Search results for: immune checkpoint inhibitors

Authors: P. O. Ughachukwu, P. O. Okonkwo, P. C. Unekwe, J. O. Ogamba

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Background: The prevalence of hepatitis B viral infection is high worldwide with liver cirrhosis and hepatocellular carcinoma as important complications. Cases of poor antibody response to hepatitis B vaccination abound. Immunosuppression, especially from glucocorticoids, is often cited as a cause of poor antibody response and there are documented evidences of irrational administration of glucocorticoids to children and adults. The study was, therefore, designed to find out if administration of glucocorticoids affects immune response to vaccination against hepatitis B in mice. Methods: Mice of both sexes were randomly divided into 2 groups. Daily intramuscular methylprednisolone injections, (15 mg kg-1), were given to the test group while sterile deionized water (0.1ml) was given to control mice for 30 days. On day 6 all mice were given 2 μg (0.1ml) hepatitis B vaccine and a booster dose on day 27. On day 34, blood samples were collected and analyzed for anti-HBs titres using enzyme-linked immunosorbent assay (ELISA). Statistical analysis was done using Graph Pad Prism 5.0 and the results taken as statistically significant at p value < 0.05. Results: There were positive serum anti-HBs responses in all mice groups but the differences in titres were not statistically significant. Conclusions: At the dosages and length of exposure used in this study, methylprednisolone injection did not significantly inhibit anti-HBs response in mice following immunization against hepatitis B virus. By extrapolation, methylprednisolone, when used in the usual clinical doses and duration of therapy, is not likely to inhibit immune response to hepatitis B vaccinations in man.

Keywords: anti-HBs, hepatitis B vaccine, immune response, methylprednisolone, mice

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Authors: Sema Şenoğlu, Sevgi Karakuş

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Hydrazone scaffold is important to design new drug groups and is found to possess numerous uses in pharmaceutical chemistry. Besides, hydrazone derivatives are also known for biological activities such as anticancer, antimicrobial, antiviral, and antifungal. Hydrazone derivatives are promising anticancer agents because they inhibit cancer proliferation and induce apoptosis. Human carbonic anhydrase IX has a high potential to be an antiproliferative drug target, and targeting this protein is also important for obtaining potential anticancer inhibitors. The protein construct was retrieved as a PDB file from the RCSB protein database. This binding interaction of proteins and ligands was performed using Discovery Studio Visualizer. In vitro inhibitory activity of hydrazone derivatives was tested against enzyme carbonic anhydrase IX on the PyRx programme. Most of these molecules showed remarkable human carbonic anhydrase IX inhibitory activity compared to the acetazolamide. As a result, these compounds appear to be a potential target in drug design against human carbonic anhydrase IX.

Keywords: cancer, carbonic anhydrase IX enzyme, docking, hydrazone

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Authors: F. Ambreen, A.Naheed

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Osteoarthritis (OA) is a degenerative disorder affecting millions of people worldwide. Nitric oxide (NO) was found to play a catabolic role in the development of osteoarthritis. It is a toxic free radical gas generated during the metabolism of L-arginine by the enzyme Nitric oxide synthase (NOS). Inducible Nitric Oxide Synthase (iNOS) is one of the isoform of NOS, and its overexpression leads to the excessive formation of NO that results in pathophysiological joint conditions. Several synthetic anti-inflammatory drugs and inhibitors are present to date, but all showed side effects and complications. Therefore, the pursuit of natural disease-modifying drugs remains a top priority. Curcumin is an active component of turmeric, and the past few decades have witnessed intense research devoted to the antioxidant and anti-inflammatory properties of curcumin. The present study focused on curcumin and its derivatives in the search for new iNOS inhibitors for the treatment of osteoarthritis. We conducted a molecular docking study on curcumin and its four derivatives; cyclocurcumin, tetrahydrocurcumin, demethoxycurcumin and curcumin monoglucoside with iNOS using CLC Drug discovery work bench 3.02. We selected two co-crystallized ligands for this study; tetrahydrobiopterin and N-omega-propyl-L-arginine present in complex with the enzyme iNOS. Results showed the best binding affinity of N-omega-propyl-L-arginine with cyclocurcumin and curcumin monoglucoside that exhibit binding energies of -65.2 kcal/mol and -68 kcal/mol respectively. Whereas with tetrahydrobiopterin, best binding scores of -64.7 kcal/mol and -62.2 kcal/mol were found with tetrahydrocurcumin and demethoxycurcumin respectively. This information could open doors of research for the designing of novel drugs using herbs such as curcumin for the treatment of inflammatory joint diseases.

Keywords: curcumin, iNOS, molecular docking, osteoarthritis

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Authors: Mudassar Hameed, Khushi Muhammad, Aamir Ghafoor, Masood Rabbani, Momena Habib, Jawad Nazir

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Comparative efficacy of three formulations (non-adjuvant, gel, and oil adjuvant) of monovalent and combined PPR and FMD virus vaccines was evaluated in goats. All kinds of monovalent PPRV vaccines elicited protective antibody titers at one-month post vaccination (PV) that remained so till six months PV. Monovalent non-adjuvant (NA) FMDV vaccine provoked non-protective antibody titers that declined to undetectable levels after three months. In case of combined vaccines, all of the formulations elicited protective antibody titers against PPRV in vaccinated animals which remained above that limit for six months. However, an exceptional immune response against FMDV was observed in combined NA vaccine group where antibody titers were extremely high and remained above protective level till 4 months PV in animals who received a single vaccine shot and till six months PV in booster group. Although, adjuvant or NA combined vaccines can induce protective antibody titers against both of the viruses within one month PV, but a booster vaccine shot is needed to retain protective antibody level for 6 months duration. Immune response elicited by combined vaccines is comparable or superior to the monovalent vaccines. Hence combined vaccine can be effectively used for the control and prevention of both of the diseases.

