Publications by authors named "Meysam Moghbeli"

63 Publications

Elucidated tumorigenic role of MAML1 and TWIST1 in gastric cancer is associated with Helicobacter pylori infection.

Microb Pathog 2021 Nov 21:105304. Epub 2021 Nov 21.

Medical Genetics Research Center, Faculty of Medical Sciences, Mashhad University of Medical Sciences, Mashhad, Iran. Electronic address:

Background: Epithelial-mesenchymal transition (EMT) has a fundamental role in tumor initiation, progression, and metastasis. Helicobacter pylori (HP) induces EMT and thus causes gastric cancer (GC) by deregulating multiple signaling pathways involved in EMT. TWIST1 and MAML1 have been confirmed to be critical inducers of EMT via diverse signaling pathways such as Notch signaling. This study aimed to investigate for the first time possible associations between TWIST1/MAML1 mRNA expression levels, HP infection, and clinicopathological characteristics in GC patients.

Method: TWIST1 and MAML1 mRNA expression levels were evaluated in tumoral and adjacent normal tissues in 73 GC patients using the quantitative reverse transcription PCR (RT-qPCR) method. PCR technique was also applied to examine the infection with HP in GC samples.

Results: Upregulation of TWIST1 and MAML1 expression was observed in 35 (48%) and 34 (46.6%) of 73 tumor samples, respectively. Co-overexpression of these genes was found in 26 of 73 (35.6%) tumor samples; meanwhile, there was a significant positive correlation between MAML1 and TWIST1 mRNA expression levels (P < 0.001). MAML1 overexpression exhibited meaningful associations with advanced tumor stages (P = 0.006) and nodal metastases (P ˂ 0.001). 34 of 73 (46.6%) tumors tested positive for HP, and meanwhile, MAML1 expression was positively related with T (P = 0.05) and grade (P = 0.0001) in these HP-positive samples. Increased TWIST1 expression was correlated with patient sex (P = 0.035) and advanced tumor grade (P = 0.017) in HP-infected tumors. Furthermore, TWIST1 and MAML1 expression levels were inversely linked with histologic grade in HP-negative tumor samples (P = 0.021 and P = 0.048, respectively).

Conclusion: We propose TWIST1 and MAML1 as potential biomarkers of advanced-stage GC that determine the characteristics and aggressiveness of the disease. Based on accumulating evidence and our findings, they can be introduced as promising therapeutic targets to modify functional abnormalities in cells that promote GC progression. Moreover, HP may enhance GC growth and metastasis by disrupting TWIS1/MAML1 expression patterns and related pathways.
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http://dx.doi.org/10.1016/j.micpath.2021.105304DOI Listing
November 2021

MicroRNAs as the critical regulators of Cisplatin resistance in ovarian cancer cells.

Authors:
Meysam Moghbeli

J Ovarian Res 2021 Sep 30;14(1):127. Epub 2021 Sep 30.

Department of Medical Genetics and Molecular Medicine, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.

Background: Ovarian cancer (OC) is one of the leading causes of cancer related deaths among women. Due to the asymptomatic tumor progression and lack of efficient screening methods, majority of OC patients are diagnosed in advanced tumor stages. A combination of surgical resection and platinum based-therapy is the common treatment option for advanced OC patients. However, tumor relapse is observed in about 70% of cases due to the treatment failure. Cisplatin is widely used as an efficient first-line treatment option for OC; however cisplatin resistance is observed in a noticeable ratio of cases. Regarding, the severe cisplatin side effects, it is required to clarify the molecular biology of cisplatin resistance to improve the clinical outcomes of OC patients. Cisplatin resistance in OC is associated with abnormal drug transportation, increased detoxification, abnormal apoptosis, and abnormal DNA repair ability. MicroRNAs (miRNAs) are critical factors involved in cell proliferation, apoptosis, and chemo resistance. MiRNAs as non-invasive and more stable factors compared with mRNAs, can be introduced as efficient markers of cisplatin response in OC patients.

Main Body: In present review, we have summarized all of the miRNAs that have been associated with cisplatin resistance in OC. We also categorized the miRNAs based on their targets to clarify their probable molecular mechanisms during cisplatin resistance in ovarian tumor cells.

Conclusions: It was observed that miRNAs mainly exert their role in cisplatin response through regulation of apoptosis, signaling pathways, and transcription factors in OC cells. This review highlighted the miRNAs as important regulators of cisplatin response in ovarian tumor cells. Moreover, present review paves the way of suggesting a non-invasive panel of prediction markers for cisplatin response among OC patients.
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http://dx.doi.org/10.1186/s13048-021-00882-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8485521PMC
September 2021

Long non-coding RNAs as the critical regulators of doxorubicin resistance in tumor cells.

Cell Mol Biol Lett 2021 Aug 23;26(1):39. Epub 2021 Aug 23.

Department of Medical Genetics and Molecular Medicine, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.

