Individual Tissues Research Articles

Tumor Vasculature as an Emerging Pharmacological Target to Promote Anti-Tumor Immunity

Tumor vasculature abnormality creates a microenvironment that is not suitable for anti-tumor immune response and thereby induces resistance to immunotherapy. Remodeling of dysfunctional tumor blood vessels by anti-angiogenic approaches, known as vascular normalization, reshapes the tumor microenvironment toward an immune-favorable one and improves the effectiveness of immunotherapy. The tumor vasculature serves as a potential pharmacological target with the capacity of promoting an anti-tumor immune response. In this review, the molecular mechanisms involved in tumor vascular microenvironment-modulated immune reactions are summarized. In addition, the evidence of pre-clinical and clinical studies for the combined targeting of pro-angiogenic signaling and immune checkpoint molecules with therapeutic potential are highlighted. The heterogeneity of endothelial cells in tumors that regulate tissue-specific immune responses is also discussed. The crosstalk between tumor endothelial cells and immune cells in individual tissues is postulated to have a unique molecular signature and may be considered as a potential target for the development of new immunotherapeutic approaches.

Bovine meat and milk factor protein expression in tumor-free mucosa of colorectal cancer patients coincides with macrophages and might interfere with patient survival.

Bovine milk and meat factors (BMMFs) are plasmid-like DNA molecules isolated from bovine milk and serum, as well as the peritumor of colorectal cancer (CRC) patients. BMMFs have been proposed as zoonotic infectious agents and drivers of indirect carcinogenesis of CRC, inducing chronic tissue inflammation, radical formation and increased levels of DNA damage. Data on expression of BMMFs in large clinical cohorts to test an association with co-markers and clinical parameters were not previously available and were therefore assessed in this study. Tissue sections with paired tumor-adjacent mucosa and tumor tissues of CRC patients [individual cohorts and tissue microarrays (TMAs) (n= 246)], low-/high-grade dysplasia (LGD/HGD) and mucosa of healthy donors were used for immunohistochemical quantification of the expression of BMMF replication protein (Rep) and CD68/CD163 (macrophages) by co-immunofluorescence microscopy and immunohistochemical scoring (TMA). Rep was expressed in the tumor-adjacent mucosa of 99% of CRC patients (TMA), was histologically associated with CD68+/CD163+ macrophages and was increased in CRC patients when compared to healthy controls. Tumor tissues showed only low stromal Rep expression. Rep was expressed in LGD and less in HGD but was strongly expressed in LGD/HGD-adjacent tissues. Albeit not reaching statistical significance, incidence curves for CRC-specific death were increased for higher Rep expression (TMA), with high tumor-adjacent Rep expression being linked to the highest incidence of death. BMMF Rep expression might represent a marker and early risk factor for CRC. The correlation between Rep and CD68 expression supports a previous hypothesis that BMMF-specific inflammatory regulations, including macrophages, are involved in the pathogenesis of CRC.

Development of cell-laden multimodular Lego-like customizable endometrial tissue assembly for successful tissue regeneration

BackgroundThe endometrium, the inner lining of the uterine cavity, plays essential roles in embryo implantation and its subsequent development. Although some positive results were preliminarily archived, the regeneration of damaged endometrial tissues by administrating stem cells only is very challenging due to the lack of specific microenvironments and their low attachment rates at the sites of injury. In this context, various biomaterial-based scaffolds have been used to overcome these limitations by providing simple structural support for cell attachment. However, these scaffold-based strategies also cannot properly reflect patient tissue-specific structural complexity and thus show only limited therapeutic effects.MethodTherefore, in the present study, we developed a customizable Lego-like multimodular endometrial tissue architecture by assembling individually fabricated tissue blocks.ResultsEach tissue block was fabricated by incorporating biodegradable biomaterials and certain endometrial constituent cells. Each small tissue block was effectively fabricated by integrating conventional mold casting and 3D printing techniques. The fabricated individual tissue blocks were properly assembled into a larger customized tissue architecture. This structure not only properly mimics the patient-specific multicellular microenvironment of the endometrial tissue but also properly responds to key reproductive hormones in a manner similar to the physiological functions.ConclusionThis customizable modular tissue assembly allows easy and scalable configuration of a complex patient-specific tissue microenvironment, thus accelerating various tissue regeneration procedures.

Endogenous miRNA-Based Innate-Immunity against SARS-CoV-2 Invasion of the Brain.

