Search results for: immune checkpoint inhibitors

Authors: Mohamad F. Jamiluddin, Emeline Sarry, Ana Bejanariu, Cécile Bauche

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Introduction: Over 360 million people are chronically infected with hepatitis B virus (HBV), of whom 1 million die each year from HBV-associated liver cirrhosis or hepatocellular carcinoma. Current treatment options for chronic hepatitis B depend on interferon-α (IFNα) or nucleos(t)ide analogs, which control virus replication but rarely eliminate the virus. Treatment with PEG-IFNα leads to a sustained antiviral response in only one third of patients. After withdrawal of the drugs, the rebound of viremia is observed in the majority of patients. Furthermore, the long-term treatment is subsequently associated with the appearance of drug resistant HBV strains that is often the cause of the therapy failure. Among the new therapeutic avenues being developed, therapeutic vaccine aimed at inducing immune responses similar to those found in resolvers is of growing interest. The high prevalence of chronic hepatitis B necessitates the design of better vaccination strategies capable of eliciting broad-spectrum of cell-mediated immunity(CMI) and humoral immune response that can control chronic hepatitis B. Induction of HBV-specific T cells and B cells by therapeutic vaccination may be an innovative strategy to overcome virus persistence. Lentiviral vectors developed and optimized by THERAVECTYS, due to their ability to transduce non-dividing cells, including dendritic cells, and induce CMI response, have demonstrated their effectiveness as vaccination tools. Method: To develop a HBV therapeutic vaccine that can induce a broad but specific immune response, we generated recombinant lentiviral vector carrying IRES(Internal Ribosome Entry Site)-containing bicistronic constructs which allow the coexpression of two vaccine products, namely HBV T- cell epitope vaccine and HBV virus like particle (VLP) vaccine. HBV T-cell epitope vaccine consists of immunodominant cluster of CD4 and CD8 epitopes with spacer in between them and epitopes are derived from HBV surface protein, HBV core, HBV X and polymerase. While HBV VLP vaccine is a HBV core protein based chimeric VLP with surface protein B-cell epitopes displayed. In order to evaluate the immunogenicity, mice were immunized with lentiviral constructs by intramuscular injection. The T cell and antibody immune responses of the two vaccine products were analyzed using IFN-γ ELISpot assay and ELISA respectively to quantify the adaptive response to HBV antigens. Results: Following a single administration in mice, lentiviral construct elicited robust antigen-specific IFN-γ responses to the encoded antigens. The HBV T- cell epitope vaccine demonstrated significantly higher T cell immunogenicity than HBV VLP vaccine. Importantly, we demonstrated by ELISA that antibodies are induced against both HBV surface protein and HBV core protein when mice injected with vaccine construct (p < 0.05). Conclusion: Our results highlight that THERAVECTYS lentiviral vectors may represent a powerful platform for immunization strategy against chronic hepatitis B. Our data suggests the likely importance of Lentiviral vector based novel bicistronic construct for further study, in combination with drugs or as standalone antigens, as a therapeutic lentiviral based HBV vaccines. THERAVECTYS bicistronic HBV vaccine will be further evaluated in animal efficacy studies.

Keywords: chronic hepatitis B, lentiviral vectors, therapeutic vaccine, virus-like particle

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Authors: Qing Zhang, Janak L. Pathak, Macro N. Helder, Richard T. Jaspers, Yin Xiao

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Introduction: Nanomaterial-based bone regeneration is greatly influenced by the immune microenvironment. Tissue-engineered nanomaterials mediate the inflammatory response of macrophages to regulate bone regeneration. Silica nanoparticles have been widely used in tissue engineering-related preclinical studies. However, the effect of topological features on the surface of silica nanoparticles on the immune response of macrophages remains unknown. Purposes: The aims of this research are to compare the influences of normal and pollen-like silica nano-surface topography on macrophage immune responses and to obtain insight into their potential regulatory mechanisms. Method: Macrophages (RAW 264.7 cells) were exposed to mesoporous silica nanoparticles with normal morphology (MSNs) and pollen-like morphology (PMSNs). RNA-seq, RT-qPCR, and LSCM were used to assess the changes in expression levels of immune response-related genes and proteins. SEM and TEM were executed to evaluate the contact and adherence of silica nanoparticles by macrophages. For the assessment of the immunomodulation-mediated osteogenic potential, BMSCs were cultured with conditioned medium (CM) from LPS pre-stimulated macrophage cultures treated with MSNs or PMSNs. Osteoimmunomodulatory potential of MSNs and PMSNs in vivo was tested in a mouse cranial bone osteolysis model. Results: The results of the RNA-seq, RT-qPCR, and LSCM assays showed that PMSNs inhibited the expression of pro-inflammatory genes and proteins in macrophages. SEM images showed distinct macrophage membrane surface binding patterns of MSNs and PMSNs. MSNs were more evenly dispersed across the macrophage cell membrane, while PMSNs were aggregated. PMSNs-induced macrophage anti-inflammatory response was associated with upregulation of the cell surface receptor CD28 and inhibition of ERK phosphorylation. TEM images showed that both MSNs and PMSNs could be phagocytosed by macrophages, and inhibiting nanoparticle phagocytosis did not affect the expression of anti-inflammatory genes and proteins. Moreover, PMSNs-induced conditioned medium from macrophages enhanced BMP-2 expression and osteogenic differentiation mBMSCs. Similarly, PMSNs prevented LPS-induced bone resorption via downregulation of inflammatory reaction. Conclusions: PMSNs can promote bone regeneration by modulating osteoimmunological processes through surface topography. The study offers insights into how surface physical contact cues can modulate the regulation of osteoimmunology and provides a basis for the application of nanoparticles with pollen-like morphology to affect immunomodulation in bone tissue engineering and regeneration.

Keywords: physical contact, osteoimmunology, macrophages, silica nanoparticles, surface morphology, membrane receptor, osteogenesis, inflammation

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Authors: Awe Ayodeji Samson, Adeuja Yetunde Omowunmi

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Corruption is a ‘monster’ that can consume a whole nation, continent and even the world if it is not destroyed while it is still immature; It grows in the mind of the people, takes over their thinking and guides their decision-making process. Corruption snowballs into socio-economic catastrophe that might be difficult to deal with. Corruption which is a disease of the mind can be alleviated in Africa and the world at large by transforming a Corruption-Prone Mind to a Corruption-Immune Mind and to achieve this, we have to change our value system because the use of anti-graft agencies alone is not enough. Therefore, we have to fight corruption from the inside and the outside. Value System is the principle of right and wrong that are accepted by an individual or a social group; the reviewing and reordering of our value system is the solution to the problem of corruption as proposed by this research because the African society has become a ‘Money and Power Driven Society’ where the ‘I am worth concept’ which is a problematic concept has created an ‘Aggressive Society’ with grasping and money-grabbing individuals. We place more priority on money and the display of opulence. Hence, this has led to a ‘Triangular Society’ where minority is lavishing in plenty and majority is gasping for little. The get rich quick syndrome, the ethnicity syndrome, weakened educational system are signs of the prevalence of corruption in Africa This research has analyzed role and impact of the change in our value system in the fight against corruption in Africa and has therefore proposed the change in our value system as the way forward in the fight against corruption in Africa.

