Farname Inc in collaboration with Iranian Society of PathologyIranian Journal of Pathology1735-530317320220701Comprehensive Assessment of Multiple Sclerosis: From Immunotherapy and Immunopathogenesis to Predictive Biomarkers24125025405410.30699/ijp.2022.541483.2755ENSoheil VazifedustBaqiyatallah Research Center for gastroenterology and Liver Diseases (BRCGL), Baqiyatallah University of Medical Sciences, Tehran, Iran0000-0001-6567-7678Hadi Esmaeili Gouvarchin GhalehApplied Virology Research Center, Baqiyatallah University of Medical Sciences, Tehran, Iran0000-0001-8562-2295Mostafa KhafaeiHuman Genetics Research Center, Baqiyatallah University of Medical Sciences, Tehran, Iran.0000-0001-5661-4544Fateme AzematiDepartment of Biology, School of Basic Sciences, Science and Research Branch, Islamic Azad University, Tehran, Iran0000-0003-1808-636XBahman Jalali KondoriBaqiyatallah Research Center for gastroenterology and Liver Diseases (BRCGL), Baqiyatallah University of Medical Sciences, Tehran, IranDepartment of Anatomical Sciences, Faculty of Medicine, Baqiyatallah University of Medical Sciences, Tehran, Iran0000-0002-6134-9965Journal Article20211027<strong>Background & Objective:</strong> Multiple sclerosis (MS) is an inflammatory neurological disorder that affects the central nervous system (CNS) and causes individuals to experience a variety of cognitive and physical problems. As proven by two decades of clinical experience with immunomodulatory therapies for MS, the disease progresses and relapses through several immunological pathways. New medicines aimed at remyelination and neurodegeneration are being developed; however, they need stronger evidence before being introduced into routine clinical care. The purpose of this study was a thorough assessment of MS immunopathology and predictive biomarkers.
<strong>Methods:</strong> Immunotherapy, immunopathogenesis, and prognostic biomarkers were all parts of the search method. Only publications in English were considered for inclusion in the study. For that purpose, we went through the current state of knowledge around MS immunopathology and related biomarkers. Immunology, as well as the identification of increased inflammation as an important component of neurodegeneration, shaped our understanding of this disease aetiology. The relevant sources examined covered the years 2015-2021.
<strong>Conclusion:</strong> We found biomarkers in the cerebrospinal fluid and blood that might be used for the prediction and diagnosis of MS, as well as for measuring treatment response and adverse effects. Many variables, including the role of some infectious organisms and the impact of environmental and social factors, might contribute to the immunological dysfunctions seen in MS. Patients with MS may benefit from better therapy options if a better understanding of MS biomarkers and immune response mechanisms would be obtained. https://ijp.iranpath.org/article_254054_5f8f4ffd914e0a04f0e7401208ebf238.pdfFarname Inc in collaboration with Iranian Society of PathologyIranian Journal of Pathology1735-530317320220701SNHG6 203 RNA May be Involved in the Cell Cycle Progression in HER2-Negative Breast Cancer Cells25126025405510.30699/ijp.2022.527346.2607ENAmin Jafari OliayiPathology and Stem Cell Research Center, Department of Pathology, Afzalipour Medical School, Kerman University of Medical Sciences, Kerman, Iran0000-0001-6966-3337Shahriar DabiriPathology and Stem Cell Research Center, Department of Pathology, Afzalipour Medical School, Kerman University of Medical Sciences, Kerman, Iran0000-0002-5922-3976Journal Article20210330<strong>Background & Objective:</strong> Long noncoding RNAs (lncRNAs) as challenging molecules are more known compared to those in the last decade. These transcripts have been validated for carcinogenesis in many types of tissue. Functions of lncRNAs in cancer induction include cell cycle, epithelial to mesenchymal transition progression, apoptosis inhibition, cell migration, and invasion stimulation . LncRNA small nucleolar host (SNHG6) have been proven as an oncogenic transcript in many types of cancer.<br /><strong>Methods:</strong> RNA extraction was performed for 47 breast specimens in patients with cancer and cDNAs were synthesized. Relative expression of target variants was determined by qPCR and calculated based on the ΔΔCt method. SNHG6 203 was cloned into pcDNA 3.1+ vector for overexpression in MCF7 (HER2-) and SK-BR3 (HER2+) cells. The cell cycle progression of transfected cells was assessed by flow cytometry. Cell migration ability of transfected cells was evaluated by the scratch method and Image J software. Finally, cell viability was assessed by the MTT method.<br /><strong>Results:</strong> Among four splice variants of SNHG6 (202, 203, 204, and 207), SNHG6 203 was proved as an overexpressed splice variant in breast cancer tumors. This transcript was expressed in HER2-negative breast tumors more frequently than in the positive ones. Overexpression of this variant in target cells resulted in cell cycle progression of MCF7 as HER2-negative cells. Moreover, the overexpression of SNHG6 203 led to a lower migration ability of MCF7 cells and a non-significant reduction of their viability as HER2-negative breast cancer cells.https://ijp.iranpath.org/article_254055_cd7fd21c372e0cde78e19cd7fab7019c.pdfFarname Inc in collaboration with Iranian Society of PathologyIranian Journal of Pathology1735-530317320220701Phenotypic and Molecular Characterization of Carbapenems Resistant Escherichia coli Isolated from Patients with Urinary Tract Infections in Ardabil Province, Iran26126725405610.30699/ijp.2022.538613.2716ENShabnam KhavandiDepartment of Microbiology, School of Medicine, Ardabil University of Medical Sciences, Ardabil IranMohsen ArzanlouDepartment of Microbiology, School of Medicine, Ardabil University of Medical Sciences, Ardabil Iran0000-0002-4233-9497Roghayeh TeimourpourDepartment of Microbiology, School of Medicine, Ardabil University of Medical Sciences, Ardabil IranHadi PeeridogahehDepartment of Microbiology, School of Medicine, Ardabil University of Medical Sciences, Ardabil Iran0000-0002-7152-1917Journal Article20211108<strong>Background & Objective:</strong> Carbapenem-resistant is Gram-negative bacteria representing a worldwide public health problem. The present study aims to survey the phenotypic and genotypic characteristics of carbapenem-resistant <em>Escherichia coli</em> isolates collected from hospitalized patients and outpatients in Ardabil province, Iran.