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Introduction: EGFR-activating overexpression or somatic mutations are common in different human cancers. In this regard, the search for promising ways to control the carcinogenic transformation of tumor cells and the progression of malignant tumors expressing EGFR seems to be one of the most promising and developing areas of modern molecular pathology and pharmacology. Material and Methods: An antitumor activity of a novel compound, a pyridine carboxylic acid derivative LHT-17-19, was studied. The molecule was developed and synthesized at the Department of Chemistry, Drug Design and Technology of All-Russian Research Center for Biological Active Compounds Safety (Russia). The study was carried out in cell cultures of stomach cancer (Hs746T, AGS and MKN1) and patient-derived organoid (PDO) model of breast cancer (BC) expressing wild-type EGFR. Results: It was shown that LHT-17-19 induced concentration-dependent cytotoxicity of EGFR-expressing gastric cancer cells of all the aforementioned cultures. Pathomorphological, immunohistochemical and molecular validation of BC organoids derived from ductal breast carcinoma cells of a 68-year-old patient was done. PDOs were established as ER-negative, PR-negative, Her2/neu-negative, EGFR-positive with 35% of the Ki-67 expression index. In addition, the tumor cells translocation was resulted in a loss of ER expression and PDOs molecular pattern conversion towards a more aggressive triple negative type. PDOs incubation with 0.5-60.0 µM LHT-17-19 was accompanied not only by inhibition of their growth and proliferation, but also by significant cytoreduction. Conclusion: Thus, in two-dimensional and three-dimensional tumor cell cultures, the possibility of controlling the oncogenic expression of EGFR with the acridone compound 9-ammonium-3,3-dimethyl-3,4-dihydroacridine-1(2H)-OH L-2-hydroxybutanedivacate (LHT-17-19) was shown.

The paper notes the potential for enhancing seed productivity through exposure to an electromagnetic field. It touches upon both theoretical and practical considerations for developing an experimental laboratory plant for pre-sowing seed treatment using a low-frequency electromagnetic field and aiming to achieve a magnetobiological effect. (Research purpose) The study aims to investigate the influence of low-frequency electromagnetic field on the composition and properties of grain seeds. (Materials and methods) Standard emitters, characterized by a magnetic induction variability of 3-75 millitesla and a radiation frequency of 1-100 Hertz, were employed to ensure the necessary treatment parameters for a batch of seeds. (Results and discussion) The study investigates the impact of magnetization on the germination process, germination energy, and the physical and chemical properties of seeds subjected to different parameters of a low-frequency electromagnetic field (ranging from 3 to 75 millitesla in magnetic induction and a radiation frequency of 10-16 Hertz).The quality of the effect was analyzed with respect to the installation parameters and seed mass, ranging from 10 to 500 grams, across various cereal crops. Subsequently, specific modes were identified, and a functional irradiation program was devised to ensure a highly effective impact on seeds, optimizing their germination, sprouting and development. (Conclusions) The impact of a low-frequency electromagnetic field on the composition and properties of grain has been studied. An experimental laboratory plant with sources of a low-frequency electromagnetic field has been developed and irradiation modes have been justified. The pre-sowing treatment of an industrial batch, the magnetobiological effect is contingent upon several factors, including the crop type and variety, activation of a biological complex in a cell that initiates the development of a seedling, seed quality and moisture content, the presence of microorganisms on the surface, pathogenic ones included, and the characteristics of irradiation sources and energy parameters. The parameters of the low-frequency electromagnetic field were determined as follows: magnetic induction ranging from 3 to 75 millitesla, a frequency 10-16 Hertz, and seed weight varying from 10 to 500 grams. These identified parameters will be applied in the development of an industrial unit designed for the preparation of seed material and enhancement of its sowing properties.

For the efficient production and processing of milk, it is important to control its quality indicators. Optical spectroscopy, in combination with statistical analysis methods, can be a useful method of evaluation due to its speed, non-invasiveness, and relative cheapness. This investigation is aimed at studying of the interrelations of the spectral patterns, the absorption parameters, and the photoluminescence values of cow’s milk during its souring. The spectral characteristics of excitation and photoluminescence were measured on a diffraction spectrofluorometer in the range of 200–500 nm. For establishing an effective control procedure during milk souring, the most informative method is found to be the use of the excitation wavelengths of 232 nm, 322 nm, 385 nm and 442 nm. These ranges correspond to the amino acids of milk proteins, the fatty acids of milk fat, and the aromatic fragments of vitamins. When using the photoluminescence flux ratios Φ232/Φ322 and Φ385/Φ442, linearly approximated dependences on acidity can be obtained with determination coefficients of 0.88–0.94. The proposed photoluminescent method can be used as a non-destructive and fast-acting tool for monitoring the properties of milk during fermentation, as well as for the subsequent creation of a portable and inexpensive sensor based on this method.

