Gholamhossein Hassanshahi - Academia.edu (original) (raw)

Papers by Gholamhossein Hassanshahi

Archives of Virology, Jan 21, 2014

Viruses, including hepatitis B virus (HBV), are the most prevalent and infectious agents that lea... more Viruses, including hepatitis B virus (HBV), are the most prevalent and infectious agents that lead to liver disease in humans. Hepatocellular carcinoma (HCC) and cirrhosis of the liver are the most serious complications arising from prolonged forms of hepatitis B. Previous studies demonstrated that patients suffering from long-term HBV infections are unable to eradicate HBV from hepatocytes completely. The mechanisms responsible for progression of these forms of infection have not yet been clarified. However, it seems that there are differences in genetic and immunological parameters when comparing patients to subjects who successfully clear HBV infections, and these may represent the causes of long-term infection. Natural killer (NK) cells, the main innate immune cells that target viral infections, play important roles in the eradication of HBV from hepatocytes. NK cells carry several stimulatory and inhibitor receptors, and binding of receptors with their ligands results in activation and suppression of NK cells, respectively. The aim of this review is to address the recent information regarding NK cell phenotype, functions and modifications in hepatitis B. This review addresses the recent data regarding the roles of NK cells as novel targets for immunotherapies that target hepatitis B infection. It also discusses the potential to reduce the risk of HCC or cirrhosis of the liver by targeting NK cells.

Clinics and Research in Hepatology and Gastroenterology, Sep 1, 2011

Background: The association between mutations in the Hepatitis B Surface antigen (HBsAg) gene and... more Background: The association between mutations in the Hepatitis B Surface antigen (HBsAg) gene and the occurrence of occult HBV (OBI) in patients has not been studied adequately to determine if the two are correlated. The current study was aimed to investigate HBsAg mutations, the genotype of HBV and co-infection with HCV in OBI in the central part of Iran to determine any possible associations. Material and methods: In this study 3700 plasma samples were examined for the presence of HBsAg, anti-HBc and HBV-DNA. All HBsAg-/anti-HBc + /HBV-DNA + samples were regarded as OBI. The genotype of HBV was identified using Gap-PCR and RT-PCR was used to determine possible co-infection with HCV. Finally, direct sequencing was performed to analyse mutations within the Surface antigen gene of HBV in occult versus acute HBV infection. Results: Of the 3700 patient samples analysed, 352 (9.5%) cases were determined to be HBsAg-/anti-HBc + in which HBV-DNA was detected in 57 (16.1%), these latter patients were classified as OBI. All of the patients studied carried the D genotype. Direct sequencing of the S-gene from occult and acute HBV patients revealed one silent and one Glycine to Arginine mutation but the acute HBV patients showed an additional mutation (Alanine to Threonine). All the mutations were outside the range of the α-determinant. Furthermore, none of the OBI patients were co-infected with HCV. Conclusions: The absence of conformational mutations in the αdeterminant of HBsAg confirmed that this antigen could be detected by commercial ELISA kits and therefore was not responsible for false negatives during blood screening. However, it can be concluded that suitable amounts of HBsAg were not expressed by HBV in the OBI patients to be detected by ELISA. Low level expression of HBsAg might be related to the D genotype of the virus. Furthermore, our results suggest that OBI is not related to co-infection with HCV.

Iranian Journal of Basic Medical Sciences, May 1, 2011

Objective(s) Deregulation of the immune system through allied factors and cytokine responses are ... more Objective(s) Deregulation of the immune system through allied factors and cytokine responses are thought to be important contributors to the pathogenesis of asthma. Vitamin D3 and its nuclear receptor appear to be factors that maybe involved in regulating i mmune responses during the progression of asthma. The aim of this study was to investigate the association between polymorphisms in intron 8 and exon 9 of the vitamin D receptor (VDR) and this disease. Materials and Methods This study was performed on 100 asthmatic patients and 100 healthy controls. PCR-RFLP was performed to examine polymorphisms in intron 8 and exon 9 of VDR gene. Results Our results showed a statistically significant difference in the Taq-1 evaluated genotypes of exon 9 of the VDR gene when comparing healthy patients to asthmatic patients. Conclusion Based on our results, it can be concluded that VDR and its functional polymorphisms may play an important role in the pathogenesis of asthma.