The severe acute respiratory syndrome Coronavirus-2 (SARS-CoV-2), the causative agent of COVID-19, possesses an unusually large positive-sense, single-stranded viral RNA (ssvRNA) genome of about ~29,903 nucleotides (nt). In many respects, this ssvRNA resembles a very large, polycistronic messenger RNA (mRNA) possessing a 5'-methyl cap (m7GpppN), a 3'- and 5'-untranslated region (3'-UTR, 5'-UTR), and a poly-adenylated (poly-A+) tail. As such, the SARS-CoV-2 ssvRNA is susceptible to targeting by small non-coding RNA (sncRNA) and/or microRNA (miRNA), as well as neutralization and/or inhibition of its infectivity via the human body's natural complement of about ~2650 miRNA species. Depending on host cell and tissue type, in silico analysis, RNA sequencing, and molecular-genetic investigations indicate that, remarkably, almost every single human miRNA has the potential to interact with the primary sequence of SARS-CoV-2 ssvRNA. Individual human variation in host miRNA abundance, speciation, and complexity among different human populations and additional variability in the cell and tissue distribution of the SARS-CoV-2 angiotensin converting enzyme-2 (ACE2) receptor (ACE2R) appear to further contribute to the molecular-genetic basis for the wide variation in individual host cell and tissue susceptibility to COVID-19 infection. In this paper, we review recently described aspects of the miRNA and ssvRNA ribonucleotide sequence structure in this highly evolved miRNA-ssvRNA recognition and signaling system and, for the first time, report the most abundant miRNAs in the control superior temporal lobe neocortex (STLN), an anatomical area involved in cognition and targeted by both SARS-CoV-2 invasion and Alzheimer's disease (AD). We further evaluate important factors involving the neurotropic nature of SARS-CoV-2 and miRNAs and ACE2R distribution in the STLN that modulate significant functional deficits in the brain and CNS associated with SARS-CoV-2 infection and COVID-19's long-term neurological effects.

Embryonic ethanol exposure disrupts craniofacial neuromuscular integration in zebrafish larvae.

Forming a vertebrate head involves the meticulous integration of multiple tissue types during development. Prenatal alcohol exposure is known to cause a variety of birth defects, especially to tissues in the vertebrate head. However, a systematic analysis of coordinated defects across tissues in the head is lacking. Here, we delineate the effects of ethanol on individual tissue types and their integration during craniofacial development. We found that exposure to 1% ethanol induced ectopic cranial muscle and nerve defects with only slight effects on skeletal pattern. Ectopic muscles were, however, unaccompanied by ectopic tendons and could be partially rescued by anesthetizing the larvae before muscle fibers appeared. This finding suggests that the ectopic muscles result from fiber detachment and are not due to an underlying muscle patterning defect. Interestingly, immobilization did not rescue the nerve defects, thus ethanol has an independent effect on each tissue even though they are linked in developmental time and space. Time-course experiments demonstrated an increase in nerve defects with ethanol exposure between 48hpf-4dpf. Time-lapse imaging confirmed the absence of nerve pathfinding or misrouting defects until 48hpf. These results indicate that ethanol-induced nerve defects occur at the time of muscle innervation and after musculoskeletal patterning. Further, we investigated the effect of ethanol on the neuromuscular junctions of the craniofacial muscles and found a reduced number of postsynaptic receptors with no significant effect on the presynaptic terminals. Our study shows that craniofacial soft tissues are particularly susceptible to ethanol-induced damage and that these defects appear independent from one another. Thus, the effects of ethanol on the vertebrate head appear highly pleiotropic.

High-depth sequencing characterization of viral dynamics across tissues in fatal COVID-19 reveals compartmentalized infection

SARS-CoV-2 distribution and circulation dynamics are not well understood due to challenges in assessing genomic data from tissue samples. We develop experimental and computational workflows for high-depth viral sequencing and high-resolution genomic analyses from formalin-fixed, paraffin-embedded tissues and apply them to 120 specimens from six subjects with fatal COVID-19. To varying degrees, viral RNA is present in extrapulmonary tissues from all subjects. The majority of the 180 viral variants identified within subjects are unique to individual tissue samples. We find more high-frequency (>10%) minor variants in subjects with a longer disease course, with one subject harboring ten such variants, exclusively in extrapulmonary tissues. One tissue-specific high-frequency variant was a nonsynonymous mutation in the furin-cleavage site of the spike protein. Our findings suggest adaptation and/or compartmentalized infection, illuminating the basis of extrapulmonary COVID-19 symptoms and potential for viral reservoirs, and have broad utility for investigating human pathogens.

