Репозиторий Университета

© 2021, The Author(s). Background: CARs are simulated receptors containing an extracellular single-chain variable fragment (scFv), a transmembrane domain, as well as an intracellular region of immunoreceptor tyrosine-based activation motifs (ITAMs) in association with a co-stimulatory signal. Main body: Chimeric antigen receptor (CAR) T cells are genetically engineered T cells to express a receptor for the recognition of the particular surface marker that has given rise to advances in the treatment of blood disorders. The CAR T cells obtain supra-physiological properties and conduct as “living drugs” presenting both immediate and steady effects after expression in T cells surface. But, their efficacy in solid tumor treatment has not yet been supported. The pivotal challenges in the field of solid tumor CAR T cell therapy can be summarized in three major parts: recognition, trafficking, and surviving in the tumor. On the other hand, the immunosuppressive tumor microenvironment (TME) interferes with T cell activity in terms of differentiation and exhaustion, and as a result of the combined use of CARs and checkpoint blockade, as well as the suppression of other inhibitor factors in the microenvironment, very promising results were obtained from the reduction of T cell exhaustion. Conclusion: Nowadays, identifying and defeating the mechanisms associated with CAR T cell dysfunction is crucial to establish CAR T cells that can proliferate and lyse tumor cells severely. In this review, we discuss the CAR signaling and efficacy T in solid tumors and evaluate the most significant barriers in this process and describe the most novel therapeutic methods aiming to the acquirement of the promising therapeutic outcome in non-hematologic malignancies.

© 2020, LLC Science and Innovations. Pancreatic cancer (PC) is one of the most fatal types of oncological disease in the world and is an extremely aggressive cancer with a poor prognosis. The objective of this review was to analyze the domestic data of the incidence of PC in the Russian Federation and to analyze the protocols that are used for the management of this group of patients in Russian clinical centers. For the analysis of the literature sources, the data in the elibrary.ru database published in the period from 2015 to 2019 were used. The methodology that was used in each study was examined in order to ensure its reliability, and these data were selected as potential sources of evidence for the preparation of national recommendations. The study results influence the level of evidence assigned to the publication. Updates to the national recommendations are conducted at least once every three years, and these updates depend on new information about the diagnosis and management of patients with PC.

© 2021, The Author(s). Background: The aim of this survey was to evaluate the severity of dental caries among children living in Zanskar Valley (Ladakh, India) and its association with anthropometric and background variables. Methods: This cross‐sectional survey was conducted on schoolchildren divided into four age groups (< 6, ≥ 6 < 11, ≥ 11 < 14 and > 14 years of age). A total of 1474 schoolchildren (607 males, 41.2%) were examined. Actual caries prevalence (dt/DT) and gingival bleeding were recorded by four calibrated dentists. An ad hoc questionnaire evaluated general health, eating habits, oral hygiene and the self-perception of oral conditions. Height, weight, waist circumference, heart-rate and oxygen-saturation were also collected directly by examiners. Responses to questionnaire items were treated as categorical or ordinal variables. The relationship between children’s caries data, gingival bleeding, gender, Body Mass Index (BMI) following the International Obesity Task Force, waist circumference and questionnaire items was assessed using the Kruskal–Wallis test and Pearson correlation. Conditional ordinal logistic regression was used to analyse associations among caries severity, gender, BMI, waist circumference, oxygen saturation and questionnaire items. A forward stepwise logistic regression procedure was also carried-out to estimate the ORs of gingival bleeding prevalence and the covariates derived from examination or questionnaire. Results: Caries was almost ubiquitarian with only 10.0% of caries-free children (dt/DT = 0). Caries severity, in both primary and permanent dentitions, was statistically significantly related to gender, waist circumference, BMI, oral hygiene frequency and self-reported chewing problems (p < 0.01 in both dentitions). An increasing relative risk for caries in permanent dentition compared to caries-free subjects was observed in children with a low BMI (RRR = 1.67, 95%CI = 1.54/2.83 for subjects with 1–3 caries lesions and RRR = 1.52, 95%CI = 1.36/1.74 for subjects with > 3 caries lesions); also, children with reduced waist circumference had a higher relative risk to have 1–3 caries lesions (RRR = 2.16, 95%CI = 1.84/2.53) and an even higher risk to have more than 3 caries lesions (RRR = 4.22, 95%CI = 3.33/5.34). Conclusions: A significant impact of untreated caries lesions was observed in Ladakh schoolchildren; low BMI values and reduced waist circumference showed to be the main caries risk predictors. Preventive and intervention programmes should be implemented to improve children's oral health.

