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Öğe Application of Next-Generation Sequencing in Neurodegenerative Diseases: Opportunities and Challenges(Humana Press Inc, 2020) Shademan, Behrouz; Biray Avci, Cigir; Nikanfar, Masoud; Nourazarian, AlirezaGenetic factors (gene mutations) lead to various rare and prevalent neurological diseases. Identification of underlying mutations in neurodegenerative diseases is of paramount importance due to the heterogeneous nature of the genome and different clinical manifestations. An early and accurate molecular diagnosis are cardinal for neurodegenerative patients to undergo proper therapeutic regimens. the next-generation sequencing (NGS) method examines up to millions of sequences at a time. As a result, the rare molecular diagnoses, previously presented with "unknown causes", are now possible in a short time. This method generates a large amount of data that can be utilized in patient management. Since each person has a unique genome, the NGS has transformed diagnostic and therapeutic strategies into sequencing and individual genomic mapping. However, this method has disadvantages like other diagnostic methods. Therefore, in this review, we aimed to briefly summarize the NGS method and correlated studies to unravel the genetic causes of neurodegenerative diseases including Alzheimer's disease, Parkinson's disease, epilepsy, and MS. Finally, we discuss the NGS challenges and opportunities in neurodegenerative diseases.Öğe CAR T Cells: Cancer Cell Surface Receptors Are the Target for Cancer Therapy(Tabriz Univ Medical Sciences & Health Services, 2022) Shademan, Behrouz; Karamad, Vahidreza; Nourazarian, Alireza; Avci, Cigir BirayImmunotherapy has become a prominent strategy for the treatment of cancer. A method that improves the immune system's ability to attack a tumor (Enhances antigen binding). Targeted killing of malignant cells by adoptive transfer of chimeric antigen receptor (CAR) T cells is a promising immunotherapy technique in the treatment of cancers. For this purpose, the patient's immune cells, with genetic engineering aid, are loaded with chimeric receptors that have particular antigen binding and activate cytotoxic T lymphocytes. That increases the effectiveness of immune cells and destroying cancer cells. This review discusses the basic structure and function of CAR-T cells and how antigenic targets are identified to treat different cancers and address the disadvantages of this treatment for cancer.Öğe Comparison between cerebrospinal fluid and serum levels of myelin-associated glycoprotein, total antioxidant capacity, and 8-hydroxy-2 '-deoxyguanosine in patients with multiple sclerosis(Elsevier, 2021) Khajenobar, Negin Bodaghi; Mahboob, Soltanali; Nourazarian, Alireza; Shademan, Behrouz; Laghousi, Delara; Moayed, Zohre Bagheri; Nikanfar, MasoudBackground: Multiple sclerosis (MS) is a chronic inflammatory disease characterized by demyelinated lesions in the brain, the spinal cord, and the optic nerve. It is one of the most common neurological disorders. in this study, serum and cerebrospinal fluid (CSF) levels of total antioxidant capacity (TAC), myelin-associated glycopmtein (MAG), and 8-hydroxy-2'-deoxyguanosine (8-OHdG) were investigated to determine their effects on MS. Materials and method: in this study, 25 serum and cerebrospinal samples from MS patients as a case group and 40 serum and CSF samples from healthy participants as a control group were collected and analyzed. Concentrations of TAC, MAG, and 8-OhdG were determined in the samples using a dedicated kit and relayed using the ELISA device. Results: The mean serum antibody levels of MAG and TAC were higher in the case group than the control group, although the difference in the MAG level was not significant (P > 0.05). However, the mean serum level of -8 OHdG was lower in the case group than the control group. Moreover, the mean levels of the evaluated biomarkers in the CSF samples were higher in the case group than in the control group. Still, the difference was only significant in terms of TAC levels (P < 0.05). Receiver operating characteristics curve analysis showed that the area under the curve was 0.71 and 0.69 for 8-OhdG and TAC serum levels, respectively, and 0.73 for both TAC and CSF levels, which was not significantly different from that in other biomarkers. Conclusion: Elevated TAC levels in serum and CSF samples and 8-OhdG in serum samples may be associated with MS pathogenesis. However, further investigation is needed to consider these cases as a follow-up to the therapeutic goals or treatment process.