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Melatonin and morphine: potential beneficial effects of co-use
No full textMorphine is a potent analgesic agent used to control acute or chronic pain. Chronic administration of morphine results in analgesic tolerance, hyperalgesia, and other side effects including dependence, addiction, respiratory depression, and constipation, which limit its clinical usage. Therefore, identifying the new analgesics with fewer side effects which could increase the effect of morphine and reduce its side effects is crucial. Melatonin, a multifunctional molecule produced in the body, is known to play an important role in pain regulation. The strong anti-inflammatory effect of melatonin is suggested to be involved in the attenuation of the pain associated with inflammation. Melatonin also increases the anti-nociceptive actions of opioids, such as morphine, and reverses their tolerance through regulating several cellular signaling pathways. In this review, published articles evaluating the effect of the co-consumption of melatonin and morphine in different conditions were investigated. Our results show that melatonin has pain-killing properties when administered alone or in combination with other anti-nociceptive drugs. Melatonin decreases morphine consumption in different pathologies. Furthermore, attenuation of morphine intake can be accompanied by reduction of morphine-associated side-effects, including physical dependence, morphine tolerance, and morphine-related hyperalgesia. Therefore, it is reasonable to believe that the combination of melatonin with morphine could reduce morphine-induced tolerance and hyperalgesia, which may result from anti-inflammatory and antioxidant properties of melatonin. Overall, we underscore that, to further ameliorate patients' life quality and control their pain in various pathological conditions, melatonin deserves to be used with morphine by anesthesiologists in clinical practice. © 2020 Société Française de Pharmacologie et de Thérapeutique
Allelic Dropout Is a Common Phenomenon That Reduces the Diagnostic Yield of PCR-Based Sequencing of Targeted Gene Panels
Full text linkPrimary cardiomyopathies (CMPs) are monogenic but multi-allelic disorders with dozens of genes involved in pathogenesis. The implementation of next-generation sequencing (NGS) approaches has resulted in more time- and cost-efficient DNA diagnostics of cardiomyopathies. However, the diagnostic yield of genetic testing for each subtype of CMP fails to exceed 60. The aim of this study was to demonstrate that allelic dropout (ADO) is a common phenomenon that reduces the diagnostic yield in primary cardiomyopathy genetic testing based on targeted gene panels assayed on the Ion Torrent platform. We performed mutational screening with three custom targeted gene panels based on sets of oligoprimers designed automatically using AmpliSeq Designer® containing 1049 primer pairs for 37 genes with a total length of 153 kb. DNA samples from 232 patients were screened with at least one of these targeted gene panels. We detected six ADO events in both IonTorrent PGM (three cases) and capillary Sanger sequencing (three cases) data, identifying ADO-causing variants in all cases. All ADO events occurred due to common or rare single nucleotide variants (SNVs) in the oligoprimer binding sites and were detected because of the presence of �marker� SNVs in the target DNA fragment. We ultimately identified that PCR-based NGS involves a risk of ADO that necessitates the use of Sanger sequencing to validate NGS results. We assume that oligoprimer design without ADO data affects the amplification efficiency of up to 0.77 of amplicons. © Copyright © 2021 Shestak, Bukaeva, Saber and Zaklyazminskaya
Sinomenine Alleviates Murine Experimental Autoimmune Encephalomyelitis Model of Multiple Sclerosis through Inhibiting NLRP3 Inflammasome
No full textMultiple sclerosis (MS) is known as a chronic neuroinflammatory disorder typified by an immune-mediated demyelination process with ensuing axonal damage and loss. Sinomenine is a natural alkaloid with different therapeutic benefits, including anti-inflammatory and immunosuppressive activities. In this study, possible beneficial effects of sinomenine in an MOG-induced model of MS were determined. Sinomenine was given to MOG35�55-immunized C57BL/6 mice at doses of 25 or 100 mg/kg/day after onset of MS clinical signs till day 30 post-immunization. Analyzed data showed that sinomenine reduces severity of the clinical signs and to some extent decreases tissue level of pro-inflammatory cytokines IL-1β, IL-6, IL-18, TNFα, IL-17A, and increases level of anti-inflammatory IL-10. In addition, sinomenine successfully attenuated tissue levels of inflammasome NLRP3, ASC, and caspase 1 besides its reduction of intensity of neuroinflammation, demyelination, and axonal damage and loss in lumbar spinal cord specimens. Furthermore, immunoreactivity for MBP decreased and increased for GFAP and Iba1 after MOG-immunization, which was in part reversed upon sinomenine administration. Overall, sinomenine decreases EAE severity, which is attributed to its alleviation of microglial and astrocytic mobilization, demyelination, and axonal damage along with its suppression of neuroinflammation, and its beneficial effect is also associated with its inhibitory effects on inflammasome and pyroptotic pathways; this may be of potential benefit for the primary progressive phenotype of MS. © 2020, Springer Science+Business Media, LLC, part of Springer Nature
Congenital Ichthyosis in a Case of Spinocerebellar Ataxia Type 34: A Novel Presentation for a Known Mutation
No full textNovel disease-causing variants in a cohort of Iranian patients with metachromatic leukodystrophy and in silico analysis of their pathogenicity
