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The role of immune cells and inflammasomes in Modulating cytokine responses in HPV-Related cervical cancer

INTERNATIONAL IMMUNOPHARMACOLOGY 2025年 145卷 113625页

作者： Aghbash, Parisa Shiri Rasizadeh, Reyhaneh Nahand, Javid Sadri baghi, hossein bannazadeh Tabriz Univ Med Sci Infect & Trop Dis Res Ctr Tabriz Iran Tabriz Univ Med Sci Fac Med Dept Virol Tabriz Iran Tabriz Univ Med Sci Immunol Res Ctr Tabriz Iran

One of the most frequent cancers associated with gynecological malignancies is cervical cancer. Nearly 99% of cervical tumor lesions are produced by prolonged infection with hr-HPV and almost 70% of cases are related to HPV-16 and HPV-18. The human immune system has a crucial role in defending against infections caused by HPV infection. As an illustration, elevation in neutrophils reduces T cell antitumor activity, which in turn results in the development of malignancies and subsequently inhibits immune system function. HPV-infected cells, also, express a significant number of genes related to pro-inflammatory mediators including IL-1 beta. Moreover, inflammasomes, which are multi-protein complexes, owing the production of the pro-inflammatory cytokines including IL-1 beta and IL-18 in response to viral infections. In other words, these multi-protein complexes have a crucial role in tumor immunity regulation through the secretion of pro-inflammatory cytokines and induction of antigen presentation and maturation by APCs including dendritic cells. In this study, we attempted to investigate the inflammasome's general role in the initiation and advancement of cervical cancer, as well as a summary of the pathways connected to the possible participation of inflammasomes in the pathological process of cervical carcinoma and immune cell engagement. Novel strategy techniques that target the inflammatory reaction of tumor-related antigens may be created with an understanding of inflammasome-dependent pathways to accomplish tumor immunotherapy and cervical tumor treatment.

关键词： Inflammasomes Cervical cancer Human papillomavirus Immune cells Antigen associated proteins

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Novel strategies in HPV-16-related cervical cancer treatment: An in vitro study of combined siRNA-E5 with oxaliplatin and ifosfamide chemotherapy

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GENE 2025年 932卷 148904页

作者： Rasizadeh, Reyhaneh Aghbash, Parisa Shiri Mokhtarzadeh, Ahad Poortahmasebi, Vahdat Oskouee, Mahin Ahangar Nahand, Javid Sadri Amini, Mohammad Mahdavi, Seyedeh Zahra Bahojb Yari, Amir hossein baghi, hossein bannazadeh Tabriz Univ Med Sci Infect & Trop Dis Res Ctr Tabriz 516615731 Iran Tabriz Univ Med Sci Immunol Res Ctr Tabriz Iran Tabriz Univ Med Sci Fac Med Dept Virol Tabriz Iran Higher Educ Inst Rab Rashid Dept Genet Tabriz Iran

Background: Cervical cancer, primarily caused by HPV infection, remains a global health concern. Current treatments face challenges including drug resistance and toxicity. This study investigates combining E5-siRNA with chemotherapy drugs, Oxaliplatin and Ifosfamide, to enhance treatment efficacy in HPV-16 positive cervical cancer cells, targeting E5 oncoprotein to overcome limitations of existing therapies. Methods: The CaSki cervical cancer cell line was transfected with E5-siRNA, and subsequently treated with Oxaliplatin/Ifosfamide. Quantitative real-time PCR was employed to assess the expression of related genes including p53, MMP2, Nanog, and Caspases. Cell apoptosis, cell cycle progression, and cell viability were evaluated using Annexin V/PI staining, DAPI staining, and MTT test, respectively. Furthermore, stemness ability was determined through a colony formation assay, and cell motility was assessed by wound healing assay. Results: E5-siRNA transfection significantly reduced E5 mRNA expression in CaSki cells compared to the control group. The MTT assay revealed that monotherapy with E5-siRNA, Oxaliplatin, or Ifosfamide had moderate effects on cell viability. However, combination therapy showed synergistic effects, reducing the IC50 of Oxaliplatin from 11.42 x 10- 8 M (45.36 mu g/ml) to 6.71 x 10- 8 M (26.66 mu g/ml) and Ifosfamide from 12.52 x 10-5 M (32.7 mu g/ ml) to 8.206 x 10-5 M (21.43 mu g/ml). Flow cytometry analysis demonstrated a significant increase in apoptosis for combination treatments, with apoptosis rates rising from 11.02 % (Oxaliplatin alone) and 16.98 % (Ifosfamide alone) to 24.8 % (Oxaliplatin + E5-siRNA) and 34.9 % (Ifosfamide + E5-siRNA). The sub-G1 cell population increased from 15.7 % (Oxaliplatin alone) and 18 % (Ifosfamide alone) to 21.9 % (Oxaliplatin + E5-siRNA) and 27.1 % (Ifosfamide + E5-siRNA), indicating cell cycle arrest. The colony formation assay revealed a substantial decrease in the number of colonies following combinatio

