ABSTRACT
Background: Aryl-carbon receptor [AhR], a ligand-activated transcription factor, is best known for its ability to mediate the effects of environmental toxins such as 2,3,7,8-tetrachlorodibenzo-p-dioxin. AhR is expressed in several tumor cells and regulates the expression of genes in the signal transduction pathways. In this study, we examined the soluble levels of AhR in patients with pancreatic cancer
Methods: 123 samples, including 59 [48%] samples of pancreatic ductal adenocarcinoma based on histological evidence and 64 [52%] healthy control samples, were evaluated to determine plasma levels of AhR by Enzyme-linked immunoassay
Results: The median of AhR among patients was 0.280 ng/mL, which differed considerably from 0.07 ng/mL in the control group [p < 0.001]. Significant differences of the AhR were observed between the plasma samples of the patients compared with the healthy group, with respect to male sex [p < 0.001], age groups [p = 0.001], diabetic status [p < 0.001], body mass index [BMI] categories [p = 0.035], and constantly smokers [p < 0.001]. We also observed significant differences between the level of AhR expression between men and women [p = 0.01] and ever to never smokers [p = 0.009] in the case group. In addition, the age of 65 and a BMI of 25 or less were significant factors in plasma AhR levels [[1.61 95%CI 1.08-2.38] and [1.84 95%CI 1.22-2.77], respectively]
Conclusion: The results of this study can add diagnostic information to pancreatic cancer involving AhR and the potential efficacy of this receptor in therapeutic strategies
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The brain-intestinal axis concept describes the communication between the intestinal microbiota as an ecosystem of a number of dynamic microorganisms and the brain. The composition of the microbial community of the human gut is important for human health by influencing the total metabolomic profile. In children with autism spectrum disorder [ASD], the composition of the fecal microbiota and their metabolic products has a different configuration of the healthy child. An imbalance in the metabolite derived from the microbiota in children with ASD affect brain development and social behavior. In this article, we review recent discoveries about intestinal metabolites derived from microbiota based on high-yield molecular studies in children with ASD as part of the ''intestinal brain axis''
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In general, both common illnesses and rare diseases can develop in people and their relatives in families. Therefore, taking family history is an effective screening tool to detect such diseases and patients should be aware of its importance in families' health with updating information in regular visiting. For more information on identifying the genetic pattern of diseases, in this article, we will first explain the evidence for genetic similarities within and between human populations and the human genetic variation. Then, we will address the importance of medical counseling and pedigree drawing and will clarify the necessity of biological samples and their collection in human genetic studies
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Background: Oxidative stress plays a major pathogenic role in liver injury following chronic hepatitis B. Glutathione peroxidase [Gpx] has a central role in regulating the oxidative state. Hepatitis B virus [HBV] results in down-regulation of Gpx. On the other hand, iron homeostasis is disrupted in HBV infected patients. Therefore, the objective of this study was to assess the interplay of Gpx and serum iron on clinical and virological characteristics of patients with chronic HBV infection
Method: One hundred and fifty adult, treatment-naïve, patients with chronic hepatitis B were randomly selected from an ongoing cohort of patients with HBV. Plasma Gpx1 concentration and HBV DNA quantity were measured. Liver stiffness was measured by transient elastography
Results: Serum iron had a positive association with HBV DNA count in the total population. Serum iron was not associated with liver stiffness. However, HBV DNA was significantly associated with liver stiffness only in male patients. Serum Gpx was inversely associated with liver stiffness. Serum iron and Gpx had indirect effects on liver stiffness via HBV DNA count. We observed distinct effects of serum iron on HBV DNA and Gpx on liver stiffness in male and female patients
Conclusion: We identified interplay of serum iron and Gpx1 in relation to level of liver fibrosis in patients with chronic hepatitis B. Our results suggest that oxidative stress and serum iron are differentially implicated in the progression of chronic hepatitis B in male and female patients
ABSTRACT