Molecular Biology Reports, Apr 16, 2014

Micro-RNAs (miRNAs) play key roles in regulating genes of the immune system. The aim of this stud... more Micro-RNAs (miRNAs) play key roles in regulating genes of the immune system. The aim of this study was to examine the expression of miR-1, 21 and 125a in the immune cells taken from the peripheral blood of patients suffering from chronic HBV infection (CHB). This cross-sectional study was performed on 60 CHB patients and 60 healthy controls and expression of miR-1, 21 and 125a was evaluated using quantitative Real-Time PCR. The results showed that expression of miR-1, 21 and 125a was significantly increased in CHB patients in comparison to healthy controls. Based on our results it may be concluded that increased expression of miR-1, 21 and 125a is significantly associated with CHB and may play key roles in the induction of impaired immune responses in CHB patients.

Clinics and Research in Hepatology and Gastroenterology, Apr 1, 2011

Background: Occult hepatitis B infection (OBI) is characterized as a form of hepatitis in which, ... more Background: Occult hepatitis B infection (OBI) is characterized as a form of hepatitis in which, despite of absence of detectable HBsAg, HBV-DNA is present in patient's peripheral blood. The aim of this study was to investigate components of humoral immunity during OBI as a possible measure of how patients respond to Hepatitis B viral infections. Material and methods: In this study, HBsAg-/anti-HBc+/HBV-DNA+ samples were assigned as OBI cases and SRID techniques were performed to measure levels of circulating antibodies (IgG, IgM and IgA) as well as C3, C4. In addition, complement system function was assessed by CH50. Results: Our results showed that the serum levels of IgG and C4 were significantly lower in OBI patients, while IgM and C3 were higher in patients when compared to healthy controls. Serum levels of IgA and CH50 were not significantly different between OBI patients and controls. Discussion: Based on these results, it could be concluded that although OBI patients produced elevated levels of IgM there may be a problem converting and progressing this response to generate enough IgG to overcome HBV infection.

Labmedicine, Dec 1, 2010

An occult hepatitis B virus (HBV) infection (OBI) is diagnosed in a patient with detectable hepat... more An occult hepatitis B virus (HBV) infection (OBI) is diagnosed in a patient with detectable hepatitis B virus DNA (HBV-DNA). It is positive for hepatitis B core antibodies, but there are no detectable serum levels of the hepatitis B surface antigen (HBsAg). 1,2 This type of hepatitis is problematic for blood transfusion services because, although all donated blood and its components are screened for HBsAg, some cases of post-transfusion HBV infection have been reported. 3 One of the main causes of post-transfusion HBV infection is OBI, 4 which we have reported recently in blood donors from the Kerman 5 and Isfahan 6 provinces of Iran. The mechanisms responsible for the development of OBI are yet to be identified; however, some investigators have suggested genetic and immunological factors may play a significant role in the pathogenesis of this disease. 7,8 The prominent role of chemotactic cytokine (CC) motif receptor type 5 (CCR5), a receptor for the CC ligands (CCLs), CCL3, CCL4, and CCL5 (also known as regulated upon activation, normal T-cell expressed, and secreted [RANTES] protein), is its involvement in the immune response to viral infections such as human immunodeficiency virus (HIV), which has been reported elsewhere. 9,10 Moreover, subsequent studies have suggested an important modulatory role for CCR5 in recruiting leukocytes into inflammatory sites. 11 In addition, CCR5 has been noted to directly regulate T-cell function in autoimmune diseases, such as multiple sclerosis, 12 rheumatoid arthritis, 13 and diabetes. 14 In support of these findings, others have shown that although natural killer (NK) cells have CCL1 and CCL3 receptors (ie, CCR1 and CCR3), optimum NK activity is mediated by CCL5 binding to CCR5. 11 In addition, CCL5 can also bind to both the CCR1 and CCR3 receptors, further supporting the preeminent role of CCL5 in promoting NK cell activity. 11 The principal immune cells involved in immunity against HBV and other viruses are NK cells. 15 In concert with cytokines, such as interleukin-2 (IL-2) and interferon-gamma (IFN-γ) released by T-cells, CCL induces proliferation and activation of NK cells to form chemokine-activated NK (CHAK) cells that destroy viral infected cells (eg, hepatocytes). 16 Chemotactic cytokine receptor type 5, also known as "cluster of differentiation 195" (CD195), is a principal agent in the recruitment and migration of NK T-cells to inflammatory sites. 17 Due to the critical role of CCR5 in antiviral host defense, we investigated the quantitative expression of CCR5/CD195 by NK cells in Iranian patients with OBI.

