Oncolytic viral therapy for gliomas: Advances in the mechanisms and approaches to delivery.

Glioma is a diverse category of tumors originating from glial cells encompasses various subtypes, based on the specific type of glial cells involved. The most aggressive is glioblastoma multiforme (GBM), which stands as the predominant primary malignant tumor within the central nervous system in adults. Despite the application of treatment strategy, the median survival rate for GBM patients still hovers around 15 months. Oncolytic viruses (OVs) are artificially engineered viruses designed to selectively target and induce apoptosis in cancer cells. While clinical trials have demonstrated encouraging results with intratumoral OV injections for some cancers, applying this approach to GBM presents unique challenges. Here we elaborate on current trends in oncolytic viral therapy and their delivery methods. We delve into the various methods of delivering OVs for therapy, exploring their respective advantages and disadvantages and discussing how selecting the optimal delivery method can enhance the efficacy of this innovative treatment approach.

Conversion of polyethylene terephthalate waste into high-yield porous carbon adsorbent via pyrolysis of dipotassium terephthalate.

A method for conversion of polyethylene terephthalate (PET) waste into porous carbon material is proposed. The recycling of PET bottle waste includes the stages of low-temperature hydrolysis of the polymer and subsequent pyrolysis at 800 °C. To provide PET hydrolysis at âˆ¼150 °C and atmospheric pressure, the polymer was pre-dissolved in dimethyl sulfoxide and then an aqueous solution of potassium hydroxide was added. The potassium terephthalate formed as a result of the alkaline hydrolysis of PET allows the carbon-containing precursor to be preserved for further activation to temperatures beyond 600 °C. The proposed method leads to the formation of a porous carbon material, increasing the yield of carbon residue to 25 wt%, which is higher compared to the yield of carbon residue in the direct pyrolysis of PET. The obtained porous carbon is characterized by graphite-like structure and specific surface area of âˆ¼1100 m2 g-1. It has been shown that PET-derived carbon material can be used to remove pollutants from aqueous media. The adsorption properties of the carbon material were demonstrated by adsorption of methylene blue from an aqueous solution. The capacity of the carbon material was found to be 443 mg g-1.

A study of prostate multiprobe cryoablation near urethra for precision treatment planning.

The simplified preoperative planning of multiprobe prostate cryoablation limits its efficiency. In order to improve it, the thermal history prediction software is being developed. However, the problem of high risks at the prostate-urethra boundary has not been solved yet. The urethral warming system is used to protect the urethral canal from freezing. On the one hand it is used to reduce the risk of damage to the urethra; on the other hand it increases the risk of insufficient ablation of the tumor. This paper presents a step towards the possibility of carrying out the precision prostate cryoablation in this region. For the experimental part, three cases of arrangement of one and two argon cryoprobes and a heating catheter have been considered. Freezing zone shape and dimensions, and temperature at control points depending on time have been obtained. Experimental results have clearly shown the effect of the heating catheter, the second cryoprobe, and the initial temperature of the biotissue phantom on the freezing zone. After, the thermal aspects of treatment simulation have been developed and verified. A series of calculations have been carried out with the goal to get the information about optimizing the prostate cryoablation on the prostate-urethra boundary. The arrangement of cryoprobes has been proposed for three different variants for prostate cryoablation (sectors of 90, 180° and 360°). The area of prostate tissues near the urethra that cannot be cooled below the necrosis temperature is shown. This information is expected to be useful for improving the quality of cryosurgery planning algorithms (e.g. for tumor treatment).

[The TLR3 induction increases content of interferons in rat's brain by TRAIL signaling during long-term alcoholization]. / Induktsiia TLR3 pri dlitel'noi alkogolizatsii uvelichivaet soderzhanie interferonov v golovnom mozge u krys posredstvom TRAIL-signalizatsii.