Human biorepositories are collection of biological samples and health information from a large number of participants generally in the cohort studies. The main purpose of established biobanks is organization of biomedical research for upgrading the knowledge of human disorders from cancer to infectious and rare disease. The studies of generation relationships and understanding the preclinical stages of ageing are also from the solution of bitobank. This review overview the significance and storage condition of biospecimens including whole blood, red blood cells [RBC], buffy coat, plasma, serum, DNA and RNA that derived from blood in human biobanks. These biological samples provide valuable information on the prevalence of germline mutations, epigenetic modifications or interaction between genes and proteins in associated with the development of certain types of disease. The quality of biospecimen in biobanks is a powerful tool for valid identification of biomarkers. Therefore optimum qualities of human biological samples in long time storage that have been assessed in several studies also indicate in this review
Subject(s)
Blood Buffy Coat , Erythrocytes , DNA , RNA , BloodABSTRACT
Successful clearance of hepatitis B virus [HBV] is a promising event in which host's immune system will attempt to get rid of the virus. The immunological events of HBsAg seroclearance have attracted great attention in both natural history investigations and therapeutic trials. Recent genome-wide association studies [GWAS] has confirmed polymorphisms in the human leukocyte antigen [HLA]-DP locus associated with spontaneous HBV clearance. In this review the impact of host immune response in declining HB5Ag during the natural history of the infection has been discussed
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There are hoarding documents for the biological importance of cyclooxygenase-2 [COX-2] in pancreatic carcinogenesis. We aimed to thoroughly investigate the DNA sequence variations of whole COX-2 exons in a large case- control study of pancreatic cancer by direct sequencing. The entire exonic regions of COX-2 including 10 exons were sequenced in the germline DNA of 96 patients with pancreatic cancer. Selected variants within exons six to seven [E6E7] amplicon from the test panel were genotyped in 96 controls. The COX-2 gene was demonstrated to be genetically conserved. Four missense mutations were found in three cases. However the common variant c.724-10_724-7deIATTT [rs20123141 1] that is located in intron 6, showed significant difference between cases and controls [21 [21.9%] vs 11 [%11.5], p=0.05]. This study determined that COX-2 has a conservative sequence, which is required for its enzymatic activity and supports the important role of this enzyme's expression in pancreatic cancer rather than any changes in its activity. The effect of intronic variant rs201231411 on COX-2 expression could be analyzed in future studies
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Colorectal cancer is one of the most commonly diagnosed cancers and cancer- related death worldwide. Identification of new specific biomarkers could be helpful to detection of this malignancy. Altered plasma microRNA expression has been identified in many cancers, including colorectal cancer. The main objective of this study was to identify the circulating microRNAs with the most expression changes in colorectal cancer patients compared with neoplasm free healthy individuals. MicroRNA expression profiling was performed on plasma samples of 37 colorectal cancer patients and 8 normal subjects using microRNA microarray. Quantitative real-time reverse transcription polymerase chain reaction was used to validate the two selected altered microR NAs. Plasma samples from 61 colorectal cancer patients and 24 normal subjects were used in our validation study. In profiling study we found a panel of six plasma microRNAs with significant downregulation. MicroRNA-142-3p and microRNA-26a-5p were selected and validated by polymerase chain reaction. Our results demonstrated that expression levels of plasma microRNA-142-3p and microRNA-26a-5p were significantly downregulated in patients with colorectal cancer when compared to control group. Our findings suggest that downregulation of plasma microRNA-142-3p and microRNA-26a-5p might serve as novel noninvasive biomarkers in the diagnosis of colorectal cancer, although more studies are needed to highlight the theoretical strengths
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Hepatitis B virus [HBV] infection is the most common cause of end stage liver disease in Iran and in Golestan province. Large-scale population-based prospective cohort studies with long term follow-up are the method of choice to accurately understand the natural course of HBV infection. To date, several studies of HBV epidemiology, natural history, progression to cirrhosis and association with HCC have been reported from other countries. However, few of these are prospective and fewer still are population-based. Moreover, the underlying molecular mechanisms and immunogenetic determinants of the outcome of HBV infection especially in low and middle income countries remains largely unknown. Therefore, the hepatitis B cohort study [HBCS], nested as part of the Golestan Cohort Study [GCS], Golestan, Iran was established in 2008 with the objective to prospectively investigate the natural course of chronic hepatitis B with reference to its epidemiology, viral/host genetic interactions, clinical features and outcome in the Middle East where genotype D HBV accounts for >90% of infections. In 2008, a baseline measurement of HBV surface antigen [HBsAg] was performed on stored serum samples of all GCS participants. A sub-cohort of 3,505 individuals were found to be HBsAg positive and were enrolled in the Golestan HBCS. In 2011, all first degree relatives of HBsAg positive subjects including their children and spouses were invited for HBV serology screening and those who were positive for HBsAg were also included in the Golestan HBCS
