Search results for: innate immune mechanisms in the liver

Authors: Abdelazeem Algammal, Reham Abouelmaatti, Xiaokun Li, Jisheng Ma, Eman Abdelnaby, Wael Elfeil

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Toll-like receptors (TLRs) are the best understood of the innate immune receptors that detect infections in vertebrates. However, the fish TLRs also exhibit very distinct features and a large diversity, which is likely derived from their diverse evolutionary history and the distinct environments that they occupy. Little is known about the fish immune system structure. Our work was aimed to identify and clone the Nile tilapiaTLR-3 as a model of freshwater fish species; we cloned the full-length cDNA sequence of Nile tilapia (Oreochromis niloticus) TLR-3 and according to our knowledge, it is the first report illustrating tilapia TLR-3. The complete cDNA sequence of Nile tilapia TLR-3 was 2736 pair base and it encodes a polypeptide of 912 amino acids. Analysis of the deduced amino acid sequence indicated that Nile tilapia TLR-3 has typical structural features and main components of proteins belonging to the TLR family. Our results illustrate a complete and functional Nile tilapia TLR-3 and it is considered an ortholog of the other vertebrate’s receptor.

Keywords: Nile tilapia, TLR-3, cloning, gene expression

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Authors: Maomao Cao

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Background and aims While the association between higher consumption of fish and lower liver cancer risk has been confirmed, however, the association between specific fish intake and liver cancer risk remains unknown. We aimed to identify the association between specific fish consumption and the risk of liver cancer. Methods: Based on a community-based seropositive hepatitis B cohort involving 18404 individuals, face to face interview was conducted by a standardized questionnaire to acquire baseline information. Three common fish types in this study were analyzed, including freshwater fish, sea fish, and small fish (shrimp, crab, conch, and shell). All participants received liver cancer screening, and possible cases were identified by CT or MRI. Multivariable logistic models were applied to estimate the odds ratio (OR) and 95% confidence intervals (CI). Multivariate multiple imputations were utilized to impute observations with missing values. Results: 179 liver cancer cases were identified. Consumption of freshwater fish and sea fish at least once a week had a strong inverse association with liver cancer risk compared with the lowest intake level, with an adjusted OR of 0.53 (95% CI, 0.38-0.75) and 0.38 (95% CI, 0.19-0.73), respectively. This inverse association was also observed after the imputation. There was no statistically significant association between intake of small fish and liver cancer risk (OR=0.58, 95%, CI 0.32-1.08). Conclusions: Our findings suggest that consumption of freshwater fish and sea fish at least once a week could reduce liver cancer risk.

Keywords: cross-sectional study, fish intake, liver cancer, risk factor

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Authors: JiYoung Park, SueGoo Rhee, HyunAe Woo

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In liver regeneration, quiescent hepatocytes need to be primed to fully respond to growth factors such as hepatocyte growth factor. To understand the priming process, it is necessary to analyze patterns of gene expression that occur during liver regeneration after partial hepatectomy (PHx). Recently, tyrosine phosphorylation of signal transducer and activator of transcription 3 (pYSTAT3) has been shown to play an important role in initiating liver regeneration. In order to evaluate the role of pYSTAT3 on liver regeneration after PHx, we used an intrabody which can selectively inhibit pYSTAT3. In our previous studies, an intrabody had been shown that it bound specifically to the pYSTAT3. Adenovirus-mediated expression of the intrabody in HepG2 cells, as well as mouse liver, blocked both accumulation of pYSTAT3 in the nucleus and downstream target of pYSTAT3. In this study, PHx was performed on intrabody-expressing mice and the expression levels of liver regeneration-related genes were analyzed. We also measured liver/body weight ratios and the related cellular signaling pathways were analyzed. Acute phase response genes were reduced in an intrabody-expressing mice during liver regeneration than in control virus-injected mice. However, the time course of liver mass restoration in intrabody-expressing mice was similar to that observed in control virus-injected mice. We also observed that the expression levels of anti-apoptotic genes, such as Bcl2 and Bcl-xL were decreased in intrabody-expressing mice whereas the expression of cell cycle-related genes such as cyclin D1, and c-myc was increased. Liver regeneration after PHx was partially impaired by the selective inhibition of pYSTAT3 with a phosphorylation site-specific intrabody and these results indicated that pYSTAT3 might have limited role in liver mass recovery.

Keywords: STAT3, pYSTAT3, liver regeneration, intrabody

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Authors: Bui Phuong Linh, Yuki Sakakibara, Ryuto Tanaka, Elizabeth H. Pigney, Taishi Hashiguchi

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Non-alcoholic steatohepatitis (NASH) is a chronic liver disease, often associated with type II diabetes, which sometimes progresses to more serious conditions such as liver fibrosis and hepatocellular carcinoma (HCC). NASH has become an important health problem worldwide, buttherapeutic agents for NASH have not yet been approved, and animal models with high clinical correlation are required. TheSTAM™ mouse shows the same pathological progression as human NASH patients and has been widely used for both drug efficacy and basic research, such as lipid profiling and gut microbiota research. In this study, we analyzed the RNA-seq data of STAM™mice at each pathological stage (steatosis, steatohepatitis, liver fibrosis, and HCC) and examined the clinical correlation at the genetic level. NASH was induced in male mice by a single subcutaneous injection of 200 µg streptozotocin solution 2 days after birth and feeding with high fat dietafter 4 weeks of age. The mice were sacrificed and livers collected at 6, 8, 10, 12, 16, and 20 weeks of age. For liver samples, the left lateral lobe was snap frozen in liquid nitrogen and stored at -80˚C for RNA-seq analysis. Total RNA of the cells was isolated using RNeasy mini kit. The gene expression of the canonical pathways in NASH progression from steatosis to hepatocellular carcinoma were analyzed, such as immune system process, oxidation-reduction process, lipid metabolic process. Moreover, since it has been reported that genetic traits are involved in the development of NASH-HCC, we next analyzed the genetic mutations in the STAM™mice. The number of individuals showing mutations in Mtorinvolved in Insulin signaling increases as the disease progresses, especially in the liver cancer phase. These results indicated a clinical correlation of gene profiles in the STAM™mouse.