The pathogenetic mechanisms associated with alcohol use include dysregulation of the innate immune system mechanisms in the brain. TLR3 expression is increased in the postmortem material of the prefrontal cortex of humans. An increase in the TLR3 signaling activity leads to the induction of interferons (IFN). IFN are associated with depressive symptoms and, therefore, may play a role in the pathogenesis of alcoholism; however, the exact mechanisms of intracellular signaling mediated by the influence of ethanol are not fully elucidated and their study was the purpose of this work. The experimental results showed that ethanol and the TLR3 agonist Poly (I:C) increased the content of TLR3, IFNß, and IFNγ mRNA in the prefrontal cortex. In addition, expression of the TRAIL encoding gene also increased, and this increase positively correlaed with the mRNA content of TLR3, IFNß and IFNγ both under alcoholization conditions and after injections of the TLR3 agonist. The data obtained may indicate that alcoholization is able to activate TLR3-TRAIL-IFN-signaling in the prefrontal cortex of the brain.

Assessing exterior egg quality indicators using machine vision.

1. The objective of this study was to develop a machine vision method for analysing exterior parameters of chicken eggs to automate the stage of primary sorting. 2. The developed algorithm based on predetermined thresholds calculated egg quality indicators, including geometric dimensions, shape index and the mottling grade. The algorithm was implemented with an experimental setup that combined the image-based and the candling methods. A total of 400 egg samples were analysed. 3. Comparison of results of the algorithm with those obtained using the traditional manual method showed that mean value of radii values difference was 0.095 ± 0.058 mm for the sharp and 0.080 ± 0.047 mm for the blunt end of the egg, with standard deviations of 0.58 mm and 0.49 mm, respectively. 4. The correlation coefficient between the shape index values determined by the two methods was 0.93; the standard deviation of absolute differences between corresponding values was 1.05%. 5. The results of mottling grade estimation were compared using F-measure and confusion matrix. 6. The results allow the possibility to perform the assessment of egg exterior quality factors in an automatic mode, independent of the expertise of a grader.

[Structural features of the lipid bilayer of the red blood cell membrane in people with isolated hypercholesterolemia without coronary artery disease and in patients with coronary artery disease]. / Strukturnye osobennosti lipidnogo bisloia éritrotsitarnoi membrany u lits s izolirovannoi giperkholesterinemiei bez ishemicheskoi bolezni serdtsa i bol'nykh s ishemicheskoi bolezn'iu serdtsa.

AIM: To identify the specific features of modifying the lipid composition of the red blood cell membrane in people with isolated hypercholesterolemia without coronary heart disease (CHD) and in CHD patients with different functional classes of angina pectoris. SUBJECTS AND METHODS: 92 men with Functional Class II-IV stable angina, 22 men with isolated hypercholesterolemia (HC) without CHD, and 18 healthy men with normal cholesterol levels were examined. Blood plasma cholesterol levels were determined in all the examinees. The erythrocyte membrane was examined for the levels of lipid peroxidation (LPO) products, free cholesterol, calcium, and phospholipid fractions and for the activity of Na+/K+-, Mg2+- and Ca2+-ATPases; a bicycle exercise test was carried out. RESULTS: As compared with persons with normal blood cholesterol levels, the examinees with HC without CHD were found to have higher levels of LPO products, lower levels of readily oxidizable phospholipid fractions, decreased activity of membrane-bound Na+/K+-, Mg2+-, and Ca2+-ATPases, and elevated concentrations of free cholesterol and calcium in the red blood cell membrane. Having the pronounced activity of free radical oxidation, the patients with CHD were detected to have deeper similar structural changes in the cell membrane, which became more severe with a larger number of affected coronary arteries. CONCLUSION: The findings suggest that the lipid structure of the cell membrane undergoes changes associated with its functional depression just at the preclinical stage of atherogenesis. Biomembrane structural modification in patients with angina pectoris progresses in proportion to the number of affected coronary arteries, by limiting the functional reserve of the cell and whole body.

[Development of a technique for the determination of inulin in natural instant chicory after enzymatic hydrolysis by high-performance liquid chromatography].