Keywords: antibody titer, protective, combined vaccine, non adjuvant

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Authors: Abdul Qadir Qadis, Satoru Goya, Minoru Yatsu, Yu-uki Yoshida, Toshihiro Ichijo, Shigeru Sato

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Bacterial probiotics are known to modulate the gut-associated lymphoid and epithelial tissue response to enhance the activities of intestinal and systemic immune system in human and animals. In cattle, the immune-stimulatory effects of probiotics have been evaluated during intestinal disorders. To investigate the effects of probiotic on the function of peripheral blood mononuclear cells, eight healthy Holstein calves (10 ± 3 weeks) were assigned to a 4 × 2 experimental design. The probiotic, consisting of Lactobacillus plantarum, Enterococcus faecium and Clostridium butyricum, was administered orally at 3.0 g/100 kg body weight to calves once daily for 5 consecutive days. Calves given no probiotic served as the control. In the treatment group, increases in numbers of CD282+ monocytes, CD3+ T-cells and CD4+, CD8+ and WC1+ γδ T- cell subsets were noted on day 7 post-placement compared to pre-dose day and the control group. Expression of interleukin-6, interferon-gamma and tumor necrosis factor-alpha was elevated in peripheral leukocytes on days 7 and 14. These results suggest that peripheral blood leukocytes in healthy calves may be stimulated via the gastrointestinal microbiota, which was increased by the oral probiotic treatment. The 5-day repeated administration of a bacterial probiotic may enhance cellular immune function in weaned calves.

Keywords: bacterial-probiotic, calf, interleukin, leukocyte

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Authors: Amna J. Ghith, Khaled Abu Zid, Khairia Youssef, Nasser Saad

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Backgrounds: The multikinase and vascular endothelial growth factor (VEGF) receptor inhibitors interrupt the pathway by which angiogenesis becomes established and promulgated, resulting in the inadequate nourishment of metastatic disease. VEGFR-2 has been the principal target of anti-angiogenic therapies. We disclose the new thieno pyrimidines as inhibitors of VEGFR-2 designed by a molecular modeling approach with increased synergistic activity and decreased side effects. Purpose: 2-substituted thieno pyrimidines are designed and synthesized with anticipated anticancer activity based on its in silico molecular docking study that supports the initial pharmacophoric hypothesis with a same binding mode of interaction at the ATP-binding site of VEGFR-2 (PDB 2QU5) with high docking score. Methods: A series of compounds were designed using discovery studio 4.1/CDOCKER with a rational that mimic the pharmacophoric features present in the reported active compounds that targeted VEGFR-2. An in silico ADMET study was also performed to validate the bioavailability of the newly designed compounds. Results: The Compounds to be synthesized showed interaction energy comparable to or within the range of the benzimidazole inhibitor ligand when docked with VEGFR-2. ADMET study showed comparable results most of the compounds showed absorption within (95-99) zone varying according to different substitutions attached to thieno pyrimidine ring system. Conclusions: A series of 2-subsituted thienopyrimidines are to be synthesized with anticipated anticancer activity and according to docking study structure requirement for the design of VEGFR-2 inhibitors which can act as powerful anticancer agents.

Keywords: docking, discovery studio 4.1/CDOCKER, heterocycles based anticancer agents, 2-subsituted thienopyrimidines

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Authors: Gema Gómez-Casado, Alba Rodríguez-Muñoz, Virginia Mela-Rivas, Pallavi Kompella, Francisco José Tinahones-Madueña, Isabel Moreno-Indias, Almudena Ortega-Gómez

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Obesity is a high-priority health problem worldwide due to its high prevalence. The proportion of obese and overweight subjects in industrialized countries exceeds half of the population in most cases. Beyond the metabolic problem, obesity boosts inflammation levels in the organism. The gut microbiota, considered an organ by itself, controls a high variety of processes at a systemic level. In fact, the microbiota interacts closely with the immune system, being crucial in determining the maturation state of neutrophils, key effectors of the innate immune response. It is known that changes in the diet exert strong effects on the variety and activity of the gut microbiota. The effect that those changes have on the axis microbiota-immune response is an unexplored field. In this study, 10 patients with obesity (weight 114,3 ± 14,5Kg, BMI 40,47±3,66) followed a Mediterranean-hypocaloric diet for 3 months, reducing their initial weight by 12,71 ± 3%. A transplant of microbiota from these patients before and after the diet was performed into wild type “germ-free” mice (n=10/group), treated with antibiotics. Six weeks after the transplant, mice were euthanized, and the presence of cells from the innate immune system were analysed in different organs (bone marrow, blood, spleen, visceral adipose tissue, and intestine) by flow cytometry. No differences were observed in the number of myeloid cells in bone marrow, blood, spleen, or visceral adipose tissue of mice transplanted with patient’s microbiota before and after following the Mediterranean diet. However, the intestine of mice that received post-diet microbiota presented a marked decrease in the number of neutrophils (whose presence is associated with tissue inflammation), as well as macrophages. In line with these findings, intestine monocytes from mice with post-diet microbiota showed a less inflammatory profile (lower Ly6Gˡᵒʷ proportion of cells). These results point toward a decrease in the inflammatory state of the intestinal tissue, derived from changes in the gut microbiota, which occurred after a 3-month Mediterranean diet.

Keywords: obesity, nutrition, Mediterranean diet, gut microbiota, immune system

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Authors: Husham Bayazed, Fatimah Yousif

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Purpose of Presentation: The infant immune system has a reputation for being weak and underdeveloped when compared to the adult immune system, but the comparison isn’t quite fair. At the start, as the COVID-19 pandemic drags on and evolves, many Pediatricians and kids' parents have been left with renewed questions about the consequences and sequel of infection on children and the steps to be taken if their child has the symptoms of COVID-19 or tests positive. Recent Findings Literature reviews and recent studies revealed that children are better than adults at controlling SARS-CoV-2. There was conflicting evidence on age-related differences in ACE2 expression in the nose and lungs. But scientists who measured the ‘viral load’ in children's upper airways have seen no clear difference between children and adults. Moreover, the hypothesis is that kids might be more exposed to other coronaviruses common cold, with a production of ready protective antibodies to lock on to the pandemic coronavirus. But the evidence suggests that adults also have this immunity too. Strikingly, these ‘cross-reactive’ antibodies don’t offer any special protection. Summary One of the few silver linings of the Covid-19 pandemic is that children are relatively spared. The kid's Innate Immunity is hardly the whole story, the innate immune response against SARS-CoV-2 infection is early initiative calm with low immunological tone to prevent an overactive immunity and with rapidly repair damage to the lungs in contrast to stormy waves in adults. Therefore, Kids are at much lower risk of Covid-19 infection, and they are still winning the battle against Covid-19 with their innate immunity.

