Publications by authors named "Hamid Reza Rahimi"

96 Publications

Prognostic value of HIF-1α in digestive system malignancies: evidence from a systematic review and meta-analysis.

Gastroenterol Hepatol Bed Bench 2022 ;15(2):108-119

Cancer Molecular Pathology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.

Aim: This meta-analysis aimed to evaluate the association of HIF-1α expression with clinicopathological features and overall survival (OS) of patients with digestive system malignancies.

Background: Numerous studies have demonstrated that hypoxia-inducible factor-1α (HIF-1α) is abnormally expressed in various solid tumors. However, the clinicopathological features and prognostic value of HIF-1α expression in patients with digestive system malignancies remain controversial.

Methods: A literature search in PubMed, Web of Science, and Scopus databases was performed to identify all relevant studies published in English until 15 October 2020. The pooled effect was calculated to evaluate the association between HIF-1α expression and clinicopathological features and overall survival in cancer patients. Pooled odds ratios (ORs) or hazard ratios (HRs) with a 95% confidence interval (CI) were calculated using fixed- or random-effects model based on between-study heterogeneity.

Results: A total of 44 eligible studies with 5,964 patients were included. The pooled results indicated a positive association of HIF-1α overexpression with poor overall survival (OS) (HR=1.990, 95% CI: 1.615-2.453, <0.001) and disease-free survival (DFS) (HR=1.90, 95% CI: 1.084-3.329, =0.043). Meta-analysis results showed that HIF-1α level expression was significantly associated with positive lymph node metastasis (OR=1.869, 95% CI: 1.488-2.248, <0.001), distance metastasis (OR=2.604, 95% CI: 1.500-4.519, <0.001), tumor stage (OR=1.801, 95% CI: 1.437-2.257, <0.001) and tumor size (OR=1.392. 95% CI: 1.068-1.815, =0.014).

Conclusion: This meta-data suggest that HIF-1α expression might serve as an independent prognostic marker and a promising therapeutic target in patients with digestive system malignancies.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9275741PMC
January 2022

Three months of combination therapy with nano-curcumin reduces the inflammation and lipoprotein (a) in type 2 diabetic patients with mild to moderate coronary artery disease: Evidence of a randomized, double-blinded, placebo-controlled clinical trial.

Biofactors 2022 Jun 8. Epub 2022 Jun 8.

Department of Cardiovascular Diseases, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.

Diabetes is one of the most common chronic diseases worldwide. Systemic inflammation (high-sensitivity C-reactive protein (hs-CRP)) and lipid metabolism disruption (lipoprotein A, LipoPr (a)) play a critical role in developing and progressing atherosclerosis and acute coronary syndrome in diabetic patients. The anti-oxidant and anti-inflammatory effects of curcumin have been emphasized previously. Therefore, we aimed to evaluate the impact of nano-curcumin on cardiovascular risk factors in type 2 diabetic patients with mild to moderate coronary artery disease (CAD). We performed a randomized, double-blinded, placebo-controlled clinical trial with type 2 diabetic patients (n = 64), and mild to moderate CAD (<70% stenosis in angiography). The patients received nano-curcumin (80 mg/day) or placebo along with optimal medications for 90 days. The biofactors, including hs-CRP and LipoPr (a), and lipid profile, were measured at the admission of patients and end of the study. Nano-curcumin significantly mitigated the hs-CRP and LipoPr (a) levels following 90 days of treatment (P < 0.001 and P = 0.043, respectively). In addition, the mean percentage of change (%Δ) in the hs-CRP and LipoPr (a) levels were meaningfully reduced in the nano-curcumin group compared to the placebo group (P < 0.001 and P = 0.007, respectively). Surprisingly, nano-curcumin notably propagated the number of patients with mild (34.35%) and moderate (62.5%) hs-CRP level category and strikingly diminished the number of patients with severe hs-CRP level category (3.125%) compared to the placebo group (P = 0.016). Nano-curcumin (80 mg/day) might prevent atherosclerosis progression and, in terms of attenuating hs-CRP levels as an inflammation index, succedent cardiovascular events in diabetic heart patients.
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http://dx.doi.org/10.1002/biof.1874DOI Listing
June 2022

MicroRNA-96: A therapeutic and diagnostic tumor marker.

Iran J Basic Med Sci 2022 Jan;25(1):3-13

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

Cancer has been always considered as one of the main human health challenges worldwide. One of the main causes of cancer-related mortality is late diagnosis in the advanced stages of the disease, which reduces the therapeutic efficiency. Therefore, novel non-invasive diagnostic methods are required for the early detection of tumors and improving the quality of life and survival in cancer patients. MicroRNAs (miRNAs) have pivotal roles in various cellular processes such as cell proliferation, motility, and neoplastic transformation. Since circulating miRNAs have high stability in body fluids, they can be suggested as efficient noninvasive tumor markers. MiR-96 belongs to the miR-183-96-182 cluster that regulates cell migration and tumor progression as an oncogene or tumor suppressor by targeting various genes in solid tumors. In the present review, we have summarized all of the studies that assessed the role of miR-96 during tumor progression. This review clarifies the molecular mechanisms and target genes recruited by miR-96 to regulate tumor progression and metastasis. It was observed that miR-96 mainly affects tumorigenesis by targeting the structural proteins and FOXO transcription factors.
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http://dx.doi.org/10.22038/IJBMS.2021.59604.13226DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9118275PMC
January 2022

Evaluation of curcumin as add-on therapy in patients with Parkinson's disease: A pilot randomized, triple-blind, placebo-controlled trial.

Clin Neurol Neurosurg 2022 07 18;218:107300. Epub 2022 May 18.

