 2016, 3:54:45 μμ
Background: The gender and sex of an individual is known to have a significant bearing on the immune system, responsible for protection against infections and disease. Contemporary evidence suggests there exists a sexual dimorphism in the hetero immune as well as autoimmune responses in human beings and females show stronger and more vigorous immune responses to antigenic stimulations, e.g infectious diseases and vaccination. The evidence supportive to gender based heterogeneity in immune responses specifically in context of periodontal disease, is mounting in contemporary literature. </p><p> Method: A thorough and methodical search for related scientific publications have been accomplished by using different key words and terms like sex or gender based immune differences in periodontal disease, both by manual methods and on various electronic databases. Primary research articles, narrative and systematic reviews of good quality, relevant to the subject were included. </p><p> Results: The aggregate effects of the factors related to gender such as the steroid hormones as well as gene based differences in both sexes as supported by published literature are in line with the observed variation in susceptibility for chronic periodontitis in both genders , with males showing more risk for disease than women. </p><p> Conclusion: Gender as a risk factor for periodontal disease needs to identified, its underlying mechanisms to contribute needs to be revealed, so that novel strategies for risk assessment, disease identification and individualized therapeutic approaches can be developed for optimized patient care. </p><p>
Predictive Efficacy Biomarkers of Programmed Cell Death 1/Programmed Cell Death 1 Ligand Blockade Therapy
Today, 12 Ιουλίου 2016, 3:54:45 μμ
Inhibitors of immune check-point molecule, programmed cell death 1 (PD-1) and its ligand, programmed cell death ligand 1 (PD-L1) have attracted much attention in cancer immunotherapy recently due to their durable antitumor effects in various malignances, especially the advanced ones. Unfortunately, only a fraction of patients with advanced tumors could benefit from anti-PD-1/PD-L1 therapy, while others still worsened. The key to this point is that there are no efficient biomarkers for screening anti-PD-1/PD-L1-sensitive patients. In this review, we aim at summarizing the latest advances of anti-PD-1/PDL1 immunotherapy and the potential predictive efficacy biomarkers to provide evidences for identifying anti-PD-1/PDL1- sensitive patients. The present article also includes the patent review coverage on this topic.
The State-of-Art in Angiogenic Properties of Latex from Different Plant Species
Today, 12 Ιουλίου 2016, 3:54:45 μμ
Background: The development of drugs capable of enhance or inhibit the cell proliferation is an area in expansion at modern biomedical sciences. Recent researches have shown that latex has strong angiogenic potential. </p> <p> Methods: We performed a bibliometric analysis on the global literature trying to identify: the main scientometrics data, the botanical families and species, the angiogenic or antiangiogenic properties and also discussed the results obtained on this topic up to now. </p> <p> Results: The different bibliometric approaches, showed a continuous increase of both quantitative and qualitative parameters in the studies of latex utilization in the angiogenesis process. From more than 35,000 lactiferous species existing only 29 have been studied and showed angiogenic potential. Then, the potential for finding new therapeutic compounds in latex is a new and promising field that needs to be better explored. Regarding the biological activity, 59% of articles have reported the angiogenic activity and 41% the antiangiogenic property. The most articles identified in this research, have been used in their experimental analysis the crude latex (73.41%). Only 26.52% of the articles used biocompounds isolated from latex. Among the weaknesses in this field, it is necessary to point: the molecular characterization of latex; the establishment of molecular mechanism of action; and demonstration of latex biocompunds safety and effectiveness in clinical trials. </p> <p> Conclusion: Those results are important to spread knowledge about the use of latex as a new biomaterial employed in medicine, indicate trends, point out the technical difficult on the development of new drugs.
Preferentially Expressed Antigen in Melanoma (PRAME) and the PRAME Family of Leucine-Rich Repeat Proteins
Today, 12 Ιουλίου 2016, 3:54:45 μμ
Preferentially expressed antigen in melanoma (PRAME) is the best characterized member of the PRAME family of leucine-rich repeat (LRR) proteins. Mammalian genomes contain multiple members of the PRAME family whereas in other vertebrate genomes only one PRAME-like LRR protein was identified. PRAME is a cancer/testis antigen that is expressed at very low levels in normal adult tissues except testis but at high levels in a variety of cancer cells. In contrast to most other cancer/testis antigens, PRAME is expressed not only in solid tumors but also in leukemia cells. Expression of PRAME and other members of the PRAME family is regulated epigenetically. PRAME interacts with varying pathways that might be directly involved in the malignant phenotype of cancer cells. For instance, PRAME is able to dominantly repress retinoic acid signaling in these cells. On the other hand, PRAME-derived peptides can be recognized as epitopes by cytotoxic T cells and PRAME represents an attractive target for immunological treatment strategies.
