Milad Shirvaliloo | Tabriz University Of Medical Sciences (original) (raw)

articles by Milad Shirvaliloo

Tissue Barriers, 2021

Blood-gas barrier (BGB) or alveolar-capillary barrier is the primary tissue barrier affected by c... more Blood-gas barrier (BGB) or alveolar-capillary barrier is the primary tissue barrier affected by coronavirus disease 2019 (COVID-19). Comprising alveolar epithelial cells (AECs), endothelial cells (ECs) and the extracellular matrix (ECM) in between, the BGB is damaged following the action of multiple pro-inflammatory cytokines during acute inflammation. The infection of AECs and ECs with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the pathogen behind COVID-19, triggers an inflammatory response at the BGB, inducing the release of interleukin 1 (IL-1), IL-6, tumor necrosis factor alpha (TNF-α), transforming growth factor beta (TGF-β), high mobility group box 1 (HMGB1), matrix metalloproteinases (MMPs), intercellular adhesion molecule-1 (ICAM-1) and platelet activating factor (PAF). The end result is the disassembly of adherens junctions (AJs) and tight junctions (TJs) in both AECs and ECs, AEC hyperplasia, EC pyroptosis, ECM remodeling and deposition of fibrin clots in the alveolar capillaries, leading to disintegration and thickening of the BGB, and ultimately, hypoxia. This commentary seeks to provide a brief account of how the BGB might become affected in COVID-19.

Journal of Medical Virology, 2021

The most consequential challenge raised by coinfection is perhaps the inappropriate generation of... more The most consequential challenge raised by coinfection is perhaps the inappropriate generation of recombinant viruses through the exchange of genetic material among different strains. These genetically similar viruses can interfere with the replication process of each other and even compete for the metabolites required for the maintenance of the replication cycle. Due to the similarity in clinical symptoms of most viral respiratory tract infections, and their coincidence with COVID-19, caused by SARS-CoV-2, it is recommended to develop a comprehensive diagnostic panel for detection of respiratory and nonrespiratory viruses through the evaluation of patient samples. Given the resulting changes in blood markers, such as coagulation factors and white blood cell count following virus infection, these markers can be of diagnostic value in the detection of mixed infection in individuals already diagnosed with a certain viral illness. In this review, we seek to investigate the coinfection of SARS-CoV-2 with other respiratory and non-respiratory viruses to provide novel insights into the development of highly sensitive diagnostics and effective treatment modalities.

Molecular Pharmacology, 2021

Autophagy is a perplexing mechanism through which a living cell can free itself of excess cytopla... more Autophagy is a perplexing mechanism through which a living cell can free itself of excess cytoplasmic components by means of certain membranous vesicles or lysosomes filled with degrading enzymes. Upon exposure to external insult or internal stimuli, the cell might opt to activate such pathway through which it can gain control over the maintenance of intracellular components. Despite such appropriateness, autophagy, might also be considered a frailty for the cell, as it has been said to have a rather complicated role in tumorigenesis. In fact, several investigations on tumorigenesis have reported diminished levels of autophagic activity in tumor cells. On the contrary, autophagy has been suggested to be a seemingly favorable mechanism to progressed malignancies, as it contributes to survival of such cells. Based on the recent literature, this mechanism might also be activated upon the entry of engineered nanomaterials inside a cell, supposedly protecting the host from foreign materials. In this review, we will discuss the signaling pathways involved in autophagy, and the significance of the mechanism itself in apoptosis and tumorigenesis, while shedding light on possible alterations in autophagy through engineered nanomaterials, and the their potential therapeutic applications in cancer. Significance Statement Autophagy has been said to have a complicated role in tumorigenesis. In the early stages of tumor formation, autophagy appears to be salutary due to its tumor-suppressing effects. On the contrary, autophagy has been suggested to be a favorable mechanism to progressed malignancies. This mechanism might be affected upon the entry of nanomaterials inside a cell. Accordingly, therapeutic interventions for modulating autophagy using nanoparticles may sensitize cancerous cells to certain therapies.