A highly specific technique for estimating inulin content in natural instant chicory based on the determination of fructose after enzymatic hydrolysis with amyloglucosidase and inulinase by high-performance liquid chromatography with refractometric detection has been developed. Determination of inulin content was carried out by a system for high performance liquid chromatography Agilent 1260 Series with a refractometer, Waters Sugar-Pak column of 10 µm × 6.5 mm × 300 mm: isocratic elution mode (mobile phase - water) with a flow rate of 0.5 ml/min, column temperature - 80 °C, injected sample volume - 10 µl. Inulin content in samples of soluble natural chicory ranges from 4 to 25%. It has been shown that the developed technique can be applied in the quality control of products used for the preparation of soluble natural chicory beverages.

[Genome-wide analysis of DNA methylation in prostate cancer using the technology of Infinium HumanMethylation450 BeadChip (HM450)].

Using the technology of DNA chips Infinium HumanMethylation 450 BeadChip it was analyzed quantitative DNA methylation status in 12 paired samples of prostate adenocarcinoma, and morphologically altered tissues. Analysis of differentially methylated regions of the genome showed an association with abnormal status for 21610 and 3852 hypomethylated hyper-methylated CpG sites. Dominance in the cancer genome hypermethylated sites and their predominant localization in the regulatory regions of genes indicate their possible role in the implementation of mechanisms of gene suppression in the pathogenesis of prostate cancer (PCa). For 14 genes studied were characterized array maximum values hypermethylation in promoter region (> 50% CpG sites) in combination with a high level of methylation differences between treatment groups (> 40%). Role of hypermethylation in some of them: AOX1, KLF8, ZNF154, TMEM106A in the pathogenesis of prostate cancer has been showed previously. Hypermethylation of genes ACSS3, TAC1, TUBA4B, ZSCAN12 not previously been shown for prostate cancer, but is characterized by the association with other cancers. In turn, the differences in the levels of methylation in genes GPRASP1, NKX2-6, ARX, CYBA, EPSTI1, RHCG been documented as a result of a number of genome-research oncology, but has not been studied in detail. To assess the diagnostic potential of epigenetic markers of prostate cancer there was carried out unbiased selection of individual CpG sites most reliably discriminate against tumor samples from a group of no tumor samples. In selected diagnostic model based on logistic regression included 9 CpG sites. Validation of the model was carried out on an independent dataset of methylation of 40 paired samples from the prostate cancer project Atlas of Cancer Genome (TCGA) analyzed on the same version of the DNA chip. Summarized rates of diagnostic informativeness of a model (specificity 95%, sensitivity of 97%, the area under the curve of the diagnostic test (ROC) - 0,96), obtained after validation, allow us to consider these CpG Sites as potential markers for molecular diagnosis of prostate cancer.

Synthesis and crystal structure of a new hexagonal perovskite 7H-Ba7Li1.75Mn3.5O15.75 with Mn(4+)/Mn(5+) charge distribution.

Ba7Li1.75Mn3.5O15.75 is a new hexagonal perovskite whose crystal structure has elements typical for the layered hexagonal perovskites and quasi-one-dimensional oxides, hence representing a new polytype. It has been synthesized via a solid-state microwave route. The crystal structure was solved using a combination of X-ray and neutron diffraction data, which show that Ba7Li1.75Mn3.5O15.75 crystallizes in a hexagonal unit cell with parameters a = 5.66274(2) Å and c = 16.7467(1) Å (V = 465.063(4) Å(3)), with one formula unit, and can be described as columns of face-shared octahedra occupied by Mn(4+) and Li(+) cations and vacancies along the c axis separated in the ab plane by barium atoms. Every sixth layer, the coordination of Mn(5+) and Li(+) changes to tetrahedral. Additional local ordering of manganese and lithium atoms among cationic sites leading to the formation of a rhombohedral supercell has been observed by scanning transmission electron microscopy.

[Influence of mediator diffusion on trigger mode of a synapse].

The model of postsynaptic membrane activation, is proposed in the paper. This model takes into account inhomogeneity of mediator's space distribution in the region of the synaptic cleft as well as nonlinear nature of interaction between the mediator and receptors on the postsynaptic membrane. Based on equations of this model stationary solutions are calculated for mediator distribution in the synaptic cleft and the number of activated receptors. Kinetics of reactions for activation and deactivation of receptors is analyzed within the concept of a trigger mode of the synapse. It is shown that activation-deactivation processes and redistribution of the mediator in the cleft can be interpreted as successive transitions between two stationary states of the system. Time of transitions between these states is found and its dependence on system parameters (in particular on the width of the synaptic cleft) is analyzed.