Department of Neurology and HTLV-1 Foundation, Ghaem Hospital, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran; Parkinson and Other Movement Disorders Center, Department of Neurosciences, University of California San Diego, La Jolla, CA 92093, USA. Electronic address:

Background And Objective: Preclinical studies suggest that curcumin might be a potential neuroprotective agent in Parkinson's disease (PD). This clinical trial aimed to evaluate the efficacy of adding nanomicelle curcumin on improving the motor and non-motor symptoms of PD patients and their quality of life.

Material And Methods: Idiopathic PD patients aged ≥30≥ 30 whose symptoms were under control were included in this pilot, randomized, triple-blind, placebo-controlled, add-on trial. Eligible patients were randomly assigned to either the curcumin (n = 30, 80 mg/day) or placebo (n = 30) groups and were followed for nine months. Primary outcomes were the Movement Disorder Society-sponsored revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS) and Parkinson's Disease Questionnaire (PDQ-39). These variables, along with demographic data, drug history, and possible side effects of curcumin, were gathered at the beginning of the study and every three months. A mixed effects model was used to compare the group-by-time interaction, followed by post hoc analysis.

Results: Although the mean MDS-UPDRS and PDQ-39 scores were not significantly different between the curcumin and placebo groups at any time points, MDS-UPDRS part III (P = 0.04) showed a significant difference in its overall trend between the study groups. However, post hoc analysis failed to spot this difference at study time points. The most common side effects of curcumin were nausea and vomiting (P = 0.25) and gastroesophageal reflux (P = 0.42).

Conclusion: While curcumin is a well-tolerated natural compound, this trial was unsuccessful in showing its efficacy in quality of life and clinical symptoms of PD patients.
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http://dx.doi.org/10.1016/j.clineuro.2022.107300DOI Listing
July 2022

Antibiotics with Antiviral and Anti-Inflammatory Potential Against Covid-19: A Review

Curr Rev Clin Exp Pharmacol 2022 01 6. Epub 2022 Jan 6.

Student Research Committee, Kerman University of Medical Sciences, Kerman, Iran | Department of Pharmacology & Toxicology, Faculty of Pharmacy, Kerman University of Medical Sciences, Kerman, Iran.

In Covid-19 cases, elderly patients in long-term care facilities, children younger than five years with moderate symptoms, and patients admitted to ICU or with comorbidities are at a high risk of coinfection due to evidence. Thus, in these patients, antibiotic therapy based on empirical evidence is necessary. Finding appropriate antimicrobial agents, especially with antiviral and anti-inflammatory properties, is a promising approach to target the virus and its complications, hyper-inflammation, and microorganisms resulting co-infection. Moreover, indiscriminate use of antibiotics can be accompanied by Clostridioides difficile colitis, the emergence of resistant microorganisms, and adverse drug reactions, particularly kidney damage and QT prolongation. Therefore, rational administration of efficient antibiotics is an important issue. The main objective of the present review is to provide a summary of antibiotics with possible antiviral activity against SARS-CoV-2 and anti-immunomodulatory effects to guide scientists for further research. Besides, the findings can help health professionals in the rational prescription of antibiotics in Covid-19 patients with a high risk of coinfection.
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http://dx.doi.org/10.2174/2772432817666220106162013DOI Listing
January 2022

Investigating the protective role of metformin on lithium-induced hypothyroidism.

J Biochem Mol Toxicol 2022 Mar 28;36(3):e22977. Epub 2021 Dec 28.

Pharmaceutics Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman, Iran.

Induction of oxidative stress events has been shown to be associated with lithium (Li) hypothyroidism induction. Metformin (MET) is a commonly used antidiabetic drug with multiple properties including antiproliferative activity, antioxidant potency, and is used in polycystic ovarian syndrome treatment. Here, in this study, we aimed to investigate the effect of different doses of MET on Li-induced hypothyroidism for elucidating its mechanism of action. The obtained results demonstrated the oxidative stress reduction in thyroid tissues upon MET treatment. Besides this, the biochemical analysis revealed a significant reduction in T and TSH levels (down to 2 ng/ml and 0.05 µU/ml, respectively) in coordination with an observable reduction in T level (up to 2.1 ng/ml). Also, a significant reduction in Li-related tissue damages including changes in the morphology and the size of follicles, rate of vascularity, detachment of follicular cells, inflammatory cells infiltration, and follicular cells hypertrophy and disruption was observed. Ultimately, regarding the significant improvement in thyroid tissues and valuable antioxidant activity determined in tissues treated with MET, it is concluded that MET co-administration with Li can significantly reduce the negative effects of Li and enhance the efficacy of Li therapy.
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http://dx.doi.org/10.1002/jbt.22977DOI Listing
March 2022

MicroRNA-217: a therapeutic and diagnostic tumor marker.

Expert Rev Mol Diagn 2022 Jan 23;22(1):61-76. Epub 2021 Dec 23.

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

Introduction: Cancer as one of the most common causes of death has always been one of the major health challenges globally. Since, the identification of tumors in the early tumor stages can significantly reduce mortality rates; it is required to introduce novel early detection tumor markers. MicroRNAs (miRNAs) have pivotal roles in regulation of cell proliferation, migration, apoptosis, and tumor progression. Moreover, due to the higher stability of miRNAs than mRNAs in body fluids, they can be considered as non-invasive diagnostic or prognostic markers in cancer patients.

Areas Covered: In the present review we have summarized the role of miR-217 during tumor progressions. The functions were categorized based on its target molecular mechanisms and signaling pathways.

Expert Opinion: It was observed that mainly exerts its function by regulation of the transcription factors during tumor progressions. The WNT, MAPK, and PI3K/AKT signaling pathways were also important molecular targets of in different cancers. The present review clarifies the molecular biology of and paves the way of introducing miR-217 as a non-invasive diagnostic marker and therapeutic target in cancer therapy.
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http://dx.doi.org/10.1080/14737159.2022.2017284DOI Listing
January 2022

Polycaprolactone/gelatin electrospun nanofibres containing biologically produced tellurium nanoparticles as a potential wound dressing scaffold: Physicochemical, mechanical, and biological characterisation.

