Relationship between Glutathione-Dependent Enzymes and the Immunohistochemical Profile of Glial Neoplasms.

This research aimed to investigate the relationships between the parameters of glutathione metabolism and the immunohistochemical characteristics of glial tumors. Postoperative material from 20 patients with gliomas of different grades of anaplasia was analyzed. Bioinformatic analysis of the interactions between the gliomas' immunohistochemical markers and their glutathione-dependent enzymes was carried out using the STRING, BioGrid, while Signor databases revealed interactions between such glioma markers as IDH and p53 and the glutathione exchange enzymes (glutathione peroxidase, glutathione reductase, glutathione S-transferase). The most pronounced relationship with glutathione metabolism was demonstrated by the level of the nuclear protein Ki67 as a marker of proliferative activity, and the presence of the IDH1 mutation as one of the key genetic events of gliomagenesis. The glutathione system is an active participant in the body's antioxidant defense, involving the p53 markers and MGMT promoter methylation. It allows characterization of the gliomal cells' status at different stages of tumor development.

Prospects for the use of blood elemental status to assess the molecular genetic profile of gliomas.

It has been established that blood element homeostasis is related to gliomagenesis which increases the attractiveness of the analysis of its components as a promising preoperative mediated characteristics of the molecular genetic profile of gliomas. The aim of this work is to analyze the relationship between mineral metabolism parameters and immunohistochemical characteristics of glial tumors and evaluate the clinical significance of blood element homeostasis analysis for preoperative assessment of the molecular profile of gliomas. The levels of cancer specific markers MGMT, Ki-67, p-53, IDH1 were determined immunohistochemically using the corresponding antibody clones. Micronutrient levels were analyzed by inductively coupled plasma atomic emission spectrometry recalculating the results per 1 g of protein which was determined by the Lowry method. The data on cancer-specific marker levels obtained in primary brain tumors (20) and in blood plasma of gliomas patients (20) and practically healthy subjects (5) were compared using a number of statistical programs. We found significant differences in the levels of sodium, potassium, zinc and copper depending on the value of the mitotic index Ki-67 and IDH1 isocitrate dehydrogenase gene mutation. For the first time, a significant correlation showing the consistency between the level of glial tumor cancer-specific markers and blood mineral metabolism was observed. The revealed correlations provide new insights into understanding of gliomagenesis mechanisms and can be used as a predictive preoperative assessment of molecular genetic markers of gliomas.

Carbohydrate Metabolism Parameters of Adult Glial Neoplasms According to Immunohistochemical Profile.

This research aimed to investigate the interrelationship of carbohydrate metabolism parameters and immunohistochemical characteristics of glial tumors. Tumor tissue, peritumoral area, and adjacent noncancerous tissue fragments of 20 patients with gliomas of varying degrees of anaplasia were analyzed. The greatest differences in the carbohydrate metabolism compared to adjacent noncancerous tissues were identified in the tumor tissue: reduction in the levels of lactate and glycogen synthase kinase-3ß. Significant differences with adjacent noncancerous tissues for the peritumoral zone were not found. The activity of the carbohydrate metabolism enzymes was different depending on the immunohistochemical glioma profile, especially from Ki 67 level. Bioinformatic analysis of the interactions of immunohistochemical markers of gliomas and carbohydrate metabolism enzymes using the databases of STRING, BioGrid, and Signor revealed the presence of biologically significant interactions with glycogen synthase kinase 3ß, hexokinase, glucose-6-phosphate dehydrogenase, and transketolase. The established interconnection of glycolysis with methylation of the promoter of O-6-methylguanine-DNA-methyltransferase (MGMT) of gliomas can be used to increase chemotherapy efficiency.

Association of saponin concentration, molecular markers, and biochemical factors with enhancing resistance to alfalfa seedling damping-off.