Keywords: Covid-19, kids, ACE2 receptors, immunity

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Authors: Azadeh Moghaddas, Mehrnoush Dianatkhah, Padideh Ghaeli

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The main characteristics of borderline personality disorder (BPD) are instable regulation of affect and self-image, impulsive behavior, and lack of interpersonal relationships. Clinically, emotional dysregulation, impulsive aggression, repeated self-injury, and suicidal thought are noted with this disorder. Proper management of patients with BPD is a difficult challenge due to the complex features of this disorder. Pharmacotherapy of BPD in order to control impulsive behavior and to stabilize affect in patients with BPD has been receiving a lot of attention. Anticonvulsant agents such as topiramate, valproate, or lamotrigine, atypical antipsychotics such as aripiprazole and olanzapine and antidepressants such as monoamine oxidase inhibitors and selective serotonin reuptake inhibitors like fluvoxamine have been implicated in the treatment of BPD. Unfortunately, none of these medications can be used alone or even in combination as sole treatment of BPD. Medications may be used mostly to resolve or reduce impulsivity and aggression in these patients. Naltrexone (NTX), a nonspecific competitive opiate antagonist has been suggested, in the literature, to control self-injurious behavior (SIB) and dissociative symptoms in patients with BPD. This brief review has been intended to look at all documented evidence on the use of NTX in the management of BPD and to reach a comprehensive conclusion.

Keywords: borderline personality disorder, naltrexone, self-injurious behavior, dissociative symptoms

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Authors: Asma Ben Hmidene, Mizuho Hanaki, Kazuma Murakami, Kazuhiro Irie, Hiroko Isoda, Hideyuki Shigemori

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Type 2 diabetes mellitus (T2DM) and Alzheimer’s disease (AD) are characterized as a peripheral metabolic disorder and a degenerative disease of the central nervous system, respectively. It is now widely recognized that T2DM and AD share many pathophysiological features including glucose metabolism, increased oxidative stress and amyloid aggregation. Amyloid beta (Aβ) is the components of the amyloid deposits in the AD brain and while the component of the amyloidogenic peptide deposit in the pancreatic islets of Langerhans is identified as human islet amyloid polypeptide (hIAPP). These two proteins are originated from the amyloid precursor protein and have a high sequence similarity. Although the amino acid sequences of amyloidogenic proteins are diverse, they all adopt a similar structure in aggregates called cross-beta-spine. Add at that, extensive studies in the past years have found that like Aβ1-42, IAPP forms early intermediate assemblies as spherical oligomers, implicating that these oligomers possess a common folding pattern or conformation. These similarities can be used in the search for effective pharmacotherapy for DM, since potent therapeutic agents such as antioxidants with a catechol moiety, proved to inhibit Aβ aggregation, may play a key role in the inhibit the aggregation of hIAPP treatment of patients with DM. Tamarix gallica is one of the halophyte species having a powerful antioxidant system. Although it was traditionally used for the treatment of various liver metabolic disorders, there is no report about the use of this plant for the treatment or prevention of T2DM and AD. Therefore, the aim of this work is to investigate their protective effect towards T2DM and AD by isolation and identification of α-glucosidase inhibitors, with antioxidant potential, that play an important role in the glucose metabolism in diabetic patient, as well as, the polymerization of hIAPP and Aβ aggregation inhibitors. Structure-activity relationship study was conducted for both assays. And as for α-glucosidase inhibitors, their mechanism of action and their synergistic potential when applied with a very low concentration of acarbose were also suggesting that they can be used not only as α-glucosidase inhibitors but also be combined with established α-glucosidase inhibitors to reduce their adverse effect. The antioxidant potential of the purified substances was evaluated by DPPH and SOD assays. Th-T assay using 42-mer amyloid β-protein (Aβ42) for AD and hIAPP which is a 37-residue peptide secreted by the pancreatic β –cells for T2DM and Transmission electronic microscopy (TEM) were conducted to evaluate the amyloid aggragation of the actives substances. For α-glucosidase, p-NPG and glucose oxidase assays were performed for determining the inhibition potential and structure-activity relationship study. The Enzyme kinetic protocol was used to study the mechanism of action. From this research, it was concluded that polyphenols playing a role in the glucose metabolism and oxidative stress can also inhibit the amyloid aggregation, and that substances with a catechol and glucuronide moieties inhibiting amyloid-β aggregation, might be used to inhibit the aggregation of hIAPP.

Keywords: α-glucosidase inhibitors, amyloid aggregation inhibition, mechanism of action, polyphenols, structure activity relationship, synergistic potential, tamarix gallica

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Authors: Mehrshad Khosraviani, Faramarz Abbaspour Leyl Abadi

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The fundamental component of the computer network of modern information society will be considered. These networks are connected to the network of the internet generally. Due to the fact that the primary purpose of the Internet is not designed for, in recent decades, none of these networks in many of the attacks has been very important. Today, for the provision of security, different security tools and systems, including intrusion detection systems are used in the network. A common diagnosis system based on artificial immunity, the designer, the Adhasaz Foundation has been evaluated. The idea of using artificial safety methods in the diagnosis of abnormalities in computer networks it has been stimulated in the direction of their specificity, there are safety systems are similar to the common needs of m, that is non-diagnostic. For example, such methods can be used to detect any abnormalities, a variety of attacks, being memory, learning ability, and Khodtnzimi method of artificial immune algorithm pointed out. Diagnosis of the common system of education offered in this paper using only the normal samples is required for network and any additional data about the type of attacks is not. In the proposed system of positive selection and negative selection processes, selection of samples to create a distinction between the colony of normal attack is used. Copa real data collection on the evaluation of ij indicates the proposed system in the false alarm rate is often low compared to other ir methods and the detection rate is in the variations.