Enhancing Tissue Impedance Measurements Through Modeling of Fluid Flow During Viscoelastic Relaxation.

Bladder cancer recurrence is an important issue after endoscopic urological surgeries. Additional sensor information such as electrical impedance measurements aim to support surgeons to ensure that the entirety of the tumor is removed. The foundation for differentiating lies in the altered sodium contents and cell structures within tumors that change their conductivity and permittivity. Mechanical deformations in the tissue expel fluid from the compressed area and pose a great difficulty, as they also lead to impedance changes. It is crucial to determine if this effect outweighs the alterations due to the tumorous tissue properties. Impedance measurements under ongoing viscoelastic relaxation are taken on healthy and tumorous tissue samples from human bladders and breasts. A fluid model to account for extra- and intracellular fluid flow under compression is derived. It is based on the fluid content within the individual tissue compartments and their outflow via diffusion. After an initial deformation, the tissue relaxes and the impedance increases. The proposed model accurately represents these effects and validates the link between fluid flow under mechanical deformation and its impact on tissue impedance. A method to compensate for these undesired effects of fluid flow is proposed and the measurements are assessed in terms of differentiability between tumorous and healthy tissue samples. The electrical parameters are found to be promising for differentiation even under varying mechanical deformation, and the distinction is additionally improved by the proposed compensation approach. Electrical impedance measurements show great potential to support urologist during endoscopic surgeries.

Distinct sets of olfactory receptors highly expressed in different human tissues evaluated by meta-transcriptome analysis: Association of OR10A6 in skin with keratinization.

Olfactory receptors (ORs) are expressed in many tissues and have multiple functions. However, most studies have focused on individual ORs. Here, we aimed to conduct a comprehensive meta-transcriptome analysis of OR gene expression in human tissues by using open-source tools to search a large, publicly available genotype-tissue expression (GTEx) data set. Analysis of RNA-seq data from GTEx revealed that OR expression patterns were tissue-dependent, and we identified distinct sets of ORs that were highly expressed in 12 tissues, involving 97 ORs in total. Among them, OR5P2, OR5P3 and OR10A6 were associated with skin. We further examined the roles of these ORs in skin by performing weighted gene correlation network analysis (WGCNA) and c3net analysis. WGCNA suggested that the three ORs are involved in epidermal differentiation and water-impermeable barrier homeostasis, and OR10A6 showed the largest gene sub-network in the c3net network. Immunocytochemical examination of human skin keratinocytes revealed a sparse expression pattern of OR10A6, suggesting that it is not uniformly distributed among all keratinocytes. An OR10A6 agonist, 3-phenylpropyl propionate (3PPP), transiently increased intracellular Ca2+ concentration and increased cornified envelope (CE) production in cultured keratinocytes. Knock-down of OR10A6 diminished the effect of 3PPP. Overall, integration of meta-transcriptome analysis and functional analysis uncovered distinct expression patterns of ORs in various human tissues, providing basic data for future studies of the biological functions of highly expressed ORs in individual tissues. Our results further suggest that expression of OR10A6 in skin is related to epidermal differentiation, and OR10A6 may be a potential target for modulation of keratinization.

NOD1 activation in 3T3-L1 adipocytes confers lipid accumulation in HepG2 cells

AimsActivation of specific innate immune receptors has been characterized to modulate nutrient metabolism in individual metabolic tissue directly or indirectly via secretory molecules. Activation of the nucleotide-binding oligomerization domain-containing protein 1 (NOD1) in adipocytes has been reported to induce lipolysis linked with insulin resistance and inflammatory response. These cues are positioned to modulate metabolic action in distal organs through paracrine/endocrine signaling. Here, we assessed the role of NOD1-mediated lipolysis and inflammatory response in adipocytes to affect lipid metabolism in hepatocytes. Main methodsHuman hepatoma cells (HepG2) were exposed to conditioned medium obtained from 3 T3-L1 adipocytes pretreated with NOD1 ligand (iE-DAP) and the effects on lipid accumulation, inflammation and insulin response were assessed. Activation of mechanisms leading to hepatic lipid accumulation was investigated by gene expression analysis. Key findingsThe conditioned medium from NOD1-activated 3 T3-L1 adipocytes (CM-DAP) induced lipid accumulation in HepG2 cells, driven by both lipolysis and inflammatory responses. The CM-DAP-induced lipid accumulation was independent to de novo lipogenesis and resulted from the enhanced transport of fatty acids inside and consequent increase in rate of triglycerides synthesis in hepatocytes. Moreover, CM-DAP-induced lipid accumulation instigated the expression of the markers of fatty acid oxidation and VLDL assembly for the export of triglycerides from hepatocyte. Furthermore, CM-DAP-induced lipid accumulation was associated with induction of inflammatory response and impairment of insulin signaling in HepG2 cells. SignificanceBeyond showing liver-specific mechanisms to adipocytes-derived factors, our findings support the involvement of adipose tissue as a mediator in NOD1-mediated biological responses to modulate hepatic metabolism.

