The Role of Alpha-Synuclein in Neurodevelopmental Diseases.

Neurodevelopmental disorders are a group of diseases with cognitive, motor, and emotional development deficits. Alpha-synuclein (α-syn) is a synaptic protein involved in transmission and neurodevelopment. This protein was previously shown to be associated with several disorders, including Parkinson's disease. Furthermore, a close link between neurodevelopmental disorders and Parkinson's has also been found. Changes in synaptic function have been noticed in neurodevelopmental disorders, including autism spectrum disorder. Impaired neurogenesis and related cognitive problems have been associated with altered expression of α-syn. Various studies reported α-syn in different body fluids and tissues such as blood and serum. Alpha-synuclein can help in better understanding the pathogenesis of neurodevelopmental diseases and facilitating their early diagnosis. This review aims to go over the recent advances in the role of α-syn in the pathophysiology of neurodevelopmental disorders, including autism spectrum disorder, attention deficit hyperactivity disorder, and motor and social impairment, and its value as a diagnostic biomarker.

Cystic echinococcosis microRNAs as potential noninvasive biomarkers: current insights and upcoming perspective.

INTRODUCTION: Echinococcosis, also known as hydatidosis, is a zoonotic foodborne disease occurred by infection with the larvae of Echinococcus spp. which can lead to the development of hydatid cysts in various organs of the host. The diagnosis of echinococcosis remains challenging due to limited diagnostic tools. AREAS COVERED: In recent years, microRNAs (miRNAs) have emerged as a promising biomarker for various infectious diseases, including those caused by helminths. Recent studies have identified several novel miRNAs in Echinococcus spp. shedding light on their essential roles in hydatid cyst host-parasite interactions. In this regard, several studies have shown that Echinococcus-derived miRNAs are present in biofluids such as serum and plasma of infected hosts. The detection of these miRNAs in the early stages of infection can serve as an early prognostic and diagnostic biomarker for echinococcosis. EXPERT OPINION: The miRNAs specific to Echinococcus spp. show great potential as early diagnostic biomarkers for echinococcosis and can also provide insights into the pathogenesis of this disease. This review attempts to provide a comprehensive overview of Echinococcus-specific miRNAs, their use as early diagnostic biomarkers, and their function in host-parasite interactions.

circGFRA1: A circular RNA with important roles in human carcinogenesis.

Circular RNAs (circRNAs) are a type of covalently closed RNA molecules, which are mainly formed by back splicing of a precursor mRNA upstream exon into a downstream exon. Abnormally expressed circRNAs can modulate gene transcription by indirectly interacting with microRNAs (miRNAs). According to the current studies, circGFRA1 has been suggested to be upregulated in various cancers. circGFRA1 (hsa_circ_005239) is a type of cancer-related circRNA, which is predicted to be originated from the GFRA1 on chromosome 10. circGFRA1 can act as a sponge for several miRNAs, including miR-34a, miR-1228, miR-361-5p, miR-149, miR-498, miR-188-3p, miR-3064-5p, miR-449a. Additionally, it can regulate signaling pathways such as TGF-ß and PI3K/ AKT. circGFRA1 upregulation has been correlated with patients' poor overall survival in diverse cancers. In the present review, we have summarized the oncogenic effect of circGFRA1 in various cancers according to the adopted criteria from in vitro, in vivo, and clinical research. Moreover, functional enrichment analysis was performed on the circGFRA1 host gene and its protein interaction network to detect gene ontology and related pathways.

Human T2R38 Bitter Taste Receptor Expression and COVID-19: From Immunity to Prognosis.

Background: Bitter taste-sensing type 2 receptor (T2Rs or TAS2Rs) found on ciliated epithelial cells and solitary chemosensory cells have a role in respiratory tract immunity. T2Rs have shown protection against SARS-CoV-2 by enhancing the innate immune response. The purpose of this review is to outline the current sphere of knowledge regarding this association. Methods: A narrative review of the literature was done by searching (T2R38 OR bitter taste receptor) AND (COVID-19 OR SARS-CoV-2) keywords in PubMed and google scholar. Results: T2R38, an isoform of T2Rs encoded by the TAS2R38 gene, may have a potential association between phenotypic expression of T2R38 and prognosis of COVID-19. Current studies suggest that due to different genotypes and widespread distributions of T2Rs within the respiratory tract and their role in innate immunity, treatment protocols for COVID-19 and other respiratory diseases may change accordingly. Based on the phenotypic expression of T2R38, it varies in innate immunity and host response to respiratory infection, systemic symptoms and hospitalization. Conclusion: This review reveals that patients' innate immune response to SARS-COV-2 could be influenced by T2R38 receptor allelic variations.