Subject(s)
Animals, Laboratory , Animals , Insecta , Cohort Studies , Prospective Studies , Hepatitis B Surface AntigensABSTRACT
Background: The ability of tumour suppressor protein p53 [P53] to regulate cell cycle processes can be modulated by hepatitis B virus [HBV]. While preliminary evidences indicates the involvement of protein-x of HBV [HBx] in altering p53 DNA binding, no further data have been accumulated for the significance of serum p53 in chronic hepatitis B virus infected patients
Methods: 72 non-cirrhotic and 19 cirrhotic patients infected by HBV were enrolled for the analysis in this study. Enzyme linked immunosorbent assay [ELISA] was performed to study the concentrations of serum p53 protein. The tertiary structures of HBx and P53 were docked by Z-dock and Hex servers for in-silico protein-protein interaction analysis
Results: There was a significant association between the serum p53 and cirrhosis [OR=1.81 95% CI: 1.017-3.2, P=0.044]. Cirrhotic patients had higher level of serum p53 compare with chronic infection of HBV [1.98 +/- 1.22 vs. 1.29 +/- 0.72 U/ml, P=0.05]. No evidence of correlation was seen between the different variables such as age, gender, log viral load, serum alkaline phosphatase [ALP] and alanine aminotransferase [ALT] with serum p53. Tertiary model shows that the amino acid residues from Arg110 to Lys132 of the N-terminal of P53 which is critical for ubiquitination, are bonded to a region in N- terminal of HBx amino acid residues from Arg19 to Ser33
Conclusion: There is an increase in serum p53 in HBV-related cirrhosis patients. In this case, HBx might be responsible for such higher concentration of p53 through HBx-p53 protein-protein interaction, as is shown by molecular modeling approach
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Hepatitis B virus [HBV] infection is the main cause of chronic hepatitis, cirrhosis and hepatocellular carcinoma [HCC]. Several factors such as serum HBV DNA level, genotype and specific viral mutations have been clarified to determine disease progression of chronic hepatitis B. Among these, mutations can also occur in chronic HBV patients with antiviral treatment such as lamivudine therapy. A better understanding of the host and viral mechanisms that influence the course of HBV infection and drug resistance to effective therapeutic approaches will improve the organization of patients with chronic HBV infection to attain viral eradication. This study aims to review the molecular biology of HBV, as well as the natural and induced genetic variations in response to anti-viral therapy in humans. The effect of host genetic factors in the outcome of HBV infection and new strategies for antiviral therapy are addressed.
Subject(s)
Humans , Mutation , Lamivudine , Hepatitis B, ChronicABSTRACT
Recent findings introduced APOBEC3G [A3G] as a host factor that blocks viral replication. It induces G to A hypermutations in viral DNA at the step of reverse transcription and in response to interferon. This study aimed to investigate the expression of liver A3G protein in association with both replication of hepatitis B virus [HBV] and frequency of G to A mutations in BCP [basal core promoter]-PC [pre-core] region. Fifty-one liver biopsies of naive chronic hepatitis B [CHB] patients enrolled for the expression of A3G were done by immunohistochemistry [IHC] standard method. The presence of HBV DNA and sequences of BCP-PC region at the time of liver biopsy was investigated in all patients. Among 34 patients with detectable HBV DNA, 31 carried 1-5 G to A mutations in the BCP-PC region. IHC results showed that the expression level of A3G in CHB patients' liver was very low. Of all patients, A3G is expressed in three undetectable HBV DNA subjects and a patient with 2.24 x 10[4] copies ml[-1] of HBV DNA. G to A mutated residues were indicated at positions 1727, 1757 and 1896 of the HBV genome of this patient. This study indicates that despite very low levels of both A3G in liver and the number of positive subjects, A3G has a potential role to restrict the in vivo replication of HBV
