Publications by authors named "Elham Ahmadian"

51 Publications

Immunosuppressant Management in Renal Transplant Patients with COVID-19.

Biomed Res Int 2021 14;2021:9318725. Epub 2021 Oct 14.

Kidney Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.

The coronavirus disease 2019 (COVID-19) pandemic poses a special risk for both immunosuppressed patients, especially transplant recipients. Although the knowledge about this infection is growing, many uncertainties remain, particularly regarding the kidney. Kidney transplant recipients (KDRs) should be considered immunocompromised hosts since a potential risk for infection, comorbidity, and immunosuppression exposure exists. Additionally, the management of immunosuppressive agents in KDRs remains challenging. Potential drug interactions with immunosuppressive treatment escalated the risk of unwanted side effects. In this review, we aimed to attain an augmented awareness and improved management immunosuppressant for COVID-19 KDRs.
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http://dx.doi.org/10.1155/2021/9318725DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8531766PMC
October 2021

The Association of Sleep Quality and Vitamin D Levels in Hemodialysis Patients.

Biomed Res Int 2021 21;2021:4612091. Epub 2021 Sep 21.

Kidney Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.

Background: To date, hemodialysis (HD) is the most common therapy for chronic kidney disease (CKD) patients. However, it causes different complications such as sleep disorders. Sleep regulation is connected to vitamin D; hence, its deficiency might influence the quality and duration of sleep. This study is aimed at evaluating the correlation of sleep quality and vitamin D levels in 80 HD patients.

Methods: This cross-sectional study was performed on 80 hemodialysis patients admitted to 29 Bahman hospitals in Tabriz, Iran. Before beginning of dialysis, serum 25 (OH) D levels were assessed among patients and the sleep patterns and sleep quality of patients were accurately calculated by the Pittsburgh sleep quality index (PSQI) standard questionnaire.

Results: Our results showed that 22 HD patients (27.5%) had severe sleep disorders. In addition, it was found that serum levels of vitamin D had significant correlation with sleep quality ( = -0.341, = 0.002) in general, even after adjusting confounding factors such as calcium (Ca), phosphate (P), and parathyroid hormone (PTH) level. In poor sleepers (PSQI ≤ 5), a negative correlation was observed between the levels of vitamin D and PSQI score ( = -0.397, = 0.004). PSQI scores in the normal range of PTH ( = -0.377, = 0.006) and in >600 pg/ml of PTH ( = -0.675, = 0.011) had a correlation with vitamin D levels. The level of vitamin D was the single independent predictor of sleep efficiency ( coefficient = -0.386, = 0.001).

Conclusion: The present project reported that the positive effect of vitamin D is associated with sleep disorder in HD patients. In future studies, normal levels of Ca and P should be considered along with normal vitamin D levels among the included patients.
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http://dx.doi.org/10.1155/2021/4612091DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8481063PMC
September 2021

The Use of Infrapatellar Fat Pad-Derived Mesenchymal Stem Cells in Articular Cartilage Regeneration: A Review.

Int J Mol Sci 2021 Aug 26;22(17). Epub 2021 Aug 26.

Department of Toxicology and Pharmacology, Maragheh University of Medical Sciences, Maragheh 78151-55158, Iran.

Cartilage is frequently damaged with a limited capacity for repair. Current treatment strategies are insufficient as they form fibrocartilage as opposed to hyaline cartilage, and do not prevent the progression of degenerative changes. There is increasing interest in the use of autologous mesenchymal stem cells (MSC) for tissue regeneration. MSCs that are used to treat articular cartilage defects must not only present a robust cartilaginous production capacity, but they also must not cause morbidity at the harvest site. In addition, they should be easy to isolate from the tissue and expand in culture without terminal differentiation. The source of MSCs is one of the most important factors that may affect treatment. The infrapatellar fat pad (IPFP) acts as an important reservoir for MSC and is located in the anterior compartment of the knee joint in the extra-synovial area. The IPFP is a rich source of MSCs, and in this review, we discuss studies that demonstrate that these cells have shown many advantages over other tissues in terms of ease of isolation, expansion, and chondrogenic differentiation. Future studies in articular cartilage repair strategies and suitable extraction as well as cell culture methods will extend the therapeutical application of IPFP-derived MSCs into additional orthopedic fields, such as osteoarthritis. This review provides the latest research concerning the use of IPFP-derived MSCs in the treatment of articular cartilage damage, providing critical information for the field to grow.
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http://dx.doi.org/10.3390/ijms22179215DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8431575PMC
August 2021

Targeting Mitochondrial Biogenesis with Polyphenol Compounds.

Oxid Med Cell Longev 2021 12;2021:4946711. Epub 2021 Jul 12.

Pharmacology and Toxicology Department, Maragheh University of Medical Sciences, Maragheh, Iran.

Appropriate mitochondrial physiology is an essential for health and survival. Cells have developed unique mechanisms to adapt to stress circumstances and changes in metabolic demands, by meditating mitochondrial function and number. In this context, sufficient mitochondrial biogenesis is necessary for efficient cell function and haemostasis, which is dependent on the regulation of ATP generation and maintenance of mitochondrial DNA (mtDNA). These procedures play a primary role in the processes of inflammation, aging, cancer, metabolic diseases, and neurodegeneration. Polyphenols have been considered as the main components of plants, fruits, and natural extracts with proven therapeutic effects during the time. These components regulate the intracellular pathways of mitochondrial biogenesis. Therefore, the current review is aimed at representing an updated review which determines the effects of different natural polyphenol compounds from various plant kingdoms on modulating signaling pathways of mitochondrial biogenesis that could be a promising alternative for the treatment of several disorders.
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http://dx.doi.org/10.1155/2021/4946711DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8289611PMC
July 2021

Osteogenic Differentiation of Mesenchymal Stem Cells via Curcumin-Containing Nanoscaffolds.