关键词： Cervical cancer Combination therapy E5 oncoprotein Oxaliplatin Ifosfamide siRNA Gene therapy

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To be or not to be: navigating the influence of MicroRNAs on cervical cancer cell death

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CANCER CELL INTERNATIONAL 2025年第1期25卷 1-23页

作者： Taghizadieh, Mohammad Kalantari, Masoumeh Bakhshali, Roksana Kobravi, Sepehr Khalilollah, Shayan baghi, hossein bannazadeh Bayat, Mobina Nahand, Javid Sadri Akhavan-Sigari, Reza Tabriz Univ Med Sci Fac Med Dept Pathol Tabriz Iran Tehran Univ Hlth Sci Dept Biol Tehran Iran Omid Canc Ctr Ahvaz Iran Islamic Azad Univ Fac Dent Dept Oral & Maxillofacial Surg Tehran Med Sci Branch Tehran Iran Islamic Azad Univ Fac Med Dept Neurosurg Tehran Med Sci Tehran Iran Tabriz Univ Med Sci Infect & Trop Dis Res Ctr Tabriz Iran Univ Med Ctr Tuebingen Dept Neurosurg Tubingen Germany Coll Humanum Warsaw Management Univ Dept Hlth Care Management & Clin Res Warsaw Poland

With all diagnostic and therapeutic advances, such as surgery, radiation- and chemo-therapy, cervical cancer (CC) is still ranked fourth among the most frequent cancers in women globally. New biomarkers and therapeutic targets are warranted to be discovered for the early detection, treatment, and prognosis of CC. As component of the non-coding RNA's family, microRNAs (miRNAs) participate in several cellular functions such as cell proliferation, gene expression, many signaling cascades, apoptosis, angiogenesis, etc. MiRNAs can suppress or induce programmed cell death (PCD) pathways by altering their regulatory genes. Besides, abnormal expression of miRNAs weakens or promotes various signaling pathways associated with PCD, resulting in the development of human diseases such as CC. For that reason, understanding the effects that miRNAs exert on the various modes of tumor PCD, and evaluating the potential of miRNAs to serve as targets for induction of cell death and reappearance of chemotherapy. The current study aims to define the effect that miRNAs exert on cell apoptosis, autophagy, pyroptosis, ferroptosis, and anoikis in cervical cancer to investigate possible targets for cervical cancer therapy. Manipulating the PCD pathways by miRNAs could be considered a primary therapeutic strategy for cervical cancer.

关键词： Cervical cancer MicroRNAs Apoptosis Ferroptosis Pyroptosis Autophagy

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A comprehensive overview on the crosstalk between microRNAs and viral pathogenesis and infection

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MEDICINAL RESEARCH REVIEWS 2025年第2期45卷 349-425页

作者： Mahdavi, Seyedeh Zahra Bahojb Jebelli, Asiyeh Aghbash, Parisa Shiri Baradaran, Behzad Amini, Mohammad Oroojalian, Fatemeh Pouladi, Nasser baghi, hossein bannazadeh de la Guardia, Miguel Mokhtarzadeh, Amir Ali Azarbaijan Shahid Madani Univ Fac Basic Sci Dept Biol Tabriz Iran Tabriz Univ Med Sci Immunol Res Ctr Tabriz Iran Higher Educ Inst Rab Rashid Fac Basic Sci Dept Biol Sci Tabriz Iran Tabriz Univ Med Sci TB & Lung Dis Res Ctr Tabriz Iran North Khorasan Univ Med Sci Sch Med Dept Adv Sci & Technol Med Bojnurd Iran Tabriz Univ Med Sci Fac Med Dept Virol Tabriz Iran Univ Valencia Dept Analyt Chem Valencia Spain

