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عضویت
فهرست مطالب نویسنده:

hamid asadzadeh-aghdaei

  • Mohammadhossein Ghorbani, Vahid Chaleshi, Nazanin Amiri, Maryam Nasserinejad, Shaghayegh Baradaran Ghavami, Shabnam Shahrokh, Massoud Vosough, Hamid Asadzadeh Aghdaei*, Mohammadreza Zali

    Inflammatory bowel disease comprising Crohn's disease and ulcerative colitis presents with periods of flares and remission. Many reports have identified different dysregulated miRNAs in patients with IBD. Finding new biomarkers in IBD patients can help to launch a novel non-invasive approach for diagnosis and prognosis for patients with UC and CD. This study aimed to evaluate the plasma expression pattern of the miRNAs panel in IBD patients compared to healthy individuals. 73 plasma samples were included; 58 patients with IBD (33 individuals in flare and 25 in remission phase) and 15 healthy controls were enrolled in the study. The miRNA expression was measured by qRT-PCR using miScript SYBR Green PCR Kit (QIAGEN). Our results showed the expression level of miR-16-5P was significantly increased in the active phase compared to the inactive phase (P=0.0138) and in CD patients compared to UC patients (P=0.0216). There was a significant difference in the expression of miR-29a in Crohn's patients compared to healthy subjects (P=0.04). Measuring the expression of mir-106a; a significant increase was observed compared to healthy individuals (P=0.03) and patients with CD (P=0.0143) in proportion of UC patients’ group. The miR-126 expression significantly increased in patients with active disease compared to patients in the inactive phase (P=0.0413) and healthy controls (P=0.0492). This study showed evidence for differential expression levels of plasma panel of miR-16, miR-29a, miR-106a, and miR-126 in IBD patients compare to healthy individuals. We illustrate that miRNAs in plasma correlate with disease activity and can be used as a practical and non-invasive biomarker for early diagnosis and monitoring of the treatment protocol.

    Keywords: Inflammatory Bowel Disease, Microrna 16, Microrna 106A, Microrna 29A, Microrna 126
  • Bahare Niknam, Arezou Azizsoltani †, Neda Heidari, Samaneh Tokhanbigli, Helia Alavifard, Mahsa Haji Valili, Davar Amani, Hamid Asadzadeh Aghdaei, Seyed Mahmoud Hashemi, Kaveh Baghaei *
    Background

    The isolation of Mesenchymal Stem Cells (MSCs) from various tissues is possible, with the umbilical cord emerging as a competitive alternative to bone marrow. In order to fulfill the demands of cell therapy, it is essential to generate stem cells on a clinical scale while minimizing time, cost, and contamination. Here is a simple and effective protocol for isolating MSC from Wharton's Jelly (WJ-MSC) using the explant method with various supplements.

    Methods

    Utilizing the explant method, small fragments of Wharton's jelly from the human umbilical cord were cultured in a flask. The multipotency of the isolated cells, were confirmed by their differentiation ability to osteocyte and adipocyte. Additionally, the immunophenotyping of WJ-MSCs showed positive expression of CD73, CD90, and CD105, while remaining negative for hematopoietic markers CD34 and CD45, meeting the criteria for WJ-MSC identification. Following that, to evaluate cells' proliferative capacity, various supplements, including basic Fibroblast Growth Factor (bFGF), Non- Essential amino acids (NEA), and L-Glutamine (L-Gln) were added to either alpha- Minimal Essential Medium (α-MEM) or Dulbecco's Modified Eagle's Medium-F12 (DMEM-F12), as the basic culture media.

    Results

    WJ-MSCs isolated by the explant method were removed from the tissue after seven days and transferred to the culture medium. These cells differentiated into adipocyte and osteocyte lineages, expressing CD73, CD90, and CD105 positively and CD34 and CD45 negatively. The results revealed that addition of bFGF to α-MEM or DMEMF12 media significantly increased the proliferation of MSCs when compared to the control group. However, there were no significant differences observed when NEA or LGln were added.

    Conclusion

    Although bFGF considerably enhances cell proliferation, our study demonstrates that MSCs can grow and expand when properly prepared Wharton's jelly tissues of the human umbilical cord.

    Keywords: Fibroblast growth factor 2, Mesenchymal stem cells, Umbilical cord
  • امیر صادقی، حمید اسد زاده عقدایی، حمید محقق شلمانی، علی قنبری مطلق، پردیس کتابی مقدم *
    Amir Sadeghi, Hamid Asadzadeh Aghdaei, Hamid Mohaghegh Shalmani, Ali Ghanbari Motlagh, Pardis Ketabi Moghadam*

    Colon cancer ranks third among the most common cancers. In Iran, this disease ranks fourth in men and second in women. The incidence and mortality caused by this cancer are different in different geographical areas. It is known to reduce the incidence of colon cancer by performing screening methods because most cases originate from polyps that can be seen and removed in colonoscopy before they become malignant. Also, screening methods are able to detect cancer in its early stages and reduce the death rate caused by this disease. However, the implementation of screening programs worldwide, including in Iran, has always faced problems such as the cost of diagnostic equipment, insurance coverage, health infrastructure, human resources, and, most importantly, acceptance by the people. Today, different methods are used for colon cancer screening in different countries, and the choice of these methods depends on several factors, including the prevalence and incidence of this disease, economic resources, and health infrastructure in each region. The purpose of this study was to investigate the common methods for colon cancer screening so that, according to the current situation and considering the screening facilities available in Iran, the best method can be suggested to cover more and more people who need screening.