Stem Cells Int 2021 17;2021:1520052. Epub 2021 Jul 17.

Food and Drug Safety Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.

The diverse pleiotropic pharmacological effects of curcumin nanoformulations have turned it into an attractive natural compound in different health-related problems. A great body of evidence has shown the impact of curcumin and its nanoformulations on the differentiation of stem cells. The current review highlights cellular and molecular mechanisms connected with the osteogenic differentiation of mesenchymal stem cells (MSCs) in the scaffolds benefiting from the presence of nanocurcumin pointing toward the role of inhibitory or stimulant signal transduction pathways in detail. Moreover, the effects of different concentrations as well as the structural modifications of curcumin on the differentiation of MSCs have been addressed.
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http://dx.doi.org/10.1155/2021/1520052DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8313343PMC
July 2021

The Impact of Intravenous Iron Supplementation on Hematinic Parameters and Erythropoietin Requirements in Hemodialysis Patients.

Adv Ther 2021 08 12;38(8):4413-4424. Epub 2021 Jul 12.

Kidney Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.

Introduction: Anemia is one of the most common complications of chronic kidney disease (CKD). As a result of the side effects of high doses of recombinant human erythropoietin (rhEPO) and the differences in the standard dose of the injectable iron, this study aimed to evaluate the effect of high and low intravenous iron supplementation on hematinic parameters and EPO requirements in patients under hemodialysis.

Methods: This multicenter, randomized, double-blind clinical trial was conducted on 60 patients with CKD admitted to Sina and 29 Bahman hospitals in Tabriz, Iran in 2019-2020 to undergo hemodialysis. In the two studied groups, low (100 mg/week) and high (400 mg/week) doses of iron were administered and subjects were followed up for 6 months. The incidence of acute myocardial ischemia, stroke, and mortality during 6 months was recorded.

Results: The required rhEPO dosage (mg/week) to maintain hemoglobin levels between 10 and 12 g/dL in the high-dose iron group was significantly decreased during the follow-up period (52,129.03 ± 23,810 vs. 45,760 ± 20,978.71, P ≤ 0.028). Transferrin saturation (TSAT) index had a significant upward trend after iron injection and significant correlations with the serum levels of Fe (r ≥ 0.353, P ≤ 0.007), ferritin (r ≥ 0.315, P ≤ 0.016), and total iron binding capacity (r ≥ 0.219, P < 0.050) during the follow-up period in the studied groups.

Conclusion: High-dose intravenous iron (400 mg/week) can reduce the mean dose of rhEPO requirements and increase the TSAT index over a period of 6 months in hemodialysis patients. High-dose IV iron administration can decrease cardiovascular events in hemodialysis patients with iron deficiency anemia.
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http://dx.doi.org/10.1007/s12325-021-01826-3DOI Listing
August 2021

Podocyte-derived microparticles in IgA nephropathy.

Biomed Pharmacother 2021 Sep 5;141:111891. Epub 2021 Jul 5.

Kidney Research Center, Tabriz University of Medical Sciences, Tabriz, Iran. Electronic address:

Microparticles are a general term for different types of cell plasma membrane-originated vesicles that are released into the extracellular environment. The paracrine action of these nano-sized vesicles is crucial for intercellular communications through the transfer of diverse lipids, cytosolic proteins, RNA as well as microRNAs. The progression of different diseases influences the composition, occurrence, and functions of these cell-derived particles. Podocyte injury has been shown to have an important role in the pathophysiology of many glomerular diseases including IgA nephropathy (IgAN). This review would focus on the possible potential of podocyte-derived microparticles detected in urine to be used as a diagnostic tool in IgAN.
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http://dx.doi.org/10.1016/j.biopha.2021.111891DOI Listing
September 2021

Application of Advanced Nanomaterials for Kidney Failure Treatment and Regeneration.

Materials (Basel) 2021 May 29;14(11). Epub 2021 May 29.

Pharmaceutical Analysis Research Center, Tabriz University of Medical Sciences, Tabriz 5166614756, Iran.

The implementation of nanomedicine not only provides enhanced drug solubility and reduced off-target adverse effects, but also offers novel theranostic approaches in clinical practice. The increasing number of studies on the application of nanomaterials in kidney therapies has provided hope in a more efficient strategy for the treatment of renal diseases. The combination of biotechnology, material science and nanotechnology has rapidly gained momentum in the realm of therapeutic medicine. The establishment of the bedrock of this emerging field has been initiated and an exponential progress is observed which might significantly improve the quality of human life. In this context, several approaches based on nanomaterials have been applied in the treatment and regeneration of renal tissue. The presented review article in detail describes novel strategies for renal failure treatment with the use of various nanomaterials (including carbon nanotubes, nanofibrous membranes), mesenchymal stem cells-derived nanovesicles, and nanomaterial-based adsorbents and membranes that are used in wearable blood purification systems and synthetic kidneys.
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http://dx.doi.org/10.3390/ma14112939DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8198057PMC
May 2021

The Potential Application of Magnetic Nanoparticles for Liver Fibrosis Theranostics.