Keywords: corruption-prone mind, corruption-immune mind, triangular society, aggressive society, money and power-driven society

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Authors: Lynda C. Mbadugha, Bankole Awuzie, Kwanda Khumalo, Lindokuhle Matsebula, Masenoke Kgaditsi

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Inadequate waste management remains a fundamental issue in the majority of cities around the globe, but it becomes a threat when it concerns informal settlements. Although studies have evaluated the performance of waste management measures, only a few have addressed that with a focus on South African informal settlements and the reasons for their apparent ineffectiveness in such locations. However, there may be evidence of variations in the extant problems due to the uniqueness of each location and the factors influencing the performance. Thus, there is a knowledge deficit regarding implementing waste management measures in South African informal settlements. This study seeks to evaluate the efficacy of waste management measures in the Alaska informal settlement in South Africa to assess the previously collected data of other areas using the degree of correlation. The research investigated a real-world scenario in the specified location using a case study approach and multiple data sources. The findings described various waste management practices used in Alaska's informal settlements; however, a correlation was found between the performance of these measures and those already used. The observed differences are primarily attributable to the physical characteristics of the locations, the lack of understanding of the environmental and health consequences of careless waste disposal, and the negative attitudes of the residents toward waste management practices. This study elucidates waste management implementation in informal settlements. It contributes to the relevant bodies of knowledge by describing these practices in South Africa. This paper's practical value emphasizes the general waste management characteristics of South Africa's informal settlements to facilitate the planning and provision of necessary interventions. The study concludes that the enablers and inhibitors are mainly political, behavioral, and environmental concerns.

Keywords: factors, informal settlement, performance, waste management

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Authors: Ananya Gupta, Sangeeta Bhaskar

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Mycobacterium indicus pranii (MIP) is a saprophytic mycobacterium. It is a predecessor of M. avium complex (MAC). Whole genome analysis and growth kinetics studies have placed MIP in between pathogenic and non-pathogenic species. It shares significant antigenic repertoire with M. tuberculosis and have unique immunomodulatory properties. MIP provides better protection than BCG against pulmonary tuberculosis in animal models. Immunization with MIP by aerosol route provides significantly higher protection as compared to immunization by subcutaneous (s.c.) route. However, mechanism behind differential protection has not been studied. In this study, using mice model we have evaluated and compared the M.tb specific immune response in lung compartments (airway lumen / lung interstitium) as well as spleen following MIP immunization via nasal (i.n.) and s.c. route. MIP i.n. vaccination resulted in increased seeding of memory T cells (CD4+ and CD8+ T-cells) in the airway lumen. Frequency of CD4+ T cells expressing Th1 migratory marker (CXCR3) and activation marker (CD69) were also high in airway lumen of MIP i.n. group. Significantly high ex vivo secretion of cytokines- IFN-, IL-12, IL-17 and TNF- from cells of airway luminal spaces provides evidence of antigen-specific lung immune response, besides generating systemic immunity comparable to MIP s.c. group. Analysis of T cell response on per cell basis revealed that antigen specific T-cells of MIP i.n. group were functionally superior as higher percentage of these cells simultaneously secreted IFN-gamma, IL-2 and TNF-alpha cytokines as compared to MIP s.c. group. T-cells secreting more than one of the cytokines simultaneously are believed to have robust effector response and crucial for protection, compared with single cytokine secreting T-cells. Adoptive transfer of airway luminal T-cells from MIP i.n. group into trachea of naive B6 mice revealed that MIP induced CD8 T-cells play crucial role in providing long term protection. Thus the study demonstrates that MIP intranasal vaccination induces M.tb specific memory T-cells in the airway lumen that results in an early and robust recall response against M.tb infection.

Keywords: airway lumen, Mycobacterium indicus pranii, Th1 migratory markers, vaccination

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Authors: T. C. C. Soo, S. Bhassu

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Unlike the common presence of both innate and adaptive immunity in vertebrates, crustaceans, in particular, shrimps, have been discovered to possess only innate immunity. This further emphasizes the importance of innate immunity within shrimps in pathogenic resistance. Under the study of pathogenic immune challenge, different shrimp species actually exhibit varying degrees of immune resistance towards the same pathogen. Furthermore, even within the same shrimp species, different batches of challenged shrimps can have different strengths of immune defence. Several important pathways are activated within shrimps during pathogenic infection. One of them is JAK-STAT pathway that is activated during bacterial, viral and fungal infections by which STAT(Signal Transducer and Activator of Transcription) gene is the core element of the pathway. Based on theory of Central Dogma, the genomic information is transmitted in the order of DNA, RNA and protein. This study is focused in uncovering the important evolutionary patterns present within the DNA (non-coding region) and RNA (coding region). The three shrimp species involved are Macrobrachium rosenbergii, Penaeus monodon and Litopenaeus vannamei which all possess commercial significance. The shrimp species were challenged with a famous penaeid shrimp virus called white spot syndrome virus (WSSV) which can cause serious lethality. Tissue samples were collected during time intervals of 0h, 3h, 6h, 12h, 24h, 36h and 48h. The DNA and RNA samples were then extracted using conventional kits from the hepatopancreas tissue samples. PCR technique together with designed STAT gene conserved primers were utilized for identification of the STAT coding sequences using RNA-converted cDNA samples and subsequent characterization using various bioinformatics approaches including Ramachandran plot, ProtParam and SWISS-MODEL. The varying levels of immune STAT gene activation for the three shrimp species during WSSV infection were confirmed using qRT-PCR technique. For one sample, three biological replicates with three technical replicates each were used for qRT-PCR. On the other hand, DNA samples were important for uncovering the structural variations within the genomic region of STAT gene which would greatly assist in understanding the STAT protein functional variations. The partially-overlapping primers technique was used for the genomic region sequencing. The evolutionary inferences and event predictions were then conducted through the Bayesian Inference method using all the acquired coding and non-coding sequences. This was supplemented by the construction of conventional phylogenetic trees using Maximum likelihood method. The results showed that adaptive evolution caused STAT gene sequence mutations between different shrimp species which led to evolutionary divergence event. Subsequently, the divergent sites were correlated to the differing expressions of STAT gene. Ultimately, this study assists in knowing the shrimp species innate immune variability and selection of disease resistant shrimps for breeding purpose. The deeper understanding of STAT gene evolution from the perspective of both purifying and adaptive approaches not only can provide better immunological insight among shrimp species, but also can be used as a good reference for immunological studies in humans or other model organisms.

Keywords: gene evolution, JAK-STAT pathway, immunology, STAT gene

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Authors: Debasmita Mukhopadhyay, Manika Pal Bhadra

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MiRNAs contribute to oncogenesis either as tumor suppressors or oncogenes. Hence, discovery of miRNA-based therapeutics are imperative to ameliorate cancer. Modulation of miRNA maturation is accomplished via several therapeutic agents, including small molecules and oligonucleotides. Due to the attractive pharmacokinetic properties of small molecules over oligonucleotides, we set to identify small molecule inhibitors of a metastasis-inducing microRNA. Cytotoxicity profile of aza-flavanone C1 was analyzed in a panel of breast cancer cells employing the NCI-60 screen protocols. Flow cytometry, immunofluorescence and western blotting of apoptotic or EMT markers were performed to analyze the effect of C1. A dual luciferase assay unequivocally suggested that C1 repressed endogenous miR-10b in MDA-MB-231 cells. A derivative of aza-flavanone C1 is shown as a strong inhibitor miR-10b. Blockade of miR-10b by C1 resulted in decreased expression of miR-10b targets in an aggressive breast cancer cell line model, MDA-MB-231. Abrogation of TWIST1, an EMT-inducing transcription factor also contributed to C1 mediated apoptosis. Moreover C1 exhibited a specific and selective down-regulation of miR-10b and did not function as a general inhibitor of miRNA biogenesis or other oncomiRs of breast carcinoma. Aza-flavanone congener C1 functions as a potent inhibitor of the metastasis-inducing microRNA, miR-10b. Our present study provides evidence for targeting metastasis-inducing microRNA, miR-10b with a derivative of Aza-flavanone. Better pharmacokinetic properties of small molecules place them as attractive agents compared to nucleic acids based therapies to target miRNA. Further work, in generating analogues based on aza-flavanone moieties will significantly improve the affinity of the small molecules to bind miR-10b. Finally, it is imperative to develop small molecules as novel miRNA-therapeutics in the fight against cancer.