Cucurbitacin B Enhances the Anticancer Effect of Imatinib Mesylate Through Inhibition of MMP-2 Expression in MCF-7 and SW480 Tumor Cell Lines
Today, 12 Ιουλίου 2016, 3:54:45 μμ
The combination of medicinal plant extracts with known chemotherapeutics offers significant potential for the development of novel therapies in cancer disease. Cucurbitacin B (CuB) is one of the most potent and widely used members of cucurbitacin family and it is known to have important effects on several diseases including cancer. To determine whether CuB can enhance chemosensitivity to imatinib mesylate (IM), in the present study, the combined effects of CuB with IM on MCF-7 and SW480 cells were investigated. The cells were treated with CuB alone or in combination with IM and the results showed that the combination treatment synergistically inhibited cell proliferation and induced apoptosis. Furthermore, the combined effect of CuB and IM on matrix metalloproteinase-2 (MMP-2) gene expression, a member of MMP family which is responsible for the degradation of extracellular matrix was also evaluated. CuB increased the inhibitory effect of IM on MMP-2 expression synergistically in a dose dependent manner. The results suggest that CuB in combination with IM may serve as a potentially useful therapeutic strategy for patients with breast and colorectal cancer.
The Functions of Histone Modification Enzymes in Cancer
Today, 12 Ιουλίου 2016, 3:54:45 μμ
Posttranslational modifications of proteins critically regulate the function, localization, and stability of target proteins. Histone modification is one of the regulatory mechanisms that modulate the chromatin structure and thereby affect various DNA-templated processes, such as gene transcription, DNA replication, DNA recombination, and DNA repair in cells. These molecular processes contribute to basic cellular functions, including cell cycle, cell growth, and apoptosis. Histone modifications consist of acetylation, methylation, phosphorylation, ubiquitination, sumoylation biotination, citrullination, poly-ADPribosylation, and N-glycosylation. The modification status of histone is balanced by two enzyme families with opposing catalytic activities: histone modifying and de-modifying enzymes. Recent studies have shown that dysfunction of histone modification enzymes is a major cause for human cancer initiation and progression. In this review, we will summarize the functions of histone modification enzymes in cancer, and the mechanisms that histone modification enzymes use to drive or suppress human malignancies.
Lipid-based Vesicular Nanocargoes as Nanotherapeutic Targets for the Effective Management of Rheumatoid Arthritis
Today, 12 Ιουλίου 2016, 3:54:45 μμ
Background: Rheumatoid arthritis (RA) is an immune mediated joint-based chronic inflammatory disorder recognized by joint inflammation, destruction, pain and remission. Currently, numerous pharmacotherapeutic strategies have gained immense popularity in RA therapy and improving the patient life. </p><p> Methods: Besides, it exhibits numerous drawbacks such as requirement of high dose of drugs, unavoidable adverse effects and diseases remission. Thus, use of currently available pharmacotherapeutics employing conventional formulations can only provide therapeutic effects to a certain extent. </p><p> Results: Recent advancements in nanotechnology-based lipidic vesicular nanocarriers have led provided improved efficacy and safety for the anti-rheumatic drugs. These include liposomes, stealth liposomes, ethosomes, transfersomes, etc., which have shown their potential to improve the therapeutic efficacy of antirheumatic drugs with lesser toxicity. Although the results of animal models for use of lipid vesicular nanocarriers for drug targeting in RA have been found to be highly promising, but lack of sufficient data in a clinical setup are still evident to demonstrate their practical utility in patient populations. In this regard, considerable research studies are required for evaluating the efficacy and safety of the aforementioned nanocarriers in RA through clinical studies. </p><p> Conclusion: The present review, therefore, covers the brief pathophysiology of RA, current medication and their challenges in RA therapy. Besides, an extensive account on recent advancements in novel lipid vesicular nanocarriers in RA therapy has also been addressed with special emphasis on the patent literature too. </p><p>
Small Molecular Inhibitors Targeting Chromatin Regulating Proteins for Cancer
Today, 12 Ιουλίου 2016, 3:54:45 μμ
Chromatin-regulating proteins modulate nucleosome structure by either modifying histones covalently or disrupting DNA-protein interaction directly with ATP hydrolysis. Evidence has shown that chromatin-regulating proteins play critical roles in regulation of molecular processes using DNA as template, including gene expression, DNA replication, DNA damage repair, and chromosome integrity. In most of human malignancies, chromatin-regulating proteins have been shown as functional oncogenes. In some scenarios, chromatin-regulating proteins also could have tumor suppressive functions. Thereby, small molecular inhibitors targeting chromatin-regulating proteins could be used for cancer therapies. Numerous small molecular inhibitors against chromatin-regulating proteins are recently developed by academic and industrial groups. These compounds are evaluated for antitumor effects in vitro and in vivo. Some of them have shown great potential to become a therapeutic drug for cancer, and is currently evaluated in clinical trials. A few compounds have been approved for clinical use in cancer treatment. In this review, we will focus on the recent progress on the development of small inhibitors of chromatin-regulating proteins for cancer therapy.