    Keywords: Colorectal cancer screening, Colonoscopy, Occult blood test, High-risk polyp, Low-risk polyp
  • Mohsen Nemati Bajestan, Moein Piroozkhah, Vahid Chaleshi, Naser Ghiasi, Negar Jamshidi, Reza Mirfakhraie, Hedieh Balaii, Shabnam Shahrokh, Hamid Asadzadeh Aghdaei, Zahra Salehi, Ehsan Nazemalhosseini Mojarad

    Inflammatory bowel disease (IBD) manifests as chronic inflammation within the gastrointestinal tract. The study focuses on a long noncoding RNA (lncRNA) known as Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1). MALAT1's misregulation has been linked with various autoimmune diseases and regulates proinflammatory cytokines. The role of IL6 in immune-triggered conditions, including IBD, is another focal point. In this research, the expression of MALAT1 and IL6 in IBD patients was meticulously analyzed to uncover potential interactions. The study involved 33 IBD patients (13 with Crohn's disease and 20 with ulcerative colitis) and 20 healthy counterparts. Quantitative real-time polymerase chain reaction determined the MALAT1 and IL6 gene expression levels. The competitive endogenous RNA (ceRNA) regulatory network was constructed using several tools, including LncRRIsearch and Cytoscape. A deep dive into the Inflammatory Bowel Disease database was undertaken to understand IL6's role in IBD. Drugs potentially targeting these genes were also pinpointed using DGIdb. Results indicated a notable elevation in the expression levels of MALAT1 and IL6 in IBD patients versus healthy controls. MALAT1 and IL6 did not show a direct linear correlation, but IL6 could serve as MALAT1's target. Analyses unveiled interactions between MALAT1 and IL6, regulated by hsa-miR-202-3p, hsa-miR-1-3p, and has-miR-9-5p. IL6's pivotal role in IBD-associated inflammation, likely interacting with other cytokines, was accentuated. Moreover, potential drugs like CILOBRADINE for MALAT1 and SILTUXIMAB for IL6 were identified. This research underscored MALAT1 and IL6's potential value as targets in diagnosis and treatment for IBD patients.

    Keywords: Crohn disease, Gene regulatory networks, Inflammatory bowel diseases, Interleukin-6, MALAT1 long non-coding RNA, human, Ulcerative colitis
  • Amir Sadeghi, Hamid Asadzadeh Aghdaei, Pardis Ketabimoghadam*, Khaled Rahmani, Mohsen Rajabnia, Niloufar Salehi, Seyedayin Hosseini, Seyedeh Melika Fanaei
    Background

    ASGE predictive model for the detection of choledocholithiasis is a reasonable approach for the management of patients with cholelithiasis. Surgeons do not pursue cholecystectomy without evaluation of the biliary system when laboratory tests and diagnostic imaging evidence show biliary duct involvement. Literature revisions reveal that the prediction of choledocholithiasis based on ASGE criteria suffers from poor accuracy which results in unnecessary ERCPs. We decided to estimate the sensitivity and specificity of the ASGE predictive model for the detection of choledocholithiasis with the hope that early EUS would obviate the need for unnecessary ERCPs among highly probable patients for choledocholithiasis based on ASGE criteria.

    Methods

    This is a prospective intervention and control study on the accuracy of ASGE criteria for the prediction of choledocholithiasis. To evaluate the sensitivity and specificity of ASGE criteria, patients were followed in two groups of controls who were treated based on ASGE guidelines and cases who underwent primary EUS. The clinical relevance of the ASGE criteria was estimated by sensitivity and specificity using SPSS Statistics 28 software. Then, absolute risk reduction utilizing primary EUS was also calculated. 

    Results

    The sensitivity and specificity of the ASGE predictive guideline for choledocholithiasis were estimated to be 62.31% and 51.85%, respectively. Evaluation of the ASGE guideline also revealed that patients in the intermediate probability group who finally required ERCP based on EUS results (false-negatives) were estimated to be 49.1% and patients who were predicted to require ERCP but finally did not need ERCP (false positives) were estimated to be 37.68%. The comparison of the two groups revealed the need for ERCP in about 55.56% of the primary EUS group and 77.42% in the ASGE group. Utilization of primary EUS reduced the need for ERCP by an absolute risk reduction of 0.299. (Primary Endpoint)

    Conclusion

    ASGE guideline is associated with the overestimation of ERCP in cholelithiasis. The usage of primary EUS will reduce the need for ERCP.

    Keywords: Cholelithiasis, Choledocholithiasis, Cholangiopancreatography, Endoscopic Retrograde (ERCP), Endoscopic Ultrasound (EUS), Pancreatitis, Cholangitis
  • Behrang Sarshari, Raziyeh Zareh-Khoshchehreh, Mohsen Keshavarz, Seyed Ali Dehghan Manshadi, SeyedAhmad SeyedAlinaghi, Hamid Asadzadeh Aghdaei, Seyed Reza Mohebbi

    Acute pancreatitis, a potentially fatal disease, with symptoms including nausea and/or vomiting, indigestion, and abdominal pain, is known to range from a mild self-limiting state up to a more severe and lethal form. This review aims toprovide a clearer picture to improve understanding the role of viral agents in the development of acute pancreatitis.Common databases including PubMed, Google Scholar, and Scopus were used for the literature search. In this review search terms including virus, viral, infection, and specific descriptive terms for a virus were considered in different combinations. Various causative agents are recognized in the development of acute pancreatitis as one of the most frequent gastrointestinal diseases, such as gallstones, alcoholism, and hypertriglyceridemia. Microbial pathogens with about 10% of acute pancreatitis cases, mainly viruses, among other factors, are thought to play a role in this regard. Once the pancreatitis diagnosis has been made, depending on thecausative agent, the management approach and specific interventions affect the final outcome. Virus-induced acute pancreatitis in patients should be considered. Advanced diagnostic tests such as PCR, in situ hybridization, and biopsy can help for a betterunderstanding of the role of viruses in causing acute pancreatitis. Improvement in the tests will lead to timely diagnosis, treatment, and better management of pancreatitis.