<br /><strong>Methods:</strong> Two hundred samples were collected from the patients who had already been referred to the hospitals in Ardabil, Iran, from January to June 2017. Each patient's social and demographic data were recorded in the first step. The resistance profile of all<em> E. coli</em> isolates against imipenem and meropenem antibiotics were determined using the Kirby-Bauer disk diffusion method. Moreover, the broth microdilution method determined the Minimum Inhibitory Concentration (MIC) of E. coli isolates to imipenem. The Carbapenem Inactivation Method (CIM) and Carba NP test were employed for screening carbapenem-resistant strains. The frequency of carbapenem-encoding genes was determined using Polymerase Chain Reaction (PCR) method. The Enterobacterial Repetitive Intergenic Consensus (ERIC)-PCR analysis was used to evaluate the genetic relatedness of <em>E. coli</em> isolates.<br /><strong>Results:</strong> Out of 200 urine samples, 66% (n = 132) of the samples were collected from women. The patients' age varied from 1 month to 93 years. Results of the disk diffusion method revealed that 33% (n=66/200) of <em>E. coli</em> isolates were resistant to imipenem. However, imipenem resistance was detected in 37% (n = 74/200) of the <em>E. coli</em> isolates using broth microdilution method. All <em>E. coli</em> isolates were negative in CIM and Carba NP tests. Moreover, we could not detect any carbapenemase encoding genes among <em>E. coli</em> isolates. The ERIC-PCR method revealed the <em>E. coli</em> strains were classified into 39 clusters with 80% similarity.<br /><strong>Conclusion:</strong> It appears that <em>E. coli</em> is the most common cause of urinary tract infection in Ardabil province.https://ijp.iranpath.org/article_254056_3398a5f1cd862bae192f89b80bc7acb6.pdfFarname Inc in collaboration with Iranian Society of PathologyIranian Journal of Pathology1735-530317320220701Revisiting Metaplastic Carcinoma of Breast: An Emphasis on the Clinico-pathological and Immunohistochemical Variables Analyzed at a Tertiary Cancer Centre in South India26827425406110.30699/ijp.2022.541798.2757ENGeetha VPatil Okaly1Department of Pathology, Kidwai Memorial Institute of Oncology, Bangalore, IndiaAkshatha CDepartment of Pathology, Kidwai Memorial Institute of Oncology, Bangalore, IndiaSandhya NDepartment of Pathology, Kidwai Memorial Institute of Oncology, Bangalore, IndiaAkina PrakashDepartment of Pathology, Kidwai Memorial Institute of Oncology, Bangalore, IndiaM NSumaDepartment of Pathology, Kidwai Memorial Institute of Oncology, Bangalore, IndiaAshwini NargundDepartment of Pathology, Kidwai Memorial Institute of Oncology, Bangalore, IndiaShankar AnandDepartment of Pathology, Kidwai Memorial Institute of Oncology, Bangalore, IndiaC RamachandraDepartment of Surgical Oncology, Kidwai Memorial Institute of Oncology, Bangalore, IndiaLibin BabuCherianDepartment of Pathology, Kidwai Memorial Institute of Oncology, Bangalore, IndiaJournal Article20211115<strong>Background & Objective:</strong> Metaplastic carcinoma is a diverse variant of invasive breast carcinomas (IBC) characterized by dedifferentiation of malignant cells towards squamous and/or mesenchymal elements. It accounts for 0.3-1.2% of all IBC. These tumors are typically triple-negative by hormonal profiling with a high proliferation index and a dismal prognosis. Lymph node metastasis is an unusual feature in metaplastic carcinoma.<br /><strong>Methods:</strong> The present study analyses 30 cases (26 cases of modified radical mastectomy and 4 cases of lumpectomy) of metaplastic carcinoma over 2018-2020 (3 years). Four oncopathologists reviewed routine histopathologic and immunohistochemical-stained slides. The clinical details were collected from the Medical Records Department of the Cancer Institute.<br /><strong>Results:</strong> A total of 20 (66.67%) cases were patients >50 years of age, 21(70%) out of which were diagnosed as invasive carcinoma, grade 3 according to the Nottingham histological score. Five (16.7%) cases presented with lymph node metastasis. While immunohistochemically 28 (93.3%) cases were triple-negativeCK5/6, P63, EGFR, and Ki-67 (more than 40%) positivity was noted in 25 (83.3%) , 26 (86,7%) , 20 (66.7%), and 25 (83.3%) cases, respectively.