In vitro Toxicity Evaluation and in vivo Biodistribution of Polymeric Micelles Derived from Poly(ethylene glycol)-b-poly(benzyl malate) Copolyme
Today, 12 Ιουλίου 2016, 3:54:45 μμ
Background: The development of polymeric micelles for site-specific drug delivery is an exponentially growing field of research. In this context, we have designed two degradable amphiphilic copolymers, the poly(ethylene glycol)-b-poly(benzyl malate) (PEG<sub>42</sub>-b-PMLABe<sub>73</sub>) and the biotin-poly(ethylene glycol)- b-poly(benzyl malate) (Biot-PEG<sub>62</sub>-b-PMLABe<sub>73</sub>). The copolymer bearing biotin residue was synthesized in order to formulate micelles for grafting biotinylated cyclic RGD peptide onto their surface via the bridging streptavidin. </p> <p> Objective: Our study aimed at investigating the in vitro and in vivo toxicity of such micelles and to evaluate the potential of these nanovectors for hepatocyte-targeted drug delivery. Methods: The toxicity of micelles obtained by the nanoprecipitation method and characterized by dynamic light scattering and zeta potential measurement was evaluated in vitro using the differentiated hepatocyte-like HepaRG cells and in vivo in mice. </p> <p> Results: The micelles derived from PEG<sub>42</sub>-b-PMLABe<sub>73</sub>, Biot-PEG<sub>62</sub>-b-PMLABe<sub>73</sub> and RGDBiot-Strept- Biot-PEG62-b-PMLABe73 did not affect the cell proliferation and apoptotic indexes in HepaRG hepatoma cells and were well tolerated in mice following systemic injection. The hydrophobic fluorescent probes DiD oil and DiR were efficiently encapsulated in PEG-b-PMLABe-derived micelles allowing the visualization of their uptake into HepaRG cells. Furthermore, the addition of RGD peptide onto micelles strongly enhanced the cell uptake in vitro and liver targeting in vivo. </p> <p> Conclusion: These data demonstrate the low toxicity of poly(benzyl malate) derived copolymers towards hepatocyte- like cells and emphasize their potential use for the design of liver targeting nanovectors.
Structure and Function of CW Domain Containing Proteins
Today, 12 Ιουλίου 2016, 3:54:45 μμ
The CW domain is a zinc binding domain, composed of approximately 50- 60 amino acid residues with four conserved cysteine (C) and two to four conserved tryptophan (W) residues. The members of the superfamily of CW domain containing proteins, comprised of 12 different eukaryotic nuclear protein families, are extensively expressed in vertebrates, vertebrate-infecting parasites and higher plants, where they are often involved in chromatin remodeling, methylation recognition, epigenetic regulation and early embryonic development. Since the first CW domain structure was determined 5 years ago, structures of five CW domains have been solved so far. In this review, we will discuss these recent advances in understanding the identification, definition, structure, and functions of the CW domain containing proteins.