IET Nanobiotechnol 2021 May 7;15(3):277-290. Epub 2021 Feb 7.

Department of Medicinal Chemistry, Faculty of Pharmacy, Kerman University of Medical Sciences, Kerman, Iran.

The biologically synthesised tellurium nanoparticles (Te NPs) were applied in the fabrication of Te NP-embedded polycaprolactone/gelatin (PCL/GEL) electrospun nanofibres and their antioxidant and in vivo wound healing properties were determined. The as-synthesised nanofibres were characterised using scanning electron microscopy (SEM), energy-dispersive X-ray (EDX) spectroscopy and elemental mapping, thermogravimetric analysis (TGA), and Fourier-transform infrared (FTIR) spectroscopy. The mechanical properties and surface hydrophobicity of scaffolds were investigated using tensile analysis and contact angle tests, respectively. The biocompatibility of the produced scaffolds on mouse embryonic fibroblast cells (3T3) was evaluated using MTT assay. The highest wound healing activity (score 15/19) was achieved for scaffolds containing Te NPs. The wounds treated with PCL/GEL/Te NPs had inflammation state equal to the positive control. Also, the mentioned scaffold represented positive effects on collagen formation and collagen fibre's horizontalisation in a dose-dependent manner. The antioxidative potency of Te NP-containing scaffolds was demonstrated with lower levels of malondialdehyde (MDA) and catalase (∼3 times) and a higher level of glutathione (GSH) (∼2 times) in PCL/GEL/Te NP-treated samples than the negative control. The obtained results strongly demonstrated the healing activity of the produced nanofibres, and it can be inferred that scaffolds containing Te NPs are suitable for wound dressing.
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http://dx.doi.org/10.1049/nbt2.12020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8675828PMC
May 2021

Differences in autoimmunity factors based on the activity of thromboangiitis obliterans.

Turk Kardiyol Dern Ars 2021 Sep;49(6):439-447

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

Objective: The treatment of Buerger's disease (BD) presents a medical problem as its etiology is still unclear. In this study, our objective was to evaluate the serum levels of autoimmune markers in patients with different clinical features of BD.

Methods: In this study, 80 BD patients were categorized in three groups using a cross-sectional design: migratory thrombophlebitis, cold sensitivity, and skin discoloration (mild symptoms); chronic ulcers, claudication, and burning pain of the feet at night (moderate symptoms); pain at rest and spontaneous gangrene (severe symptoms). Enzyme-linked immunosorbent assay was performed to measure antibodies against immunoglobulin M rheumatoid factor (IgM RF), anti-nuclear antibodies (ANA), antibodies against cyclic citrullinated peptide (anti-CCP), antiphospholipid antibodies (APA), anti-cardiolipin antibodies (ACLA), anti-double stranded DNA (anti-dsDNA), and extractable nuclear antigen (ENA) profile.

Results: Patients with severe symptoms showed the lowest age (p=0.031), ESR (p<0.001), and highest prevalence of ischemia (p<0.001). In all the patients, the serum levels of ANA and IgM RF were higher than 1 U and 15 IU/mL, respectively. However, the progression of the disease from mild to moderate did not affect these markers significantly (p>0.05). Other markers were negative in patients with BD.

Conclusion: The findings of this study indicate that BD may closely be correlated to transient autoimmune phenomena, despite the fact that further research is required to investigate how transient unspecific autoimmune reactions contribute to the BD pathogenesis.
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http://dx.doi.org/10.5543/tkda.2021.19014DOI Listing
September 2021

A review of biosensors for the detection of B-type natriuretic peptide as an important cardiovascular biomarker.

Anal Bioanal Chem 2021 Oct 16;413(24):5949-5967. Epub 2021 Aug 16.

Department of Medical Biotechnology and Nanotechnology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, 9177948564, Iran.

Heart disease, as the most serious threat to human health globally, is responsible for rising mortality rates, largely due to lifestyle and diet. Unfortunately, the main problem for patients at high risk of heart disease is the validation of prognostic tests. To this end, the detection of cardiovascular biomarkers has been employed to obtain pathological and physiological information in order to improve prognosis and early-stage diagnosis of chronic heart failure. Short-term changes in B-type natriuretic peptide are known as a standard and important biomarker for diagnosis of heart failure. The most important problem for detection is low concentration and short half-life in the blood. The normal concentration of BNP in blood is less than 7 nM (25 pg/mL), which increases significantly to more than 80 pg/mL. Therefore, the development of new biosensors with better sensitivity, detection limit, and dynamic range than current commercial kits is urgently needed. This review classifies the biosensors designed for detection of BNP into electrochemical, optical, microfluidic, and lateral-flow immunoassay techniques. The review clearly demonstrates that a variety of immunoassay, aptasensor, enzymatic and catalytic nanomaterials, and fluorophores have been successfully employed for detection of BNP at low attomolar ranges. Dtection of B-type natriuretic peptide with biosensors.
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http://dx.doi.org/10.1007/s00216-021-03490-6DOI Listing
October 2021

Targeting Nuclear Factor-Kappa B Signaling Pathway by Curcumin: Implications for the Treatment of Multiple Sclerosis.

Adv Exp Med Biol 2021 ;1291:41-53

Neurogenic Inflammation Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.

Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system, which involves an auto-immune mechanism that leads to perivascular demyelination. The role of nuclear factor-kappa B (NF-κB) signaling pathway in the pathogenesis of MS has been suggested by genome-wide association studies. Therefore, strategies targeting this pathway could be potentially beneficial. Curcumin is the active component of turmeric and a phenolic phytochemical. This phytochemical has anti-inflammatory properties and has been shown by multiple studies to downregulate NF-κB and its downstream gene targets including cyclooxygenase-2, tumor necrosis factor-α, interleukin-1, and interleukin-6. This review discusses the modulatory effects of curcumin on the NF-κB signaling pathway and its downstream effectors, and the therapeutic implications of this modulation on MS.
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http://dx.doi.org/10.1007/978-3-030-56153-6_3DOI Listing
August 2021

A review on the pharmacokinetic properties and toxicity considerations for chloroquine and hydroxychloroquine to potentially treat coronavirus patients.

Toxicol Res 2022 Apr 19;38(2):137-148. Epub 2021 Jul 19.

Student Research Committee, Faculty of Pharmacy, Kerman University of Medical Sciences, Kerman, Iran.

The SARS-CoV-2 virus, caused a novel emerged coronavirus disease, is growing rapidly worldwide. Few studies have evaluated the efficacy and safety of Chloroquine (CQ), an old antimalarial drug, and Hydroxychloroquine (HCQ) in the treatment of COVID-19 infection. HCQ is derived from CQ by adding a hydroxyl group into it and is a less toxic derivative of CQ for the treatment of COVID-19 infection because it is more soluble. This article summarizes pharmacokinetic properties and toxicity considerations for CQ and HCQ, drug interactions, and their potential efficacy against COVID-19. The authors also look at the biochemistry changes and clinical uses of CQ and HCQ, and supportive treatments following toxicity occurs. It was believed that CQ and HCQ may provide few benefits to COVID-19 patients. A number of factors should be considered to keep the drug safe, such as dose, in vivo animal toxicological findings, and gathering of metabolites in plasma and/or tissues. The main conclusion of this review is that CQ and HCQ with considered to their ADMET properties has major shortcomings and fully irresponsible.
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http://dx.doi.org/10.1007/s43188-021-00101-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8286988PMC
April 2022

Effects of probiotics on pentylenetetrazol-induced convulsions in mice.

Epilepsy Res 2021 10 12;176:106723. Epub 2021 Jul 12.

Student Research Committee, Faculty of Pharmacy, Kerman University of Medical Sciences, Kerman, Iran; Department of Toxicology & Pharmacology, Faculty of Pharmacy, Kerman University of Medical Sciences, Kerman, Iran. Electronic address:

Objective: There are some reports of the effect of the gut microbiota on the central nervous system. The aim of this study was to find out the effect of probiotics on pentylenetetrazol (PTZ)-induced convulsions in mice.

Methods: The mice were pretreated with probiotic powder (Lactobacillus acidophilus, Lactobacillus casei, and Bifidobacterium bifidum) suspended in normal saline by intragastric gavage (IG-gavage) for 14 (group 1) or 28 (group 2) days prior to injection of PTZ (90 mg/kg, intraperitoneally). Diazepam (DZP, 1 mg/kg, intraperitoneally) was used as the reference drug. The latency and duration of induced convulsion, as well as mortality protection percentage were recorded 30 min after PTZ injection. For the next step, flumazenil (FLZ) was used to block the effect of DZP.

Results: Pretreatment with probiotics for 14 or 28 days had not a significant effect on the latency and duration of seizures induced by PTZ. Neither seizure nor mortality was observed in co-administration of probiotics with DZP. FLZ pretreatment decreased the DZP-induced seizure latency; however, FLZ could not have such an effect in probiotic and DZP group.

Conclusion: Probiotics alone did not show anticonvulsant effects, but enhanced the anticonvulsant effect of DZP; this suggests the involvement of GABAergic system.
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http://dx.doi.org/10.1016/j.eplepsyres.2021.106723DOI Listing
October 2021

Antidepressants with anti-tumor potential in treating glioblastoma: A narrative review.

Fundam Clin Pharmacol 2022 Feb 29;36(1):35-48. Epub 2021 Jul 29.

Pharmaceutics Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman, Iran.

Glioblastoma multiforme (GBM) is known as the deadliest form of brain tumor. In addition, its high treatment resistance, heterogeneity, and invasiveness make it one of the most challenging tumors. Depression is a common psychological disorder among patients with cancer, especially GBM. Due to the high occurrence rates of depression in GBM patients and the overlap of molecular and cellular mechanisms involved in the pathogenesis of these diseases, finding antidepressants with antitumor effects could be considered as an affordable strategy for the treatment of GBM. Antidepressants exert their antitumor properties through different mechanisms. According to available evidence in this regard, some of them can eliminate the adverse effects resulting from chemo-radiotherapy in several cancers along with their synergistic effects caused by chemotherapy. Therefore, providing comprehensive insight into this issue would guide scientists and physicians in developing further preclinical studies and clinical trials, in order to evaluate antidepressants' antitumor potential. Considering that no narrative review has been recently published on this issue, specifically on these classes of drugs, we present this article with the purpose of describing the antitumor cellular mechanisms of three classes of antidepressants as follows: tricyclic antidepressants (TCAs), selective serotonin reuptake inhibitors (SSRIs), and monoamine oxidase inhibitors (MAOIs) in GBM.
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http://dx.doi.org/10.1111/fcp.12712DOI Listing
February 2022

Determining the Interaction Behavior of Calf Thymus DNA with Anastrozole in the Presence of Histone H1: Spectroscopies and Cell Viability of MCF-7 Cell Line Investigations.

DNA Cell Biol 2021 Aug 24;40(8):1039-1051. Epub 2021 Jun 24.

Department of Biology, Faculty of Sciences, Islamic Azad University, Mashhad Branch, Mashhad, Iran.