Öğe CRISPR Technology in Cancer Diagnosis and Treatment: Opportunities and Challenges(Springer/Plenum Publishers, 2022) Shademan, Behrouz; Masjedi, Sepideh; Karamad, Vahidreza; Isazadeh, Alireza; Sogutlu, Fatma; Rad, Mohammad Hosein Saeedi; Nourazarian, AlirezaA novel gene editing tool, the Cas system, associated with the CRISPR system, is emerging as a potential method for genome modification. This simple method, based on the adaptive immune defense system of prokaryotes, has been developed and used in human cancer research. These technologies have tremendous therapeutic potential, especially in gene therapy, where a patient-specific mutation is genetically corrected to cure diseases that cannot be cured with conventional treatments. However, translating CRISPR/Cas9 into the clinic will be challenging, as we still need to improve the efficiency, specificity, and application of the technology. In this review, we will explain how CRISPR-Cas9 technology can treat cancer at the molecular level, focusing on ordination and the epigenome. We will also focus on the promise and shortcomings of this system to ensure its application in the treatment and prevention of cancer.Öğe CRISPR Technology in Gene-Editing-Based Detection and Treatment of SARS-CoV-2(Frontiers Media Sa, 2022) Shademan, Behrouz; Nourazarian, Alireza; Hajazimian, Saba; Isazadeh, Alireza; Biray Avci, Cigir; Oskouee, Mahin AhangarOutbreak and rapid spread of coronavirus disease (COVID-19) caused by coronavirus acute respiratory syndrome (SARS-CoV-2) caused severe acute respiratory syndrome (SARS-CoV-2) that started in Wuhan, and has become a global problem because of the high rate of human-to-human transmission and severe respiratory infections. Because of high prevalence of SARS-CoV-2, which threatens many people worldwide, rapid diagnosis and simple treatment are needed. Genome editing is a nucleic acid-based approach to altering the genome by artificially changes in genetic information and induce irreversible changes in the function of target gene. Clustered, regularly interspaced short palindromic repeats (CRISPR/Cas) could be a practical and straightforward approach to this disease. CRISPR/Cas system contains Cas protein, which is controlled by a small RNA molecule to create a double-stranded DNA gap. Evidence suggested that CRISPR/Cas was also usable for diagnosis and treatment of SARS-CoV-2 infection. In this review study, we discoursed on application of CRISPR technology in detection and treatment of SARS-CoV-2 infection. Another aspect of this study was to introduce potential future problems in use of CRISPR/Cas technology.Öğe Diagnostic Potential of Autophagy-5 Protein, Apolipoprotein B-48, and Oxidative Stress Markers in Serum of Patients with Early-Stage Ischemic Stroke(Elsevier Science Inc, 2022) Ajoolabady, Amir; Shademan, Behrouz; Avci, Cigir Biray; Nikanfar, Masoud; Nourazarian, Alireza; Laghousi, Delara-OBJECTIVE: Strokes are among the leading causes of death worldwide and have different characteristics. Different physiopathological mechanisms characterize the -umerous subtypes of ischemic stroke (IS). In this study, we investigated the relationship between serum levels of autophagy-5 protein, apolipoprotein B-48, and oxidative stress markers in patients with ischemic stroke.-METHODS: For this study, 100 participants were recruited, of which 50 were patients with IS and 50 were healthy individuals. We conducted a case-control study at Imam Reza Hospital from March 2019 to April 2020. Serum levels of ATG5, apo B-48, and oxidative stress markers were determined in both groups. Our Receiver Operating Characteristic Analysis evaluated the additional diagnostic value of these factors in both groups. -RESULTS: Diabetes, smoking, age, sex, alcohol con-sumption, weight, and height did not differ significantly between the 2 groups (P > 0.05). However, the 2 groups had significant differences in hypertension and body mass in-dex (P < 0.05). Fifty-four percent (27 patients) of patients with IS had an ischemic stroke in large vessels, while 46% (23 patients) had an ischemic stroke in small vessels. Serum levels of ATG5, apo B-48, and oxidative stress markers were higher in the case group than in the control group (P< 0.0001).