© 2020, LLC Science and Innovations. Pancreatic cancer (PC) is one of the most fatal types of oncological disease in the world and is an extremely aggressive cancer with a poor prognosis. The objective of this review was to analyze the domestic data of the incidence of PC in the Russian Federation and to analyze the protocols that are used for the management of this group of patients in Russian clinical centers. For the analysis of the literature sources, the data in the elibrary.ru database published in the period from 2015 to 2019 were used. The methodology that was used in each study was examined in order to ensure its reliability, and these data were selected as potential sources of evidence for the preparation of national recommendations. The study results influence the level of evidence assigned to the publication. Updates to the national recommendations are conducted at least once every three years, and these updates depend on new information about the diagnosis and management of patients with PC.

© 2021, The Author(s). Background: The aim of this survey was to evaluate the severity of dental caries among children living in Zanskar Valley (Ladakh, India) and its association with anthropometric and background variables. Methods: This cross‐sectional survey was conducted on schoolchildren divided into four age groups (< 6, ≥ 6 < 11, ≥ 11 < 14 and > 14 years of age). A total of 1474 schoolchildren (607 males, 41.2%) were examined. Actual caries prevalence (dt/DT) and gingival bleeding were recorded by four calibrated dentists. An ad hoc questionnaire evaluated general health, eating habits, oral hygiene and the self-perception of oral conditions. Height, weight, waist circumference, heart-rate and oxygen-saturation were also collected directly by examiners. Responses to questionnaire items were treated as categorical or ordinal variables. The relationship between children’s caries data, gingival bleeding, gender, Body Mass Index (BMI) following the International Obesity Task Force, waist circumference and questionnaire items was assessed using the Kruskal–Wallis test and Pearson correlation. Conditional ordinal logistic regression was used to analyse associations among caries severity, gender, BMI, waist circumference, oxygen saturation and questionnaire items. A forward stepwise logistic regression procedure was also carried-out to estimate the ORs of gingival bleeding prevalence and the covariates derived from examination or questionnaire. Results: Caries was almost ubiquitarian with only 10.0% of caries-free children (dt/DT = 0). Caries severity, in both primary and permanent dentitions, was statistically significantly related to gender, waist circumference, BMI, oral hygiene frequency and self-reported chewing problems (p < 0.01 in both dentitions). An increasing relative risk for caries in permanent dentition compared to caries-free subjects was observed in children with a low BMI (RRR = 1.67, 95%CI = 1.54/2.83 for subjects with 1–3 caries lesions and RRR = 1.52, 95%CI = 1.36/1.74 for subjects with > 3 caries lesions); also, children with reduced waist circumference had a higher relative risk to have 1–3 caries lesions (RRR = 2.16, 95%CI = 1.84/2.53) and an even higher risk to have more than 3 caries lesions (RRR = 4.22, 95%CI = 3.33/5.34). Conclusions: A significant impact of untreated caries lesions was observed in Ladakh schoolchildren; low BMI values and reduced waist circumference showed to be the main caries risk predictors. Preventive and intervention programmes should be implemented to improve children's oral health.