Epigenomics, 2021

Epigenomics is the collective study of all epigenetic modifications that can affect the genome, t... more Epigenomics is the collective study of all epigenetic modifications that can affect the genome, the most pivotal of which are DNA methylation (DNAm), histone modifications (e.g., acetylation, citrullination and phosphorylation) and nucleosome remodeling. The latter refers to the dynamic reorganization in the spatial arrangement of chromatin by means of repositioning the nucleosomes, which are short segments of DNA, consisting of approximately 200 base pairs, coiled around eight histone proteins. The resulting alterations in the structure of these bead-like complexes may favor or oppose transcription, determining the course of disease pathogenesis [1], such as coronavirus disease 2019 (COVID-19). Known to correlate inversely with gene expression, DNAm might be associated with increased susceptibility of the pulmonary tissue to COVID-19 [2] and a higher predisposition to this viral disease in patients with pancreatic [3] and prostate cancer [4]. A lesser known epigenetic mechanism, 'X inactivation' is thought to be connected with the function of innate immunity against COVID-19, particularly in male patients [5]. Furthermore, immunity is also influenced by the extensively diverse histone modifications, especially histone citrullination [6]. Nucleosome remodeling, mediated by contextually important proteins such as SMARCA4 and SMAD3, is another epigenetic mechanism that can affect the course of disease, assuming a patient-wise unfavorable role in the case of COVID-19 [7]. The footprint of epigenomics can even be traced back to prenatal life, when developmentally crucial genes such as PEG10 and ECE1, can be affected by DNAm in response to maternal COVID-19 [8], indicating the overall significance of epigenetics in the recent viral pandemic. COVID-19: unwelcome infection facilitated by epigenetic modifications A consequence of SARS coronavirus 2 (SARS-CoV-2) infection, COVID-19 is perhaps the greatest health issue of the century, affecting more than 45 million individuals, with a global death toll exceeding one million [7]. The recent, less-anticipated advent of novel SARS-CoV-2 variants with altered Spike proteins, including the strain with 'Spike N453Y' mutation reported in Netherlands and Denmark; and the more overwhelming variants with 'Spike D614G' and 'N501Y' mutations spreading in England, has caused concerns regarding the efficacy of the recently approved vaccines in the future. The N501Y variant, in particular, has been suggested to be 56% more transmissible, owing to the enhanced binding affinity of the Spike protein to its polypeptide receptor, ACE2, on the host cell [9]; a finding with potential epigenetic implications. Containing a positive-sense ssRNA, SARS-CoV-2 is an enveloped β-coronavirus coated with Spike protein on its surface, which relies on the interaction between this protein and the transmembrane ACE2 on the host cell for viral entry. The epigenetic modifications, especially DNAm, regulating the expression of ACE2 had been known well before the emergence of SARS-CoV-2 [2]. Nonetheless, the rising prominence of epigenomics in the expansive research field of COVID-19 is not solely due to the role of ACE2 in the pathophysiology of the disease, as 332 human proteins have recently been identified to interact with SARS-CoV-2 proteins in several ways. A noteworthy example is HDAC2, which is involved in the initiation of immune responses against viruses [10]. HDAC2 contains a cleavage site that can be targeted by NSP5, Epigenomics

Blood Purification, 2021

Since early 2020, COVID-19 has wreaked havoc in many societies around the world. As of the presen... more Since early 2020, COVID-19 has wreaked havoc in many societies around the world. As of the present, the SARS-CoV-2-borne disease is propagating in almost all countries, affecting hundreds of thousands of people in an unprecedented way. As the name suggests, the novel coronavirus, widely known as SARS-CoV-2, is a new emerging human pathogen. A novel disease of relatively unknown origin, COVID-19 does not seem to be amenable to the currently available medicines since there is no specific cure for the disease. In the absence of any vaccine or effective antiviral medication, we have no tools at our disposal, but the method of quarantine, be it domestic or institutional, to hinder any further progression of this outbreak. However, there is a record of physicians in the past who practiced convalescent blood transfusion. To their awe, the method seemed to be useful. It is anticipated that these contemporary methods will outdo any other vaccination process in the time being, as blood transfusion is instead a cost-effective and time-friendly technique. Following a successful trial, this new approach of contemporary nature to a viral disease may serve as an emergency intervention to intercept infectious outbreaks and prevent an impending epidemic/pandemic. In this review, we document the most recent evidence regarding the efficiency of convalescent plasma and serum therapy on SARS, MERS, and particularly COVID-19, while discussing potential advantages and possible risks of such practice.

