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Article ; Online: The impact of hypoxia on tumor-mediated bypassing anti-PD-(L)1 therapy.

Mortezaee, Keywan / Majidpoor, Jamal / Kharazinejad, Ebrahim

Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie

2023 Volume 162, Page(s) 114646

Abstract: Extending the durability of response is the current focus in cancer immunotherapy with immune checkpoint inhibitors (ICIs). However, factors like non-immunogenic tumor microenvironment (TME) along with aberrant angiogenesis and dysregulated metabolic ... ...

Abstract	Extending the durability of response is the current focus in cancer immunotherapy with immune checkpoint inhibitors (ICIs). However, factors like non-immunogenic tumor microenvironment (TME) along with aberrant angiogenesis and dysregulated metabolic systems are negative contributors. Hypoxia is a key TME condition and a critical promoter of tumor hallmarks. It acts on immune and non-immune cells within TME in order for promoting immune evasion and therapy resistance. Extreme hypoxia is a major promoter of resistance to the programmed death-1 (PD-1)/programmed death-ligand 1 (PD-L1) inhibitor therapy. Hypoxia inducible factor-1 (HIF-1) acts as a key mediator of hypoxia and a critical promoter of resistance to the anti-PD-(L)1. Targeting hypoxia or HIF-1 can thus be an effective strategy for reinvigoration of cellular immunity against cancer. Among various strategies presented so far, the key focus is over vascular normalization, which is an approach highly effective for reducing the rate of hypoxia, increasing drug delivery into the tumor area, and boosting the efficacy of anti-PD-(L)1.
MeSH term(s)	Humans ; Neoplasms/metabolism ; Hypoxia ; Immunotherapy ; Tumor Microenvironment
Language	English
Publishing date	2023-04-01
Publishing country	France
Document type	Journal Article ; Review
ZDB-ID	392415-4
ISSN	1950-6007 ; 0753-3322 ; 0300-0893
ISSN (online)	1950-6007
ISSN	0753-3322 ; 0300-0893
DOI	10.1016/j.biopha.2023.114646
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Article: Circulating afamin positively correlated with the miR-122 expression and type 2 diabetes mellitus-related phenotype according to the duration of diabetes.

Mokhtari Ardekani, Abnoos / Kharazinejad, Ebrahim / Ghasemi, Ehsan / Ghasemi, Hassan / Soltani, Rahmatollah

Heliyon

2024 Volume 10, Issue 7, Page(s) e28053

Abstract: Background: Afamin is a hepatokine that involves in glucose and lipids metabolism. miR-122 is mainly expressed in liver and involves in lipid and carbohydrate metabolism. This study aimed at investigating the circulating afamin, its correlation with ... ...

Abstract	Background: Afamin is a hepatokine that involves in glucose and lipids metabolism. miR-122 is mainly expressed in liver and involves in lipid and carbohydrate metabolism. This study aimed at investigating the circulating afamin, its correlation with type 2 diabetes mellitus (T2DM) and miR-122 gene expression in T2DM patients and healthy control subjects according to the duration of diabetes. Methods: This case-control study included 220 participants, with 100 individuals serving as controls and 120 individuals diagnosed with type 2 diabetes mellitus (T2DM). The miR-122 gene expression was assessed using real-time PCR. The serum concentration of biochemical parameters such as glucose levels, lipid profile, and small-dense low-density lipoprotein (sdLDL) were measured using colorimetric kits. Circulating afamin and insulin levels were assayed using an ELISA kit. Glycated hemoglobin (HbA1c) was measured using capillary electrophoresis. Results: Circulating afamin level was significantly higher in T2DM patients compared to the control group, (73.8 ± 10.8 vs. 65.9 ± 8.7, respectively; P < 0.001). Similarly, miR122 expression was significantly increased in T2DM patients compared to healthy control subjects (4.24 ± 2.01 vs. 1.00 ± 0.85, respectively; P < 0.001). Among patients diagnosed with T2DM, those with longstanding diabetes (>5 years) exhibited significantly higher levels of circulating afamin and miR-122 expression compared to individuals with a shorter duration of diabetes (≤5 years) (P < 0.05). Circulating afamin levels were significantly correlated with waist circumference, small-dense low-density lipoprotein (sdLDL), fasting blood sugar (FBS), insulin, resistance to insulin, and miR-122 expression, depending on the duration of the disease (P < 0.05). Furthermore, the performance of afamin as a diagnostic marker for T2DM was confirmed through receiver operating characteristic (ROC) analysis, yielding an area under the curve (AUC) of 0.7 (P < 0.001). Conclusions: Circulating afamin involved in the T2DM-related complications and its concentration is positively correlated to the miR-122 expression, especially in patient with longstanding diabetes.
Language	English
Publishing date	2024-03-20
Publishing country	England
Document type	Journal Article
ZDB-ID	2835763-2
ISSN	2405-8440
ISSN	2405-8440
DOI	10.1016/j.heliyon.2024.e28053
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Article ; Online: Epithelial-mesenchymal transition in cancer stemness and heterogeneity: updated.

