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Alzheimer's disease is a progressive neurodegenerative disorder characterized by mitochondria dysfunction, accumulation of beta-amyloid plaques, and hyperphosphorylated tau tangles in the brain leading to memory loss and cognitive deficits. There is currently no cure for this condition, but the potential of stem cells for the therapy of neurodegenerative pathologies is actively being researched. This review discusses preclinical and clinical studies that have used mouse models and human patients to investigate the use of novel types of stem cell treatment approaches. The findings provide valuable insights into the applications of stem cell-based therapies and include the use of neural, glial, mesenchymal, embryonic, and induced pluripotent stem cells. We cover current studies on stem cell replacement therapy where cells can functionally integrate into neural networks, replace damaged neurons, and strengthen impaired synaptic circuits in the brain. We address the paracrine action of stem cells acting via secreted factors to induce neuroregeneration and modify inflammatory responses. We focus on the neuroprotective functions of exosomes as well as their neurogenic and synaptogenic effects. We look into the shuttling of mitochondria through tunneling nanotubes that enables the transfer of healthy mitochondria by restoring the normal functioning of damaged cells, improving their metabolism, and reducing the level of apoptosis.

Stroke represents a significant global health burden, with a substantial impact on mortality, morbidity, and long-term disability. The examination of stroke biomarkers, particularly the oral microbiome, offers a promising avenue for advancing our understanding of the factors that contribute to stroke risk and for developing strategies to mitigate that risk. This review highlights the significant correlations between oral diseases, such as periodontitis and caries, and the onset of stroke. Periodontal pathogens within the oral microbiome have been identified as a contributing factor in the exacerbation of risk factors for stroke, including obesity, dyslipidemia, atherosclerosis, hypertension, and endothelial dysfunction. The alteration of the oral microbiome may contribute to these conditions, emphasizing the vital role of oral health in the prevention of cardiovascular disease. The integration of dental and medical health practices represents a promising avenue for enhancing stroke prevention efforts and improving patient outcomes.

CNS diseases associated with compromised blood supply and/or vascular integrity are one of the leading causes of mortality and disability in adults worldwide and are also among 10 most common causes of death in children. Angiogenesis is an essential element of regeneration processes upon nervous tissue damage and can play a crucial role in neuroprotection. Here we review the features of cerebral vascular regeneration after ischemic stroke, including the complex interactions between endothelial cells and other brain cell types (neural stem cells, astrocytes, microglia, and oligodendrocytes). The mechanisms of reciprocal influence of angiogenesis and neurogenesis, the role of astrocytes in the formation of the blood-brain barrier, and roles of microglia and oligodendrocytes in vascular regeneration are discussed. Understanding the mechanisms of angiogenesis regulation in CNS is of critical importance for the development of new treatments of neurovascular pathologies., (© 2024. Springer Science+Business Media, LLC, part of Springer Nature.)

S. salivarius M18 administration has been proven to provide positive effects on periodontal health; however, there is still no consensus on the optimum duration of probiotic administration. This study aimed to evaluate the effect of three months of probiotic supplementation on bleeding on probing, signs of gingival inflammation, and dental biofilm. Sixty-two eligible individuals with gingivitis were enrolled in this placebo-controlled, double-blind trial and randomly allocated to the M18 or control groups. Primary outcomes were changes in gingival condition (gingival index, GI; gingival bleeding index, GBI) after 1, 2, and 3 months of lozenges administration and after a one-month washout. Secondary outcomes included changes in the Quigley-Hein plaque index (modified by Turesky et al.) after 1, 2, and 3 months of lozenges administration and after a washout. In total, 60 individuals completed the study (31 and 29 in the M18 group and the control group, respectively). No severe adverse events were reported. Probiotic supplementation resulted in a significant decrease in gingival bleeding at 1 month (effect size 1.09 [CI95%: 0.55-1.63]), 2 months (effect size 0.78 [CI95%: 0.26-1.30]), and 3 months (effect size 0.67 [CI95%: 0.15-1.18]) and a significant reduction in dental plaque accumulation at 2 months (effect size 0.63 [CI95%: 0.12-1.14]) and 3 months (effect size 0.55 [CI95%: 0.03-1.05]). A three-month supplementation with the probiotic resulted in a significant reduction in gingival bleeding and biofilm accumulation; however, a long-lasting effect is not expected, indicating the need for probiotic intake on a long-term basis.