Keywords: steatosis, non-alcoholic steatohepatitis, fibrosis, hepatocellular carcinoma, RNA-seq

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Authors: S. Essa, H. Safar, R. Raghupathy

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Human cytomegalovirus (CMV) continues to be a source of severe complications to immunologically immature and immune-compromised hosts. Effective CMV vaccine that diminishes CMV disease in transplant patients and avoids congenital infection remains of high importance as no approved vaccines exist. Though the exact links of defense mechanisms are unidentified, viral-specific antibodies and Th1/Th2 cytokine responses have been involved in controlling viral infections. CMV envelope glycoprotein B (UL55/gB), the matrix proteins (UL83/pp65, UL99/pp28, UL32/pp150), and the assembly protein UL80a/pp38 are known to be targets of antiviral immune responses. In this study, mice were immunized with five HCMV antigens (UL32/pp150, UL80a/pp38, UL99/pp28, and UL83/pp65), and serum samples were collected and evaluated for eliciting viral-specific antibody responses. Moreover, Splenocytes were collected, stimulated, and assessed for cytokine responses. The results demonstrated a CMV-antigen-specific antibody response to pp38 and pp65 (E/C >2.0). The highest titers were detected with pp38 (average E/C 16.275) followed by pp65 (average E/C 7.72). Compared to control cells, splenocytes from PP38 antigen immunized mice gave a significantly higher concentration of GM-CSF, IFN-γ, IL-2 IL-4, IL-5, and IL-17A (P<0.05). Also, splenocytes from pp65 antigen immunized mice resulted in a significantly higher concentration of GM-CSF, IFN-γ, IL-2 IL-4, IL-10, IL-12, IL-17A, and TNF- α. The designation of target CMV peptides by identifying viral-specific antibodies and cytokine responses is vital for understanding the protective immune mechanisms during CMV infection and identifying appropriate viral antigens to develop novel vaccines.

Keywords: hepatitis C virus, peripheral blood mononuclear cells, neutrophils, cytokines

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Authors: Xia Huo

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Children are more vulnerable to environmental toxicants compared to adults, and their developing immune system is among the most sensitive targets regarding toxicity of environmental toxicants. Studies have found that exposure to environmental toxicants is associated with impaired immune function in children, but only a few studies have focused on the relationship between environmental toxicant exposure and vaccine antibody potency and immunoglobulin (Ig) levels in children. These studies investigated the associations of exposure to polychlorinated biphenyls (PCBs), perfluorinated compounds (PFCs), heavy metals (Pb, Cd, As, Hg) and PM2.5 with the serum-specific antibody concentrations and Ig levels against different vaccines, such as anti-Hib, tetanus, diphtheria toxoid, and analyze the possible mechanisms underlying exposure-related alterations of antibody titers and Ig levels against different vaccines. Results suggest that exposure to these toxicants is generally associated with decreased potency of antibodies produced from childhood immunizations and an overall deficiency in the protection the vaccines provide. Toxicant exposure is associated with vaccination failure and decreased antibody titers, and increased risk of immune-related diseases in children by altering specific immunoglobulin levels. Age, sex, nutritional status, and co-exposure may influence the effects of toxicants on the immune function in children. Epidemiological evidence suggests that exposure-induced changes to humoral immunerelated tissue/cells/molecules response to vaccines may have predominant roles in the inverse associations between antibody responsiveness to vaccines and environmental toxicants. These results help us to conduct better immunization policies for children under environmental toxicant burden.

Keywords: environmental toxicants, immunotoxicity, vaccination, antibodies, children's health

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Authors: Atefeh Esmailnejad, Gholamreza Nikbakht Brujeni

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Major histocompatibility complex (MHC) is one of the best characterized genetic regions associated with immune responses and controlling disease resistance in chicken. Association of the MHC with a wide range of immune responses makes it a valuable predictive factor for the disease pathogenesis and outcome. In this study, the association of MHC with cell-mediated immune responses was analyzed in commercial broiler chicken. The tandem repeat LEI0258 was applied to investigate the MHC polymorphism. Cell-mediated immune response was evaluated by peripheral blood lymphocyte proliferation assay using MTT method. Association study revealed a significant influence of MHC alleles on cellular immune responses in this population. Alleles 385 and 448 bp were associated with elevated cell-mediated immunity. Haplotypes associated with improved immune responses could be considered as candidate markers for disease resistance and applied to breeding strategies.

Keywords: MHC, cell-mediated immunity, broiler, chicken

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Authors: Fatemeh Keshavarz

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

Keywords: schizophrenia, microglia, autoantibodies, IL-32

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Authors: Belgherbi Aicha, Bessaid Abdelhafid

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In the recent years a great deal of research work has been devoted to the development of semi-automatic and automatic techniques for the analysis of abdominal CT images. The first and fundamental step in all these studies is the semi-automatic liver and spleen segmentation that is still an open problem. In this paper, a semi-automatic liver and spleen segmentation method by the mathematical morphology based on watershed algorithm has been proposed. Our algorithm is currency in two parts. In the first, we seek to determine the region of interest by applying the morphological to extract the liver and spleen. The second step consists to improve the quality of the image gradient. In this step, we propose a method for improving the image gradient to reduce the over-segmentation problem by applying the spatial filters followed by the morphological filters. Thereafter we proceed to the segmentation of the liver, spleen. The aim of this work is to develop a method for semi-automatic segmentation liver and spleen based on watershed algorithm, improve the accuracy and the robustness of the liver and spleen segmentation and evaluate a new semi-automatic approach with the manual for liver segmentation. To validate the segmentation technique proposed, we have tested it on several images. Our segmentation approach is evaluated by comparing our results with the manual segmentation performed by an expert. The experimental results are described in the last part of this work. The system has been evaluated by computing the sensitivity and specificity between the semi-automatically segmented (liver and spleen) contour and the manually contour traced by radiological experts. Liver segmentation has achieved the sensitivity and specificity; sens Liver=96% and specif Liver=99% respectively. Spleen segmentation achieves similar, promising results sens Spleen=95% and specif Spleen=99%.