Keywords: artificial immune system, abnormality detection, intrusion detection, computer networks

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Authors: Rahma Souli-Jbali, Minyar Sassi Hidri, Rahma Ben Ayed

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Grid of computing nodes has emerged as a representative means of connecting distributed computers or resources scattered all over the world for the purpose of computing and distributed storage. Since fault tolerance becomes complex due to the availability of resources in decentralized grid environment, it can be used in connection with replication in data grids. The objective of our work is to present fault tolerance in data grids with data replication-driven model based on clustering. The performance of the protocol is evaluated with Omnet++ simulator. The computational results show the efficiency of our protocol in terms of recovery time and the number of process in rollbacks.

Keywords: data grids, fault tolerance, clustering, chandy-lamport

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Authors: Daniela V. Bavaresco, Tamy Colonetti, Antonio Jose Grande, Francesc Colom, Joao Quevedo, Samira S. Valvassori, Maria Ines da Rosa

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Objective: Performed a systematic review and meta-analysis to evaluated the potential effect of the cyclo-oxygenases (Cox)-2 inhibitor Celecoxib adjunct treatment in Bipolar Disorder (BD), through of randomized controlled trials. Method: A search of the electronic databases was proceeded, on MEDLINE, EMBASE, Scopus, Cochrane Central Register of Controlled Trials (CENTRAL), Biomed Central, Web of Science, IBECS, LILACS, PsycINFO (American Psychological Association), Congress Abstracts, and Grey literature (Google Scholar and the British Library) for studies published from January 1990 to February 2018. A search strategy was developed using the terms: 'Bipolar disorder' or 'Bipolar mania' or 'Bipolar depression' or 'Bipolar mixed' or 'Bipolar euthymic' and 'Celecoxib' or 'Cyclooxygenase-2 inhibitors' or 'Cox-2 inhibitors' as text words and Medical Subject Headings (i.e., MeSH and EMTREE) and searched. The therapeutic effects of adjunctive treatment with Celecoxib were analyzed, it was possible to carry out a meta-analysis of three studies included in the systematic review. The meta-analysis was performed including the final results of the Young Mania Rating Scale (YMRS) at the end of randomized controlled trials (RCT). Results: Three primary studies were included in the systematic review, with a total of 121 patients. The meta-analysis had significant effect in the YMRS scores from patients with BD who used Celecoxib adjuvant treatment in comparison to placebo. The weighted mean difference was 5.54 (95%CI=3.26-7.82); p < 0.001; I2 =0%). Conclusion: The systematic review suggests that adjuvant treatment with Celecoxib improves the response of major treatments in patients with BD when compared with adjuvant placebo treatment.

Keywords: bipolar disorder, Cox-2 inhibitors, Celecoxib, systematic review, meta-analysis

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Authors: Luana N. Cardozo, Debora A. S. Coutinho, Fabiola Lagher, Bruno J. G. Silva, Ivonilce Venture, Mainara Tesser, Graciela Venera

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Ostrich oil is used as food in Brazil, and it has been the subject of scientific research because it contains essential fatty acids (Omega 3, 6, 7, and 9), which provide benefits to human health. Alkylglycerols are lipid ethers consisted of a saturated or unsaturated hydrocarbon chain joined by ether-type bonding to one of the glycerol hydroxyls. It is known that supplementation with alkylglycerols can act significantly on the functioning of immune system cells, both in pathological situations and in homeostasis. Objective: Analyze the presence of alkylglycerols in ostrich oil. Methods: The ostrich oil was bought from an industry that manufactures the product for sale as food, located in Mirante da Serra, northern Brazil. The samples were sent for analysis to the chemistry department of the Federal University of Paraná, where they were analyzed by the gas chromatography method. Results: The analysis of the ostrich oil presented alkylglycerols in area 514505154. Comparison, it is possible to observe that shark liver oil contains the area 26190196, and the difference between both is highly significant. Conclusion: The importance of alkylglycerol supplementation for the immune system is known. The analysis of the results made it possible to verify the presence of alkylglycerols in the ostrich oil, which is five times higher than in the shark liver oil, that would be the largest source food, but was surpassed by the ostrich oil until the present time. The present study emphasizes that ostrich oil can be considered a food source of alkylglycerols and may play a promising role in the immune system because it contains such substance, but further studies are needed to prove its performance in the body.

Keywords: ostrich oil, nutritional composition, alkylglycerols, food

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Authors: Lea Boidin, Martha Baydoun, Bertrand Leroux, Olivier Morales, Samir Acherar, Celine Frochot, Nadira Delhem

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Ovarian cancer (OC) is one of the most defying diseases in gynecologic oncology. Even though surgery remains crucial in the therapy of patients with primary ovarian cancer, recurrent recidivism calls for the development of new therapy protocols to propose for patients dealing with this cancer. FRα is described as a tumor‐associated antigen in OC, where FRα expression is usually linked with more poorly differentiated, aggressive tumors. The Photodynamic treatment (PDT) available data have shown improvements in the uptake of small tumors and in the induction of a proper anti-tumoral immune response. In order to target specifically peritoneal metastatis, which overexpress FRα, a new-patented PS coupled with folic acid has been developed in our team. Herein we propose PDT using this new patented PS for PDT applied in an in vivo mice model. The efficacy of the treatment was evaluated in mice without and with PBMC reconstitution. Mice were divided into four groups: Non-Treated, PS, Light Only, and PDT Treated and subjected to illumination by laser set at 668nm with a duration of illumination of 45 minutes (or 1 min of illumination followed by 2 minutes of pause repeated 45 times). When mice were not reconstituted and after fractionized PDT protocol, a significant decrease in the tumor volume was noticed. An induction in the anti-tumoral cytokine IFNγ chaperoned this decrease while a subsequent inhibition in the cytokine TGFβ. Even more crucial, when mice were reconstituted and upon PDT, the fold of tumor decrease was even higher. An immune response was activated decoded with an increase in NK, CD3 +, LT helper and Cytotoxic T cells. Thereafter, an increase in the expression of the cytokines IFNγ and TNFα were noticed while an inhibition in TGFβ, IL8 and IL10 accompanied this immune response activation. Therefore, our work has shown for the first time that a fractionized PDT protocol using a folate-targeted PDT is effective for treatment of ovarian cancer. The interest in using PDT in this case, goes beyond the local induction of tumor apoptosis only, but can promote subsequent anti-tumor response. Most of the therapies currently used to treat ovarian cancer, have an uncooperative outcomes on the host immune response. The readiness of a tumor adjuvant treatment like PDT adequate in eliminating the tumor and in concert stimulating anti-tumor immunity would be weighty.