-CONCLUSIONS: In patients with IS, serum levels of ATG5, apoB-48, malonaldehyde, total oxidative stress, and total antioxidant capacity can be used as novel biomarkers to predict or treat the disease.Öğe Diagnostic Value of ATG5, Apo-Lipoprotein B-48, Thyroid Hormones, and Homocysteine in Patients with Alzheimer's Disease(Clin Lab Publ, 2023) Hoseinlar, Seyedeh Fatemeh; Nikanfar, Masoud; Laghousi, Delara; Darabi, Masoud; Shademan, Behrouz; Nourazarian, AlirezaBackground: Alzheimer's disease (AD) is the most common form of dementia. In this study, serum levels of autophagy-related 5 (ATG5), apolipoprotein B-48, thyroid hormones, and homocysteine were examined in patients with AD to determine their diagnostic and predictive value for early diagnosis and prevention of AD.Materials: For this study, fifty serum samples were obtained from patients with AD and fifty serum samples from healthy controls. Serum levels of ATG 5, apo B48, thyroid hormones, homocysteine, vitamin B12, and folic acid were determined by ELISA. Spectrophotometry was used to determine serum lipid concentrations.Results: The mean age of the case group was 69 +/- 6.4 years and that of the control group was 67 +/- 4.2 years. There were differences between the control and case groups in serum levels of homocysteine, apo B48, ATG5, hsCRP, LDL, HDL, cholesterol, and VitB12 (p < 0.05). According to the results of the ROC curve, measurements of serum levels of ATG5, homocysteine, and apo B48 have excellent performance in distinguishing patients with Alzheimer's disease from patients without AD.Conclusions: This study suggests that the measurement of serum levels of ATG5, homocysteine, and apo B48, along with other available biomarkers, can be helpful in the diagnosis and management of patients with AD in the early stages of their disease. (Clin. Lab. 2023;69:xx-xx. DOI: 10.7754/Clin.Lab.2022.220614)Öğe Effect of valproic acid on miRNAs affecting histone deacetylase in a model of anaplastic thyroid cancer(Springer, 2021) Gunel, Nur Selvi; Birden, Nihal; Kurt, Cansu Caliskan; Bagca, Bakiye Goker; Shademan, Behrouz; Sogutlu, Fatma; Ozates, Neslihan PinarBackground Thyroid cancer is the most common malignant tumor of the endocrine system seen in the thyroid gland. More than 90% of thyroid cancers comprise papillary thyroid cancer (PTC) and follicular thyroid cancer (FTC). Although anaplastic thyroid carcinoma (ATC) accounts for less than 2% of thyroid cancer. But patients' lifespan after diagnosis is about 6 months. Surgical interventions, radioactive iodine use, and chemotherapy are not sufficient in the treatment of ATC, so alternative therapies are needed. Methods and results The WST-1 assay test was performed to evaluate the anti-proliferative effects of Valproic acid (VPA). Also, the effect of VPA on miRNAs affecting histone deacetylase was determined by Quantitative RT-PCR. In the SW1736 cell line, IC50 dose for VPA was found 1.6 mg/ml. In our study, the level of oncogenic genes expression in cells treated with VPA, including miR-184, miR-222-5p, miR-124-3p, and miR-328-3p, decreased. Also, the expression of tumor inhibitory genes including miR-323-5p, miR-182-5p, miR-138-5p, miR-217, miR-15a-5p, miR-29b-3p, miR-324-5p and miR-101-5p increased significantly. Conclusions VPA can ad-just countless gene expression patterns, including microRNAs (miRNAs), by targeting histone deacetylase (HDAC). However, further studies are required for more accurate results.