Search results for: immune checkpoint inhibitors

Authors: Teodora Mocan, Matea Cristian, Cornel Iancu, Flaviu A. Tabaran, Florin Zaharie, Bartos Dana, Lucian Mocan

Abstract:

Colon cancer (CC) a lethal human malignancy, is one of the most commonly diagnosed cancer. With its high increased mortality rate, as well as low survival rate combined with high resistance to chemotherapy CC, represents one of the most important global health issues. In the presented research, we have developed a distinct nanostructured colon carcinoma vaccine model based on a nano-biosystem composed of 39 nm gold nanoparticles conjugated to colon cancer epitopes. We prove by means of proteomic analysis, immunocytochemistry, flow cytometry and hyperspectral microscopy that our developed nanobioconjugate was able to contribute to an optimal prophylactic effect against CC by promoting major histocompatibility complex mediated (MHC) antigen presentation by dendritic cells. We may conclude that the proposed immunoprophylactic approach could be more effective than the current treatments of CC because it promotes recognition of the tumoral antigens by the immune system.

Keywords: anticancer vaccine, colon cancer, gold nanoparticles, tumor antigen

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Authors: Abbassi Daloii Asieh, Yazdani Hoda

Abstract:

Background and Objective: evidence supports systemic inflammation in obesity and insulin resistance. Apelin that is secreted by adipose tissue plays an important role in the inflammation process and appear act as an anti-inflammatory cytokines. The aim of this study was the effect of eight weeks aerobic training and nitro-L-arginine-methyl ester (L-NAME) on plasma apelin in male’s rats. Materials and Methods: For this purpose, 24 male Wistar rats aged 20 months were randomly assigned into four groups: Control, training, training and L-NAME and L-NAME. Training intervention was eight weeks aerobic exercise (5 time/weekly) at 75-80 (%) of maximal oxygen consumption. All rats were killed 72 hours after lasted exercise session; blood samples collected and plasma were stored. Data was analyzed by one way ANOVA and Tucky Test. A p value less than 0.05 was considered statistically signigcant. Results: The results showed that after eight weeks of endurance training exercise Apelin plasma compared to the control group did not change significantly. Also, the results showed that there was significant difference in plasma Apelin between groups(P > 0/05). Also, the results showed no significant difference between the insulin levels and glucose of four groups (P > 0/05). Conclusion: It seems that aerobic exercise plasma Apelin levels in male rats is not affected. On the other hand, nitric oxide inhibitors can reduce levels of plasma Apelin.

Keywords: aerobic training, L-NAME, plasma Apelin, male’s rats

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Authors: Emmanuel Uba, Lily Chimuanya, Maryam Tar

Abstract:

Orthographic engineering is no longer the preserve of the Short Messaging Service (SMS), which is characterised by limited space. Such stylistic creativity or deviation is fast creeping into real-time messaging, popularly known as Instant Messaging (IM), despite the large number of characters allowed. This occurs at various linguistic levels: phonology, morphology, syntax, etc. Nigerians are not immune to this linguistic stylisation. This study investigates the phonological and meta-phonological conventions of the messages sent and received via WhatsApp by Nigerian graduates. This is ontological study of 250 instant messages collected from 98 graduates from different ethnic groups in Nigeria. The selection and analysis of the messages are based on figure and ground principle. The results reveal the use of accent stylisation, phoneme substitution, blending, consonantisation (a specialised form of deletion targeting vowels), numerophony (using a figure/number, usually 1-10, to represent a word or syllable that has the same sound) and phonetic respelling in the IMs sent by Nigerians. The study confirms the existence of linguistic creativity.

Keywords: figure and ground principle, instant messaging, linguistic stylisation, meta-phonology

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Authors: Mohamed Sadek Bachene, Soraya Temim, Hassina Ainbaziz, Asma Bachene

Abstract:

The present study was conducted to assess the safety and the efficacy of a vaccine containing the Algerian precocious strains of Eimeria magna and Eimeria media used separately or together against rabbit coccidiosis. The samples consisted of 56 young rabbits reared in specific pathogen-free conditions. Following the challenge inoculation, statistically significant decreases in oocyst excretion were noticed in the vaccinated rabbits with the precocious strain of Eimeria magna, Eimeria media, and both species leading toa good immune response acquired by the vaccination associated with a good growth rate. Moreover, there was a statistically significant increase in oocyst output following the challenge in all challenged groups. Unlike the vaccinated groups, the challenged groups showed poor weight gains. More than 50% of the young rabbits from all the challenged groups presented diarrhea. Consequently, these precocious strains constitute good candidates for mono or polyvalent anticoccidial vaccines in the future.

Keywords: precocious strain, rabbits, vaccination, wild strain

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Authors: Nurkhairul Bariyah Baharun, Afzan Adam, Reena Rahayu Md Zin

Abstract:

Tumor microenvironment (TME) in breast cancer is mainly composed of cancer cells, immune cells, and stromal cells. The interaction between cancer cells and their microenvironment plays an important role in tumor development, progression, and treatment response. The TME in breast cancer includes tumor-infiltrating lymphocytes (TILs) that are implicated in killing tumor cells. TILs can be found in tumor stroma (sTILs) and within the tumor (iTILs). TILs in triple negative breast cancer (TNBC) have been demonstrated to have prognostic and potentially predictive value. The international Immune-Oncology Biomarker Working Group (TIL-WG) had developed a guideline focus on the assessment of sTILs using hematoxylin and eosin (H&E)-stained slides. According to the guideline, the pathologists use “eye balling” method on the H&E stained- slide for sTILs assessment. This method has low precision, poor interobserver reproducibility, and is time-consuming for a comprehensive evaluation, besides only counted sTILs in their assessment. The TIL-WG has therefore recommended that any algorithm for computational assessment of TILs utilizing the guidelines provided to overcome the limitations of manual assessment, thus providing highly accurate and reliable TILs detection and classification for reproducible and quantitative measurement. This study is carried out to develop a TNBC digital whole slide image (WSI) dataset from H&E-stained slides and IHC (CD4+ and CD8+) stained slides. TNBC cases were retrieved from the database of the Department of Pathology, Hospital Canselor Tuanku Muhriz (HCTM). TNBC cases diagnosed between the year 2010 and 2021 with no history of other cancer and available block tissue were included in the study (n=58). Tissue blocks were sectioned approximately 4 µm for H&E and IHC stain. The H&E staining was performed according to a well-established protocol. Indirect IHC stain was also performed on the tissue sections using protocol from Diagnostic BioSystems PolyVue™ Plus Kit, USA. The slides were stained with rabbit monoclonal, CD8 antibody (SP16) and Rabbit monoclonal, CD4 antibody (EP204). The selected and quality-checked slides were then scanned using a high-resolution whole slide scanner (Pannoramic DESK II DW- slide scanner) to digitalize the tissue image with a pixel resolution of 20x magnification. A manual TILs (sTILs and iTILs) assessment was then carried out by the appointed pathologist (2 pathologists) for manual TILs scoring from the digital WSIs following the guideline developed by TIL-WG 2014, and the result displayed as the percentage of sTILs and iTILs per mm² stromal and tumour area on the tissue. Following this, we aimed to develop an automated digital image scoring framework that incorporates key elements of manual guidelines (including both sTILs and iTILs) using manually annotated data for robust and objective quantification of TILs in TNBC. From the study, we have developed a digital dataset of TNBC H&E and IHC (CD4+ and CD8+) stained slides. We hope that an automated based scoring method can provide quantitative and interpretable TILs scoring, which correlates with the manual pathologist-derived sTILs and iTILs scoring and thus has potential prognostic implications.

Keywords: automated quantification, digital pathology, triple negative breast cancer, tumour infiltrating lymphocytes

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Authors: Swarnali Chakma, Akihiko Hokugo

Abstract:

Research on three case studies reviewed here explains many aspects and complications of evacuation behavior during an emergency period. The scenario and phenomenon of the disaster were different, but the similarities are that after receiving the warning peoples does not take it seriously. Many individuals evacuated after taking some kind of action, for example; return to home, searching for family members, prepared valuable things etc. Based on a review of the literature, the data identified a number of factors that help explain evacuation behavior during the disaster. In the case of Japan, cultural inhibitors impact people’s behavior; for example, following the traffic rules, some people lost their time to skip because of the slow-moving car makes overcrowded traffic and some of them were washed away by the tsunami. In terms of Bangladeshi culture, women did not want to evacuate without men because staying men and women who do not know each other under the same roof together is not regular practice or comfortable. From these three case studies, it is observed that early warning plays an important role in cyclones, typhoons and earthquakes. A high level of trust from residents in the warning system is important to real evacuation. It is necessary to raise awareness of disaster and provide information on the vulnerability to cyclones, typhoons and earthquakes hazards at community levels. The local level may help decision makers and other stakeholders to make a better decision regarding an effective disaster management.

Keywords: disaster management, emergency period, evacuation, shelter, typhoon

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Authors: Nouf A. Aldarmahi, Nesrin I. Tarbiah, Nuha A. Alkhattabi, Huda F. Alshaibi

Abstract:

Nigella sativa which is known as dark cumin is a well-known example for a widely applicable herbal medicine. Nigella sativa can be effective in a variety of diseases such as hypertension, diabetes, bronchitis, gastrointestinal upset, and cancer. The anticancer effect of Nigella sativa appeared to be mediated by immune-modulatory effect through stimulating human natural killer (NK) cells. This is a type of lymphocytes which is part of the innate immunity, also known as the first line of defense in the body against pathogens. This study investigated the effect of thymoquinone as a major component of Nigella sativa on the molecular cytotoxic pathway of NK cell and the role of thymoquinone therapeutic effect on NK cells. NK cells were cultured with breast tumor cells in different ways and cultured media was collected and the concentration of perforin, granzyme B and interferon-α were measured by ELISA. The cytotoxic effect of NK cells on breast tumor cells was enhanced in the presence of thymoquinone, with increased activity of perforin in NK cells. This improved anticancer effect of thymoquinone on breast cancer cells.

Keywords: breast cancer, cancer cells, natural killer cells, thymoquinone

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Authors: Aleksandra Twarda, Dobrosława Krzemień, Grzegorz Dubin, Tad A. Holak

Abstract:

Stabilin-2 belongs to the group of scavenger receptors and plays a crucial role in clearance of more than 10 ligands from the bloodstream, including hyaluronic acid, products of degradation of extracellular matrix and metabolic products. The Link domain, a defining feature of stabilin-2, has a sequence similar to Link domains in other hyaluronic acid receptors, such as CD44 or TSG-6, and is responsible for most of ligands binding. Present knowledge of signal transduction by stabilin-2, as well as ligands’ recognition and binding mechanism, is limited. Until now, no experimental structures have been solved for any segments of stabilin-2. It has recently been demonstrated that the stabilin-2 knock-out or blocking of the receptor by an antibody effectively opposes cancer metastasis by elevating the level of circulating hyaluronic acid. Moreover, loss of expression of stabilin-2 in a peri-tumourous liver correlates with increased survival. Solving of the crystal structure of stabilin-2 and elucidation of the binding mechanism of hyaluronic acid could enable the precise characterization of the interactions in the binding site. These results may allow for designing specific small-molecule inhibitors of stabilin-2 that could be used in cancer therapy. To carry out screening for crystallization of stabilin-2, we cloned constructs of the Link domain of various lengths with or without surrounding domains. The folding properties of the constructs were checked by nuclear magnetic resonance (NMR). It is planned to show the binding of hyaluronic acid to the Link domain using several biochemical methods, i.a. NMR, isothermal titration calorimetry and fluorescence polarization assay.