Mortezaee, Keywan / Majidpoor, Jamal / Kharazinejad, Ebrahim

Medical oncology (Northwood, London, England)

2022 Volume 39, Issue 12, Page(s) 193

Abstract: Epithelial-mesenchymal transition (EMT) as a trans-differentiation program and a key process in tumor progression is linked positively with increased expansion of cancer stem cells and cells with stem-like properties. This is mediated through modulation ... ...

Abstract	Epithelial-mesenchymal transition (EMT) as a trans-differentiation program and a key process in tumor progression is linked positively with increased expansion of cancer stem cells and cells with stem-like properties. This is mediated through modulation of critical tumorigenic events and is positively correlated with hypoxic conditions in tumor microenvironment. The presence of cells eliciting diverse phenotypical states inside tumor is representative of heterogeneity and higher tumor resistance to therapy. In this review, we aimed to discuss about the current understanding toward EMT, stemness, and heterogeneity in tumors of solid organs, their contribution to the key tumorigenic events along with major signaling pathway involved, and, finally, to suggest some strategies to target these critical events.
MeSH term(s)	Carcinogenesis/pathology ; Epithelial-Mesenchymal Transition ; Humans ; Neoplasms/therapy ; Neoplastic Stem Cells/pathology ; Tumor Microenvironment
Language	English
Publishing date	2022-09-07
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	1201189-7
ISSN	1559-131X ; 0736-0118 ; 1357-0560
ISSN (online)	1559-131X
ISSN	0736-0118 ; 1357-0560
DOI	10.1007/s12032-022-01801-0
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Article ; Online: Liquid biopsy in ovarian cancer: advantages and limitations for prognosis and diagnosis.

Karimi, Farzaneh / Azadbakht, Omid / Veisi, Ali / Sabaghan, Mohammad / Owjfard, Maryam / Kharazinejad, Ebrahim / Dinarvand, Negar

Medical oncology (Northwood, London, England)

2023 Volume 40, Issue 9, Page(s) 265

Abstract: Ovarian cancer (OC) is a highly fatal gynecologic malignancy, often diagnosed at an advanced stage which presents significant challenges for disease management. The clinical application of conventional tissue biopsy methods and serological biomarkers has ...