Resistance against conventional chemotherapeutic agents is one of the main reasons for tumor relapse and poor clinical outcomes in cancer patients. Various mechanisms are associated with drug resistance, including drug efflux, cell cycle, DNA repair and apoptosis. Doxorubicin (DOX) is a widely used first-line anti-cancer drug that functions as a DNA topoisomerase II inhibitor. However, DOX resistance has emerged as a large hurdle in efficient tumor therapy. Furthermore, despite its wide clinical application, DOX is a double-edged sword: it can damage normal tissues and affect the quality of patients' lives during and after treatment. It is essential to clarify the molecular basis of DOX resistance to support the development of novel therapeutic modalities with fewer and/or lower-impact side effects in cancer patients. Long non-coding RNAs (lncRNAs) have critical roles in the drug resistance of various tumors. In this review, we summarize the state of knowledge on all the lncRNAs associated with DOX resistance. The majority are involved in promoting DOX resistance. This review paves the way to introducing an lncRNA panel marker for the prediction of the DOX response and clinical outcomes for cancer patients.
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http://dx.doi.org/10.1186/s11658-021-00282-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8381522PMC
August 2021

Molecular mechanisms of the microRNA-132 during tumor progressions.

Cancer Cell Int 2021 Aug 21;21(1):439. Epub 2021 Aug 21.

Department of Chemistry, Faculty of Science, Ferdowsi University of Mashhad, Mashhad, Iran.

Cancer as one of the leading causes of human deaths has always been one of the main health challenges in the world. Despite recent advances in therapeutic and diagnostic methods, there is still a high mortality rate among cancer patients. Late diagnosis is one of the main reasons for the high ratio of cancer related deaths. Therefore, it is required to introduce novel early detection methods. Various molecular mechanisms are associated with the tumor progression and metastasis. MicroRNAs (miRNAs) are a class of non-coding RNAs (ncRNAs) family that has important functions in regulation of the cellular processes such as cell proliferation, apoptosis, and tumor progression. Moreover, they have higher stability in body fluids compared with mRNAs which can be introduced as non-invasive diagnostic markers in cancer patients. MiR-132 has important functions as tumor suppressor or oncogene in different cancers. In the present review, we have summarized all of the studies which have been reported the role of miR-132 during tumor progressions. We categorized the miR-132 target genes based on their cell and molecular functions. Although, it has been reported that the miR-132 mainly functions as a tumor suppressor, it has also oncogenic functions especially in pancreatic tumors. MiR-132 mainly exerts its roles during tumor progressions by regulation of the transcription factors and signaling pathways. Present review clarifies the tumor specific molecular mechanisms of miR-132 to introduce that as an efficient non-invasive diagnostic marker in various cancers.
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http://dx.doi.org/10.1186/s12935-021-02149-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8379808PMC
August 2021

Genetics and molecular biology of male infertility among Iranian population: an update.

Am J Transl Res 2021 15;13(6):5767-5785. Epub 2021 Jun 15.

Department of Medical Genetics and Molecular Medicine, School of Medicine, Mashhad University of Medical Sciences Mashhad, Iran.

Infertility is one of the main social and health problems among young couples. Although a noticeable ratio of infertilities are asymptomatic, about half of the cases are observed among males. Various environmental factors such as life style, dietary patterns, and pathogens are associated with male infertility. Mutations and chromosomal abnormalities are also the most important genetic risk factors of male infertility. Similar to other populations, there is a dramatically rising trend of male infertility among Iranian. Regarding the high ratio of asymptomatic cases, it is required to clarify the molecular biology and cellular processes involved in male infertility in this population to suggest an efficient panel of diagnostic markers. In this review, we have summarized all of the cellular and molecular processes which have been reported among Iranian infertile males to clarify the molecular biology of male infertility in this population. It was observed that the stress response, cellular detoxification, and DNA repair processes were the most common aberrant cellular mechanisms among Iranian infertile males. This review paves the way of introducing a population-based diagnostic panel of genetic markers among Iranian infertile males.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8290737PMC
June 2021

The Level of Mesenchymal-Epithelial Transition Autophosphorylation is Correlated with Esophageal Squamous Cell Carcinoma Migration.

Iran Biomed J 2021 07 1;25(4):243-54. Epub 2021 Jul 1.

Medical Genetics Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.

Background: The MET receptor is a critical member of cancer-associated receptor tyrosine kinases and plays an important role in different biological activities, including differentiation, migration, and cell proliferation.

Methods: In this study, novel MET inhibitors were introduced and applied on esophageal squamous carcinoma cell line KYSE-30, and the level of proliferation and migration, as well as the activated form of MET receptor protein were assessed in the examined cells. The human KYSE-30 cell line was cultured according to ATCC recommendations. The mRNA level of the MET gene was measured in the examined cell line using the quantitative RT-PCR assay. Cytotoxicity evaluation test was performed at different concentrations of heterocyclic anti-MET compounds (i.e. D1, D2, D5, D6, D7, and D8). Finally, the capability of these compounds in MET receptor inhibition was evaluated using the migration assay and Western blot. All experiments were performed in triplicate and repeated three times with similar results.

Results: Cell growth and proliferation were significantly inhibited (p ≤ 0.05) by all the above-mentioned compounds. Moreover, the majority of compounds significantly prevented the cell migration (p ≤ 0.05) and inhibited MET autophosphorylation. Interestingly, the level of phosphorylated MET was significantly correlated with KYSE-30 cell migration.

Conclusion: The obtained data introduced and confirmed the biological activities of the mentioned novel compounds in KYSE-30 cells and proposed that the therapeutic inhibition of MET with these compounds may be a powerful approach for inhibiting cancer cell migration and proliferation although some structural optimizations are needed to improve their inhibitory functions.
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http://dx.doi.org/10.52547/ibj.25.4.243DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8334392PMC
July 2021

MicroRNAs as the critical regulators of cisplatin resistance in gastric tumor cells.

Genes Environ 2021 Jun 7;43(1):21. Epub 2021 Jun 7.