Fifteen alfalfa populations were tested for resistance to the seedling damping-off disease sourced by Rhizoctonia solani, Fusarium solani, and Macrophomina phaseolina. In a laboratory experiment, saponin treatment significantly diminished the mycelial growth of the causal fungi of alfalfa damping-off disease. Roots of the fifteen alfalfa populations varied in saponin and lignin content. Selection for the considerably resistant plants leads to the best growth performance, desirable yield, and high nutritive values such as crude protein (CP), crude fier (CF), nitrogen free extract (NFE), ash, and ether extract (EE) contents. For the PCR reaction, 10 SSR pairs of the JESPR series primers and the cDNA-SCoT technique with seven primers were used. SSR and SCoT revealed some unique markers that could be linked to resistance to damping-off disease in alfalfa that appeared in the considerably resistant alfalfa population (the promised pop.). SSR and SCoT markers can be an excellent molecular method for judging genetic diversity and germplasm classification in tetraploid alfalfa. We recommend breeding for saponin concentration in the alfalfa plant may affect resistance to some diseases like root rot and damping-off because saponin might improve plant growth, yield, and nutritional values.

Mutations in Epigenetic Regulation Genes in Gastric Cancer.

We have performed mutational profiling of 25 genes involved in epigenetic processes on 135 gastric cancer (GC) samples. In total, we identified 79 somatic mutations in 49/135 (36%) samples. The minority (n = 8) of mutations was identified in DNA methylation/demethylation genes, while the majority (n = 41), in histone modifier genes, among which mutations were most commonly found in KMT2D and KMT2C. Somatic mutations in KMT2D, KMT2C, ARID1A and CHD7 were mutually exclusive (p = 0.038). Mutations in ARID1A were associated with distant metastases (p = 0.03). The overall survival of patients in the group with metastases and in the group with tumors with signet ring cells was significantly reduced in the presence of mutations in epigenetic regulation genes (p = 0.036 and p = 0.041, respectively). Separately, somatic mutations in chromatin remodeling genes correlate with low survival rate of patients without distant metastasis (p = 0.045) and in the presence of signet ring cells (p = 0.0014). Our results suggest that mutations in epigenetic regulation genes may be valuable clinical markers and deserve further exploration in independent cohorts.

Analysis of the association of BRAFV600E mutation and Ki-67 overexpression with clinical and pathological characteristics in papillary thyroid cancer.

In recent years, many studies were dedicated to the search for genetic markers in thyroid malignancies, including papillary thyroid cancer. This study was designed to investigate the prevalence of BRAFV600E mutation in the PTC in the Kazakh population, to evaluate the relationship between BRAF V600E mutation status and the clinicopathological features of PTC. Besides, we aimed at assessing of the relationship between the high proliferation index and the clinicopathological features of PTC and also between the concomitant coexistence of BRAFV600E and the high proliferative index with clinicopathological features of PTC. We carried out a cross-sectional study on 123 patients with PTC of Kazakh ethnicity and analyzed their clinical, laboratory, and genetic findings. The study groups were pooled based on the presence of mutated or wild-type BRAFV600E and quantitative assessment of Ki-67 marker expression. In the course of our study, we found that the age of patients from the group of BRAF gene mutation was significantly higher than that of patients from the wild-type group (48.63 ± 14.07 years versus 40.23 ± 14.34 years) (t = - 3.257; p = 0.001). Correlation analysis between BRAF mutation, Ki-67 expression, their combination and various clinical and pathological parameters in PTC patients showed that older age was positively correlated with higher frequency of mutant BRAF gene (r = 0.284; p < 0.001), while more advanced stage of tumor was positively correlated with higher expression of Ki-67 (r = 0.307; p < 0.001). To understand the significance of detecting the BRAFV600E mutation and an increased level of Ki-67 expression in the choice of patient therapy tactics, larger studies are required with patient survival as one of the primary outcomes.

Genetic identification of Anisakis spp. (Nematoda: Anisakidae) from cetaceans of the Southwestern Atlantic Ocean: ecological and zoogeographical implications.