Keywords: CT images, liver and spleen segmentation, anisotropic diffusion filter, morphological filters, watershed algorithm

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Authors: H. Tanyildizi, M. Abuqebitah, I. Cavdar, M. Demir, L. Kabasakal

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Aim: Whole liver radiation has the modest benefit in the treatment of unresectable hepatic metastases but the radiation doses must keep in control. Otherwise, RILD complications may arise. In this study, we aimed to calculate amount of maximum permissible activity (MPA) and critical organ absorbed doses with MIRD methodology, to evaluate tumour doses for treatment response and whole liver doses for RILD and to find optimal liver function test additionally. Materials and Methods: This study includes 29 patients who attended our nuclear medicine department suffering from Y-90 microspheres treatment. 10 mCi Tc-99m MAA was applied to the patients for dosimetry via IV. After the injection, whole body SPECT/CT images were taken in one hour. The minimum therapeutic tumour dose is on the point of being 120 Gy1, the amount of activities were calculated with MIRD methodology considering volumetric tumour/liver rate. A sub-working group was created with 11 patients randomly and liver clearance rate with Tc-99m-Mebrofenin was calculated according to Ekman formalism. Results: The volumetric tumour/liver rates were found between 33-66% (Maksimum Tolarable Dose (MTD) 48-52Gy3) for 4 patients, were found less than 33% (MTD 72Gy3) for 25 patients. According to these results the average amount of activity, mean liver dose and mean tumour dose were found 1793.9±1.46 MBq, 32.86±0.19 Gy, and 138.26±0.40 Gy. RILD was not observed in any patient. In sub-working group, the relationship between Bilirubin, Albumin, INR (which show presence of liver disease and its degree), liver clearance with Tc-99m-Mebrofenin and calculated activity amounts were found r=0.49, r=0.27, r=0.43, r=0.57, respectively. Discussions: The minimum tumour dose was found 120 Gy for positive dose-response relation. If volumetric tumour/liver rate was > 66%, dose 30 Gy; if volumetric tumour/liver rate 33-66%, dose escalation 48 Gy; if volumetric tumour/liver rate < 33%, dose 72 Gy. These dose limitations did not create RILD. Clearance measurement with Mebrofenin was concluded that the best method to determine the liver function. Therefore, liver clearance rate with Tc-99m-Mebrofenin should be considered in calculation of yttrium-90 microspheres dosimetry.

Keywords: clearance, dosimetry, liver, RILD

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Authors: Zahra Azizi, Ashkan Karbasi, Farzin Firouzian, Sara Soleimani Asl, Akram Ranjbar

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Background: One of the most often used herbicides in agriculture is paraquat (PQ), which is very harmful to both people and animals. Chitosan is a well-known, non-toxic polymer commonly used in preparing particles via ionotropic gelation facilitated by negatively charged agents such as sodium alginate. This study aimed to compare the effects of PQ and nanoparaquat (PQNPs) on liver function in male rats. Materials & Methods: Rats were exposed to PQ & PQNPs (4 mg/kg/day, intraperitoneally) for seven days. Then, rats were anesthetized, and serum and liver samples were collected. Later, enzymatic activities such as alanine transaminase (ALT), aspartate transaminase (AST), and alkaline phosphatase (ALP) in serum and oxidative stress biomarkers such as lipid peroxidation (LPO), total antioxidant capacity (TAC) and total thiol groups (TTG) levels in liver tissue were measured by colorimetric methods. Also, histological changes in the liver were evaluated. Results: PQ altered the levels of ALT, AST, and ALP while inducing oxidative stress in the liver. Additionally, liver homogenates with PQ exposure had challenged LPO, TAC, and TTG levels. The severe liver damage is indicated by a significant increase in the enzyme activity of AST, ALT, and ALP in serum. According to the results of the current study, PQNPs, as compared to PQ and the control group, lowered ALT, AST, ALP, and LPO levels while increasing TAC and TTG levels. Conclusion: According to biochemical and histological investigations, PQ loaded in chitosan-alginate particles is more efficient than free PQ at reducing liver toxicity.

Keywords: paraquat, paraquat nanoparticles, liver, oxidative stress

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Authors: Taher Eid Shaaban Ahmed Mousa

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Non-Alcoholic fatty liver disease (NAFLD) is a major cause of multiple liver disorders, which strongly linked to a poor lifestyle. This study aiming to elucidate the exercise program’s effectiveness on hepatic fat mobilization among nonalcoholic fatty liver patients. Subjects: A purposive sample of 150 adult male & female patients. Setting: National institute of liver out patient's clinics of Menoufia University. Tools: three tools I: An interviewing structured questionnaire, II: International Physical Activity Questionnaire, III: compliance assessment sheet. Results: There was statistically significant difference pre and post exercise program regarding total body weight, physical activity level and compliance that prevent new fat development with resolution of existing one. Conclusion: regular exercise is the best implemented approach as an initial step for the prevention, treatment and management of NAFLD. Recommendation: It is highly important to unravel the mechanism and dose by which each exercise specifically resolve various stages of liver diseases.