Department of Medical Genetics and Molecular Medicine, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.

Combined chemotherapeutic treatment is the method of choice for advanced and metastatic gastric tumors. However, resistance to chemotherapeutic agents is one of the main challenges for the efficient gastric cancer (GC) treatment. Cisplatin (CDDP) is used as an important regimen of chemotherapy for GC which induces cytotoxicity by interfering with DNA replication in cancer cells and inducing their apoptosis. Majority of patients experience cisplatin-resistance which is correlated with tumor metastasis and relapse. Moreover, prolonged and high-dose cisplatin administrations cause serious side effects such as nephrotoxicity, ototoxicity, and anemia. Since, there is a high rate of recurrence after CDDP treatment in GC patients; it is required to clarify the molecular mechanisms associated with CDDP resistance to introduce novel therapeutic methods. There are various cell and molecular processes associated with multidrug resistance (MDR) including drug efflux, detoxification, DNA repair ability, apoptosis alteration, signaling pathways, and epithelial-mesenchymal transition (EMT). MicroRNAs are a class of endogenous non-coding RNAs involved in chemo resistance of GC cells through regulation of all of the MDR mechanisms. In present review we have summarized all of the miRNAs associated with cisplatin resistance based on their target genes and molecular mechanisms in gastric tumor cells. This review paves the way of introducing a miRNA-based panel of prognostic markers to improve the efficacy of chemotherapy and clinical outcomes in GC patients. It was observed that miRNAs are mainly involved in cisplatin response of gastric tumor cells via regulation of signaling pathways, autophagy, and apoptosis.
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http://dx.doi.org/10.1186/s41021-021-00192-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8182944PMC
June 2021

Single nucleotide polymorphisms as the efficient prognostic markers in breast cancer.

Curr Cancer Drug Targets 2021 May 25. Epub 2021 May 25.

Medical Genetics Research Center, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.

Background: Breast cancer (BC) is known as the most common malignancy in women. Environmental and genetic factors are associated with BC progression. Genetic polymorphisms have been reported as important risk factors of BC prognosis and drug response. Main body: Therefore, in the present review, we have summarized all single nucleotide polymorphisms (SNPs) which have been significantly associated with drug response in BC patients around the world. We have also categorized the reported SNPs based on their related genes functions to clarify the molecular biology of drug responses in BC.

Conclusion: The majority of SNPs were reported in detoxifying enzymes, which introduced such genes as the main genetic risk factors during BC drug responses. This review paves the way for introducing a prognostic panel of SNPs for the BC patients in the world.
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http://dx.doi.org/10.2174/1568009621666210525151846DOI Listing
May 2021

MAEL as a diagnostic marker for the early detection of esophageal squamous cell carcinoma.

Diagn Pathol 2021 Apr 26;16(1):36. Epub 2021 Apr 26.

Department of Medical Genetics and Molecular Medicine, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.

Background: Esophageal cancer is one of the most common malignancies among Iranians and is categorized as adenocarcinoma and squamous cell carcinoma. Various environmental and genetic factors are involved in this malignancy. Despite the recent advances in therapeutic modalities there is still a noticeable mortality rate among such patients which can be related to the late diagnosis. Regarding high ratio of esophageal squamous cell carcinoma (ESCC) in Iran, therefore it is required to assess molecular biology of ESCC to introduce novel diagnostic markers. In present study we assessed the role of Maelstrom (MAEL) cancer testis gene in biology of ESCC among Iranian patients.

Methods: Forty-five freshly normal and tumor tissues were enrolled to evaluate the levels of MAEL mRNA expression using Real time polymerase chain reaction.

Results: MAEL under and over expressions were observed in 12 (26.7%) and 9 (20%) of patients, respectively. MAEL fold changes were ranged between -4.33 to -1.87 (mean SD: -2.90± 0.24) and 1.92 to 7.72 (mean SD: 3.97± 0.69) in under and over expressed cases, respectively. There was a significant association between stage and MAEL expression in which majority of MAEL over expressed tumors (8/9, 88.9%) were in stage I/II (p<0.001). There was also a significant correlation between MAEL expression and depth of invasion in which tumor with T1/2 had higher levels of MAEL expression compared with T3/4 tumors (p=0.017). Moreover, there were significant correlations between MAEL expression, tumor size (p=0.028), and grade (p=0.003) among male patients.

Conclusions: Our data showed that the MAEL was mainly involved in primary stages of tumor progression and it has a declining expression levels toward the advanced stages and higher depth of tumor invasions. Therefore, MAEL can be efficiently introduced as an early detection marker among Iranian ESCC patients.
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http://dx.doi.org/10.1186/s13000-021-01098-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8077922PMC
April 2021

Methylation as a critical epigenetic process during tumor progressions among Iranian population: an overview.

Genes Environ 2021 Apr 21;43(1):14. Epub 2021 Apr 21.

Department of Medical Genetics and Molecular Medicine, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.