© 2017 EDIZIONIMINERVAMEDICA. BACKGROUND: Goals of vestibular schwannoma (VS) microsurgery are maximal resection, facial nerve (FN) preservation and in selected cases, hearing preservation (HP). Postoperative HP rates are related to clinical and radiographic factors: Size of tumor, preoperative hearing, hypertension, diabetes, and presence or absence of preoperative tinnitus. In this retrospective review we evaluated the influence of preoperative tinnitus on HP after VS surgery in patients with preoperative socially useful hearing (SUH). METHODS: Twenty-five patients with SUH underwent VS micro neurosurgery by retrosigmoid (RS) approach. Selection criteria were pure tone audiogram ≤50dB loss and speech discrimination score >50% (50/50 criterion, AAO-HNS class A-B). In relation to maximum diameter, we identified two size-groups: 1) group A ≤2cm (13 cases); 2) group B >2cm (12 cases). HP attempt was assisted by intraoperative ABR evoked by LS CE-Chirp® (Interacustics, Middelfart, Denmark) acoustic stimuli. RESULTS: Mean age was 44.3 years (20-64); average maximum diameter 2,0cm (0,8-4). Preoperative tinnitus was present in 10 patients (40%): All of them had a Class B-hearing. Total and nearly-total (>95%) resection was possible in all. Mortality and major morbidity were zero. In all, facial nerve (FN) was anatomically and functionally preserved; in 10 an incomplete FN deficit was followed by complete recovery within 2-8 weeks. At a follow-up ranging from 8 to 17 months (average 12.7 months), socially useful hearing (SUH) preservation rate was 52%, with significant differences in relation to size: 61.5% group A and 41.7% group B (P=0.014). Postoperative AAO-HNS C (serviceable) hearing was observed in 36%, deafness in 12%. At last follow-up, among the 10 patients with preoperative tinnitus 6 worsened from Class-B to Class-C, 3 remained in Class-B, and one was deaf. As regards SUH preservation, 3 of 10 patients with preoperative tinnitus and 10 of 15 without it remained in Class-A-B (P=0.006). CONCLUSIONS: Microsurgery represents the first therapeutic option for small growing VS with SUH. Our data confirm that key-hole RS rea moval of VS with intraoperative LS-CE-Chirp ABR monitoring allows good rate of SUH preservation, especially maximum diameter does not exceed 2cm. Preoperative tinnitus seems to indicate a lower hearing reserve and predicts a lower likelihood of HP.

© 2021, The Author(s). Background: The morphometric analysis of the individual bones of the human skeleton can be used to estimate the sex of unidentified corpses. Our aims were as follows: to test whether thyroid cartilage can be used for forensic purposes as a predictor of biological sex; to establish the level of sexual dimorphism of the thyroid cartilage in a sample of adult subjects from a population of European Russia; and to test the accuracy of the morphometric parameters obtained from the thyroid cartilage. Results: The thyroid cartilage from 100 adults of known age (50 males and 50 females) was obtained during forensic examination; morphometric tests were conducted using Vernier Digital ROKTOOLS ABS DIN 862 0-200/6 inch with measurement accuracy ± 0.01 mm. The measured parameters were N = 31 for each subject. Intra- and inter-observer reproducibility was tested. Multivariate statistical analysis was applied to the measurements. To check the data set for normal distribution, the Kolmogorov-Smirnov test was used. Finally, to estimate the sex of the observed individuals, a stepwise discriminant analysis was conducted, using the Wilks’ lambda selection method. The most significant parameters were the outer distance between bases of inferior horn; the inner distance between distal ends of inferior horns; distance between distal ends of left superior and inferior horns; left superior horn length (distance between left superior horn distal end and base); distance between superior and inferior notches; thyroid angle; left lamina height (vertical line along left lamina middle); horizontal distance between anterior intermedium line and the right lamina posterior edge; distance between inferior thyroid notch and line connecting left and right thyroid laminae; and left superior horn thickness at mid-line. The stepwise discriminant analysis resulted in an equation with ten parameters. Conclusions: The results of the current study indicated that in the European Russian population, the equation obtained in the stepwise discriminant analysis makes it possible to predict sex with a probability of 100% on the validation set. On the test set, the resultant accuracy was 100% for females and 100% for males. Our findings confirm the scientific evidence that the thyroid cartilage has a pronounced sexual dimorphism.