<br /><strong>Conclusion:</strong> Metaplastic carcinoma is characteristically triple-negative breast malignancies (TNBC) exhibiting a high Ki-67 index and a lower rate of lymph node metastasis. CK5/6, p63, and EGFR are pertinent immunohistochemical markers that may aid in diagnosis. However, those markers are non-specific for the disease and morphologic features are always the key to the diagnosis of the process.https://ijp.iranpath.org/article_254061_7274cd5f8df15234dab1b0e6d700d759.pdfFarname Inc in collaboration with Iranian Society of PathologyIranian Journal of Pathology1735-530317320220701Study of Podoplanin Expression in Head and Neck Squamous Cell Carcinoma27528425406210.30699/ijp.2022.547004.2809ENAnjali MaryJIbiDepartment of Pathology, JSS Medical College, JSS Academy of Higher Education and Research, Mysuru, Karnataka, IndiaVijaya BasavarajDepartment of Pathology, JSS Medical College, JSS Academy of Higher Education and Research, Mysuru, Karnataka, IndiaJournal Article20220128<strong>Background & Objective:</strong> Head and Neck Squamous cell carcinoma (HNSCC) is one of the leading cancers worldwide. Cervical lymph node metastasis is the most adverse prognostic factor for patients with HNSCC. As there are no reliable factors in predicting lymph node metastasis, recent researchers focus on identifying various metastasis markers that will aid treatment selection. Podoplanin is a recent marker strongly associated with lymph node metastasis, aggressive tumor behavior, and poor prognosis. The expression of podoplanin in human squamous cell cancers and its association with cancer cell motility suggest a possibility that it could be used as a biomarker to predict lymph node metastasis. To study the expression of podoplanin in head and neck squamous cell carcinoma, determine its association with clinicopathological variables, and predict its use as a biomarker in predicting lymph node metastasis.<br /><strong>Methods:</strong> The present study was conducted in a tertiary care hospital. Podoplanin expression was studied in 45 cases of HNSCC and its association with clinicopathological variables. The predictive power of podoplanin was further analyzed using univariate and multivariate logistic regression analysis. The positive and negative predictive values of podoplanin were determined concerning the presence or absence of lymph node metastasis.<br /><strong>Results:</strong> Podoplanin expression is significantly associated with histological grade (<em>P</em>=0.03) and lymph node metastasis (<em>P</em>=0.01). In logistic regression analysis, podoplanin expression (Odds Ratio: 5.66, Confidence Interval: 1.23 -25.87, <em>P</em>=0.02) was a significant independent predictor of lymph node metastasis.<br /><strong>Conclusion:</strong> Our study demonstrates that podoplanin provides prognostic information and predicts lymph node metastasis which was consistent with our studies in the literature. Thus, podoplanin may help better stratify patients selected for elective neck node dissection in early tumor stages and clinically negative regional disease.https://ijp.iranpath.org/article_254062_53e51bb19ec94c85500b7146c9e76d12.pdfFarname Inc in collaboration with Iranian Society of PathologyIranian Journal of Pathology1735-530317320220701Anti-biofilm Activity of a Lytic Phage Against Vancomycin-Resistant Enterococcus faecalis28529425406310.30699/ijp.2022.541855.2760ENForough GoodarziDepartment of Microbiology, School of Medicine, Iran University of Medical Sciences, Tehran, IranMasoumeh HallajzadehDepartment of Microbiology, School of Medicine, Iran University of Medical Sciences, Tehran, IranMohammad SholehDepartment of Microbiology, School of Medicine, Iran University of Medical Sciences, Tehran, IranMalihe TalebiDepartment of Microbiology, School of Medicine, Iran University of Medical Sciences, Tehran, IranVahid Pirhajati MahabadiNeuroscience Research Center, Iran University of Medical Sciences, Tehran, IranCellular and Molecular Research Center, Iran University of Medical Sciences, Tehran, IranNour AmirmozafariDepartment of Microbiology, School of Medicine, Iran University of Medical Sciences, Tehran, IranJournal Article20211107<strong>Background & Objective:</strong> This study aims to isolate a lytic bacteriophage against planktonic <em>Enterococcus faecalis</em> V583 culture and evaluate its ability to disrupt and inhibit biofilm.<br /><strong>Methods:</strong> An anti-<em>E. faecalis</em> phage was isolated from sewage and visualized by electron microscopy, the vB_EfsS_V583 (V583) host range was determined by spot test on 13 <em>E. faecalis </em>clinical strains. Inhibition and degradation experiments were designed to investigate the effect of phage on biofilm. In the inhibition and degradation assay, biofilms were formed in the presence and absence of phage, respectively. Finally, crystal violet method tested the effect of phage on biofilm.<br /><strong>Results:</strong> Phage V583 belongs to the <em>Siphoviridae</em><em> </em>family and can infect all <em>E. faecalis </em>strains. Antibacterial activity has been shown to degrade and inhibit biofilm produced by V583. The study results showed that phage v583 is more efficient in biofilm inhibition than biofilm degradation. In both assays, phage-treated wells' absorption is less than untreated wells. These results were confirmed by Colony-forming unit reduction in the treated biofilm.<br /><strong>Conclusion:</strong> The anti-biofilm activity showed that phage therapy using phage V583<strong> </strong>might be an alternative tool to remove <em>E. faecalis</em> biofilms.https://ijp.iranpath.org/article_254063_8662aced09273ef39731d3a1fac40e1b.pdfFarname Inc in collaboration with Iranian Society of PathologyIranian Journal of Pathology1735-530317320220701The Antibacterial and Anti-biofilm Traits of the Novel BMAP-27-Melittin Conjugated Peptide Nanoparticle Against Streptococcus mutans: Clinical Isolates from Oral Cavity29430225406610.30699/ijp.2022.547555.2817ENMohammad PourahmadiDepartment of Anatomical Sciences, Jahrom University of Medical Sciences, Jahrom, IranKimia PourahmadiStudent Research Committee, School of Dentistry, Shiraz University of Medical Sciences, Shiraz, IranFarzan ModaresiDepartments of Microbiology, Advanced Medical Sciences and Technology, Jahrom University of Medical Sciences, Jahrom, IranShekoufeh AtashpoorDepartments of Microbiology, Advanced Medical Sciences and Technology, Jahrom University of Medical Sciences, Jahrom, IranDepartment of Pharmacology, Advanced Medical Sciences and Technology, Jahrom University of Medical Sciences, Jahrom, Iran0000-0003-2777-1131Azita AzadOral and