Keywords: breast cancer, microRNA, metastasis, EMT

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Authors: Asghar Arif

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Lung cancer has been recognized as one of the greatest common cancers, causing the annual mortality rate of about 1.2 million people in the world. Lung cancer is the most prevalent cancer in men and the third-most common cancer among women (after breast and digestive cancers).Recent evidences have shown the inflammatory process as one of the potential factors of cancer. Tuberculosis (TB), pneumonia, and chronic bronchitis are among the most important inflammation-inducing factors in the lungs, among which TB has a more profound role in the emergence of cancer.TB is one of the important mortality factors throughout the world, and 205,000 death cases are reported annually due to this disease. Chronic inflammation and fibrosis due to TB can induce genetic mutation and alternations. Parenchyma tissue of lung is involved in both diseases of TB and lung cancer, and continuous cough in lung cancer, morphological vascular variations, lymphocytosis processes, and generation of immune system mediators such as interleukins, are all among the factors leading to the hypothesis regarding the role of TB in lung cancer Some reports have shown that the induction of necrosis and apoptosis or TB reactivation, especially in patients with immune-deficiency, may result in increasing IL-17 and TNF_α, which will either decrease P53 activity or increase the expression of Bcl-2, decrease Bax-T, and cause the inhibition of caspase-3 expression due to decreasing the expression of mitochondria cytochrome oxidase. It has been also indicated that following the injection of BCG vaccine, the host immune system will be reinforced, and in particular, the rates of gamma interferon, nitric oxide, and interleukin-2 are increased. Therefore, CD4 + lymphocyte function will be improved, and the person will be immune against cancer.Numerous prospective studies have so far been conducted on the role of TB in lung cancer, and it seems that this disease is effective in that particular cancer.One of the main challenges of lung cancer is its correct and timely diagnosis. Unfortunately, clinical symptoms (such as continuous cough, hemoptysis, weight loss, fever, chest pain, dyspnea, and loss of appetite) and radiological images are similar in TB and lung cancer. Therefore, anti-TB drugs are routinely prescribed for the patients in the countries with high prevalence of TB, like Pakistan. Regarding the similarity in clinical symptoms and radiological findings of lung cancer, proper diagnosis is necessary for TB and respiratory infections due to nontuberculousmycobacteria (NTM). Some of the drug resistive TB cases are, in fact, lung cancer or NTM lung infections. Acid-fast staining and histological study of phlegm and bronchial washing, culturing and polymerase chain reaction TB are among the most important solutions for differential diagnosis of these diseases. Briefly, it is assumed that TB is one of the risk factors for cancer. Numerous studies have been conducted in this regard throughout the world, and it has been observed that there is a significant relationship between previous TB infection and lung cancer. However, to prove this hypothesis, further and more extensive studies are required. In addition, as the clinical symptoms and radiological findings of TB, lung cancer, and non-TB mycobacteria lung infections are similar, they can be misdiagnosed as TB.

Keywords: TB and lung cancer, TB people, TB servivers, TB and HIV aids

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Authors: Saekil Yun, Sib Sankar Giri, Jin Woo Jun, Hyoun Joong Kim, Sang Guen Kim, Sang Wha Kim, Jung Woo Kang, Se Jin Han, Se Chang Park

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In aquaculture, vaccination is important to control and prevent diseases. In the study, we utilized poly D,L-lactide-co-glycolic acid (PLGA) microparticles (MPs) for encapsulating formalin-killed Aeromonas hydrophila cells. To assess the innate and adaptive immune responses, carps and loaches were used for the experiments. Fish were divided into three groups (A, B, C). Total antigen of 0.1 ml vaccine was adjusted by 2 x 108 CFU and injected via intraperitoneal route. Group A was vaccinated with 0.1 ml of PLGA vaccine, group B was with 0.1 ml of FKC vaccine and group C was with 0.1 ml of sterile PBS. All three groups were challenged with A. hydrophila and challenge dose was lethal dose (LD50). Loaches and carp were then challenged with A. hydrophila at 12 and 20 weeks post vaccination (wpv), and 10 and 14 wpv, respectively, and relative survival rates were calculated. For both fish species, the curve of antibody titer over time was shallower in the PLGA group than the FKC group and the PLGA groups demonstrated higher survival rates at all time-points. In the groups of PLGA-MP, relative mRNA levels of IL-1β, TNF-α, lysozyme C and IgM were significantly upregulated than FKC treated groups. Biodegradable PLGA microparticle vaccine could induce longer immune responses than original FKC vaccines to protect from A. hydrophila infection.

Keywords: PLGA, microparticles, Aeromonas hydrophila, vaccine

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Authors: Maryam Amiri Resketi, Sakineh Yeganeh, Khosro Jani Khalili

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The aim of this study was to investigate the effect of dietary lemon peel essential oil (Citrus limon) on serum parameters and liver enzyme activity of rainbow trout (Oncorhynchus mykiss) was exposed to deltamethrin. The 96-hour lethal concentrations of the toxin on rainbow trout (Oncorhynchus mykiss), was determined according to standard procedures O.E.C.D in static (Static). 96-hour LC50 was obtained 0.0082 mg/l by using statistical methods Probit program version. The maximum allowable concentration of deltamethrin was calculated 0.00082 mg/l in natural environment and was used for this experiment. Eight treatments were designed based on 3 levels of lemon essential oil 200, 400 and 600 mg/kg and 2 levels of deltamethrin 0 and 0.00082. Rainbow trout with an average weight of 95.14 ± 3.8 g were distributed in 300-liter tanks and cultured for eight weeks. Fish were fed in an amount of 2% of body weight. Water changes were done on a daily basis (90 percent of the tank). About the tanks containing 10 % deltamethrin, after dewatering, suitable concentration of toxin was added to water. At the end of the test, serum biochemical parameters (total protein, albumin, glucose, cholesterol, and triglycerides) and liver enzymes (ALP, AST, ALT and LDH) were evaluated. In treatments without and with toxin, increasing 400 mg/kg oil increased total protein and albumin levels and lower cholesterol and triglycerides were observed (p < 0.05). Rise to the level of 400 mg/kg of lemon peel essential oil treatments contain pesticides, reduced the amount of enzymes ALP, ALT and LDH compared to treatment of toxin-free lemon peel essential oil (p < 0.05). The results showed that usage of lemon peel essential oil in fish diet can increase the immune system parameters and strengthen it with strong antioxidant activity followed by reducing the effect of deltamethrin on the immune system of fish and effective dose can prevent the adverse effects of toxin due to the weakening of the fish immune system at the time of toxic pollutant entrance in fish farms.