© 2021, The Author(s). Background: The morphometric analysis of the individual bones of the human skeleton can be used to estimate the sex of unidentified corpses. Our aims were as follows: to test whether thyroid cartilage can be used for forensic purposes as a predictor of biological sex; to establish the level of sexual dimorphism of the thyroid cartilage in a sample of adult subjects from a population of European Russia; and to test the accuracy of the morphometric parameters obtained from the thyroid cartilage. Results: The thyroid cartilage from 100 adults of known age (50 males and 50 females) was obtained during forensic examination; morphometric tests were conducted using Vernier Digital ROKTOOLS ABS DIN 862 0-200/6 inch with measurement accuracy ± 0.01 mm. The measured parameters were N = 31 for each subject. Intra- and inter-observer reproducibility was tested. Multivariate statistical analysis was applied to the measurements. To check the data set for normal distribution, the Kolmogorov-Smirnov test was used. Finally, to estimate the sex of the observed individuals, a stepwise discriminant analysis was conducted, using the Wilks’ lambda selection method. The most significant parameters were the outer distance between bases of inferior horn; the inner distance between distal ends of inferior horns; distance between distal ends of left superior and inferior horns; left superior horn length (distance between left superior horn distal end and base); distance between superior and inferior notches; thyroid angle; left lamina height (vertical line along left lamina middle); horizontal distance between anterior intermedium line and the right lamina posterior edge; distance between inferior thyroid notch and line connecting left and right thyroid laminae; and left superior horn thickness at mid-line. The stepwise discriminant analysis resulted in an equation with ten parameters. Conclusions: The results of the current study indicated that in the European Russian population, the equation obtained in the stepwise discriminant analysis makes it possible to predict sex with a probability of 100% on the validation set. On the test set, the resultant accuracy was 100% for females and 100% for males. Our findings confirm the scientific evidence that the thyroid cartilage has a pronounced sexual dimorphism.

© 2021, The Author(s). Background: Feature tracking (FT) has become an established tool for cardiovascular magnetic resonance (CMR)-based strain analysis. Recently, the compressed sensing (CS) technique has been applied to cine CMR, which has drastically reduced its acquisition time. However, the effects of CS imaging on FT strain analysis need to be carefully studied. This study aimed to investigate the use of CS cine CMR for FT strain analysis compared to conventional cine CMR. Methods: Sixty-five patients with different left ventricular (LV) pathologies underwent both retrospective conventional cine CMR and prospective CS cine CMR using a prototype sequence with the comparable temporal and spatial resolution at 3 T. Eight short-axis cine images covering the entire LV were obtained and used for LV volume assessment and FT strain analysis. Prospective CS cine CMR data over 1.5 heartbeats were acquired to capture the complete end-diastolic data between the first and second heartbeats. LV volume assessment and FT strain analysis were performed using a dedicated software (ci42; Circle Cardiovasacular Imaging, Calgary, Canada), and the global circumferential strain (GCS) and GCS rate were calculated from both cine CMR sequences. Results: There were no significant differences in the GCS (− 17.1% [− 11.7, − 19.5] vs. − 16.1% [− 11.9, − 19.3; p = 0.508) and GCS rate (− 0.8 [− 0.6, − 1.0] vs. − 0.8 [− 0.7, − 1.0]; p = 0.587) obtained using conventional and CS cine CMR. The GCS obtained using both methods showed excellent agreement (y = 0.99x − 0.24; r = 0.95; p < 0.001). The Bland–Altman analysis revealed that the mean difference in the GCS between the conventional and CS cine CMR was 0.1% with limits of agreement between -2.8% and 3.0%. No significant differences were found in all LV volume assessment between both types of cine CMR. Conclusion: CS cine CMR could be used for GCS assessment by CMR-FT as well as conventional cine CMR. This finding further enhances the clinical utility of high-speed CS cine CMR imaging.

© 2021, The Author(s). Background: The synaptic vesicle glycoprotein 2 (SV2) family is essential to the synaptic machinery involved in neurotransmission and vesicle recycling. The isoforms SV2A, SV2B and SV2C are implicated in neurological diseases such as epilepsy, Alzheimer’s and Parkinson’s disease. Suitable cell systems for studying regulation of these proteins are essential. Here we present gene expression data of SV2A, SV2B and SV2C in two human neuroblastoma cell lines after differentiation. Methods: Human neuroblastoma cell lines SiMa and IMR-32 were treated for seven days with growth supplements (B-27 and N-2), all-trans-retinoic acid (ATRA) or vasoactive intestinal peptide (VIP) and gene expression levels of SV2 and neuronal targets were analyzed. Results: The two cell lines reacted differently to the treatments, and only one of the three SV2 isoforms was affected at a time. SV2B and choline O-acetyltransferase (CHAT) expression was changed in concert after growth supplement treatment, decreasing in SiMa cells while increasing in IMR-32. ATRA treatment resulted in no detected changes in SV2 expression in either cell line while VIP increased both SV2C and dopamine transporter (DAT) in IMR-32 cells. Conclusion: The synergistic expression patterns between SV2B and CHAT as well as between SV2C and DAT mirror the connectivity between these targets found in disease models and knock-out animals, although here no genetic alteration was made. These cell lines and differentiation treatments could possibly be used to study SV2 regulation and function.