The interaction of calf thymus DNA (ct DNA) with anastrozole, which is acknowledged as an antineoplastic drug, has been enquired into in the absence and presence of histone H1, through the means of absorbance, fluorescence, circular dichroism spectroscopy, viscosity, thermal melting, and molecular modeling techniques. In addition, the effects of anastrozole on MCF 7 cell line have been thoroughly investigated. Fluorescence spectroscopy results have indicated that quenching mechanism of ct DNA-anastrozole are known as static quenching procedures, since the Stern-Volmer quenching constant (K) seems to face a decrease as the temperature is enhanced; this is a significant evidence for intercalative binding mode of anastrozole with ct DNA. Regarding the ternary system in the presence of H1, the constant of Stern-Volmer quenching was increased as the temperature was heightened. The thermodynamic parameters suggested that the binding could be characterized as exothermic by negative and positive enthalpy and entropy changes in both binary and ternary systems, respectively. It is vital to mention that hydrogen bonds and hydrophobic contributions play significant roles in anastrozole association to ct DNA in the absence and presence of H1. In accordance to the absorption spectroscopy and melting temperature curve outcomes, the binding mode of anastrozole with ct DNA in absence and presence of H1 was indicative of intercalative and nonintercalative bindings, respectively. The viscosity results as binary and ternary systems, which have been elucidated from a sensitive viscometer, have confirmed the fluorescence spectroscopy determinations. The intercalation of anastrozole to ct DNA seemed to be significantly related to an induced reduction in MCF-7 cell proliferation. The molecular modeling results have suggested that anastrozole could bind to H1 in ct DNA-H1 complex in ternary systems, which supports the conclusions that have been obtained from experimental data.
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http://dx.doi.org/10.1089/dna.2021.0052DOI Listing
August 2021

Unlocking G-Quadruplexes as Antiviral Targets.

Pharmacol Rev 2021 07;73(3):897-923

Department of Medicinal Chemistry, Faculty of Pharmacy, Kerman University of Medical Sciences, Kerman, Iran (A.A., S.N.); Institut Pasteur, Department of Virology, UMR 3569 CNRS, Paris, France (M.L.); Faculty of Medicine, Kerman University of Medical Sciences, Kerman, Iran (M.R.); Dioscuri Center of Chromatin Biology and Epigenomics, Nencki Institute of Experimental Biology, Polish Academy of Sciences, Warsaw, Poland (P.Z.); Faculty of Medicine, Cardinal Stefan Wyszyński University in Warsaw, Warsaw, Poland (P.Z.); Laboratoire d'Optique et Biosciences, Ecole Polytechnique, CNRS, INSERM, Institut Polytechnique de Paris, Palaiseau cedex, France (J.-L.M.); Pharmaceutics Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman, Iran (H.-R.R.); and Department of Pharmacology and Toxicology, Faculty of Pharmacy, Kerman University of Medical Sciences, Kerman, Iran (H.-R.R.)

Guanine-rich DNA and RNA sequences can fold into noncanonical nucleic acid structures called G-quadruplexes (G4s). Since the discovery that these structures may act as scaffolds for the binding of specific ligands, G4s aroused the attention of a growing number of scientists. The versatile roles of G4 structures in viral replication, transcription, and translation suggest direct applications in therapy or diagnostics. G4-interacting molecules (proteins or small molecules) may also affect the balance between latent and lytic phases, and increasing evidence reveals that G4s are implicated in generally suppressing viral processes, such as replication, transcription, translation, or reverse transcription. In this review, we focus on the discovery of G4s in viruses and the role of G4 ligands in the antiviral drug discovery process. After assessing the role of viral G4s, we argue that host G4s participate in immune modulation, viral tumorigenesis, cellular pathways involved in virus maturation, and DNA integration of viral genomes, which can be potentially employed for antiviral therapeutics. Furthermore, we scrutinize the impediments and shortcomings in the process of studying G4 ligands and drug discovery. Finally, some unanswered questions regarding viral G4s are highlighted for prospective future projects. SIGNIFICANCE STATEMENT: G-quadruplexes (G4s) are noncanonical nucleic acid structures that have gained increasing recognition during the last few decades. First identified as relevant targets in oncology, their importance in virology is now increasingly clear. A number of G-quadruplex ligands are known: viral transcription and replication are the main targets of these ligands. Both viral and cellular G4s may be targeted; this review embraces the different aspects of G-quadruplexes in both host and viral contexts.
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http://dx.doi.org/10.1124/pharmrev.120.000230DOI Listing
July 2021

Para-Clinical and Immunological Evaluation in Buerger's Disease as a Suspected Autoimmune Disease: Case Series.

Rep Biochem Mol Biol 2021 Jan;9(4):379-384

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

Background: Autoimmunity causes the loss of normal immune homeostasis and involves the presence of autoantibodies and inflammation. Thromboangiitis obliterans or Buerger's disease (BD) refers to a type of vascular obstructive syndrome, with tobacco exposure accounting for disease formation and progression. However, the current understanding of autoimmunity is unclear in the context of BD, and the scientific findings are not enough to support autoimmune mechanisms. This study was aimed at investigating autoimmunity factors in patients with BD.

Methods: Clinical and experimental examinations were performed on 80 patients with BD. The diagnostic work-up for autoimmunity was composed of IgM rheumatoid factor (RF), anti-nuclear antibodies (ANA), The erythrocyte sedimentation rate (ESR), anti-cyclic citrullinated peptide (CCP) antibodies, Antiphospholipid antibodies (APA), Anti-cardiolipin antibodies (ACLA), anti-double-stranded DNA (ds-DNA), and extractable nuclear antigen (ENA) profile. Immunomarkers were detected using the quantitative enzyme-linked immunosorbent assay (ELISA).