    Keywords: Acute pancreatitis, Virus, Gastrointestinal, Abdominal pain
  • Binazir Khanabadi, Diba Najafgholizadeh Seyfi, Leili Rejali, Mohammad Yaghoob taleghani, Shabnam Shahrokh, Mehdi Tavallaei, Elahe Daskar Abkenar, Fatemeh Naderi Noukabadi, Hamid Asadzadeh Aghdaei, Ehsan Nazemalhosseini mojarad

    Based on the analysis of patients with Peutz-Jeghers syndrome (PJS), Serine threonine kinase11 (STK11)is known as a tumor suppressor gene, which is involved in cell polarization, regulation of apoptosis, and DNA damage response. In this case report study, weexamined STK11 gene sequencing in a 42-year-old woman with mucocuta neous pigmentation and positive family history. Endoscopy and colonoscopy showed >1000 polyps throughout the stomach/colon (PJ-type hamartomas). The larger polyp in the stomach was resected and the small bowel imaging detected multiple jejunum/ileum small polyps. The data released from the sequencing results revealed five alterations in exons 1 to 5. The major mutation in stop codon was reported as converted to the amino acid tryptophan (TRP) to tyrosine (TER). The TGG codon was converted to TAG by mutation. Finally, another novel mutation in STK11 stop codon as a ‘de novo’ variant was seen. It is predicted that stop codon mutations make the affected person susceptible to developing colorectal cancer.

    Keywords: Peutz-Jeghers syndrome (PJS), STK11gene, Novel mutation, Sequencing, Genetic analysis
  • Zeinab Ghazvinian, Shahrokh Abdolahi, Mohammad Ahmadvand, Amir Hossein Emami, Samad Muhammadnejad, Hamid Asadzadeh Aghdaei, Jafar Ai, Mohammad Reza Zali, Iman Seyhoun, Javad Verdi, Kaveh Baghaei *
    Introduction

    Gastric cancer is one of the most commonly known malignancies and is the fifth cancer-related death globally. Whereas natural killer (NK) cells play a critical role in tumor elimination; therefore, adoptive NK cell therapy has become a promising approach in cancer cytotherapy. Hence, this study investigated the chemoimmune cell therapy in MKN-45 derived xenograft gastric cancer model.

    Methods

    Three groups of animals have received the following treatments separately: activated NK cells, capecitabine, the combination of capecitabine and activated NK cells, and one was considered as the control group. Morphometric properties of tumor samples were evaluated at the end of the study. NK cells infiltration was evaluated by immunohistochemistry (IHC) of hCD56. Mitotic count and treatment response was assessed by hematoxylin and eosin (H&E) staining. The proliferation ratio to apoptosis was determined by IHC assessment of Ki67 and caspase 3.

    Results

    The results indicated that the NK cell therapy could effectively decrease the mitotic count in pathology assessment, but the tumor was not completely eradicated. In combination with metronomic chemotherapy (MC) of capecitabine, NK cell therapy demonstrated a significant difference in tumor morphometric properties compared to the control group. The proliferation ratio to apoptosis was also in line with pathology data.

    Conclusion

    Although NK cell therapy could effectively decrease the mitotic count in vivo, the obtained findings indicated lesser potency than MC despite ex vivo activation. In order to enhance NK cell therapy effectiveness, suppressive features of the tumor microenvironment and inhibitory immune checkpoints blockade should be considered.

    Keywords: Gastric cancer, Capecitabine, Adoptive NK cell therapy, Chemo-immune cell therapy, Metronomic chemotherapy
  • Samaneh Tokhanbigli, Helia Alavifard, Hamid Asadzadeh Aghdaei, Mohammad Reza Zali, Kaveh Baghaei*
    Introduction

    The maturation faith of dendritic cells is restrained by the inflammatory environment and cytokines, such as interleukin-6 and its downstream component. Therefore, introducing the suitable antigen to dendritic cells is crucial. However, reducing the severity of the suppressive tumor microenvironment is indispensable. The present study examined the combination therapy of lymphocyte antigen 6 family member E (LY6E) pulsed mature dendritic cells (LPMDCs) and pioglitazone against colorectal cancer (CRC) to elevate the effectiveness of cancer treatment through probable role of pioglitazone on inhibiting IL-6/STAT3 pathway.

    Methods

    Dendritic cells were generated from murine bone marrow and were pulsed with lymphocyte antigen 6 family member E peptide to assess antigen-specific T-cell proliferation and cytotoxicity assay with Annexin/PI. The effect of pioglitazone on interleukin (IL)-6/STAT3 was evaluated in vitro by real-time polymerase chain reaction (PCR). Afterward, the CRC model was established by subcutaneous injection of CT26, mouse colon carcinoma cell line, in female mice. After treatment, tumor, spleen, and lymph nodes samples were removed for histopathological, ELISA, and real-time PCR analysis.

    Results

    In vitro results revealed the potential of lysate-pulsed dendritic cells in the proliferation of double-positive CD3-8 splenocytes and inducing immunogenic cell death responses, whereas pioglitazone declined the expression of IL-6/STAT3 in colorectal cell lines. In animal models, the recipient of LPMDCs combined with pioglitazone demonstrated high tumor-infiltrating lymphocytes. Elevating the IL-12 and interferon-gamma (IFN-γ) levels and prolonged survival in lysate-pulsed dendritic cell and combination groups were observed.

    Conclusion

    Pioglitazone could efficiently ameliorate the immunosuppressive feature of the tumor microenvironment, mainly through IL-6. Accordingly, applying this drug combined with LPMDCs provoked substantial CD8 positive responses in tumor-challenged animal models.

    Keywords: Tumor-associated antigen, Dendritic cells, Thiazolidinediones, Colorectal cancer, Lymphocyte antigen 6 familymember E, Pioglitazone
  • Kaveh Naseri, Saeede Saadati, Fereshteh Pashayee-Khamene, Azita Hekmatdoost, Hamid Asadzadeh-Aghdaei, Seyyed Reza Sobhani, MohammadAmin Shahrbaf, Komeil Esmaeilinejad, Fatemeh Hosseini-Oskuiee, Amir Sadeghi*, Shima Hadavi, Mohammad Nazari

    Dietary intake is one of the modifiable risk factors for biliary stones. In recent studies, plant protein intake is associated with a lower risk of biliary stones in comparison to animal protein intake; however, the results are contradictory. The current study aims to compare the effect of animal protein and plant protein on the formation of biliary stone in one of the gastroenterology and liver disease centers in Iran.

    Methods

    110 participants who had a history of biliary stone and 230 controls who were normal in terms of biliary diseases and referred to the medical center from November 2017 to October 2018 enrolled in this study. Food frequency questionnaire (FFQ) was used for the nutritional assessment; moreover, demographic and anthropometric data, habitual history and comorbidities were collected. Statistical analysis was conducted by SPSS software.