Keywords: folate receptor, ovarian cancer, photodynamic therapy, humanized mice model

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Authors: Fatemeh Keshavarz

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Background: Schizophrenia is a disease of the nervous system, and immune system disorders can affect its pathogenesis. Activation of microglia, proinflammatory cytokines, disruption of the blood-brain barrier (BBB) due to inflammation, activation of autoreactive B cells, and consequently the production of autoantibodies against system antigens are among the immune processes involved in neurological diseases. interleukin 32 (IL-32) a proinflammatory cytokine that important player in the activation of the innate and adaptive immune responses. This study aimed to measure the serum level of IL-32 as well as the frequency of autoantibody positivity against several nervous system antigens in patients with schizophrenia. Material and Methods: This study was conducted on 40 patients with schizophrenia and 40 healthy individuals in the control group. Serum IL-32 levels were measured by ELISA. The frequency of autoantibodies against Hu, Ri, Yo, Tr, CV2, Amphiphysin, SOX1, Zic4, ITPR1, CARP, GAD, Recoverin, Titin, and Ganglioside antigens were measured by indirect immunofluorescence method. Results: Serum IL-32 levels in patients with schizophrenia were significantly higher compared to the control group. Autoantibodies were positive in 8 patients for GAD antigen and 5 patients for Ri antigen, which showed a significant relationship compared to the control group. Autoantibodies were also positive in 2 patients for CV2, in 1 patient for Hu, and in 1 patient for CARP. Negative results were reported for other antigens. Conclusion: Our findings suggest that elevated the serum IL-32 level and autoantibody positivity against several nervous system antigens may be involved in the pathogenesis of schizophrenia.

Keywords: schizophrenia, microglia, autoantibodies, IL-32

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Authors: Majid Goudarzi

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This experiment was designed to study the effects of feeding different levels of Peganum harmala seeds (PHS) and antibiotic on serum biochemical parameters, immune response and intestinal microflora composition in Ross broiler chickens. A total of 240 one-d-old unsexed broiler chickens were randomly allocated to each of the four treatment groups, each with four replicate pens of 15 chicks. The dietary treatments included of control (C) - without PHS and antibiotic - the diet contains 300 mg/kg Lincomycin 0.88% (A) and the diets contain 2 g/kg (H1) and 4 g/kg (H2) PHS. The chicks were raised on floor pens and received diets and water ad libitum for six weeks. Blood samplings were performed for the determination of antibody titer against Newcastle disease on 14 and 21 days and for biochemical parameters on 42 days of age. The populations of Lactobacilli spp. and Escherichia coli were enumerated in ileum by conventional microbiological techniques using selective agar media. Inclusion of PHS in diet resulted in a significant decrease in total cholesterol and significant increase in HDL relative to the control and antibiotic groups. Antibody titer against NDV was not affected by experimental treatments. E. coli population in birds supplemented with antibiotic and PHS was significantly lower than control, but Lactobacilli spp. population increased only by antibiotic and not by PHS. In conclusion, the results of this study showed that addition of PHS powder seem to have a positive influence on some biochemical parameters and gastrointestinal microflora.

Keywords: antibiotic, biochemical parameters, immune system, Peganum harmala

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Authors: Chung-Young Lee, Se-Hee Ahn, Jun-Gu Choi, Youn-Jeong Lee, Hyuk-Joon Kwon, Jae-Hong Kim

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A/chicken/Korea/01310/2001 (H9N2) (01310) was passaged through embryonated chicken eggs (ECEs) by 20 times (01310-E20), and it has been used for an inactivated oil emulsion vaccine in Korea. After sequential passages, 01310-E20 showed higher pathogenicity in ECEs and acquired multiple mutations including a potential N-glycosylation at position 133 (H3 numbering) in HA and 18aa-deletion in NA stalk. To evaluate the effect of these mutations on the mammalian pathogenicity and resistance to non-specific inhibitors, we generated four PR8-derived recombinant viruses with different combinations of HA and NA from 01310-E2 and 01310-E20 (rH2N2, rH2N20, rH20N2, and rH20N20). According to our results, recombinant viruses containing 01310 E20 HA showed higher growth property in MDCK cells and higher virulence on mice than those containing 01310 E2 HA regardless of NA. The hemagglutination activity of rH20N20 was less inhibited by egg white and mouse lung extract than that of other recombinant viruses. Thus, the increased pathogenicity of 01310-E20 may be related to both higher replication efficiency and resistance to non-specific inhibitors in mice.

Keywords: avian influenza virus, egg adaptation, H9N2, N-glycosylation, stalk deletion of neuraminidase

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Authors: N. A. Kazemi Sefat, M. M. Mohammadi, J. Hadjati, S. Talebi, M. Ajami, H. Daneshvar

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Colorectal cancer metastases result in a significant number of cancer related deaths. Histone deacetylase (HDAC) inhibitors induce growth arrest and apoptosis in a variety of human cancer cells. Sodium butyrate (SB) is a short chain fatty acid, belongs to HDAC inhibitors which is released in the colonic lumen as a consequence of fiber fermentation. In this study, we are about to assess the effect of sodium butyrate on HCT116 human colorectal carcinoma cell line. The viability of cells was measured by microscopic morphologic study and MTT assay. After 48 hours, treatments more than 10 mM lead to cell injury in HCT116 by increasing cell granulation and decreasing cell adhesion (p>0.05). After 72 hours, treatments at 10 mM and more lead to significant cell injury (p<0.05). Our results may suggest that the gene expression which is contributed in cell proliferation and apoptosis has been changed under pressure of HDAC inhibition.