Front Chem 2021 14;9:674786. Epub 2021 May 14.

Center of Experimental Orthopaedics, Saarland University Medical Center, Homburg, Germany.

Liver fibrosis is a major cause of morbidity and mortality worldwide due to chronic liver damage and leading to cirrhosis, liver cancer, and liver failure. To date, there is no effective and specific therapy for patients with hepatic fibrosis. As a result of their various advantages such as biocompatibility, imaging contrast ability, improved tissue penetration, and superparamagnetic properties, magnetic nanoparticles have a great potential for diagnosis and therapy in various liver diseases including fibrosis. In this review, we focus on the molecular mechanisms and important factors for hepatic fibrosis and on potential magnetic nanoparticles-based therapeutics. New strategies for the diagnosis of liver fibrosis are also discussed, with a summary of the challenges and perspectives in the translational application of magnetic nanoparticles from bench to bedside.
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http://dx.doi.org/10.3389/fchem.2021.674786DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8161198PMC
May 2021

Vitamin D Receptor and Vitamin D Binding Protein Gene Polymorphisms Are Associated with Renal Allograft Outcome.

Nutrients 2021 Mar 27;13(4). Epub 2021 Mar 27.

Center of Experimental Orthopaedics, Saarland University Medical Center, D-66421 Homburg, Germany.

Vitamin D deficiency has adverse effects on renal allograft outcomes, and polymorphisms of genes encoding vitamin D-binding protein (VDBP) and vitamin D receptor (VDR) are defined to play a role in these conditions. The goal of the current investigation was to evaluate the connection between those polymorphisms with acute rejection, viral infection history, and recipients' vitamin D status. In this study, 115 kidney transplant recipients and 100 healthy individuals were included. VDR polymorphisms including I (rs2228570), (rs7975232), (rs1544410), as well as VDBP (rs7040) polymorphisms were studied using high resolution melting (PCR-HRM) analysis among the studied groups. The frequency of G allele in rs7975232 polymorphism in the kidney transplant recipients was 0.63 times lower than healthy individuals ( = 0.026). Further, the G allele frequency in VDBP rs7040 polymorphism was significantly lower in patients with allograft rejection ( = 0.002). Considering the incidence of viral infection, significant differences were identified between the frequencies of VDR I (OR = 2.035; 95% CI 1.06-2.89, = 0.030) and VDBP rs7040 (OR = 0.40; 95% CI 0.24-0.67, < 0.001) T alleles in the studied groups. Moreover, the VDBP rs7040 GG genotype distribution was low in the recipients with a history of viral infection ( = 0.004). VDR (I) and VDBP (rs7040) alleles and their genotype distribution are significantly associated with allograft outcomes including allograft rejection and viral infection in the studied population.
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http://dx.doi.org/10.3390/nu13041101DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8067077PMC
March 2021

A Comprehensive Review of Detection Methods for SARS-CoV-2.

Microorganisms 2021 Jan 22;9(2). Epub 2021 Jan 22.

Center of Experimental Orthopaedics, Saarland University Medical Center, D-66421 Homburg/Saar, Germany.

Recently, the outbreak of the coronavirus disease 2019 (COVID-19), caused by the SARS-CoV-2 virus, in China and its subsequent spread across the world has caused numerous infections and deaths and disrupted normal social activity. Presently, various techniques are used for the diagnosis of SARS-CoV-2 infection, with various advantages and weaknesses to each. In this paper, we summarize promising methods, such as reverse transcription-polymerase chain reaction (RT-PCR), serological testing, point-of-care testing, smartphone surveillance of infectious diseases, nanotechnology-based approaches, biosensors, amplicon-based metagenomic sequencing, smartphone, and wastewater-based epidemiology (WBE) that can also be utilized for the detection of SARS-CoV-2. In addition, we discuss principles, advantages, and disadvantages of these detection methods, and highlight the potential methods for the development of additional techniques and products for early and fast detection of SARS-CoV-2.
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http://dx.doi.org/10.3390/microorganisms9020232DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7911200PMC
January 2021

Dysregulated levels of glycogen synthase kinase-3β (GSK-3β) and miR-135 in peripheral blood samples of cases with nephrotic syndrome.

PeerJ 2020 16;8:e10377. Epub 2020 Dec 16.

Center of Experimental Orthopaedics, Universität des Saarlandes, Homburg/Saar, Germany.

Background: Glycogen synthase kinase-3 (GSK-3β) is a serine/threonine kinase with multifunctions in various physiological procedures. Aberrant level of GSK-3β in kidney cells has a harmful role in podocyte injury.

Methods: In this article, the expression levels of GSK-3β and one of its upstream regulators, miR-135a-5p, were measured in peripheral blood mononuclear cells (PBMCs) of cases with the most common types of nephrotic syndrome (NS); focal segmental glomerulosclerosis (FSGS) and membranous glomerulonephritis (MGN). In so doing, fifty-two cases along with twenty-four healthy controls were included based on the strict criteria.