Cancer is one of the main health challenges and leading causes of deaths in the world. Various environmental and genetic risk factors are associated with tumorigenesis. Epigenetic deregulations are also important risk factors during tumor progression which are reversible transcriptional alterations without any genomic changes. Various mechanisms are involved in epigenetic regulations such as DNA methylation, chromatin modifications, and noncoding RNAs. Cancer incidence and mortality have a growing trend during last decades among Iranian population which are significantly related to the late diagnosis. Therefore, it is required to prepare efficient molecular diagnostic panels for the early detection of cancer in this population. Promoter hyper methylation is frequently observed as an inhibitory molecular mechanism in various genes associated with DNA repair, cell cycle regulation, and apoptosis during tumor progression. Since aberrant promoter methylations have critical roles in early stages of neoplastic transformations, in present review we have summarized all of the aberrant methylations which have been reported during tumor progression among Iranian cancer patients. Aberrant promoter methylations are targetable and prepare novel therapeutic options for the personalized medicine in cancer patients. This review paves the way to introduce a non-invasive methylation specific panel of diagnostic markers for the early detection of cancer among Iranians.
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http://dx.doi.org/10.1186/s41021-021-00187-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8059047PMC
April 2021

MicroRNAs as the critical regulators of Doxorubicin resistance in breast tumor cells.

Cancer Cell Int 2021 Apr 15;21(1):213. Epub 2021 Apr 15.

Department of Medical Genetics and Molecular Medicine, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.

Background: Chemotherapy is one of the most common treatment options for breast cancer (BC) patients. However, about half of the BC patients are chemotherapeutic resistant. Doxorubicin (DOX) is considered as one of the first line drugs in the treatment of BC patients whose function is negatively affected by multi drug resistance. Due to the severe side effects of DOX, it is very important to diagnose the DOX resistant BC patients. Therefore, assessment of molecular mechanisms involved in DOX resistance can improve the clinical outcomes in BC patients by introducing the novel therapeutic and diagnostic molecular markers. MicroRNAs (miRNAs) as members of the non-coding RNAs family have pivotal roles in various cellular processes including cell proliferation and apoptosis. Therefore, aberrant miRNAs functions and expressions can be associated with tumor progression, metastasis, and drug resistance. Moreover, due to miRNAs stability in body fluids, they can be considered as non-invasive diagnostic markers for the DOX response in BC patients.

Main Body: In the present review, we have summarized all of the miRNAs that have been reported to be associated with DOX resistance in BC for the first time in the world.

Conclusions: Since, DOX has severe side effects; it is required to distinguish the non DOX-responders from responders to improve the clinical outcomes of BC patients. This review highlights the miRNAs as pivotal regulators of DOX resistance in breast tumor cells. Moreover, the present review paves the way of introducing a non-invasive panel of prediction markers for DOX response among BC patients.
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http://dx.doi.org/10.1186/s12935-021-01873-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8170947PMC
April 2021

Molecular interactions of miR-338 during tumor progression and metastasis.

Authors:
Meysam Moghbeli

Cell Mol Biol Lett 2021 Apr 7;26(1):13. Epub 2021 Apr 7.

Department of Medical Genetics and Molecular Medicine, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.

Background: Cancer, as one of the main causes of human deaths, is currently a significant global health challenge. Since the majority of cancer-related deaths are associated with late diagnosis, it is necessary to develop minimally invasive early detection markers to manage and reduce mortality rates. MicroRNAs (miRNAs), as highly conserved non-coding RNAs, target the specific mRNAs which are involved in regulation of various fundamental cellular processes such as cell proliferation, death, and signaling pathways. MiRNAs can also be regulated by long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs). They are highly stable in body fluids and have tumor-specific expression profiles, which suggest their suitability as efficient non-invasive diagnostic and prognostic tumor markers. Aberrant expression of miR-338 has been widely reported in different cancers. It regulates cell proliferation, migration, angiogenesis, and apoptosis in tumor cells.

Main Body: In the present review, we have summarized all miR-338 interactions with other non-coding RNAs (ncRNAs) and associated signaling pathways to clarify the role of miR-338 during tumor progression.

Conclusions: It was concluded that miR-338 mainly functions as a tumor suppressor in different cancers. There were also significant associations between miR-338 and other ncRNAs in tumor cells. Moreover, miR-338 has a pivotal role during tumor progression using the regulation of WNT, MAPK, and PI3K/AKT signaling pathways. This review highlights miR-338 as a pivotal ncRNA in biology of tumor cells.
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http://dx.doi.org/10.1186/s11658-021-00257-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8028791PMC
April 2021

Genetic and molecular biology of autism spectrum disorder among Middle East population: a review.

Hum Genomics 2021 03 12;15(1):17. Epub 2021 Mar 12.

Department of Medical Genetics and Molecular Medicine, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.

Background: Autism spectrum disorder (ASD) is a neurodevelopmental disease, characterized by impaired social communication, executive dysfunction, and abnormal perceptual processing. It is more frequent among males. All of these clinical manifestations are associated with atypical neural development. Various genetic and environmental risk factors are involved in the etiology of autism. Genetic assessment is essential for the early detection and intervention which can improve social communications and reduce abnormal behaviors. Although, there is a noticeable ASD incidence in Middle East countries, there is still a lack of knowledge about the genetic and molecular biology of ASD among this population to introduce efficient diagnostic and prognostic methods.

Main Body: In the present review, we have summarized all of the genes which have been associated with ASD progression among Middle East population. We have also categorized the reported genes based on their cell and molecular functions.

Conclusions: This review clarifies the genetic and molecular biology of ASD among Middle East population and paves the way of introducing an efficient population based panel of genetic markers for the early detection and management of ASD in Middle East countries.
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http://dx.doi.org/10.1186/s40246-021-00319-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7953769PMC
March 2021

Cytokines and the immune response in obesity-related disorders.

Adv Clin Chem 2021 24;101:135-168. Epub 2020 Sep 24.

