scholarly journals Therapeutic effect of soluble factors of M2 phenotype macrophages in children with language impairments

2021 ◽  
Vol 23 (5) ◽  
pp. 1137-1150
Author(s):  
E. Ya. Shevela ◽  
V. G. Degtyareva ◽  
A. V. Sosnovskaya ◽  
E. V. Voronova ◽  
M. Yu. Kafanova ◽  
...  

The aim of the present study was to assess safety and clinical efficacy of inhalation immunotherapy based on intranasal administration of bioactive factors produced by the M2 phenotype macrophages in children with language impairments, as well as to study the effect of inhalation immunotherapy on the cytokine profile in the patients' blood serum. The study was carried out according to the NCT04689282 protocol (www.ClinicalTrials.gov) and included 14 children (9 boys / 5 girls), aged 3 to 8 years, with language impairments associated with perinatal or postnatal CNS lesions of various origin. The children recruited into the study were assessed by a neurologist and speech therapist before the therapy, at the end of the course (1 month), and 6 months later. Serum samples for cytokine analysis were obtained before and 1 month after therapy. The course of intranasal inhalations by the conditioned M2 media (2 ml one time per day for 28-30 days) was safe and well tolerated. None of the 14 treated children had significant adverse reactions and severe undesirable events. Intranasal immunotherapy led to a decrease in the severity of language problems, which manifested by improved speech understanding by 45%; the sensorimotor level of speech, by 51%; word formation skills, by 72%, as well as a twofold increase in general and fine motor skills. In children with signs of autism spectrum disorders, along with a language improvement, a decrease in the severity of autistic symptoms was registered, as evidenced by statistically significant decrease in the CARS score from 42.5 to 38.5 after 1 month, and to 33 points after 6 months (p < 0.05). The clinical effect was revealed rather soon, i.e., within a month after the first procedure, being maintained or intensified during a follow-up for 6 months. At the same time, two-thirds of the children showed a clear clinical improvement, with insignificant effect in the rest of patients. Comparative analysis of the serum cytokine levels in these subgroups showed that children with a pronounced positive response to inhaled immunotherapy differed in the following parameters: (1) initially higher level of VEGF and IGF-1, and (2) decrease the level of TNFα in response to intranasal immunotherapy. In summary, we first tested a fundamentally new approach based on the use of soluble factors from M2-type macrophages and intranasal route of their administration in order to treat the children with severe language impairments, demonstrating safety and obtained preliminary data on effectiveness of such approach.

2021 ◽  
Author(s):  
Gagandeep Kaur ◽  
Shaiesh Yogeswaran ◽  
Thivanka Muthumalage ◽  
Irfan Rahman

AbstractBackgroundTobacco smoking is known to be involved in the pathogenesis of several cardiopulmonary diseases, and smokers are susceptible to infectious agents. However, the progression of lung injury based on COVID-19 susceptibility and severity amongst smokers and those with pre-existing pulmonary diseases is not known. We determined the systemic expression and activity of COVID-19 related proteins, cytokine/chemokines, and lipid mediators (lipidomics) amongst COVID-19 patients with and without a history of smoking with a view to define biomarkers.MethodsWe obtained serum from COVID-19 positive and COVID-19 recovered patients with and without a history of smoking. We conducted a Luminex multiplex assay (cytokine levels), LC/MS (eicosanoids or oxylipin panel) and enzymatic activity assays on the serum samples to study the systemic changes in COVID-19 patients.ResultsOn comparing the cytokine profiles among COVID-19 positive and COVID-19 negative patients, we found a significant upregulation in the production of pro-inflammatory cytokines like IL-1α, IL-8, IL-2, VEGF and IL-10 in COVID-19 positive patients as compared to the respective controls. Interestingly, smoking history resulted in further augmentation of the release of some hyper-inflammatory cytokines, like IFN-γ, Eotaxin, MCP-1 and IL-9 amongst COVID-19 positive patients. The enzymatic activity for ACE2, the binding partner for SARS-CoV2 virus in the host cell, was found to be significantly increased in the serum of patients with a smoking history compared to the serum collected from the non-smoking controls. Similarly to our cytokine analysis, our measurement of serum Furin levels was also affected by the patient’s smoking history, in which we reported a substantial rise in serum Furin levels of COVID-19 patients. The analysis of lipid mediators revealed a distinct signature amongst the COVID-19 positive versus recovered subjects in PGF2α, HETEs, LXA4 and LTB4 levels. However, we did not find any changes in the levels of any lipid mediators based on the smoking history of the patients. Overall, our results point towards distinct systemic signatures amongst COVID-19 positive patients. We also show that smoking adversely affects the systemic levels of inflammatory markers and COVID-19 related proteins, thus suggesting that COVID-19 infection may have severe outcomes amongst smokers which is reflected systemically.


2007 ◽  
Vol 62 (9) ◽  
pp. 1030-1037 ◽  
Author(s):  
Taro Endo ◽  
Toshiki Shioiri ◽  
Hideaki Kitamura ◽  
Teruo Kimura ◽  
Sumio Endo ◽  
...  

2018 ◽  
Vol Volume 14 ◽  
pp. 2973-2980 ◽  
Author(s):  
Xiao Hu ◽  
Li Yin ◽  
Mingjing Situ ◽  
Kuifang Guo ◽  
Pingyuan Yang ◽  
...  