Associations between non-suicidal self-injury and experiential avoidance: A systematic review and Robust Bayesian Meta-analysis

ObjectivesNon-suicidal self-injury (NSSI) is the intentional and deliberate damage to an individual's own body tissue without the intent to suicide. Individuals who have higher self-reported levels of experiential avoidance are more likely to report a history of NSSI. The current study systematically reviewed the literature and meta-analysed studies assessing associations between experiential avoidance and self-injury. MethodAn extensive review was conducted of several databases (including ProQuest, Joanna Briggs, Web of Science, PsychArticles, PubMed, Scopus, and Ovid). Nineteen articles (two dissertations) met the inclusion criteria for the systematic review and 14 were analysed in a Robust Bayesian Meta-analysis. This review was registered through PROSPERO (CRD42020198041). ResultsThere was a small to medium, pooled effect size (d = 0.48, 95 % Credibility Interval 0.00–0.85). There was strong evidence for this effect size (Bayes Factor = 12.16), although there was considerable heterogeneity between studies (τ =0.68, 95 % CI [0.44, 0.1.05]). The analysis testing whether these findings may be due to publication bias was inconclusive (Bayes Factor = 2.45). LimitationsThe majority of studies included were cross-sectional, in English, and most studies were of university students. While some studies reported on recency/frequency of NSSI there was not enough data to conduct meta-analysis. ConclusionThese results suggest there is a robust association between history of NSSI and experiential avoidance. However, as most studies operationalise avoidance as a unidimensional construct, it is not clear which aspects of avoidance differentiate individuals with and without a history of NSSI.

Методика оценки радиационного риска медицинского облучения при прохождении компьютерной томографии с учётом неопределённостей модели риска

The paper presents analysis of different factors affecting the uncertainty model for estimating ra-diation risk from computed tomography (CT). Uncertainties in radiation doses estimates caused by measurement (instrumental) errors or used dose estimation methods, the size of the scanned area and the type of CT scanner. The uncertainty of radiation dose due to measurement errors or dose estimation methods, the size of the scanned area and type of a CT scan may cause the uncertainties as well. Data used for calculating equivalent doses in individual organs and tissues and for calculating lifetime radiation risk of cancer development due to routine CT testing were updated. Conversion factors for DLP, a measure of radiation dose a patient received during CT exams of thoracic, abdomen and head organs, were determined and used for conversion of the CT doses to equivalent doses for individual organs and tissues exposed to radiation. Data for 15 state-of-the-art CT scanners with varying scanning geometry were updated. Uncertainties in life-time radiation risk were determined by estimating 95% confidence intervals for mean dose-proportionality ratios. Standard deviations related to specific dose distribution, scanning geometry and other factors that impact on uncertainty of radiation risk estimates were calculated. The standard deviations associated with the specifics of the dose distribution, scanning geometry and other factors affecting the uncertainties of radiation risk assessments were calculated. In the course of simulation modelling, organs and tissues were identified that are most exposed to radiation during CT of the chest, abdomen and head.