Human-induced airway basal cells (hiBCs) derived from human-induced pluripotent stem cells (hiPSCs) offer a promising cell model for studying lung diseases, regenerative medicine, and developing new gene therapy methods. We analyzed existing differentiation protocols and proposed our own protocol for obtaining hiBCs, which involves step-by-step differentiation of hiPSCs into definitive endoderm, anterior foregut endoderm, NKX2.1+ lung progenitors, and cultivation on basal cell medium with subsequent cell sorting using the surface marker CD271 (NGFR). We derived hiBCs from two healthy cell lines and three cell lines with cystic fibrosis (CF). The obtained hiBCs, expressing basal cell markers (NGFR, KRT5, and TP63), could differentiate into lung organoids (LOs). We demonstrated that LOs derived from hiBCs can assess cystic fibrosis transmembrane conductance regulator (CFTR) channel function using the forskolin-induced swelling (FIS) assay. We also carried out non-viral (electroporation) and viral (recombinant adeno-associated virus (rAAV)) serotypes 6 and 9 and recombinant adenovirus (rAdV) serotype 5 transgene delivery to hiBCs and showed that rAAV serotype 6 is most effective against hiBCs, potentially applicable for gene therapy research., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Demchenko, Belova, Balyasin, Kochergin-Nikitsky, Kondrateva, Voronina, Pozhitnova, Tabakov, Salikhova, Bukharova, Goldshtein, Kondratyeva, Kyian, Amelina, Zubkova, Popova, Ozharovskaia, Lavrov and Smirnikhina.)

Cell therapy represents a promising approach to the treatment of neurological diseases, offering potential benefits not only by cell replacement but also through paracrine secretory activities. However, this approach includes a number of limiting factors, primarily related to safety. The use of conditioned stem cell media can serve as an equivalent to cell therapy while avoiding its disadvantages. The present study was a comparative investigation of the antioxidant, neuroprotective and neurotrophic effects of conditioned media obtained from neuronal and glial progenitor cells (NPC-CM and GPC-CM) on the PC12 cell line in vitro. Neuronal and glial progenitor cells were obtained from iPSCs by directed differentiation using small molecules. GPC-CM reduced apoptosis, ROS levels and increased viability, expressions of the antioxidant response genes HMOX1 and NFE2L2 in a model of glutamate-induced oxidative stress. The neurotrophic effect was evidenced by a change in the morphology of pheochromocytoma cells to a neuron-like phenotype. Moreover, neurite outgrowth, expression of GAP43 , TUBB3 , MAP2 , SYN1 genes and increased levels of the corresponding MAP2 and TUBB3 proteins. Treatment with NPC-CM showed moderate antiapoptotic effects and improved cell viability. This study demonstrated the potential application of CM in the field of regenerative medicine.