Abstract	Ovarian cancer (OC) is a highly fatal gynecologic malignancy, often diagnosed at an advanced stage which presents significant challenges for disease management. The clinical application of conventional tissue biopsy methods and serological biomarkers has limitations for the diagnosis and prognosis of OC patients. Liquid biopsy is a novel sampling method that involves analyzing distinctive tumor elements secreted into the peripheral blood. Growing evidence suggests that liquid biopsy methods such as circulating tumor cells, cell-free RNA, circulating tumor DNA, exosomes, and tumor-educated platelets may improve early prognosis and diagnosis of OC, leading to enhanced therapeutic management of the disease. This study reviewed the evidence demonstrating the utility of liquid biopsy components in OC prognosis and diagnosis, and evaluated the current advantages and limitations of these methods. Additionally, the existing obstacles and crucial topics for future studies utilizing liquid biopsy in OC patients were discussed.
MeSH term(s)	Humans ; Female ; Prognosis ; Ovarian Neoplasms/pathology ; Liquid Biopsy/methods ; Exosomes/pathology ; DNA, Neoplasm ; Biomarkers, Tumor/genetics ; Neoplastic Cells, Circulating/pathology
Chemical Substances	DNA, Neoplasm ; Biomarkers, Tumor
Language	English
Publishing date	2023-08-10
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	1201189-7
ISSN	1559-131X ; 0736-0118 ; 1357-0560
ISSN (online)	1559-131X
ISSN	0736-0118 ; 1357-0560
DOI	10.1007/s12032-023-02128-0
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Article ; Online: Diabetes and ovarian cancer: risk factors, molecular mechanisms and impact on prognosis.

Karimi, Farzaneh / Dinarvand, Negar / Sabaghan, Mohammad / Azadbakht, Omid / Ataee, Shima / Kharazinejad, Ebrahim / Moazamfard, Mostafa

Endocrine

2023 Volume 83, Issue 1, Page(s) 1–9

Abstract: Background and aim: Diabetes mellitus has been linked to a lower rate of cancer survival and an increase in the incidence of most malignancies. Investigations showed that diabetes might affect ovarian cancer (OC) prognosis and survival. Based on the ... ...

Abstract	Background and aim: Diabetes mellitus has been linked to a lower rate of cancer survival and an increase in the incidence of most malignancies. Investigations showed that diabetes might affect ovarian cancer (OC) prognosis and survival. Based on the current information, this study intends to review the risk factors, molecular pathways, and impact of diabetes on OC. Methods: The data was derived from online databases, including Web of Science, PubMed, and Scopus. The inclusion criteria were original studies, which included the risk factors, molecular mechanisms, and impact of diabetes on OC. The effect of different antidiabetic drugs was also discussed in this manuscript. All of the clinical, in vivo, and in vitro studies were included in the present study. Results: The diagnosis of diabetes mellitus negatively affects the survival and prognosis in OC cases. The epidemiologic data shows that the risk of OC increases in patients with diabetes mellitus compared to the healthy population. Insulin-like growth factors family was raised in diabetic patients, which target several mechanisms, including targeting oxidative stress, angiogenesis, and tumor markers. Antidiabetic drugs such as metformin, sitagliptin, and rosiglitazone have a promising effect on elongation of survival and enhancement of prognosis in OC patients. Conclusions: Diabetes mellitus is a significant risk factor for OC in women, and it negatively impacts survival and prognosis. Molecular mechanisms such as IGF family, oxidative stress, and inflammatory cytokines have been identified to explain this relationship. Antidiabetic drugs like metformin, sitagliptin, and rosiglitazone have shown promise in improving survival and prognosis of OC patients.
MeSH term(s)	Humans ; Female ; Rosiglitazone ; Diabetes Mellitus/epidemiology ; Hypoglycemic Agents/therapeutic use ; Risk Factors ; Metformin/therapeutic use ; Ovarian Neoplasms/epidemiology ; Prognosis ; Sitagliptin Phosphate
Chemical Substances	Rosiglitazone (05V02F2KDG) ; Hypoglycemic Agents ; Metformin (9100L32L2N) ; Sitagliptin Phosphate (TS63EW8X6F)
Language	English
Publishing date	2023-08-08
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	1194484-5
ISSN	1559-0100 ; 1355-008X ; 0969-711X
ISSN (online)	1559-0100
ISSN	1355-008X ; 0969-711X
DOI	10.1007/s12020-023-03477-6
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Article: How COVID-19 affects the use of evidence informed policymaking among iranian health policymakers and managers.

Bastani, Peivand / Bahmaei, Jamshid / Kharazinejad, Ebrahim / Samadbeik, Mahnaz / Liang, Zhanming / Schneider, Carmen Huckel

Archives of public health = Archives belges de sante publique

2022 Volume 80, Issue 1, Page(s) 16

Abstract: Background: The COVID-19 pandemic increased the need for new valid scientific evidence to support urgent clinical and policy decision making; as well as improved processes for the rapid synthesis, uptake and application of that evidence. Evidence ... ...

