The Use of Umbilical Cord Blood Nucleated Cells in the Treatment of Regressive Autism: A Case Report

BACKGROUND: Interest in the issue of childhood autism has surged in the recent decades. At the same time, despite the significant progress achieved in understanding the etiological and pathogenetic aspects of the condition, effective ways to treat it have continued to elude us. Stem cell therapy appears to hold great promise in the treatment and rehabilitation of patients with both neurological diseases (cerebral palsy, hydrocephalus) and mental disorders (autism, schizophrenia). METHODS: This article presents a case report describing the use of nucleated cord blood cells in a patient with regressive autism and resistance to standard therapies. The child’s condition was assessed before treatment and 6 and 12 months after. RESULTS: Clinical observation, psychometric, and instrumental diagnostic methods led to a significant improvement in the child’s condition in the form of perception development, reduction of somatosensory disorders, normalization of emotional status, and a development of social and communication skills. CONCLUSION: We assume that the result obtained may be associated with the normalization of the immunological status of our patient thanks to the cord blood cells therapy and consider it necessary to conduct further studies into the effectiveness of the method, taking the pathogenic mechanisms of autism into account

Dysregulation of Long Intergenic Non-Coding RNA Expression in the Schizophrenia Brain

BACKGROUND: Transcriptomic studies of the brains of schizophrenia (SZ) patients have produced abundant but largely inconsistent findings about the disorders pathophysiology. These inconsistencies might stem not only from the heterogeneous nature of the disorder, but also from the unbalanced focus on particular cortical regions and protein-coding genes. Compared to protein-coding transcripts, long intergenic non-coding RNA (lincRNA) display substantially greater brain region and disease response specificity, positioning them as prospective indicators of SZ-associated alterations. Further, a growing understanding of the systemic character of the disorder calls for a more systematic screening involving multiple diverse brain regions. AIM: We aimed to identify and interpret alterations of the lincRNA expression profiles in SZ by examining the transcriptomes of 35 brain regions. METHODS: We measured the transcriptome of 35 brain regions dissected from eight adult brain specimens, four SZ patients, and four healthy controls, using high-throughput RNA sequencing. Analysis of these data yielded 861 annotated human lincRNAs passing the detection threshold. RESULTS: Of the 861 detected lincRNA, 135 showed significant region-dependent expression alterations in SZ (two-way ANOVA, BH-adjusted p 0.05) and 37 additionally showed significant differential expression between HC and SZ individuals in at least one region (post hoc Tukey test, p 0.05). For these 37 differentially expressed lincRNAs (DELs), 88% of the differences occurred in a cluster of brain regions containing axon-rich brain regions and cerebellum. Functional annotation of the DEL targets further revealed stark enrichment in neurons and synaptic transmission terms and pathways. CONCLUSION: Our study highlights the utility of a systematic brain transcriptome analysis relying on the expression profiles measured across multiple brain regions and singles out white matter regions as a prospective target for further SZ research

Aminoazole-Based Diversity-Oriented Synthesis of Heterocycles

The comprehensive review contains the analysis of literature data concerning reactions of heterocyclization of aminoazoles and demonstrates the application of these types of transformations in diversity-oriented synthesis. The review is oriented to wide range of chemists working in the field of organic synthesis and both experimental and theoretical studies of nitrogen-containing heterocycles

Supramolecular nanoscale systems based on amphiphilic tetramethylensulfonatocalix[4]resorcinarenes and cationic polyelectrolyte with controlled guest molecule binding