    Results

    Plant protein consumption was significantly lower (P=0.03) and animal protein intake was significantly higher (P=0.02) among men in case compared to controls. Furthermore, the relationship between biliary stone disease and animal protein intake was significant in crude model for men (OR: 1.03, 95% CI=1.01-1.05). In addition, the risk of biliary stone was significantly lower in patients with higher consumption of plant protein (for women: OR: 0.94, 95% CI=0.89-0.99, for both sexes: OR: 0.96, 95%CI=0.93-0.99).

    Conclusion

    The present study suggested that consumption of animal protein sources increased the risk of biliary stone, and intake of plant protein sources decreased the risk of biliary stone

    Keywords: Biliary stone, Plant protein, Animal protein
  • Hamid Asadzadeh-Aghdaei, Leili Rejali, Mahyar Nourian, Vahid Chaleshi, Naghmeh Zamani, Shaghayegh Baradaran-Ghavami, Mohsen Nemati, Shabnam Shahrokh, Mohsen Norouzinia, Massoud Vosough, Ehsan Nazemalhosseini-Mojarad, Mohammadreza Zali
    Background

    Ulcerative colitis (UC) and Crohn’s disease (CD) are two major types of inflammatory bowel diseases (IBDs). Toll‑like receptors (TLRs) are expressed in the innate immune system compartments, in charge of identifying a wide range of microorganisms. The aim of the present study was to evaluate the expression of TLR‑2, ‑7, and ‑8 in peripheral blood mononuclear cells (PBMC) of UC patients as a novel non‑invasive primary inflammation sensor for monitoring the clinical course of UC candidates.

    Materials and Methods

    In this cross‑sectional study, total RNA was extracted from the PBMC of 42 UC patients along with 20 healthy donors. The mRNA levels of TLR‑2, ‑7, and ‑8 were assessed using the quantitative real‑time polymerase chain (qRT‑PCR) reaction.

    Results

    The present research study demonstrated no significant changes in TLR‑2 mRNA expression in UC patients in comparison with the control group (P = 0.1264), whereas significant elevation (P = 0.0008) was distinguished in the TLR‑7 expression of UC participants specifically during the remission course compared with healthy donors and flareup patients (P = 0.0004 and P = 0.0063, respectively). The last selected TLR, TLR‑8 was not shown remarkable changes either between UC patients and the control group or between clinical courses of the disease.

    Conclusion

    Here, among three nominated TLRs for predicting UC patients, TLR‑7 was potentially selected according to the significant difference in mRNA expression in flareup UC patients and control donors. TLR‑7 could be used as a novel non‑invasive biomarker for monitoring UC patients in the active course of the disease.

    Keywords: Biomarkers, colitis, inflammatory bowel disease, remission, toll‑like receptor 7
  • Hamid Asadzadeh Aghdaei, Amir Sadeghi, Gholamreza Nouri, Naghmeh Salarieh, Pardis Ketabi Moghadam

    Esophageal-pleural (E-P) fistula is introduced to be an uncommon clinical finding maybe due to non-specific clinical pointers and vague radiologic clues. In this regard, the main drivers are esophageal traumatization, endoscopic dilation, irradiation and corrosive agent ingestion as well as major underlying esophageal diseases like carcinomas and tuberculosis. The presented case is a 51-year-old man with medical record of recurrent pneumonias resulted in right lobectomy who admitted to the medical institution with a significant empyema leading to chest tube insertion. It should be noted that the presence of food particles in the chest bottle in addition to the history of previous surgery raised suspicion of a post-surgical E-P fistula formation. Attempts were made to find fistula tract and insert an esophageal stent bypassing the fistula opening. However, investigations argued against E-P fistula as an ensuing event after surgery and arose the question that whether E-P fistula would be the cause or effect of pneumonia in the presented case?

    Keywords: Recurrent pneumonia, EsophaGeal-pleural fistula, Esophageal foreign body
  • Fedra Mokhtari, Hami Kaboosi, Seyed Reza Mohebbi, Hamid Asadzadeh Aghdaei, MohammadReza Zali
    Aim

    Development of an amplification method for further investigation of HBV S gene variation patterns.

    Background

    Pre-S/S variants in patients with chronic HBV infection may contribute to the progression of liver damage and Hepatocellular carcinoma (HCC).

    Methods

    This study wasperformed on ten patients with chronic HBV infection. Viral DNA was extracted from patient's plasma, primer design was performed, and a semi-nested PCR method was set up to amplify the pre-S/S region of HBV genome. Subsequently, sequencing was performed to analyze the variants of this region.

    Results

    In the current study, the semi-nested PCR method was successfully set up, and types of variation in the studied samples were investigated.

    Conclusion

    Pre-S/S variants should be routinely determined in HBV carriers to help identify individuals who may be at a high risk of less favorable liver disease progression. This study showed that the technique could accurately amplify the pre-S/S region, and the product can be successfully used for variation detection bydirect sequencing.

    Keywords: Hepatitis B virus, PreS, S variations, Semi nested PCR
  • فدرا مختاری، حامی کابوسی، سید رضا محبی*، حمید اسدزاده عقدائی، محمدرضا زالی
    زمینه و اهداف

      میکروRNA های در گردش، این پتانسیل را دارند که به عنوان نشانگرهای زیستی تشخیصی در پیشگیری و پیشرفت بیماری ها از جمله بیماری های کبدی مورد استفاده قرار گیرند. بنابراین، در این مطالعه، تغییرات سطح بیان microRNA-222 (miR-222) در بیماران مبتلا به هپاتیت ب مزمن به عنوان یک نشانگر زیستی بالقوه تشخیصی مورد ارزیابی قرار گرفت.