Curcumin effects on chronic obstructive pulmonary disease: A systematic review.

Introduction: Chronic obstructive pulmonary disease (COPD) is a common disease of the lungs known as the third reason for death worldwide. Frequent COPD exacerbations compel health care workers to apply interventions that are not adverse effect free. Accordingly, adding or replacing Curcumin, a natural meal flavoring, may indicate advantages in this era by its antiproliferative and anti-inflammatory effects. Methods: The PRISMA checklist was employed for the systematic review study. On June 3, 2022, PubMed/Medline, Scopus, and Web of Science were searched for studies associated with COPD and Curcumin in the last 10 years. Duplicate or non-English publications and articles with irrelevant titles and abstracts were excluded. Also, preprints, reviews, short communications, editorials, letters to the editor, comments, conference abstracts, and conference papers were not included. Results: Overall, 4288 publications were found eligible, after the screening, 9 articles were finally included. Among them, one, four, and four in vitro, in vivo, and both in vivo and in vitro research exist respectively. According to the investigations, Curcumin can inhibit alveolar epithelial thickness and proliferation, lessen the inflammatory response, remodel the airway, produce ROS, alleviate airway inflammation, hinder emphysema and prevent ischemic complications. Conclusion: Consequently, the findings of the current review demonstrate that Curcumin's modulatory effects on oxidative stress, cell viability, and gene expression could be helpful in COPD management. However, for data confirmation, further randomized clinical trials are required.

The Role of p66Shc in Diabetes: A Comprehensive Review from Bench to Bedside.

It is well-documented that diabetes is an inflammatory and oxidative disease, with an escalating global burden. Still, there is no definite treatment for diabetes or even prevention of its harmful complications. Therefore, understanding the molecular pathways associated with diabetes might help in finding a solution. p66Shc is a member of Shc family proteins, and it is considered as an oxidative stress sensor and regulator in cells. There are inconsistent data about the role of p66Shc in inducing diabetes, but accumulating evidence supports its role in the pathogenesis of diabetes-related complications, including macro and microangiopathies. There is growing hope that by understanding and targeting molecular pathways involved in this network, prevention of diabetes or its complications would be achievable. This review provides an overview about the role of p66Shc in the development of diabetes and its complications.

Diabetes and skin cancers: Risk factors, molecular mechanisms and impact on prognosis.

Diabetes and skin cancers have emerged as threats to public health worldwide. However, their association has been less intensively studied. In this narrative review, we explore the common risk factors, molecular mechanisms, and prognosis of the association between cutaneous malignancies and diabetes. Hyperglycemia, oxidative stress, low-grade chronic inflammation, genetic, lifestyle, and environmental factors partially explain the crosstalk between skin cancers and this metabolic disorder. In addition, diabetes and its related complications may interfere with the appropriate management of cutaneous malignancies. Antidiabetic medication seems to exert an antineoplastic effect, however, future large, observation studies with a prospective design are needed to clarify its impact on the risk of malignancy in diabetes. Screening for diabetes in skin cancers, as well as close follow-up for the development of cutaneous malignancies in subjects suffering from diabetes, is warranted.

Asthma and Vitamin D Deficiency: Occurrence, Immune Mechanisms, and New Perspectives.

Asthma, as a chronic inflammatory condition of the airways, has a considerable prevalence among children. Vitamin D might play a role in asthma pathogenesis by affecting the development of the lung, regulating the immune responses, and remodeling of airway smooth muscle (ASM). Study results on the association between the serum level of vitamin D and asthma severity have suggested a converse relationship between lower vitamin D levels and more severe clinical courses. However, they are not consistent in these findings and have shown insignificant correlations, as well. The possible effects of vitamin D on asthma have led researchers to consider this vitamin a potential prophylactic and therapeutic tool for managing children with variant degrees of asthma. Adding vitamin D to the routine corticosteroid therapy of asthmatic children is another field of interest that has shown promising results. In this narrative review study, we aim to elaborate on the existing knowledge on the role of vitamin D in asthma pathogenesis and prognosis, explain the controversies that exist on the effectiveness of treating patients with vitamin D supplements, and make a general conclusion about how vitamin D actually is linked to asthma in children.