Infections caused by viruses as the smallest infectious agents, pose a major threat to global public health. Viral infections utilize different host mechanisms to facilitate their own propagation and pathogenesis. MicroRNAs (miRNAs), as small noncoding RNA molecules, play important regulatory roles in different diseases, including viral infections. They can promote or inhibit viral infection and have a pro-viral or antiviral role. Also, viral infections can modulate the expression of host miRNAs. Furthermore, viruses from different families evade the host immune response by producing their own miRNAs called viral miRNAs (v-miRNAs). Understanding the replication cycle of viruses and their relation with host miRNAs and v-miRNAs can help to find new treatments against viral infections. In this review, we aim to outline the structure, genome, and replication cycle of various viruses including hepatitis B, hepatitis C, influenza A virus, coronavirus, human immunodeficiency virus, human papillomavirus, herpes simplex virus, Epstein-Barr virus, Dengue virus, Zika virus, and Ebola virus. We also discuss the role of different host miRNAs and v-miRNAs and their role in the pathogenesis of these viral infections.

关键词： coronavirus hepatitis B hepatitis C host miRNAs human immunodeficiency virus human papillomavirus influenza A virus viral miRNAs virus

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MicroRNAs and human viral diseases: A focus on the role of microRNA-29

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BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE 2025年第1期1871卷 167500页

作者： Kesheh, Mina Mobini Bayat, Mobina Kobravi, Sepehr Lotfalizadeh, Mohammad Hassan Heydari, Azhdar Memar, Mohammad Yousef baghi, hossein bannazadeh Kermanshahi, Atefeh Zamani Ravaei, Fatemeh Taghavi, Seyed Pouya Zarepour, Fatemeh Nahand, Javid Sadri Hashemian, Seyed Mohammad Reza Mirzaei, Hamed Iran Univ Med Sci Sch Med Dept Virol Tehran Iran Tabriz Univ Med Sci Infect & Trop Dis Res Ctr Tabriz Iran Tehran Azad Univ Fac Dent Dept Oral & Maxillofacial Surg Tehran Iran North Khorasan Univ Med Sci Sch Dent Bojnurd Iran Kashan Univ Med Sci Physiol Res Ctr Inst Basic Sci Kashan Iran Tabriz Univ Med Sci Fac Med Dept Virol Tabriz Iran Kashan Univ Med Sci Sch Med Kashan Iran Kashan Univ Med Sci Student Res Comm Kashan Iran Shahid Beheshti Univ Med Sci Natl Res Inst TB & Lung Dis NRITLD Chron Resp Dis Res Ctr CRDRC Tehran Iran Kashan Univ Med Sci Res Ctr Biochem & Nutr Metab Dis Inst Basic Sci Kashan Iran Kashan Univ Med Sci Sch Med Dept Physiol & Pharmacol Kashan Iran

The viral replication can impress through cellular miRNAs. Indeed, either the antiviral responses or the viral infection changes through cellular miRNAs resulting in affecting many regulatory signaling pathways. One of the microRNA families that is effective in human cancers, diseases, and viral infections is the miR-29 family. Members of miR-29 family are effective in different viral infections as their roles have appeared in regulation of immunity pathways either in innate immunity including interferon and inflammatory pathways or in adaptive immunity including activation of T-cells and antibodies production. Although miR-29a affects viral replication by suppressing antiviral responses, it can inhibit the expression of viral mRNAs via binding to their 3 ' UTR. In the present work, we discuss the evidence related to miR-29a and viral infection through host immunity regulation. We also review roles of other miR-29 family members by focusing on their role as biomarkers for diagnosing and targets for viral diseases management.

关键词： microRNA miR-29 family members Viral infection Biomarker

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The interaction of human papillomaviruses and adeno-associated viruses in suppressive co-infections

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INFECTION GENETICS AND EVOLUTION 2019年 73卷 66-70页

作者： Hemmat, Nima baghi, hossein bannazadeh Tabriz Univ Med Sci Immunol Res Ctr Tabriz Iran Tabriz Univ Med Sci Infect & Trop Dis Res Ctr Tabriz 516615731 Iran Tabriz Univ Med Sci Drug Appl Res Ctr Tabriz Iran Tabriz Univ Med Sci Fac Med Dept Microbiol Tabriz Iran

Human papillomavirus (HPV) is one of the most common oncogenic viruses which cause malignancy in different epithelial surfaces of the human body and its infection is the main cause of cervical cancer. However, research suggests that this virus might not be the sole cause of infection in target cells. It is believed that, other infectious agents could co-infect the same cell with HPV including;bacteria, viruses, and parasites, which may have different effects on the carcinogenesis of HPV infections. One of the most important viruses is adeno-associated virus (AAV), which comes from the parvoviridae family. The function of this virus is associated with several stages of HPV carcinogenicity, which leads to the suppression of HPV oncogenesis. The inhibition effects of AAV are exerted not only in viral parts but also in cellular parts. This suppression illuminates a new therapeutic approach in the way of HPV-associated cervical cancer. In the present review we consider the exact roles of AAV infection in this suppression.