Keywords: exercise program, hebatic fat mobilization, nonalcoholic fatty liver patients, sport science

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Authors: Monika Malik, Pooja Arora, Ruchi Sachdeva, Vishnampettai G. Ramachandran, Rahul Pal

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Apoptotic debris is believed to be the antigenic trigger in lupus. Whether such debris and autoantibodies induced in lupus-prone mice which specifically recognize its constituents can mediate differential effects on innate and humoral responses in such mice was assessed. The influence of apoptotic blebs and apoptotic cell-reactive monoclonal antibodies on phenotypic markers expressed on bone marrow-derived dendritic cells (BMDCs) and secreted cytokines were evaluated. Sera from lupus-prone and healthy mice immunized with the antibodies were analyzed for anti-self reactivity. Apoptotic blebs, as well as somatically-mutated IgG and non-mutated IgM apoptotic-cell reactive monoclonal antibodies, induced the preferential maturation of BMDCs derived from lupus-prone mice relative to BMDCs derived from healthy mice; antibody specificity and cell genotype both influenced the secretion of inflammatory cytokines. Immunization of lupus-prone mice with IgM and IgG antibodies led to hypergammaglobulinemia; elicited antibodies were self-reactive, and exhibited enhanced recognition of lupus-associated autoantigens (dsDNA, Ro60, RNP68, and Sm) in comparison with adjuvant-induced sera. While ‘natural’ IgM antibodies are believed to contribute to immune homeostasis, this study reveals that apoptotic cell-reactive IgM antibodies can promote inflammation and drive anti-self responses in lupus. Only in lupus-prone mice did immunization with IgG auto-antibodies enhance the kinetics of humoral anti-self responses, resulting in advanced-onset glomerulosclerosis. This study reveals that preferential innate and humoral recognition of the products of cell death in an autoimmune milieu influences the indices associated with lupus pathology.

Keywords: antigen spreading, apoptotic cell-reactive pathogenic IgG, and IgM autoantibodies, glomerulosclerosis, lupus

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Authors: Hussein Alahmer, Amr Ahmed

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Liver cancer is one of the common diseases that cause the death. Early detection is important to diagnose and reduce the incidence of death. Improvements in medical imaging and image processing techniques have significantly enhanced interpretation of medical images. Computer-Aided Diagnosis (CAD) systems based on these techniques play a vital role in the early detection of liver disease and hence reduce liver cancer death rate.  This paper presents an automated CAD system consists of three stages; firstly, automatic liver segmentation and lesion’s detection. Secondly, extracting features. Finally, classifying liver lesions into benign and malignant by using the novel contrasting feature-difference approach. Several types of intensity, texture features are extracted from both; the lesion area and its surrounding normal liver tissue. The difference between the features of both areas is then used as the new lesion descriptors. Machine learning classifiers are then trained on the new descriptors to automatically classify liver lesions into benign or malignant. The experimental results show promising improvements. Moreover, the proposed approach can overcome the problems of varying ranges of intensity and textures between patients, demographics, and imaging devices and settings.

Keywords: CAD system, difference of feature, fuzzy c means, lesion detection, liver segmentation

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Authors: Husham Bayazed

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Immune responses following surgical trauma play a pivotal role in predicting postoperative outcomes from healing and recovery to postoperative complications. Postoperative complications, including infections and protracted recovery, occur in a significant number of about 300 million surgeries performed annually worldwide. Complications cause personal suffering along with a significant economic burden on the healthcare system in any community. The accurate prediction of postoperative complications and patient-targeted interventions for their prevention remain major clinical provocations. Recent Findings: Recent studies are focusing on immune dysregulation mechanisms that occur in response to surgical trauma as a key determinant of postoperative complications. Antecedent studies mainly were plunging into the detection of inflammatory plasma markers, which facilitate in providing important clues regarding their pathogenesis. However, recent Single-cell technologies, such as mass cytometry or single-cell RNA sequencing, have markedly enhanced our ability to understand the immunological basis of postoperative immunological trauma complications and to identify their prognostic biological signatures. Summary: The advent of proteomic technologies has significantly advanced our ability to predict the risk of postoperative complications. Multiomic modeling of patients' immune states holds promise for the discovery of preoperative predictive biomarkers and providing patients and surgeons with information to improve surgical outcomes. However, more studies are required to accurately predict the risk of postoperative complications in individual patients.

Keywords: immune dysregulation, postoperative complications, surgical trauma, flow cytometry

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Authors: Wirot Likittrakulwong, Pisit Poolprasert, Tossaporn Incharoen

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Germinated paddy rice (GPR) has the potential to be used as a feed ingredient. However, their properties have not been fully investigated. This paper examined the nutrient digestibility and the relationship to immune activity in Roman hens fed with GPR. It was found that true and apparent metabolizable energy (ME) values of GPR were 3.20 and 3.28 kcal/g air dry, respectively. GPR exhibited high content of phytonutrients, especially GABA. GPR showed similar protein profiles in comparison to non-germinated paddy rice. For immune activity, the feed with GPR enhanced the immune activity of Roman hens under high stocking density stress as evidenced by the activity of superoxide dismutase (SOD) and lysozyme activity. In this study, GPR is proved to be a good source of functional ingredient for chicken feed.