Keywords: stabilin-2, Link domain, X-ray crystallography, NMR, hyaluronic acid, cancer

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Authors: Abuelquasim. M. Hassan, Namarig .S. Mohammed, Samah F. Mohammed, Wafaa. A. Mohammed, Wafaa M. Edriss, Amel A. Ahmed, Elfadil M. Abass

Abstract:

Introduction: Cytomegalovirus (CMV), a common virus, usually causes asymptomatic infections in immunocompetent hosts; however, it may lead to serious complications especially in cancer patients. Objectives: This study was conducted to determine the seroprevalence of human cytomegalovirus (HCMV) among leukemia, breast and prostate cancer patients attending at Radiation Isotope-Center-Khartoum (RICK) from April to August 2016. Material and Methods: A total of 91 subjects were included: 30 leukemic, 22 breast cancer and 29 prostate cancer patients.10 of them were healthy and used as control group, serum samples were collected and tested for CMV IgG & IgM using enzyme-linked immune sorbent assay (ELISA). Result: Of the control group, 9/10 (9.9%) were seropositive for CMV IgG and 1/10 (1.09%) were sero positive for IgM. Also, all cancer groups demonstrated presence of IgG antibody classes as: The percentage of positive results in prostate, breast cancer and leukemia were 35.8 %, 37.2%, and 35.3% respectively. Conclusion: There was no significant correlation between leukemia, breast, prostate and HCMV.

Keywords: cytomegalovirus, serodiagnostic, breast cancer, leukemia

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Authors: Jagdish S. Patel, Piyush Chudasama

Abstract:

Context: Over-expression of P-glycoprotein (P-gp) plays critical role in absorption of many drug candidates which results into lower bioavailability of the drug. P-glycoprotein also over expresses in many pathological conditions like diabetes, affecting the drug therapy. Modulation of P-gp expression using inhibitors can help in designing novel formulation enhancing the bioavailability of the drug in question. Objectives: The main focus of the study was to develop advanced glycation end products (AGEs) induced P-gp over expression in Caco-2 cells. Curcumin, piperine and epigallocatechin gallate were used to evaluate their P-gp inhibitory action using combinatorial approach. Materials and methods: Methylglyoxal (MG) induced P-gp over expression was checked in Caco-2 cells using real time PCR. P-gp inhibitory effects of the phytochemicals were measured after induction with MG alone and in combination of any two compounds. Cytotoxicity of each of the phytochemical was evaluated using MTT assay. Results: Induction with MG (100mM) significantly induced the over expression of P-glycoprotein in Caco-2 cells after 24 hr. Curcumin, piperine and epigallocatechin gallate alone significantly reduced the level of P-gp within 6 hr of treatment period monitored by real time PCR. The combination of any two phytochemical also down regulated the expression of P-gp in cells. Combinations of Curcumin and epigallocatechin gallate have shown significant down regulation when compared with other two combinations. Conclusions: Combinatorial approach for down regulating the expression of P-gp, in pathological conditions like diabetes, has demonstrated promising approach for therapeutic purpose.

Keywords: p-glycoprotein, curcumin, piperine, epigallocatechin gallate, p-gp inhibition

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Authors: Osama Sassi, Manal Eltorki, Iftikhar Ahmad

Abstract:

Poor integrity is one of the major causes of leaks and accidents in gas transmission pipelines. To ensure safe operation, it is must to have efficient and effective pipeline integrity management (PIM) system. The corrosion management is one of the important aspects of successful pipeline integrity management program together design, material selection, operations, risk evaluation and communication aspects to maintain pipelines in a fit-for-service condition. The objective of a corrosion management plan is to design corrosion mitigation, monitoring, and inspection strategy, and for maintenance in a timely manner. This paper presents the experience of corrosion management of a gas transmission pipeline from Wafa field to Mellitah gas plant in Libya. The pipeline is 525.5 km long and having 32 inches diameter. It is a buried pipeline. External corrosion on pipeline is controlled with a combination of coatings and cathodic protection while internal corrosion is controlled with a combination of chemical inhibitors, periodic cleaning and process control. The monitoring and inspection techniques provide a way to measure the effectiveness of corrosion control systems and provide an early warning when changing conditions may be causing a corrosion problem. This paper describes corrosion management system used in Mellitah Oil & Gas BV for its gas transmission pipeline based on standard practices of corrosion mitigation and inspection.

Keywords: corrosion mitigation on gas transmission pipelines, pipeline integrity management, corrosion management of gas pipelines, prevention and inspection of corrosion

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Authors: Tahsien Okasha

Abstract:

Transplantation medicine is one of the most challenging and complex areas of modern medicine. Some of the key areas for medical management are the problems of transplant rejection, during which the body has an immune response to the transplanted organ, possibly leading to transplant failure and the need to immediately remove the organ from the recipient. When possible, transplant rejection can be reduced through serotyping to determine the most appropriate donor-recipient match and through the use of immunosuppressant drugs. Postoperative care actually begins before the surgery in terms of education, discharge planning, nutrition, pulmonary rehabilitation, and patient/family education. This also allows for expectations to be managed. A multidisciplinary approach is the key, and collaborative team meetings are essential to ensuring that all team members are "on the same page.". The following clinical pathway map and guidelines with the aim to decrease alteration in clinical practice and are intended for those healthcare professionals who look after organ transplant patients. They are also intended to be useful to both medical and surgical trainees as well as nurse specialists and other associated healthcare professionals involved in the care of organ transplant patients. This pathway is general pathway include the general guidelines that can be applicable for all types of organ transplant with special considerations to each organ.