Dental Disease Research Center, Department of Oral & Maxillofacial Medicine, School of Dentistry, Shiraz University of Medical Sciences, Shiraz, Iran0000-0002-1073-4134Alireza RanjbaranOral and Dental Disease Research Center, Department of Oral & Maxillofacial Medicine, School of Dentistry, Shiraz University of Medical Sciences, Shiraz, Iran0000-0003-3562-6874Abdolmajid GhasemianNoncommunicable Diseases Research Center, Fasa University of Medical Sciences, Fasa, Iran0000-0002-6227-3376Journal Article20220212<strong>Background & Objective:</strong> The spread and development of drug-resistant bacterial strains has prompted the hunt for novel antibacterial polypeptides undergoing conformational changes to confer rapid bactericidal effects. The aim of this study was to evaluate the effect of novel BMAP27-Melittin conjugated peptide- nanoparticle (NP) against <em>Streptococcus mutans </em>as the primary pathogen from subgingival plaques.<br /><strong>Methods:</strong> Sixty subgingival plaque samples were collected, and 39 <em>S. mutans</em> isolates were identified<em>.</em> The BMAP27-Melittin conjugated peptide was purchased from GenScript Company, USA. Minimum Inhibitory Concentration (MIC), Minimum Bactericidal Concentration (MBC), Biofilm Inhibitory Concentration (BIC), and Biofilm Eradication Concentration (BEC) of BMAP27-Melittin-NP were calculated using the microtiter method.<br /><strong>Results:</strong> Thirty-nine infected subjects were reported, including 24 males and 15 females (<em>P</em>=0.299). MIC, MBC, BIC, and BEC of BMAP27-Melittin–NP against <em>S. mutans</em> were 1.8, 2.9, 2.1, and 3.8μg/mL, respectively. The mean MBC, BEC, and BIC values were significantly lower among clinical isolates than <em>S. mutans</em> ATCC 35688 standard strain (<em>P</em>=0.032, 0.001, and 0.001, respectively).<br /><strong>Conclusion:</strong> BMAP27-Melittin-NP demonstrated significant antibacterial and anti-biofilm effects against clinical isolates of <em>S. mutans</em> which can be considered a promising compound to prevent or treat dental caries and eradicate the oral infections.https://ijp.iranpath.org/article_254066_e7cb5456def6886f844e862050b2e34b.pdfFarname Inc in collaboration with Iranian Society of PathologyIranian Journal of Pathology1735-530317320220701Evaluation of Triple Fragment Vaccine HSPX (Rv2031c) + PPE44 (Rv2770c) + Mouse IgG1 (Fcγ2a) with Auxiliary Adjuncts IL-22 in Comparison with BCG Vaccine30331325406710.30699/ijp.2022.549673.2849ENAzar ValizadehClinical Microbiology Research Center, Ilam University of Medical Sciences, Ilam, Iran.Fra KhosraviClinical Microbiology Research Center, Ilam University of Medical Sciences, Ilam, Iran0000-0002-8685-6832Hamid SedighianApplied Microbiology Research Center, Systems biology and poisonings institute, Baqiyatallah University of Medical Sciences, Tehran, Iran0000-0002-7609-9938Elham BehzadiAcademy of Medical Sciences of the IR of Iran, Tehran, Iran0000-0001-9050-3127Elaheh ParizadClinical Microbiology Research Center, Ilam University of Medical Sciences, Ilam, Iran.0000-0002-7700-5702Abbas Ali Imani FooladiApplied Microbiology Research Center, Systems biology and poisonings institute, Baqiyatallah
University of Medical Sciences, Tehran, Iran0000-0001-7339-8257Journal Article20220227<strong>Background & Objective:</strong> Despite the vaccination with the BCG vaccine, tuberculosis (TB) remains one of the major health problems in the world. The aim of this study was to evaluate our newly designed vaccine using IL-22 as an adjuvant in comparison with the common BCG vaccine.<br /><strong>Methods:</strong> The gene constructs were cloned into the expression vector of pET28a and then into the recombinant vector of PET28a – HSPX, and PPE44 was transformed into <em>Escherichia coli</em> BL21 (DE3). Finally, the immunogenicity of recombinant proteins with and without BCG and IL-22 in BALB/c mice was investigated.<br /><strong>Results:</strong> The key cytokines INF-γ and TNF-α were elevated more greatly in BCG immunized group than in PHF immunized group.<br />Immunization with PHF showed a significant increase in IL-4 levels versus the BCG group. Adding IL-22 to the vaccine formulations indicated a tiny increase in IL-4 levels compared to their related vaccine groups.<br />Specific total IgG1 in the experimental groups showed an increase in comparison with control groups, but in the vaccinated groups, no significant differences were observed, and the presence of IL-22 in the vaccine formulations indicated a slight decrease compared with the related mere vaccine groups. Results of specific total IgG2a in the experimental groups revealed that only in the PHF group formulated with IL-22 a significant increase occurs compared with all other experimental groups.<br /><strong>Conclusion:</strong> It seems that BCG, as the only licensed vaccine for TB infection, could be more potent than a recombinant vaccine in the induction of cellular and humoral immune responses.https://ijp.iranpath.org/article_254067_2019d02d0291ef14405139a32c95d328.pdfFarname Inc in collaboration with Iranian Society of PathologyIranian Journal of Pathology1735-530317320220701Crosstalk Between Programmed Death Ligand 1, Ki-67 Labelling Index, and Tumor-Infiltrating Lymphocytes in Invasive Breast Cancer and Clinicopathological Correlations in a Tertiary Care Center in Western India31432225406810.30699/ijp.2022.539946.2737ENRashim SharmaDepartment of Pathology and Laboratory Medicine, All India Institute of Medical Sciences, Jodhpur, Rajasthan, India0000-0003-4748-3049Poonam AbhayElhenceDepartment of Pathology and Laboratory Medicine, All India Institute of Medical Sciences, Jodhpur, Rajasthan, India0000-0002-4660-389XMeenakshi RaoDepartment of Pathology and Laboratory Medicine, All India Institute of Medical