Keywords: germinated paddy rice, nutrient digestibility, immune activity, functional property

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Authors: Gajendra Kumar Mourya, Dinesh Bhatia, Akash Handique, Sunita Warjri, Syed Achaab Amir

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Nowadays, Medical imaging has become an integral part of modern healthcare. Abdominal CT images are an invaluable mean for abdominal organ investigation and have been widely studied in the recent years. Diagnosis of liver pathologies is one of the major areas of current interests in the field of medical image processing and is still an open problem. To deeply study and diagnose the liver, segmentation of liver is done to identify which part of the liver is mostly affected. Manual segmentation of the liver in CT images is time-consuming and suffers from inter- and intra-observer differences. However, automatic or semi-automatic computer aided segmentation of the Liver is a challenging task due to inter-patient Liver shape and size variability. In this paper, we present a technique for automatic segmenting the liver from CT images using Random Forest Classifier. Random forests or random decision forests are an ensemble learning method for classification that operate by constructing a multitude of decision trees at training time and outputting the class that is the mode of the classes of the individual trees. After comparing with various other techniques, it was found that Random Forest Classifier provide a better segmentation results with respect to accuracy and speed. We have done the validation of our results using various techniques and it shows above 89% accuracy in all the cases.

Keywords: CT images, image validation, random forest, segmentation

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Authors: Mukta Singh, Ratan Kumar Saha, Himadri Saha, Paramveer Singh

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The present study evaluated the effect of sub-lethal doses of antifungal drug miconazole nitrate (MCZ) on immunological responses including immune-related gene expression and its role as a prophylactic drug against S. parasitica in Labeo rohita fingerlings. Fish were fed with sub lethal doses of MCZ i.e., T1- 6.30 mg MCZ kgBW⁻¹, T2- 12.61 mg MCZ kgBW⁻¹ and T3- 25.22 mg MCZ kgBW⁻¹ and sampling was done at different time intervals for 240 h. Immunological parameters viz. lysozyme activity, oxygen radical production and plasma anti-protease activity showed significant enhancement (p < 0.05) in fish fed with T2 and T3 doses. Significant reduction in plasma protein content was observed in all the dietary groups as compared to control. Expression of immune-relevant genes like TLR-22 and β2-M showed significantly higher expression at six h and 24 h of sampling in both liver and head-kidney. However, these genes showed a down-regulation after 120 h of sampling in both the tissues. Preventive efficacy study showed that single dose of MCZ provides protection against oomycetes up to the fourth day of infection. Significantly higher mortality was observed in control diet-fed fish as compared to fish fed with MCZ medicated diet. Thus, from the study, it can be concluded that the MCZ can act as a potent antifungal agent for preventing oomycetes infection as well as to enhance the immune response.

Keywords: antifungal, immune gene, immunological, miconazole nitrate, prophylactic

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Authors: Chaoran Liu

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Bioactive polysaccharides and polysaccharide-protein complex derived from mushrooms and fungi have a wide range of immunomodulatory activity with low side-effects and have therefore the potential to be developed as an adjuvant in cancer therapies. Mushrooms sclerotium is rich in polysaccharides and the polysaccharides isolated from the sclerotium of Polyporus rhinocerus have shown potent in vivo and in vitro immunomodulatory effects. Macrophages are considered to be an important component of the innate immune response against bacterial infection and cancer. To better understanding the immunomodulatory effects and its underlying mechanisms of sclerotial water-soluble polysaccharides extracted from P. rhinocerus on macrophages, the objectives of this study are to purify the water-soluble novel sclerotial polysaccharides and to characterize the structure and properties as well as to study the detailed molecular mechanisms of the in vitro immunomodulating effects in murine macrophages. The hot water-soluble fraction PRW from the sclerotium of P. rhinocerus was obtained using solvent extraction. PRW was further fractionated by membrane ultrafiltration to a give a fraction (PRW1) with molecular mass less than 50 kDa. PRW1 was characterized to be a polysaccharide-protein complex composed of 45.7% polysaccharide and 44.2% protein. The chemical structure of the carbohydrate moiety of PRW1 was elucidated by GC and FTIR to be mainly beta-D-glucan with trace amount of galactose and mannose. The immunomodulatory effects of PRW1 on murine RAW 264.7 macrophages were demonstrated in terms of the increase in nitric oxide production and cytokine production. Mechanistically, PRW1 initiates ERK phosphorylation to activate macrophages within 15 min and significantly improves the expression level of inducible NOS (iNOS) from 6 h after treatment. In summary, this study indicates that PRW1 is a potent immunomodulatory agent for macrophages and suggests that mushroom sclerotia from Polyporus rhinocerus requires for further investigation in cancer research.

Keywords: Polyporus rhinocerus, mushroom sclerotia, Polysaccharide-Protein Complex, macrophage activation

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Authors: Joshua I. Izegaegbe, Femi F. Oloye, Catherine E. Nasiru

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This study determined the level of manganese, zinc, copper, and nickel in the liver and muscle of the African Catfish, Clarias gariepinus from Ilushi River, Edo State, Nigeria with a view to determining the extent of contamination. Heavy metal determination of digested fish samples was done using the atomic absorption spectrophotometric method. The results show that the muscles and livers were contaminated to varying levels with the presence of some non-metallic elements. The heavy metal load revealed that zinc had the highest mean concentration of 0.217±0.008µg/g in liver and 0.130±0.006µg/g in muscle, while copper recorded the least concentration in liver 0.063±0.004µg/g and 0.027±0.003µg/gin muscle. The distribution of the heavy metals in the muscles and livers of Clarias gariepinus showed significant variations and the results also revealed that the concentration of heavy metals (Zn, Cu,Ni and Mn) found in the liver was higher than those found in the muscle. This indicates that the liver is a better accumulator of heavy metal in Clarias gariepinus than the muscles. On comparison with WHO/FAO/FEPA/USFDA standards, the study shows that the concentrations of heavy metals in liver and muscle were within permissible limits safe for human consumption.