Nature against Diabetic Retinopathy: A Review on Antiangiogenic, Antioxidant, and Anti-Inflammatory Phytochemicals.

Background and Purpose. Diabetes mellitus (DM), hyperglycemia, and hypertension can result in diabetic retinopathy (DR), which is a major cause of blindness on a global scale. Development of DR is associated with decreased endothelial cells, increased basal membrane thickness, permeation of the retinal blood barrier, and neovascularization in patients. The purpose of the present review is to provide an overview of the findings regarding applications of phytochemicals for DR treatment and could be a beneficial resource for further clinical studies and also a basis for pharmaceutical purposes for drug design. Materials and Methods. A narrative literature review was performed from electronic databases including Web of Science, PubMed, and Scopus to analyze the effects of different phytochemicals to prevent or treat oxidation, angiogenesis, and inflammation in diabetic retinopathy. The inclusion criteria were original studies, which included the effects of different phytochemicals on diabetic retinopathy. The exclusion criteria included studies other than original articles, studies which assessed the effects of phytochemicals on nondiabetic retinopathy, and studies which used phytochemical-rich extracts. Results and Conclusions. Studies have shown that increased levels of inflammatory cytokines, angiogenic, and oxidative stress factors are involved in the progression and pathogenesis of DR. Therefore, phytochemicals with their anti-inflammatory, antiangiogenic, and antioxidant properties can prevent DR progression and retinal damage through various cellular mechanisms. It is also shown that some phytochemicals can simultaneously affect the inflammation, oxidation, and angiogenesis in DR.

Oral lesions after COVID-19 vaccination: Immune mechanisms and clinical approach.

COVID-19 vaccination, although is a promising tool to overcome the pandemic, has side effects. There are increasing reports of oral lesions after COVID-19 vaccination. The aim of this review is to identify the occurrence of some oral lesions after COVID-19 vaccination, and highlight the underlying immune mechanisms involved. A narrative literature review was performed by searching electronic databases including PubMed, Scopus and Web of Science to investigate the oral lesions after COVID-19 vaccination. The inclusion criteria were original studies, including the case reports, case series, letter to the editor, and cross-sectional studies. The exclusion criteria included the studies which examined the oral lesions caused by COVID-19 infection. The information, including the number of participant(s) receiving vaccine, type of vaccine, dose number, side effect(s), time of onset following vaccination, healing time, treatment strategies for the existing lesions, and related mechanisms were then summarized in a data extraction sheet. The results of this review showed that some vaccines had side effects with oral involvement such as pemphigus vulgaris, bullous pemphigoid, herpes zoster, lichen planus, Stevens-Johnson syndrome and Behçet's disease. Future research needs to elucidate the physiopathology of oral manifestations after the COVID-19 vaccination, and better understand the risk factors associated with such responses. Sometimes vaccine's side effects may be due to the nocebo effect, which means that the person expects some adverse events to occur following the vaccine administration.

Noncoding RNA Roles in Pharmacogenomic Responses to Aspirin: New Molecular Mechanisms for an Old Drug.

Aspirin, as one of the most frequently prescribed drugs, can have therapeutic effects on different conditions such as cardiovascular and metabolic disorders and malignancies. The effects of this common cardiovascular drug are exerted through different molecular and cellular pathways. Altered noncoding RNA (ncRNA) expression profiles during aspirin treatments indicate a close relationship between these regulatory molecules and aspirin effects through regulating gene expressions. A better understanding of the molecular networks contributing to aspirin efficacy would help optimize efficient therapies for this very popular drug. This review is aimed at discussing and highlighting the identified interactions between aspirin and ncRNAs and their targeting pathways and better understanding pharmacogenetic responses to aspirin.

Flavonoids as Promising Antiviral Agents against SARS-CoV-2 Infection: A Mechanistic Review.