<p>The water-soluble tetramethylensulfonatocalix[4]resorcinarene with methyl (<b>C1</b>) and pentyl (<b>C5</b>) substitutes on the lower rim forms colloid nanoscale aggregates with poly(diallyldimethylammonium chloride) (<b>PDDA</b>) in aqueous solutions. The size and stability of nanoparticles depend on concentrations of the components and their ratio in the ‘calixarene-polymer’ system. Ternary supramolecular complexes «polymer–macrocycle–guest molecule L-tryptophan (<b>Trp</b>) in conditions of spontaneous pH (3.80 and 4.78 for <b>C1-PDDA</b> and <b>C5-PDDA</b> systems, respectively) in an aqueous solution and in phosphate buffer (pH 7) were investigated by fluorescence method. The addition of the third component – <b>PDDA –</b> to the «non-aggregated <b>C1</b>–<b>Trp</b>» associates leads to the release of <b>Trp</b> in all studied conditions. The possibility of the «binding–release» process of L-tryptophan in «<b>C5</b>–<b>Trp</b>» associates after <b>PDDA</b> addition in the ternary complex is achieved and controlled by the structure of the macrocyclic self-associates and pH conditions.</p

Nanoconjugates of a calixresorcinarene derivative with methoxy poly(ethylene glycol) fragments for drug encapsulation

In order to obtain a non-toxic amphiphilic calixresorcinarene capable to form nanoconjugates for drug encapsulation, tetraundecylcalixresorcinarene functionalized by methoxy poly(ethylene glycol) chains has been synthesized. The macrocycle obtained is characterized by low hemotoxicity. In aqueous solution it forms nanoassociates that are able to encapsulate organic substrates of different hydrophobicity, including drugs (doxorubicin, naproxen, ibuprofen, quercetin). The micelles of the macrocycle slowed down the release of the hydrophilic substrates in vitro. In physiological sodium chloride solution and phosphate-buffered saline, the micelles of the macrocycle acquire thermoresponsive properties and exhibit a temperature-controlled release of doxorubicin in vitro. The combination of the low toxicity and the encapsulation properties of the obtained calixresorcinarene–mPEG conjugate shows promising potential for the use as a supramolecular drug-delivery system

Bacterial Metabolites of Human Gut Microbiota Correlating with Depression

Depression is a global threat to mental health that affects around 264 million people worldwide. Despite the considerable evolution in our understanding of the pathophysiology of depression, no reliable biomarkers that have contributed to objective diagnoses and clinical therapy currently exist. The discovery of the microbiota-gut-brain axis induced scientists to study the role of gut microbiota (GM) in the pathogenesis of depression. Over the last decade, many of studies were conducted in this field. The productions of metabolites and compounds with neuroactive and immunomodulatory properties among mechanisms such as the mediating effects of the GM on the brain, have been identified. This comprehensive review was focused on low molecular weight compounds implicated in depression as potential products of the GM. The other possible mechanisms of GM involvement in depression were presented, as well as changes in the composition of the microbiota of patients with depression. In conclusion, the therapeutic potential of functional foods and psychobiotics in relieving depression were considered. The described biomarkers associated with GM could potentially enhance the diagnostic criteria for depressive disorders in clinical practice and represent a potential future diagnostic tool based on metagenomic technologies for assessing the development of depressive disorders

Alterations of the Composition and Neurometabolic Profile of Human Gut Microbiota in Major Depressive Disorder

Major depressive disorder (MDD) is among the most prevalent mental disorders worldwide. Factors causing the pathogenesis of MDD include gut microbiota (GM), which interacts with the host through the gut–brain axis. In previous studies of GM in MDD patients, 16S rRNA sequencing was used, which provided information about composition but not about function. In our study, we analyzed whole metagenome sequencing data to assess changes in both the composition and functional profile of GM. We looked at the GM of 36 MDD patients, compared with that of 38 healthy volunteers. Comparative taxonomic analysis showed decreased abundances of Faecalibacterium prausnitzii, Roseburia hominis, and Roseburia intestinalis, and elevated abundances of Escherichia coli and Ruthenibacterium lactatiformans in the GM of MDD patients. We observed decreased levels of bacterial genes encoding key enzymes involved in the production of arginine, asparagine, glutamate, glutamine, melatonin, acetic, butyric and conjugated linoleic acids, and spermidine in MDD patients. These genes produced signature pairs with Faecalibacterium prausntizii and correlated with decreased levels of this species in the GM of MDD patients. These results show the potential impact of the identified biomarker bacteria and their metabolites on the pathogenesis of MDD, and should be confirmed in future metabolomic studies