Keywords: clarias gariepinus, heavy metals, liver, muscle

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Authors: Mohammad Jamal

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Non-alcoholic fatty liver disease (NAFLD) has become one of the most chronic liver diseases, prevalent among people with morbid obesity. NAFLD does not develop clinically significant liver disease, however cirrhosis and liver cancer develop in subset and currently there are no approved therapies for the treatment of NAFLD. The study is aimed to understand the various key genes involved in the mechanism of NAFLD which can be valuable for developing diagnostic and predictive biomarkers based on their histologic stage of liver. The study was conducted on 16 male Sprague Dawley rats. The animals were divided in two groups: control group (n=8) fed on ad libitum normal chow and regular water and the cafeteria group (CAF)) (n=8) fed on high fatty/ carbohydrate diet. The animals received their respective diet from 4 weeks onwards from D.O.B until 25 weeks. Liver was extracted and RT² Profiler PCR Array was used to assess the NAFLD related genes. Histological evaluation was performed using H&E stain in liver tissue sections. Our PCR array results showed that genes involved in anti-inflammatory activity (Ifng, IL10), fatty acid uptake/oxidation (Fabp5), apoptosis (Fas), lipogenesis (Gck and Srebf1), Insulin signalling (Igfbp1) and metabolic pathway (pdk4) were upregulated in the liver of cafeteria fed obese rats. Bloated hepatocytes, displaced nucleus and higher lipid content were seen in the liver of cafeteria fed obese rats. Although Liver biopsies remain the gold standard in evaluating NAFLD, however an approach towards non-invasive markers could be used in understanding the physiology, therapeutic potential, and the targets to combat NAFLD.

Keywords: biomarkers, cafeteria diet, obesity, NAFLD

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Authors: Holm Zerbe, Laura Macias, Hans-Joachim Schuberth, Wolfram Petzl

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Mastitis is among the most important production diseases in cows. It accounts for large parts of antimicrobial drug use in the dairy industry worldwide. Due to the imminent normative to reduce the use of antimicrobial drugs in livestock, new ways for therapy and prophylaxis of mastitis are needed. Recently epigenetic regulation of inflammation by chromatin modifications has increasingly drawn attention. Currently, some epigenetic modifiers have already been approved for the use in humans, however little is known about their actions in the bovine system. The aim of our study was to investigate whether three selected epigenetic modifiers (Vitamin D3, SAHA and S2101) influence the initial immune response towards mastitis pathogens in bovine udder tissue in vitro. Tissue explants of the teat cistern and udder parenchyma were collected from 21 cows and were incubated for 36 hours in the absence and presence of epigenetic modifiers. Additionally, the tissue was stimulated with heat-inactivated particles of Escherichia coli and Staphylococcus aureus, which are regarded as two of the most important mastitis pathogens. After incubation, the explants were tested by RT-qPCR for transcript abundances of immune-related candidate genes. Gene expression was validated in culture supernatants by an AlphaLISA assay. Furthermore, the culture supernatants were analyzed for their chemotactic capacity through a chemotaxis assay. Statistical analysis of data was performed with the program ‘R’ version 3.2.3. Vitamin D3 had no effect on the immune response of udder tissue in vitro after stimulation with mastitis pathogens. The epigenetic modifiers SAHA and S2101 however significantly blocked the pathogen-induced upregulation of CXCL8, TNFα, S100A9 and LAP (P < 0.05). The regulation of IL10 was not affected by treatment with SAHA and S2101. Transcript abundances for CXCL8 were reflected by IL8 contents and chemotactic activity in culture supernatants. In conclusion, these data show the potential of epigenetic modifiers (SAHA and S2101) to block overshooting inflammation in the udder. Thus epigenetic modifiers may serve in future as immune modulators for the treatment and/or prophylaxis of clinical mastitis. (Funded by Deutsche Forschungsgemeinschaft PE 1495/2-1).

Keywords: mastitis, cattle, epigenetics, immunomodulation

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Authors: Ziwei Song, Junjun Fan, Jeremy Teo, Yang Yu, Yukun Ma, Jie Yan, Shupei Mo, Lisa Tucker-Kellogg, Peter So, Hanry Yu

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Liver is the center of detoxification and exposed to toxic metabolites all the time. It is highly regenerative after injury, with the ability to restore even after 70% partial hepatectomy. Most of the previous studies were using hepatectomy as injury models for liver regeneration study. There is limited understanding of small-scale liver injury, which can be caused by either low dose drug consumption or hepatocyte routine metabolism. Although these small in situ injuries do not cause immediate symptoms, repeated injuries will lead to aberrant wound healing in liver. Therefore, the cellular dynamics during liver regeneration is critical for our understanding of liver regeneration mechanism. We aim to study the liver regeneration of small-scale in situ liver injury in transgenic mice labeling actin (Lifeact-GFP). Previous studies have been using sample sections and biopsies of liver, which lack real-time information. In order to trace every individual hepatocyte during the regeneration process, we have developed and optimized an intravital imaging system that allows in vivo imaging of mouse liver for consecutive 5 days, allowing real-time cellular tracking and quantification of hepatocytes. We used femtosecond-laser ablation to make controlled and repeatable liver injury model, which mimics the real-life small in situ liver injury. This injury model is the first case of its kind for in vivo study on liver. We found that small-scale in situ liver injury is repaired by the coordination of hypertrophy and migration of hepatocytes. Hypertrophy is only transient at initial phase, while migration is the main driving force to complete the regeneration process. From cellular aspect, Akt/mTOR pathway is activated immediately after injury, which leads to transient hepatocyte hypertrophy. From mechano-sensing aspect, the actin cable, formed at apical surface of wound proximal hepatocytes, provides mechanical tension for hepatocyte migration. This study provides important information on both chemical and mechanical signals that promote liver regeneration of small in situ injury. We conclude that hypertrophy and migration play a dominant role at different stages of liver regeneration.