Adult Anisakis Dujardin, 1845 were found in two specimens of killer whale Orcinus orca and one specimen of franciscana Pontoporia blainvillei stranded from off the coast of Buenos Aires Province, Argentina. Genetic identification of the nematodes (N = 144) was performed by sequence analysis of the mitochondrial (mtDNA cox2) and the nuclear (nas 10 nDNA) gene loci. Anisakis pegreffii and Anisakis berlandi were detected in the two individuals of O. orca, while Anisakis typica and A. pegreffii were identified in P. blainvillei. Morphological and morphometric analysis also carried out on adult specimens of A. pegreffii and A. berlandi has allowed to underlining the usefulness of genetic/molecular markers in their recognition. This represents the first record of A. pegreffii in O. orca and P. blainvillei and of A. berlandi in O. orca. This is also the first sympatric and syntopic occurrence, as adults, of A. pegreffii and A. berlandi from the Austral Region of the Atlantic Ocean waters. These results provide insights into the knowledge of the host ranges and geographical distribution of these parasites in the basin waters of the region. Pontoporia blainvillei showed low abundance values of infection with Anisakis spp., which is the general pattern for coastal dolphins in the area, whereas O. orca harboured higher abundance of Anisakis spp. than those previously recorded among cetacean species in the Argentine Sea. Differences in the Anisakis spp. distribution and their parasitic loads, observed among the three host specimens, are discussed in relation to the oceanographic parameters, as well as to the host ecology. The usefulness of genetic/molecular markers in the recognition of adults of the sibling species A. pegreffii and A. berlandi with considerable overlapping in morphometric and morphological characters was underlined. The distribution of Anisakis species from Southwestern Atlantic waters is discussed in relation to their value as indicators for studies on the zoogeography of their hosts at a regional-scale level.

[Hepatocellular carcinoma: new provisions of the WHO classification, 5th edition, 2019]. / Gepatotsellyulyarnaya kartsinoma ­ novye polozheniya klassifikatsii VOZ 2019, 5-e izdanie.

The WHO Classification of Digestive System Tumors (WHO, 5th Edition, 2019) presents new provisions on the morphological, molecular genetic, and therapeutic aspects of hepatocellular carcinoma (HCC). This classification versus the 2010 edition underwent substantial changes. Undifferentiated carcinoma (ICD-0: 8020/3) was excluded. The TNM staging system introduces additional gradations. Based on new evidence, HCC types and subtypes (scirrhous, clear cell, steatohepatic, and others) were identified depending on gene mutations according to ICD-11. The classification changes are of not only important theoretical, but also applied significance. These are valuable for oncologists and pathologists.

COVID-19 and Individual Genetic Susceptibility/Receptivity: Role of ACE1/ACE2 Genes, Immunity, Inflammation and Coagulation. Might the Double X-chromosome in Females Be Protective against SARS-CoV-2 Compared to the Single X-Chromosome in Males?

In December 2019, a novel severe acute respiratory syndrome (SARS) from a new coronavirus (SARS-CoV-2) was recognized in the city of Wuhan, China. Rapidly, it became an epidemic in China and has now spread throughout the world reaching pandemic proportions. High mortality rates characterize SARS-CoV-2 disease (COVID-19), which mainly affects the elderly, causing unrestrained cytokines-storm and subsequent pulmonary shutdown, also suspected micro thromboembolism events. At the present time, no specific and dedicated treatments, nor approved vaccines, are available, though very promising data come from the use of anti-inflammatory, anti-malaria, and anti-coagulant drugs. In addition, it seems that males are more susceptible to SARS-CoV-2 than females, with males 65% more likely to die from the infection than females. Data from the World Health Organization (WHO) and Chinese scientists show that of all cases about 1.7% of women who contract the virus will die compared with 2.8% of men, and data from Hong Kong hospitals state that 32% of male and 15% of female COVID-19 patients required intensive care or died. On the other hand, the long-term fallout of coronavirus may be worse for women than for men due to social and psychosocial reasons. Regardless of sex- or gender-biased data obtained from WHO and those gathered from sometimes controversial scientific journals, some central points should be considered. Firstly, SARS-CoV-2 has a strong interaction with the human ACE2 receptor, which plays an essential role in cell entry together with transmembrane serine protease 2 (TMPRSS2); it is interesting to note that the ACE2 gene lays on the X-chromosome, thus allowing females to be potentially heterozygous and differently assorted compared to men who are definitely hemizygous. Secondly, the higher ACE2 expression rate in females, though controversial, might ascribe them the worst prognosis, in contrast with worldwide epidemiological data. Finally, several genes involved in inflammation are located on the X-chromosome, which also contains high number of immune-related genes responsible for innate and adaptive immune responses to infection. Other genes, out from the RAS-pathway, might directly or indirectly impact on the ACE1/ACE2 balance by influencing its main actors (e.g., ABO locus, SRY, SOX3, ADAM17). Unexpectedly, the higher levels of ACE2 or ACE1/ACE2 rebalancing might improve the outcome of COVID-19 in both sexes by reducing inflammation, thrombosis, and death. Moreover, X-heterozygous females might also activate a mosaic advantage and show more pronounced sex-related differences resulting in a sex dimorphism, further favoring them in counteracting the progression of the SARS-CoV-2 infection.