© 2021, The Author(s). Background: With an increasing aging population and a lower ratio between the active and the dependent population, population aging is considered a global social and health challenge, associated with increased demand in health care needs and social pension. This study projects the Greek and Cypriot population to guide future planning of social and health policies and services. Methods: The total population by sex and age groups, Total Fertility Rate (TFR), life-expectancies at birth and Potential Support Ratio PSR (persons aged 20–64 years per person 65+ years) are projected probabilistically by the year 2100 using Bayesian hierarchical models and United Nations’ population data for Greece and Cyprus from the period of 1950 to 2015. Results: The TFR is projected to be around 1.5 children per woman in 2050 and around 1.75 in 2100 for both countries, with all values of prediction intervals being around or below the Replacement level fertility. PSR is expected to decrease remarkably and be 2.5 in 2050 and 1.6 in 2100 for Cyprus while for Greece it will be around 1.5 for both years 2050 and 2100. Life-expectancy is expected to increase to 84 years for men and 87 years for women in 2050 and 90 years for men and 94 years for women in 2100 for both countries. The share of the population aged 65 years and over is projected to increase in both countries and be the one third of the population by 2100. Conclusions: Greece and Cyprus will acquire the characteristics of an aging population, putting a significance pressure on the social and health systems of both countries. Both countries should reform their social and health policy agenda to confront population aging and its consequence. They should adopt fertility incentives and family policies to increase fertility and migrants’ inclusiveness policies to improve the demographic structure and the economic activity. The national health systems should promote prevention strategies at the primary health sector and promote healthy aging while health research policy should aim to promote research in innovative technologies and digital health to create assistive technology for self-care and greater independence of older people.

© 2021, The Author(s). Background: The synaptic vesicle glycoprotein 2 (SV2) family is essential to the synaptic machinery involved in neurotransmission and vesicle recycling. The isoforms SV2A, SV2B and SV2C are implicated in neurological diseases such as epilepsy, Alzheimer’s and Parkinson’s disease. Suitable cell systems for studying regulation of these proteins are essential. Here we present gene expression data of SV2A, SV2B and SV2C in two human neuroblastoma cell lines after differentiation. Methods: Human neuroblastoma cell lines SiMa and IMR-32 were treated for seven days with growth supplements (B-27 and N-2), all-trans-retinoic acid (ATRA) or vasoactive intestinal peptide (VIP) and gene expression levels of SV2 and neuronal targets were analyzed. Results: The two cell lines reacted differently to the treatments, and only one of the three SV2 isoforms was affected at a time. SV2B and choline O-acetyltransferase (CHAT) expression was changed in concert after growth supplement treatment, decreasing in SiMa cells while increasing in IMR-32. ATRA treatment resulted in no detected changes in SV2 expression in either cell line while VIP increased both SV2C and dopamine transporter (DAT) in IMR-32 cells. Conclusion: The synergistic expression patterns between SV2B and CHAT as well as between SV2C and DAT mirror the connectivity between these targets found in disease models and knock-out animals, although here no genetic alteration was made. These cell lines and differentiation treatments could possibly be used to study SV2 regulation and function.