Öğe Effects of metformin and pioglitazone combination on apoptosis and AMPK/mTOR signaling pathway in human anaplastic thyroid cancer cells(Wiley, 2020) Kutbay, Nilufer Ozdemir; Avci, Cigir Biray; Yurekli, Banu Sarer; Kurt, Cansu Caliskan; Shademan, Behrouz; Gunduz, Cumhur; Erdogan, MehmetAnaplastic cancer constitutes 1% of thyroid cancers, and it is one of the most aggressive cancers. Treatment options are external radiation therapy and/or chemotherapy. the success rate with these treatment modalities is not satisfactory. We aimed to evaluate the effects of metformin (MET) and pioglitazone (PIO) combination on apoptosis and AMP-activated protein kinase/mammalian target of rapamycin (mTOR) signaling pathway in human anaplastic thyroid cancer cells. in this study, we evaluated the effects of MET and PIO individually and the combination of the two drugs on the cellular lines SW1736 and C643 ATC. Genes contained in the mTOR signaling pathway were examined using human mTOR Signalization RT(2)Profiler PCR Array. in C643 and SW1736 cell lines, IC(50)doses of MET and PIO were found out as 17.69 mM, 11.64 mM, 27.12 mu M, and 23.17 mu M. Also, the combination of MET and PIO was determined as an additive according to isobologram analyses. We have found the downregulation of the expression levels of oncogenic genes:AKT3, CHUK, CDC42, EIF4E, HIF1A, IKBKB, ILK, MTOR, PIK3CA, PIK3CG, PLD1, PRKCA, andRICTORgenes, in the MET and PIO combination-treated cells. in addition, expression levels of tumor suppressorgenes, DDIT4, DDIT4L, EIF4EBP1, EIF4EBP2, FKBP1A, FKBP8, GSK3B, MYO1C, PTEN, ULK1, andULK2, were found to have increased significantly. the MET + PIO combination was first applied to thyroid cancer cells, and significant reductions in the level of oncogenic genes were detected. the decreases, particularly, inAKT3, DEPTOR, EIF4E, ILK, MTOR, PIK3C, andPRKCAexpressions indicate that progression can be prevented in thyroid cancer cells and these genes could be selected as therapeutic targets.Öğe Effects of rapamycin and AZD3463 combination on apoptosis, autophagy, and cell cycle for resistance control in breast cancer(Pergamon-Elsevier Science Ltd, 2021) Ozates, Neslihan Pinar; Sogutlu, Fatma; Lerminoglu, Ferzan; Demir, Busra; Gunduz, Cumhur; Shademan, Behrouz; Avci, Cigir BirayBreast cancer is the most common cancer in women and the leading cause of cancer mortality in women over 40 it's the year. The existence of the PI3K/AKT/mTOR pathway aberrations in more than 70% of breast cancer has caused to become a therapeutic target. AZD3463 is an anti-cancer agent used as a potential inhibitor of ALK/IGF1R. It also induces apoptosis and autophagy of the PI3K/AKT/mTOR pathway in cancer cells. Although the mTOR signaling might be inhibited by rapamycin treatment, signals transmitted from the upstream pathway supports cell survival and proliferation. The WST-1 assay test was performed to evaluate the anti-proliferative effects of rapamycin and AZD3463. Besides, the effects of them on apoptosis, autophagy, cytostatic, and metabolism in MCF7 breast cancer cells were investigated. Also, changes in the expression of apoptotic regulatory genes, cell cycle, and metabolism in the PI3K/AKT/mTOR Pathway were determined by Quantitative RT-PCR. The results showed that rapamycin and AZD3463 treatments significantly reduced survival in MCF7 cells. Also, apoptosis, autophagy, and cell population in the G0/G1 stage in the MCF7 cell category in the treatment group showed an increase compared to the control group. The combination of rapamycin and AZD3463 (AZD-RAPA) was determined as an additive according to isobologram analysis. in the combination of rapamycin with AZD3463, the expression of CDKN1B, PTEN, FOXO3, and APC genes increases, and the expression of PRKCB and PIK3CG genes decreases. Our results showed that the use of AZD-RAPA reduced the resistance of cancer cells to treatment and it leads cancer cells to apoptosis.Öğe Enhanced Anti-cancer Potency Using a Combination of Oleanolic Acid and Maslinic Acid to Control Treatment Resistance in Breast Cancer(Tabriz Univ Medical Sciences & Health Services, 2023) Biray Avcı, Çığır; Soğutlu, Fatma; Özateş, Neslihan Pınar; Shademan, Behrouz; Gündüz, CumhurPurpose: The phosphatidylinositol 3-kinase/AKT/mammalian target of rapamycin (PI3K/AKT/ mTOR) pathway is a complex intracellular metabolic pathway that leads to cell growth and tumor proliferation and plays a key role in drug resistance in breast cancer. Therefore, the anti-cancer effects of oleanolic acid (OA), maslinic acid (MA), and their combination were investigated to improve the performance of the treatment strategy. Methods: We investigated the effect of OA and MA on cell viability using the WST-1 method. The synergistic effect of the combination was analyzed by isobologram