A newly diagnosed coronavirus in 2019 (COVID-19) has affected all human activities since its discovery. Flavonoids commonly found in the human diet have attracted a lot of attention due to their remarkable biological activities. This paper provides a comprehensive review of the benefits of flavonoids in COVID-19 disease. Previously-reported effects of flavonoids on five RNA viruses with similar clinical manifestations and/or pharmacological treatments, including influenza, human immunodeficiency virus (HIV), severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS), and Ebola, were considered. Flavonoids act via direct antiviral properties, where they inhibit different stages of the virus infective cycle and indirect effects when they modulate host responses to viral infection and subsequent complications. Flavonoids have shown antiviral activity via inhibition of viral protease, RNA polymerase, and mRNA, virus replication, and infectivity. The compounds were also effective for the regulation of interferons, pro-inflammatory cytokines, and sub-cellular inflammatory pathways such as nuclear factor-κB and Jun N-terminal kinases. Baicalin, quercetin and its derivatives, hesperidin, and catechins are the most studied flavonoids in this regard. In conclusion, dietary flavonoids are promising treatment options against COVID-19 infection; however, future investigations are recommended to assess the antiviral properties of these compounds on this disease.

Role of microRNAs in the anticancer effects of the flavonoid luteolin: a systematic review.

Flavonoids, a broad class of polyphenolic compounds, can potentially have several therapeutic properties in human diseases, including protective effects against oxidative stress, inflammation, cardiovascular disease, diabetes, neurodegenerative disorders, and cancers. Luteolin as a member of flavonoids has been found to exhibit several anticancer properties mainly through cell apoptosis induction, inhibition of invasion, cell proliferation, network formation, and migration. Recent studies have revealed that phytochemicals such as luteolin may exert therapeutic properties through microRNAs (miRNAs or miRs), which have been emerged as important molecules in cancer biology in recent years. miRNAs, as a class of noncoding RNAs, have several important roles in cancer progression or regression. In this review, we aimed to summarize and discuss the role of miRNAs in the luteolin effects on different cancers. This review can be in line with the studies, which have shown that miRNAs may be potential therapeutic targets in cancer treatment.

Applying computer simulations in battling with COVID-19, using pre-analyzed molecular and chemical data to face the pandemic.

Coronavirus disease 2019 (COVID-19) has made many concerns for healthcare services especially, in finding useful therapeutic(s). Despite the scientists' struggle to find and/or creating possible drugs, so far there is no treatment with high efficiency for the disease. During the pandemic, researchers have performed some molecular analyses to find potential therapeutics out of both the natural and synthetic available medicines. Computer simulations and related data have shown a significant role in drug discovery and development before. In this field, antiviral drugs, phytochemicals, anti-inflammatory agents, etc. were essential groups of compounds tested against COVID-19, using molecular modeling, molecular dynamics (MD), and docking tools. The results indicate promising effects of such compounds to be used in further experimental and clinical trials; Chloroquine, Chloroquine-OH, and Umifenovir as viral entry inhibitors, Remdesivir, Ribavirin, Lopinavir, Ritonavir, and Darunavir as viral replication inhibitors, and Sirolimus are the examples, which were tested clinically on patients after comprehensive assessments of the available data on molecular simulation. This review summarizes the outcomes of various computer simulations data in the battle against COVID-19.

MicroRNAs in the anticancer effects of celecoxib: A systematic review.

Cyclooxygenase-2 (COX-2) is known as an important enzyme in the inflammation process that has tumorigenesis function in various cancers through the induction of epithelial-to-mesenchymal transition (EMT), cell proliferation, migration, and invasion that lead to metastasis. Celecoxib is a nonsteroidal anti-inflammatory drug (NSAID) that can selectively target COX-2, suppress downstream pathways, and finally lead to anticancer potentiality. microRNAs (miRNAs), as a class of small noncoding RNAs, play pivotal roles in cancers through the tumor-suppressive or oncogenic effects, by post-transcriptional regulation of their target genes. In this regard, shreds of evidence have shown that, COX-2 reveals its action through miRNA regulation. So, in this systematic review, we aimed to highlight the tumorigenic role of COX-2 in cancer development and the therapeutic effects of celecoxib, as a selective COX-2 drug, through the regulation of miRNAs.