Application of Mesenchymal Stem Cells in the Targeted Gene Therapy for Gastric Cancer
Today, 12 Ιουλίου 2016, 3:54:45 μμ
The incidence of gastric cancer is third most prevalent among all malignant tumors in China. The conventional therapies for advanced gastric cancer are futile. Targeted gene therapy has become a promising alternative approach. Mesenchymal stem cells (MSCs) can be used as potential cellular vehicles for cancer therapy in vivo. This review will summarize the published data about the application of MSC-based targeted therapy for gastric cancer, and discuss some of the challenges associated with this method.
Disease Progression in HIV Late Presenters: the Role of HIV Clinical Indicator Diseases Prior to HIV Diagnosis
Today, 12 Ιουλίου 2016, 3:54:45 μμ
Background: Late diagnosis represents a major challenge in the control of HIV epidemics. The rate of disease progression is higher among late presenters. In Europe, HIV Clinical Indicator Diseases (CIDs) have been proposed to improve early diagnosis. </p><p> Objectives: Our observational study evaluated the presence of these HIV CIDs prior to HIV diagnosis among a population of late presenters and assessed its correlation to disease progression. </p><p> Method: A retrospective cohort study was conducted in HIV late presenters diagnosed from 2007 to 2013 at University Hospital of Ferrara (Italy). Hazard Ratios (H.R.s) for disease progression (new AIDS-events and death) were estimated by Cox proportional hazard model. </p><p> Results: We analysed 77 patients and we found that those with CIDs prior to HIV diagnosis (22%) had a 2.8 fold higher rate of disease progression compared to those without HIV CIDs (H.R. 2.82; 95% CI 1.21-6.53; P 0.02). Other factors associated with disease progression were AIDS presentation, HCV coinfection and Haemoglobin levels, with H.R.s of 3.14 (95%CI 1.23-7.99), 2.95 (95% CI 1.14-7.61) and 0.74 (95% CI 0.60-0.91), respectively. </p><p> Conclusion: HIV CIDs confer a higher risk for disease progression even after adjustment for these confounding factors. Evaluation of previous HIV CIDs at HIV diagnosis could be an additional tool to identify and better manage HIV late presenters with higher risks of disease progression. </p><p>
Neuroprotective Strategies in Glaucoma
Today, 12 Ιουλίου 2016, 3:54:45 μμ
Background: Glaucoma is characterized as a neuropathic disease that causes progressive degeneration of retinal ganglion cells (RGCs) in the retina, resulting in irreversible loss of vision. All conventional treatments for glaucoma are focused on reducing intraocular pressure (IOP) in the anterior chamber of the eye. However, these treatments alone are insufficient to halt the progression of the disease. As a result, neuroprotective strategies have been developed that prevent retinal neuron loss and disease progression. Methods: The goal of this review is to summarize and discuss neuroprotective strategies in glaucoma at the level of the retina and the ganglion cell layer instead of treatments targeting IOP. Recent and past neuroprotective therapies used to prevent the loss of retinal ganglion cells, the loss of axons in the optic nerve and the loss of vision and function associated with glaucoma are presented. Results: Pharmacological approaches have targeted specific receptors, signaling cascades and neurotrophic factors to induce neuroprotection in the retina, while others have focused on the mechanism of cellular loss associated with glaucoma, including excitotoxicity, oxidative stress and apoptotic processes. In addition to neuroprotective pharmacological treatments, stem cell, gene therapy and viral research have demonstrated neuroprotection against the loss of RGCs in glaucomatous conditions. Conclusion: It is likely that future development for glaucoma treatment will include a combination of these treatments to prevent the pathophysiology of glaucoma.
Emerging Immunotargets in Bladder Cancer
Today, 12 Ιουλίου 2016, 3:54:45 μμ
Bladder cancer treatment, namely systemic therapy, was dominated in the last three decades due to the absence of newer therapeutic options other than chemotherapy regimens. Chemotherapy, by itself, both in first and second-line seems to have achieved the modest plateau of its possibilities at the cost of non-negligible toxicity. Targeted therapies, which changed the therapy of many different tumors, seem rather ineffective in bladder cancer. More recently, a new generation of Immunotherapy based regimens represent the most promising avenue for the future systemic treatment of bladder cancer. Checkpoint inhibition, namely PD1/PD-L1 pathway inhibition, showed impressive results in many other tumor types and are expected to become a major player in the treatment of bladder cancer. Other immunotherapy strategies such as fusion proteins represent distant, although promising, options. A brief overview of the current status of bladder cancer immunotherapy is presented.