Results: Levels of GSK-3β mRNA and miR-135 were measured with quantitative real-time PCR. There were statistically significant increases in GSK-3β expression level in NS ( = 0.001), MGN ( = 0.002), and FSGS ( = 0.015) groups compared to the control group. Dysregulated levels of miR-135a-5p in PBMCs was not significant between the studied groups. Moreover, a significant decrease was observed in the expression level of miR-135a-5p in the plasma of patients with NS ( = 0.020), MGN ( = 0.040), and FSGS ( = 0.046) compared to the control group. ROC curve analysis approved a diagnostic power of GSK-3β in discriminating patients from healthy controls (AUC: 0.72,  = 0.002) with high sensitivity and specificity.

Conclusions: Dysregulated levels of GSK-3β and its regulator miR-135a may participate in the pathogenesis of NS with different etiology. Therefore, more research is needed for understanding the relationship between them.
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http://dx.doi.org/10.7717/peerj.10377DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7749650PMC
December 2020

Nrf-2 as a therapeutic target in acute kidney injury.

Life Sci 2021 Jan 13;264:118581. Epub 2020 Oct 13.

Kidney Research Center, Tabriz University of Medical Sciences, Tabriz, Iran. Electronic address:

Multifaceted cellular pathways exhibit a crucial role in the preservation of homeostasis at the molecular, cellular, and organism levels. One of the most important of these protective cascades is Nuclear factor E2-related factor (Nrf-2) that regulates the expression of several genes responsible for cellular detoxification, antioxidant function, anti-inflammation, drug/xenobiotic transportation, and stress-related factors. A growing body of evidence provides information regarding the protective role of Nrf-2 against a number of kidney diseases. Acute kidney injury (AKI) is a substantial clinical problem that causes a huge social burden. In the kidneys, Nrf-2 exerts a dynamic role in improving the injury triggered by inflammation and oxidative stress. Understanding of the exact molecular mechanisms underlying AKI is vital in order to determine the equilibrium between renal adaptation and malfunction and thus reduce disease progression. This review highlights the role of Nrf-2 targeting against AKI and provides evidence that targeting Nrf-2 to prevail oxidative damage and its consequences might exhibit protective effects in kidney diseases.
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http://dx.doi.org/10.1016/j.lfs.2020.118581DOI Listing
January 2021

Therapeutic benefits of rutin and its nanoformulations.

Phytother Res 2021 Apr 15;35(4):1719-1738. Epub 2020 Oct 15.

Department of Oral Medicine, Faculty of Dentistry, Tabriz University of Medical Sciences, Tabriz, Iran.

Background: Rutin as a natural flavonoid compound has revealed an extensive range of therapeutic potentials.

Purpose: The current paper is focused on the numerous studies on rutin nanoformulations regarding its broad spectrum of therapeutic potentials.

Study And Methods: A review was conducted in electronic databases (PubMed) to identify relevant published literature in English. No restrictions on publication date were imposed.

Results: The literature search provided 7,078 results for rutin. Among them, 25 papers were related to the potential biological activities of rutin nanoformulations. Polymeric nanoparticles were the most studied nanoformulations for rutin (14 titles) and lipid nanoparticles (5 titles) were in second place. The reviewed literature showed that rutin has been used as an antimicrobial, antifungal, and anti-allergic agent. Improving the bioavailability of rutin using novel drug-delivery methods will help the investigators to use its useful effects in the treatment of various chronic human diseases.

Conclusion: It can be concluded that the preparation of rutin nanomaterials for the various therapeutic objects confirmed the enhanced aqueous solubility as well as enhanced efficacy compared to conventional delivery of rutin. However, more investigations should be conducted to confirm the improved bioavailability of the rutin nanoformulations.
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http://dx.doi.org/10.1002/ptr.6904DOI Listing
April 2021

Covid-19 and kidney injury: Pathophysiology and molecular mechanisms.

Rev Med Virol 2021 05 6;31(3):e2176. Epub 2020 Oct 6.

Kidney Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.

The novel coronavirus (SARS-CoV-2) has turned into a life-threatening pandemic disease (Covid-19). About 5% of patients with Covid-19 have severe symptoms including septic shock, acute respiratory distress syndrome, and the failure of several organs, while most of them have mild symptoms. Frequently, the kidneys are involved through direct or indirect mechanisms. Kidney involvement mainly manifests itself as proteinuria and acute kidney injury (AKI). The SARS-CoV-2-induced kidney damage is expected to be multifactorial; directly it can infect the kidney podocytes and proximal tubular cells and based on an angiotensin-converting enzyme 2 (ACE2) pathway it can lead to acute tubular necrosis, protein leakage in Bowman's capsule, collapsing glomerulopathy and mitochondrial impairment. The SARS-CoV-2-driven dysregulation of the immune responses including cytokine storm, macrophage activation syndrome, and lymphopenia can be other causes of the AKI. Organ interactions, endothelial dysfunction, hypercoagulability, rhabdomyolysis, and sepsis are other potential mechanisms of AKI. Moreover, lower oxygen delivery to kidney may cause an ischaemic injury. Understanding the fundamental molecular pathways and pathophysiology of kidney injury and AKI in Covid-19 is necessary to develop management strategies and design effective therapies.
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http://dx.doi.org/10.1002/rmv.2176DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7646060PMC
May 2021

Asthma and metabolic syndrome: a comprehensive systematic review and meta-analysis of observational studies.

J Cardiovasc Thorac Res 2020 31;12(2):120-128. Epub 2020 May 31.