Abstract	Background: The COVID-19 pandemic increased the need for new valid scientific evidence to support urgent clinical and policy decision making; as well as improved processes for the rapid synthesis, uptake and application of that evidence. Evidence informed policymaking (EIPM) can be considered as a way to access and use the results of evidence in practice. This study aimed to determine what effects COVID-19 had on the way Iranian health managers and policymakers use evidence in their decisions. Methods: This study was conducted in 2021 applying a qualitative research design. Data was collected through semi-structured interviews. Thirty health care managers, policy makers and medical university faculty members were recruited as the study participants, initially via a purposive sample, followed by snowballing. A conventional content analysis presented by Hsieh and Shannon (2005) was applied for data analysis. Results: Ten main themes emerged from the data including: 1) roles and duties of knowledge brokers (KBs); 2-5) the roles, benefits, barriers and necessities of applying Knowledge Translation Exchange (KTE) tools; 6-8) the facilitators, benefits and barriers to the application of evidence during COVID-19; 9) challenges of rapid evidence production evidence during COVID-19 and 10) consequences of not applying evidence during COVID-19. According to the present conceptual framework, KBs act as an intermediator between the large amounts of knowledge produced and decision makers. KTE tools should be applied to enhance EIPM during COVID-19. Attention should be paid to the facilitators, barriers, benefits and necessities of evidence application during COVID-19 to avoid negative consequences for the health system. Conclusions: Results of this study show that developing KTE tools and activating KBs can be among the main strategies to produce applied actionable messages for policymakers to move toward EIPM; and that this applies even when rapid decision making is required, such as during the COVID-19 pandemic. It is strongly recommended to reinforce the local capacities through supporting scientific networks and relationships between research centers and local and national policymakers. At the same time, attention to local barriers to and facilitators of the application of evidence while facing a pandemic can pave the way to better identification of health system`s problems and rapid responses.
Language	English
Publishing date	2022-01-05
Publishing country	England
Document type	Journal Article
ZDB-ID	1117688-x
ISSN	2049-3258 ; 0778-7367 ; 0003-9578
ISSN (online)	2049-3258
ISSN	0778-7367 ; 0003-9578
DOI	10.1186/s13690-021-00757-3
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Article ; Online: Effects of kisspeptin on the maturation of human ovarian primordial follicles

Rezaei-Tazangi, Fatemeh / Kooshesh, Leila / Tayyebiazar, Ali / Taghizabet, Neda / Tavakoli, Anahita / Hassanpour, Ashraf / Aliakbari, Fereshteh / Kharazinejad, Ebrahim / Sharifi, Ali-Mohammad

Zygote (Cambridge, England)

2023 Volume 32, Issue 1, Page(s) 66–70

Abstract: At this time, with advances in medical science, many cancers and chronic diseases are treatable, but one of their side effects is infertility. Some women also want to delay pregnancy for personal reasons. There has been some evidence that kisspeptin ... ...

Abstract	At this time, with advances in medical science, many cancers and chronic diseases are treatable, but one of their side effects is infertility. Some women also want to delay pregnancy for personal reasons. There has been some evidence that kisspeptin activates broad signals by binding to its receptor, suggesting that the role of kisspeptin in direct control of ovarian function includes follicle growth and steroid production. In this study, the effect of kisspeptin on improving the quality and results for human ovarian follicles was investigated. A section of ovary was removed laparoscopically from women between 20 and 35 years of age (
MeSH term(s)	Pregnancy ; Humans ; Female ; Ovary ; Kisspeptins/genetics ; Kisspeptins/pharmacology ; Kisspeptins/metabolism ; Ovarian Follicle/physiology
Chemical Substances	Kisspeptins
Language	English
Publishing date	2023-12-15
Publishing country	England
Document type	Journal Article
ZDB-ID	1166294-3
ISSN	1469-8730 ; 0967-1994
ISSN (online)	1469-8730
ISSN	0967-1994
DOI	10.1017/S0967199423000527
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Article ; Online: The Comparative Effects of Schwann Cells and Wharton's Jelly Mesenchymal Stem Cells on the AIM2 Inflammasome Activity in an Experimental Model of Spinal Cord Injury.