Journal of Neuro-Oncology, 2021

Introduction: Hyperthermia therapy (HT) is a recognized treatment modality, that can sensitize tu... more Introduction: Hyperthermia therapy (HT) is a recognized treatment modality, that can sensitize tumors to the effects of radiotherapy (RT) and chemotherapy by heating up tumor cells to 40-45 °C. The advantages of noninvasive inductive magnetic hyperthermia (MH) over RT or chemotherapy in the treatment of recurrent/progressive glioma have been confirmed by several clinical trials. Thus, here we have conducted a systematic review to provide a concise, albeit brief, account of the currently available literature regarding this topic.
Methods: Five databases, PubMed/Medline, Embace, Ovid, WOS, and Scopus, were investigated to identify clinical studies comparing overall survival (OS) following RT/chemotherapy versus RT/chemotherapy + MH.
Results: Eleven articles were selected for this systematic review, including reports on 227 glioma patients who met the study inclusion criteria. The papers included in this review comprised nine pilot clinical trials, one non-randomized clinical trial, and one retrospective investigation. As the clinical trials suggested, MH improved OS in primary glioblastoma (GBM), however, in the case of recurrent glioblastoma, no significant change in OS was reported. All 11 studies ascertained that no major side effects were observed during MH therapy.
Conclusion: Our systematic review indicates that MH therapy as an adjuvant for RT could result in improved survival, compared to the therapeutic outcomes achieved with RT alone in GBM, especially by intratumoral injection of magnetic nano-particles. However, heterogeneity in the methodology of the most well-known studies, and differences in the study design may significantly limit the extent to which conclusions can be drawn. Thus, further investigations are required to shed more light on the efficacy of MH therapy as an adjuvant treatment modality in GBM.

Applied Microbiology and Biotechnology, 2021

A most discussed topic of the new decade, COVID-19 is an infectious disease caused by the recentl... more A most discussed topic of the new decade, COVID-19 is an infectious disease caused by the recently discovered SARS-CoV-2. With an exceedingly high transmission rate, COVID-19 has affected almost all the countries in the world. Absent any vaccine or specific treatment, the humanity is left with nothing but the legacy method of quarantine. However, quarantine can only be effective when combined with early diagnosis of suspected cases. With their high sensitivity and unmatched specificity, biosen-sors have become an area of interest for development of novel diagnostic methods. Compared to the more traditional diagnostics, nanobiotechnology introduces biosensors as different diagnostics with greater versatility in application. Today, a growing number of analytes are being accurately identified by these nanoscopic sensing machines. Several reports of validated application with real samples further strengthen this idea. As of recent, there has been a rise in the number of studies on portable biosensors. Despite the slow progression, certain devices with embedded biosensors have managed to be of diagnostic value in several countries. The perceptible increase in development of mobile platforms has revolutionized the healthcare delivery system in the new millennium. The present article reviews the most recent advancements in development of diagnostic nanobiosensors and their application in the clinical fields.

Future Cardiology, 2021

With their dual inhibitory effects on SARS-CoV-2 3C Lpro and the NO/cGMP/PDE5 pathway, PDE5 inhib... more With their dual inhibitory effects on SARS-CoV-2 3C Lpro and the NO/cGMP/PDE5 pathway, PDE5 inhibitors suggestively act in more than one way against COVID-19, leading to the inhibition of viral replication and downregulation of pro-inflammatory pathways concerned with the induction of iNOS and instigation of thromboembolism.

Current Immunology Reviews, Dec 20, 2020

It is not unbeknownst to us that since the very onset of the COVID-19 outbreak, many patients fro... more It is not unbeknownst to us that since the very onset of the COVID-19 outbreak, many patients from different age groups have suffered greatly, and in a remarkable number of cases, succumbed to their untimely demise as a result of infection with the novel coronavirus or SARS-CoV-2. The elderly are perhaps the most vulnerable community, who stand at the pinnacle of morbidity and mortality rates due to contracting severe forms of COVID-19. Hopefully, based on the recent findings and the present evidence, there might be a number of medications that would possibly be of great prophylactic and therapeutic value to the elderly patients diagnosed with COVID-19. According to an interventional study, Thymosin α1 is arguably one such medication that has recently been indicated to be an effective therapeutic agent for inpatient management of lymphocytopenia and T cell exhaustion caused by COVID-19.

Journal of Molecular Neuroscience, Jun 5, 2020

Schizophrenia (SCZ) is a multifactorial disorder caused by environmental and genetic factors. Stu... more Schizophrenia (SCZ) is a multifactorial disorder caused by environmental and genetic factors. Studies have shown that various single-nucleotide polymorphisms (SNPs) in the binding sites of microRNAs contribute to the risk of developing SCZ. We aimed to investigate whether the variants located in the 3′-UTR region of LIF (rs929271T>G) and ATF6B (rs8283G>A) were associated with increased susceptibility to SCZ in a population from the southeast of Iran. In this case-control study, a total of 396 subjects were recruited. SNPs were genotyped via polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Genotyping results showed that the G allele of rs929271 significantly increased the risk of SCZ (OR = 1.58 95%CI = 1.19-2.10, p = 0.001). As for rs929271, the GG genotype of co-dominant (OR = 2.54 95%CI = 1.39-4.64, p = 0.002) and recessive (OR = 2.91 95%CI = 1.77-4.80, p < 0.001) models were strongly linked to SCZ. No significant differences were observed between rs8283 polymorphism and predisposition to SCZ. In silico analyses predicted that rs929271 might alter the binding sites of microRNAs, which was believed to have an unclear role in the development of SCZ. Moreover, rs929271 polymorphism changed the LIF-mRNA folding structure. These findings provide fine pieces of evidence regarding the possible effects of LIF polymorphism in the development of SCZ and regulation of the LIF gene targeted by microRNAs.