    مواد و روش کار

      بیان miR-222 در 86 نمونه پلاسما شامل 43 بیمار مبتلا به هپاتیت مزمن ب و 43 فرد سالم به عنوان گروه کنترل بررسی گردید. فرآیند استخراج RNA و سنتز cDNA انجام و سپس بیان این miRNA با استفاده از تکنیک qRT-PCR و روش delta-delta Ct اندازه گیری شد. نتایج توسط آزمون Mann-Whitney U-test Spearman برای نشان دادن همبستگی بین miR-222 و پارامترهای بالینی مورد تجزیه و تحلیل قرار گرفت.

    یافته ها

      با وجود اینکه در سطح بیان  miR-222بین گروه بیمار و کنترل تفاوت مشاهده گردید (تغییر برابری miRNA-222= 1/384)، اما این تفاوت از نظر آماری معنی دار نبود (p value=0/269).

    نتیجه گیری:  

    مطالعه حاضر نشان داد که علیرغم تغییرات در سطح بیان miR-222 در گروه بیماران مبتلا به هپاتیت مزمن B نسبت به گروه سالم، برای تعیین نقش این microRNA به عنوان یک بایومارکر غیر تهاجمی تشخیصی در بیماران مبتلا به هپاتیت مزمن ب به مطالعات بیشتر و در مقیاس وسیع تر نیاز است.

    کلید واژگان: میکرو آر ان ای, ویروس هپاتیت ب, بایومارکر غیرتهاجمی, عفونت مزمن
    Fedra Mokhtari, Hami Kaboosi, Seyed Reza Mohebbi*, Hamid Asadzadeh Aghdaei, MohammadReza Zali Zali
    Background and Aim

     Circulating microRNAs have the potential to serve as biomarkers in diagnostics and monitoring of disease progression, including liver diseases. Therefore, this study investigated the alteration in the expression levels of microRNA-222 (miR-222) in patients with chronic hepatitis B (CHB) as a potential diagnostic biomarker.

    Materials and Methods

     MiR-222 expression was analyzed in the 86 plasma samples, including 43 patients with CHB and 43 healthy individuals as a control group. RNA extraction and cDNA synthesis processes were done, and then the expression of the miR-222 was measured by qRT-PCR. The Mann-Whitney U-test Spearman analyzed the results to show the correlation between miR-222 and clinical parameters.

    Results

    MiR-222 had a difference in expression levels between the patient and control groups (miRNA-222 Fold change= 1.384). Nevertheless, a statically significant difference was not observed (p value=0.269).

    Conclusion

     Our study showed that even though changes in miR-222 expression levels in the group of patients with chronic hepatitis B compared to the healthy group, it could not be utilized as a precise diagnostic biomarker, and more studies, on a broader scale, are needed to determine the role of this microRNA in patients with CHB.

    Keywords: Hepatitis B virus, chronic Infection, liver diseases, MicroRNAs
  • Azadeh Rezaie, Meysam Nasiri *, Behzad Hatami, Kaveh Baghaie, Hamid Asadzadeh-Aghdaei, MohammadReza Zali

    Recent studies have shown that the level of hepatocyte-derived mitochondrial DNA is elevated in plasma samples obtained from mice and NASH patients, and it has the ability to toll-like receptor 9 (TLR9) activation resulting in steatosis, hepatocyte injury, and fibrosis. In this study, we explored the association between TLR9 rs5743836, rs352140, and rs187084 polymorphism and its plasma mRNA level in non-alcoholic fatty liver (NAFL) patients with different liver fibrosis scores compared to healthy controls. Seventy Iranian patients diagnosed with NAFL, based on fibroscan testing results, were divided into F0-F1 (N=33), F2-F3 (N=19), and F4 (N=18) hepatic fibrosis groups and compared to 22 healthy controls. Genotyping was done using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and the mRNA expression level of TLR9 was determined using Real-Time PCR analysis. Results showed no significant association between allelic and genotypic distribution frequency of TLR9 rs5743836, rs352140, and rs187084 polymorphisms in NAFL patients with hepatic fibrosis compared to healthy controls (P>0.05). However, the mRNA level of TLR9 was significantly elevated in correlation with hepatic fibrosis progression in NAFL patients compared to healthy controls (P<0.05). As a preliminary study, our data showed a correlative overexpression of TLR9 mRNA with hepatic fibrosis progression in NAFL patients without the effectiveness of TLR9 gene polymorphisms.

    Keywords: Hepatic fibrosis, Non-alcoholic fatty liver, Polymorphism, Toll-like receptor
  • Nastaran Asri, Nazanin Taraghikhah, Reyhaneh Baniasadi, Sauid Ishaq, Mostafa Rezaei-Tavirani, Amir Sadeghi, Mohammad-Javad Ehsani-Ardakani, Somayeh Jahani-Sherafat, Hamid Asadzadeh Aghdaei, Mohammad Rostami-Nejad*
    Background

    A gluten-free diet (GFD) is the only effective treatment of celiac disease (CD) that is associated with body mass index (BMI) changes. This study aimed to determine how GFD duration affects the BMI of Iranian patients with CD.

    Methods

    In this prospective study, 215 patients with CD, who were on a GFD, were categorized into three groups according to the duration of compliance to GFD: 1. patients with less than 6 months of diet, 2. Patients who had a diet for 6 months to 2 years, and 3. patients with more than 2 years of diet. The BMI changes were assessed before and after adherence to the GFD.

    Results

    Most patients’ weight remains in the same BMI category during different courses of GFD adherence. Patients who were underweight showed significant changes in their BMI following the diet in less than 6 months (P=0.033) and more than 2 years (P<0.001), and the number of weight gain cases increased over time.

    Conclusion

    There is a need for careful, updated, and personalized nutrition management of patients with CD in different periods of the diet. Conducting similar studies with larger sample sizes in different regions can lead to providing expert dietary counseling for patients with CD.

    Keywords: Celiac disease, Gluten, Gluten-free diet, Body mass index
  • Marzieh Mobaraki, Seyed Abdolhamid Angaji, Ehsan Nazemalhosseini-Mojarad *, Sedigheh Arbabian, Hamid Asadzadeh Aghdaei
    Background

    Recently, it has been shown that, piRNAs as a new class of non-coding RNAs (ncRNAs), play crucial roles in germline development and carcinogenesis. Despite this, the study on the effects of piRNAs polymorphism (piR-SNP) on colorectal cancer (CRC) risk is scarce. We evaluate the impact of rs11776042 in piRNA 015551 on CRC initiation and development in the Iranian population.