Inflammation, Aug 24, 2012

Studies indicated that CC receptor 5 (CCR5), as a receptor for CC ligand 3, CCL4, and CCL5, plays... more Studies indicated that CC receptor 5 (CCR5), as a receptor for CC ligand 3, CCL4, and CCL5, plays important roles in the recruitment of T cytotoxic lymphocytes to the liver of chronic HBV (CHB)-infected patients. The main purpose of this study was to investigate the expression levels of CCR5 on the CD8(+) T lymphocytes of CHB patients. This clinical study was performed on 63 CHB patients and 96 healthy controls. Flow cytometric analysis was performed to examine the expression of CCR5 on CD8(+) T cells of CHB patients. Real-time PCR was also used for HBV-DNA quantification. The results of our study demonstrated that CCR5 expressing T cytotoxic cells were decreased significantly in CHB patients in comparison to healthy control. Based on our results, it can be concluded that the percent of CCR5(+)/CD8(+) T cells in Iranian CHB patients is significantly decreased, hence their migration to the infected liver, and HBV eradication from the hepatocytes is disrupted.

Hepatitis Monthly, Sep 30, 2011

Hepatitis B is one of the most frequent post-transfusion infections. Occult hepatitis B infection... more Hepatitis B is one of the most frequent post-transfusion infections. Occult hepatitis B infection (OBI) is a form of hepatitis B infection in which, despite the presence of HBV-DNA in the serum and hepatocytes of the carrier, HBsAg is absent. In addition to the risk of transmission through the transfusion of infected blood, reactivation of hepatitis B in OBI patients and recipients of their blood can lead to cirrhosis, hepatic cancer, and reactivation of viral replication in the carrier. Therefore, effective assays to assess and screen for OBI in blood donors are of paramount importance and require urgent attention. Recently, several investigations in various regions of Iran have reported OBI in blood donors. In response, there has been a drive to apply more specific, sensitive, and accurate methods for the detection of HBV, which should become an obligatory screening process for all blood transfusion services. In this review, we address the progression of occult hepatitis B and the common problems associated with occult hepatitis B worldwide. Finally, we reflect on the research and screening that is being performed in Iran to deal with this problem.

Inflammation, Sep 8, 2011

Occult hepatitis B infection (OBI) is characterized as a form of hepatitis in which detectable 7 ... more Occult hepatitis B infection (OBI) is characterized as a form of hepatitis in which detectable 7 amounts of HBV-DNA can be monitored in the peripheral blood of patients whereas the hepatitis B 8 surface antigen is undetectable. The main aim of this study was to investigate whether there is a relati-9 onship between OBI and single nucleotide polymorphisms in the −592 region of the IL-10 gene. In this 10 study, the polymorphism at position −592 of the IL-10 promoter of 57 OBI cases was compared and 11 correlated to that of 100 healthy controls by PCR-RFLP techniques. Our results showed that patient and 12 control groups had significant differences regarding genotypes and alleles of the −592 polymorphism in 13 the IL-10 gene. Based on our results, it can be concluded that the −592 polymorphism within the 14 promoter of the IL-10 gene is associated with OBI.

Inflammation, Aug 11, 2012

Immune responses are the main causes of immune system-related diseases such as hypersensitivities... more Immune responses are the main causes of immune system-related diseases such as hypersensitivities and autoimmunity. It has also been established that cytokines play key roles in the regulation of immune responses which have been shown to be important in the pathogenesis of the diseases. IL-10, the main anti-inflammatory cytokine, is produced by several immune cells such as T regulatory and Th2 lymphocytes, activated macrophages, B regulatory lymphocytes as well as other cell types. It plays a key role in the regulation of immune responses after microbe elimination (homeostasis) and against self-antigens to prevent hypersensitivity and autoimmune diseases, respectively. Studies showed that a single nucleotide polymorphism (SNP) at the -592 position of IL-10 is associated with its regulation of expression. This review addresses the recent information regarding the association of the polymorphism at position -592 of IL-10 with immune-related diseases including type 2 diabetes with and without nephropathy, multiple sclerosis, and asthma with an emphasize on Iranian patients.