Social Determinants of Health Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

This study aimed to perform a meta-analysis on the prevalence of metabolic syndrome (MetS) among patients with asthma and to measure the association asthma has with MetS. The Web of Science, Medline, Scopus, Embase and Google Scholar were searched using the "Asthma", "Metabolic Syndrome", "Dysmetabolic Syndrome", "Cardiovascular Syndrome", "Insulin Resistance Syndrome", "Prevalence", "Odds Ratio", "Cross-Sectional Studies", and "Case-Control Studies" keywords. All observational studies reporting the prevalence of MetS among people with and without asthma were included in the study. In the presence of heterogeneity, random-effects models were used to pool the prevalence and odds ratios (OR), as measures of association in cross-sectional and case-control/ cohort studies, respectively. The prevalence of MetS among patients with asthma (8 studies) and the OR comparing the prevalence of MetS among patients with and without asthma (5 studies) were pooled separately. The pooled prevalence of MetS among patients with asthma was found to be 25% (95% confidence interval (CI): 13%-38%). In contrast, the overall pooled OR for MetS in patients with asthma, compared to healthy controls, was 1.34 (95% CI: 0.91-1.76), which was not statistically significant. The prevalence of MetS was relatively high in patients with asthma. Furthermore, the odds of MetS was higher in patients with asthma, compared to healthy controls, although this difference was not statistically significant. More original studies among different populations are needed in order to more accurately examine the association between asthma and MetS, as well as the relationship asthma has with the individual components of MetS.
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http://dx.doi.org/10.34172/jcvtr.2020.20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7321001PMC
May 2020

Effects of quercetin loaded nanostructured lipid carriers on the paraquat-induced toxicity in human lymphocytes.

Pestic Biochem Physiol 2020 Jul 19;167:104586. Epub 2020 Apr 19.

Department of Biophysics and Molecular Biology, Baku State University, Baku, Azerbaijan; Russian Institute for Advanced Study, Moscow State Pedagogical University, 1/1, Malaya Pirogovskaya St, Moscow 119991, Russian Federation; Joint Ukraine-Azerbaijan International Research and Education Center of Nanobiotechnology and Functional Nanosystems, Drohobych, Ukraine, Baku, Azerbaijan.

Paraquat (PQ) as a herbicide and an environmental pollutant with increasing importance due to its toxicity to humans and animals. This study aimed to evaluate the protective and antioxidant activity of quercetin loaded Nanostructured Lipid Carriers (QNLC) against toxicity induced by PQ. Blood lymphocytes were prepared using Ficoll polysaccharide and subsequently by gradient centrifugation. The QNLC was prepared using an ultra-sonication method, which was characterized by dynamic light scattering (DLS) and transmission electron microscopy (TEM). The viability, reactive oxygen species (ROS), lipid peroxidation (LPO), mitochondrial membrane potential (MMP), lysosome membrane integrity, Bax and Bcl2 gene expression were evaluated in human isolated lymphocytes. The results showed spherical QNLCs with nano-size range (52.7 nm) and high drug encapsulation efficiency (98.5% -96%). The results also indicated that PQ induced cell death, as well as ROS production, decreased by QNLC in human lymphocytes. Also, QNLC meaningfully restored MMP reduction, lysosomal membrane destabilization, and lipid peroxidation and were capable of preventing PQ-treated change in Bax and Bcl2 gene expression. We report that QNLC, have a significantly higher capacity to prevent PQ-induced toxicity than Q itself. It is suggested that the QNLC is a promising antioxidant for drug delivery to be used as a therapeutic and prophylactic agent for PQ poisoning.
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http://dx.doi.org/10.1016/j.pestbp.2020.104586DOI Listing
July 2020

Monitoring of drug resistance towards reducing the toxicity of pharmaceutical compounds: Past, present and future.

J Pharm Biomed Anal 2020 Jul 19;186:113265. Epub 2020 Mar 19.

Pharmaceutical Analysis Research Center, Tabriz University of Medical Sciences, Tabriz, Iran. Electronic address:

Drug resistance is worldwide health care crisis which decrease drug efficacy and developing toxicities. Effective resistance detection techniques could alleviate treatment cost and mortality associated with this crisis. In this review, the conventional and modern analysis methods for monitoring of drug resistance are presented. Also, various types of emerging rapid and sensitive techniques including electrochemical, electrical, optical and nano-based methods for the screening of drug resistance were discussed. Applications of various methods for the sensitive and rapid detection of drug resistance are investigated. The review outlines existing key issues in the determination which must be overcome before any of these techniques becomes a feasible method for the rapid detection of drug resistance. In this review, the roles of nanomaterials on development of novel methods for the monitoring of drug resistance were presented. Also, limitations and challenges of conventional and modern methods were discussed.
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http://dx.doi.org/10.1016/j.jpba.2020.113265DOI Listing
July 2020

Pre-Eclampsia: Microbiota possibly playing a role.

Pharmacol Res 2020 05 15;155:104692. Epub 2020 Feb 15.