Keywords: organ transplant, clinical pathway, postoperative care, same page

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Authors: Swati Gautam, Salman Akhtar, S. P. Jaiswar, Amita Jain

Abstract:

Background: FGTB is now a major global health problem mostly in developing countries including India. In humans, Mycobacterium Tuberculosis (M.tb) is a causating agent of infection. High index of suspicion is required for early diagnosis due to asymptomatic presentation of FGTB disease. In macrophages Toll Like Receptor-2 (TLR-2) is one which mediated host’s immune response to M.tb. The expression of TLR-2 on macrophages is important to determine the fate of innate immune responses to M.tb. TLR-2 have two work. First its high expression on macrophages worsen the outer of infection and another side, it maintains M.tb to its dormant stage avoids activation of M.tb from latent phase. Single Nucleotide Polymorphism (SNP) of TLR-2 gene plays an important role in susceptibility to TB among different populations and subsequently, in the development of infertility. Methodology: This Case-Control study was done in the Department of Obs and Gynae and Department of Microbiology at King George’s Medical University, U.P, Lucknow, India. Total 300 subjects (150 Cases and 150 Controls) were enrolled in the study. All subjects were enrolled only after fulfilling the given inclusion and exclusion criteria. Inclusion criteria: Age 20-35 years, menstrual-irregularities, positive on Acid-Fast Bacilli (AFB), TB-PCR, (LJ/MGIT) culture in Endometrial Aspiration (EA). Exclusion criteria: Koch’s active, on ATT, PCOS, and Endometriosis fibroid women, positive on Gonococal and Chlamydia. Blood samples were collected in EDTA tubes from cases and healthy control women (HCW) and genomic DNA extraction was carried out by salting-out method. Genotyping of TLR2 genetic variants (Arg753Gln and Arg677Trp) were performed by using single amplification refractory mutation system (ARMS) PCR technique. PCR products were analyzed by electrophoresis on 1.2% agarose gel and visualized by gel-doc. Statistical analysis of the data was performed using the SPSS 16.3 software and computing odds ratio (OR) with 95% CI. Linkage Disequiliribium (LD) analysis was done by SNP stats online software. Results: In TLR-2 (Arg753Gln) polymorphism significant risk of FGTB observed with GG homozygous mutant genotype (OR=13, CI=0.71-237.7, p=0.05), AG heterozygous mutant genotype (OR=13.7, CI=0.76-248.06, p=0.03) however, G allele (OR=1.09, CI=0.78-1.52, p=0.67) individually was not associated with FGTB. In TLR-2 (Arg677Trp) polymorphism a significant risk of FGTB observed with TT homozygous mutant genotype (OR= 0.020, CI=0.001-0.341, p < 0.001), CT heterozygous mutant genotype (OR=0.53, CI=0.33-0.86, p=0.014) and T allele (OR=0.463, CI=0.32-0.66, p < 0.001). TT mutant genotype was only found in FGTB cases and frequency of CT heterozygous more in control group as compared to FGTB group. So, CT genotype worked as protective mutation for FGTB susceptibility group. In haplotype analysis of TLR-2 genetic variants, four possible combinations, i.e. (G-T, A-C, G-C, and A-T) were obtained. The frequency of haplotype A-C was significantly higher in FGTB cases (0.32). Control group did not show A-C haplotype and only found in FGTB cases. Conclusion: In conclusion, study showed a significant association with both genetic variants of TLR-2 of FGTB disease. Moreover, the presence of specific associated genotype/alleles suggest the possibility of disease severity and clinical approach aimed to prevent extensive damage by disease and also helpful for early detection of disease.

Keywords: ARMS, EDTA, FGTB, TLR

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Authors: H. Noureddine, P. Rao, R. Guru, A. Chandratreya

Abstract:

The nice guidance for elective total knee replacements states that patients should be given mechanical thrombo-prophylaxis, and if no contraindications chemical thromboprophylaxis in the form of Dabigatran etexilate, Rivaroxiban, UFH, LMWH, or Fondaparinux sodium (CG92, 1.5.14, January 2010). In Practice administering oral agents has been the dominant practice as it reduces the nursing needs, and shortens hospital stay and is generally received better by patients. However, there are well documented associated bleeding risks, and their effects are difficult to reverse in case of major bleeding. Our experience with oral factor 10 inhibitors used for thromboprophylaxis was marked with several patients developing complications necessitating return to the theatre for wound washouts. This has led us to try a different protocol for thromboprophylaxis that we applied on our patients undergoing total and unicondylar knee replacements. We applied mechanical thromboprophylaxis in the form of intermittent pneumatic pressure devices, and chemical thromboprophylaxis in the form of a dose of prophylactic LMWH pre-op, then 150 mg of Aspirin to start 24 hours after the surgery and to continue for 6 weeks, alongside GI cover with PPIs or antihistamines. We also administered local anaesthetics intra-operatively in line with the ERAS protocol thus encouraging early mobilization. We have identified a cohort of 133 patients who underwent one of the aforementioned procedures in the same trust, and by the same surgeon, where this protocol was applied and examined their medical notes retrospectively with a mean follow-up period of 14 months, to identify the rate and percentage of patients who had thrombo-embolic events in the post-operative period.

Keywords: aspirin, heparin, knee arthroplasty, thromboprophylaxis

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Authors: Arleta Rifati Nixha, Mustafa Arslan, Adem Ergün, Nahit Gencer

Abstract:

Polyphenol oxidase (PPO), sometimes referred to as phenol oxidase, catecholase, phenolase, catechol oxidase, or even tyrosinase, is considered to be an o-dipenol. PPO (EC 1.14.18.1), a multifunctional copper containing enzyme, is widely distributed in nature. It catalyzes two distinct reactions of melanin synthesis: a hydroxylation of monophenols to o-diphenols (monophenolase activity) and an oxidation of o-diphenols to o-quinones (diphenolase activity), both using molecular oxygen. Additionaly, investigation demonstrated that various dermatological disorders, such as age spots and freckle, were caused by the accumulation of an excessive level of epidermal pigmentation. Tyrosinase has also been linked to Parkinson’s and other neurodegenerative diseases. Nitrogen heterocycles have received a great deal of attention in the literature because of biological properties. Especially, among these heterocyclic systems, pyridine containing compounds have been the subject of expanding research efforts in heteroaromatic and biological chemistry. The pyrido [2,3-d] pyrimidine heterocycles, which are those annelated to a pyrimidine ring, are important because of their wide range of biological and pharmaceutical applications (i.e., bronchodilators, vasodilators) and their anti-allergic, cardiotonic, antihypertensive, and hepatoprotective activities. In this study series of 12 new carbazole substituted pyridopyrimidine urea(thiourea) derivatives were synthesized and evaluated effect on PPO. Additionally, we presented structure-activity relationship analyses and theoretical calculations of the compounds.