Sciences, Jodhpur, Rajasthan, India0000-0003-1310-2578Sudeep KheraDepartment of Pathology and Laboratory Medicine, All India Institute of Medical Sciences, Jodhpur, Rajasthan, India0000-0002-2413-5749Deepak VedantDepartment of Pathology and Laboratory Medicine, All India Institute of Medical Sciences, Jodhpur, Rajasthan, India0000-0003-0041-9314Ramkaran ChaudharyDepartment of General Surgery, All India Institute of Medical Sciences, Jodhpur, Rajasthan, IndiaPuneet PareekDepartment of Radiation Oncology, All India Institute of Medical Sciences, Jodhpur, Rajasthan, India0000-0002-6055-9872Jeewan RamVishnoiDepartment of Surgical Oncology, All India Institute of Medical Sciences, Jodhpur, Rajasthan, India0000-0003-1484-8929Sanjeev MisraDepartment of Surgical Oncology, All India Institute of Medical Sciences, Jodhpur, Rajasthan, IndiaJournal Article20211016<strong>Background & Objective:</strong> Breast cancer is the leading cancer among Indian women and accounts for about 25% of all cancer cases worldwide. The present study aimed to assess Programmed Death Ligand-1 (PD-L1) expression in tumoral cells and tumor-infiltrating lymphocytes (TILs) and evaluate their correlations with the Ki-67 labelling index in invasive breast carcinomas (IBC).<br /><strong>Methods:</strong> This descriptive observational study was conducted during 2016-2018 and included all diagnosed cases of IBC. The relationships between PD-L1 expression, TILs, hormone receptors, Ki-67, and clinicopathological parameters were studied in IBC. Statistical analysis was performed by SPSS version 23.<br /><strong>Results:</strong> Out of<strong> </strong>114 evaluated cases, 33.33% (N=38) showed PD-L1+ expression in tumor cells and 47.37% (N=54) had PD-L1+ expression in TILs. A high Ki-67 index was observed in 96 cases. Moreover, 49 patients were estrogen receptor (ER)- and 65 were ER+. We observed that 22 of 49 ER- and 49 of 65 ER+ subjects showed PD-L1+ expression, respectively.<br /><strong>Conclusion:</strong> Our results showed a significant relationship between PD-L1 expression in tumoral cells and TILs, as well as between Ki-67 and TILs. In addition, an inverse correlation was noted between PD-L1 expression and ER. The PD-L1 expression in tumors and TILs and correlation with high Ki-67 may prove the importance of PD-L1 in targeted chemotherapy. An inverse relationship between PD-L1 and ER expression in tumoral cells suggests scope for immunotherapy in ER- IBC. However, further research with more cases is required.https://ijp.iranpath.org/article_254068_be0ffd6cb6ff1246d4ceea629e474ffa.pdfFarname Inc in collaboration with Iranian Society of PathologyIranian Journal of Pathology1735-530317320220701Evaluation of the Relationship Between Serum and Urine Ferritin Level of Low Birth Weight Infants32332725406910.30699/ijp.2022.546540.2807ENHassan BazmamounDepartment of Pediatric Gastroenterology, Hamadan University of Medical Sciences, Hamadan, IranSoheila NarimaniDepartment of Pediatrics, Hamadan University of Medical Sciences, Hamadan, IranMaryam ShokohiDepartment of Neonatal-Perinatal Medicine, Hamadan University of Medical Science, Hamadan, IranHossein EsfahaniDepartment of Pediatric Hematology/Oncology, Hamadan University of Medical Science, Hamadan, IranAli RezaSoltanianDepartment of Biostatistics, Hamadan University of Medical Sciences, Hamadan, IranAlireza Rastgoo HaghiDepartment of Pathology, Hamadan University of Medical Science, Hamadan, Iran0000-0003-4034-7415Journal Article20220110<strong>Background & Objective:</strong> Iron deficiency before birth or in infancy can cause long-term behavioral and neurological disorders. Measuring serum ferritin is an effective way to diagnose iron deficiency but requires significant blood volume from a low birth weight infant. Therefore, the present study was performed to investigate the relationship between serum and urinary ferritin levels in low birth weight infants.<br /><strong>Methods:</strong> In this cross-sectional study, 76 infants weighing less than 2500 g were studied. To measure serum ferritin level, 1.5 mL of blood and to measure urinary ferritin level, at least 1 mL of urine was collected from each infant. Then the results were compared. Data analysis was performed using SPSS software version 16, and the significance level was considered less than 0.05.<br /><strong>Results:</strong> Out of 76 neonates studied, 51.3% were boys, and 80.3% were premature infants. The mean birth weight of infants was 2056.31±318.74 g, and the mean serum and urinary ferritin levels were 134.77±72.35 and 85.55±70.97 ng, respectively. There was a statistically significant relationship between serum and urinary ferritin levels. Also, serum ferritin and urinary ferritin levels had a statistically significant relationship with birth weight and gestational age. The higher the birth weight as well as the age at birth, the higher the serum ferritin and urinary ferritin.<br /><strong>Conclusion:</strong> According to the findings of this study, measurement of urinary ferritin level can be used as a noninvasive tool for iron deficiency screening in low birth weight infants instead of serum ferritin level.https://ijp.iranpath.org/article_254069_56e9a3dd886000a40b96ce95806b321f.pdfFarname Inc in collaboration with Iranian Society of PathologyIranian Journal of Pathology1735-530317320220701Accuracy of Paris 2016 System for Non-invasive Diagnosis Bladder Malignancy32833425407010.30699/ijp.2022.548036.2833ENAzadeh RakhshanMen's Health and Reproductive Health Research Center, Shahid Beheshti University of Medical Sciences, Tehran, IranEsmat ArvinMen's Health and Reproductive Health Research Center, Shahid Beheshti University of Medical Sciences, Tehran, IranSam AlahyariFaculty of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran0000-0001-5190-0082Behrang