The role of surgery in grade II/III oligodendroglial tumors.

Supratentorial gliomas WHO grade II and III with an oligodendroglial phenotype are highly infiltrative lesions that preferentially originate in lobar location. Open tumor resection represents one of the mainstays of management as beneficial decompressive effects for large space-occupying lesions and oncologically relevant cytoreductive effects from complete resection can be expected. In patients not eligible for safe tumor resection meticulous histological and molecular-genetic evaluation can be obtained from advanced stereotactic biopsy techniques. In this perspective, important aspects of open tumor surgery and stereotactic biopsy are discussed within the context of diagnosis, prognosis and treatment of oligodendrogliomas and oligoastrocytomas WHO grade II and III. Practical considerations are provided in order to integrate the place of surgery into an increasingly personalized management concept. For highly selected patients interstitial brachytherapy is introduced as an alternative surgically performed treatment option.

Biological characteristics of Echinococcus f elidis / 中国人兽共患病学报

This review focuses on biological characteristics of Echinococcus f elidis including molecular genetic markers , species status ,host coverage ,geographical distribution ,epidemiological implications ,phylogeny ,and evolution .The molecular genetic markers are involved in mitochondrial cox1 (cytochrome C oxidase subunit 1) and nad1 (nicotinamide adenine dinucle-otide dehydrogenase subunit 1) genes ,nuclear protein-coding gene sequences such as elp (ezrin-radixin-moesin-like protein) , e f1a (elongation factor 1 alpha) ,pepck (phosphoenolpyruvate carboxykinase ) ,pold (DNA polymerase delta ) ,and ribosome RNA gene sequences such as ITS1 and 18S rRNA .The establishment of species status is based on distinctly discriminated mor-phological characteristics such as hooks on the rostrum with apparent rugae ,the special definitive host (lions) ,and divergence of DNA sequences ,etc .between E . f elidis and other Echinococcus species .In brief ,the review has provided researchers and ex-perts in the field of echinococcosis with fundamental background knowledge and guidelines for future research directions ,clinical and epidemiological investigations ,and prevention and control of echinococcosis .

Research progress of genetic monitoring methods in guinea pig / 中国比较医学杂志

Guinea pig as a commonly used laboratory animal is widely used in various fields of biomedical research.The stability of genetic quality directly affects its development and application .Genetic testing is designed to confirm the genetic characteristics of each strain , to verify whether there are genetic mutations and other genetic contamination, to ensure that the test object meets the requirements of this strain .Along with the emerge of biochemical and molecular marker technology , a more convenient and reliable means is provided for research of genetic homozygosity , genetic type detection and genetic quality monitoring of guinea pigs .In this paper, the application and research progress of biochemical, cytological and molecular markers in studies of guinea pig diversity will be summarized , and provide some help for genetic testing guinea pig.

Sources of contradictions in the evaluation of population genetic consequences after the chernobyl disaster.

The review covers the analysis of our own and published data pertaining to population and genetic consequences in various mammalian species under conditions of high levels of ionizing radiation as a result of the Chernobyl accident. The findings indicate that these conditions have promoted the reproduction of heterozygotes in polyloci spectra of molecular genetic markers and animals with a relatively increased stability of the chromosomal apparatus. The prospects of using the reproductive "success" of the carriers of these characteristics as an integral indicator of the selective influence of environmental stress factors are discussed.