Keywords: carbazole, pyridopyrimidine, urea, thiourea, tyrosinase inhibitors

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Authors: Austin Belfiori, Kevin Rinek, Zach Barcroft, Jennifer Berglind

Abstract:

Diet influences the composition of the gut microbiota and host's health. Disruption of the balance among the microbiota, epithelial cells, and resident immune cells in the intestine is involved in the pathogenesis of inflammatory bowel disease (IBD). To study the role of gut microbiota in intestinal inflammation, the microbiome of control mice (C57BL6) given a gluten-containing standard diet versus C57BL6 mice given the gluten-free (GF) feed (n=10 in each group) was examined. All mice received the 3% DSS for 5 days. Throughout the study, feces were collected and processed for DNA extraction and MiSeq Illumina sequencing of V4 region of bacterial 16S rRNA gene. Alpha and beta diversities and compositional differences at phylum and genus levels were determined in intestinal microbiota. The mice receiving the GF diet showed a significantly increased abundance of Firmicutes and a decrease of Bacteroides and Lactobacillus at phylum level. Therefore, the gluten free diet led to reductions in beneficial gut bacteria populations. These findings indicate a role of wheat gluten in dysbiosis of the intestinal microbiota.

Keywords: gluten, colitis, microbiota, DSS, dextran sulphate sodium

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Authors: Tamar Lin, Nufar Buchshtab, Yifat Elharar, Julian Nicenboim, Rotem Edgar, Iddo Weiner, Lior Zelcbuch, Ariel Cohen, Sharon Kredo-Russo, Inbar Gahali-Sass, Naomi Zak, Sailaja Puttagunta, Merav Bassan

Abstract:

Background: Atopic dermatitis (AD) is a chronic, relapsing inflammatory skin disorder that is characterized by dry skin and flares of eczematous lesions and intense pruritus. Multiple lines of evidence suggest that AD is associated with increased colonization by Staphylococcus aureus, which contributes to disease pathogenesis through the release of virulence factors that affect both keratinocytes and immune cells, leading to disruption of the skin barrier and immune cell dysfunction. The aim of the current study is to develop a bacteriophage-based product that specifically targets S. aureus. Methods: For the discovery of phage, environmental samples were screened on 118 S. aureus strains isolated from skin samples, followed by multiple enrichment steps. Natural phages were isolated, subjected to Next-generation Sequencing (NGS), and analyzed using proprietary bioinformatics tools for undesirable genes (toxins, antibiotic resistance genes, lysogeny potential), taxonomic classification, and purity. Phage host range was determined by an efficiency of plating (EOP) value above 0.1 and the ability of the cocktail to completely lyse liquid bacterial culture under different growth conditions (e.g., temperature, bacterial stage). Results: Sequencing analysis demonstrated that the 118 S. aureus clinical strains were distributed across the phylogenetic tree of all available Refseq S. aureus (~10,750 strains). Screening environmental samples on the S. aureus isolates resulted in the isolation of 50 lytic phages from different genera, including Silviavirus, Kayvirus, Podoviridae, and a novel unidentified phage. NGS sequencing confirmed the absence of toxic elements in the phages’ genomes. The host range of the individual phages, as measured by the efficiency of plating (EOP), ranged between 41% (48/118) to 79% (93/118). Host range studies in liquid culture revealed that a subset of the phages can infect a broad range of S. aureus strains in different metabolic states, including stationary state. Combining the single-phage EOP results of selected phages resulted in a broad host range cocktail which infected 92% (109/118) of the strains. When tested in vitro in a liquid infection assay, clearance was achieved in 87% (103/118) of the strains, with no evidence of phage resistance throughout the study (24 hours). A S. aureus host was identified that can be used for the production of all the phages in the cocktail at high titers suitable for large-scale manufacturing. This host was validated for the absence of contaminating prophages using advanced NGS methods combined with multiple production cycles. The phages are produced under optimized scale-up conditions and are being used for the development of a topical formulation (BX005) that may be administered to subjects with atopic dermatitis. Conclusions: A cocktail of natural phages targeting S. aureus was effective in reducing bacterial burden across multiple assays. Phage products may offer safe and effective steroid-sparing options for atopic dermatitis.

Keywords: atopic dermatitis, bacteriophage cocktail, host range, Staphylococcus aureus

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Authors: Arredondo Valdés Roberto, Hernández Castillo Francisco Daniel, Laredo Alcalá Elan Iñaky, Gonzalez Gallegos Esmeralda, Castro Del Angel Epifanio

Abstract:

The common bean or Phaseolus vulgaris L. is the most important food legume for direct consumption in the world. Fusarium dry rot in the major fungus disease affects Phaseolus vulgaris L, after planting. In another hand, Rhizoctonia can be found on all underground parts of the plant and various times during the growing season. In recent years, the world has conducted studies about the use of natural products as substitutes for herbicides and pesticides, because of possible ecological and economic benefits. Plants respond to fungal invasion by activating defense responses associated with accumulation of several enzymes and inhibitors, which prevent pathogen infection. This study focused on the role of proteins, peroxidase (POD), phenylalanine ammonia lyase (PAL), in imparting resistance to soft rot pathogens by applied different bacterial consortium, formulated and provided by Biofertilizantes de Méxicanos industries, analyzing the enzyme activity at different times of application (6 h, 12 h and 24 h). The resistance of these treatments was correlated with high POD and PAL enzyme activity as well as increased concentrations of proteins. These findings show that PAL, POD and synthesis of proteins play a role in imparting resistance to Phaseolus vulgaris L. soft rot infection by Fusarium and Rhizoctonia.