Keywords: deltamethrin, Oncorhynchus mykiss, LC5096h, lemon peel (citrus limon) essential oil, serum parameters, liver enzymes

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Authors: S. Ibrahim, D. Salilew-Wondim, M. Hoelker, C. Looft, E. Tholen, C. Grosse-Brinkhaus, K. Schellander, C. Neuhoff, D. Tesfaye

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Bovine endometrial cells appear to have a key role in innate immune defense of the female genital tract. A better understanding of molecular changes in microRNAs (miRNAs) and their target genes expression may identify reliable prognostic indicators for cows that will resolve inflammation and resume cyclicity. In the current study, we hypothesized that let-7 miRNAs family has a primary role in the innate immune defence of the endometrium tissue against bacterial infection, which is partly achieved via regulating mRNA stability of pro-inflammatory cytokines at the post-transcriptional level. Therefore, we conducted two experiments. In the first experiment, primary bovine endometrial cells were challenged with clinical (3.0 μg/ml) and sub-clinical (0.5 μg/ml) doses of lipopolysaccharide (LPS) for 24h. In the 2nd experiment, we have investigated the potential role of let-7 miRNAs (let-7a and let-7f) using gain and loss of function approaches. Additionally, tumor necrosis factor alpha (TNFα), transforming growth factor beta 1 induced transcript 1 (TGFB1I1) and serum deprivation response (SDPR) genes were validated using reporter assay. Here we addressed for the first time that let-7 miRNAs have a precise role in bovine endometrium, where LPS dysregulated let-7 miRNAs family expression was associated with an increased pro-inflammatory cytokine level by directly/indirectly targeting the TNFα, interleukin 6 (IL6), nuclear factor kappa-light-chain enhancer of activated B cells (NFκB), TGFβ1I1 and SDPR genes. To our knowledge, this is the first study showing that TNFα, TGFβ1I1 and SDPR were identified and validated as novel let-7 miRNAs targets and could have a distinct role in inflammatory immune response of LPS challenged bovine endometrial cells. Our data represent a new finding by which uterine homeostasis is maintained through functional regulation of let-7a by down-regulation of pro-inflammatory cytokines expression (TNFα and IL6) at the mRNA and protein levels. These findings suggest that LPS serves as a negative regulator of let-7 miRNAs expression and provides a mechanism for the persistent pro-inflammatory phenotype, which is a hallmark of bovine subclinical endometritis.

Keywords: bovine endometrial cells, let-7, lipopolysaccharide, pro-inflammatory cytokines

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Authors: Mitakshara Sharma, Sonal Sharma

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Vesiculobullous diseases are heterogeneous group of dermatological disorders with protean manifestations. The most important technique for the patients with vesiculobullous diseases is conventional histopathology and confirmatory tests like direct immunofluorescence (DIF) and indirect immunofluorescence (IIF). DIF has been used for decades to investigate pathophysiology and in the diagnosis. It detects molecules such as immunoglobulins and complement components. It is done on the perilesional skin. Diagnosis of DIF test depends on features like primary site of the immune deposits, class of immunoglobulin, number of immune deposits and deposition at other sites. The aim of the study is to correlate DIF with clinical and histopathological findings and to analyze the utility of DIF in the diagnosis of these disorders. It is a retrospective descriptive study conducted for 2 years from 2015 to 2017 in Department of Pathology, GTB Hospital on perilesional punch biopsies of vesiculobullous lesions. Biopsies were sent in Michael’s medium. The specimens were washed, frozen and incubated with fluorescein isothiocyanate (FITC) tagged antihuman antibodies IgA, IgG, IgM, C3 & F and were viewed under fluorescent microscope. Out of 401 skin biopsies submitted for DIF, 285 were vesiculobullous diseases, in which the most common was Pemphigus vulgaris (34%) followed by Bullous pemphigoid (21.5%), Dermatitis herpetiformis (16%), Pemphigus foliaceus (11.9%), Linear IgA disease (11.9%), Epidermolysisbullosa (2.39%) and Pemphigus herpetiformis (1.7%). We will be presenting the DIF findings in the all these vesiculobullous diseases. DIF in conjugation with histopathology gives the best diagnostic yield in these lesions. It also helps in the diagnosis whenever there is a clinical and histopathological overlap.

Keywords: antibodies, direct immunofluorescence, pemphigus, vesiculobullous

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Authors: Kun Li, Yuzheng Liu, Xiuqi Fan

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High-security standard and high efficiency of screening seem to be contradictory to each other in the airport security check process. Improving the efficiency as far as possible while maintaining the same security standard is significantly meaningful. This paper utilizes the knowledge of Operation Research and Stochastic Process to establish mathematical models to explore this problem. We analyze the current process of airport security check and use the M/G/1 and M/G/k models in queuing theory to describe the process. Then we find the least efficient part is the pre-check lane, the bottleneck of the queuing system. To improve passenger throughput and reduce the variance of passengers’ waiting time, we adjust our models and use Monte Carlo method, then put forward three modifications: adjust the ratio of Pre-Check lane to regular lane flexibly, determine the optimal number of security check screening lines based on cost analysis and adjust the distribution of arrival and service time based on Monte Carlo simulation results. We also analyze the impact of cultural differences as the sensitivity analysis. Finally, we give the recommendations for the current process of airport security check process.

Keywords: queue theory, security check, stochatic process, Monte Carlo simulation

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Authors: Khadijeh Abhari, Seyed Shahram Shekarforoush, Saeid Hosseinzadeh

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Probiotics have been considered as an approach to treat and prevent a wide range of inflammatory diseases. The spore forming probiotic strain Bacillus coagulans has demonstrated anti-inflammatory and immune-modulating effects in both animals and humans. The prebiotic, inulin, also potentially affects the immune system as a result of the change in the composition or fermentation profile of the gastrointestinal microbiota. An in vivo trial was conducted to evaluate the effects of probiotic B. coagulans, and inulin, either separately or in combination, on down regulate immune responses and progression of rheumatoid arthritis using induced arthritis rat model. Forty-eight male Wistar rats were randomly divided into 6 groups and fed as follow: 1) control: Normal healthy rats fed by standard diet, 2) Disease control (RA): Arthritic induced (RA) rats fed by standard diet, 3) Prebiotic (PRE): RA+ 5% w/w long chain inulin, 4) Probiotic (PRO): RA+ 109 spores/day B. coagulans by orogastric gavage, 5) Synbiotic (SYN): RA+ 5% w/w long chain inulin and 109 spores/day B. coagulans and 6) Treatment control: (INDO): RA+ 3 mg/kg/day indomethacin by orogastric gavage. Feeding with mentioned diets started on day 0 and continued to the end of study. On day 14, rats were injected with complete Freund’s adjuvant (CFA) to induce arthritis. Arthritis activity was evaluated by biochemical parameters and paw thickness. Biochemical assay for Fibrinogen (Fn), Serum Amyloid A (SAA), TNF-α and Alpha-1-acid glycoprotein (α1AGp) was performed on day 21, 28 and 35 (1, 2 and 3 weeks post RA induction). Pretreatment with PRE, PRO and SYN diets significantly inhibit SAA and Fn production in arthritic rats (P < 0.001). A significant decrease in production of pro-inflammatory cytokines, TNF-α, was seen in PRE, PRO and SYN groups (P < 0.001) which was similar to the effect of the anti-inflammatory drug Indomethacin. Further, there were no significant anti-inflammatory effects observed following different treatments using α1AGp as a RA indicator. Pretreatment with all supplied diets significantly inhibited the development of paw swelling induced by CFA (P < 0.001). Conclusion: Results of this study support that oral intake of probiotic B. coagulans and inulin are able to improve biochemical and clinical parameters of induced RA in rat.