KazeminezhadDepartment of Pathology, Faculty of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, IranTahmineh MollasharifiDepartment of Pathology, Faculty of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran0000-0003-4123-4543Alireza BagheriMen's Health and Reproductive Health Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran0000-0001-7890-7049Fereshte AliakbariMen's Health and Reproductive Health Research Center, Shahid Beheshti University of Medical Sciences, Tehran, IranSeyed Jalil HosseiniMen's Health and Reproductive Health Research Center, Shahid Beheshti University of Medical Sciences, Tehran, IranMohammad SoleimaniDepartment of Urology, Faculty of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, IranMahsa AhadiMen's Health and Reproductive Health Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran0000-0002-0995-3102Elena JamaliDepartment of Pathology, Faculty of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran00000001-5536-9727Afshin MoradiDepartment of Pathology, Faculty of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran0000-0003-1544-0992Zahra SadeghzadehMen's Health and Reproductive Health Research Center, Shahid Beheshti University of Medical Sciences, Tehran, IranSaleh GhiasiDepartment of Urology, Faculty of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, IranMalihe NasiriDepartment of Biostatics, Shahid Beheshti University of Medical Sciences, Tehran, IranFarzad AllamehMen's Health and Reproductive Health Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran0000-0003-4536-6404Journal Article20220205<strong>Background & Objective:</strong> The Paris System for Reporting Urinary Cytology (TPS) is a new method for evaluating urinary cytology designed to reduce unreproducible reports. The aim of this study was to reclassify and compare urinary cytology reports with TPS criteria to determine the frequency of unreproducible reports compared to the previous system.<br /><strong>Methods:</strong> In this study, the laboratory electronic registration system analyzed patients' urine samples taken by voided or washing and brushing methods. The cytological evaluation was performed considering the previous system and TPS by a pathologist. The results of the two systems were compared, and the sensitivity and specificity of TPS were calculated.<br /><strong>Results:</strong> Urine samples were taken from 876 patients. The mean age of patients was 63.36 ± 12.62. Comparing the routine classification system and TPS, it was observed that the number of atypical reports in the TPS system decreased by 12%, and all of these cases were downgraded to the negative group in the new classification. The sensitivity and specificity of TPS were 29.4% and 95.1%, respectively, if suspected malignancy and positive reports for malignancy were considered. Finally, if positive reports for malignancy were selected, sensitivity and specificity changed to 11.8% and 100%, respectively.<br /><strong>Conclusion:</strong> Although the TPS system has low sensitivity for the diagnosis of urothelial malignancies, due to its high specificity, it is possible to consider and use this classification for screening patients.https://ijp.iranpath.org/article_254070_97253a34a92fe3def1e04248102573cf.pdfFarname Inc in collaboration with Iranian Society of PathologyIranian Journal of Pathology1735-530317320220701Long-term Effects of Regular Whole Blood Donation on Peripheral Blood CD34+ Cells Population with using Leukoreduction Filters33534125413910.30699/ijp.2022.540459.2746ENParvaneh Abbasi SourkiDepartment of Hematology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, IranAli Akbar PourfathollahDepartment of Immunology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, IranMahdi PakjooDepartment of Hematology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, IranZahra Abbasi-MalatiBlood Transfusion Research Center, High Institute for Research and Education in Transfusion Medicine, Tehran, IranMona A. A.TajrishiBlood Transfusion Research Center, High Institute for Research and Education in Transfusion Medicine, Tehran, IranJournal Article20211015<strong>Background & Objective:</strong> Trapped cell population in leukoreduction filters (LRFs) contains such a significant number of CD34<sup>+</sup> hematopoietic stem cells that can be recovered to be used in research studies.<br /><strong>Methods:</strong> Samples (n=20) were obtained from 10 first-time donors and 10 regular blood donors with more than 30 times blood donation. After separating leukocytes from LRFs by backflushing, total leukocyte number and differential count were determined in both groups using an automated haemocytometer. Then cell viability and CD34<sup>+ </sup>cell quantification were assessed using 7- amino-actinomycin D and fluorescent-labeled monoclonal antibodies using flow cytometry, respectively.<br /><strong>Results:</strong> Total leukocyte count was 665±164.92×10<sup>6</sup> in the first-time blood donors and 883±233.89×10<sup>6</sup> in the regular donors, which were not significantly different (<em>P</em>=0.08). While the number of CD34<sup>+</sup> cells was significantly reduced in the regular donors compared to the first-time donors (0.58±0.20×10<sup>6</sup>/µL vs<em>. </em>0.36±0.22×10<sup>6</sup>/µL; <em>P</em>=0.034). There was no significant difference in terms of absolute neutrophil count (10.58±3.66×0<sup>6 </sup>vs. 13.17±6.45×10<sup>6</sup>/µL; <em>P</em>=0.349), lymphocytes (7.75±3.11×10<sup>6 </sup>vs. 10.38±3.77×10<sup>6 </sup>/µL; <em>P</em>=0.917), and monocytes (2.31±0.88×10<sup>6 </sup>vs.<em> </em>2.59±1.09×10<sup>6</sup>/µL; <em>P</em>=0.591) between the first-time and regular donor groups, respectively. Based on the correlation coefficients, the participants’ age had no significant effect on these variables.