Keywords: fusarium, peroxidase, phenylalanine ammonia lyase, rhizoctonia

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Authors: Hatem Shreha

Abstract:

Aromatase inhibitors administered before sexual differentiation of the gonads can induce sex reversal in female chickens (phenotypic male). To analyze the process of sex reversal, we have followed for several months the changes induced by Fadrozole, a nonsteroidal aromatase inhibitor on the morphology of female sex-reversed and female sex-reversed supplemented with L-tyrosine which was previously shown to stimulate the release of Gn Rh. Fadrozole (1mg/egg) was injected into eggs on day four of incubation, phenotypic males and phenotypic males treated with L-tyrosine and males hatched from eggs injected Fadrozole were sacrificed by slaughtering at 16 weeks old and the remaining chicks were sacrificed at 28 weeks old. Both sexes from control chickens were sacrificed at the same age (16 &28 weeks). Hatchability, behavior, body weight, shank length, comb weight, testes weight, blood cells count and wattle weight of sex reversal were tested at 16 and 28 weeks. The results showed that body weight, comb weight, wattles weight and shank length of sex-reversed females were significantly different from control female. Behavior of phenotypic males and phenotypic males fed on L- tyrosine showed aggressive sexual behavior like that of control males and absence of laying behavior. In conclusion our results confirm that Fedrazole injection in eggs before sex differentiation produce a male behavior and morphological index of male in female chicken.

Keywords: sex reversal, fadrozole, phenotypic male, L- tyrosine

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Authors: Tahsien Okasha

Abstract:

Transplantation medicine is one of the most challenging and complex areas of modern medicine. Some of the key areas for medical management are the problems of transplant rejection, during which the body has an immune response to the transplanted organ, possibly leading to transplant failure and the need to immediately remove the organ from the recipient. When possible, transplant rejection can be reduced through serotyping to determine the most appropriate donor-recipient match and through the use of immunosuppressant drugs. Postoperative care actually begins before the surgery in terms of education, discharge planning, nutrition, pulmonary rehabilitation, and patient/family education. This also allows for expectations to be managed. A multidisciplinary approach is the key, and collaborative team meetings are essential to ensuring that all team members are "on the same page." .The following clinical pathway map and guidelines with the aim to decrease alteration in clinical practice and are intended for those healthcare professionals who look after organ transplant patients. They are also intended to be useful to both medical and surgical trainees as well as nurse specialists and other associated healthcare professionals involved in the care of organ transplant patients. This pathway is general pathway include the general guidelines that can be applicable for all types of organ transplant with special considerations to each organ.

Keywords: postoperative care, organ transplant, clinical pathway, patient

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Authors: Wan Shan Chiang, Charn Ting Wang, Wei-Chih Kan, Hui-Chen Huang

Abstract:

Dialysis patients have risk in Zoster virus because of low immune. Valacyclovir (product name: Valtex) 500mg/tab, an anti-zoster virus medicine, is digested in kidney and it has side-effect of nervous system in patients with malfunction kidneys. Although the clinical basis of the proposed administration, we found that patients still have side effects. So we want to explore the appropriate dose of peritoneal dialysis patients. We read small samples of case reports and analyze 8 cases in our hospital, some patients’ Kt/v, match the standard of dialysis, and still go to the toilet, they still have side effect seriously with 500mg portion. The solution to this includes stopping medicine, reduction of medicine, increase of liquid change and timely hemodialysis and all of them speed up the recovery. The safety of medication needs extra attention of medical care employee. If they can tell the doctor if the patient has urine or not in his or her Kt/v, the doctor can prescribe the medicine accordingly. About the limitation, due to the lack of cases and related pharmacokinetics numbers. Therefore, for peritoneal patients, we think 500mg/48hoursis the saves. We also want to remind pharmaceuticals to revise the portion taken by patients, so that the doctor may judge the use.

Keywords: herpes zoster, Valacyclovir, peritoneal dialysis, health education

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Authors: Laura Bellassen, Idit Shachar

Abstract:

Multiple sclerosis (MS) is a chronic neurological disorder characterized by demyelination of the central nervous system (CNS), leading to a wide range of physical and cognitive impairments. Myeloid cells in the CNS, such microglia and border associated macrophage cells, participate in the neuroinflammation in MS. Activation of those cells in MS contributes to the inflammatory response in the CNS and recruitment of immune cells in the this compartment. SLAMF5 is a cell surface receptor that functions as a homophilic adhesion molecule, whose signaling can activate or inhibit leukocyte function. In the current study we followed the expression and function of SLAMF5 in myeloid cells in the CNS and in the periphery in the murine model for MS, the experimental autoimmune encephalomyelitis model (EAE). Our results show that SLAMF5 deficiency or blocking decreases the expression of activation molecules and costimulatory molecules such as MHCII and CD80, resulting in delayed onset and reduced progression of the disease. Moreover, blocking SLAMF5 in peripheral monocytes derived from MS patients and iPSC-derived microglia cells, controls the expression of HLA-DR and CD80. Thus, SLAMF5 is a regulator of myeloid cells function and can serve as a therapeutic target in autoimmune disorders as Multiple Sclerosis.

Keywords: multiple sclerosis, EAE model, myeloid cells, new antibody, neuroimmunology

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Authors: Yu-Hsiang Yu

Abstract:

The immunomodulatory effect of propolis has been widely investigated in the past decade. However, the beneficial effects in broilers are still poorly understood. The aim of this study was to evaluate the effect of propolis added in drinking water on immunomodulatory and antibody production in broiler. Total of 48 chicks were randomly allocated into four groups with 12 broilers per group. All birds were intranasal inoculated with Newcastle Disease vaccine at 4 and 14 days old of age. Four groups, including control without any treatment, groups of A, B and F [3 days of anterior (A), 3 days of posterior (P) and 6 days of full (F)] were supplied the propolis at 300 ppm in drinking water when vaccination was performed, respectively. Our results showed that no significant difference was found in growth performance, antibody production and immune organ index among groups. However, propolis treatments in broilers significantly reduced IL-4 expression in spleen at 14 days-old of age and bursa at 28 days-old of age compared with control group. The expression of IFN-gamma in spleen (A, P and F group) and bursal (F group) were elevated compared with control group at 28 days-old of age. In conclusion, our results indicated that propolis-treated birds could bear the capability for immunomodulatory effects by change Th1 subset cytokine expression in vaccination.