Keywords: rheumatoid arthritis, bacillus coagulans, inulin, animal model

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Authors: Kumari Rekha, Mathur K Dhananjay, Maheshwari Deepanshu, Nautiyal Nidhi, Shubham Smriti, Laal Deepika, Sinha Swati, Kumar Anupam, Biswas Subhrajit, Shiv Kumar Sarin

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Background: Mesenchymal stem cells are multipotent stem cells derived from mesoderm and are used for therapeutic purposes because of their self-renewal, homing capacity, Immunomodulatory capability, low immunogenicity and mitochondrial transfer signaling. MSCs have the ability to regulate the mechanism of both innate as well as adaptive immune responses through the modulation of cellular response and the secretion of inflammatory mediators. Different sources of MSC are UC MSC, BM MSC, Dental Pulp, and Adipose MSC. The most frequent source used is umbilical cord tissue due to its being easily available and free of limitations of collection procedures from respective hospitals. The immunosuppressive role of MSCs is particularly interesting for clinical use since it confers resistance to rejection by the host immune response. Methodology: In this study, T helper cells (TH4), Cytotoxic T cells (CD-8), immunoregulatory cells (CD25 +FOXP3+) are compared from isolated MSC from three different methods, UC Dissociation Kit (Miltenyi), Explant Culture and Collagenase Type-IV. To check the immunomodulatory property, these MSCs were seeded with PBMC(Coculture) in CD3 coated 24 well plates. Cd28 antibody was added in coculture for six days. The coculture was analyzed in FACS Verse flow cytometry. Results: From flow cytometry analysis of coculture, it found that All over T helper cells (CD4+) number p<0.0264 increases in (All Enzymes) MSC rather than explant MSC(p>0.0895) as compared to Collagenase(p>0.7889) in a coculture of Activated T cell and Mesenchymal Stem Cell. Similar T reg cells (CD25+, FOXP3+) expression p<0.0234increases in All Enzymes), decreases in Explant and Collagenase. Experiments have shown that MSCs can also directly prevent the cytotoxic activity of CD8 lymphocytes mainly by blocking their proliferation rather than by inhibiting the cytotoxic effect. And promoting the t-reg cells, which helps in the mediation of immune response in various diseases. Conclusion: MSC suppress Cytotoxic CD8 T cell and Enhance immunoregulatory T reg (CD4+, CD25+, FOXP3+) Cell expression. Thus, MSC maintains a proper balance(ratio) between CD4 T cells and Cytotoxic CD8 T cells.

Keywords: MSC, disease, T cell, T regulatory

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Authors: Yu-Ling Tsai, Chih-Jung Chang, Chia-Chen Lu, Eric Wu, Chuan-Sheng Lin, Tzu-Lung Lin, Hsin-Chih Lai

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It is urgent that novel anti-obesity measures that are safe, effective and widely available are developed for counteracting the rapidly growing obesity epidemics. In the present study, we show that a probiotic bacterium Parabacteroides goldsteinii screened through culture under the high molecular weight polysaccharides prepared from two iconic medicinal fungi, the Ganoderma lucidum and the Hirsutella sinensis, reduced body weight by ca. 20% in high-fat diet (HFD)-fed mice. The bacterium also decreased intestinal permeability, metabolic endotoxemia, inflammation and insulin resistance. Notably, oral administration of live, but not high temperature-killed, P. goldsteinii to HFD fed mice considerably reduces weight gain and obesity-associated metabolic disorders. A three months feeding of the mice with P. goldsteinii did not show any aberrant side effects, indicating the safety of this bacterium. Transcriptome analysis indicated that P. goldsteinii enhances immunity in resting dendritic cells, but reduces inflammation in lipopolysaccharide (LPS)-induced dendritic cells. On top, Naïve T-cells were skewed towards regulatory T-cells after encountering with dendritic cells (DCs) pretreated with P. goldsteinii. These results indicated P. goldsteinii showed anti-inflammatory effects and can work as a potential probiotic ameliorating obesogenicity and related metabolic syndromes.

Keywords: Parabacteroides goldsteinii, gut microbiome, obesity, immune modulation

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Authors: Ping-Lun Jiang, Hung-Jun Lin, Shen-Fu Lin, Mei-Yin Chien, Ting-Wei Li, Chun-Han Lin, Der-Zen Liu

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Mucosal vaccine induces both mucosal (secretory IgA) and systemic immune responses and it is considered an ideal vaccination strategy for prevention of infectious diseases. One important point to be considered in mucosal vaccination is effective antigen delivery system which can manage effective delivery of antigen to antigen-presenting cells (APCs) of mucosal. In the present study, cationic gelatin nanoparticles were prepared as ideal carriers for more efficient antigen delivery. The average diameter of cationic gelatin nanoparticle was approximate 190 nm, and the zeta potential was about +45 mV, then ovalbumin (OVA) was physically absorbed onto cationic gelatin nanoparticle. The OVA absorption rate was near 95% the zeta potential was about +20 mV. We show that cationic gelatin nanoparticle effectively facilitated antigen uptake by mice bone marrow-derived dendritic cells (mBMDCs) and RAW264.7 cells and induced higher levels of pro-inflammatory cytokines. C57BL/6 mice twice immunized intranasally with OVA-absorbed cationic gelatin nanoparticle induced high levels of OVA-specific IgG in the serum and IgA in their in the nasal and lung wash fluid. These results indicate that nasal administration of cationic gelatin nanoparticles induced both mucosal and systemic immune responses and cationic gelatin nanoparticles might be a potential antigen delivery carrier for further clinical applications.

Keywords: antigen delivery, antigen-presenting cells, gelatin nanoparticle, mucosal vaccine

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Authors: Chro Kavian

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The studies conducted show that cancer is a disease caused by populations of microbes, a notion gaining traction as the interaction between the human microbiome and the tumor microenvironment (TME) increasingly shows how environment and microbes dictate the progress and treatment of neoplastic diseases. A person’s human microbiome is defined as a collection of bacteria, fungi, viruses, and other microorganisms whose structure and composition influence biological processes like immune system modulation and nutrient metabolism, which, in turn, affect how susceptible a person is to neoplastic diseases, and response to different therapies. Recent reports demonstrated the influence specific microbiome bacterial populations have on the TME, thereby altering tumoral behaviors and the TME’s contributing factors that impact patients' lives. In addition, gut microbes and their SCFA products are important determinants of the inflammatory landscape of tumors and augment anti-tumor immunity, which can influence immunotherapy outcomes. Studies have also found that dysbiosis, or microbial imbalance, correlates with biological processes such as cancer progression, metastasis, and therapy resistance, leading scientists to explore the use of microbiome deficiencies as adjunctive approaches to chemotherapy and other, more traditional treatments. Nonetheless, mental health practitioners struggling to comprehend the existent gap between cancer patients with pronounced resolutive capabilities and the profound clinical impact Microbiome-targeted cancer therapy has been proven to possess.

Keywords: microbiome, cancer, tumor, immune system

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Authors: Valizadeh Gever Bita, Joel Caren, Louisa Huand, Yu-Cheng Zhu, Esmaeil Amiri

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Within a honey bee colony, queen is the sole reproducer of fertilized eggs, while queens are safeguarded by worker bees, trophallactic behavior and food sharing activities could expose them to agrochemicals. Here, we assessed the effects of three widely used pesticides—Acephate, Bifenthrin, and Chlorantraniliprole— on worker bees, to investigate indirect effects on the physiology and reproductive traits of queens as well as the eggs they produce. Using RT-qPCR we measured the expression of several detoxification and immune genes in adult worker bees, queens, and freshly laid eggs after pesticide exposure. These analyses aimed to elucidate the physiological changes in queens and potential transgenerational effects. While no significant changes in reproductive traits were observed following Chlorantraniliprole and Bifenthrin exposure, Acephate caused adverse effects on egg size, egg-laying activity, and queen weight. The expression of detoxification, immune and antioxidant-related genes in workers, queens and freshly laid eggs changed over time in response to these pesticides. The results of this investigation revealed that pesticides can cause negative impact on queen physiology and reproduction indirectly through their effects on exposed worker bees. These effects can potentially extend to the next generation of honey bees.