    Matherials & METHODS

    The association of novel polymorphisms rs11776042 in piRNA 015551 gene with CRC risk using a case-control study on the Iranian population was estimated. All subjects were evaluated by TETRA primer-Amplification refractory mutation system polymerase chain reaction (TP-ARMS- PCR assay)

    Results

    The genotypes frequency was 27%, 68% and 0.05% for C/C, C/T and T/T in controls and 31%, 65% and 0.04% in CRC patients respectively. The frequency of the C allele was 63% in patients versus 61% in controls and, T allele frequency was 37% in patients versus 39% in controls.

    Conclusion

    No significant difference was found in genotype and allele frequencies between the cases and controls for rs11776042 polymorphism in piRNA 015551 in our population.

    Keywords: Colorectal Neoplasm (Colorectal Cancer), piR-SNPs, rs 11776042, piR, 015551
  • Hamid Asadzadeh Aghdaei, Sama Rezasoltani *, Meisam Olfatifar, Ehsan Nazemalhosseini Mojarad, Ghazal Sherkat, Abbas Yadegar, Mohammad Mehdi Feizabadi, Mohammad Reza Zali
    Background

    Toll-Like Receptors (TLRs) are the critical mediators of inflammatory routs in the gut, which play an essential role in regulating the immune responses towards various ligands derived from pathogenic bacteria. Also, TLR signaling has been implicated in the development of Inflammatory Bowel Disease (IBD), Adenomatous Polyp (AP), and Colorectal Cancer (CRC). Here, we aimed to examine the expression of some TLRs concerning certain fecal bacteria in AP and CRC patients with and without IBD.

    Methods

    This case-control study collected fecal and colonic tissue samples from 93 patients versus Normal Controls (NC) via colonoscopy. Fecal samples were used for DNA extraction, and the abundance of selected fecal bacteria was determined by absolute real-time PCR. Also, the gene expression of TLR2, 4, and 5 was analyzed using RT-PCR on the colonic tissues of participants.

    Results

    Compared to NC individuals, in AP and CRC patients, the mRNA expressions of TLR4 and TLR2 were significantly increased while TLR5 was decreased. A meaningful association between TLRs mRNA expression levels and the abundance of some selected fecal bacteria was detected. Also, there was a significant relationship between participant’s food regimes, smoking habit and intestinal TLRs expression.

    Conclusion

    Our study proposed the important role of TLRs during adenomatous and CRC formation. Alterations in TLRs expression associated with certain gut bacteria may contribute to disease development.

    Keywords: Adenomatous polyp, Colorectal cancer, Fecal bacteria, Inflammatory boweldisease, Toll-like receptor
  • Amir Sadeghi, Hamid Asadzadeh Aghdaei, Pardis Ketabi Moghadam, Forough Mangeli, Niloufar Salehi, Mohsen Rajabnia

    Simultaneous occurrence of immune-based gastrointestinal diseases and autoimmune hepatitis although is not common but is of clinical importance. Some clinical and laboratory findings such as severe pruritus and an elevation in alkaline phosphatase raise suspicion of a biliary disease which overlaps autoimmune hepatitis. A strong clinical suspicion of overlap syndrome in a patient with autoimmune hepatitis prompts more diagnostic evaluations like MRCP, liver biopsy and secondary laboratory tests. Patients who fall into the category of overlap syndrome would be proceeded with timely monitoring of known complications including colorectal carcinomas, cholangiocarcinomas and gallbladder cancers. So, it is highly recommended to search for all simultaneous immune-based involvements prior to labelling a patient as having pure autoimmune hepatitis. In this study, attempts have been made to express all challenges about a case with overlap syndrome referred to gastroenterology ward of Taleghani hospital and review the latest articles and related guidelines about the diagnosis, treatment, complications, and surveillance of the mentioned patient with autoimmune hepatitis (AIH), primary sclerosing cholangitis (PSC), and inflammatory bowel disease (IBD).

    Keywords: Autoimmune Hepatitis, Primary Sclerosing Cholangitis, Inflammatory Bowel Disease, Ulcerative Colitis, overlap syndrome
  • Sama Rezasoltani, Niloufar Amir Ebrahimi, Reza Khadivi Boroujeni, Hamid Asadzadeh Aghdaei, Mohsen Norouzinia

    Aflatoxins are poisonous substances produced by certain kinds of fungi that are found naturally all over the world. They can contaminate food crops and pose a serious health threat to humans and livestock. The current study aimed at removing aflatoxin from the reconstituted milk by adding three probiotics Saccharomyces boulardii, Lactobacillus casei and Lactobacillus acidophilus.

    Materials and Methods

     The probiotics of S. boulardii , L.casei and L. acidophilus with 109 and 107 CFU concentration were exposed to aflatoxin M1 (0.5 and 0.75 ng/ml). The ELISA test was performed using 144 falcon tubes containing AFM1. Sterile water was added to each probiotic pellet and finally added to pre-prepare contaminated milk. After the specified times, the milk layer was analyzed to measure AFM1 levels. Each sample was analyzed using HPLC system. Subsequently, the percentage of AFM1, which was bound to the bacterial suspension, was calculated.

    Results

    boulardii had the greatest ability in AFM1 removal from milk medium (96.88 ± 3.79) over time in the early hours with increasing concentration of AFM1 (0.75 ng/ml) and a concentration of 109 CFU/ml at 37 °C. The highest activity of L.casei in the removal of AFM1 toxin was observed at a concentration of 107 CFU/ml in 0.75 ng/ml AFM1 level and 37 °C. And the highest marginal estimation percentage of AFM1 removal from the milk medium at 4 °C in initial minutes belonged to L. acidophilus.

    Conclusion

    The results revealed the possibility of using S. boulardii in combination with selected strains of LAB (L.casei, L. acidophilus) in detoxification of AFM1-contaminated milk.

