A novel dihydroacridine derivative targets epidermal growth factor receptor-expressing cancer cells and .

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 , and . This was an , and experimental study.

Optical polarization from colliding stellar stream shocks in a tidal disruption event.

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.

Novel Hydroxypyridine Compound Protects Brain Cells against Ischemic Damage In Vitro and In Vivo.

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.

Polarized x-rays constrain the disk-jet geometry in the black hole x-ray binary Cygnus X-1.

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.

Association of the Serum Folate and Total Calcium and Magnesium Levels Before Ovarian Stimulation With Outcomes of Fresh Fertilization Cycles in Normogonadotropic Women.

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).

Expression of p53 Protein Associates with Anti-PD-L1 Treatment Response on Human-Derived Xenograft Model of GATA3/CR5/6-Negative Recurrent Nonmuscular Invasive Bladder Urothelial Carcinoma.

Background: The possible involvement of p53 signaling, FGFR3 expression, and mutation rates in the prediction of the NMIBC anti-PD-L1 treatment response needs to be clarified. The main aim of our study was to explore predictive value of p53 expression, FGFR3 expression, and its gene mutation status for the therapeutic success of anti-PD-L1 treatment in the patient-derived murine model of recurrent high-PD-L1(+) GATA3(-)/CR5/6(-) high-grade and low-grade NMIBC.

Methods: twenty lines of patient-derived xenografts (PDXs) of relapsed high-PD-L1(+) double-negative NMIBC were developed, of which 10 lines represented high-grade tumors and the other ones-low-grade bladder cancer.

Cerium-Containing N-Acetyl-6-Aminohexanoic Acid Formulation Accelerates Wound Reparation in Diabetic Animals.

Background: The main goal of our study was to explore the wound-healing property of a novel cerium-containing N-acethyl-6-aminohexanoate acid compound and determine key molecular targets of the compound mode of action in diabetic animals.

Methods: Cerium N-acetyl-6-aminohexanoate (laboratory name LHT-8-17) as a 10 mg/mL aquatic spray was used as wound experimental topical therapy. LHT-8-17 toxicity was assessed in human skin epidermal cell culture using (4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay.

Prognostic Role of Expression Status and Tumor-Related MicroRNAs Level in Association with PD-L1 Expression in Primary Luminal Non-Muscular Invasive Bladder Carcinoma.

Background: bladder cancer is one of the most common urinary tract malignancies. Establishment of robust predictors of disease progression and outcome is important for personalizing treatment of non-muscular invasive bladder carcinoma (NMIBC). In this study we evaluated association of PD-L1 expression with other prognostic biomarkers, such as expression of miRNA-145 and miRNA-200a, gene expression, and mutation status in tissue specimens of the luminal subtype of newly diagnosed high and low grade NMIBC.

[Solitary fibrous tumor of pleura (symptoms, diagnosis, treatment)].

Objective: Optimization of diagnosis and treatment of patients with solitary fibrous tumor of pleura, analysis of overall survival and disease-free survival, predictors of recurrence.

Material And Methods: There were 66 patients with solitary fibrous tumor of pleura (26 men and 40 women) aged 57.6 years (range 26-80 years).

Relapse-Free Survival and PD-L1 Expression in First High- and Low-Grade Relapsed Luminal, Basal and Double-Negative P53-Mutant Non-Muscular Invasive Bladder Cancer Depending on Previous Chemo- and Immunotherapy.

The goal of this study was to assess how PD-L1 expression in tissue specimens of patients with main molecular subtypes of NMIBC (luminal, basal and double-negative p53-mutant) associates with relapsed-free survival in dependence on the tumor grade and prior treatment of primary bladder cancer. PD-L1 expressions on the membrane of neoplastic and CD8+ immune cells were assessed in tumor specimens ( = 240) of primary and relapsed luminal, basal and double-negative p53-mutant NMIBC. Association between relapse-free survival and PD-L1 expression was estimated for high- and low-grade relapsed NMIBC according to previous treatment and their molecular profile, using the Kaplan-Meier method, and assessed by using the log-rank test.