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Regression of precancerous lesions after H. pylori eradication remains controversial. This study evaluates the change and topography in first degree relatives [FOR] of gastric cancer [GC] patients following H. pylori eradication. Participants underwent endoscopy with antrum and corpus histological examinations. Subjects with pangastritis were randomly allocated to placebo or eradication therapy and followed over 41/2 years. Among 989 evaluated FDR, we excluded 468 patients as follows: 108 had macroscopic lesions, 243 had no evidence of any H. pylori infection, and 117 were excluded for other reasons. The remaining subjects [n = 521] were allocated to therapy [group A, n = 261] or placebo [group B, n = 260] groups. Interim analysis of 403 subjects [201 placebo, 202 therapy] showed regression of atrophy [60 out of 97 in the antrum and 37 out of 104 in the corpus] in H. pylori-eradicated versus regression of atrophy [57 out of 184 in the antrum and 23 out of 173 in the corpus] in non-H. pylori-eradicated cases over 21/2 years [P < 0.0001]. No regression of intestinal metaplasia [IM] occurred in the antrum and corpus of treated subjects over 41/2 years. However, progression of IM occurred in the antrum in 17 out of 90 patients in the non-H. pylori-eradicated versus 4 out of 68 H. pylori-eradicated subjects after 41/2 years [P < 0.05]. Eradication of H. pylori is associated with regression of gastric atrophy but not IM, even in its early stages. Gastric atrophy and IM in the antrum have shown more rapid progression in cases not treated for H. pylori infection [over 41/2 years follow-up] compared to H. pylori-eradicated cases
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Saliva is multifunctional; it is a lubricant for speech, aide for food digestion, and protective against microorganisms. It is voluntarily accessible, composed of proteins and electrolytes, and is ideal for the early detection of a wide range of diseases. Because of a complex protein mixture, saliva proteomics has the potential to be a novel approach in the search for protein biomarkers. Most salivary proteomics research has been performed in academic institutions that study oral health. However, saliva offers a promising clinical strategy for characterizing the association between salivary protein markers and pancreatic cancer. In this review we focus on the protein composition of saliva as it represents an important field, both for the oral environment, as well as disease diagnosis and monitoring.
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The association between hepatitis B virus [HBV] mutations and hepatocar-cinogenesis were reported in the literature. Preference for G over C in the leading DNA strand has been reported to account for the asymmetry in nucleotide [nt] composition. The aim of this study was to analyze the complete genome sequence and compositional asymmetry of HBV in different stages of hepatitis B. Full genome sequencing of 24 patients with chronic hepatitis B, some of whom also had cirrhosis and hepatocellular carcinoma [HCC] was performed. Mutations analysis was implemented in a comparison with a HBV genotype D reference from an international DNA database. CpGProD, a web-based application, was used to evaluate CG content and predict CpG islands. All strains were 3182 base pairs [bp] in length, except for two cases of HCC in which 9 and 21 nt, respectively, were deleted in preS2. The genetic relatedness of these isolates was 97%-100%. There were common CpG-rich regions in all 24 isolated full genome sequences, however a strong negative GC skew for forming a CpG island in the minus strand were exhibited in overlap with enhancer I in three HCC patients, a cirrhotic patient and three with chronic hepatitis. The high percentage of sequence identity between HBV isolates in our patients demonstrates that genomic factors, except for genotype, are involved in hepatocarcinogenesis. Variations in GC content which were caused by a different spectrum of mutations may affect DNA compositional asymmetry and epigenetic modification of HBV DNA in HCC
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Hepatitis B virus initiates a complicated cascade process leading to chronic hepatitis B, cirrhosis, and hepatocellular carcinoma. In inflammatory situations, myeloperoxidase is released in plasma and binds to apolipoprotein A-1 in high-density lipoproteins. This study aims to evaluate the level of plasma myeloperoxidase as well as the pattern of plasma proteins in patients with chronic hepatitis B. Included in this study were 30 male subjects: 19 chronic hepatitis B patients, 6 HBV-related cirrhotic patients, and 5 healthy controls. Plasma myeloperoxidase was measured using enzyme-linked immunosorbent assay. Proteomic analysis of plasma proteins was performed by two-dimensional gel electrophoresis [2-DE] and mass spectrometry. One way ANOVAwas used for data analysis. Mean plasma myeloperoxidase levels were higher in patients with liver cirrhosis [65.5 +/- 12.5; P=0.007] and chronic hepatitis B [53.7 +/- 10.6; P=0.18] when compared with healthy subjects [45 +/- 7.6]. Moreover, a positive correlation was found between plasma myeloperoxidase levels and hepatic fibrosis stage [r=0.53, P=0.002; r=0.63, P=0.000]. Proteomic analysis showed an altered plasma protein pattern in progressive hepatitis B and down-regulation of the major apolipoprotein A-1 along with the appearance of a variety of spots noted to be apolipoprotein A-1isoforms with different molecular masses. In this study, progressive liver injury due to HBV infection correlated with higher plasma myeloperoxidase and an altered plasma apolipoprotein A-1 pattern