© 2021, The Author(s). Background: With an increasing aging population and a lower ratio between the active and the dependent population, population aging is considered a global social and health challenge, associated with increased demand in health care needs and social pension. This study projects the Greek and Cypriot population to guide future planning of social and health policies and services. Methods: The total population by sex and age groups, Total Fertility Rate (TFR), life-expectancies at birth and Potential Support Ratio PSR (persons aged 20–64 years per person 65+ years) are projected probabilistically by the year 2100 using Bayesian hierarchical models and United Nations’ population data for Greece and Cyprus from the period of 1950 to 2015. Results: The TFR is projected to be around 1.5 children per woman in 2050 and around 1.75 in 2100 for both countries, with all values of prediction intervals being around or below the Replacement level fertility. PSR is expected to decrease remarkably and be 2.5 in 2050 and 1.6 in 2100 for Cyprus while for Greece it will be around 1.5 for both years 2050 and 2100. Life-expectancy is expected to increase to 84 years for men and 87 years for women in 2050 and 90 years for men and 94 years for women in 2100 for both countries. The share of the population aged 65 years and over is projected to increase in both countries and be the one third of the population by 2100. Conclusions: Greece and Cyprus will acquire the characteristics of an aging population, putting a significance pressure on the social and health systems of both countries. Both countries should reform their social and health policy agenda to confront population aging and its consequence. They should adopt fertility incentives and family policies to increase fertility and migrants’ inclusiveness policies to improve the demographic structure and the economic activity. The national health systems should promote prevention strategies at the primary health sector and promote healthy aging while health research policy should aim to promote research in innovative technologies and digital health to create assistive technology for self-care and greater independence of older people.

© 2021, The Author(s). Background: With an increasing aging population and a lower ratio between the active and the dependent population, population aging is considered a global social and health challenge, associated with increased demand in health care needs and social pension. This study projects the Greek and Cypriot population to guide future planning of social and health policies and services. Methods: The total population by sex and age groups, Total Fertility Rate (TFR), life-expectancies at birth and Potential Support Ratio PSR (persons aged 20–64 years per person 65+ years) are projected probabilistically by the year 2100 using Bayesian hierarchical models and United Nations’ population data for Greece and Cyprus from the period of 1950 to 2015. Results: The TFR is projected to be around 1.5 children per woman in 2050 and around 1.75 in 2100 for both countries, with all values of prediction intervals being around or below the Replacement level fertility. PSR is expected to decrease remarkably and be 2.5 in 2050 and 1.6 in 2100 for Cyprus while for Greece it will be around 1.5 for both years 2050 and 2100. Life-expectancy is expected to increase to 84 years for men and 87 years for women in 2050 and 90 years for men and 94 years for women in 2100 for both countries. The share of the population aged 65 years and over is projected to increase in both countries and be the one third of the population by 2100. Conclusions: Greece and Cyprus will acquire the characteristics of an aging population, putting a significance pressure on the social and health systems of both countries. Both countries should reform their social and health policy agenda to confront population aging and its consequence. They should adopt fertility incentives and family policies to increase fertility and migrants’ inclusiveness policies to improve the demographic structure and the economic activity. The national health systems should promote prevention strategies at the primary health sector and promote healthy aging while health research policy should aim to promote research in innovative technologies and digital health to create assistive technology for self-care and greater independence of older people.

© 2021, The Author(s). A crosstalk established between tumor microenvironment and tumor cells leads to contribution or inhibition of tumor progression. Mesenchymal stem cells (MSCs) are critical cells that fundamentally participate in modulation of the tumor microenvironment, and have been reported to be able to regulate and determine the final destination of tumor cell. Conflicting functions have been attributed to the activity of MSCs in the tumor microenvironment; they can confer a tumorigenic or anti-tumor potential to the tumor cells. Nonetheless, MSCs have been associated with a potential to modulate the tumor microenvironment in favouring the suppression of cancer cells, and promising results have been reported from the preclinical as well as clinical studies. Among the favourable behaviours of MSCs, are releasing mediators (like exosomes) and their natural migrative potential to tumor sites, allowing efficient drug delivering and, thereby, efficient targeting of migrating tumor cells. Additionally, angiogenesis of tumor tissue has been characterized as a key feature of tumors for growth and metastasis. Upon introduction of first anti-angiogenic therapy by a monoclonal antibody, attentions have been drawn toward manipulation of angiogenesis as an attractive strategy for cancer therapy. After that, a wide effort has been put on improving the approaches for cancer therapy through interfering with tumor angiogenesis. In this article, we attempted to have an overview on recent findings with respect to promising potential of MSCs in cancer therapy and had emphasis on the implementing MSCs to improve them against the suppression of angiogenesis in tumor tissue, hence, impeding the tumor progression.