Metabolic Syndrome Research Center, Mashhad University of Medical Sciences, Mashhad, Iran. Electronic address:

The increasing prevalence of obesity and the associated morbidity and mortality are important public health problems globally. There is an important relationship between an unhealthy lifestyle and increased serum inflammatory cytokines. Adipocytes secrete several pro-inflammatory cytokines involved in the recruitment and activation of macrophages resulting in chronic low-grade inflammation. Increased cytokines in obese individual are related to the progression of several disorders including cardiovascular disease, hypertension, and insulin resistance. In present review we have summarized the crucial roles of cytokines and their inflammatory functions in obesity-related immune disorders.
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http://dx.doi.org/10.1016/bs.acc.2020.06.004DOI Listing
July 2021

Chemokines as the critical factors during bladder cancer progression: an overview.

Int Rev Immunol 2021 16;40(5):344-358. Epub 2021 Feb 16.

Department of Medical Genetics and Molecular Medicine, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.

Bladder cancer (BCa) is one of the most frequent urogenital malignancies which is mainly observed among men. There are various genetic and environmental risk factors associated with BCa progression. Transurethral endoscopic resection and open ablative surgery are the main treatment options for muscle invasive BCa. BCG therapy is also employed following the endoscopic resection to prevent tumor relapse. The tumor microenvironment is the main interaction site of tumor cells and immune system in which the immune cells are recruited via chemokines and chemokine receptors. In present review we summarized the main chemokines and chemokine receptors which have been associated with histopathological features of BCa patients in the world. This review highlights the chemokines and chemokine receptors as critical markers in early detection and therapeutic purposes among BCa patients and clarifies their molecular functions during BCa progression and metastasis.
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http://dx.doi.org/10.1080/08830185.2021.1877287DOI Listing
October 2021

Genetic and molecular biology of systemic lupus erythematosus among Iranian patients: an overview.

Auto Immun Highlights 2021 Jan 30;12(1). Epub 2021 Jan 30.

Department of Medical Genetics and Molecular Medicine, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.

Background: Systemic lupus erythematosus (SLE) is a clinicopathologically heterogeneous chronic autoimmune disorder affecting different organs and tissues. It has been reported that there is an increasing rate of SLE incidence among Iranian population. Moreover, the Iranian SLE patients have more severe clinical manifestations compared with other countries. Therefore, it is required to introduce novel methods for the early detection of SLE in this population. Various environmental and genetic factors are involved in SLE progression.

Main Body: In present review we have summarized all of the reported genes which have been associated with clinicopathological features of SLE among Iranian patients.

Conclusions: Apart from the reported cytokines and chemokines, it was interestingly observed that the apoptosis related genes and non-coding RNAs were the most reported genetic abnormalities associated with SLE progression among Iranians. This review clarifies the genetics and molecular biology of SLE progression among Iranian cases. Moreover, this review paves the way of introducing an efficient panel of genetic markers for the early detection and better management of SLE in this population.
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http://dx.doi.org/10.1186/s13317-020-00144-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7847600PMC
January 2021

Non coding RNAs as the critical factors in chemo resistance of bladder tumor cells.

Diagn Pathol 2020 Nov 12;15(1):136. Epub 2020 Nov 12.

Department of Medical Genetics and Molecular Medicine, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.

Background: Bladder cancer (BCa) is the ninth frequent and 13th leading cause of cancer related deaths in the world which is mainly observed among men. There is a declining mortality rates in developed countries. Although, the majority of BCa patients present Non-Muscle-Invasive Bladder Cancer (NMIBC) tumors, only 30% of patients suffer from muscle invasion and distant metastases. Radical cystoprostatectomy, radiation, and chemotherapy have proven to be efficient in metastatic tumors. However, tumor relapse is observed in a noticeable ratio of patients following the chemotherapeutic treatment. Non-coding RNAs (ncRNAs) are important factors during tumor progression and chemo resistance which can be used as diagnostic and prognostic biomarkers of BCa.

Main Body: In present review we summarized all of the lncRNAs and miRNAs associated with chemotherapeutic resistance in bladder tumor cells.

Conclusions: This review paves the way of introducing a prognostic panel of ncRNAs for the BCa patients which can be useful to select a proper drug based on the lncRNA profiles of patients to reduce the cytotoxic effects of chemotherapy in such patients.
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http://dx.doi.org/10.1186/s13000-020-01054-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7659041PMC
November 2020

A Positive Association between a Western Dietary Pattern and High LDL-C among Iranian Population.

J Res Health Sci 2020 Jul 25;20(3):e00485. Epub 2020 Jul 25.

Department of Medical Genetics and Molecular Medicine, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.

Background: The association between the presence of dyslipidemia and major dietary patterns was examined in an adult Iranian population.

Study Design: A cross-sectional study.

Methods: This cross-sectional study was conducted among 4672 adults aged 35-65 yr old based on data from the Mashhad Stroke And Heart Atherosclerotic Disorder (MASHAD) Study initiated in 2010. Anthropometric and blood laboratory measurements were collected for all participants. Dietary intake was assessed using a validated 65-item food frequency questionnaire (FFQ). Dietary patterns were identified using factor analysis.