    Keywords: Aflatoxin M1, detoxification, S. boulardii, L. casei, L. acidophilus
  • Vahid Chaleshi, Saeideh Oloumi Kalantar, Iman Salahshourifar, Shabnam Shahrokh, Hamid Asadzadeh Aghdaei*, Mohammad Reza Zali
    Background & Objective

    Inflammatory bowel disease (IBD) is characterized by the chronic gastrointestinal inflammation. The two common forms of IBD are ulcerative colitis (UC) and Crohn’s disease (CD) that are distinguished by their location and depth of involvement in the diffuse inflammation of the colonic mucosa and affects the rectum (proctitis). A novel class of LncRNAs transcribed from ultra-conserved regions (UCRs) is a recently identified ultra-conserved region (T-UCR) transcript that is involved in the cellular function in a variety of pathways. However, the regulation of LncRNA uc.173 in IBD remains to be fully elucidated. In this study, we aimed to examine the expression of LncRNA uc.173 and Occludin genes in an Iranian population with inflammatory bowel disease.

    Materials & Methods

    This case-control study was performed on 33 inflammatory bowel disease patients including 13 Crohn's disease, 20 ulcerative colitis and 20 healthy controls. The mRNA levels of LncRNA uc.173 and Occludin genes were assessed using the quantitative Real-time polymerase chain reaction. The B2M was used as an internal control. The 2 -ΔΔCq method was used to determine the expression fold changes.

    Results

    Statistically, the level of the LncRNA uc.173 gene expression between the UC and normal tissues increased significantly(P=0.0024). Also, the expression analysis revealed no significant difference between the samples of CD patients compared to the controls (P>0.05). In order to further evaluate the role of LncRNA uc.173 in IBD, the associations between the transcript levels of the LncRNA uc.173 and Occludin mRNA demonstrated significant difference in the CD tissue (R=0.59; P=0.002). In our study, the mRNA expression of Occludin gene did not show any changes in the IBD patients compared to the healthy controls.

    Conclusion

    The increased expression of LncRNA uc.173 in the tissues of UC patients may be considered as a diagnostic or prognostic biomarker. Also, there was no correlation found between Occludin and LncRNA uc.173 expressions in the IBD patients' tissues.

    Keywords: Inflammatory bowel disease, Ulcerative colitis, Crohn's disease, LncRNA uc.173, Occludin
  • Kaveh Naseri, Saeede Saadati, Hamid Asadzadeh-Aghdaei, Azita Hekmatdoost, Amir Sadeghi, Seyyed Reza Sobhani, Khadijeh Abhari, Alireza Bahrami, Fatemeh Rahimi, Sakak, Negin Jamshidfar, Mohammadreza Zali
    Background

    Nutrition‑related factors have been of great interest as one of risk factors of biliary stones. This study evaluated the association of dietary patterns with biliary stone among Iranians.

    Methods

    This is a hospital‑based case‑control study, which was conducted in a general hospital in Tehran, Iran. A total of 110 patients with gallstone or common bile duct (CBD) stone confirmed by Ultrasonography within the last 6 months before collecting data were recruited. Controls were age‑matched patients admitted to the other wards of the same hospital for a broad spectrum of disorders including traumas and orthopedic conditions, or elective surgeries, or throat/ear/nose disease and had no gallbladder disorders, participated in this study. We used a valid and reliable food frequency questionnaire to assess dietary intakes of participants. Dietary patterns were determined by factor analysis.

    Results

    By design, age was similar in both groups (57.66 ± 16.39 years vs . 56.00 ± 10.64 years in cases and controls, respectively). Two dietary patterns were extracted; “Unhealthy” (high consumption of artificial juice, processed meats, refined grains, sweets and desserts, pickles, snacks, and red meats), and “Healthy” (high consumption of vegetable oils, vegetables, fruits, fish, legumes, and nuts, as well as low consumption of hydrogenated fats and salt). Participants in the highest tertile of “Healthy” dietary pattern were significantly less likely to have the gallstones disease (OR: 0.33, 95% CI = 0.120.89) compared to the reference group (low tertile of “Healthy” dietary pattern) (P = 0.02).

    Conclusions

    High consumption of vegetable oils, vegetables, fruits, fish, legumes, and nuts, as well as low consumption of hydrogenated fats and salt in context of healthy dietary pattern are inversely associated with risk of gallstones.

    Keywords: Cholecystectomy, dietary, gallbladder diseases, gallstones, Iran, patterns
  • Amir Sadeghi, Mohsen Rajabnia, Mohammad Bagheri, Shaghayegh Jamshidizadeh, Samane Saberi, PariaShahnazi, Leila Pasharavesh, Mohamad Amin Pourhoseingholi, Mona Mirzaei, Hamid Asadzadeh Aghdaei, Mohammad Reza Zali
    Aim

    This study aimed to evaluate the effects of factors like demographic items, comorbidities, and drug history on the inadequacy of colonic preparation before colonoscopy.

    Background

    Inadequate bowel preparation can lead to lower polyp detection rates, longer procedure times, and lower cecal intubation rates.

    Methods

    This population-based study was conducted on 2476 Iranian adults who were referred to two tertiary centers for elective colonoscopy between 2017 and 2018. Bowel preparation quality was scored by the Boston bowel preparation scale (BBPS). Univariate and multivariate logistic regressions were used to find the independent predictors of bowel preparation inadequacy.

    Results:

    The results showed that 31.8% of patients had inadequate bowel preparation before their colonoscopy. Higher age, BMI>25, abdominal circumference>95 cm, low fruit consumption, and history of smoking were independently correlated with bowel preparation inadequacy. Additionally, using NSAIDs and SSRIs were correlated with bowel preparation adequacy in multivariate regression analysis. Finally, age, gender, ethnicity, BMI, abdominal circumference, fruit consumption, smoking, NSAIDs, SSRIs, education, constipation, physical activity, and diabetes entered the predictive model of this study. The area under the curve (AUC) reached 0.70 in the final step.

    Conclusion

    The independent risk factors associated with colonic preparation inadequacy were identified, and herein, a predictive model is suggested for identifying patients with a high risk of bowel preparation inadequacy before a colonoscopy so that alternative preparation techniques can be employed among high-risk groups to yield optimal preparation quality.