© 2021, The Author(s). A crosstalk established between tumor microenvironment and tumor cells leads to contribution or inhibition of tumor progression. Mesenchymal stem cells (MSCs) are critical cells that fundamentally participate in modulation of the tumor microenvironment, and have been reported to be able to regulate and determine the final destination of tumor cell. Conflicting functions have been attributed to the activity of MSCs in the tumor microenvironment; they can confer a tumorigenic or anti-tumor potential to the tumor cells. Nonetheless, MSCs have been associated with a potential to modulate the tumor microenvironment in favouring the suppression of cancer cells, and promising results have been reported from the preclinical as well as clinical studies. Among the favourable behaviours of MSCs, are releasing mediators (like exosomes) and their natural migrative potential to tumor sites, allowing efficient drug delivering and, thereby, efficient targeting of migrating tumor cells. Additionally, angiogenesis of tumor tissue has been characterized as a key feature of tumors for growth and metastasis. Upon introduction of first anti-angiogenic therapy by a monoclonal antibody, attentions have been drawn toward manipulation of angiogenesis as an attractive strategy for cancer therapy. After that, a wide effort has been put on improving the approaches for cancer therapy through interfering with tumor angiogenesis. In this article, we attempted to have an overview on recent findings with respect to promising potential of MSCs in cancer therapy and had emphasis on the implementing MSCs to improve them against the suppression of angiogenesis in tumor tissue, hence, impeding the tumor progression.

© 2021, The Author(s). Background: Human immunodeficiency virus (HIV) remains a public health priority in Latin America. While the burden of HIV is historically concentrated in urban areas and high-risk groups, subnational estimates that cover multiple countries and years are missing. This paucity is partially due to incomplete vital registration (VR) systems and statistical challenges related to estimating mortality rates in areas with low numbers of HIV deaths. In this analysis, we address this gap and provide novel estimates of the HIV mortality rate and the number of HIV deaths by age group, sex, and municipality in Brazil, Colombia, Costa Rica, Ecuador, Guatemala, and Mexico. Methods: We performed an ecological study using VR data ranging from 2000 to 2017, dependent on individual country data availability. We modeled HIV mortality using a Bayesian spatially explicit mixed-effects regression model that incorporates prior information on VR completeness. We calibrated our results to the Global Burden of Disease Study 2017. Results: All countries displayed over a 40-fold difference in HIV mortality between municipalities with the highest and lowest age-standardized HIV mortality rate in the last year of study for men, and over a 20-fold difference for women. Despite decreases in national HIV mortality in all countries—apart from Ecuador—across the period of study, we found broad variation in relative changes in HIV mortality at the municipality level and increasing relative inequality over time in all countries. In all six countries included in this analysis, 50% or more HIV deaths were concentrated in fewer than 10% of municipalities in the latest year of study. In addition, national age patterns reflected shifts in mortality to older age groups—the median age group among decedents ranged from 30 to 45 years of age at the municipality level in Brazil, Colombia, and Mexico in 2017. Conclusions: Our subnational estimates of HIV mortality revealed significant spatial variation and diverging local trends in HIV mortality over time and by age. This analysis provides a framework for incorporating data and uncertainty from incomplete VR systems and can help guide more geographically precise public health intervention to support HIV-related care and reduce HIV-related deaths.