Pancreatic fat necrosis and hemorrhagic necrosis as separate morphological and functional entities.

Peculiarities of pathomorphogenesis of two destructive forms of acute pancreatitis were compared using three experimental models. We have shown that the direction of the pathological process is determined by specific combinations of pathogenic factors. Pathological processes caused by common bile duct ligation (ductal hypertension) alone and in combination with injection of phospholipase A2 are characterized by mixed pattern with strong predominance of fat necrosis symptoms (coagulative acinar necrosis, inflammatory demarcation, and sites of lipolysis) and hemorrhagic necrosis, respectively. Trypsin injection into the pancreatic tissue induces rapidly progressing hemorrhagic pancreatic necrosis with massive hemorrhages, extensive acinar necrosis, and weak cell reaction. Considerable differences in pathomorphogenesis and outcome of the pathological process allow us to consider pancreatic fat necrosis and hemorrhagic necrosis as separate morphological and functional entities, which is essential for the prognosis and treatment strategy.

[1,10-phenantroline europium complexes: their inclusion in liposomes and cytotoxicity].

For a series of 1,10-phenantroline tris-beta-diketonate europium complexes (EuC), cytotoxic activity on the HBL-100 human breast carcinoma cells was determined. Liposomal preparation of the most active EuC, V12, was also tested for cytotoxicity. Testing of this preparation in vivo on starting lethal murine model of T cell leukemic lymphoma ASF-LL showed that the inclusion of V12 in liposomes did not increase its antitumour activity in a local mode of administration.

Synthesis and spectral properties of novel fluorescent poly(oxyethylene phosphate) tris(beta-diketonate) europium (III) complexes.

Novel poly(oxyethylene phosphate) tris(beta-diketonate) europium (III) complexes have been synthesized by an improved procedure using the Atherton-Todd reaction conditions. N-ethyldiisopropylamine has been used as a mild base and propylene oxide as an acid scavenger in order to obtain poly(oxyethylene phosphate) in yield and purity higher than those achieved by conventional methods. The compounds have been characterized by 1H, 13C, and 31P NMR and FTIR techniques. Their absorption, fluorescent excitation and emission spectra of chloroform and abs. ethanol solutions have been recorded and studied. The luminescent quantum yields and decay times have been determined and a dependence on the length of the oxyethylene spacer between phosphate groups has been established. The new polymer complexes are water soluble and have increased luminescence decay time in comparison with corresponding ternary complexes.

Hemorheological and cerebroprotective activity of Lychnis chalcedonica L. extract in rats with cerebral ischemia.

Considerable hemorheological changes and depression of EEG parameters were revealed in rats with cerebral ischemia. Course peroral treatment with scarlet lightning extract in a daily dose of 150 mg/kg for 5 days reduced the severity of hemorheological disorders. It manifested in a decrease in whole blood viscosity, plasma viscosity, erythrocyte aggregation, and fibrinogen concentration and increase in deformability. The extract of lightning extract improved EEG activity in rats with cerebral ischemia.

[Diagnostic significance of type IV collagen and hyaluronic acid in the serum of patients with chronic hepatitis C for staging hepatic fibrosis].

AIM: To evaluate diagnostic value of serologic fibrosis markers (hyaluronic acid--HA and type IV collagen C-IV) in patients with chronic hepatitis C (CHC) and hepatic cirrhosis (HC). MATERIAL AND METHODS: HA and C-IV were measured in 88 CHC patients with fibrosis stage 1 (n = 63) and 3 (n = 25), 13 patients with acute hepatitis C (AHC), 28 patients with hepatic cirrhosis (HC), 19 patients with pulmonary fibrosis (PF). The control group consisted of 32 healthy subjects. RESULTS: HA concentrations in the serum of CHC patients with mild to severe inflammation and fibrosis (F1 and F3) were normal (100 ng/ml). For HC diagnosis, HA test proved highly sensitive and specific (in HA 100 ng/ml sensitivity was 100%, specificity 84.6%), but this method cannot stage hepatic fibrosis. HA test was inferior to C-IV test. A mean C-IV concentration in the serum of CHC patients at the stage of marked fibrosis (F3) is significantly higher than in F1, in HC (A) patients higher than in patients with CHC F3. CONCLUSION: It is shown than concentration of C-IV above 196 ng/ml can differentiate fibrosis stage 1 from stage 3 with specificity 58.7 and sensitivity 88%.