Small molecules are considered a source of novel medicines targeting carcinogenic intracellular pathways including epidermal growth factor receptor (EGFR) signaling. The main goal of the study is to assess whether LHT-17-19 could be considered an effective target molecule against EGFR-expressing tumor cells in silico , in vitro, and in vivo . This was an in vivo , ex vivo, and in vivo experimental study. LHT-17-19 affinity to EGFR's kinase domain was assessed by the ligand's molecular docking. EGFR-expressing Hs746T human gastric cancer cell culture and patient-derived organoid (PDO) model of EGFR-positive breast cancer (BC) were used for in vitro assessment of the molecule anticancer property. IC 50 and GI 50 indexes were estimated using MTT- and MTS-based tests, respectively. Anticancer activity of LHT-17-19 against EGFR-expressing mutant lung carcinoma was studied on patient-derived xenograft (PDX) model established in 10 humanized BALB/c male mice. Continuous variables were presented as a mean ± standard deviation. Intergroup differences were assessed by two-way t -test. Kaplan-Meier's curves were used for survival analysis. High affinity of LHT-17-19 for the EGFR kinase domain with dG score -7.9 kcal/mol, EDoc-5.45 kcal/mol, and Ki 101.24 uM was due to intermolecular π-σ bonds formation and the ligand intramolecular transformation. LHT-17-19 induced anti-EGFR-expressing gastric cancer cells cytotoxicity with IC 50 0.32 µM (95% confidence interval [CI] 0.11-0.54 µM). The derivative inhibited growth of EGFR-expressing BC PDO with GI 50 16.25 µM (95% CI 4.44-28.04 µM). 2 mg/kg LHT-17-19 intravenously daily during 7 days inhibited PDX tumor growth and metastatic activity, prolonged animals' survival, and eliminated EGFR-mutant lung cancer cells from residual tumor's node. LHT-17-19 may be considered a molecular platform for further search of promising molecules, EGFR-expressing cancer cell inhibitors., Competing Interests: There are no conflicts of interest., (Copyright: © 2024 Journal of Advanced Pharmaceutical Technology & Research.)

A tidal disruption event (TDE) occurs when a supermassive black hole rips apart a passing star. Part of the stellar material falls toward the black hole, forming an accretion disk that in some cases launches a relativistic jet. We performed optical polarimetry observations of a TDE, AT 2020mot. We find a peak linear polarization degree of 25 ± 4%, consistent with highly polarized synchrotron radiation, as is typically observed from relativistic jets. However, our radio observations, taken up to 8 months after the optical peak, do not detect the corresponding radio emission expected from a relativistic jet. We suggest that the linearly polarized optical emission instead arises from shocks that occur during accretion disk formation, as the stream of stellar material collides with itself.

A black hole x-ray binary (XRB) system forms when gas is stripped from a normal star and accretes onto a black hole, which heats the gas sufficiently to emit x-rays. We report a polarimetric observation of the XRB Cygnus X-1 using the Imaging X-ray Polarimetry Explorer. The electric field position angle aligns with the outflowing jet, indicating that the jet is launched from the inner x-ray-emitting region. The polarization degree is 4.01 ± 0.20% at 2 to 8 kiloelectronvolts, implying that the accretion disk is viewed closer to edge-on than the binary orbit. These observations reveal that hot x-ray-emitting plasma is spatially extended in a plane perpendicular to, not parallel to, the jet axis.