Keywords: hepatocyte, hypertrophy, intravital imaging, liver regeneration, migration

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Authors: Hager Elsheikh

Abstract:

Context: Pancreatitis is a condition characterized by inflammation in the pancreas, which can lead to serious complications if untreated. Both acute and chronic pancreatitis are associated with immune reactions and fibrosis, which further damage the pancreas. The type 2 immune response, primarily driven by alternative activated macrophages (AAMs), plays a significant role in the development of fibrosis. The IL-4/STAT6 pathway is a crucial signaling pathway for the activation of M2 macrophages. Pancreatic fibrosis is induced by dysregulated inflammatory responses and can result in the autodigestion and necrosis of pancreatic acinar cells. Research Aim: The aim of this study is to investigate the impact of STAT6, a crucial molecule in the IL-4/STAT6 pathway, on the severity and development of fibrosis during acute and chronic pancreatitis. The research also aims to understand the influence of the JAK/STAT6 signaling pathway on the balance between fibrosis and regeneration in the presence of different macrophage populations. Methodology: The research utilizes murine models of acute and chronic pancreatitis induced by cerulean injection. Animal models will be employed to study the effect of STAT6 knockout on disease severity and fibrosis. Isolation of acinar cells and cell culture techniques will be used to assess the impact of different macrophage populations on wound healing and regeneration. Various techniques such as PCR, histology, immunofluorescence, and transcriptomics will be employed to analyze the tissues and cells. Findings: The research aims to provide insights into the mechanisms underlying tissue fibrosis and wound healing during acute and chronic pancreatitis. By investigating the influence of the JAK/STAT6 signaling pathway and different macrophage populations, the study aims to understand their impact on tissue fibrosis, disease severity, and pancreatic regeneration. Theoretical Importance: This research contributes to our understanding of the role of specific signaling pathways, macrophage polarization, and the type 2 immune response in pancreatitis. It provides insights into the molecular mechanisms underlying tissue fibrosis and the potential for targeted therapies. Data Collection and Analysis Procedures: Data will be collected through the use of murine models, isolation and culture of acinar cells, and various experimental techniques such as PCR, histology, immunofluorescence, and transcriptomics. Data will be analyzed using appropriate statistical methods and techniques, and the findings will be interpreted in the context of the research objectives. Conclusion: By investigating the mechanisms of tissue fibrosis and wound healing during acute and chronic pancreatitis, this research aims to enhance our understanding of the disease progression and potential therapeutic targets. The findings have theoretical importance in expanding our knowledge of pancreatic fibrosis and the role of macrophage polarization in the context of the type 2 immune response.

Keywords: immunity in chronic diseases, pancreatitis, macrophages, immune response

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Authors: Justina I. R. Udotong, Ofonime U. M. John

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Toxicity of copper (Cu), lead (Pb) and iron (Fe) to Tilapia guinensis was carried out for 4 days with a view to determining their effects on the liver and muscle tissues. Tilapia guinensis samples of about 10 - 14cm length and 0.2 – 0.4kg weight each were obtained from University of Calabar fish ponds and acclimated for three (3) days before the experimental set up. Survivors after the 96-hr LC50 test period were selected from test solutions of the heavy metals for the histopathological studies. Histological preparations of liver and muscle tissues were randomly examined for histopathological lesions. Results of the histological examinations showed gross abnormalities in the liver tissues due to pathological and degenerative changes compared to liver and muscle tissues from control samples (tilapia fishes from aquaria without heavy metals). Extensive hepatocyte necrosis with chronic inflammatory changes was observed in the liver of fishes exposed to Cu solution. Similar but less damaging effects were observed in the liver of fishes exposed to Pb and Fe. The extent of lesion observed was therefore heavy metal-related. However, no pathologic changes occurred in the muscle tissues.

Keywords: degenerative changes, heavy metal, hepatocyte necrosis, histopathology, toxicity

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Authors: Sara Grazhdani, Alma Cili, Arben Ivanaj

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Immune Thrombocytopenic Purpura is an autoimmune disease characterized by the destruction of platelets by immune mediators, their deficient production in the red bone marrow and increased splenic sequestration, leading to the appearance of thrombocytopenia and increased risk of hemorrhage. Treatment is indicated in patients with low platelet counts (<30 x 10 9 /L) who present clinically with hemorrhagic events or are at increased risk for hemorrhage. The goal of the treatment remains (I) prevention of hemorrhagic events and deaths resulting from them, (II) reaching an adequate level of the number of platelets, (III) treatment of patients with as few toxic effects as possible. Corticosteroid therapy remains the first choice in the treatment of patients with Primary Immune Thrombocytopenic Purpura. Rituximab (Mabthera) remains the first choice in the second line in the treatment of patients with Immune Thrombocytopenic Purpura, refractory to the use of cortisones.