analysis. In addition, the effects of the two compounds, individually and in combination, on apoptosis, autophagy, and the cell cycle were investigated in MCF7 cells. In addition, changes in the expression of PI3K/AKT/mTOR genes involved in apoptosis, cell cycle and metabolism were determined by quantitative RT-PCR. Results: MA, OA, and a combination of both caused G0/G1 arrest. Apoptosis also increased in all treated groups. The autophagosomal LC3-II formation was induced 1.74-fold in the MA -treated group and 3.25-fold in the MA-OA-treated group. The combination treatment resulted in increased expression of genes such as GSK3B, PTEN, CDKN1B and FOXO3 and decreased expression of IGF1, PRKCB and AKT3 genes. Conclusion: The results showed that the combination of these two substances showed the highest synergistic effect at the lowest dose and using MA-OA caused cancer cells to undergo apoptosis. The use of combination drugs may reduce the resistance of cancer cells to treatment.Öğe Enhanced anticancer potency of hydroxytyrosol and curcumin by PLGA-PAA nano-encapsulation on PANC-1 pancreatic cancer cell line(Wiley, 2021) Jadid, Mahdieh Farhoudi Sefidan; Shademan, Behrouz; Chavoshi, Reza; Seyyedsani, Nasrin; Aghaei, Elnaz; Taheri, Elham; Sabet, Mehrdad NasrollahzadehMany chemotherapeutic regimens have been investigated for advanced unresectable and metastatic pancreatic cancer (PC), but with only minimal improvement in survival and prognosis. Here, we investigated anti-cancer function of free and nano-encapsulated hydroxytyrosol (Hyd) and curcumin (Cur), and its combinations (Hyd-Cur) on PANC-1 cell line. The poly lactide-co-glycolide-co-polyacrylic acid (PLGA-co-PAA) nano-encapsulated Hyd and Cur were synthesized, and MTT assay was performed to evaluate cytotoxic effects of free and nano-encapsulated Hyd, Cur, and Hyd-Cur. Effects of free and nano-encapsulated Hyd, Cur, and Hyd-Cur were evaluated on viability, migration, morphological alterations, colony formation, and apoptosis on PANC-1 cells. We observed that free and nano-encapsulated Hyd, Cur, and Hyd-Cur significantly increased apoptosis rates as well as significantly decreased viability, migration, and colony formation in PANC-1 cells. According to our results, Hyd-Cur combination and nano-encapsulation therapy exerts more profound apoptotic and anti-proliferative effects on PANC-1 cells than free Hyd or Hyd monotherapy.Öğe Evaluation of the serum levels of Mannose binding lectin-2, tenascin-C, and total antioxidant capacity in patients with coronary artery disease(Wiley, 2021) Mehri, Hamed; Aslanabadi, Naser; Nourazarian, Alireza; Shademan, Behrouz; Khaki-Khatibi, FatemehBackground Coronary artery disease (CAD) develops as a result of atherosclerosis. Atherosclerosis is a condition that leads to clogged arteries and can be caused by a variety of factors. Several studies have shown that various factors contribute to the development and progression of CAD. The aim of this study was to investigate the serum levels of MBL-2, TNC and TAC in patients with CAD and the relationship between these biochemical parameters and the progression of CAD. Methods In this study, 60 serum samples were obtained from CAD patients as the case group and 20 healthy serum samples as the control group. Serum levels of MBL-2 and TNC were measured by the ELISA method. Serum TAC level was determined by calorimetry (spectrophotometry). In addition, MDA serum level was measured by reaction with thiobarbituric acid (TBA). Results The mean age in the case and control groups was 58.4 +/- 9.5 years and 85 +/- 9.8 years, respectively. There was no significant difference in age, sex and family history in patients with CAD (p > 0.05), but there was a significant difference in blood pressure and smoking history (p > 0.05). Serum cholesterol, triglyceride, and LDL levels were significantly increased in the case group compared to the control group, while serum HDL-C levels were significantly decreased in the case group. Serum levels of MBL-2, TNC, and MDA were significantly increased in the case group compared to the control group. The serum level of TAC was significantly lower in the case group than in the control group. Conclusion This study suggests that it is possible to diagnose patients with coronary artery disease (CAD) in the early stages of their disease and take preventive measures by measuring these parameters in serum. However, more research is needed before these serum parameters can be considered diagnostic biomarkers or therapeutic targets.