Targeting Cholesterol Biosynthesis with Statins Synergizes with AKT Inhibitors in Triple-Negative Breast Cancer.

Triple-negative breast cancer (TNBC) is responsible for a disproportionate number of breast cancer patient deaths due to extensive molecular heterogeneity, high recurrence rates, and lack of targeted therapies. Dysregulation of the phosphoinositide 3-kinase (PI3K)/AKT pathway occurs in approximately 50% of TNBC patients. Here, we performed a genome-wide CRISPR/Cas9 screen with PI3Kα and AKT inhibitors to find targetable synthetic lethalities in TNBC.

[Effectiveness of physical rehabilitation methods based on the impact of eccentric load in upper limb injuries].

Unlabelled: The rehabilitation of patients after upper limb injuries is becoming increasingly relevant in current medical practice considering that this pathology is often occurred in professional athletes, elderly people, people with active lifestyle.

Objective: To study the effectiveness of isolated therapeutic exercises (TE) with eccentric muscle loads when using rubber cable compared to traditional TE to restore functional capabilities of patients after upper limb injuries.

Material And Methods: The study included 38 patients with upper limb injuries diagnosed by orthopedic surgeon.

Inhibition of Ephrin B2 Reverse Signaling Abolishes Multiple Myeloma Pathogenesis.

Unlabelled: Bone marrow vascular endothelial cells (BM EC) regulate multiple myeloma pathogenesis. Identification of the mechanisms underlying this interaction could lead to the development of improved strategies for treating multiple myeloma. Here, we performed a transcriptomic analysis of human ECs with high capacity to promote multiple myeloma growth, revealing overexpression of the receptor tyrosine kinases, EPHB1 and EPHB4, in multiple myeloma-supportive ECs.

Differences in syncytia formation by SARS-CoV-2 variants modify host chromatin accessibility and cellular senescence via TP53.

Coronavirus disease 2019 (COVID-19) remains a significant public health threat due to the ability of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants to evade the immune system and cause breakthrough infections. Although pathogenic coronaviruses such as SARS-CoV-2 and Middle East respiratory syndrome (MERS)-CoV lead to severe respiratory infections, how these viruses affect the chromatin proteomic composition upon infection remains largely uncharacterized. Here, we use our recently developed integrative DNA And Protein Tagging methodology to identify changes in host chromatin accessibility states and chromatin proteomic composition upon infection with pathogenic coronaviruses.

Differences in syncytia formation by SARS-CoV-2 variants modify host chromatin accessibility and cellular senescence via TP53.

COVID-19 remains a significant public health threat due to the ability of SARS-CoV-2 variants to evade the immune system and cause breakthrough infections. Although pathogenic coronaviruses such as SARS-CoV-2 and MERS-CoV lead to severe respiratory infections, how these viruses affect the chromatin proteomic composition upon infection remains largely uncharacterized. Here we used our recently developed integrative DNA And Protein Tagging (iDAPT) methodology to identify changes in host chromatin accessibility states and chromatin proteomic composition upon infection with pathogenic coronaviruses.

The impact of fever as a testing indication on the detection rate of deep vein thrombosis in neurocritically ill patients.

Aim: Deep vein thrombosis (DVT) is considered a possible source of non-infectious, non-central fever in the intensive care unit (ICU). In the neurocritically ill, it is unknown whether lower extremity venous Doppler ultrasonography (LEVDUS) for DVT in the setting of fever leads to a higher detection rate than the baseline detection rate of DVT in this population. The aim of this study was to compare the DVT detection rate of LEVDUS performed for the indication of fever to LEVDUS performed for other indications in a neurosciences ICU.

Implication of integrin α5β1 in senescence of SK-Mel-147 human melanoma cells.

Downregulation of α5β1 integrin in the SK-Mel-147 human melanoma culture model sharply inhibits the phenotypic manifestations of tumor progression: cell proliferation and clonal activity. This was accompanied by a 2-3-fold increase in the content of SA-β-Gal positive cells thus indicating an increase in the cellular senescence phenotype. These changes were accompanied by a significant increase in the activity of p53 and p21 tumor suppressors and components of the PI3K/Akt/mTOR/p70 signaling pathway.