    Keywords: Colonoscopy, Colon cleaning, Bowel preparation, Risk factors of bowel cleansing, Quality of colonoscopy
  • مریم خداپناه، محمد رستمی نژاد*، مهرداد هاشمی، حمید اسدزاده عقدائی

    گیرنده های سایتوتوکسیک طبیعی از جمله NKP46 می توانند در تقویت و تداوم پاسخ های ایمنی علیه عفونت ویروسی، که از جمله عوامل موثر بر پیشرفت التهاب در بیماری سلیاک است، نقش مهمی داشته باشند. از طرفی اینترلوکین 15، که از جمله سایتوکاین های التهابی مهم در بیماری زایی سلیاک است، نیز میتواند با تاثیر بر تغییر بیان این نوع از گیرنده ها سبب آتروفی پرزهای روده ای گردد. هدف از انجام این مطالعه بررسی بیان ژن NKP46 در بیماران مبتلا به بیماری سلیاک تحت رژیم غذایی بدون گلوتن د ر مقایسه با افراد سالم بود. ابتدا تعداد 20 نمونه بیوپسی روده باریک از بیماران مبتلا به سلیاک و 20 نمونه از افراد سالم جمع آوری شد. پس از استخراج RNA و سنتز cDNA ، جفت پرایمر اختصاصی ژن طراحی و PCR انجام گردید و سپس بررسی بیان ژنNKP46 با روش Real-time PCR صورت گرفت .8 نفر زن (40%) و 12 نفر مرد (60%) در گروه بیمار و تعداد 7 نفر زن (35%) و 13 نفر مرد (65%) در گروه کنترل بررسی شدند. بیان ژن NKP46 در بیماران سلیاکی تحت رژیم فاقد گلوتن در مقایسه با افراد سالم اختلاف معناداری نشان نداد. عدم مشاهده اختلاف معنادار بین گروه بیمار و کنترل میتواند ناشی از تاثیرات رعایت رژیم غذایی توسط این بیماران باشد. انجام مطالعات تکمیلی جهت دستیابی به پروفایل بیان کامل تری از این گیرنده ها و همچنین ارزیابی جهش های موثربر بیان آنها در بیماران مبتلا به بیماری سلیاک درمان شده و درمان نشده در مطالعات بعدی توصیه میگردد.

    کلید واژگان: بیماری سلیاک, NKP46, رژیم فاقد گلوتن, پرایمر, PCR
    Maryam Khodapanah, Mohammad Rostami Nejad *, Mehrdad Hashemi, Hamid Asadzadeh Aghdaei

    According to the previous studies, natural cytotoxicity receptors including NKP46 can play an important role in strengthening and sustaining immune responses against viral infection, which may have a role in the progression of inflammation in celiac disease. Moreover, Interleukin-15, which is one of the most important inflammatory cytokines in celiac disease pathogenesis, can also change the expression of this type of receptors that leads to atrophy of intestinal villi. The aim of this study was to evaluate the intestinal expression of NKP46 gene in patients with celiac disease on a gluten-free diet in comparison with healthy individuals. In this study, 20 small intestinal biopsy samples were collected from patients with celiac disease and 20 samples from healthy subjects. After RNA extraction and cDNA synthesis, gene-specific primer pairs were designed, PCR conducted and NKP46 gene expression was evaluated by real-time PCR method. 8 females (40%) and 12 males (60%) in the patient group and 7 females (35%) and 13 males (65%) in the control group were studied. NKP46 gene expression was not significantly different between celiac patients who were on a gluten-free diet and healthy individuals (Pvalue: 0.4). The lack of significant difference in the expression of this receptor between the patient and control groups can be due to the effects of gluten-free diet adherence. Additional studies are recommended to achieve a more complete expression profile of these receptors and possible mutations affecting their expression in treated and untreated celiac disease patients.

    Keywords: Celiac disease, NKP46, Gluten-free diet, primer, PCR
  • Meysam Olfatifar, Hamid Asadzadeh Aghdaei, Mohamad Amin Pourhoseingholi, Hedieh Balaii, SaeedHashemi Nazari, Shabnam Shahrokh, Siamak Sabour, _ Maria Ivanchuk, Pavlo Ivanchuk, SoheilaKhodakarim, Mohammad Reza Zali, Pejman Rohani, Gholamhossein Mehralian
    Aim

    Description of the inflammatory bowel disease natural history in Tehran province.

    Background

    Inflammatory bowel disease (IBD) is a non-homogeneous disorder with an unpredictable natural history that impairs a patient's quality of life over the course of their life. As a result, providing evidence for efficient patient management is critical.

    Methods

    In this case series study, 198 IBD patients who were visited in our clinic at least three times routinely from Oct 2015 to May 2020 were included. Then, two panel-based approaches, the Multi-State Model (MSM) and random-effect ordered logistic, were used to deduce the clinical course of IBD, which included remission, mild, moderate to severe, and surgical states. Results For ulcerative colitis (UC), women had a slightly poorer condition for remission but better for moderate to severe and a faster transition from moderate to severe to mild (HR=1.490, 95% CI: 1.02-2.16) compared to men. For Crohn's disease (CD), they had a better condition for remission but a slightly poorer condition for the severe state and higher transition from mild to moderate to severe (HR=1.221, 95% CI: 0.471- 3.22) than men. Oral 5-ASA had better efficacy in people with remission and/or mild states but not for those with moderate to severe states, especially in CD (mild to moderate to serve, HR=1.526, 95% CI: 0.59-3.89). Immunosuppressive drugs were better for patients with lower disease severity, especially with UC (mild to remission, HR=1.258, 95% CI: 0.75-2.09).

    Conclusion

    Panel approaches have the potential efficacy to tackle the unpredictable clinical course of IBD (UC/CD). Hence, we highly recommend that our findings be included into the Iranian routine clinical environment of IBD and/or that related studies be conducted in Iran and other regions to gain a better understanding of the natural history of IBD.

    Keywords: Inflammatory bowel disease, Multi-state model, Panel data, Crohn's disease, Ulcerative colitis
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