Keywords: apis mellifera, egg laying, detoxification enzymes, gene expression, honey bee queen

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Authors: Razieh Zareia, Hassan ZMB, Darush Moslemic, Amrollah Mostafa-Zaded

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Introduction: Shark is a murine organism and its cartilage has antitumor peptides to prevent angiogenesis, at least, in vitro. The purpose of our research was to evaluate the immune-effectiveness on imbalance between IL-23/IL-17 axis, as an inflammatory pathway and TGF/Foxp3 T regulatory as a inhibitory pathway of commercial shark cartilage that is available as a non-common dietary supplement in IRAN. Materials and Methods: First investigated an imbalanced supernatant of cytokines exist in patients with gastric cancer by ELISA. Associated with cytokines measuring such as IL-23, IL-17, TGF-β, IL-4, and γ-IFN, then flow cytometry was employed to determine whether the peripheral blood mononuclear cells such as CD4+CD25+Foxp3highT regulatory cells in patients with gastric cancer were changed correspondingly. Results: The simultaneously presented up-regulation IL-17A indicated, at least cytokine level without changing in TGF-β amount or CD4+CD25+Foxp3 T regulatory cells, that there are not a direct correlation between IL-23/IL-17 axis and Treg/TGF-β pathway in patients with gastric cancer treated by shark cartilage, but IL-23 was not expressed differentially in this group. So, accompany these changes, an imbalance between Th1 immunity (γ-IFN production) and TH2 immunity (IL-4 secretion) evaluated in patients with gastric cancer treated by shark cartilage. Conclusion: On the basis of results, we propose that shark cartilage, by reducing IL-4, decreasing IL-17 a central cytokine in angiogenesis and increasing γ-IFN amplify anti-tumor immune responses in patients with gastric cancer.

Keywords: IL-23/IL17 axis, TGF-β/CD4+CD25+Foxp3high T regulatory pathway, γ-IFN, IL-4, shark cartilage, gastric cancer

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Authors: J. B. Minari, O. B. Oloyede

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Polymorphonuclear neutrophils (PMNs) play a crucial role in a variety of infections caused by bacteria, fungi, and parasites. Indeed, the involvement of PMNs in host defence against Plasmodium falciparum is well documented both in vitro and in vivo. Many of the antimalarial drugs such as chloroquine used in the treatment of human malaria significantly reduce the immune response of the host in vitro and in vivo. Myeloperoxidase is the most abundant enzyme found in the polymorphonuclear neutrophil which plays a crucial role in its function. This study was carried out to investigate the effect of chloroquine on the enzyme. In investigating the effects of the drug on myeloperoxidase, the influence of concentration, pH, partition ratio estimation and kinetics of inhibition were studied. This study showed that chloroquine is concentration-dependent inhibitor of myeloperoxidase with an IC50 of 0.03 mM. Partition ratio estimation showed that 40 enzymatic turnover cycles are required for complete inhibition of myeloperoxidase in the presence of chloroquine. The influence of pH on the effect of chloroquine on the enzyme showed significant inhibition of myeloperoxidase at physiological pH. The kinetic inhibition studies showed that chloroquine caused a non-competitive inhibition with an inhibition constant Ki of 0.27mM. The results obtained from this study shows that chloroquine is a potent inhibitor of myeloperoxidase and it is capable of inactivating the enzyme. It is therefore considered that the inhibition of myeloperoxidase in the presence of chloroquine as revealed in this study may partly explain the impairment of polymorphonuclear neutrophil and consequent immunosuppression of the host defence system against secondary infections.

Keywords: myeloperoxidase, chloroquine, inhibition, neutrophil, immune

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Authors: Chakrit Thapphan, Suteeraporn Chaowattanapanit, Sorutsiri Chareonsudjai, Wisitsak Phoksawat, Supranee Phantanawiboon, Kiatichai Faksri, Steve W. Edwards, Kanin Salao

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Background: Psoriasis is a chronic inflammatory disease of the skin that is mediated by crosstalk between keratinocytes and immune cells, especially CD4+ T helper (Th) cells. To date, psoriasis is established as a T helper 17 (Th17) cell-mediated inflammatory process driven by the over-expression of Th17. However, the role of other CD4+T helper cells is rather controversial. Objective: Our study, thereby, aimed to characterize and analyze T cell subsets in the circulating blood of psoriasis patients and compare them to healthy controls. Methods: Peripheral blood mononuclear cells were isolated from the participants and stained with fluorescent dye-conjugated monoclonal antibodies specific for intracellular cytokines, including interferon-gamma (IFN- γ), interleukin (IL-4), IL-17 and forkhead box P3 (FOXP3), that can be used to define T helper 1 (Th1) cells, T helper 2 (Th2), T helper 17 (Th17) and regulatory T cells (Treg) respectively. Results: We found that the numbers of Th2 (59.6% ± 17.0) and Th17 (4.0% ± 2.0) cells in the circulating blood of psoriasis patients were significantly higher than those of the healthy controls (p= 0.0007 and 0.0013 respectively). In contrast, the numbers of Th1 and Treg cells were not significantly different between psoriasis patients and healthy controls (p= 0.0593 and 0.8518, respectively). Additionally, when adjusting these numbers of Th cells to Treg, we observed a similar trend that the ratio of Th2/Treg and Th17/Treg also elevated (p = 0.0007 and 0.0047, respectively). Conclusion: Taken together, our results suggest an imbalanced T exhibit toward the Th2 and Th17 skewed-immune responses in psoriasis patients.

Keywords: psoriasis, Th cell subsets, Th2 cells, Th17 cells, Treg cells

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Authors: Murali Aarthy, Sanjeev Kumar Singh

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High risk human papillomaviruses are highly associated with the carcinoma of the cervix and the other genital tumors. Cervical cancer develops through the multistep process in which increasingly severe premalignant dysplastic lesions called cervical intraepithelial neoplastic progress to invasive cancer. The oncoprotein E7 of human papillomavirus expressed in the lower epithelial layers drives the cells into S-phase creating an environment conducive for viral genome replication and cell proliferation. The replication of the virus occurs in the terminally differentiating epithelium and requires the activation of cellular DNA replication proteins. To date, no suitable drug molecule is available to treat HPV infection whereas identification of potential drug targets and development of novel anti-HPV chemotherapies with unique mode of actions are expected. Hence, our present study aimed to identify the potential inhibitors analogous to EGCG, a green tea molecule which is considered to be safe to use for mammalian systems. A 3D similarity search on the natural small molecule library from natural product database using EGCG identified 11 potential hits based on their similarity score. The structure based docking strategies were implemented in the potential hits and the key interacting residues of protein with compounds were identified through simulation studies and binding free energy calculations. The conformational changes between the apoprotein and the complex were analyzed with the simulation and the results demonstrated that the dynamical and structural effects observed in the protein were induced by the compounds and indicated the dominance to the oncoprotein. Overall, our study provides the basis for the structural insights of the identified potential hits and EGCG and hence, the analogous compounds identified can be potent inhibitors against the HPV 16 E7 oncoprotein.