Mitochondrial Dysfunction in Gliomas: Pharmacotherapeutic Potential of Natural Compounds
Today, 12 Ιουλίου 2016, 3:54:45 μμ
Gliomas are the most common primary brain tumors either benign or malignant originating from the glial tissue. Glioblastoma multiforme (GBM) is the most prevalent and aggressive form among all gliomas, associated with decimal prognosis due to it's high invasive nature. GBM is also characterized by high recurrence rate and apoptosis resistance features which make the therapeutic targeting very challenging. Mitochondria are key cellular organelles that are acting as focal points in diverse array of cellular functions such as cellular energy metabolism, regulation of ion homeostasis, redox signaling and cell death. Eventual findings of mitochondrial dysfunction include preference of glycolysis over oxidative phosphorylation, enhanced reactive oxygen species generation and abnormal mitochondria mediated apoptotic machinery are frequently observed in various malignancies including gliomas. In particular, gliomas harbor mitochondrial structure abnormalities, genomic mutations in mtDNA, altered energy metabolism (Warburg effect) along with mutations in isocitrate dehydrogenase (IDH) enzyme. Numerous natural compounds have shown efficacy in the treatment of gliomas by targeting mitochondrial aberrant signaling cascades. Some of the natural compounds directly target the components of mitochondria whereas others act indirectly through modulating metabolic abnormalities that are consequence of the mitochondrial dysfunction. The present review offers a molecular insight into mitochondrial pathology in gliomas and therapeutic mechanisms of some of the promising natural compounds that target mitochondrial dysfunction. This review also sheds light on the challenges and possible ways to overcome the hurdles associated with these natural compounds to enter into the clinical market.
Ellagic Acid Increases Osteocalcin and Alkaline Phosphatase After Tooth Extraction in Nicotinic-Treated Rats
Today, 12 Ιουλίου 2016, 3:54:45 μμ
Objectives:-To examine the effect of nicotine (Ni) on bone socket healing treated with Ellagic acid (EA) after tooth extraction in rat. Materials and Methods: Thirty-Two Sprague Dawley (SD) male rats were divided into four groups. The group 1 was administrated with distilled water intragastrically and injected sterile saline subcutaneously. The group 2 was administrated with EA orally and injected with sterile saline subcutaneously. The groups 3 & 4 were subcutaneously exposed to Ni for 4 weeks twice daily before tooth extraction procedure, and maintained Ni injection until the animals were sacrificed. After one month Ni exposure, the group 4 was fed with EA while continuing Ni injection. All the groups were anesthetized, and the upper left incisor was extracted. Four rats from each group were sacrificed on 14<sup>th</sup> and 28<sup>th</sup> days. Tumour necrosis factor alpha (TNFα), Interleukin-1 beta (IL-1β) and Interleukin-6 (IL-6) were applied to assess in serum rat at 14th and 28<sup>th</sup> days. Superoxide dismutase (SOD) and Thiobarbituric acid reactive substances (TBRAS) levels were assessed to evaluate the antioxidant status and lipid peroxidation accordingly after tooth extraction in homogenized gingival maxilla tissue of rat at 14<sup>th</sup> and 28<sup>th</sup> days. The socket hard tissue was stained by eosin and hematoxylin (H&E); immunohistochemical technique was used to assess the healing process by Osteocalcin (OCN) and Alkaline Phosphatase (ALP) biomarkers. Results: Ni-induced rats administered with EA compound (Group 4) dropped the elevated concentration of pro-inflammatory cytokines significantly when compared to Ni-induced rats (Group 3) (p<0.05). Ni-induced rats administrated with EA compound (Group 4) showed significant production of SOD and recession in TBRAS level when compared to Ni-induced rats (Group 3) (p<0.05). The immunohistochemistry analysis has revealed that OCN and ALP have presented stronger expression in Ni-induced rats treated with EA (Group 4), as against Ni-induced rats (Group 3). Conclusion: We have concluded that, Ni-induced rats, treated with EA have exerted positive effect on the trabecular bone formation after tooth extraction in nicotinic rats could be due to the antioxidant activity of EA which lead to upregulate of OCN and ALP proteins which are responsible for osteogenesis.
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