Kharazinejad, Ebrahim / Hassanzadeh, Gholamreza / Sahebkar, Amirhossein / Yousefi, Behpour / Reza Sameni, Hamid / Majidpoor, Jamal / Golchini, Ehsan / Taghdiri Nooshabadi, Vajihe / Mousavi, Mahboubeh

Neuroscience

2023 Volume 535, Page(s) 1–12

Abstract: Inflammasome activation and the consequent release of pro-inflammatory cytokines play a crucial role in the development of sensory/motor deficits following spinal cord injury (SCI). Immunomodulatory activities are exhibited by Schwann cells (SCs) and ... ...

Abstract	Inflammasome activation and the consequent release of pro-inflammatory cytokines play a crucial role in the development of sensory/motor deficits following spinal cord injury (SCI). Immunomodulatory activities are exhibited by Schwann cells (SCs) and Wharton's jelly mesenchymal stem cells (WJ-MSCs). In this study, we aimed to compare the effectiveness of these two cell sources in modulating the absent in melanoma 2 (AIM2) inflammasome complex in rats with SCI. The Basso, Beattie, Bresnahan (BBB) test, Nissl staining, and Luxol fast blue (LFB) staining were performed to evaluate locomotor function, neuronal survival, and myelination, respectively. Real-time polymerase chain reaction (RT-PCR), Western blotting, and enzyme-linked immunosorbent assay (ELISA) were employed to analyze the gene and protein expressions of inflammasome components, including AIM2, ASC, caspase-1, interleukin-1β (IL-1β), and IL-18. Both gene and protein expressions of all evaluated factors were decreased after SC or WJ-MSC treatment, with a more pronounced effect observed in the SCs group (P < 0.05). Additionally, SCs promoted neuronal survival and myelination. Moreover, the administration of 3 × 10
MeSH term(s)	Animals ; Rats ; Cell Differentiation ; Cells, Cultured ; DNA-Binding Proteins/metabolism ; Inflammasomes/metabolism ; Melanoma/metabolism ; Mesenchymal Stem Cells ; Models, Theoretical ; Schwann Cells/metabolism ; Spinal Cord Injuries/metabolism ; Wharton Jelly/metabolism
Chemical Substances	AIM2 protein, rat ; DNA-Binding Proteins ; Inflammasomes
Language	English
Publishing date	2023-10-27
Publishing country	United States
Document type	Comparative Study ; Journal Article
ZDB-ID	196739-3
ISSN	1873-7544 ; 0306-4522
ISSN (online)	1873-7544
ISSN	0306-4522
DOI	10.1016/j.neuroscience.2023.10.011
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Article ; Online: Pathological Mechanisms Induced by TRPM2 Ion Channels Activation in Renal Ischemia-Reperfusion Injury

Khanahmad, Hossein / Mirbod, Seyedeh Mahnaz / karimi, Farzaneh / Kharazinejad, Ebrahim / Owjfard, Maryam / Najaflu, Malihe / Tavangar, Mehrsa

Mol Biol Rep. 2022 Nov., v. 49, no. 11 p.11071-11079

2022

Abstract: Renal ischemia-reperfusion (IR) injury triggers a cascade of signaling reactions involving an increase in Ca² ⁺ charge and reactive oxygen species (ROS) levels resulting in necrosis, inflammation, apoptosis, and subsequently acute kidney injury (AKI) ... ...