Метод оценки радиационного риска медицинского облучения при прохождении компьютерной томографии детей и подростков на основе данных протоколов сканирования

Computed tomography (CT) scan is a fairly accurate and reliable method for diagnosing various diseases, however, based on irradiation of the patient with ionizing radiation, it can lead to an excess risk of developing malignant neoplasms. According to the safety standards of the International Atomic Energy Agency, no patient can be exposed to medical radiation unless he or she has been informed of the risks associated with radiation exposure. This requirement is also contained in the Russian Radiation Safety Standards (NRB-99/2009). Radiation risk is estimated on the basis of calculated values of equivalent doses in the patient's organs and tissues using radiation risk models of the International Commission on Radiological Protection. This article is devoted to the improvement of the method for calculating equivalent doses in the organs and tissues of patients with computed tomography scan for further assessment of radiation risks. For 15 modern computed tomography scanners, with different geometry of patient scanning, the data necessary for calculating the equivalent doses in organs and tissues based on the parameters of the children's phantom were updated. The coefficients of conversion of the surrogate measure of the patient's radiation dose for the entire CT scan study, namely, the value of the "Dose Length Product" (DLP), into the values of equivalent doses in individual organs and tissues exposed to radiation were determined. The results of the calculation are given for five typical scan areas: chest, abdomen, pelvis, head and neck. In the course of simulation numerical modeling, organs and tissues with the highest equivalent doses were determined during CT scan examinations of children and adolescents. Unlike adult patients, for children and adolescents, the dose load on the surface of the bone is significantly lower and does not stand out in any of the considered types of CT scan examinations. It should be noted that with CT scan of the cervical spine, due to the specifics of the geometry of scanning new types of tomography scanners, the dose load on the thyroid gland of boys increased. The dose conversion factors obtained in this paper with estimates of standard deviations make it possible to assess the radiation risks of children and adolescents during examinations on modern CT scanners and optimize their dose loads.

Neurological aspects of connective tissue dysplasia

Disturbances in the formation of connective tissue lead to significant pathological changes in both individual organs and tissues, and at the organismal level. The complexity of diagnostics is also connected with the fact that there is no single terminology, a single view of the diagnostic criteria, a single approach among doctors of different specialties. The prevalence of external phenotypic signs of connective dysplasia is quite high, which can lead to overdiagnosis. On the other hand, insufficient attention to the manifestations of dysplasia can lead to delayed diagnosis, which can cause adverse complications. The most studied are clinical manifestations in dysplastic changes in the cardiovascular system, musculoskeletal system. This article provides an overview of current data on changes in the nervous system. Sufficient attention was paid to the pathology of the nervous system in differentiated forms (Marfan syndrome, Ehlers-Danlos, etc.). Currently, the role of various vascular anomalies, aneurysms associated with undifferentiated forms of connective tissue dysplasia is widely discussed. Much attention is also paid to clinical manifestations of the autonomic nervous system: sympathicotonic manifestations predominate in connective tissue dysplasia. There is evidence of an association of headaches, musculoskeletal pain, and connective tissue dysplasia in both children and adults.

Significance of molecular diagnostics for therapeutic decision-making in recurrent glioma.

Targeted therapies have substantially improved survival in cancer patients with malignancies outside the brain. Whether in-depth analysis for molecular alterations may also offer therapeutic avenues in primary brain tumors remains unclear. We herein present our institutional experience for glioma patients discussed in our interdisciplinary molecular tumor board (MTB) implemented at the Comprehensive Cancer Center Munich (LMU). We retrospectively searched the database of the MTB for all recurrent glioma patients after previous therapy. Recommendations were based on next-generation sequencing results of individual patient's tumor tissue. Clinical and molecular information, previous therapy regimens, and outcome parameters were collected. Overall, 73 consecutive recurrent glioma patients were identified. In the median, advanced molecular testing was initiated with the third tumor recurrence. The median turnaround time between initiation of molecular profiling and MTB case discussion was 48 ± 75 days (range: 32-536 days). Targetable mutations were found for 50 recurrent glioma patients (68.5%). IDH1 mutation (27/73; 37%), epidermal growth factor receptor amplification (19/73; 26%), and NF1 mutation (8/73; 11%) were the most detected alterations and a molecular-based treatment recommendation could be made for all of them. Therapeutic recommendations were implemented in 12 cases (24%) and one-third of these heavily pretreated patients experienced clinical benefit with at least disease stabilization. In-depth molecular analysis of tumor tissue may guide targeted therapy also in brain tumor patients and considerable antitumor effects might be observed in selected cases. However, future studies to corroborate our results are needed.