Kidney Research Center, Tabriz University of Medical Sciences, Tabriz, Iran. Electronic address:

Pre-eclampsia (PE) is a complication of pregnancy that is associated with mortality and morbidity in mothers and fetuses worldwide. Oxygen dysregulation in the placenta, abnormal remodeling of the spiral artery, defective placentation, oxidative stress at the fetal-maternal border, inflammation and angiogenic impairment in the maternal circulation are the main causes of this syndrome. These events result in a systemic and diffuse endothelial cell dysfunction, an essential pathophysiological feature of PE. The impact of bacteria on the multifactorial pathway of PE is the recent focus of scientific inquiry since microbes may cause each of the aforementioned features. Microbes and their derivatives by producing antigens and other inflammatory factors may trigger infection and inflammatory responses. A mother's bacterial communities in the oral cavity, gut, vagina, cervix and uterine along with the placenta and amniotic fluid microbiota may be involved in the development of PE. Here, we review the mechanistic and pathogenic role of bacteria in the development of PE. Then, we highlight the impact of alterations in a set of maternal microbiota (dysbiosis) on the pathogenesis of PE.
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http://dx.doi.org/10.1016/j.phrs.2020.104692DOI Listing
May 2020

Cell junction proteins: Crossing the glomerular filtration barrier in diabetic nephropathy.

Int J Biol Macromol 2020 Apr 18;148:475-482. Epub 2020 Jan 18.

Kidney Research Center, Tabriz University of Medical Sciences, Tabriz, Iran. Electronic address:

Diabetic nephropathy as a deleterious complication of diabetes mellitus and an important cause of end-stage renal failure is characterized by changes in the molecular and cellular levels. Cell-cell communication via the gap and tight junctions are involved in the pathogenesis of diseases such as diabetes and kidney failure. Studying cell junctions including gap junctions, tight junctions, and anchoring junctions within the nephron can be used as an early sign of diabetic nephropathy. Furthermore, cell junctions may be an upcoming target by pharmacological methods to improve treatments of diabetic nephropathy and pave the way to introduce promising therapeutic strategies based on cell-cell communications effects and its translation into clinical studies for the treatment of diabetic nephropathy.
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http://dx.doi.org/10.1016/j.ijbiomac.2020.01.168DOI Listing
April 2020

The Use of Nanomaterials in Tissue Engineering for Cartilage Regeneration; Current Approaches and Future Perspectives.

Int J Mol Sci 2020 Jan 14;21(2). Epub 2020 Jan 14.

Center of Experimental Orthopaedics, Saarland University Medical Center, D-66421 Homburg/Saar, Germany.

The repair and regeneration of articular cartilage represent important challenges for orthopedic investigators and surgeons worldwide due to its avascular, aneural structure, cellular arrangement, and dense extracellular structure. Although abundant efforts have been paid to provide tissue-engineered grafts, the use of therapeutically cell-based options for repairing cartilage remains unsolved in the clinic. Merging a clinical perspective with recent progress in nanotechnology can be helpful for developing efficient cartilage replacements. Nanomaterials, < 100 nm structural elements, can control different properties of materials by collecting them at nanometric sizes. The integration of nanomaterials holds promise in developing scaffolds that better simulate the extracellular matrix (ECM) environment of cartilage to enhance the interaction of scaffold with the cells and improve the functionality of the engineered-tissue construct. This technology not only can be used for the healing of focal defects but can also be used for extensive osteoarthritic degenerative alterations in the joint. In this review paper, we will emphasize the recent investigations of articular cartilage repair/regeneration via biomaterials. Also, the application of novel technologies and materials is discussed.
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http://dx.doi.org/10.3390/ijms21020536DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7014227PMC
January 2020

Hepatoprotective role of berberine against paraquat-induced liver toxicity in rat.

Environ Sci Pollut Res Int 2020 Feb 16;27(5):4969-4975. Epub 2019 Dec 16.

Pharmacology and Toxicology Department, Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran.

Paraquat (PQ) is a herbicide agent commonly used in agricultural applications. Hepatotoxicity is among clinical complications associated with PQ intoxication. Oxidative stress and its subsequent events are major mechanisms identified in PQ-induced liver toxicity. Berberine (BBR) is a natural antioxidant widely investigated for its hepatoprotective effects. The present study designed to evaluate the potential cytoprotective properties of BBR against PQ-induced cytotoxicity in primary cultured rat hepatocytes and in vivo test of liver function enzymes. Cellular and biochemical parameters including lactate dehydrogenase (LDH), cell viability, ROS formation, glutathione (GSH) content, and mitochondrial membrane potential in the PQ-treated hepatocytes were measured, and the mentioned markers were evaluated in the presence of BBR. BBR treatment caused significant decrease in PQ-induced cell death, ROS formation, and LDH release. On the other hand, it was found that BBR inhibits cellular glutathione depletion in PQ-treated hepatocytes. Also, BBR treatment significantly diminished PQ-induced the liver function enzyme elevation. These data mention the potential hepatoprotective effect of BBR with therapeutic capability against PQ-induced liver damage.
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http://dx.doi.org/10.1007/s11356-019-07232-1DOI Listing
February 2020

Detection of pathogenic bacteria via nanomaterials-modified aptasensors.

Biosens Bioelectron 2020 Feb 28;150:111933. Epub 2019 Nov 28.