Keywords: colorectal cancer, sodium butyrate, cytotoxicity, MTT

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Authors: Mary-Ann N. Jallad, Dalal F. Jaber, Alexander M. Abdelnoor

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Introduction: Current evidence confirms that both innate and adaptive immune systems are capable of recognizing and abolishing malignant cells. The emergence of cancerous tumors in patients is, therefore, an indication that certain cancer cells can resist elimination by the immune system through a process known as “immune evasion”. In fact, cancer cells often exploit regulatory mechanisms to escape immunity. Such mechanisms normally exist to control the immune responses and prohibit exaggerated or autoimmune reactions. Recently, immunotherapies have shown promising yet limited results. Therefore this study investigates several immunotherapeutic combinations and devises a triple immunotherapy which harnesses the innate and acquired immune responses towards the annihilation of malignant cells through overcoming their ability of immune evasion, consequently hampering malignant progression and eliminating established tumors. The aims of the study are to rule out acute/chronic toxic effects of the proposed treatment combinations, to assess the effect of these combinations on tumor growth and survival rates, and to investigate potential mechanisms underlying the phenotypic results through analyzing serum levels of anti-tumor cytokines, angiogenic factors and tumor progression indicator, and the tumor-infiltrating immune-cells populations. Methodology: For toxicity analysis, cancer-free C57BL/6 mice are randomized into 9 groups: Group 1 untreated, group 2 treated with sterile saline (solvent of used treatments), group 3 treated with Monophosphoryl-lipid-A, group 4 with anti-CTLA4-antibodies, group 5 with 1-Methyl-Tryptophan (Indolamine-Dioxygenase-1 inhibitor), group 6 with both MPLA and anti-CTLA4-antibodies, group 7 with both MPLA and 1-MT, group 8 with both anti-CTLA4-antibodies and 1-MT, and group 9 with all three: MPLA, anti-CTLA4-antibodies and 1-MT. Mice are monitored throughout the treatment period and for three following months. At that point, histological sections from their main organs are assessed. For tumor progression and survival analysis, a murine melanoma model is generated by injecting analogous mice with B16F10 melanoma cells. These mice are segregated into the listed nine groups. Their tumor size and survival are monitored. For a depiction of underlying mechanisms, melanoma-bearing mice from each group are sacrificed at several time-points. Sera are tested to assess the levels of Interleukin-12 (IL-12), Vascular-Endothelial-Growth Factor (VEGF), and S100B. Furthermore, tumors are excised for analysis of infiltrated immune cell populations including T-cells, macrophages, natural killer cells and immune-regulatory cells. Results: Toxicity analysis shows that all treated groups present no signs of neither acute nor chronic toxicity. Their appearance and weights were comparable to those of control groups throughout the treatment period and for the following 3 months. Moreover, histological sections from their hearts, kidneys, lungs, and livers were normal. Work is ongoing for completion of the remaining study aims. Conclusion: Toxicity was the major concern for the success of the proposed comprehensive combinational therapy. Data generated so far ruled out any acute or chronic toxic effects. Consequently, ongoing work is quite promising and may significantly contribute to the development of more effective immunotherapeutic strategies for the treatment of cancer patients.

Keywords: cancer immunotherapy, check-point blockade, combination therapy, melanoma

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Authors: N. Saki, S. Nalbantoglu, M. Akin, G. Arabaci

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Walnut has a great range of phenolic profile and it is used in Asia and Africa for treatment of many diseases and cancer. Phenolic compounds play a number of crucial roles in complex metabolism of plants and of also fruit trees. Consumption of certain phenolics in the food is considered beneficial for human nutrition. Phenolic compounds known as anti-radical inactivators with their high antioxidant activities and these activities play an important role in inhibition of multi-metal corrosion. Many common corrosion inhibitors that are still in use today are health hazards. Therefore, there is still an increased attention directed towards the development of environmentally compatible, nonpolluting corrosion inhibitors. The present study reports the total phenols content, antioxidant potentials and tyrosinase inhibitory activity of the walnut (Juglans regia L.) produced in Turkey. The anti-tyrosinase activity was investigated for walnut at 2 h extraction time and all extracts exhibited tyrosinase activity. The results of this study suggested that walnut can be used as an excellent, easily accessible source of natural antioxidant.

Keywords: antioxidant activity, Juglans Regia, total phenols, tyrosinase activity

Procedia PDF Downloads 271

Authors: Q. B. Maria de la Luz Ortega Juárez, Saúl Rojas Hernández, Itzel Berenice Rodríguez Mera, María Maricela Carrasco Yépez, Mara Gutierrez Sánchez

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Naegleria fowleri is a free-living amoeba found mainly in temperate freshwater and is the etiologic agent of primary amebic meningoencephalitis (PAM), a fatal acute disease with a mortality rate greater than 95%. At present, there are no treatments available for MAP, and the development of effective vaccines that generate long-term immunological memory allowing protection against MAP would be of great importance. The objective of this work was to analyze the effector and memory immune response in BALB/c mice immunized with total extract of N. fowleri co-administered with cholera toxin. In this study, BALB/c mice were immunized four times intranasally with ET of N. fowleri adjuvanted with CT with or without booster at three months and were challenged or not with the lethal dose of N. fowleri, determining survival, the humoral, effector and memory response, by ELISA and flow cytometry techniques. The results obtained showed that the survival of mice immunized with booster had 60% protection compared to the group without booster, which obtained 20% protection. Evaluating the humoral response, it was found that both IgG and IgA levels were higher in sera than in nasal washes in both treatments. In the cellular response, the increase in the percentage of positive cells was found for effector T and B lymphocytes in the nasal passages (NP) in the group with boost and nasopharynx-associated lymphoid tissue (NALT) in the group without boost and lymphocytes only. B in both treatments, as well as in memory cells treatment with boost T lymphocytes in PN and NALT and without boost in cervical lymph nodes (CG) with respect to B lymphocytes, in PN, GC and NALT in treatment with boost and NALT in treatment without booster. Therefore, the involvement of the effector immune response and memory play a fundamental role for protection against N. fowleri and for the development of vaccine candidates.