Over recent years, mesenchymal stem/stromal cells (MSCs) and their potential biomedical applications have received much attention from the global scientific community in an increasing manner. Firstly, MSCs were successfully isolated from human bone marrow (BM), but in the next steps, they were also extracted from other sources, mostly from the umbilical cord (UC) and adipose tissue (AT). The International Society for Cellular Therapy (ISCT) has suggested minimum criteria to identify and characterize MSCs as follows: plastic adherence, surface expression of CD73, D90, CD105 in the lack of expression of CD14, CD34, CD45, and human leucocyte antigen-DR (HLA-DR), and also the capability to differentiate to multiple cell types including adipocyte, chondrocyte, or osteoblast in vitro depends on culture conditions. However, these distinct properties, including self-renewability, multipotency, and easy accessibility are just one side of the coin; another side is their huge secretome which is comprised of hundreds of mediators, cytokines, and signaling molecules and can effectively modulate the inflammatory responses and control the infiltration process that finally leads to a regulated tissue repair/healing or regeneration process. MSC-mediated immunomodulation is a direct result of a harmonic synergy of MSC-released signaling molecules (i.e., mediators, cytokines, and chemokines), the reaction of immune cells and other target cells to those molecules, and also feedback in the MSC-molecule-target cell axis. These features make MSCs a respectable and eligible therapeutic candidate to be evaluated in immune-mediated disorders, such as graft versus host diseases (GVHD), multiple sclerosis (MS), Crohn’s disease (CD), and osteoarthritis (OA), and even in immune-dysregulating infectious diseases such as the novel coronavirus disease 2019 (COVID-19). This paper discussed the therapeutic applications of MSC secretome and its biomedical aspects related to immune-mediated conditions. Sources for MSC extraction, their migration and homing properties, therapeutic molecules released by MSCs, and the pathways and molecular mechanisms possibly involved in the exceptional immunoregulatory competence of MSCs were discussed. Besides, the novel discoveries and recent findings on immunomodulatory plasticity of MSCs, clinical applications, and the methods required for their use as an effective therapeutic option in patients with immune-mediated/immune-dysregulating diseases were highlighted.

Posttranscriptional gene regulation includes mRNA transport, localization, translation, and regulation of mRNA stability. CPEB (cytoplasmic polyadenylation element binding) family proteins bind to specific sites within the 3′-untranslated region and mediate poly- and deadenylation of transcripts, activating or repressing protein synthesis. As part of ribonucleoprotein complexes, the CPEB proteins participate in mRNA transport and localization to different sub-cellular compartments. The CPEB proteins are evolutionarily conserved and have similar functions in vertebrates and invertebrates. In the nervous system, the CPEB proteins are involved in cell division, neural development, learning, and memory. Here we consider the functional features of these proteins in the nervous system of phylogenetically distant organisms: Drosophila, a well-studied model, and mammals. Disruption of the CPEB proteins functioning is associated with various pathologies, such as autism spectrum disorder and brain cancer. At the same time, CPEB gene regulation can provide for a recovery of the brain function in patients with fragile X syndrome and Huntington's disease, making the CPEB genes promising targets for gene therapy.

Background: Although the relationship between acute alcohol consumption and injuries is well recognized, studies exploring how the time of day the drinking commences affects alcohol-related injuries have been scarce. This contribution examines the associations between the time at which the drinking began and the duration of the drinking, the volume of alcohol consumed, the injury type, and the blood alcohol concentration (BAC) level. Method: This study employed a cross-sectional survey, which was conducted in two hospital emergency departments (ED) in Chiangmai Province, Thailand. The sample was composed of 519 injured patients aged 18 years and older. Outcome measures included the BAC and type of injury. Exposures included the quantity of alcohol consumed, the time the drinking commenced, and the pattern of drinking involved. Results: The injured patients who drank alcohol within six hours prior to sustaining their injury were more likely to get injured and present themselves at the ED at night (20:00–04:00) compared to those who sustained an injury but did not drink in the hours prior. However, this relationship was only true for unintentional injuries, not intentional ones. The majority of participants consumed their first drink between 16:00 and 20:00. On average, among the 104 patients who drank prior to sustaining an injury, the total amount of alcohol consumed was 6.9 drinks, the duration of drinking was 2.6 h, the rate of drinking was 6.0 drinks/hour, and the BAC was 0.119 gm%. Every drink increased the BAC by 0.012 gm% and each year of increasing age increased the BAC by 0.003 gm%. People who were older, less educated, and drank more frequently tended to have their first drink earlier than other drinkers. An earlier start to their drinking resulted in a faster pace of drinking and a higher BAC. Conclusions: BAC increased with the total amount of alcohol consumed and the age of the drinker. Different groups of people had their first drink at different times of the day, resulting in differences in the rate of drinking, the BAC, the time of injury, and the time they presented to the ED after injury.