Abstract	Renal ischemia-reperfusion (IR) injury triggers a cascade of signaling reactions involving an increase in Ca² ⁺ charge and reactive oxygen species (ROS) levels resulting in necrosis, inflammation, apoptosis, and subsequently acute kidney injury (AKI).Transient receptor potential (TRP) channels include an essential class of Ca²⁺ permeable cation channels, which are segregated into six main channels: the canonical channel (TRPC), the vanilloid-related channel (TRPV), the melastatin-related channel (TRPM), the ankyrin-related channel (TRPA), the mucolipin-related channel (TRPML) and polycystin-related channel (TRPP) or polycystic kidney disease protein (PKD2). TRP channels are involved in adjusting vascular tone, vascular permeability, cell volume, proliferation, secretion, angiogenesis and apoptosis.TRPM channels include eight isoforms (TRPM1–TRPM8) and TRPM2 is the second member of this subfamily that has been expressed in various tissues and organs such as the brain, heart, kidney and lung. Renal TRPM2 channels have an important role in renal IR damage. So that TRPM2 deficient mice are resistant to renal IR injury. TRPM2 channels are triggered by several chemicals including hydrogen peroxide, Ca²⁺, and cyclic adenosine diphosphate (ADP) ribose (cADPR) that are generated during AKI caused by IR injury, as well as being implicated in cell death caused by oxidative stress, inflammation, and apoptosis.
Keywords	acute kidney injury ; adenosine diphosphate ; angiogenesis ; apoptosis ; brain ; calcium ; cations ; heart ; hydrogen peroxide ; inflammation ; kidneys ; lungs ; necrosis ; oxidative stress ; permeability ; polycystic kidney diseases ; ribose ; secretion
Language	English
Dates of publication	2022-11
Size	p. 11071-11079.
Publishing place	Springer Netherlands
Document type	Article ; Online
Note	Review
ZDB-ID	186544-4
ISSN	1573-4978 ; 0301-4851
ISSN (online)	1573-4978
ISSN	0301-4851
DOI	10.1007/s11033-022-07836-w
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: A review of methods for preserving male fertility.

Aliakbari, Fereshteh / Taghizabet, Neda / Azizi, Faezeh / Rezaei-Tazangi, Fatemeh / Samadee Gelehkolaee, Keshvar / Kharazinejad, Ebrahim

Zygote (Cambridge, England)

2021 Volume 30, Issue 3, Page(s) 289–297

Abstract: Male infertility is responsible for 50% of men's health problems and has always been a concern for personal and social issues. A survey of global statistics suggests an increase in infertility rate as one of the critical issues documented in studies. ... ...

Abstract	Male infertility is responsible for 50% of men's health problems and has always been a concern for personal and social issues. A survey of global statistics suggests an increase in infertility rate as one of the critical issues documented in studies. There are different ways of maintaining fertility in men, depending on their age. In this paper, we review the preservation methods used for fertility treatment in Iran and other countries. Available data were reviewed from Google Scholar, PubMed, Scopus, Web of Science, IranMedex, MEDLIB, IranDoc and Scientific Information Database and searched for articles published up to 2018, using the medical subject heading (MeSH) terms for cryopreservation, sperm, testicular, spermatogonia stem cell, male infertility and/or Iranian and in the world, to provide evidence from evaluation of fertility preservation the methods. Based the search strategy, 274 manuscripts were found. After reviewing the titles, abstracts and manuscripts in their entirety, 119 articles were obtained and selected according to the eligibility criteria. The 85 studies mentioned above were divided into three categories (sperm, testis, and spermatogonia stem cells (SSCs)), and methods of fertility preservation were investigated. Ways to maintain male fertility were different depending on age, and included sperm, testicular, and SSC freezing. The number of studies on testicular tissue and SSCs was low for human samples, and more studies are still needed. Sperm freezing at infertility centres is the top for male fertility preservation.
MeSH term(s)	Cryopreservation/methods ; Fertility Preservation/methods ; Humans ; Infertility, Male/therapy ; Iran ; Male ; Spermatogonia ; Testis
Language	English
Publishing date	2021-10-22
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	1166294-3
ISSN	1469-8730 ; 0967-1994
ISSN (online)	1469-8730
ISSN	0967-1994
DOI	10.1017/S0967199421000071
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