关键词： Human papillomavirus Adeno-associated virus Cervical cancer Co-infection

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Presepsin: A promising biomarker for the detection of bacterial infections

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BIOMEDICINE & PHARMACOTHERAPY 2019年 111卷 649-656页

作者： Memar, Mohammad Yousef baghi, hossein bannazadeh Tabriz Univ Med Sci Immunol Res Ctr Tabriz Iran Tabriz Univ Med Sci Infect & Trop Dis Res Ctr Tabriz 516615731 Iran Tabriz Univ Med Sci Students Res Comm Tabriz Iran Tabriz Univ Med Sci Dept Microbiol Fac Med Tabriz Iran

Appropriate recognition of bacterial infections in health care setting is the basis for effective treatment and control of infectious diseases. The positivity rate of traditional methods is low and is influenced by quality and quantity of specimens, patient antibiotic administration, severity of infection, and laboratory sufficiency. Currently, there are novel non-culture-based techniques that are being accomplished to improve the identification of infections. Several immunologic biomarkers have been assessed to develop the best indicator of infections. Presepsin is an immunologic biomarker which has been demonstrated as new, emerging, early indicator for the detection of different infections. The biological function of presepsin is not well known. However, it is believed that it may be a regulatory molecule of the adaptive immune system and also a stimulator of monocyte phagocytosis. The early increased levels of presepsin during the sepsis and other bacterial infections have made it an attractive indicator for laboratory testing. Several studies have investigated the capacity of presepsin for use in clinical settings. The aim of the present study was review the clinical application of presepsin in diagnosis and prediction of infections. To achieve this objective, the documents on diagnostic and clinical assessment were evaluated in PubMed and Scopus databases regarding the use of presepsin as indicators of infections.

关键词： Biomarker Diagnosis Infections Presepsin Sepsis

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Impact of equine herpesvirus type 1 (EHV-1) infection on the migration of monocytic cells through equine nasal mucosa

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COMPARATIVE IMMUNOLOGY MICROBIOLOGY AND INFECTIOUS DISEASES 2014年第5-6期37卷 321-329页

作者： baghi, hossein bannazadeh Nauwynck, Hans J. Univ Ghent Fac Vet Med Dept Virol Parasitol & Immunol Virol Lab B-9820 Merelbeke Belgium

The mucosal surfaces are important sites of entry for a majority of pathogens, and viruses in particular. The migration of antigen presenting cells (APCs) from the apical side of the mucosal epithelium to the lymph node is a key event in the development of mucosal immunity during viral infections. However, the mechanism by which viruses utilize the transmigration of these cells to invade the mucosa is largely unexplored. Here, we establish an ex vivo explant model of monocytic cell transmigration across the nasal mucosal epithelium and lamina propria. Equine nasal mucosal CD172a(+) cells (nmCD172a(+) cells), blood-derived monocytes and monocyte-derived DCs (moDCs) were labeled with a fluorescent dye and transferred to the apical part of a polarized mucosal explant. Confocal imaging was used to monitor the migration patterns of monocytic cells and the effect of equine herpesvirus type 1 (EHV-1) on their transmigration. We observed that 16-26% of mock-inoculated nmCD172a(+) cells and moDCs moved into the nasal epithelia, and 1-7% moved further in the lamina propria. The migration of EHV-1 inoculated monocytic cells was not increased in these tissues compared to the mock-inoculated monocytic cells. Immediate early protein positive (IEP+) cells were observed beneath the basement membrane (BM) 48 hours post addition (hpa) of moDCs and nmCD172a(+) cells, but not blood-derived monocytes. Together, our finding demonstrate that monocytic cells may become infected with EHV-1 in the respiratory mucosa and transport the virus from the apical side of the epithelium to the lamina propria en route to the lymph and blood circulation. (C) 2014 Elsevier Ltd. All rights reserved.