Öğe Exploring potential serum levels of Homocysteine, interleukin-1 beta, and apolipoprotein B 48 as new biomarkers for patients with ischemic stroke(Wiley, 2021) Shademan, Behrouz; Nourazarian, Alireza; Laghousi, Delara; Karamad, Vahidreza; Nikanfar, MasoudBackground: Stroke is the second leading cause of death worldwide with heterogeneous characteristics. The subtypes of stroke are due to different pathophysiological regulations and causes. This study aimed to investigate the correlation of serum levels of apolipoprotein B 48, interleukin-1 beta and Homocysteine with BMI in patients with ischemic stroke (IS). Methods: Over one hundred controls (120) and an equal number of IS patients, including 31 women and 89 men, were recruited to participate in the case-control study conducted at Imam Reza Hospital (Tabriz, Iran) from February 2019 to March 2020. We measured serum levels of apolipoprotein B 48, interleukin-1 beta, and Homocysteine. Receiver operating characteristic analysis (ROC) was performed to evaluate the diagnostic value of these indices in patients and control groups. Results: The mean serum levels of apolipoprotein B 48, interleukin-1 beta, and Homocysteine, were significantly increased in the experimental group compared to the control group with a p-value of 0.001. The ROC curve analysis showed that the area under the curve for apo B48, IL-1 beta, hs-CRP, and Homocysteine serum levels were 0.94, 0.98, 0.99, and 1, respectively. Conclusions: The results of our current study show that the determination of serum levels of apolipoprotein B 48, interleukin-1 beta, and Homocysteine can potentially be used to monitor and diagnose IS patients. However, there was no statistically significant correlation between serum levels of apolipoprotein B 48, interleukin 1 beta and Homocysteine and BMI in the patient group. However, there was a statistically significant inverse correlation between serum levels of high-sensitivity C-reactive protein (hs-CRP) and BMI in the patient group.Öğe Exploring the intricate relationship between miRNA dysregulation and breast cancer development: insights into the impact of environmental chemicals(Frontiers Media Sa, 2024) Abolhasanzadeh, Narges; Sarabandi, Sajed; Dehghan, Bahar; Karamad, Vahidreza; Avci, Cigir Biray; Shademan, Behrouz; Nourazarian, AlirezaBreast cancer stands as the most prevalent form of cancer among women globally, influenced by a combination of genetic and environmental factors. Recent studies have investigated changes in microRNAs (miRNAs) during breast cancer progression and the potential impact of environmental chemicals on miRNA expression. This review aims to provide an updated overview of miRNA alterations in breast cancer and to explore their potential association with environmental chemicals. We will discuss the current knowledge on dysregulated miRNAs in breast cancer, including both upregulated and downregulated miRNAs. Additionally, we will review the influence of environmental chemicals, such as endocrine-disrupting compounds, heavy metals, and air pollutants, on miRNA expression and their potential contribution to breast cancer development. This review aims to advance our understanding of the complex molecular mechanisms underlying miRNA dysregulation in breast cancer by comprehensively examining miRNA alterations and their association with environmental chemicals. This knowledge is crucial for the development of targeted therapies and preventive measures. Furthermore, identifying specific miRNAs affected by environmental chemicals may allow the prediction of individual susceptibility to breast cancer and the design of personalized intervention strategies.