Results: The overall prevalence of dyslipidemia was 88% including elevated total cholesterol (38.9%), triglyceride (35.2%), low-density lipoprotein cholesterol (LDL-C) (35.3%) or decreased level of high-density lipoprotein cholesterol (HDL-C) (68.9%). After adjusting for potential confounding factors, participants with higher scores for a Western pattern with lower physical activity level and educational attainment, and higher current smoking habit, increased the risk of having a raised LDL-C (OR=1.17; 95% CI: 1.02, 1.34; P=0.02). However, there was no significant association between adherence to this dietary pattern and other types of dyslipidemia. There was no significant association between a balanced dietary pattern and dyslipidemia and its components (OR=0.90; 95% CI: 0.68, 1.18; P=0.431).

Conclusion: Dyslipidemia was more prevalent among individuals with higher consumption of a western dietary pattern. A direct association was found between adherence to Western dietary pattern and LDL-C level.
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http://dx.doi.org/10.34172/jrhs.2020.19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7585768PMC
July 2020

Role of tyrosine kinases in bladder cancer progression: an overview.

Cell Commun Signal 2020 08 14;18(1):127. Epub 2020 Aug 14.

Department of Medical Genetics and Molecular Medicine, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.

Background: Bladder cancer (BCa) is a frequent urothelial malignancy with a high ratio of morbidity and mortality. Various genetic and environmental factors are involved in BCa progression. Since, majority of BCa cases are diagnosed after macroscopic clinical symptoms, it is required to find efficient markers for the early detection. Receptor tyrosine-kinases (RTKs) and non-receptor tyrosine-kinases (nRTKs) have pivotal roles in various cellular processes such as growth, migration, differentiation, and metabolism through different signaling pathways. Tyrosine-kinase deregulations are observed during tumor progressions via mutations, amplification, and chromosomal abnormalities which introduces these factors as important candidates of anti-cancer therapies.

Main Body: For the first time in present review we have summarized all of the reported tyrosine-kinases which have been significantly associated with the clinicopathological features of BCa patients.

Conclusions: This review highlights the importance of tyrosine-kinases as critical markers in early detection and therapeutic purposes among BCa patients and clarifies the molecular biology of tyrosine-kinases during BCa progression and metastasis. Video abstract.
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http://dx.doi.org/10.1186/s12964-020-00625-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7427778PMC
August 2020

Role of extra cellular proteins in gastric cancer progression and metastasis: an update.

Genes Environ 2020 15;42:18. Epub 2020 May 15.

2Department of Medical Genetics and Molecular Medicine, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.

Background: Gastric cancer (GC) is one of the most common cancers in the world with a high ratio of mortality. Regarding the late diagnosis, there is a high ratio of distant metastasis among GC cases. Despite the recent progresses in therapeutic modalities, there is not still an efficient therapeutic method to increase survival rate of metastatic GC cases.

Main Body: Apart from the various intracellular signaling pathways which are involved in tumor cell migration and metastasis, the local microenvironment is also a critical regulator of tumor cell migration. Indeed, the intracellular signaling pathways also exert their final metastatic roles through regulation of extra cellular matrix (ECM). Therefore, it is required to assess the role of extra cellular components in biology of GC.

Conclusion: In the present review, we summarize 48 of the significant ECM components including 17 ECM modifying enzymes, seven extracellular angiogenic factors, 13 cell adhesion and cytoskeletal organizers, seven matricellular proteins and growth factors, and four proteoglycans and extra cellular glycoproteins. This review paves the way of determination of a specific extra cellular diagnostic and prognostic panel marker for the GC patients.
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http://dx.doi.org/10.1186/s41021-020-00157-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7227337PMC
May 2020

Genetics of blood malignancies among Iranian population: an overview.

Diagn Pathol 2020 May 6;15(1):44. Epub 2020 May 6.

Department of Medical Genetics and Molecular Medicine, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.

Background: Blood malignancies are among the leading causes of cancer related deaths in the world. Different environmental and genetic risk factors are involved in progression of blood malignancies. It has been shown that the lifestyle changes have affected the epidemiological patterns of these malignancies. Hematologic cancers are the 5th common cancer among Iranian population. It has been observed that there is a rising trend of blood malignancies incidences during the recent decades. Therefore, it is required to design novel diagnostic methods for the early detection of such malignancies in this population.

Main Body: In present review we have summarized all of the significant genes which have been reported among Iranian patients with blood malignancies. The reported genes were categorized based on their cell and molecular functions to clarify the molecular biology and genetics of blood malignancies among Iranian patients.

Conclusion: It was observed that the epigenetic and immune response factors were the most frequent molecular processes associated with progression of blood malignancies among Iranian population. This review paves the way of introducing a population based panel of genetic markers for the early detection of blood malignancies in this population.
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http://dx.doi.org/10.1186/s13000-020-00968-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7201799PMC
May 2020

Genetic and molecular biology of bladder cancer among Iranian patients.

Mol Genet Genomic Med 2020 06 6;8(6):e1233. Epub 2020 Apr 6.

Department of Medical Genetics and Molecular Medicine, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.

Background: Bladder cancer (BC) is the sixth common cancer among Iranians. Various risk factors such as smoking, body mass index, chronic infection, age, and genetic factors are associated with BC progression.

Methods: It has been shown that a significant ratio of patients have tumors with muscle bladder layer invasion and poor prognosis at the time of diagnosis. Therefore, the early detection of tumors is required to reduce the mortality rate of BC cases. Since there is a wide geographical incidence variation in BC in Iran, it seems that the ethnic and genetic factors can be the main risk factors among Iranian BC patients.

Results: For the first time, in present review we have summarized all of the reported genes among Iranian BC patients until now which were significantly associated with tumorigenesis. Moreover, we categorized all of the reported genes based on their cell and molecular functions to clarify the genetic and molecular biology of BC among Iranian population.