[Experimental study of the effectiveness of local anesthetic activity of a new dimethylphenylacetamide-containing pharmaceutical composition in chronic periodontitis].

Novel anaesthetic formulation LHT-15-32 was studied. The experimental study involved 66 white mice, 15 Rana radibunda frogs and 50 male Sprague Dawley rats. Its acute intravenous and subcutaneous toxicity was determined in mice.

Novel Dimethylacetamide-Containing Formulation Improves Infraorbital Anaesthesia Efficacy in Rats with Periodontitis.

Background: To evaluate acute toxicity and local anaesthetic activity of a formulation containing a novel dimethylacetamide derivative, antioxidant, and vasoconstrictor in rats with chronic periodontitis.

Methods: Novel anaesthetic dimethylacetamide-containing formulation LHT-15-32 was studied as 2% water solution. Its acute intravenous and subcutaneous toxicity was determined in mice.

Programmed death-ligand 1 signaling pathway involves in bladder cancer growth and progression.

Context: Exploration of the biological property of programmed death-ligand 1 (PD-L1) signaling that may impact bladder tumor growth in humanized animals and cell culture.

Aims: The aim of this study is to evaluate how PD-L1 signaling involves bladder cancer growth and progression.

Settings And Design: This study design involves experimental and study.

Patient-Derived Non-Muscular Invasive Bladder Cancer Xenografts of Main Molecular Subtypes of the Tumor for Anti-Pd-l1 Treatment Assessment.

Background: Establishment of heterotopic patient-derived xenografts of primary and relapsed non-muscular invasive bladder cancer (NMIBC) to explore the biological property of PD-L1 signaling that may impact bladder tumor growth in humanized animals.

Methods: Tumor cells of luminal, basal, and p53 subtypes of primary and relapsed NMIBC were engrafted to irradiated (3.5 Gy) NOG/SCID female mice along with intraperitoneal transplantation of human lymphocytes (5 × 10 cells/mouse); a role of PD-L1 signaling pathway inhibition for bladder cancer growth was assessed in humanized animals that carried PD-L1-expressing main molecular subtypes of bladder carcinoma patient-derived xenografts (PDX) and provided with selective anti-PD-L1 treatment.

Novel aminochromone derivative inhibits tumor growth on xenograft model of lung cancer in mice.

2-Amino-4H-chromene derivatives possess anticancer property proved on different and models of malignancies such breast, nasopharyngeal, bladder, ovary carcinomas, astrocytoma, and osteosarcoma. We assumed it might be effective to apply one of the derivatives as promising approach to lung carcinoma treatment. to evaluate how novel 4-aryl substituted 2-amino-4H-chromene derivative AX-554 impacts tumor growth and progression, as well as possible mechanisms for anticancer effect development on patient-derived heterotopic xenograft model of lung carcinoma in mice.

Aminoethane Sulfonic Acid Magnesium Salt Inhibits Ca Entry Through NMDA Receptor Ion Channel In Vitro.

The effect of a cerebroprotective agent magnesium bis-aminoethanesulfonate (laboratory code FS-LKhT-317) on intracellular calcium concentration was studied by the fluorescent imaging technique on neuroglial cell culture from Spraque-Dawley rat hippocampus. The substance produced a pronounced inhibitory effect and suppressed NMDA receptor activity in concentrations of ≥50 μM. The observed effects were reversible or partially reversible and were detected by a decrease in Ca signal amplitude in neurons in response to NMDA applications in a Mg-free medium and by inhibition of Ca pulses in magnesium-free medium (elimination of magnesium block).

[Prevalence of nonalcoholic fatty liver disease in outpatients in Rostov-on-Don: Regional results of the DIREG-2 study].

Aim: to analyze and summarize the data of the DIREG-2 study of the nonalcoholic fatty liver disease (NAFLD) register in Rostov-on-Don versus those in Russia.

Material And Methods: The prospective disease registry study encompasses an epidemiologic, observational, cross-sectional, multicenter study estimating the prevalence of NAFLD in outpatients in Rostov-on-Don. A total of 3200 patients participated in this study.