Results: Raynaud's phenomenon (84.93%), cold sensitivity (76.25%), and claudication (73.75%) were the most common symptoms in the BD patients. Also, 64.29% represented with high ANA levels and positive RF, while 42.11% were found with increased ANA and ESR levels. The ANA/RF positive BD patients had ESR> 15 mm/hr and a high prevalence of cold sensitivity, claudication, and Raynaud's phenomenon (p> 0.05).

Conclusion: There is a possibility of a non-specific autoimmune disposition among BD patients. RF and ANA could be considered for predicting disease progression.
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http://dx.doi.org/10.52547/rbmb.9.4.373DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8068440PMC
January 2021

The effects of nano-curcumin supplementation on glycemic control, blood pressure, lipid profile, and insulin resistance in patients with the metabolic syndrome: A randomized, double-blind clinical trial.

Phytother Res 2021 Jul 13;35(7):3945-3953. Epub 2021 Apr 13.

Clinical Nutrition and Dietetics Department, Faculty of Nutrition Sciences and Food Technology, National Nutrition and Food Technology Research Institute, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Metabolic syndrome (MetS) is one of the most important health hazards. Curcumin is extracted from Curcuma longa (turmeric), which can affect the components of MetS. To increase the oral bioavailability of curcumin, nano-micelle curcumin is used instead of curcumin powder. In this randomized, double-blind, controlled clinical trial, 50 patients with MetS were randomly assigned to two groups to receive either 80 mg/day nano-curcumin (n = 25) or placebo (n = 25), for 12 weeks anthropometric measurements, blood pressure, and biochemical factors-including fasting blood sugar (FBS), Hemoglobin A1c (HbA1c), homeostatic model assessment (HOMA) for insulin resistance (HOMA-IR), pancreatic β cell function (HOMA-β) and lipid profile-were assessed at the baseline and the end of the study. Statistical analyses were done using SPSS software (Version 23). The analysis between the two groups has illustrated a significant reduction in the average change of triglyceride (TG) levels (-60.5 ± 121.7 vs. 13.1 ± 78.1 mg/dL; p < .05) and HOMA-β (-5.7 ± 48.2 vs. -4.01 ± 16.9; p < .05). But there were no significant differences in anthropometric measurements, blood pressure and biochemical factors-including FBS, HbA1c, HOMA-IR, HOMA-β, and lipid profile variables include (total cholesterol, LDL-C, and HDL-C) at the end of the study. In conclusion, supplementation with nano-micelle curcumin significantly improved serum TG in MetS patients.
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http://dx.doi.org/10.1002/ptr.7109DOI Listing
July 2021

Bioactive anti-oxidative polycaprolactone/gelatin electrospun nanofibers containing selenium nanoparticles/vitamin E for wound dressing applications.

J Biomater Appl 2021 08 15;36(2):193-209. Epub 2021 Mar 15.

Department of Pharmaceutical Biotechnology, Faculty of Pharmacy, Kerman University of Medical Sciences, Kerman, Iran.

In this study, polycaprolactone/gelatin (PCL/GEL) electrospun nanofibers containing biogenic selenium nanoparticles (Se NPs) and Se NPs/vitamin E (VE) with average diameters of 397.8 nm and 279.5 nm, respectively (as determined by SEM inspection) were prepared and their effect on wound healing was evaluated using in-vivo studies. The energy dispersive X-ray (EDX) mapping, TEM micrograph, and FTIR spectra of the prepared nanofibers strongly demonstrated well entrapment of Se NPs and VE into scaffolds. An amount of 57% Se NPs and 43% VE were gradually released from PCL/GEL/Se NPs/VE scaffold after 4 days immersion in PBS solution (pH 7.4). The both PCL/GEL/Se NPs and PCL/GEL/Se NPs/VE scaffolds supported 3T3 cell proliferation and attachment as confirmed by MTT assay and SEM imaging. Complete re-epithelialization, low level of edema and inflammatory cells in coordination with high level of oriented collagens demonstrated the wound healing activity of PCL/GEL/Se NPs/VE. Besides, significant antioxidant efficacy of PCL/GEL/Se NPs and PCL/GEL/Se NPs/VE scaffolds was demonstrated according to GSH and MDA assays. To sum up, the prepared PCL/GEL/Se NPs/VE scaffold in the present study represented suitable healing effect on animal model which candidate it for further studies.
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http://dx.doi.org/10.1177/08853282211001359DOI Listing
August 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

The effects of nanomicelle of curcumin on the matrix metalloproteinase (MMP-2, 9) activity and expression in patients with coronary artery disease (CAD): A randomized controlled clinical trial.

ARYA Atheroscler 2020 May;16(3):136-145

Associate Professor, Pharmacological Research Center of Medicinal Plants AND Department of Clinical Biochemistry, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.

Background: Coronary artery disease (CAD) is the most common type of cardiovascular disease. Increasing the expression and activity of matrix metalloproteinases (MMPs) facilitates vascular remodeling and cardiovascular complications. Curcumin (the active ingredient of turmeric) is a potent natural anti-inflammatory agent, with cardiovascular protective effects. The present study was a clinical trial for investigating the effects of curcumin on activity and gene expression of MMP-2 and MMP-9 in patients with CAD.

Methods: In this study, 70 patients with CAD (with 40%-50% stenosis) were randomly divided into two groups of curcumin (80 mg nanomicelle per day) and placebo. The intervention lasted 3 months. The activity levels of MMP-2 and MMP-9 in serum samples of patients were measured using gelatin zymography assay before and after the intervention. MMP-2 and MMP-9 gene expression in peripheral blood mononuclear cells (PBMCs) was also analyzed using real-time polymerase chain reaction (PCR). Statistical significance was set at P < 0.0500.