Conclusion: This review paves the way of determination of a population-based genetic panel markers for the early detection of BC in this population.
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http://dx.doi.org/10.1002/mgg3.1233DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7284045PMC
June 2020

The effect of edelfosine on GRA1 and MIC3 expressions in acute toxoplasmosis.

Parasitol Res 2020 Apr 22;119(4):1371-1380. Epub 2020 Jan 22.

Toxoplasma Research Center, Mazandaran University of Medical Sciences, Sari, Iran.

Phosphoinositide-dependent phospholipase-C (PI-PLC) triggers the calcium signaling pathway which plays an important role in dense granule and microneme secretion and pathogenesis of Toxoplasma gondii (T. gondii). There are limited data about the effects of phospholipid analogues against T. gondii. The current study assessed the effect of edelfosine, as a phospholipid analogue, on GRA1 and MIC3 expressions using in vitro and in vivo models of acute toxoplasmosis. Infected Vero cells were treated by edelfosine in two subgroups: 24 h following the cell infection and treatment at the same time of cell infection. Animal study was performed on forty mice in four groups including non-infected, infected untreated, infected edelfosine-treated, and infected pyrimethamine-treated. Gene and protein expression analyses were done using quantitative real-time PCR and western blot, respectively. Edelfosine significantly reduced the GRA1 (P < 0.01) and MIC3 (P < 0.01) mRNA and protein expressions in 24 h following the cell infection and at the same time of cell infection groups. In vivo study showed that the edelfosine significantly reduced the GRA1 expression in eye, and MIC3 expression in brain and liver. Moreover, the edelfosine-treated infected mice had significant higher survival rate compared with uninfected mice. The reducing effect of edelfosine on GRA1 and MIC3 mRNA and protein levels 24 h following the cell infection was more than treatment at the same time of cell infection group. Moreover, the effect of edelfosine on GRA1 and MIC3 expression in animal tissues was variable. These data showed that the edelfosine may decrease the T. gondii excretory/secretory antigens through inhibition of PI-PLC.
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http://dx.doi.org/10.1007/s00436-020-06601-xDOI Listing
April 2020

Long non-coding RNAs as the critical factors during tumor progressions among Iranian population: an overview.

Cell Biosci 2020 14;10. Epub 2020 Jan 14.

2Department of Medical Genetics and Molecular Medicine, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.

Background: Cancer is associated with various genetic and environmental risk factors. Beside the mutations or aberrant expression of protein-coding genes, the genetic deregulation of non-coding RNAs has also an important role during tumor progression and metastasis. Long non-coding RNAs (lncRNAs) are a class of ncRNAs larger than 200 nucleotides that may function as tumor-suppressor or oncogene.

Main Body: There is a raising trend of cancer incidence among Iranian population during the last decades. Therefore, it is required to prepare a general population specific panel of genetic markers for the early detection of cancer in this population. The tissue-specific expression characteristics and high stability in body fluids highlight the lncRNAs as efficient diagnostic and prognostic noninvasive biomarkers in cancer. In present review we summarized all of the lncRNAs which have been reported until now in different tumors among Iranian patients.

Conclusions: This review paves the way of introducing a population based noninvasive diagnostic panel of lncRNAs for the early detection of tumor cells among Iranian population.
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http://dx.doi.org/10.1186/s13578-020-0373-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6961246PMC
January 2020

Genetic and molecular determinants of prostate cancer among Iranian patients: An update.

Crit Rev Clin Lab Sci 2020 01 6;57(1):37-53. Epub 2019 Sep 6.

Medical Genetics Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.

Prostate cancer (PCa) is one of the most common age-related cancers among men. Various environmental and genetic factors are involved in the development and progression of PCa. In most cases, the primary symptoms of disease are not severe. Therefore, it is common for patients to be referred with severe clinical manifestations at advanced stages of disease. Since this malignancy is age related and Iran will face a significant increase in the number of seniors, it is expected that the prevalence of PCa among Iranian men will rise. PCa progression has been observed to be associated with genetic and ethnic factors. It may therefore be clinically useful to determine a panel of genetic markers, in addition to routine diagnostic methods, to detect tumors in the early stages. In the present review, we have summarized the reported genetic markers in PCa Iranian patients to pave the way for the determination of an ethnic specific genetic marker panel for the early detection of PCa. To understand the genetic and molecular biology of PCa among Iranians, we have categorized these genetic markers based on their cellular functions.
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http://dx.doi.org/10.1080/10408363.2019.1657061DOI Listing
January 2020

Reducing effect of insulin resistance on alpha-synuclein gene expression in skeletal muscle.

Diabetol Metab Syndr 2019 2;11:99. Epub 2019 Dec 2.

6Student Research Committee, School of Medicine, North Khorasan University of Medical Sciences, Bojnurd, Iran.

Background: Alpha-synuclein (SNCA) as the presynaptic protein is expressed in different tissues and prevents insulin-resistance (IR) through increasing glucose-uptake by adipocytes and muscles. However, the effect of insulin metabolism on SNCA expression has scarcely elucidated. In present study we assessed the probable effect of insulin resistance on SNCA expression in muscle C2C12 cells and also skeletal muscle tissues of type 2 diabetic mice.