Department of Pharmaceutical Sciences, Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, M5S 3M2, Canada. Electronic address:

Detection and identification of special cells via aptamer-based nano-conjugates sensors have been revolutionized over the past few years. These sensing platforms rely on selecting aptamers using systematic evolution of ligands by exponential enrichment (SELEX) in vitro, which allows for sensitive detection of cells. Integration of the aptamer-based sensors (aptasensors) with nanomaterials offers enhanced specificity and sensitivity, which in turn, offers great promise for numerous applications, spanning from bioanalysis to biomedical applications. Accordingly, the demand for using aptamer-conjugated nanomaterials for various applications has progressively increased over the past years. In light of this, this Review seeks to highlight the recent advances in the development of aptamer-conjugated nanomaterials and their utilization for the detection of various pathogens involved in infectious diseases and food contamination.
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http://dx.doi.org/10.1016/j.bios.2019.111933DOI Listing
February 2020

Global, Regional, and National Cancer Incidence, Mortality, Years of Life Lost, Years Lived With Disability, and Disability-Adjusted Life-Years for 29 Cancer Groups, 1990 to 2017: A Systematic Analysis for the Global Burden of Disease Study.

JAMA Oncol 2019 12;5(12):1749-1768

Department of Family and Community Medicine, Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia.

Importance: Cancer and other noncommunicable diseases (NCDs) are now widely recognized as a threat to global development. The latest United Nations high-level meeting on NCDs reaffirmed this observation and also highlighted the slow progress in meeting the 2011 Political Declaration on the Prevention and Control of Noncommunicable Diseases and the third Sustainable Development Goal. Lack of situational analyses, priority setting, and budgeting have been identified as major obstacles in achieving these goals. All of these have in common that they require information on the local cancer epidemiology. The Global Burden of Disease (GBD) study is uniquely poised to provide these crucial data.

Objective: To describe cancer burden for 29 cancer groups in 195 countries from 1990 through 2017 to provide data needed for cancer control planning.

Evidence Review: We used the GBD study estimation methods to describe cancer incidence, mortality, years lived with disability, years of life lost, and disability-adjusted life-years (DALYs). Results are presented at the national level as well as by Socio-demographic Index (SDI), a composite indicator of income, educational attainment, and total fertility rate. We also analyzed the influence of the epidemiological vs the demographic transition on cancer incidence.

Findings: In 2017, there were 24.5 million incident cancer cases worldwide (16.8 million without nonmelanoma skin cancer [NMSC]) and 9.6 million cancer deaths. The majority of cancer DALYs came from years of life lost (97%), and only 3% came from years lived with disability. The odds of developing cancer were the lowest in the low SDI quintile (1 in 7) and the highest in the high SDI quintile (1 in 2) for both sexes. In 2017, the most common incident cancers in men were NMSC (4.3 million incident cases); tracheal, bronchus, and lung (TBL) cancer (1.5 million incident cases); and prostate cancer (1.3 million incident cases). The most common causes of cancer deaths and DALYs for men were TBL cancer (1.3 million deaths and 28.4 million DALYs), liver cancer (572 000 deaths and 15.2 million DALYs), and stomach cancer (542 000 deaths and 12.2 million DALYs). For women in 2017, the most common incident cancers were NMSC (3.3 million incident cases), breast cancer (1.9 million incident cases), and colorectal cancer (819 000 incident cases). The leading causes of cancer deaths and DALYs for women were breast cancer (601 000 deaths and 17.4 million DALYs), TBL cancer (596 000 deaths and 12.6 million DALYs), and colorectal cancer (414 000 deaths and 8.3 million DALYs).

Conclusions And Relevance: The national epidemiological profiles of cancer burden in the GBD study show large heterogeneities, which are a reflection of different exposures to risk factors, economic settings, lifestyles, and access to care and screening. The GBD study can be used by policy makers and other stakeholders to develop and improve national and local cancer control in order to achieve the global targets and improve equity in cancer care.
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http://dx.doi.org/10.1001/jamaoncol.2019.2996DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6777271PMC
December 2019

The Potential Applications of Hyaluronic Acid Hydrogels in Biomedicine.

Drug Res (Stuttg) 2020 Jan 25;70(1):6-11. Epub 2019 Sep 25.

Faculty of Dentistry, Tabriz University of Medical Sciences, Tabriz, Iran.

Hyaluronic acid (HA) is widely used in the biomedicine due to its biocompatibility, biodegradability, and nontoxic properties. It is crucial for cell signaling role during morphogenesis, inflammation, and wound repair. After hydrogel formation, HA easily is converted to elastic sheets in order to use in preclinical and clinical applications. In addition, HA-derived hydrogels are easily used as vectors for cell and medication in tissue repairing and regenerative medicine. Moreover, in comparison with other polymers, HA -based hydrogels play a key role in in cellular behavior, including stem cell differentiation. The current paper reviews both basic concepts and recent advances in the development of HA-based hydrogels for biomedical applications.
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http://dx.doi.org/10.1055/a-0991-7585DOI Listing
January 2020

Stem Cell Therapy: Curcumin Does the Trick.

Phytother Res 2019 Nov 26;33(11):2927-2937. Epub 2019 Aug 26.

Faculty of Dentistry, Tabriz University of Medical Sciences, Tabriz, Iran.

Curcumin is a dietary polyphenol and a bioactive phytochemical agent that possesses anti-inflammatory, antioxidant, anticancer, and chemopreventive properties. Some of the predominant activities of stem cells include regeneration of identical cells and the ability to maintain the proliferation and multipotentiality. However, these cells could be stimulated to differentiate into specific cell types. Curcumin protects some stem cells from toxicity and can stimulate proliferation and differentiation of stem cells. In the present review, we summarize the antioxidant, stemness activity, antiaging, and neuroprotective as well as wound healing and regenerative effects of curcumin.
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http://dx.doi.org/10.1002/ptr.6482DOI Listing
November 2019

The effect of hyaluronic acid hydrogels on dental pulp stem cells behavior.