A non-surgical pharmacological approach to control cellular vitality and functionality during ischemic and/or reperfusion-induced phases of strokes remains extremely important. The synthesis of 2-ethyl-6-methyl-3-hydroxypyridinium gammalactone-2,3-dehydro-L-gulonate (3-EA) was performed using a topochemical reaction. The cell-protective effects of 3-EA were studied on a model of glutamate excitotoxicity (GluTox) and glucose-oxygen deprivation (OGD) in a culture of NMRI mice cortical cells. Ca 2+ dynamics was studied using fluorescent bioimaging and a Fura-2 probe, cell viability was assessed using cytochemical staining with propidium iodide, and gene expression was assessed by a real-time polymerase chain reaction. The compound anti-ischemic efficacy in vivo was evaluated on a model of irreversible middle cerebral artery (MCA) occlusion in Sprague-Dawley male rats. Brain morphological changes and antioxidant capacity were assessed one week after the pathology onset. The severity of neurological disorder was evaluated dynamically. 3-EA suppressed cortical cell death in a dose-dependent manner under the excitotoxic effect of glutamate and ischemia/reoxygenation. Pre-incubation of cerebral cortex cells with 10-100 µM 3-EA led to significant stagnation in Ca 2+ concentration in a cytosol ([Ca2+]i) of neurons and astrocytes suffering GluTox and OGD. Decreasing intracellular Ca 2+ and establishing a lower [Ca2+]i baseline inhibited necrotic cell death in an acute experiment. The mechanism of 3-EA cytoprotective action involved changes in the baseline and ischemia/reoxygenation-induced expression of genes encoding anti-apoptotic proteins and proteins of the oxidative status; this led to inhibition of the late irreversible stages of apoptosis. Incubation of brain cortex cells with 3-EA induced an overexpression of the anti-apoptotic genes BCL-2 , STAT3 , and SOCS3 , whereas the expression of genes regulating necrosis and inflammation ( TRAIL , MLKL , Cas-1 , Cas-3 , IL-1β and TNFa ) were suppressed. 3-EA 18.0 mg/kg intravenous daily administration for 7 days following MCA occlusion preserved rats' cortex neuron population, decreased the severity of neurological deficit, and spared antioxidant capacity of damaged tissues. 3-EA demonstrated proven short-term anti-ischemic activity in vivo and in vitro, which can be associated with antioxidant activity and the ability to target necrotic and apoptotic death. The compound may be considered a potential neuroprotective molecule for further pre-clinical investigation.

Background: Women of reproductive age are recommended to consume folic acid and other supplements before conception and during pregnancy. We aimed to investigate the association of the serum folate and total magnesium (Mg) and calcium (Ca) levels before ovarian stimulation with the outcomes of assisted reproductive technology (ART) in normogonadotropic women., Methods: We used a subanalysis of data obtained from a multicentre, randomized prospective study (NCT03088137). A total of 110 normogonadotropic, non-advanced aged, non-obese women with tubal and/or male infertility factors were enrolled for the single fresh ovarian stimulation GnRH antagonist cycle. The main outcome measures were the total oocyte yield, mature oocytes, fertilization rate, biochemical, clinical pregnancy, and live birth. Multivariable generalized linear models adjusted for covariates were used with a Poisson distribution and the log link function for adjusted oocyte counts, and a binomial distribution and the log link function were used for adjusted clinical ART outcomes., Results: The medians (interquartile range (IQR)) were as follows: baseline serum folate, 20.55 ng/ml (10.8, 32.9); Mg, 19.4 mg/L (18.7, 20.7); Ca, 94 mg/L (91.2, 96.4); and Ca/Mg ratio, 4.78 (4.55, 5.02). Women with higher serum folate concentrations (Q4≥33.0 ng/ml) had significantly lower total numbers of oocytes retrieved (adjusted mean (95% CI) 9.2 (7.6-11.3) vs 12.9 (10.9-15.4, p-trend=0.006)) and lower odds ratios (ORs) (95% CI) of 0.12 (0.02, 0.79) for clinical pregnancy and 0.10 (0.01, 0.70) for live birth compared with women in the lowest quartile (<10.8 ng/ml), all p-trend<0.001. Women in the highest Ca/Mg ratio quartile (≥5.02) had ORs (95% CI) of 6.58 (1.31, 33.04) for biochemical pregnancy, 4.85 (1.02, 23.08) for clinical pregnancy and 4.07 (0.83, 19.9) for the live birth rate compared with women in the lowest quartile (<4.55), all p-trend<0.001., Conclusions: Using multivariable models, we suggested that a baseline elevated serum folate level (≥33.0 ng/ml) and a lower Ca/Mg ratio were associated with worse ART outcomes in normogonadotropic women. Our findings might be useful for choosing safe dosages of folate, calcium, magnesium and complex supplementation for both fertile women and women undergoing infertility treatment. Further preconception large-scale studies with known micro- and macronutrient statuses of both parents and serum folate, Ca, Mg, and hormone levels, are needed., Competing Interests: MP is employed by IVFarma LLC; the parental study NCT03088137 was financed by IVFarma LLC. DB served as a medical affairs consultant to Sanofi, Merck and Dr. Reddy’s. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Polzikov, Blinov, Barakhoeva, Vovk, Fetisova, Ovchinnikova, Tischenko, Zorina, Yurasov, Ushakova and Sergeyev.)