Öğe First Serological & Molecular Study of Coxiella burnetii in Stray, Domestic Cats, and Their Owners in Iran(W B Saunders Co-Elsevier Inc, 2020) Mousapour, Morteza; Oveisi, Amin; Key, Yashar Azari; Mikaeili, Ehsan; Rahimi, Farzad; Shademan, Behrouz; Taefehshokr, SinaCoxiella burnetii, the agent of Q fever, is recognized as a worldwide zoonosis a wide host and potentially com-plex reservoir systems. Infected ruminants are the main source of infection for humans, but cats also represent a potential source of infection. The prevalence of C burnetii in cats in Iran is unknown and the risks of transmission to humans are undetermined. This study aimed to determine the prevalence of C burnetii in domestic cats and their owners. An Enzyme-linked immunosorbent assay was used for detection of anti-C burnetii antibodies in both cats and humans. Cats serum samples and humans serum samples (n = 85) were tested with indirect ELISA. C burnetii was diagnosed using real timepolymerase chain reaction. Antibodies were detected in 19 sera of 85 (22.35%) samples in stray cats, 9 sera of 78 (11.53%) samples of domestic cats and 4 sera of 78 (5.12%) samples of their owners. This first study of C burnetii prevalence in cats in Iran has indicated that positive samples can be found throughout the country and these results confirm that Iranian cats have been exposed to C burnetii. Moreover, this study demonstrates that cat owners, breeders and veterinary personnel might be at higher risk of exposure of C burnetii. (c) 2020 Elsevier Inc. All rights reserved.Öğe The future of cancer therapy: exploring the potential of patient-derived organoids in drug development(Frontiers Media Sa, 2024) Avci, Cigir Biray; Bagca, Bakiye Goker; Shademan, Behrouz; Takanlou, Leila Sabour; Takanlou, Maryam Sabour; Nourazarian, AlirezaCancer therapy is on the brink of a significant transformation with the inclusion of patient-derived organoids (PDOs) in drug development. These three-dimensional cell cultures, directly derived from a patient's tumor, accurately replicate the complex structure and genetic makeup of the original cancer. This makes them a promising tool for advancing oncology. In this review, we explore the practical applications of PDOs in clinical drug screening and pharmacognostic assessment, as well as their role in refining therapeutic strategies. We provide insights into the latest advancements in PDO technology and its implications for predicting treatment responses and facilitating novel drug discoveries. Additionally, we address the operational challenges associated with incorporating PDOs into the drug development process, such as scaling up organoid cultures, ensuring consistent results, and addressing the ethical use of patient-derived materials. Aimed at researchers, clinicians, and key stakeholders in oncology, this article aims to succinctly present both the extraordinary potential and the obstacles to integrating PDOs, thereby shedding light on their prospective impact on the future of cancer treatment.Öğe Gene polymorphism of leptin and risk for heart disease, obesity, and high BMI: a systematic review and pooled analysis in adult obese subjects(Walter De Gruyter Gmbh, 2022) Khaki-Khatibi, Fatemeh; Shademan, Behrouz; Gholikhani-Darbroud, Reza; Nourazarian, Alireza; Radagdam, Saeed; Porzour, MaghsoudObjectives Leptin polymorphism (LEP) has been associated with coronary heart disease (CAD), obesity, and high body mass index (BMI). However, we performed a systematic review and meta-analysis to discover the association because previous studies reached different conclusions. Methods Review Manager, version 5.3.5, and Stata, version 15.0, were used for statistical analysis. We calculated the effect size of the studies using the OR with the corresponding 95% CI, and two-sided (bilateral) p-values of 0.05 were considered significant. To determine heterogeneity among the selected studies, the Q test and I2 statistics were used. Meta-regression was used to examine the disease (heart disease, obesity, and high BMI) and heterogeneity between these subgroups. Results Eleven studies with 18,984 subjects were included in this study. The G-2548A (rs12112075), rs7799039, and A19G (rs2167270) polymorphisms of the leptin gene (but not the Lys656Asn (rs1805094) polymorphism) are associated with an increased risk of cardiovascular disease. Our pooled analysis revealed an association between the G-2548A (rs12112075) polymorphism and heart disease, high BMI, and obesity. This indicates that individuals carrying the AA allele are at an increased risk for heart disease, high BMI, and obesity. People with heart failure and coronary artery disease did not have the rs7799039 polymorphism or its alleles linked to them. Conclusions Combined analysis of data from current and published research suggests that the leptin gene polymorphisms G-2548A (rs12112075), rs7799039, and A19G (rs2167270) (but not the Lys656Asn (rs1805094) polymorphism) are associated with an increased risk of cardiovascular disease. Further research is needed to understand this association.