关键词： EHV-1 Monocytic cells Migration Nasal mucosa

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Effect of equine herpesvirus type 1 (EHV-1) infection of nasal mucosa epithelial cells on integrin alpha 6 and on different components of the basement membrane

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ARCHIVES OF VIROLOGY 2016年第1期161卷 103-110页

作者： baghi, hossein bannazadeh Nauwynck, Hans J. Tabriz Univ Med Sci Immunol Res Ctr Tabriz Iran Tabriz Univ Med Sci Fac Med Dept Microbiol Tabriz Iran Univ Ghent Dept Virol Parasitol & Immunol Virol Lab Merelbeke Belgium

The respiratory mucosa is the common port of entry of equine herpesvirus type 1 (EHV-1) and several other alphaherpesviruses. An important prerequisite for successful host invasion of the virus is to cross the epithelial cell layer and the underlying basement membrane barrier. In the present study, an analysis was performed to see if an EHV-1 infection of nasal mucosa epithelial cells leads to damage of the underlying extracellular matrix proteins. Nasal mucosa explants were inoculated with EHV-1 and collected at 0, 24 and 48 hours post-inoculation (hpi). Then, double immunofluorescence staining was performed to detect viral-antigen-positive cells on the one hand and integrin alpha 6, laminin, collagen IV and collagen VII on the other hand. The area of these extracellular matrix proteins was measured in regions of interest (ROIs) at a magnification of 200X by means of the software imaging system ImageJ. ROIs were defined beneath uninfected and infected regions. In uninfected regions, 22-28 % of the ROI was stained for integrin alpha 6, 18-37 % for laminin, 14-38 % for collagen IV and 18-26 % for collagen VII. In infected regions, the percentage positive for integrin alpha 6 was significantly decreased to 0.1-9 % and 0.1-6 % after 24 and 48 hours of inoculation, respectively. Infection did not alter the percentages for laminin and collagen IV. For collagen VII, an increase in the percentage (from 18-26 % to 28-39 %) could be observed underneath EHV-1-infected plaques at 48 hours of inoculation. In conclusion, the results revealed a substantial impact of EHV-1 infection on integrin alpha 6 and collagen VII, two important components of the extracellular matrix, which are associated with the basement membrane and may facilitate virus penetration via hijacked leukocytes to underlying tissues.

关键词： EQUINE herpesvirus 1 NASAL mucosa EPITHELIAL cells INTEGRINS CELL membranes EXTRACELLULAR matrix proteins

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Notes on three periods of rabies focus in the Middle East: From progress during the cradle of civilization to neglected current history

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ZOONOSES AND PUBLIC HEALTH 2021年第7期68卷 697-703页

作者： baghi, hossein bannazadeh Rupprecht, Charles E. Tabriz Univ Med Sci Infect & Trop Dis Res Ctr Tabriz 516615731 Iran Tabriz Univ Med Sci Immunol Res Ctr Tabriz Iran Tabriz Univ Med Sci Fac Med Dept Virol Tabriz Iran LYSSA LLC Atlanta GA USA

Rabies is a historical scourge as well as one of the most neglected infectious diseases. While the developed world has rolled back dog-mediated human rabies, thanks to social interventions and modern rabies vaccines, African and Asian countries still struggle with a significant burden due to this viral zoonosis. The Middle East, which includes both Asian and African countries, still has localities in which dog-mediated rabies remains endemic although it is the region that first documented rabies historically. The oldest putative record of this fatal encephalitis may date back at least 4,000 years and is believed to originate from ancient Mesopotamia. In this historical review, we describe rabies through three major time periods (ancient, the Islamic Golden Age and more recent history) of the Middle East. Inarguably, the Middle East experienced great medical development during the Islamic Golden Age. Proof of early rabies prevention, control and proposed treatment strategies existed which we only perceive anew via modern science. Such rabies strategies were neglected severely due in no small part to the influence of Middle Eastern rulers, who steered scholars away from this field to a broader toxicological focus, because they feared assassination from poisoning. Such setbacks are coupled with constant social and political unrest and continuous wars in the Middle East to modern times. This situation leads to an inconstancy in rabies surveillance and reporting of data, neglect of prevention and control strategies, and subsequently a devolvement of rabies management strategies in this unstable region of the world.

关键词： epidemiology history middle east rabies

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