Materials And Methods: Sixteen male C57BL/6 mice were divided into two experimental groups, including control and type 2 diabetic mice with IR (induced by high-fat diet + low-dose streptozotocin). The animals of the study involved the measurements of fasting blood glucose, oral-glucose-tolerance-test, as well as fasting plasma insulin. Moreover, insulin-resistant and insulin-sensitive muscle C2C12 cells were prepared. The insulin-resistance was confirmed by the glucose-uptake assay. Comparative quantitative real time PCR was used to assess the expression.

Results: The obtained results have showed a significant ~ 27% decrease in expression level in muscle tissue of diabetic mice (P = 0.022). Moreover, there was a significant change of expression in insulin-resistant C2C12 cells (P < 0.001).

Conclusion: Type 2 diabetes due to insulin-resistance can decrease gene expression in muscles. In addition to the role of SNCA in cell susceptibility to insulin and glucose uptake, the SNCA expression can also be affected by insulin metabolism.
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http://dx.doi.org/10.1186/s13098-019-0499-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6889442PMC
December 2019

Ovarian cancer stem cells and targeted therapy.

J Ovarian Res 2019 Dec 6;12(1):120. Epub 2019 Dec 6.

Medical Genetics Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.

Background: Ovarian cancer has the highest ratio of mortality among gynecologic malignancies. Chemotherapy is one of the most common treatment options for ovarian cancer. However, tumor relapse in patients with advanced tumor stage is still a therapeutic challenge for its clinical management.

Main Body: Therefore, it is required to clarify the molecular biology and mechanisms which are involved in chemo resistance to improve the survival rate of ovarian cancer patients. Cancer stem cells (CSCs) are a sub population of tumor cells which are related to drug resistance and tumor relapse.

Conclusion: In the present review, we summarized the recent findings about the role of CSCs in tumor relapse and drug resistance among ovarian cancer patients. Moreover, we focused on the targeted and combinational therapeutic methods against the ovarian CSCs.
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http://dx.doi.org/10.1186/s13048-019-0588-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6896744PMC
December 2019

Genetic and Molecular Biology of Multiple Sclerosis Among Iranian Patients: An Overview.

Authors:
Meysam Moghbeli

Cell Mol Neurobiol 2020 Jan 3;40(1):65-85. Epub 2019 Sep 3.

Medical Genetics Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.

Multiple sclerosis (MS) is one if the common types of autoimmune disorders in developed countries. Various environmental and genetic factors are associated with initiation and progression of MS. It is believed that the life style changes can be one of the main environmental risk factors. The environmental factors are widely studied and reported, whereas minority of reports have considered the role of genetic factors in biology of MS. Although Iran is a low-risk country in the case of MS prevalence, it has been shown that there was a dramatically rising trend of MS prevalence among Iranian population during recent decades. Therefore, it is required to assess the probable MS risk factors in Iran. In the present study, we summarized all of the reported genes until now which have been associated with MS susceptibility among Iranian patients. To clarify the probable molecular biology of MS progression, we categorized these reported genes based on their cellular functions. This review paves the way of introducing a specific population-based diagnostic panel of genetic markers among the Iranian population for the first time in the world.
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http://dx.doi.org/10.1007/s10571-019-00731-2DOI Listing
January 2020

Genetic and molecular bases of esophageal Cancer among Iranians: an update.

Diagn Pathol 2019 Aug 31;14(1):97. Epub 2019 Aug 31.

Medical Genetics Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.

Background: Esophageal cancer is one of the leading causes of cancer related deaths among the Iranians. There is still a high ratio of mortality and low 5 years survival which are related to the late onset and diagnosis. Majority of patients refer for the treatment in advanced stages of tumor progression.

Main Body: It is required to define an efficient local panel of diagnostic and prognostic markers for the Iranians. Indeed such efficient specific panel of markers will pave the way to decrease the mortality rate and increase the 5 years survival among the Iranian patients via the early diagnosis and targeted therapy.

Conclusion: in present review we have reported all of the molecular markers in different signaling pathways and cellular processes which have been assessed among the Iranian esophageal cancer patients until now.
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http://dx.doi.org/10.1186/s13000-019-0875-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6717340PMC
August 2019

Genetics of recurrent pregnancy loss among Iranian population.

Authors:
Meysam Moghbeli

Mol Genet Genomic Med 2019 09 30;7(9):e891. Epub 2019 Jul 30.

Medical Genetics Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.

Background: Recurrent pregnancy loss (RPL) is one of the most common reproductive disorders which is defined as the occurrence of recurrent miscarriage before 24 weeks of gestation and is observed among 1%-5% of women.

Methods: Various factors are associated with RPL such as immunological disorders, maternal age, obesity, alcohol, chromosomal abnormality, endocrine disorders, and uterine abnormalities. About half of the RPL cases are related with chromosomal abnormalities. Therefore, RPL genetic tests are mainly limited to karyotyping. However, there is a significant proportion of RPL cases without any chromosomal abnormalities that can be related to the single-gene aberrations. Therefore, it is required to prepare a diagnostic panel of genetic markers besides karyotyping.

Results: In the present review, we have summarized all the significant reported genes until now which are associated with RPL among Iranian women. We categorized all the reported genes based on their cellular and molecular functions in order to determine the molecular bases of RPL in this population.

Conclusion: This review paves the way of introducing a population-based diagnostic panel of genetic markers for the first time among Iranian RPL cases. Moreover, this review clarifies the genetic and molecular bases of RPL in this population.
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http://dx.doi.org/10.1002/mgg3.891DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6732315PMC
September 2019
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