Prospects for using charity lotteries in social marketing.

The purpose of this work is to study the prospects of using charity lotteries as a marketing tool for involving consumers and employees in charitable activities. The research methodology is based on the principles of the theory of planned behavior by Ajzen. The study confirmed that behavioral intention is correlated with actual behavior.

[Integrin α3β1 signaling in regulation of the SK-Mel-147 melanoma cell senescence].

Using a model of the human SK-Mel-147 melanoma cell line, it was shown that blocking the expression of integrin α3β1 by transduction of cells with α3-specific shRNA did not affect their proliferation, but sharply increased the proportion of SA-β-Gal-positive cells, a phenotypic feature of cell senescence. These findings were accompanied by a significant increase in the activity of the Akt and mTOR protein kinases and the expression of p53 and p21 oncosupressors. Pharmacological inhibition of mTORC1 reduced the number SA-β-Gal-positive cells in the SK-Mel-147 cell population depleted of α3β1.

A monoclinic semiorganic molecular crystal GUHP for terahertz photonics and optoelectronics.

In this paper we describe the properties of the crystal of guanylurea hydrogen phosphate (NH[Formula: see text])[Formula: see text]CNHCO(NH[Formula: see text])H[Formula: see text]PO[Formula: see text] (GUHP) and propose its application in terahertz photonics and optoelectronics. GUHP crystal has a wide window of transparency and a high optical threshold in the visible and NIR spectral regions and narrow absorption bands in the terahertz frequency range. The spectral characteristics of absorption and refraction in the THz range were found to be strongly dependent on crystal temperature and orientation.

Acute amiodarone pulmonary toxicity in the form of organizing pneumonia triggered by orthotopic heart transplantation.

We report a case of a 60-year-old man who underwent orthotopic heart transplantation after short-term receipt of low-dose oral amiodarone for the management of ventricular tachycardia. Prior to transplant surgery, he had a normal chest radiograph and was free of supplemental oxygen. His initial postoperative chest radiograph showed subtle infiltrates, and thereafter his chest imaging continued to worsen.

Efficacy evaluation of case-specific approach for surgical treatment of incisional ventral hernia.

<b>Aim:</b> The aim of this research is to improve the results of surgical treatment of incisional ventral hernia by applying a case-specific approach and a new method of plastic repair of the anterior abdominal wall.<br/> <br/> <b>Methods:<b/> The prospective controlled dynamic study is based on incisional ventral hernia treatment results with the use of meshed endoprostheses among 219 patients. On-lay alloplasty was used in patients younger than 60 years of age, without severe concomitant pathology, with small and medium hernias and anterior abdominal wall defect of up to 10 cm (W1-W2).

Implication of integrin α2β1 in senescence of SK-Mel-147 human melanoma cells.

This investigation addressed the impact of integrin-initiated signaling pathways on senescence of tumor cells. In a model of human SK-Mel-147 melanoma cells, the silencing of integrin α2β1 strongly reduced cell proliferation and enhanced the percentage of SA-β-Gal-positive cells, a phenotypic feature of cellular senescence. These changes were accompanied by a significant increase in the activity of Akt and mTOR protein kinases and also in the expression of p53 and p21 oncosuppressors.

Efficacy Evaluation of a Case-Specific Approach for Surgical Treatment of Inicisional Ventral Hernia.

Background: The research aims to improve the surgical treatment results of incisional ventral hernia by applying a case-specific approach and a new method of anterior abdominal wall surgery.

Materials And Methods: The paper reports the results of the prospective dynamic cohort study on 219 patients under 60 years of age, with small and medium hernias and up to 10 cm defects in the anterior abdominal wall (W1-W2), who underwent incisional ventral hernia treatment with mesh endoprostheses.

Results: The paper offers a selection algorithm for anterior abdominal wall repair surgery and an original proprietary technique.

Pneumothorax in critically ill patients with COVID-19 infection: Incidence, clinical characteristics and outcomes in a case control multicenter study.

Background: The clinical features and outcomes of mechanically ventilated patients with COVID-19 infection who develop a pneumothorax has not been rigorously described or compared to those who do not develop a pneumothorax.