Background: Cell therapy using neural progenitor cells (NPCs) is a promising approach for ischemic stroke treatment according to the results of multiple preclinical studies in animal stroke models. In the vast majority of conducted animal studies, the therapeutic efficacy of NPCs was estimated after intracerebral transplantation, while the information of the effectiveness of systemic administration is limited. Nowadays, several clinical trials aimed to estimate the safety and efficacy of NPCs transplantation in stroke patients were also conducted. In these studies, NPCs were transplanted intracerebrally in the subacute/chronic phase of stroke. The results of clinical trials confirmed the safety of the approach, however, the degree of functional improvement (the primary efficacy endpoint) was not sufficient in the majority of the studies. Therefore, more studies are needed in order to investigate the optimal transplantation parameters, especially the timing of cell transplantation after the stroke onset. This study aimed to evaluate the therapeutic effects of intra-arterial (IA) and intravenous (IV) administration of NPCs derived from induced pluripotent stem cells (iNPCs) in the acute phase of experimental stroke in rats. Induced pluripotent stem cells were chosen as the source of NPCs as this technology is perspective, has no ethical concerns and provides the access to personalized medicine., Methods: Human iNPCs were transplanted IA or IV into male Wistar rats 24 h after the middle cerebral artery occlusion stroke modeling. Therapeutic efficacy was monitored for 14 days and evaluated in comparison with the cell transplantation-free control group. Additionally, cell distribution in the brain was assessed., Results: The obtained results show that both routes of systemic transplantation (IV and IA) significantly reduced the mortality and improved the neurological deficit of experimental animals compared to the control group. At the same time, according to the MRI data, only IA administration led to faster and prominent reduction of the stroke volume. After IA administration, iNPCs transiently trapped in the brain and were not detected on day 7 after the transplantation. In case of IV injection, transplanted cells were not visualized in the brain. The obtained data demonstrated that the systemic transplantation of human iNPCs in the acute phase of ischemic stroke can be a promising therapeutic strategy., Competing Interests: The authors declare there are no competing interests., (©2023 Cherkashova et al.)

We aimed to assess the effect of oral probiotic containing the Streptococcus salivarius M18 strain on gingival inflammation, bleeding on probing, and oral biofilm. Sixty-one consenting participants aged between 18 and 25 with gingivitis were recruited in this double-blind, parallel-group study and randomly divided into the probiotic group ( n = 31) and the placebo group ( n = 30). Fifty-seven participants completed the entire study protocol, 27 in the probiotic group and 30 in the placebo group. The outcomes were assessed after 4 weeks of intervention and 4 weeks of follow-up. There was a significant decrease in the Gingival Index, with the effect size of 0.58 [95%CI 0.05-1.10], and Turesky modification of the Quigley and Hein Plaque Index, with the effect size of 0.55 [95%CI: 0.02-1.07], in the probiotic group after the intervention. However, after a 4-week follow-up, the only significant treatment outcome was improved gingival condition according to the Gingival Index. The Gingival Bleeding Index also decreased significantly in the probiotic group after the intervention period; after the follow-up, this parameter did not differ significantly in both groups from the baseline values. In the placebo group, there were no significant improvements in the assessed parameters throughout this study. No serious side effects were registered. Within the limitations of this study, we conclude that the use of oral probiotic containing the Streptococcus salivarius M18 strain resulted in a significant improvement in gingival condition and oral hygiene level in young adults with gingivitis. Trial registration NCT05727436. Funding: none.

Recombinant adeno-associated viruses (rAAVs) may be useful for the development of gene therapy for hereditary diseases. Patient-specific human induced pluripotent stem cells (hiPSCs) can be differentiated into a variety of cells which are difficult or impossible to obtain by biopsy. To date, few research on the efficiency of rAAV transduction of hiPSCs has been published, but the obtained data are very contradictory and do not answer the actual question: how effective are rAAVs for the delivery of transgenes into hiPSCs. In this work, we used rAAV serotypes 5, 6, and 9 carrying the GFP transgene. The transduction efficiency of rAAV2/9-GFP and rAAV2/6-GFP for the immortalized tracheal epithelial cell line derived from a patient with cystic fibrosis (CFTE29o-) was relatively high. At the same time, the efficiency of transduction of iPSCs from a healthy donor and a cystic fibrosis (CF) donor was extremely low. Thus, our results show that the efficiency of hiPSC transduction by rAAV serotypes 5, 6, and 9 is not suitable for the delivery of transgenes., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