Results: After 3 months of medication, the expression of MMP-9 produced by PBMCs significantly decreased in the curcumin group (0.811 ± 0.25) in comparison with the placebo group (2.23 ± 0.94) (P < 0.0001). Furthermore, the zymographic analysis showed that the administration of curcumin significantly inhibited the activity levels of MMP-2 (12469.7 ± 5308.64 pixels) and MMP-9 (14007.2 ± 5371.67 pixels) in comparison with that in patients receiving placebo (MMP-2: 17613.8 ± 5250.68 pixels; MMP-9: 20010.1 ± 3259.37 pixels) (P < 0.0500).

Conclusion: Our results show that curcumin can significantly reduce the expression and activity of MMP-2 and MMP-9. Because of the anti-inflammatory effects of curcumin, this compound can be considered as a new strategy for the prevention of cardiovascular events.
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http://dx.doi.org/10.22122/arya.v16i3.1938DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7778509PMC
May 2020

Controlled and cellulose eco-friendly synthesis and characterization of BiOCO quantum dot nanostructures (QDNSs) and drug delivery study.

Sci Rep 2020 12 4;10(1):21302. Epub 2020 Dec 4.

Neuroscience Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman, Iran.

This work aimed to prepare solvent-free or green BiOCO for quantum dot nanostructures (QDNSs) based on cellulose as a stabilizer and green capping agent to sorafenib delivery for liver targeting. Because the walnut tree is one of the most abundant trees in Iran, it was tried to synthesize BiOCO QDNSs using a walnut skin extract. The saturation magnetization for BiOCO QDNSs was calculated to be 68.1. Also, the size of products was measured at around 60-80 nm with the Debye-Scherrer equation. Moreover, the morphology, functional groups, and crystallography of the BiOCO nanoparticles were investigated using atomic force microscopy, scanning electron microscopy, vibrating-sample magnetometer, and Uv-vis spectroscopy. The results demonstrated that BiOCO QDNSs have opto-magnetic properties and they can be suggested as the candidate materials for the sorafenib delivery on the liver tissue. The optical band gap estimated for BiOCO QDNSs was found to be red-shift from 3.22 eV. This study suggests the preparation of the BiOCO QDNSs based on cellulose as new opto-magnetic materials at different temperatures of 180 °C, 200 °C, 220 °C, and 240 °C for sorafenib delivery as a type of biological therapy drug.
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http://dx.doi.org/10.1038/s41598-020-78266-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7718884PMC
December 2020

Cytokine Analysis in Patients with Different Stages of Thromboangiitis Obliterans.

Curr Mol Med 2021 ;21(9):812-818

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

Background: Studies suggest that cytokines are involved in the development of both inflammatory disorders and vascular diseases.

Objective: The changes in transforming growth factor β (TGFβ), interleukin 6 (IL6), tumor necrosis factor α (TNFα), and interferon γ (IFNγ) with the progression of the thromboangiitis obliterans (TAO) symptoms were investigated in this research.

Methods: This study included 80 patients with TAO, who were selected from the Vascular and Endovascular Research Center in Alavi Hospital, from the year 2012 to 2016. They were then categorized into three groups: Mild (migratory thrombophlebitis, cold sensitivity or Raynaud's phenomenon, and skin discoloration), moderate (chronic ulcers, claudication, and burning pain of the feet at night), and severe (pain at rest and spontaneous gangrene) symptoms. The serum levels of TGFβ, IL6, TNFα, and IFNγwere determined by the ELISA method and compared among the groups.

Results: The first three predominant symptoms were pulse disorder (n = 76, 95.00%), cold intolerance (n = 61, 76.25%), and claudication (n = 59, 73.75%). A comparison of the analysis of covariance (ANCOVA) revealed that both TGFβ and IL6 were dysregulated as the severity of the symptoms increased from the moderate to the severe stages; however, such changes were not significant (p > 0.05). In the multiple logistic regression model, increased TNFα levels were seen in the presence of moderate symptoms as compared to the severe ones (p < 0.05).

Conclusion: It could be concluded that TNFα, as part of the defining cytokineproduction profile of T helper cells, can be significantly involved in the progression of TAO from the moderate to the severe stages.
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http://dx.doi.org/10.2174/1566524020666201120112828DOI Listing
April 2022

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

Verapamil Inhibits Mitochondria-Induced Reactive Oxygen Species and Dependent Apoptosis Pathways in Cerebral Transient Global Ischemia/Reperfusion.

Oxid Med Cell Longev 2020 17;2020:5872645. Epub 2020 Oct 17.

Anatomical Sciences Department, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran.

The prefrontal cortex is the largest lobe of the brain and is consequently involved in stroke. There is no comprehensive practical pharmacological strategy for ameliorating prefrontal cortex injury induced by cerebral ischemia. Therefore, we studied the neuroprotective properties of verapamil (Ver) on mitochondrial dysfunction and morphological features of apoptosis in transient global ischemia/reperfusion (I/R). Ninety-six Wistar rats were allocated into four groups: control, I/R, I/R+Ver (10 mg/kg twice 1 hour prior to ischemia and 1 hour after reperfusion phase), and I/R+NaCl (vehicle). Animals were sacrificed, and mitochondrial dysfunction parameters (i.e., mitochondrial swelling, mitochondrial membrane potential, ATP concentration, ROS production, and cytochrome c release), antioxidant defense (i.e., superoxide dismutase, malondialdehyde, glutathione peroxidase, catalase, and caspase-3 activation), and morphological features of apoptosis were determined. The results showed that mitochondrial damage, impairment of antioxidant defense system, and apoptosis were significantly more prevalent in the I/R group in comparison with the other groups. Ver decreased mitochondrial damage by reducing oxidative stress, augmented the activity of antioxidant enzymes in the brain, and decreased apoptosis in the I/R neurons. The current study confirmed the role of oxidative stress and mitochondrial dysfunction in I/R progression and indicated the possible antioxidative mechanism of the neuroprotective activities of Ver.
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http://dx.doi.org/10.1155/2020/5872645DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7591985PMC
May 2021

Dietary Inflammatory Index is associated with Healthy Eating Index, Alternative Healthy Eating Index, and dietary patterns among Iranian adults.