Keywords: ITP, rituximab, prednisolone, relapse

Procedia PDF Downloads 76

Authors: Ae Ra Han, Seoung Eun Huh, Ji Yeon Kim, Joanne Kwak-Kim, Sung Ki Lee

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Objective: Prevalence of osteoporosis, cardiovascular disorders, and Alzheimer's disease rapidly increase after menopause. Immune activation and inflammation are suggested as an important pathogenesis of these serious diseases. Several pro-inflammatory cytokines are increased in women with surgical or natural menopause. However, the little is known about IL-17 producing T cells and Foxp3+ regulatory T (Treg) cells in post-menopause. Methods: A total of 34 postmenopausal women, who had no active cardiovascular, endocrine and infectious disorders were recruited as study group and healthy premenopausal women participated as controls. Peripheral blood mononuclear cells were isolated. Immuno-morphologic (CD3, CD4, CD8, CD19, CD56/CD16), intracellular cytokine (TNF-alpha, IFN-gamma, IL-10, IL-17), and Treg cell (Foxp3) studies were carried out using flow cytometry. The proportion of peripheral lymphocytes, including IL-17 producing and Foxp3+ Treg cells immune cell in each group were statistically analyzed. Results: The proportion of NK cells was significantly increased in menopausal women as compared to that of controls (P=.005). The ratios of TNF-alpha/IL-10 producing CD3+CD4+ T cells were increased in postmenopausal women. CD3+IL-17+ T cell level was higher in postmenopausal women and CD4+ Foxp3+ Treg cells was lower than that of controls. The ratios of CD3+IL-17+ T cell to CD3+Foxp3+ and to CD4+Foxp3+ Treg cells were significantly increased in postmenopausal women (P=.001). Conclusions: We found enhanced innate immunity and Th1- and Th17-mediated adaptive immunity in postmenopausal women. This may explain increasing prevalence of chronic inflammatory diseases after menopause. Further studies are needed to elucidate what factors contribute to this inflammatory shift in the postmenopause.

Keywords: inflammation, immune cell, menopause, Th17, regulatory T cell

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Authors: Ferjani Hanen, El Arem Amira, Boussema Ayed Imen, Bacha Hassen

Abstract:

Tacrolimus (TAC), a calcineurin inhibitor, is clinically used as an immunosuppressive agent in the transplant recipient, but its use associated-hepatotoxicity. Mycophenolate mofetil (MMF), an anti-metabolite, is a potent immunosuppressive drug. MMF is not hepatotoxic and is the most common adjunctive immunosuppressant for TAC. The effects of TAC and MMF combination in the liver is still not well understood. This work aimed to investigate their combined effect against in liver in rats Wistar after 24 h. The oral median lethal doses (LD50) of TAC and MMF alone were evaluated in rats are 240 mg/kg and 500 mg/kg respectively. Oral administration of the MMF at 50 mg/kg to male Wistar intoxicated with TAC at 60 mg/kg, demonstrated a significant protective effect by lowering the levels of hepatic markers enzymes (AST, ALT) in the serum rat. MMF attenuated oxidative stress by restoring the activities of SOD, CAT and by reducing the malondialdehyde (MDA) and protein carbonyl levels liver. This study provided evidence that MMF protects rat liver from TAC-induced injury and suggests a most combination use for organ transplantation.

Keywords: tacrolimus, mycophenolate mofetil, combination, liver, rat

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Authors: R. R. Ramsheeja, R. Sreeraj

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For view the internal structures of the human body such as liver, brain, kidney etc have a wide range of different modalities for medical images are provided nowadays. Computer Tomography is one of the most significant medical image modalities. In this paper use CT liver images for study the use of automatic computer aided techniques to calculate the volume of the liver tumor. Segmentation method is used for the detection of tumor from the CT scan is proposed. Gaussian filter is used for denoising the liver image and Adaptive Thresholding algorithm is used for segmentation. Multiple Region Of Interest(ROI) based method that may help to characteristic the feature different. It provides a significant impact on classification performance. Due to the characteristic of liver tumor lesion, inherent difficulties appear selective. For a better performance, a novel proposed system is introduced. Multiple ROI based feature selection and classification are performed. In order to obtain of relevant features for Support Vector Machine(SVM) classifier is important for better generalization performance. The proposed system helps to improve the better classification performance, reason in which we can see a significant reduction of features is used. The diagnosis of liver cancer from the computer tomography images is very difficult in nature. Early detection of liver tumor is very helpful to save the human life.

Keywords: computed tomography (CT), multiple region of interest(ROI), feature values, segmentation, SVM classification

Procedia PDF Downloads 489

Authors: Hai-Ying Liu, Yi-Hao Chen, Shu-Yin Pang, Feng-Hua Wang, Xiao-Fang Peng, Li-Yuan Yang, Zheng-Rong Chen, Yi Chen, Bing Zhu

Abstract:

Objective: Biliary atresia (BA) is characterized by progressive liver fibrosis. Epithelial-mesenchymal transition (EMT) has been implicated as a key mechanism in the pathogenesis of organ fibrosis. MiR-200a has been shown to repress EMT. We aim to explore the role of miR-200a in the fibrogenesis of BA. Methods: We obtained the plasma samples and liver samples from patients with BA or controls to examine the role of miR-200a. Histological liver fibrosis was assessed using the Ishak fibrosis scores. Reverse transcription quantitative polymerase chain reaction (RT-qPCR) was performed to detect the expression of miR-200a in plasma. We also evaluated the expression of miR-200a in liver tissues using tyramide signal amplification fluorescence in situ hybridization (TSA-FISH). The expression of EMT related proteins zinc finger E-box-binding homeobox 1 (ZEB1), E-cadherin and α-smooth muscle actin (α-SMA) in the liver sections were detected by immunohistochemical staining. Results: We found that the expression of miR-200a was both elevated in the plasma and liver tissues from BA patients compared with the controls. The hepatic expression of ZEB1 and α-SMA were markedly increased in the liver sections from BA patients compared to the controls, whereas E-cadherin was downregulated in the BA group. Simultaneously, we noted that the hepatic expression of miR-200a, E-cadherin and α-SMA were upregulated with the progression of liver fibrosis in the BA group, while ZEB1 was downregulated with the progression of liver fibrosis in BA patients. Conclusion: These findings suggest EMT has a critical effect on the fibrotic process of BA, and the interaction between miR-200a and ZEB1 may regulate EMT and eventually influence liver fibrogenesis of BA.

Keywords: biliary atresia, liver fibrosis, MicroRNA, epithelial-mesenchymal transition, zinc finger E-box-binding homeobox 1

Procedia PDF Downloads 338