This cross-sectional survey assessed the knowledge of and the attitude towards probiotics of dental students and academics at Sechenov University, Moscow, Russia. Our questionnaire consisted of 15 questions divided into 3 sections: respondents' sociodemographic data, knowledge on probiotics, and attitude towards probiotics. The data were analyzed using the Mann-Whitney U test, Fisher's exact test, and Spearman's rank correlation coefficient. Out of the 658 questionnaires distributed, a total of 239 questionnaires were completed by the undergraduates, yielding a response rate of 39.6%, and 54 by the teaching staff (response rate = 100%). Most students (53.6%) and teachers (55.5%) had a fair knowledge of probiotics ( p = 0.3135). A vast majority of dental students (97.9%) and all teachers had a positive attitude towards probiotics, with higher mean scores among academics ( p < 0.001). A positive weak correlation was found between knowledge and attitude (Spearman r = 0.17, p = 0.0027). The results obtained reveal the need for more evidence-based educational trainings for university teachers and a course on probiotics to be included in the curriculum for dental students.

Airway and lung organoids derived from human-induced pluripotent stem cells (hiPSCs) are current models for personalized drug screening, cell-cell interaction studies, and lung disease research. We analyzed the existing differentiation protocols and identified the optimal conditions for obtaining organoids. In this article, we describe a step-by-step protocol for differentiating hiPSCs into airway and lung organoids. We obtained airway and lung organoids from a healthy donor and from five donors with cystic fibrosis. Analysis of the cellular composition of airway and lung organoids showed that airway organoids contain proximal lung epithelial cells, while lung organoids contain both proximal and distal lung epithelial cells. Forskolin-induced swelling of organoids derived from a healthy donor showed that lung organoids, as well as airway organoids, contain functional epithelial cells and swell after 24 h exposure to forskolin, which makes it a suitable model for analyzing the cystic fibrosis transmembrane conductance regulator (CFTR) channel conductance in vitro. Thus, our results demonstrate the feasibility of generating and characterizing airway and lung organoids from hiPSCs, which can be used for a variety of future applications.

We aimed to assess the effect of oral probiotics containing the Streptococcus salivarius K12 strain on the salivary level of secretory immunoglobulin A, salivation rate, and oral biofilm. Thirty-one consenting patients meeting the inclusion criteria were recruited in this double-blind, placebo-controlled, two-arm, parallel-group study and randomly divided into probiotic ( n = 15) and placebo ( n = 16) groups. Unstimulated salivation rate, concentration of salivary secretory immunoglobulin A, Turesky index, and Papillary-Marginal-Attached index were assessed after 4 weeks of intervention and 2 weeks of washout. Thirty patients completed the entire study protocol. We found no increase in salivary secretory immunoglobulin A levels and salivary flow rates in the probiotic group compared with placebo. Baseline and outcome salivary secretory immunoglobulin A concentrations (mg/L) were 226 ± 130 and 200 ± 113 for the probiotic group and 205 ± 92 and 191 ± 97 for the placebo group, respectively. A significant decrease in plaque accumulation was observed in the probiotic group at 4 and 6 weeks. Within the limitations of the present study, it may be concluded that probiotic intake ( Streptococcus salivarius K12) does not affect salivation rates and secretory immunoglobulin A salivary levels but exhibits a positive effect on plaque accumulation. Trial registration NCT05039320. Funding: none.