Int J Biol Macromol 2019 Nov 13;140:245-254. Epub 2019 Aug 13.

Dental and Periodontal Research Center, Tabriz University of Medical Sciences, Tabriz, Iran; Faculty of Dentistry, Tabriz University of Medical Sciences, Tabriz, Iran. Electronic address:

Dental caries and trauma, particularly in childhood, are among the most prevalent teeth problems, which result in the creation of cavities and probably tooth loss. Thus, novel regenerative approaches with high efficiency and less toxicity are required. Stem cell therapy along with the implementation of scaffolds has provided excellent opportunities in the regeneration of teeth structure. Hyaluronic acid (HA) hydrogels have enticed great attention in the field of regenerative medicine. The unique chemical and structural properties of HA and its derivatives have enabled their application in tissue engineering. Several factors such as the location and type of the lesion, teeth age, the type of capping materials determine the success rate of pulp therapy. HA hydrogels have been considered as biocompatible and safe scaffold supports in human dental cell therapies.
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http://dx.doi.org/10.1016/j.ijbiomac.2019.08.119DOI Listing
November 2019

Cell junctions and oral health.

EXCLI J 2019 7;18:317-330. Epub 2019 Jun 7.

Department of In Vitro Toxicology and Dermato-Cosmetology, Vrije Universiteit Brussel, Brussels, Belgium.

The oral cavity and its appendices are exposed to considerable environmental and mechanical stress. Cell junctions play a pivotal role in this context. Among those, gap junctions permit the exchange of compounds between cells, thereby controlling processes such as cell growth and differentiation. Tight junctions restrict paracellular transportation and inhibit movement of integral membrane proteins between the different plasma membrane poles. Adherens junctions attach cells one to another and provide a solid backbone for resisting to mechanistical stress. The integrity of oral mucosa, normal tooth development and saliva secretion depend on the proper function of all these types of cell junctions. Furthermore, deregulation of junctional proteins and/or mutations in their genes can alter tissue functioning and may result in various human disorders, including dental and periodontal problems, salivary gland malfunction, hereditary and infectious diseases as well as tumorigenesis. The present manuscript reviews the role of cell junctions in the (patho)physiology of the oral cavity and its appendices, including salivary glands.
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http://dx.doi.org/10.17179/excli2019-1370DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6635732PMC
June 2019

In vivo articular cartilage regeneration through infrapatellar adipose tissue derived stem cell in nanofiber polycaprolactone scaffold.

Tissue Cell 2019 Apr 14;57:49-56. Epub 2019 Feb 14.

Dental and Periodontal Research Center, Tabriz University of Medical Sciences, Tabriz, Iran" and "Students' Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran".

In this study, we report the development of a nanofiber polycaprolactone scaffold that can act as a stem cell carrier to induce chondrogenesis and promote cartilage repair in vivo. Infrapatellar fat pads were obtained from sheep knee and the stem cells were isolated and characterized by flow cytometry. Defects were created in sheep knee, two defects received adipose tissue derived stem cells (ASCs)-polycaprolactone construct, second group received polycaprolactone (PCL), the third group was chosen as the ASCs group and the fourth group was control group. Morphological evaluation showed that defects treated with ASCs-scaffold constructs were completely filled with cartilage-like tissue, while other groups revealed the formation of a thin layer of cartilage-like tissue in the defects. Real-Time RT-PCR showed the increase in collagen type 2 mRNA levels, aggrecan and Sox9 in ASCs/PCL groups in comparison with the other groups. Immunofluorescence and toluidine blue staining results showed the protein expression of collagen type 2 and formation of round and polygonal clusters of chondrocytes in ASCS/PCL group. According to our results nanofiber polycaprolactone promoted the chondrogenesis of infrapatellar adipose tissue derived stem cells in vivo and could offer significant promise in the biological functionality of stem cell tissue engineering in clinical practice.
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http://dx.doi.org/10.1016/j.tice.2019.02.002DOI Listing
April 2019

The role and therapeutic potential of connexins, pannexins and their channels in Parkinson's disease.

Cell Signal 2019 06 12;58:111-118. Epub 2019 Mar 12.

Department of In Vitro Toxicology and Dermato-Cosmetology, Vrije Universiteit Brussel, Laarbeeklaan 103, B-1090 Brussels, Belgium. Electronic address:

Lack of effective medication for slowing down progression of Parkinson's disease (PD) as a highly prevalent neurodegenerative disorder requires novel avenues of scientific investigation to elucidate the underlying molecular and cellular mechanisms. Studying connexins, pannexins and their channels has uncovered their potential role in mediating communication and signaling pathways that drive neurodegenerative diseases, including PD. Indeed, given their critical role in tissue homeostasis, it is not surprising that connexins, pannexins and their channels are frequently involved in pathological processes. For this reason, pharmacological tools to further clarify their functions and to validate connexins, pannexins and their channels as drug targets for the development of novel therapies for PD treatment are urgently needed. In this paper, a state-of-the-art overview is provided of current neuropathological and molecular understanding of PD. Focus is put on the roles of connexins, pannexins and their channels, in particular in the development of potential innovative disease-modifying therapies for PD treatment.
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http://dx.doi.org/10.1016/j.cellsig.2019.03.010DOI Listing
June 2019
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