Keywords: immune response, immunological memory, naegleria fowleri, primary amebic meningoencephalitis

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Authors: Azam Bayat, Aref Khalkhali, Ali Reza Mahjoub

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Healthy and viable herbal supplement were prepared from wheat by a green route. This organic biomaterial was named Nutrition Bio-shield Superfood (NBS). The NBS supplement had various vitamins, macro and micro molecules, and ingredients. In this study, 20 small Balb/C labile specimens were used in a weighing 30 ± 5 range. The samples were randomly divided into different groups, then the groups were divided into 5 groups. According to the results of this study, the mean number of white blood cells and neutrophil percentage in the experimental group receiving healthy and live dietary supplement showed a significant increase at the 5% probability level in all three groups received 50, 100 and 150 mg/ kg body weight of the mouse compared to the control group. In general, the dietary supplement increases the level of immunity.

Keywords: healthy and live herbal supplement, biomaterial, immune system, enhancement

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Authors: O. J. Jesumoroti, Faridoon, R. Klein, K. A. Iobb, D. Mnkadhla, H. C. Hoppe, P. T. Kaye

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The 1, 3-aryl diketo acids (DKA) based agents represent an important class of HIV integrase (IN) strand transfer inhibitors. In other to study the chelating role of the divalent metal ion in the inhibition of IN strand transfer, we designed and synthesized a series of 2-hydroxy-3-oxo-3-phenyl propionate derivatives with the notion that such compounds could interact with the divalent ion in the active site of IN. The synthetic sequence to the desired compounds involves the concept of Doebner knoevenagel condensation, Fischer esterification and ketohydroxylation using neuclophilic re-oxidant; compounds were characterized by their IR, IHNMR, 13CNMR, HRMS spectroscopic data and melting point determination. Also, molecular docking was employed in this study and it was revealed that there is interaction with the active site of the enzyme. However, there is disparity in the corresponding anti-HIV activity determined by the experimental bioassay. These compounds lack potency at low micromolar concentration when compared to the results of the docking studies. Nevertheless, the results of the study suggest modification of the aryl ring with one or two hydroxyl groups to improve the inhibitory activity.

Keywords: anti-HIV-1 integrase, ketohydroxylation, molecular docking, propionate derivatives

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Authors: Yulin Rao, Zhixuan Li, Burra Venkata Durga Kumar

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Intrusion detection refers to monitoring the actions of internal and external intruders on the system and detecting the behaviours that violate security policies in real-time. In intrusion detection, there has been much discussion about the application of neural network technology and artificial immune system (AIS). However, many solutions use static methods (signature-based and stateful protocol analysis) or centralized intrusion detection systems (CIDS), which are unsuitable for real-time intrusion detection systems that need to process large amounts of data and detect unknown intrusions. This article proposes a framework for a distributed intrusion detection system (DIDS) with multi-agents based on the concept of AIS and neural network technology to detect anomalies and intrusions. In this framework, multiple agents are assigned to each host and work together, improving the system's detection efficiency and robustness. The trainer agent in the central server of the framework uses the artificial neural network (ANN) rather than the negative selection algorithm of AIS to generate mature detectors. Mature detectors can distinguish between self-files and non-self-files after learning. Our analyzer agents use genetic algorithms to generate memory cell detectors. This kind of detector will effectively reduce false positive and false negative errors and act quickly on known intrusions.

Keywords: artificial immune system, distributed artificial intelligence, multi-agent, intrusion detection system, neural network

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Authors: Sirikwan Ponprateep, Anchalee Tassanakajon, Vichien Rimphanitchayakit

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A Kazal-type serine proteinase inhibitor, SPIPm2, was abundantly expressed in the hemocytes and secreted into shrimp plasma has anti-viral property against white spot syndrome virus (WSSV). To discover the molecular mechanism of antiviral activity, the binding assay showed that SPIPm2 bind to the components of viral particle and shrimp hemocyte. From our previous report, viral target protein of SPIPm2 was identified, namely WSV477 using yeast two-hybrid screening. WSV477 is an early gene product of WSSV and involved in viral propagation. In this study, the co-immunoprecipitation technique and Tandem Mass Spectrometry (LC-MS/MS) was used to identify the target protein of SPIPm2 from shrimp hemocyte. The target protein of SPIPm2 was cyclophilin A. In vertebrate, cyclophilin A or peptidylprolyl isomerase A was reported to be the immune suppressor interacted with cyclosporin A involved in immune defense response. The recombinant cyclophilin A from Penaeus monodon (rPmCypA) was produced in E.coli system and purified using Ni-NTA column to confirm the protein-protein interaction. In vitro pull-down assay showed the interaction between rSPIPm2 and rPmCypA. To study the biological function of these proteins, the expression analysis of immune gene in shrimp defense pathways will be investigated after rPmCypA administration.

Keywords: cyclophilin A, protein-protein interaction, Kazal-type serine proteinase inhibitor, Penaeus monodon

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Authors: Hassan Nour, Nouh Mounadi, Oussama Abchir, Belaidi Salah, Samir Chtita

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Cholinesterase enzymes are biological catalysts essential for the transformation of acetylcholine, which is a neurotransmitter implicated in memory and learning, into acetic acid and choline, altering the neurotransmission process in Alzheimer’s disease patients. Therefore, inhibition of cholinesterase enzymes is a relevant strategy for the symptomatic treatment of Alzheimer’s disease. The current investigation aims to explore potential Cholinesterase (ChE) inhibitors through a comprehensive computational approach. Forty-nine phytoconstituents extracted from Cannabis sativa L were in-silico screened using molecular docking, pharmacokinetic and toxicological analysis to evaluate their possible inhibitory effect towards the cholinesterase enzymes. Two phytoconstituents belonging to cannabinoid derivatives were revealed to be promising candidates for Alzheimer therapy by acting as cholinesterase inhibitors. They have exhibited high binding affinities towards the cholinesterase enzymes and showed their ability to interact with key residues involved in cholinesterase enzymatic activity. In addition, they presented good ADMET profiles allowing them to be promising oral drug candidates. Furthermore, molecular dynamics (MD) simulations were executed to explore their interactions stability under mimetic biological conditions and thus support our findings. To corroborate the docking results, the binding free energy corresponding to the more stable ligand-ChE complexes was re-estimated by applying the MM-PBSA method. MD and MM-PBSA studies affirmed that the ligand-ChE recognition is spontaneous reaction leading to stable complexes. The conducted investigations have led to great findings that would strongly guide the pharmaceutical industries towards the rational development of potent anti-Alzheimer agents.