Purpose: To determine the incidence, clinical characteristics, and outcomes of critically ill patients with COVID-19 infection who developed pneumothorax. In addition, we compared the clinical characteristics and outcomes of mechanically ventilated patients who developed a pneumothorax with those who did not develop a pneumothorax.

Implication of integrins α3β1 and α5β1 in invasion and anoikis of SK-Mel-147 human melanoma cells: non-canonical functions of protein kinase Akt.

Downregulation of integrins α3β1 and α5β1 strongly decreased cell colony formation and in vitro invasion and markedly enhanced anoikis in SK-Mel-147 human melanoma cells. These modifications were accompanied by a marked increase in the levels of active Akt protein kinase, which indicated it played a non-canonical function in the melanoma cells. Pharmacological inhibition of Akt1, an Akt isozyme, in cells depleted of α3β1 or α5β1 restored their invasive activity, while inhibition of the Akt 2 isoform did not cause a visible effect.

mRNA with Mammalian Codon Bias Accumulates in Yeast Mutants with Constitutive Stress Granules.

Stress granules and P bodies are cytoplasmic structures assembled in response to various stress factors and represent sites of temporary storage or decay of mRNAs. Depending on the source of stress, the formation of these structures may be driven by distinct mechanisms, but several stresses have been shown to stabilize mRNAs via inhibition of deadenylation. A recent study identified yeast gene deletion mutants with constitutive stress granules and elevated P bodies; however, the mechanisms which trigger its formation remain poorly understood.

The Interplay of the Extracellular Matrix and Stromal Cells as a Drug Target in Stroma-Rich Cancers.

The tumor microenvironment (TME) is a complex neighborhood that consists of immune cells, fibroblasts, pericytes, adipocytes, endothelial and neuronal cells, and the extracellular matrix proteins. TME also consists of physical factors, such as oxygen availability, changing pH, interstitial fluid pressure, and tissue stiffness. As cancer progresses, the physical properties and the cells in the TME change significantly, impacting the efficacy of the therapies and modulating drug resistance.

Environmental assessment of livestock farms in the context of BAT system introduction in Russia.

The article focuses on the environmental and economic assessment of animal/poultry manure utilisation technologies as the sources of the greatest negative impact on environment from agriculture. This procedure is especially topical in the context of current transition to BAT system in Russia. Russian BAT reference books on intensive rearing of pigs and intensive rearing of poultry came into force on June 1, 2018.

The Pro-Oncogenic Adaptor CIN85 Acts as an Inhibitory Binding Partner of Hypoxia-Inducible Factor Prolyl Hydroxylase 2.

The EGFR adaptor protein, CIN85, has been shown to promote breast cancer malignancy and hypoxia-inducible factor (HIF) stability. However, the mechanisms underlying cancer promotion remain ill defined. Here we show that CIN85 is a novel binding partner of the main HIF-prolyl hydroxylase, PHD2, but not of PHD1 or PHD3.

Implication of integrin α2β1 in anoikis of SK-Mel-147 human melanoma cells: a non-canonical function of Akt protein kinase.

Suppression of anoikis, a kind of apoptosis caused by disruption of contacts between cell and extracellular matrix, is an important prerequisite for cancer cell metastasis. In this communication, we demonstrate that shRNA-mediated depletion of α2 integrin subunit induces anoikis and substantially decreases colony-forming potential in SK-Mel-147 human melanoma cells. Suppression of α2β1 upregulates the levels of pro-apoptotic protein p53 and cyclin-dependent kinase inhibitors p21 and p27.

KLF9-dependent ROS regulate melanoma progression in stage-specific manner.

Although antioxidants promote melanoma metastasis, the role of reactive oxygen species (ROS) in other stages of melanoma progression is controversial. Moreover, genes regulating ROS have not been functionally characterized throughout the entire tumor progression in mouse models of cancer. To address this question, we crossed mice-bearing knock-out of Klf9, an ubiquitous transcriptional regulator of oxidative stress, with two conditional melanocytic mouse models: Braf mice, where Braf causes premalignant melanocytic hyperplasia, and Braf/Pten mice, where Braf and loss of Pten induce primary melanomas and metastases.