Archives of Pathology & Laboratory Medicine, Nov 1, 2013

Context.-Toll-like receptors (TLRs) play crucial roles in immune responses, especially innate imm... more Context.-Toll-like receptors (TLRs) play crucial roles in immune responses, especially innate immunity, against viral infections. Toll-like receptor 9 recognizes intracellular viral double-strand DNA, which leads to the activation of nuclear factor B (NF-jB) through the myeloid differentiation primary response 88 (MYD88) pathway. Defects in the expression of TLR9 and its signaling molecules may cause attenuated immune responses against hepatitis B virus. Objective.-To determine expression levels of TLR9 messenger RNA along with MYD88, interleukin 1 receptor-associated kinase 1 (IRAK1), tumor necrosis factor receptor-associated factor 6 (TRAF6), and NF-jB in the peripheral blood mononuclear cells obtained from chronic hepatitis B virus (CHB)-infected patients. Design.-In this study, 60 CHB patients and 60 healthy controls were recruited and the expression of TLR9 and its downstream signaling molecules was examined by realtime polymerase chain reaction techniques using b-actin as a housekeeping gene. Results.-Our results showed that expression of TLR9, MYD88, IRAK1, TRAF6, and NF-jB in peripheral blood mononuclear cells of CHB patients was significantly decreased in comparison with healthy controls. Conclusions.-According to our results, it appears that CHB patients are unable to appropriately express genes in the TLR9 pathway, which may impede immune responses against hepatitis B virus infection. These results suggest a mechanism that may partially explain the fact that immune responses are disrupted in CHB patients.

Inflammation, Oct 4, 2011

Introduction: Several environmental and genetic factors are believed to influence the onset of di... more Introduction: Several environmental and genetic factors are believed to influence the onset of diabetes and its complications. It has also been established that cytokines play a key role in the pathogenesis of type 2 diabetes. Previous studies have revealed that polymorphism in the Stromal-Derived Factor 1α (SDF-1α) 3`A polymorphism r e g u l a t e s t h e expression of SDF-1α. This study was aimed to explore this polymorphism in parallel with SDF-1β serum level in type 2 diabetic patients. Material and methods: In this assessment peripheral blood samples were collected from 200 type 2 diabetic patients and 200 healthy controls. DNA was extracted and a PCR-RFLP screening was applied to examine the SDF-1β 3`A polymorphism. We also applied ELISA to measure serum levels of SDF-1α (CXCL12). Results: Our results showed that there were no significant correlations between SDF-1β 3′Α Polymorphism in type 2 diabetic patients when compared to controls. However, our results did show that the serum levels of SDF-1α (CXCL12) were significantly increased in the patients when compared to controls. Discussion: Based on the results of this study, we concluded that SDF-1β 3′Α polymorphism do no play a role in the pathogenesis of type 2 diabetes but that elevated serum levels of SDF-1α (CXCL12) may be important for the eiteology of type 2 diabetes but are unrelated to the SDF-1α 3′Α polymorphism.

Labmedicine, May 1, 2012

Background: This study aimed to investigate the serum levels of interleukin-12 (IL-12), interleuk... more Background: This study aimed to investigate the serum levels of interleukin-12 (IL-12), interleukin-10 (IL-10), and interleukin-6 (IL-6) in preterm neonates and their mothers and to compare them with those of full-term neonates and their mothers. Materials and Methods: One hundred cord blood specimens from full-term neonates and 60 from preterm neonates were collected. Likewise, 100 plasma samples from the mothers of the full-term neonates and 60 from the mothers of the preterm neonates were collected. Serum levels of IL-12, IL-10, and IL-6 were measured by enzyme-linked immunosorbent assay (ELISA). Results: Cord blood levels of IL-12 and serum levels of IL-6 were higher in preterm neonates and their mothers, respectively. Conclusion: Based on these findings, serum levels of IL-6 and IL-12 may be associated with preterm delivery. More studies must be completed to confirm the key role of these cytokines for the prognosis of preterm labor.