No full textObjective: Metachromatic leukodystrophy (MLD) is an autosomal recessive leukodystrophy caused by deficiency of aryl sulfatase A (ASA) activity affecting the nervous system. MLD and mutations in ARSA have not been widely studied in non-European cohorts. The genotype-phenotype spectrum of MLD patients was investigated in this study of a cohort of Iranian leukodystrophy patients. In silico analysis was performed to investigate the pathogenicity of the variants. Methods: Genetic analysis for 25 patients was performed with direct sequencing of the ARSA gene. The missense variants underwent in silico analysis to characterize the pathogenicity based on predicted structural and stability changes. Results: 19 patients had variants in ARSA genes, including 18 homozygotes and one compound heterozygote individual. In 6 individuals no mutations were found in ARSA gene, suggesting an alternative cause of their leukodystrophy. We found 5 novel disease causing variants: p.Phe64Ile, p.Ser292Alafs*34, p.Arg99Profs*35, p.Phe400Leu and p.Leu429Pro. 32 of the patients had p.Gly311Ser substitution and resulted in juvenile MLD type. Different in silico analysis showed variable pathogenic effect for the variants. Conclusion: c.931 G > A (p.Gly311Ser) and c.465 + 1 G > A variants are the most frequent alleles among Iranian MLD patients and five mutations appear to be confined to the Iranian patients. Population screening for these variants may be helpful to reduce the burden of the disease in this part of the world. © 2020 Elsevier B.V
The role of Th17 cells in viral infections
No full textThe present review provides an overview of recent advances regarding the function of Th17 cells and their produced cytokines in the progression of viral diseases. Viral infections alone do not lead to virus-induced malignancies, as both genetic and host safety factors are also involved in the occurrence of malignancies. Acquired immune responses, through the differentiation of Th17 cells, form the novel components of the Th17 cell pathway when reacting with viral infections all the way from the beginning to its final stages. As a result, instead of inducing the right immune responses, these events lead to the suppression of the immune system. In fact, the responses from Th17 cells during persistent viral infections causes chronic inflammation through the production of IL-17 and other cytokines which provide a favorable environment for tumor growth and its development. Additionally, during the past decade, these cells have been understood to be involved in tumor progression and metastasis. However, further research is required to understand Th17 cells� immune mechanisms in the vast variety of viral diseases. This review aims to determine the roles and effects of the immune system, especially Th17 cells, in the progression of viral diseases; which can be highly beneficial for the diagnosis and treatment of these infections. © 2020 Elsevier B.V
Various wastewaters treatment by sono-electrocoagulation process: A comprehensive review of operational parameters and future outlook
No full textElectrochemical processes are a promising alternative to traditional water treatment systems because they have advantages than conventional techniques such as chemical storage, small treatment systems, no alkalinity depletion, remote adjustment, and cost-effectiveness. The most crucial electrochemical method is Electrocoagulation (EC). Through creating cationic species, the EC causes the neutralization of pollutant surface charges and destabilizes suspended, emulsified or dissolved contaminants led to attracting particles of opposite charge and form flocculants. The main drawback of the EC process is a passive film forming on the electrode surface over time. Ultrasonic (US) waves breaking down sediments formed at the electrode surface and generate high amounts of radical species to remove pollutants by creating high-pressure points inside the solution during the cavitation phenomenon. Although EC systems are considered as an exemplary renaissance in water and wastewater treatment, various parameters related to these types of systems in pollutant degradation have not been fully addressed. To present a comprehensive vision of the current state of the art, and progress the treatment efficiency and agitate new studies in these fields, this review aimed to provide an overview of electrocoagulation's application in pollutant degradation, besides the advantages, associated disadvantages and further strategies for improving the performance of this technique. Moreover, this review discussed various parameters affecting the EC/US process, including nanoparticles addition, electrolyte concentration, current intensity, electrode distance, temperature, oxidant addition, pH, pollutant concentration, reaction time, and electrode combination, chloride addition, and ultrasonic frequency. Also, the efficiency of the EC/US process for disinfection, as well as treatment of car-washing, textile, pulp, and paper industry, oily, brewery wastewater, surfactant, humic acid, and heavy metals, are addressed. © 2020 Elsevier Lt
A new model for investigating the role of knowledge management system on the mental health of employees