ОДЭК: уровень радиологической защиты населения с учётом современной модели «доза-эффект» МКРЗ

After receiving the notification of the license granting and its registration in the license register it has become topical the preparation of the final version of the project documentation to guarantee the safety of the public residing in the proximity of the operating Pilot-demonstration energy complex (PDEC), which includes a reactor unit BREST-OD-300, reprocessing module and a fuel fabrication/refabrication module. Currently International Commission on Radiological Protection (ICRP, Publication 103) recommends for estimating radiological protection of the public to use carcinogenic risks estimates for individual organs and tissues, with account of equivalent doses and modern models of «dose-effect» relationship instead of the use of committed effective doses. The article demonstrates the 5-7 times spread of lifetime carcinogenic radiation risk values from exposure to different radionuclides, while the committed effective dose from intakes of the same radionuclides do not differ. The distinguishing characteristic of updated ICRP recommendations is consideration of gender and age of the exposed population when assessing radiation-related carcinogenic risks. The article presents estimates of lifetime attributable risk for critical groups of the public residing in the proximity of the PDEC; the risk was calculated with the use of estimates of annual air emissions from normally operated PDEC. Tritium (H-3) and cesium (Cs-137) emissions limit values have been calculated, the radionuclides ensure the normal functioning of the complex in a negligible radiation risk range for the population (Radiation Safety Standards (RSS-99/2009)).

Next Generation Sequencing Analysis and its Benefit for Targeted Therapy of Lung Adenocarcinoma.

Targeted therapy has become increasingly important in treating lung adenocarcinoma, the most common subtype of lung cancer. Next-generation sequencing (NGS) enables precise identification of specific genetic alterations in individual tumor tissues, thereby guiding targeted therapy selection. This study aimed to analyze mutations present in adenocarcinoma tissues using NGS, assess the benefit of targeted therapy and evaluate the progress in availability of targeted therapies over last five years. The study included 237 lung adenocarcinoma patients treated between 2018-2020. The Archer FusionPlex CTL panel was used for NGS analysis. Gene variants covered by the panel were detected in 57% patients and fusion genes in 5.9% patients. At the time of the study, 34 patients (14.3% of patients) were identified with a targetable variant. Twenty-five patients with EGFR variants, 8 patients with EML4-ALK fusion and one patient with CD74-ROS1 fusion received targeted therapy. Prognosis of patients at advanced stages with EGFR variants treated by tyrosine kinase inhibitors and patients with EML4-ALK fusion treated by alectinib was significantly favorable compared to patients without any targetable variant treated by chemotherapy (p=0.0172, p=0.0096, respectively). Based on treatment guidelines applicable in May 2023, the number of patients who could profit from targeted therapy would be 64 (27.0% of patients), this is an increase by 88% in comparison to recommendations valid in 2018-2020. As lung adenocarcinoma patients significantly benefit from targeted therapy, the assessment of mutational profiles using NGS could become a crucial approach in the routine management of oncological patients.

Морозостійкість великоплідних сортів черешні (Cerasus avium Moench.) в умовах правобережної частини Західного Лісостепу

The results of determining the potential level of frost resistance of 27 promising large-fruited cherry varieties using the laboratory freezing method are presented. The purpose of the research was to study the adaptive potential of promising large-fruited cherry varieties of Ukrainian breading program in terms of determining their resistance to the impact of critical low temperatures. The degree of tissues frost damage of shoots and buds was assessed according to intensity of their browning on transverse anatomical sections based on microscopic analysis on a six-point scale. According to the results of research, varieties with the highest level of frost resistance were selected. Laboratory freezing of one-year branches of large-fruited cherries varieties during a period of relative rest under the temperatures of -25 and -30 °С, should the features of freezing of their tissues and parts of growths. A higher degree of freezing of the tops of one-year branches compared to their middle part was established. It also was revealed a high potential frost resistance of the researched varieties at temperatures of minus 25 °С. At the same time, at – 30 °С, severe damage of individual tissues of one-year branches was found in the varieties Dzherelo, Regina, Prostir, Vasylisa Prekrasna and Temporion, which were marked by a high indexed score of damage - 61.8-72.3 % (for the minimum permissible 50 %). Against their background, the most frost-resistant varieties were selected, such as Donchanka, Anons, Kazka, Etyka, Krupnoplidna, Valeriia and Anshlag, which had the lowest indexed damage score (30.4-43.8 %) and may be promising for growing in the right bank part of the west Lisosteppe of Ukraine, because they were characterized by a greater adaptability to the impact of low critical temperatures during a period of relative rest. Key words: cherry, cultivar, laboratory freezing, temperature, critical tissue damage, frost resistance.