<br /><strong>Conclusion:</strong> The results of this study depicted that regular blood donation reduces the number of CD34<sup>+</sup> cells in the peripheral blood (PB) of regular donors while it has no significant effect on the ratio of myeloid to lymphoid cells of the two groups.https://ijp.iranpath.org/article_254139_3b66452b82854f589ac25b233680deff.pdfFarname Inc in collaboration with Iranian Society of PathologyIranian Journal of Pathology1735-530317320220701Alpha-Synuclein Clearance through Inhibiting Akt/mTOR Pathway by Microfluidic Encapsulated Induced Conjunctival MSCs in a Parkinsonian Model34235325414010.30699/ijp.2022.553459.2890ENMeysam ForouzandehFaculty of Life Sciences, Shahid-Beheshti University, Tehran, IranMohammad Reza BigdeliInstitute for Cognitive and Brain Science, Shahid Beheshti University, Tehran, IranFaculty of Life Sciences, Shahid-Beheshti University, Tehran, IranHossein MostafaviDepartment o Physiology, School of Medicine, Zanjan University of Medical Sciences, IranCancer Gene Therapy Research Center, Zanjan University of Medical Sciences, Zanjan, IranSamad NadriDepartment of Medical Nanotechnology, School of Medicine, Zanjan University of Medical Sciences, Zanjan, IranMehdi EskandariDepartment o Physiology, School of Medicine, Zanjan University of Medical Sciences, IranJournal Article20220514<strong>Background & Objective:</strong> Parkinson's disease (PD) is a progressive neurodegenerative disorder in which the cause is attributed to the alpha-synuclein (α-Syn) accumulation due to the decreased rate of autophagy. Due to the many advantages, mesenchymal stem cells (MSCs), such as the secretion of neurotrophic factors, have been proposed for PD cell therapy. The present study, in continuation of the previous study, aimed to investigate the therapeutic effect of human-derived Conjunctival MSCs (CJ-MSCs) on the clearance of α-Syn by the microRNA-149(miR-149)/Akt/mTOR/ pathway.<br /><strong>Methods:</strong> Stereotaxic 6-hydroxy dopamine (6-OHDA) was injected directly into the medial forebrain bundle (MFB) to induce Parkinson's disease. An apomorphine-induced rotation test was used to confirm the model establishment. CJ-MSCs were encapsulated in alginate microgel using a microfluidic system. The green fluorescent protein (GFP) labeled CJ-MSCs were encapsulated, and free cells were transplanted into the rats' right striatum. Behavioral and molecular analyses evaluated the potency of CJ-MSCs (encapsulated and free cells) in PD rats. Real-Time Quantitative Reverse Transcription PCR (qRT-PCR) was performed to investigate the expression of the miR-149-5p, Akt, mTOR, and α-Syn.<br /><strong>Results:</strong> Our obtained results indicated that transplantation of CJ-MSCs leads to a decrease in the number of rotations while raising the balance and motor abilities. The gene expression evaluation showed a significant reduction in Akt, mTOR, and α-Syn mRNA levels and a significant increase in the level of miR-149-5p compared to the control group. <br /><strong>Conclusion:</strong> It seems that CJ-MSCs can promote the degradation of intracellular α-Syn by miR-149-5p/Akt/mTOR pathway and improve rats' motor functions.https://ijp.iranpath.org/article_254140_7a885efdca5a42fa427a248558f0c2e9.pdfFarname Inc in collaboration with Iranian Society of PathologyIranian Journal of Pathology1735-530317320220701Histopathology Study of Patients with Delayed Mustard Gas Keratopathy 30 Years After Exposure35435925407110.30699/ijp.2022.538950.2722ENSeyed Hashem DaryabariChemical Injuries Research Center, Systems biology and Poisonings Institute, Baqiyatallah University of Medical Sciences, Tehran, IranHossein AghamollaeiChemical Injuries Research Center, Systems biology and Poisonings Institute, Baqiyatallah University of Medical Sciences, Tehran, IranFahimeh Asadi AmoliEye Research Center, Farabi Eye Hospital, Tehran University of Medical Sciences, Tehran, IranKhosrow JadidiChemical Injuries Research Center, Systems biology and Poisonings Institute, Baqiyatallah University of Medical Sciences, Tehran, IranVision Health Research Center, Semnan University of Medical Sciences, Semnan, IranHamid TebyanianResearch Center for Prevention of Oral and Dental Diseases, Baqiyatallah University of Medical Sciences, Tehran, IranJournal Article20211011<strong>Background & Objective:</strong> Delayed mustard gas keratopathy (DMGK) is the main chronic outcome in eye-chemical injured patients. The aim of this study was the histopathological evaluation of mustard-exposed cornea after more than 30 years.<br /><strong>Methods:</strong> Fourteen corneas after Lamellar keratoplasty were evaluated in this study. Corneal tissues were prepared by histologic methods and stained by H&E.<br /><strong>Results:</strong> The main histopathological findings in these cases were the presence of severe stromal edema and corneal scar. In the sections with visible superficial epithelium, subepithelial bullae formation was observed. Focal or diffuse disruption of Bowman's membrane and replacement with fibrosis were also seen. There was no evidence of stromal vascularization and inflammation in all specimens.