[THE STUDY OF THE EFFECTS OF ANXYOLYTIC, ANTIOXIDANT, IMMUNOCORRECTOR AND HYPERBARIC OXYGENATION ON THE DYNAMICS OF MAIN BLOOD GAS AND ELECTROLYTE INDICES AND BEHAVIORAL RESPONSE IN EXPERIMENTAL STRESS MODEL].

Experiments on the model of immobilization stress in albino mice showed that a combination of mexidol, thymogen, and hyperbaric oxygenation reduced adverse effects of diazepam on behavioral response of animals in the black-and-white chamber and elevated cross maze tests and led to optimization of the blood gas composition as manifested by increased oxygen tension, normalization of the partial pressure of carbon dioxide, and restoration of the acid-base balance and blood bicarbonate level. The proposed combined treatment can be recommended for the treatment of patients with stress-induced pathology.

A PROTECTIVE ROLE FOR MAGNESIUM 2-AMINOETHANSULFONATE IN PARACETAMOL AND ETHANOL-INDUCED LIVER INJURY IN PREGNANT RATS.

Unlabelled: The goal: to investigate a preventive activity for novel medication magnesium 2-aminoethansulfonate in experimental hepatitis in pregnant rats.

Material And Methods: The study has been conducted in firs week pregnant rats with paracetamol and ethanol-induced liver injury.

Results: There has been found out that new domestic compound magnesium 2-aminoethansulfonate (laboratory name LBK-527) introduced daily at a dose of 28 mg/kg per os during 6 days, limits cytolysis and cholestasis caused by either paracetamol or ethanol intake in experiments in pregnant rats.

[Magnesium deficiency and stress: Issues of their relationship, diagnostic tests, and approaches to therapy].

Magnesium plays an important role in the functions of the central nervous system. It takes part in the regulation of the cell membrane, the transmembrane transport of calcium and sodium ions, and metabolic reactions that produce, accumulate, transfer, and utilize energy, free radicals, and their oxidation products. The magnesium-containing substances include many sequestered antigens, such as glial fibrillary acidic protein, S100, and neuron-specific enolase; magnesium may act as a neuroprotector that is able to modulate the regulation of blood-brain barrier permeability.

[THE CLINICAL ORGANIZATIONAL SUBSTANTIATION OF NEW TECHNOLOGY OF HOSPITAL PSYCHIATRIC CARE].

The new technology of hospital psychiatric care, developed and implemented in the Mordovia republican clinical hospital, permits resolving problems of hospitalism, lethality, pharmaceutical resistance and others. The essence of this technology is in staging of hospital care under condition of intensification and standardization of curative diagnostic process, implementation of complex approach to treatment of psychiatric disorders. The patient sequentially passes through three stages: intensive diagnostics and intensive treatment (intensive care department, intensive therapy department), supportive therapy (general psychiatric department); rehabilitation measures (curative rehabilitative department).

[Hygienic characteristics of the population's morbidity rate associated with iodine deficiency in the Republic of Mordovia].

In the article there are presented the results of research on naturally conditioned insufficiency of trace elements, particularly iodine, in the Republic of Mordovia. Iodine deficiency disorders are referred to the most common non-infectious human pathology. According to WHO data, about two billion people on Earth live in conditions of in iodine deficiency.

[Comparative study of the toxicity and antiarrhythmic activity of some organic derivatives of dimethylacetamide].

A comparative study of the acute toxicity and antiarrhythmic activity of new domestic derivatives of dimethylacetamide showed that the introduction of amino and carboxylic acid residues into the structure of compounds is accompanied by reduction of the toxic properties of new substances on the average 2.73 times (p = 0.002) upon intraperitoneal introduction to animals.

Error correction in intracellular transport: numerical investigation of rerouting of a pulse of misdirected axonal cargos in a dendrite.

This paper develops a transient three-kinetic state model that simulates rerouting of a pulse of axonal cargos that were initially misdirected to a dendrite. The following three cargo populations are included in the model: (i) anterogradely running cargos, (ii) retrogradely running cargos, and (iii) free (diffusion-driven) cargos that are detached from microtubules. The dynamics of cargo concentrations in various kinetic states are studied.