Keywords: propolis, broiler, immunomodulatory, vaccination

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Authors: Nada Alqadri, Omaima Nasir

Abstract:

Natural compounds are an important source of potential inhibitors; they have a lot of pharma potential with less adverse effects. The effective antiviral activities of natural products have been proved in different studies. The outbreak of COVID-19 in Wuhan, Hubei, in December 2019, coronavirus has had a significant impact on people's health and lives. Based on previous studies, natural products can be introduced as preventive and therapeutic agents in the fight against COVID-19; considering that no food or supplement has been authorized to prevent COVID-19, individuals continue to search for and consume specific herbs, foods, and commercial supplements for this purpose. This study will be aimed to estimate the uses of herbal and natural products during the COVID-19 infection to determine their usage reasons and evaluate their potential side effects. An online cross-sectional survey of different participants will be conducted and will be a focus on respondents’ chronic disease histories, socio-dmographic characteristics, and frequency and trends of using these products. Descriptive and univariate analyses will be performed to determine prevalence and associations between various products used and respondents’ socio-demographic data. Relationships will be tested using Pearson’s chi-square test or an exact probability test. Our main findings will give evidence of beneficial uses of natural products and herbal medicine as prophylactic and will be a vigorous approach to stop or at least slow down COVID-19 infection and transmission. This will be of great interest of public health, and the results of our study will lend health officials better control on the current pandemic.

Keywords: COVID-19, herbs, natural products, saudi arabia

Procedia PDF Downloads 218

Authors: M. Samsami, A. Hekmatdoost, N. Ebrahimi Daryani, P. Rezanejad Asl

Abstract:

Ulcerative colitis (UC) is an inflammatory bowel disease in which immune and inflammatory factors are thought to be effective in this disease. Resveratrol is an antioxidant and anti-inflammatory compound. This study determined the effects of resveratrol compound on inflammatory factors in patients with ulcerative colitis. This study was a double-blind randomized clinical trial conducted on 50 patients with UC. Subjects received one capsule daily for 6 wk of either resveratrol (500 mg) or a placebo. Inflammatory factors, anthropometric measures, and IBDQ-9 (Inflammatory Bowel Disease Questionnaire-9) scores were assessed at baseline and at the end of the study. STATA12 software was used for data analysis. No significant differences were found in the background variables between the two groups at baseline. The results indicated that resveratrol supplementation for 6 week significantly decreased plasma levels of TNF-a and hs-CRP and the activity of NF-κB over the placebo group (p<0.001). Significant differences remained after adjustment for vitamin C (p<0.0001). The IBDQ-9 scores increased significantly in the resveratrol group over the placebo group (p<0.001). The findings of this study showed that resveratrol supplementation can be useful in patients with ulcerative colitis.

Keywords: IBD, inflammation, resveratrol, ulcerative colitis

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Authors: Sudeshna Chandra, Christian Gäbler, Christian Schliebe, Heinrich Lang

Abstract:

Highly branched dendrimers provide structural homogeneity, controlled composition, comparable size to biomolecules, internal porosity and multiple functional groups for conjugating reactions. Electro-active dendrimers containing multiple redox units have generated great interest in their use as electrode modifiers for development of biosensors. The electron transfer between the redox-active dendrimers and the biomolecules play a key role in developing a biosensor. Ferrocenes have multiple and electrochemically equivalent redox units that can act as electron “pool” in a system. The ferrocenyl-terminated polyamidoamine dendrimer is capable of transferring multiple numbers of electrons under the same applied potential. Therefore, they can be used for dual purposes: one in building a film over the electrode for immunosensors and the other for immobilizing biomolecules for sensing. Electrochemical immunosensor, thus developed, exhibit fast and sensitive analysis, inexpensive and involve no prior sample pre-treatment. Electrochemical amperometric immunosensors are even more promising because they can achieve a very low detection limit with high sensitivity. Detection of the cancer biomarkers at an early stage can provide crucial information for foundational research of life science, clinical diagnosis and prevention of disease. Elevated concentration of biomarkers in body fluid is an early indication of some type of cancerous disease and among all the biomarkers, IgG is the most common and extensively used clinical cancer biomarkers. We present an IgG (=immunoglobulin) electrochemical immunosensor using a newly synthesized redox-active ferrocenyl dendrimer of generation 2 (G2Fc) as glassy carbon electrode material for immobilizing the antibody. The electrochemical performance of the modified electrodes was assessed in both aqueous and non-aqueous media using varying scan rates to elucidate the reaction mechanism. The potential shift was found to be higher in an aqueous electrolyte due to presence of more H-bond which reduced the electrostatic attraction within the amido groups of the dendrimers. The cyclic voltammetric studies of the G2Fc-modified GCE in 0.1 M PBS solution of pH 7.2 showed a pair of well-defined redox peaks. The peak current decreased significantly with the immobilization of the anti-goat IgG. After the immunosensor is blocked with BSA, a further decrease in the peak current was observed due to the attachment of the protein BSA to the immunosensor. A significant decrease in the current signal of the BSA/anti-IgG/G2Fc/GCE was observed upon immobilizing IgG which may be due to the formation of immune-conjugates that blocks the tunneling of mass and electron transfer. The current signal was found to be directly related to the amount of IgG captured on the electrode surface. With increase in the concentration of IgG, there is a formation of an increasing amount of immune-conjugates that decreased the peak current. The incubation time and concentration of the antibody was optimized for better analytical performance of the immunosensor. The developed amperometric immunosensor is sensitive to IgG concentration as low as 2 ng/mL. Tailoring of redox-active dendrimers provides enhanced electroactivity to the system and enlarges the sensor surface for binding the antibodies. It may be assumed that both electron transfer and diffusion contribute to the signal transformation between the dendrimers and the antibody.