Clinical Laboratory, 2013

ABSTRACT Recent evidence has demonstrated that environment and genetic factors play pivotal roles... more ABSTRACT Recent evidence has demonstrated that environment and genetic factors play pivotal roles in diabetes and its related complications. The significant contributory role of cytokines in pathogenesis of type 2 diabetes is also well documented. This study was aimed to examine and compare both CXCL1 (GRO-alpha) and CXCL10 (IP-10) circulating levels in type 2 diabetic patients and healthy controls. Peripheral blood samples were collected from 100 type 2 diabetic patients and 150 healthy controls. Circulating CXCL1 and CXCL10 levels were measured by ELISA. Elevated serum levels of both CXCL1 and CXCL10 were found in type 2 diabetic patients in comparison to controls. Elevated levels of CXCL1 and CXCL10 could possibly be used as a marker of inflammation and angiogenesis/angiostasis in type 2 diabetes.

Saudi Journal of Gastroenterology, 2011

Journal of Gastroenterology and Hepatology, 2010

e224 14th International Congress on Infectious Diseases (ICID) Abstracts A*3303 and DRB1*1301 wer... more e224 14th International Congress on Infectious Diseases (ICID) Abstracts A*3303 and DRB1*1301 were the predominant subtypes of HLA-A*33 and DRB1*13 alleles in Iranian HBV infected patients.

Hepatitis Monthly, May 21, 2013

Pharmaceutical Sciences, Oct 29, 2014

Iranian Journal of Immunology, Jun 1, 2006

Background: It is now well established that several environmental stress factors cause activation... more Background: It is now well established that several environmental stress factors cause activation of p38 MAP kinase and JNK in various cell types to produce chemokines. Objective: To investigate the expression of CXC chemokines Gro/KC and SDF-1α in rat's H4 hepatoma cells in response to heat shock, hyperosmolarity and oxidative stress. Methods: Hepatoma cells were maintained in MEM medium. Cells were subjected to different stresses [(H 2 O 2 0.15% (w/v), manitol and NaCl (160 mM) and heat shock (42 °C for 20 minutes)]. Cells were harvested and RNA was extracted, purified and the CXC chemokine Gro/KC and SDF-1α expression was analysed by RT-PCR. cDNA was separated by gel electrophoresis on a 1% (w/v) agarose gel and visualized under a UV transilluminator. Results: There was detectable but low expression of both SDF-1α and Gro/KC in H4 hepatoma cells. Heat shock failed to induce expression of SDF-1α and Gro/KC in H4 hepatoma cells of rat. Hyperosmolarity also did not stimulate SDF-1α and Gro/KC expression. In this study we have also shown that oxidative stress did not induce expression of SDF-1α and Gro/KC. Overall, although detection is possible but regulatory responses were not observed in H4 hepatoma cells. Conclusion: Several known injurious conditions cause recruitment of macrophages, neutrophils and other immune cells to the liver. Immune cells are recruited to the hepatic vasculature following local liver injury and subsequent chemokine production. Our results demonstrated that failure to produce chemokines by hepatoma cells may be a way to escape from mechanism of immune surveillance.

Hepatitis Monthly, Nov 30, 2012

This article is research study on chronic HBV infected patients to evaluate TGF-β serum levels. T... more This article is research study on chronic HBV infected patients to evaluate TGF-β serum levels. This article can be useful for hepatologists, gastroentestinalists, Immunologists and virologists. Background: The transforming growth factor-β (TGF-β) is an important cytokine with anti-inflammatory properties. Objectives: The main purpose of this study was to compare the serum levels of TGF-β in a group of chronic HBV infected (CHB) patients as well as healthy individuals from SouthEast of Iran. Patients and Methods: Sixty patients with CHB as well as sixty healthy individuals were enrolled in the study. ELISA technique was applied to measure the serum levels of TGF-β in both groups. Results: Our results revealed that the serum levels of TGF-β were significantly increased in CHB patients in compare to healthy controls. Conclusions: According to this result, it may be concluded that high serum levels of TGF-β may be a mechanism by which immune response against HBV is suppressed.