International Journal of Molecular and Cellular Medicine, 2019

Circulating microRNAs have been recognized as promising biomarkers for the detection of lung canc... more Circulating microRNAs have been recognized as promising biomarkers for the detection of lung cancer. The objective of this study was to evaluate miR-10b, miR-1 and, miR-30a in the plasma samples of lung cancer patients to confirm any possible relevance in the early detection of lung cancer. Plasma samples from 47 non-small-cell lung cancer patients and 41 cancer-free subjects were evaluated for selected microRNAs using the real-time PCR method. To evaluate the tobacco smoking effects on microRNAs expression, the studied groups were categorized into two subgroups: never-smokers and smokers. MiR-1/miR-30a expression levels were significantly reduced in lung cancer, while the miR-10b level was significantly elevated. We found that smoking had significant effects on the levels of circulating microRNAs in the smokers of the cancer-free group (a significant up-regulation of miR-10b and significant down-regulation of miR-1/miR-30a), and lung cancer patients (a significant elevation of miR-10b). Receiver operating characteristic curve analysis showed that miR-10b with an area under the curve of 0.861, and miR-1/miR-30a with values of0.905 and 0.889 for the same parameter, could distinguish non-small-cell lung cancer patients from cancer-free subjects. Our findings demonstrated significant differences in the expression of microRNAs in lung cancer and the considerable effects of smoking on microRNAs levels. Area under curve analysis showed that miR-10b with 78% sensitivity/78% specificity, miR-1 with 95% sensitivity/80% specificity and miR-30a with 87% sensitivity/83% specificity,might be good (miR-10b/miR-30a) and excellent (miR-1) markers for lung cancer detection.

Journal of Cellular Physiology, 2020

Months after the outbreak of a new flu-like disease in China, the entire world is now in a state ... more Months after the outbreak of a new flu-like disease in China, the entire world is now in a state of caution. The subsequent less-anticipated propagation of the novel coronavirus disease, formally known as COVID-19, not only made it to headlines by an overwhelmingly high transmission rate and fatality reports, but also raised an alarm for the medical community all around the globe. Since the causative agent, SARS-CoV-2, is a recently discovered species, there is no specific medicine for downright treatment of the infection. This has led to an unprecedented societal fear of the newly born disease, adding a psychological aspect to the physical manifestation of the virus. Herein, the COVID-19 structure, epidemiology, pathogenesis, etiology, diagnosis, and therapy have been reviewed.

Current Molecular Medicine, 2020

In both men and women around the world, lung cancer accounts as the principal cause of cancer-rel... more In both men and women around the world, lung cancer accounts as the principal cause of cancer-related death after breast cancer. Therefore, early detection of the disease is a cardinal step in improving prognosis and survival of patients. Today, the newly-defined microRNAs regulate about 30 to 60 percent of the gene expression. Changes in microRNA Profiles are linked to numerous health conditions, making them sophisticated biomarkers for timely, if not early, detection of cancer. Though evaluation of microRNAs in real samples has proved to be rather challenging, which is largely attributable to the unique characteristics of these molecules. Short length, sequence similarity, and low concentration stand among the factors that define microRNAs. Recently, diagnostic technologies with a focus on wide-scale point of care have recently garnered attention as great candidates for early diagnosis of cancer. Electrochemical nano-biosensors have recently garnered much attention as a molecular method, showing great potential in terms of sensitivity, specificity and reproducibility, and last but not least, adaptability to point-of-care testing. Application of nanoscale materials in electrochemical devices as promising as it is, brings multiplexing potential for conducting simultaneous evaluations on multiple cancer biomarkers. Thanks to their enthralling properties, these materials can be used to improve the efficiency of cancer diagnostics, offer more accurate predictions of prognosis, and monitor response to therapy in a more efficacious way. This article presents a concise overview of recent advances in the expeditiously evolving area of electrochemical biosensors for microRNA detection in lung cancer.