No full textPurpose: Knowledge management (KM) implementation is the ideal solution for enhancing employee�s abilities like mental health and performance. This study aims at testing the impact of KM mechanism on personnel�s mental health at the Iran University of Medical Sciences. Design/methodology/approach: The study is a descriptive, correlational and applied one. The library and field studies have been used to collect data through the questionnaire. The proposed model and the data have been analyzed using Smart PLS software. A questionnaire has been conducted by an arbitrary sampling method. Findings: The results have shown that the main factors of KM have a direct, meaningful positive impact on innovation. Besides, the critical parameters of KM success, strategy and process have a significant and direct positive effect on the tendency for knowledge-sharing behavior. Further, the direct relationship of the trend for knowledge-sharing behavior with the mental health of employees has positively been confirmed. The results have also indicated that psychological empowerment has a positive and significant effect on the mental health of employees. Research limitations/implications: This study has investigated the four parameters (i.e. key factors for KM success, KM strategy, KM processes and psychological empowerment) impacting the knowledge-sharing intention, conduct of the people and the mental health of the employees. Scholars can investigate other personal and organizational parameters such as probable backgrounds of the knowledge-sharing intention, conduct and the mental health of the employees. Practical implications: These findings will be essential in the understanding of the interplay among various signals in theory and the understanding of patients� choices in the electronic health (e-health) community in practice. The results have implications for existing health management and e-health literature. The present paper will help policymakers, healthcare executives and project managers to effectively set their operations and make them maintainable, prevent unpredicted obstacles and better allocate their resources. Overall, the result of this paper will guide researchers who are working in the field of e-health. Originality/value: The findings can develop robust knowledge-sharing platforms and offer insightful suggestions for management practitioners in emerging markets. © 2021, Emerald Publishing Limited
Genetically engineered fusion of allergen and viral-like particle induces a more effective allergen-specific immune response than a combination of them
No full textAbstract: Chimeric virus-like particles (VLPs) were developed as a candidate for allergen-specific immunotherapy. In this study, hepatitis B core antigen (HBcAg) that genetically fused to Chenopodium album polcalcin (Che a 3)�derived peptide was expressed in E. coli BL21, purified, and VLP formation was evaluated using native agarose gel electrophoresis (NAGE) and transmission electron microscopy (TEM). Chimeric HBc VLPs were characterized in terms of their reactivity to IgE, the induction of blocking IgG and allergen-specific IgE, basophil-activating capacity, and Th1-type immune responses. Results from IgE reactivity and basophil activation test showed that chimeric HBc VLPs lack IgE-binding capacity and basophil degranulation activity. Although chimeric HBc VLPs induced the highest level of efficient polcalcin-specific IgG antibody in comparison to those induced by recombinant Che a 3 (rChe a 3) mixed either with HBc VLPs or alum, they triggered the lowest level of polcalcin-specific IgE in mice following immunization. Furthermore, in comparison to the other antigens, chimeric HBc VLPs produced a polcalcin-specific Th1 cell response. Taken together, genetically fusion of allergen derivatives to HBc VLPs, in comparison to a mix of them, may be a more effective way to induce appropriate immune responses in allergen-specific immunotherapy. Key points: � The insertion of allergen-derived peptide into major insertion region (MIR) of hepatitis B virus core (HBc) antigen resulted in nanoparticles displaying allergen-derived peptide upon its expression in prokaryotic host. � The resultant VLPs (chimeric HBc VLPs) did not exhibit IgE reactivity with allergic patients� sera and were not able to degranulate basophils. � Chimeric HBc VLPs dramatically improved protective IgG antibody response compared with those induced by allergen mixed either with HBc VLPs or alum. � Chimeric HBc VLPs induced Th1 responses that were counterparts of Th2 responses (allergic). � Chimeric HBc VLPs increased IgG2a/ IgG1 ratio and the level of IFN-γ compared to those induced by allergen mixed with either HBc VLPs or alum. Figure not available: see fulltext. © 2020, Springer-Verlag GmbH Germany, part of Springer Nature
Exosomal microRNAs and exosomal long non-coding RNAs in gynecologic cancers
No full textGynecologic cancer is a group of any malignancies affecting reproductive tissues and organs of women, including ovaries, uterine, cervix, vagina, vulva, and endometrium. Several types of molecular mechanisms are associated with the progression of gynecologic cancers. Among it can be referred to the most widely studied non-coding RNAs (ncRNAs), specifically microRNAs (miRNAs) and long ncRNAs (lncRNAs). As yet, lncRNAs are known to serve key biological roles via various mechanisms, such as splicing regulation, chromatin rearrangement, translation regulation, cell-cycle control, genetic imprinting and mRNA decay. Besides, miRNAs govern gene expression by modulation of mRNAs and lncRNAs degradation, suggestive of needing more research in this field. Generally, driving gynecological cancers pathways by miRNAs and lncRNAs lead to the current improvement in cancer-related technologies. Exosomes are extracellular microvesicles which can carry cargo molecules among cells. In recent years, more studies have been focused on exosomal non-coding RNAs (exo-ncRNAs) and exosomal microRNAs (exo-miRs) because of being natural carriers of lnc RNAs and microRNAs via programmed process. In this review we summarized recent reports concerning the function of exosomal microRNAs and exosomal long non-coding RNAs in gynecological cancers. © 2021 Elsevier Inc