Keywords: EGCG, oncoprotein, molecular dynamics simulation, analogues

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Authors: Sweta Pandey, Samridhi Dhyani, Susmita Chaudhuri

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Klebsiella pneumoniae bacteria is a global threat to human health due to an increase in multi-drug resistance among strains. The hypervirulent strains of Klebsiella pneumoniae is a major trouble due to their association with life-threatening infections in a healthy population. One of the major virulence factors of hyper virulent strains of Klebsiella pneumoniae is the T6SS (Type six secretary system) which is majorly involved in microbial antagonism and causes interaction with the host eukaryotic cells during infections. T6SS mediates some of the crucial factors for establishing infection by the bacteria, such as cell adherence, invasion, and subsequent in vivo colonisation. The antibacterial activity and the cell invasion property of the T6SS system is a major requirement for the establishment of K. pneumoniae infections within the gut. The T6SS can be an appropriate target for developing therapeutics. The T6SS consists of an inner tube comprising hexamers of Hcp (Haemolysin -regulated protein) protein, and at the top of this tube sits VgrG (Valine glycine repeat protein G); the tip of the machinery consists of PAAR domain containing proteins which act as a delivery system for bacterial effectors. For this study, immune response to recombinant VgrG protein was generated to establish this protein as a potential immunogen for the development of therapeutic leads. The immunogenicity of the selected protein was determined by predicting the B cell epitopes by the BCEP analysis tool. The gene sequence for multiple domains of VgrG protein (phage_base_V, T6SS_Vgr, DUF2345) was selected and cloned in pMAL vector in E. coli. The construct was subcloned and expressed as a fusion protein of 203 residue protein with mannose binding protein tag (MBP) to enhance solubility and purification of this protein. The purified recombinant VgrG fusion protein was used for mice immunisation. The antiserum showed reactivity with the recombinant VgrG in ELISA and western blot. The immunised mice were challenged with K. pneumoniae bacteria and showed bacterial clearance in immunised mice. The recombinant VgrG protein can further be used for studying downstream signalling of VgrG protein in mice during infection and for therapeutic MAb development to eradicate K. pneumoniae infections.

Keywords: immune response, Klebsiella pneumoniae, multi-drug resistance, recombinant protein expression, T6SS, VgrG

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Authors: Sule Yucelbas, Gulay Tezel, Cuneyt Yucelbas, Seral Ozsen

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In this study, it was tried to identify some heart rhythm disorders by electrocardiography (ECG) data that is taken from MIT-BIH arrhythmia database by subtracting the required features, presenting to artificial neural networks (ANN), artificial immune systems (AIS), artificial neural network based on artificial immune system (AIS-ANN) and particle swarm optimization based artificial neural network (PSO-NN) classifier systems. The main purpose of this study is to evaluate the performance of hybrid AIS-ANN and PSO-ANN classifiers with regard to the ANN and AIS. For this purpose, the normal sinus rhythm (NSR), atrial premature contraction (APC), sinus arrhythmia (SA), ventricular trigeminy (VTI), ventricular tachycardia (VTK) and atrial fibrillation (AF) data for each of the RR intervals were found. Then these data in the form of pairs (NSR-APC, NSR-SA, NSR-VTI, NSR-VTK and NSR-AF) is created by combining discrete wavelet transform which is applied to each of these two groups of data and two different data sets with 9 and 27 features were obtained from each of them after data reduction. Afterwards, the data randomly was firstly mixed within themselves, and then 4-fold cross validation method was applied to create the training and testing data. The training and testing accuracy rates and training time are compared with each other. As a result, performances of the hybrid classification systems, AIS-ANN and PSO-ANN were seen to be close to the performance of the ANN system. Also, the results of the hybrid systems were much better than AIS, too. However, ANN had much shorter period of training time than other systems. In terms of training times, ANN was followed by PSO-ANN, AIS-ANN and AIS systems respectively. Also, the features that extracted from the data affected the classification results significantly.

Keywords: AIS, ANN, ECG, hybrid classifiers, PSO

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Authors: Roman Khanferyan

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Endurance exercises and strenuous muscle activity are accompanied by multiple immune dysfunctions due to the activation of cytokines and chemokines synthesis. This study assesses changes in the synthesis of immune regulatory mediators in elite athletes during endurance sports activity. The concentrations of cytokines/chemokines (IL-2, IL-6, IL-8, IL-10, IL-18, MIP-1 beta, GRO-alpha, RANTES, SDF-1a, VEGF) in sera of hockey athletes (n=33) and in supernatants of 24-h cultivated peripheral blood mononuclear cells (PBMC) of boxers (n=6) assayed by ELISA and Luminex xMAP multiplex assays. Estimation of body composition studied by using bioimpedance technology. The dietary energy consumption per person has been estimated using an album of different sizes of portions of the most frequently consumed foods. It has been demonstrated that endurance sports activity enhances the secretions of most pro- and anti-inflammatory cytokines and chemokines in more than 2-6 fold. The study demonstrated that the high increase of more than 3-4 times in the concentration of IL-18 in sera of athletes (327.86 + 45.67 pg/ml) didn’t correlate with BMI (p=0.040) but demonstrated a low correlation with MMI (p=0.234) and BMR (p=0,231). The opposite impact on the concentration of IL-10 has been demonstrated in athletes. It has been shown a negative correlation between its concentration and BMI (p= - 0.251), MMI (p= - 0.327), and BMR (p= - 0.301). In vitro studies in boxers showed greater amounts of chemokines in the PBMC supernatants, including MIP-1β, GRO-α, RANTES, SDF-1α, and IL-8 (P<0.05). At the same time, healthy controls had greater supernatant levels of MCP-1, Eotaxin, and MIP-1α. The study demonstrated a high correlation between physical activity, usual athletes' diet, and consumption of specialized sports nutrition products.

Keywords: sport nutrition, cytokines, chemokines, endurace exercises

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Authors: Ahmed Chetouani

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Corrosion is a natural occurring process where it can be defined as the deterioration of materials properties due to its interaction with its environment. Corrosion can lead to failures in plant infrastructure and machines which are usually costly to repair. In terms of loss of contaminated products which will cause environmental damage and possibly costly in terms of human health. The driving force that causes metals to corrode is due to the natural consequence of their temporary existence in metallic form. There is a growing trend in utilizing plant extracts and pharmaceutical compounds as corrosion inhibitors. Exquisite identification of the essential oil of aerial parts of Pelargonium was obtained using hydrodistillation and identification using GC (gas chromatography) and GC/MS (gas chromatography-mass spectrometry). The oil was predominated by Citronellol (22.8%). The inhibitory effect of essential oil and extract of Pelargonium was estimated on the corrosion of mild steel in 1M hydrochloric acid (HCl) using weight loss, Electrochemical Impedance Spectroscopy (EIS) and Tafel polarization curves. Inhibition was found to increase with increasing concentration of the essential oil and extract of Pelargonium. The effect of temperature on the corrosion behaviour of mild steel in 1M HCl with addition of essential oil and extract was also studied and the thermodynamic parameters were determined and discussed. Values of inhibition efficiency were calculated from weight loss, Tafel polarization curves, and EIS. All results are in good agreement. Polarization curves showed that essential oil and extract of Pelargonium behave as mixed type inhibitors in hydrochloric acid. The results obtained showed that the essential oil and extract of Pelargonium could serve as an effective inhibitor of the corrosion of mild steel in Hydrochloric acid solution. To avoid any surprise of toxicity, the majority compounds have been studied by using POM analyses.