Öğe Investigation of iso-propylchaetominine anticancer activity on apoptosis, cell cycle and Wnt signaling pathway in different cancer models(Elsevier, 2024) Karamad, Vahidreza; Sogutlu, Fatma; Ozkaya, Ferhat Can; Shademan, Behrouz; Ebrahim, Weaam; El-Neketi, Mona; Avci, Cigir BirayDysregulation of the Wnt signaling pathway contributes to the development of many cancer types. Natural compounds produced with biotechnological systems have been the focus of research for being a new drug candidate both with unlimited resources and cost-effective production. In this study, it was aimed to reveal the effects of isopropylchaetominine on cytotoxic, cytostatic, apoptotic and Wnt signaling pathways in brain, pancreatic and prostate cancer. The IC50 values of isopropylchaetominine in U-87 MG, PANC1, PC3 and LNCaP cells were calculated as 91.94 mu M, 41.68 mu M, 54.54 mu M and 7.86 mu M in 72nd h, respectively. The metabolite arrests the cell cycle in G0/G1 phase in each cancer cells. Iso-propylchaetominine induced a 4.3-fold and 1.9-fold increase in apoptosis in PC3 and PANC1 cells, respectively. The toxicity of isopropylchaetominine in healthy fibroblast cells was assessed using the annexin V method, and no significant apoptotic activity was observed between the groups treated with the active substance and untreated. In U-87 MG, PANC1, PC3, and LNCaP cells under treatment with iso-propylchaetominin, the expression levels of DKK3, TLE1, AES, DKK1, FRZB, DAB2, AXIN1/2, PPARD, SFRP4, APC and SOX17 tumor suppressor genes increased significantly. Decreases in expression of Wnt1, Wnt2, Wnt3, Wnt4, Wnt5, Wnt6, Wnt10, Wnt11, FRZ2, FRZ3, FRZ7, TCF7L1, BCL9, PYGO, CCND2, c-MYC, WISP1 and CTNNB1 oncogenic genes were detected. All these result shows that isopropylchaetominine can present promising new treatment strategy in different cancer types.Öğe Investigation of serum levels of orexin-A, transforming growth factor beta, and leptin in patients with multiple sclerosis(Wiley, 2022) Moharami, Sepideh; Nourazarian, Alireza; Nikanfar, Masoud; Laghousi, Delara; Shademan, Behrouz; Khanghah, Omid Joodi; Khaki-Khatibi, FatemehBackground: Multiple sclerosis (MS) is a chronic inflammatory and autoimmune disease affecting various inflammatory and nutritional parameters. Therefore, this study aimed to investigate the relationship between the Body Mass Index (BMI) of MS patients and the serum levels of leptin, orexin-A, and Transforming Growth Factor beta (TGF-beta). Methods: This cross-sectional study included 25 patients suffering from MS and 40 healthy individuals as the case and control groups, respectively. The serum levels of leptin, orexin-A, and TGF-beta were assessed in the participants using the Enzyme-Linked Immunosorbent Assay methods. Moreover, data were analyzed using the descriptive statistical indices, t-test, chi-square test, and linear regression test. Results: According to our results, the participants' mean age was 38.04 +/- 7.53 and 40.23 +/- 5.88 in the case and control groups, respectively. Also, the groups were riot significantly different in gender, age, alcohol consumption, and smoking (p > 0.05). It was found that the mean serum levels of orexin-A and TGF-beta were significantly lower in the MS patients compared to the control group, while the mean serum leptin levels were significantly higher (42.8 vs. 18.9 ng/ml, p < 0.001). Moreover, there was no significant relationship between the BMI of the MS patients and their serum levels of orexin-A, TGF-beta, and leptin (p > 0.05). Conclusions: In conclusion, we found significantly lower levels of orexin-A and TGF-beta and a significantly higher level of leptin in the MS patients compared to the control group. In addition, there was no significant relationship between the BMI and the serum levels of orexin-A, TGF-beta, and leptin in MS patients.