PS-B03-3: THE CD153-CPG VACCINE IS A NOVEL SENOTHERAPEUTIC OPTION TO REMOVE SENESCENCE-ASSOCIATED T CELLS

Cellular senescence in primary culture cells has allowed us to understand basic individual tissue aging and cancer inhibition from the view of cellular aging. Senescent cells accumulate gradually and systemically with age, and secrete various inflammatory cytokines or chemokines, which is different from the cell fate in apoptosis. These phenomena describe the so-called senescence-associated secretory phenotype, and chronic inflammation and carcinogenesis are induced in the surrounding tissues through senescence-associated secretory phenotype factors. The senescence-associated T cells do not proliferate in response to T-cell receptor stimulation, and produce abundant inflammatory cytokines including osteopontin. Senescence-associated T cells are also increased in adipose tissue under a high-fat diet, which might be related to the progress of obesity or diabetes. We evaluated the long-lasting effect of using CD153 vaccination to remove senescent T cells from high-fat diet (HFD)-induced obese C57BL/6J mice. We administered a CD153 peptide-KLH (keyhole limpet hemocyanin) vaccine with CpG oligodeoxynucleotide (ODN) 1585 (CD153-CpG) and confirmed an increase in anti-CD153 antibody levels that was sustained for several months. After being fed a HFD for 10–11 weeks, adipose senescent T cell accumulation was significantly reduced in the VAT of CD153-CpG-vaccinated mice, accompanied by glucose tolerance and insulin resistance. A histological analysis also indicated that the accumulation of macrophages and senescence-associated T cells in adipose tissues successfully reduced in the CD153-CpG-vaccinated mice. The CD153-CpG vaccine is an optional tool for senolytic therapy. We further modify the vaccine to remove the target cells now.

番茄生长过程储存模态信息的植株生物电路模型构建

During the growth and development of tomato plants, its different cells or tissues would store external environmental information and express it in the form of ion transportation. In order to better examine the storage model of tomato plants, the tomato individual tissue and whole plant biological circuit models were closely examined based on the idea of modal theory. According to the parameter inversion theory, in the frequency range of 0.1Hz - 1MHz, the impedance spectrum measurement and dielectric properties of tomato plants in four modal periods of germination stage were carried out. The stages were namely the seedling stage, flowering and fruit setting stage, and fruiting stage respectively. Impedance spectrum fitting was performed with the ZSimpWin software. Then, the biological circuit model of each tissue of tomato plant was obtained. Next, the parameter inversion was used to calculate the value of each element of the biological circuit model. Lastly, the biological circuit model of the tomato plant body in each period was obtained. Through the charging and discharging test of the model of the tomato plant body at each stage, the corresponding parameter value relationship was obtained according to the capacitance characteristics. This would be compared with the component values obtained from the parameter inversion in the model. Results showed that the errors were all less than 4.8%, which verified the rationality of the model. This system acted as a theoretical guidance for the research on the growth and development of tomato and other plants.

Internal Dosimetry: State of the Art and Research Needed

Internal dosimetry is a discipline which brings together a set of knowledge, tools and procedures for calculating the dose received after incorporation of radionuclides into the body. Several steps are necessary to calculate the committed effective dose (CED) for workers or members of the public. Each step uses the best available knowledge in the field of radionuclide biokinetics, energy deposition in organs and tissues, the efficiency of radiation to cause a stochastic effect, or in the contributions of individual organs and tissues to overall detriment from radiation. In all these fields, knowledge is abundant and supported by many works initiated several decades ago. That makes the CED a very robust quantity, representing exposure for reference persons in reference situation of exposure and to be used for optimization and assessment of compliance with dose limits. However, the CED suffers from certain limitations, accepted by the International Commission on Radiological Protection (ICRP) for reasons of simplification. Some of its limitations deserve to be overcome and the ICRP is continuously working on this. Beyond the efforts to make the CED an even more reliable and precise tool, there is an increasing demand for personalized dosimetry, particularly in the medical field. To respond to this demand, currently available tools in dosimetry can be adjusted. However, this would require coupling these efforts with a better assessment of the individual risk, which would then have to consider the physiology of the persons concerned but also their lifestyle and medical history. Dosimetry and risk assessment are closely linked and can only be developed in parallel. This paper presents the state of the art of internal dosimetry knowledge and the limitations to be overcome both to make the CED more precise and to develop other dosimetric quantities, which would make it possible to better approximate the individual dose.