2020 ◽  
Vol 11 (2) ◽  
pp. 351-357
Author(s):  
Renu Rathi ◽  
Bharat Rathi ◽  
Rakesh Khatana ◽  
Suraj Sankh

Background: Rett syndrome-RS comes under Autism spectrum disorder-ASD which is a neurodevelopmental syndrome. It is diagnosed by the main differentiating features of lack of interpersonal and communication skills, poor eye contact, delayed speech with pervasive abnormal body movements. Aim and Objectives: This case report is aimed at dissemination of comprehensive role of Ayurveda in management of ASD, Rett syndrome. Material and Methods: RS is the severe form of ASD. This case study of 2.3 year’s girl presented with RS and global delay, being treated with wholistic approach. It comprises Ayurveda chikitsa and other therapies like Yoga, hydrotherapy, occupational, music, physiotherapy and many more. Observation and Result: Patient has shown promising results in all developmental milestones such as gross motor, fine motor and personal social in 6 months duration except language. Different varieties of massage therapy, diet and Basti, Nasya (Panchkarma) procedures, Omkar mantra chanting, passive Yogasana were done. Conclusion: In this case report, mainly Ayurveda interventions were implemented with wholistic approach as an adjuvant, received good result in gross motor development which is very difficult in RS, hence it is a unique case. It also opened the door of wholistic approach with the hope to deliver the good result in similar disorders.


2018 ◽  
Vol 16 (3) ◽  
pp. 17-22
Author(s):  
T.V. Korotkaya

Development of fine motor skills is an important part of corrective work with children with autism spectrum disorders. The salted dough is well suited for this purpose: the dough can be rolled, kneaded, rolled out with a rolling pin, wiped through a strainer and grated, which causes a lot of interest in children and motivates them to the lessons. The stages and techniques of teaching children at classes within the creative workshop “We Shape the World with Our Own” in the Federal Resource Center for Organization of Comprehensive Support for Children with Autism Spectrum Disorders are described. Recommendations are given on the use of techniques for working with salt dough.


2007 ◽  
Vol 15 (1) ◽  
pp. 42-48 ◽  
Author(s):  
Gary Toedter ◽  
Karen Hayden ◽  
Carrie Wagner ◽  
Carrie Brodmerkel

ABSTRACT The accurate detection and quantitation of cytokines in serum are important in the study of disease mechanisms, pathogenesis, and treatment. Serum cytokines can reflect processes that are occurring at the cellular or tissue level and thus provide a means of indirectly monitoring these processes. Multiplex detection of cytokines allows the simultaneous measurement of multiple cytokines in a sample, increasing the efficiency of measuring the cytokines while reducing the serum sample volumes required for the testing. Two commercially available multiplex platforms were evaluated (Pierce SearchLight and Meso Scale Discovery), using multiplexes capable of simultaneously detecting eight cytokines. The cytokines analyzed in this study were gamma interferon, vascular endothelial growth factor, tumor necrosis factor alpha, interleukin-6 (IL-6), macrophage inflammatory protein 1β, monocyte chemoattractant protein 1, IL-12p40, and IL-4. The range of quantitation of the platforms, the recovery of spiked cytokines, and the detection of the cytokines in serum samples from subjects with ulcerative colitis, Crohn's disease, rheumatoid arthritis, and psoriasis were examined. The findings showed that the detection of the cytokines was highly dependent upon the platform, with the consistency of the detection of cytokines across platforms being dependent upon the cytokine being analyzed. A careful examination of platform assay performance must be made prior to utilizing multiplex platforms in a study. While some cytokines will give similar patterns of results across platforms, others will be highly variable. The use of the same platform within a study or across studies where data will be compared is advised.


2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Annamaria Srancikova ◽  
Zuzana Bacova ◽  
Jan Bakos

Abstract Epigenetic mechanisms greatly affect the developing brain, as well as the maturation of synapses with pervasive, long-lasting consequences on behavior in adults. Substantial evidence exists that implicates dysregulation of epigenetic mechanisms in the etiology of neurodevelopmental disorders. Therefore, this review explains the role of enzymes involved in DNA methylation and demethylation in neurodevelopment by emphasizing changes of synaptic genes and proteins. Epigenetic causes of sex-dependent differences in the brain are analyzed in conjunction with the pathophysiology of autism spectrum disorders. Special attention is devoted to the epigenetic regulation of the melanoma-associated antigen-like gene 2 (MAGEL2) found in Prader-Willi syndrome, which is known to be accompanied by autistic symptoms.


2020 ◽  
Vol 9 (10) ◽  
pp. 3101 ◽  
Author(s):  
Joanna Samborska-Mazur ◽  
Anna Kostiukow ◽  
Izabela Miechowicz ◽  
Dorota Sikorska ◽  
Rafał Rutkowski ◽  
...  

Autism spectrum disorder (ASD) is characterized by neurodevelopmental disorders and alterations in immune function and cytokine levels. The aim of this study is to determine the salivary levels of interleukin-1β (IL-1β), interleukin-6 (IL-6), interleukin-8 (IL-8), tumor necrosis factor α (TNFα), monocyte chemoattractant protein-1 (MCP-1), Regulated on Activation, Normal T-cell Expressed and Secreted (RANTES), and Eotaxin in children with ASD and in healthy controlsto assess their predictive potential. We explored correlations between the cytokine levels and the neurodevelopmental disorders related to ASD. The study comprised 19 children with ASD and 19 typically developing (TD) ones. We analyzed salivary levels of IL-1β, IL-6, IL-8, TNFα, MCP-1, RANTES, and eotaxin on Luminex with custom-designed 7-plex kits. The level of RANTES in ASD children was significantly lower than those of TD. In TDs, the salivary levels of IL-1β, MCP-1, and TNFα correlated positively with age. In ASD, the cytokine levels did not correlate with age. There were statistically significant differences between the RANTES level and aggression and gait disturbances, between IL-8 level and fixations/stimulations, and between IL-1β level and no active speech. The levels of the cytokine detected can manifest both systemic and local changes related to ASD. The cytokine pattern cannot be used as a sole ASD predictor, but the salivary levels may be helpful in categorizing the ASD subtype.


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