J Clin Lab Anal 2020 Dec 27;34(12):e23523. Epub 2020 Aug 27.

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

Background: Recent investigations have evaluated the effect of the inflammatory potential of diet in several populations by calculating the Dietary Inflammatory Index (DII) score. We aimed to evaluate the association of the DII with the Healthy Eating Index (HEI), the Alternative Healthy Eating Index (AHEI), and dietary pattern (DP) among healthy Iranian adults.

Methods: A cross-sectional study was conducted among 4365 middle-aged adults. Major DPs and DII score were identified using a validated semi-quantitative food frequency questionnaire (FFQ). Poisson regression was used to evaluate the association of DPs, HEI, and AHEI across tertiles of DII.

Results: After adjustment for confounding variables, a low HEI (HEI < 55) and AHEI (AHEI < 56.5) were more prevalent among the participants in the highest tertile of DII compared to the first tertile (PR: 1.13, P-value <.05; PR: 1.10, P-value <.05; respectively). Adherence to a balanced healthy dietary pattern was significantly lower in subjects with a diet that was more pro-inflammatory compared to those with anti-inflammatory diet (PR: 0.85, P-value P < .01). No significant association was found between the DII and a western DP. High levels of HDL and hip and waist circumference were observed in the highest tertile of DII, and high levels of dietary intake of protein and fiber, minerals, fasting blood glucose, and monounsaturated fat were reported in the lowest tertile of DII.

Conclusion: The highest tertile of the DII (a pro-inflammatory diet) was associated with a lower HEI, AHEI, and lower adherence to balanced DP in a representative sample of adults in Iran.
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http://dx.doi.org/10.1002/jcla.23523DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7755771PMC
December 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

ADME and toxicity considerations for tramadol: from basic research to clinical implications.

Expert Opin Drug Metab Toxicol 2020 Jul 27;16(7):627-640. Epub 2020 Jun 27.

Pharmaceutics Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences , Kerman, Iran.

Introduction: Tramadol is widely being used in chronic pain management for improving patients' life quality and reducing trauma. Although it is listed in several medicinal guidelines, its use is controversial because of the conflicting results obtained in pharmacokinetic/pharmacodynamic studies. This multi-receptor drug acts as µopioid receptor agonist, monoamine reuptake inhibitor, and inhibitor of ligand-gated ion channels and some special protein-coupled receptors.

Areas Covered: This review provides a comprehensive view on the pharmacokinetic, pharmacodynamic, and toxicity of tramadol with a deep look on its side effects, biochemical and pathological changes, and possible drug interactions. In addition, the main ways of tramadol poisoning management describe according to  and clinical trial studies.

Expert Opinion: Given the broad spectrum of targets, increasing the cases of overdoses and toxicity, and probable drugs interaction, it is necessary to take another look at the pharmacology of tramadol. Regarding the adverse effects of tramadol on different tissues, especially the nervous system and liver tissue, more attentions to tramadol metabolites, their interaction with other drugs, and active agents seem critical. Seizure as the most cited effect of tramadol and its destructive effects on tissues would alleviate by co-administration with drugs with antioxidant properties.
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http://dx.doi.org/10.1080/17425255.2020.1776700DOI Listing
July 2020

Dyslipidemia and cardiovascular disease risk among the MASHAD study population.

Lipids Health Dis 2020 Mar 16;19(1):42. Epub 2020 Mar 16.

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

Introduction: Dyslipidemia may be defined as increased levels of serum total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), triglycerides (TG), or a decreased serum high-density lipoprotein cholesterol (HDL-C) concentration. Dyslipidemia is an established risk factor for cardiovascular disease (CVD). We aimed to investigate the association of dyslipidemia and CVD events among a population sample from Mashhad, in northeastern Iran.

Material And Methods: This prospective cohort study comprised a population of 8698 men and women aged 35-65 years who were recruited from the Mashhad Stroke and Heart Atherosclerotic Disorder (MASHAD) study. Socioeconomic and demographic status, anthropometric parameters, laboratory evaluations, lifestyle factors, and medical history were gathered through a comprehensive questionnaire and laboratory and clinical assessment for all participants. Cox regression model and 95% confidence interval (CI) were used to evaluate the association of dyslipidemia and its components with CVD incidence.

Results: After 6 years of follow-up, 233 cases of CVD (including 119 cases of unstable angina [US], 74 cases of stable angina [SA], and 40 cases of myocardial infarction [MI]) were identified in the study population. Unadjusted baseline serum LDL-C, TC, and TG levels were positively associated with the risk of total CVD events among the entire population (HR: 1.54, 95% CI: 1.19-2; P-value< 0.01; HR: 1.53; 95% CI: 1.18-1.98; P < 0.01; HR: 1.57; 95% CI: 1.27-2.03; P < 0.01, respectively). However, after adjusting for confounding factors (age, body mass index [BMI], family history of CVD, smoking status [non-smoker, ex-smoker and current smoker], lipid lowering drug treatment, anti-hypertensive drug treatment, hypertension, healthy eating index [HEI], total energy intake, and presence of diabetes mellitus), a significant direct association only remained between TC and MI risk in men (HR: 2.71; 95%CI: 1.12-6.57; P-value< 0.05).

Conclusion: In the present study, TC baseline level was significantly associated with the risk of MI among men.
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http://dx.doi.org/10.1186/s12944-020-01204-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7075010PMC
March 2020
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