Keywords: alzheimer’s disease, molecular docking, cannabis sativa l, cholinesterase inhibitors

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Authors: Alyaa Ahmed Farid, Aida Ismail, Ibrahim Rabia, Azza Fahmy, Azza El Amir

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This study was designed for assessment of 3 types of Cysteine protease inhibitors (CPIs) fluromethylketone (FMK), vinyl sulfone (VS) and sodium nitro prussid (SNP), to define which of them is the best? The experiments aimed to define the protective power of each inhibitor alone or combined with PZQ for curing S. mansoni infection in mice. In vitro, treated S. mansoni adult worms recorded a mortality rate after 1 hr of exposure to 500 ppm of FMK, VS and SNP as 75, 70 and 60%, while, treated cercaria recorded 75, 60 and 50%, respectively. FMK+PZQ treatment recorded the maximum reduction in worm burden (97.2% at 5 wk PI). VS treatment alone or combined with PZQ increases IgM, total IgG, IgG2 and IgG4 levels. In EM study of worm tegument, while only detachment of spines was observed in PZQ treated group, the completely implanted spines were reported in the degenerated tegument of adult worms in all groups treated with CPIs. Treatment with VS+PZQ increased Igs levels but, its effect was different on worm reduction. So, it is not enough to eliminate the infection and FMK+PZQ considered the antischistosomicidal drug of choice.

Keywords: praziquantel, fluromethylketone, vinyl sulfone, worm burden, immunoglobulin pattern

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Authors: Tefera Worku Mekonnen, Hiseh Chih Tsai

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Enhancement of drug efficacy is essential in cancer treatment. The immune stimulator ovalbumin (Ova)-coated citric acid (AC-)-stabilized iron oxide nanoparticles (AC-IO-Ova NPs) and enhanced permeability and retention (EPR) based tumor targeted 4.5 (4.5G) poly(amidoamine) dendrimer-cisplatin nanocomplex (4.5GDP-Cis-pt NC) were used for enhanced anticancer efficiency. The formations of 4.5GDP-Cis-pt NC, AC-IO, and AC-IO-Ova NPs have been examined by FTIR, X-ray diffraction, Raman, and X-ray photoelectron spectroscopy. The conjugation of cisplatin (Cis-pt) with 4.5GDP was confirmed using carbon NMR. The tumor-specific 4.5GDP-Cis-pt NC provided ~45% and 28% cumulative cisplatin release in 72 h at pH 6.5 and 7.4, respectively. A significant immune response with high TNF-α and IL-6 cytokine secretion was confirmed when the co-incubation of AC-IO-Ova with RAW 264.7 or HaCaT cells. AC-IO-Ova NP was biocompatible in different cell lines, even at a high concentration (200 µg mL−1). In contrast, AC-IO-Ova NPs mixed with 4.5GDP-Cis-pt NC (Cis-pt at 15 µg mL−1) significantly increased the cytotoxicity against the cancer cells, which is dose-dependent on the concentration of AC-IO-Ova NPs. The increased anticancer effects may be attributed to the generation of reactive oxygen species (ROS). Moreover, the efficiency of anticancer cells may be further assisted by induction of an innate immune response via M1 macrophage polarization due to the presence of AC-IO-Ova NPs. We provide a better synergestic chemoimmunotherapeutic strategy to enhance the efficiency of anticancer of cisplatin via chemotherapeutic agent 4.5GDP-Cis-pt NC and induction of proinflammatory cytokines to stimulate innate immunity through AC-IO-Ova NPs against tumors.

Keywords: cisplatin-release, iron oxide, ovalbumin, poly(amidoamine) dendrimer

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Authors: Kalbiye Konanc, Ergin Ozturk

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To examine the effects of an ethanol liquid extract obtained from raw bee propolis (PE) on fattening performance and physiology such as vaccine-antibody relationship, microbial profile, immune status and some blood parameters of broiler chickens were used a total of 600 broiler (Ross 308) chicks, obtained from eggs of 288, 38-weeks-old broiler breeding. There were 6 groups: CC (Parent-Control and Offspring-Control, CP (Parent-Control and Offspring-propolis extract, Cip (Parent-Control and Offspring-in-ovo propolis extract), Cis (Parent-Control and Chickens-in-ovo saline), PeC (Parent-propolis extract and Offspring-Control), PeP (Parent-Propolis extract and Offspring-Propolis extract). Each group was consisted of 10 replications with 10 broiler offspring, and the experiment was lasted for 6 weeks with ethanol-extracted propolis concentration is 400 ppm/kg diet. While the highest feed consumptions at 0-21 days and 0-42 days were found in PeC, the best feed conversion ratio at 0-42 days was found in CP group. The live weight gains were found not to be different among the groups. The highest alanine aminotransferase activities were found in CC and CP and aspartate aminotransferase activities in PeP and PeC groups. The highest triglyceride and total antioxidant levels were found highest in CC and the highest total oxidant level in Cip group. IgA level in hatched eggs and IgM value after slaughtering were highest in Cip group. The best immune response was obtained for 21st day Newcastle Disease vaccine in CC and Cis groups and for 28th day Infectious Bursal Disease vaccine in CP group. The highest total aerobic microorganism and the lowest total fungi count were found in PeP group. In conclusion, it was determined that in-ovo propolis ethanol extract (Cip) increased the maternal antibody levels, that had not consistent effects on blood biochemical parameters except for triglyceride, that led to decrease in E. coli counts and that it can provide strong immune response against Infectious Bursal Disease.

Keywords: bee propolis, in-ovo feeding, immune parameters, poultry, maternal antibody, microorganisms

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