Keywords: corrosion inhibition, mild steel, pelargonium oil, extract, electrochemical system, hydrodistillation, side effects, POM Analyses

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Authors: Viktoriia Burkina, Vladimir Zlabek, Galia Zamaratskaia

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Cytochromes P450 (CYP) are important family of enzymes in Phase I metabolism. Environmental pollutants often act as inducers of the gene expression and activities CYP1A1 and CYP3A-like isoforms in fish. The activities are generally measured in the fish liver or gills, and less is known about tissue distribution of expression. In present study, the CYP1A1 and CYP3A-like activities were measured in rainbow trout liver, gill, intestine, heart, brain and gonads. The activities of CYP1A1 and CYP3A-like proteins were estimated as the rates of 7-ethoxyresorufin-O-deethylation (EROD) and benzyloxy-4-trifluoromethylcoumarin-O-debenzyloxylation (BFCOD), respectively. The CYP1A1 and CYP3A-like activities were detectable in all investigated fish tissues, with the highest activity in hepatic tissue followed by heart > brain > gill > intestine > gonads. To confirm the presence of CYP1A1 in different tissues, EROD activity was measured in presence of the selective inhibitors ellipticine (CYP1A1), ketoconazole (CYP3A), 8-methoxypsoralen (human CYP2A) and diallyl sulphide (CYP2E1). It was found that ellipticine, ketoconazole and 8-methoxypsoralen inhibited hepatic EROD activity by 88-98%. Ellipticine inhibited gill, intestine, and gonad EROD activity by 50%. In conclusion, EROD and BFCOD activities were detected in rainbow trout liver, gill, intestine, heart, brain and gonads. Further studies are needed to fully identify all CYP450 isoforms responsible for these activities. Acknowledgement: The study was financially supported by the Ministry of Education, Youth and Sports of the Czech Republic - projects „CENAKVA “(No. CZ.1.05/2.1.00/01.0024), “CENAKVA Center Development “(No. CZ.1.05/2.1.00/19.0380), “CENAKVA II “(No. LO1205 under the NPU I program), and "Development of USB - International mobility (No. CZ.02.2.69/0.0/0.0/16_027/0008364).

Keywords: BFCOD, EROD, fish, phase I metabolism, selective inhibitors

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Authors: Natasa Ilic, Alisa Gruden-Movsesijan, Maja Kosanovic, Sofija Glamoclija, Marina Bekic, Ljiljana Sofronic-Milosavljevic, Sergej Tomic

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As a very promising candidate for modulation of immune response in the sense of biasing the inflammatory towards an anti-inflammatory type of response, Trichinella spiralis infection was shown to successfully alleviate the severity of experimental autoimmune encephalomyelitis, the animal model of human disease multiple sclerosis. This effect is achieved via its excretory-secretory muscle larvae (ES L1) products which affect the maturation status and function of dendritic cells (DCs) by inducing the tolerogenic status of DCs, which leads to the mitigation of the Th1 type of response and the activation of a regulatory type of immune response both in vitro and in vivo. ES L1 alone or via treated DCs successfully mitigated EAE in the same manner as the infection itself. On the other hand, it has been shown that T. spiralis infection slows down the tumour growth and significantly reduces the tumour size in the model of mouse melanoma, while ES L1 possesses a pro-apoptotic and anti-survival effect on melanoma cells in vitro. Hence, although the mechanisms still need to be revealed, T. spiralis infection and its ES L1 products have a bit of controversial potential to modulate both inflammatory diseases and malignancies. The recent discovery of T. spiralis extracellular vesicles (TsEVs) suggested that the induction of complex regulation of the immune response requires simultaneous delivery of different signals in nano-sized packages. This study aimed to explore whether TsEVs bare the similar potential as ES L1 to influence the status of DCs in initiation, progression and regulation of immune response, but also to investigate the effect of both ES L1 and TsEVs on myeloid derived suppressor cells (MDSC) which present the regular tumour tissue environment. TsEVs were enriched from the conditioned medium of T. spiralis muscle larvae by differential centrifugation and used for the treatment of human monocyte-derived DCs and MDSC. On DCs, TsEVs induced low expression of HLA DR and CD40, moderate CD83 and CD86, and increased expression of ILT3 and CCR7 on treated DCs, i.e., they induced tolerogenic DCs. Such DCs possess the capacity to polarize T cell immune response towards regulatory type, with an increased proportion of IL-10 and TGF-β producing cells, similarly to ES L1. These findings indicated that the ability of TsEVs to induce tolerogenic DCs favoring anti-inflammatory responses may be helpful in coping with diseases that involve Th1/Th17-, but also Th2-mediated inflammation. In MDSC in vitro model, although both ES L1 and TsEVs had the same impact on MDSC phenotype i.e., they acted suppressive, ES L1 treated MDSC, unlike TsEVs treated ones, induced T cell response characterized by the increased RoRγT and IFN-γ, while the proportion of regulatory cells was decreased followed by the decrease in IL-10 and TGF-β positive cells proportion within this population. These findings indicate the interesting ability of ES L1 to modulate T cells response via MDSC towards pro-inflamatory type, suggesting that, unlike TsEVs which consistently demonstrate the suppresive effect on inflammatory response, it could be used also for the development of new approaches aimed for the treatment of malignant diseases. Acknowledgment: This work was funded by the Promis project – Nano-MDCS-Thera, Science Fund, Republic of Serbia.

Keywords: dendritic cells, myeloid derived suppressor cells, immunomodulation, Trichinella spiralis

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Authors: Tooba N. Shamsi, Romana Perveen, Sadaf Fatima

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Protease Inhibitors (PIs) are widespread in nature, produced by animals, plants and microorganisms. They play vital role in various biological activities by keeping a check on activity of proteases. Present study aims to investigate antioxidant and anti-inflammatory properties of PPI from Cajanus cajan (CCTI) and Phaseolus limensis (LBTI). PPI was purified from C. cajan (PUSA-992) by ammonium sulfate precipitation followed by ion exchange chromatography. The anti-oxidant activity was analyzed by two most common radical scavenging assays of FRAP (ferric reducing antioxidant power) and DPPH (1,1- diphenyl-2-picrylhydrazyl). Also, in-vitro anti-inflammatory activity was evaluated using albumin denaturation assay and membrane stabilization assay at different concentrations. Ascorbic acid and aspirin were used as a standards for antioxidant and anti-inflammatory assays respectively. The PPIs were also checked for antimicrobial activity against a number of bacterial strains. The CCTI and LBTI showed DPPH radical scavenging activity in a concentration–dependent manner with IC50 values 544 µg/ml and 506 µg/ml respectively comparative to ascorbic acid which was 258 µg/ml. Following FRAP assay, it was evaluated that LBTI had 87.5% and CCTI showed 84.4% antioxidant activity, taking value of standard ascorbic acid to be 100%. The PPIs also showed in-vitro anti‐inflammatory activity by inhibiting the heat induced albumin denaturation with IC50 values of 686 µg/ml and 615 µg/ml for CCTI and LBTI respectively compared to the standard (aspirin) which was 70.8 µg/ml. Red blood cells membrane stabilization with IC50 values of 641 µg/ml and 587 µg/ml for CCTI and LBTI respectively against aspirin which showed IC50 value of 70.4 µg/ml. PPIs showed antibacterial activity against 7 known strains while there was apparently no action against fungi.

Keywords: Cajanus cajan, Phaseolus limensis, Lima beans, protein protease inhibitor, antioxidant, anti-inflammatory, antimicrobial activity

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