Transplantation of various types of stem cells as a possible therapy for stroke has been tested for years, and the results are promising. Recent investigations have shown that the administration of the conditioned media obtained after stem cell cultivation can also be effective in the therapy of the central nervous system pathology (hypothesis of their paracrine action). The aim of this study was to evaluate the therapeutic effects of the conditioned medium of hiPSC-derived glial and neuronal progenitor cells in the rat middle cerebral artery occlusion model of the ischemic stroke. Secretory activity of the cultured neuronal and glial progenitor cells was evaluated by proteomic and immunosorbent-based approaches. Therapeutic effects were assessed by overall survival, neurologic deficit and infarct volume dynamics, as well as by the end-point values of the apoptosis- and inflammation-related gene expression levels, the extent of microglia/macrophage infiltration and the numbers of formed blood vessels in the affected area of the brain. As a result, 31% of the protein species discovered in glial progenitor cells-conditioned medium and 45% in neuronal progenitor cells-conditioned medium were cell type specific. The glial progenitor cell-conditioned media showed a higher content of neurotrophins (BDNF, GDNF, CNTF and NGF). We showed that intra-arterial administration of glial progenitor cells-conditioned medium promoted a faster decrease in neurological deficit compared to the control group, reduced microglia/macrophage infiltration, reduced expression of pro-apoptotic gene Bax and pro-inflammatory cytokine gene Tnf , increased expression of anti-inflammatory cytokine genes ( Il4 , Il10 , Il13 ) and promoted the formation of blood vessels within the damaged area. None of these effects were exerted by the neuronal progenitor cell-conditioned media. The results indicate pronounced cytoprotective, anti-inflammatory and angiogenic properties of soluble factors secreted by glial progenitor cells.

We performed comparative analysis of paracrine activity of neuronal and glial progenitors derived from induced pluripotent stem cells under conditions of hypoxia modeled by addition of cobalt dichloride. Neuronal and glial progenitors produced neuroprotective and neurotrophic effects on SHSY-5Y neuroblastoma cells in co-culture during the post-hypoxic recovery and reduced the number of apoptotic and necrotic cells. Moreover, they produced a neurotrophic effect and promote the formation and growth of neurites in neuroblastoma cells. The paracrine effect of glial progenitors was more pronounced, which can be explained by more intensive expression and secretion of neurotrophic factors in these cells.

We compared the effects of placental mesenchymal stromal cells and neural progenitor cells derived from induced human pluripotent cells after their intravenous administration to rats in 24 h after transitory occlusion of the middle cerebral artery. The therapeutic effects were evaluated by the dynamics of animal survival, body weight, neurological deficit, and the volume of infarction focus in 7, 14, 30, and 60 days after surgery. Intravenous injection of neural progenitor cells produced a therapeutic effect on the course of experimental ischemic stroke by increasing animal survival in the most acute period and accelerating compensation of neurological deficit and body weight recovery. Neural progenitor cells were more effective than mesenchymal stromal cells from human placenta. The effectiveness of intravenous transplantation of neural progenitor cells in the model of occlusion of the middle cerebral artery is shown by us for the first time, although the therapeutic effect of their direct transplantation into the brain has already been described.

The most specific method of the recording of the rate offree radical reactions is the method of electron paramagnetic resonance (EPR) spectroscopy, but it is rarely used in applied biology due to expensive equipment and complexity of the execution of measurements. However chemists have found a number of colored organic radicals which lose the coloring under transition into diamagnetic form. In the given paper there are presented results of our studies on the development of methods for the assessment of oxidant equilibrium in biological media with a use of stable radical 2,2-diphenyl-1-picrylhydrazyl (DPPH) and cation-radicals of N,N-diethyl-p-phenylenediamine (DEPPD). We have developed the new modification of DPPH test, replacing methanol-based incubation medium by non-ionic detergent solution, compatible with native blood serum. Modified DPPH test conserved typical biphasic kinetics of the origin variant, had the similar sensitivity to model antioxidants (IC values 49, 38 and 13 mkMfor ascorbate, a-tocopherol and quercetine, correspondingly) and was applied in experiments on laboratory animals treated with nano- and ionic silver, carbon nanotubes, microfine coal and electrolytic dust. We have tried also the assay of serum lipid hydroperoxides based on Fe-initiated DEPPD oxidation (Alberti et al., 2000). The comparison of kinetics of DEPPD oxidation in model (HO/Fe) and biologic (rat serum/Fe) systems, before and after Fe addition, seems to be an evidence that ceruloplasmin (CP) was involved in the resulting process, but failed to determine its polynomial kinetics, at least for the rat serum and DEPPD excess. The use of CP monoclonal antibodies seems to be the best way for the clarification of the mechanism of this reaction.