Keywords: ferrocenyl dendrimers, electrochemical immunosensors, immunoglobulin, amperometry

Procedia PDF Downloads 337

Authors: Nneka Nkechi Uchegbu, Temitope Omolayo Fasuan

Abstract:

This study investigated how to reduce bio-compounds and amino acids in V. amygdalina leaf during processing as a functional food ingredient. Fresh V. amygdalina leaf was processed using thermal oil-aqueous mixtures (soybean oil: aqueous and palm oil: aqueous) at 1:40 and 130 (v/v), respectively. Results indicated that the hot soybean oil-aqueous mixture was the most effective in preserving the bio-compounds and amino acids with retention potentials of 80.95% of the bio-compounds at the rate of 90-100%. Hot palm oil-aqueous mixture retained 61.90% of the bio-compounds at the rate of 90-100% and hot aqueous retained 9.52% of the bio-compounds at the same rate. During the debittering process, seven new bio-compounds were formed in the leaves treated with hot soybean oil-aqueous mixture, six in palm oil-aqueous mixture, and only four in hot aqueous leaves. The bio-compounds in the treated leaves have potential functions as antitumor, antioxidants, antihistaminic, anti-ovarian cancer, anti-inflammatory, antiarthritic, hepatoprotective, antihistaminic, haemolytic 5-α reductase inhibitor, nt, immune-stimulant, diuretic, antiandrogenic, and anaemiagenic. Alkaloids and polyphenols were retained at the rate of 81.34-98.50% using oil: aqueous mixture while aqueous recorded the rate of 33.47-41.46%. Most of the essential amino acids were retained at a rate above 90% through the aid of oil. The process is scalable and could be employed for domestic and industrial applications.

Keywords: V. amygdalina leaf, bio-compounds, oil-aqueous mixture, amino acids

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Authors: Ragy Raafat Gaber Attaalla

Abstract:

PIP: This review, based on 2 large-scale studies, discusses the pharmacology and physiology of oral steroid contraceptives (OCs). The pharmacological distinction between synthetic and naturally occurring steroids centers on changes in biological activity dependent on compound formulation and an individual's metabolism. OC mechanism of action is explained as the main prevention of ovulation by interference with gonadotropin-releasing hormone. Since some 52 metabolic alterations have been reported in OC users, these phenomena are dealt with in 3 categories: 1) effects on the primary target organs of the female reproductive tract (ovary, myometrium, endometrium, cervix, vagina, breasts, and hypothalamus), 2) general metabolic effects (serum proteins, carbohydrate metabolism, lipid metabolism, water and electrolyte metabolism, body weight, tryptophan metabolism, and vitamins and minerals), and 3) effects on other organ systems (liver, central nervous system, skin, genitourinary, gastrointestinal tract, eye, immune phenomena, and effect on subsequent fertility). The choice of the proper OC formulation and use of OCs by adolescents are discussed. Assessment of OC safety, contraindications, and patient monitoring are provided.

Keywords: steroid oral contraceptives, ovulation, female reproductive tract, metabolic effects

Procedia PDF Downloads 96

Authors: J. Carlos Kuri, Varun Vij, Raymond J. Turner, Orly Yadid-Pecht

Abstract:

Celiac disease (CD) is an immune system disorder that is triggered by ingesting gluten. As a gluten-free (GF) diet has become a concern of many people for health reasons, a gold standard had to be nominated. Enzyme-linked immunosorbent assay (ELISA) has taken the seat of this role. However, multiple limitations were discovered, and with that, the desire for an alternative method now exists. Nucleic acid-based aptamers have become of great interest due to their selectivity, specificity, simplicity, and rapid-testing advantages. However, fluorescence-based aptasensors have been tagged as unstable, but lifespan details are rarely stated. In this work, the lifespan stability of a fluorescence-based aptasensor is shown over an 8-week-long study displaying the accuracy of the sensor and false negatives. This study follows 22 different samples, including GF and gluten-rich (GR) and soy sauce products, off-the-shelf products, and reference material from laboratories, giving a total of 836 tests. The analysis shows an accuracy of correctly classifying GF and GR products of 96.30% and 100%, respectively when the protocol is augmented with molecular sieves. The overall accuracy remains around 94% within the first four weeks and then decays to 63%.

Keywords: aptasensor, PEG, rGO, FAM, RM, ELISA

Procedia PDF Downloads 124

Authors: Shikha Masand, Sudesh Kumar Yadav

Abstract:

Certain protein kinases have been shown to be crucial for plant cell signaling pathways associated with plant immune responses. Here we identified a horsegram [Macrotyloma uniflorum (Lam.) Verdc.] malectin-like leucine rich receptor-like protein kinase (RLK) gene MuRLK. The functional MuRLK protein preferentially binds to mannose and N-acetyl glucosamine residues. MuRLK exists in the cytoplasm and also localizes to the plasma membrane of plant cells via its N-terminus. Over-expression of MuRLK in Arabidopsis enhances the basal resistance to infection with Pseudomonas syringae pv. tomato, Alternaria brassicicola and Hyaloperonospora arabidopsidis, are associated with elevated ROS bursts, MAPK activation, thus ultimately leading to hypersensitive cell death. Moreover, salicylic acid-dependent and jasmonic acid-dependent defense responses are also enhanced in the MuRLK-overexpressed plants that lead to HR-induced cell death. Together, these results suggest that MuRLK plays a key role in the regulation of plant cell death, early and late defense responses after the recognition of microbial pathogens.

Keywords: horsegram, Pseudomonas syringae pv. tomato, MuRLK, ROS burst, cell death, plant defense

Procedia PDF Downloads 248