[Invariants of spatial summation for S (short wavelength) cone vision]. / Invarianty prostranstvennoi summatsii dlia S (korotkovolnovogo) kolbochkovogo zreniia.

Spatial summation in the human visual system was studied as a function of retinal eccentricity upon selective stimulation of the short-wavelength sensitive cones. The area of complete spatial summation (Ricco's area) was found to increase with retinal eccentricity while the threshold of stimuli equal in size with Ricco's area remained constant. Comparisons with known morphology of the small bistratified retinal ganglion cells, the only cells known to be excited by S-one ON stimulation, showed that Ricco's area included 2-4 such cells and is up to 1.5 times larger than the dendritic field of a single cell. These relationships were relatively constant within the eccentricity range tested (5-20 deg along the temporal horizontal meridian) and might be the source of threshold invariance of stimuli matching Ricco's area.

[Study of mineral saturation of lumbar vertebral bones in th course of systemic exposure to +Gz accelerations]. / Issledovanie mineralnoi nasyshchennosti kostnoi tkani poiasnichnykh pozvonkov v protsesse sistematicheskogo vozdeistviia peregruzok +Gz.

Of a pressing aspect of pilots' exposure to high levels of head-to-seat accelerations (+Gz) is the high risk of vertebral traumatization. In this connection, mineral saturation of the lumbar vertebral in test subjects systematically exposed to +Gz accelerations on centrifuge over two months and pilots of highly manouevrable fighters has been investigated. Results of the study point it out that systematic flight g-loads bring about an increase in vertebral bone mineralization. Thus, following a series of +Gz exposures of the test subjects the integrated content of mineral substances and the density of structural composition of vertebrals Z2-Z4 showed the average rises by 4.6% and 4.15%, respectively; however, the same parameters in the pilots were higher than in the control group by 8.8% and 10.6%, respectively. The paper discusses possible mechanisms underlying these phenomena.

[Prevalence of tuberculosis and chronic non-specific lung diseases in the towns of the Far North]. / Rasprostranennost tuberkulëza i khronicheskikh nespetsificheskikh boleznei lëgkikh v poselkakh Krainego Severa.

In the settlements of the Far North there is a significant reservoir of tuberculosis infection that makes up 40% and 16% in the aborigines and migrants, respectively. The alarming epidemiological prognosis, as well as the developmental association and the coincidence of clinical and social groups at risk for specific and non-specific abnormalities make it expedient to maintain annual mass fluorographic examinations by using screenings to detect the groups to be studied with auxiliary techniques and to actively detect chronic non-specific respiratory diseases.

[Hemostasis in hens with exposure to low-dose gamma-irradiation in the embryonal period]. / Sistema gemostaza kur pri deistvii malykh doz gamma-oblucheniia v émbrionalnom periode.

Exposure of hen's eggs to irradiation by doses 0.05-1.66 Gy (dose rate 2.56x10-4 Gy/s) in early embryonal period (1st day of incubation of eggs doesn't essentially affect on indices of functional state of haemostasis system of two-month aged individuals, except the activation of contact phase of blood coagulation, in which a hypercoagulation shift within normal fluctuations has been noted.

[DNA synthesis and DNA and RNA content in lymphocytes with x-ray irradiation in guinea pigs]. / Sintez DNK i soderzhanie DNK i RNK v limfotsitakh morskikh svinok pri deistvii rentgenovskogo izlucheniia.

A study was made of the effect of X-radiation (2.6 and 180.6 mC/kg) on proliferative activity and DNA and RNA content of guinea pig lymphocytes. There was a considerable decrease in proliferative activity and a slight increase in DNA and RNA content in 24 h after irradiation.