<br /><strong>Conclusion:</strong> After more than 30 years, an extensive corneal scar is seen in sulfur mustard exposed patients. Scar tissue without vascularization and fibroblastic proliferation is the main finding in the sulfur mustard exposed cornea. This pathology result is different from other scars. No evidence of inflammation or immune cell infiltration should be considered in managing DMGK.https://ijp.iranpath.org/article_254071_d363ccfa4534d6ca143ad83be276c127.pdfFarname Inc in collaboration with Iranian Society of PathologyIranian Journal of Pathology1735-530317320220701Foamy Cell Angiosarcoma in a Patient with Xeroderma Pigmentosum: A Case Report and Comprehensive Review of the Literature36037025407210.30699/ijp.2022.539239.2729ENFatemeh MontazerDepartment of Pathology, Firoozabadi Hospital, Iran University of Medical Sciences, Tehran, Iran0000-0002-4487-1399Ali Zare DehnaviTehran University of Medical Sciences, Tehran, IranAbbas DehghaniDepartment of Dermatology, Rasool Akram Medical Complex, School of Medicine، Iran University of Medical Sciences (IUMS), Tehran, IranArash MaboudiPrivate Practitioner, Dermatologist, Amol, Mazandaran, IranAzadeh Goodarzi5. Department of Dermatology, Rasool Akram Medical Complex Clinical Research Development Center (RCRDC), School of Medicine, Iran University of Medical Sciences, Tehran, Iran0000-0002-1249-4429Journal Article20211018Xeroderma pigmentosum (XP) is a rare autosomal recessive disorder characterized by a DNA repair defect caused by ultraviolet light and cutaneous manifestations, including solar lentigines, xerosis, actinic damage, and cutaneous neoplasms (e.g., basal cell carcinoma, squamous cell carcinoma, and melanoma). Cutaneous angiosarcoma (AS) is a rare group of aggressive skin tumors that infrequently occur in patients with XP, usually involving the scalp or face. The AS has three subtypes: idiopathic, complicating lymphedema, and post-irradiation. The AS has diverse histopathological types, and the uncommon variants are clear cell, epithelioid, granular cell, pseudo lymphomatous, verrucous, and signet-ring cell variants. Although the foamy cell variant of AS is the rarest type, its diagnosis would be really challenging due to the wide variety of differential diagnoses, especially for poorly differentiated ones. Therefore, definitive diagnosis and effective management in the early stages are crucial, and immunohistochemical (IHC) tests are essential. Here we report a 50-year-old Iranian man with AS complicating XP who presented with an ulcerative erythematous and progressive plaque. Histopathologic studies revealed foamy cells and vascular markers (i.e., CD 31 and CD 34) were positive, immunohistochemically which was found unusual features. In addition,, we review previously reported cases in the literature to provide some information on the diagnosis and management of such cases.https://ijp.iranpath.org/article_254072_27ad3fdf8b00deaeaec81484cd6fb01a.pdfFarname Inc in collaboration with Iranian Society of PathologyIranian Journal of Pathology1735-530317320220701A Young Iranian Woman with Pure Primary Ovarian Neuroendocrine Tumor: A Case Report37137525408510.30699/ijp.2022.542788.2766ENFatemeh Samiee RadClinical Research Development Unit, Kosar Hospital, Qazvin University of Medical Sciences, Qazvin, Iran0000-0001-6091-4347Mehdi GhaebiClinical Research Development Unit, Kosar Hospital, Qazvin University of Medical Sciences, Qazvin, Iran0000-0001-7136-3886Arezoo BajelanClinical Research Development Unit, Kosar Hospital, Qazvin University of Medical Sciences, Qazvin, Iran0000-0002-6680-7830Journal Article20211114Pure ovarian neuroendocrine tumors are very rare. Herein, we present a young Iranian woman with a pure primary ovarian neuroendocrine tumor.<br />A 26-year-old female presented with chronic abdominal pain and progressive constipation and was referred to the emergency room. Imaging findings confirmed a mass in the right adnexa. Following the resectional surgery of the ovarian mass, histopathological and immunohistochemistry results disclosed a mixed type of primary ovarian neuroendocrine tumor. The patient did not experience tumor recurrence afterward.<br />Due to the rarity and low prevalence of primary pure ovarian neuroendocrine tumors, the histopathologic diagnosis should be confirmed by an immunohistochemistry study.https://ijp.iranpath.org/article_254085_d065846ed5c43f139804e6252bb37e7e.pdfFarname Inc in collaboration with Iranian Society of PathologyIranian Journal of Pathology1735-530317320220701A Rare Case of Intra-Oral Dirofilariasis Manifesting on The Buccal Mucosa37638025408610.30699/ijp.2022.548111.2829ENRakesh SureshDepartment of Oral & Maxillofacial Pathology and Microbiology, Amrita School of Dentistry, Amrita Vishwa Vidyapeetham, Kochi, India0000-0003-3605-9103Mahija JanardhananDepartment of Oral & Maxillofacial Pathology and Microbiology, Amrita School of Dentistry, Amrita Vishwa Vidyapeetham, Kochi, India0000-0002-2155-4876Vindhya SavithriDepartment of Oral & Maxillofacial Pathology and Microbiology, Amrita School of Dentistry, Amrita Vishwa Vidyapeetham, Kochi, India0000-0001-6503-4306Thara AravindDepartment of Oral & Maxillofacial Pathology and Microbiology, Amrita School of Dentistry, Amrita Vishwa Vidyapeetham, Kochi, India0000-0002-3408-1094Journal Article20220209Dirofilariasis is a rare zoonotic disease endemic in tropical and sub-tropic countries, including India. Caused by the nematode of the genus Dirofilaria, the disease usually affects canines which form the primary hosts. Humans rarely get infected through the bite of potential mosquito vectors. Manifestations in humans have been reported to affect the orbital region, and intra-oral involvement is rarely reported. Our case was a 5-year-old boy who presented with a slow-growing diffuse swelling on the buccal mucosa. Dirofilariasis was diagnosed when the excised specimen was subject for histopathologic evaluation, yielding the identification of the Dirofilaria worm with the typical morphologic characteristics in the tissue sections. An extremely rare occurrence intra-orally, dirofilariasis can manifest as subcutaneous nodules. Pathologists have an important role in the final diagnosis of the disease through identifying the adult worm in the tissue sections of the biopsy specimen. Dental practitioners must be aware of such an entity as rarely this can be encountered in routine dental practice. https://ijp.iranpath.org/article_254086_f86a4f076e33a2eb27e2f9df6c17ab3c.pdf