[TREATMENT AND PREVENTION OF METASTASIS TO THE PRE- AND PARATRACHEAL LYMPH NODES IN CANCER OF THE LARYNX WITH SPREAD TO THE SUBGLOTTIC SECTION].

Based on the specificity of the subglottic cancer, the basic method of treatment is surgical, because many years of experience have shown the ineffectiveness of chemotherapy and the low effectiveness of radiation therapy. We have developed and introduced in practice the method of extended-combined laryngectomy is effective not only in terms of treating the underlying disease, but also for preventive purposes, reducing the risk of metastases in pre- and paratracheal lymphatic zones. The method of extended-combined laryngectomy includes mobilization of the larynx and its removal at level V or VI of the tracheal rings, lymph node dissection at level VI, both on the affected side and prophylactically from the opposite side, as well as removal of either the thyroid gland on the side of the lesion subglottic cancer, or at its circulatory location total removal of the gland.

Exploring Dual-Substrate Cultivation Strategy of 1,3-Propanediol Production Using Klebsiella pneumoniae.

1,3-Propanediol (1,3-PDO) has numerous industrial applications in the synthesis of the monomer of the widely used fiber polytrimethylene terephthalate. In this work, the production of 1,3-PDO by Klebsiella pneumoniae is increased by dual-substrate cultivation and fed-batch fermentation. Experimental results indicate that the production of 1,3-PDO can be elevated to 16.

sp. A01 laccase: thermostable, detergent resistant, anti-environmental and industrial pollutants enzyme.

Laccase (EC 1.10.3.

Improved stability of polyclonal antibodies: A case study with lyophilization-conserved antibodies raised against epitopes from the malaria parasite Plasmodium falciparum.

Antibodies can be produced as polyclonal (pAb) or monoclonal (mAb) liquid formulations with limited shelf-life. For pAbs, unlike mAbs, only little is known about excipients and lyophilization affecting antibody stability upon reconstitution. We used a model pAb directed against Plasmodium falciparum (Pf) pyridoxal 5'-phosphate synthase 2 (Pdx2) to systemically study effects of bulking agents (amino acids, phosphate buffers, salt solutions), sugar(alcohols), surfactants and protein additions (bovine serum albumin, BSA) in liquid pAb formulations (isolated or in combinations) on the activity to detect the antigen in Pf extracts by Western blots.

Transcriptomics-based screening of molecular signatures associated with patients overall survival and their key regulators in subtypes of breast cancer.

Molecular subtypes of breast cancer are associated with differences in prognosis and strategies of molecular targeted therapies. Gene regulatory mechanisms as one of the reasons might modulate these differences. In the present study, we proposed a comprehensive data analysis and systems biology approach to explore molecular signatures which reduce the chance of patients overall survival and the possible mechanisms of their regulation by transcription factors (TFs) and microRNAs (miRNAs) in the main subtypes of breast tumor consist of Basal like, Her2 enriched, Luminal A and Luminal B breast cancer.

A bioinformatics analysis of exosomal microRNAs released following mycobacterial infection.

Background: Tuberculosis (TB) still remains a major health threat worldwide. The current TB diagnostics are suboptimal, and there is a high clinical need for identifying novel biomarkers of disease prevalence. Circulating exosomes have been currently attractive as novel biomarkers in a wide range of pathological conditions.

CK19 stabilizes CFTR at the cell surface by limiting its endocytic pathway degradation.

Protein interactions that stabilize the cystic fibrosis (CF) transmembrane conductance regulator (CFTR) at the apical membranes of epithelial cells have not yet been fully elucidated. We identified keratin 19 (CK19 or K19) as a novel CFTR-interacting protein. CK19 overexpression stabilized both wild-type (WT)-CFTR and Lumacaftor (VX-809)-rescued F508del-CFTR (where F508del is the deletion of the phenylalanine residue at position 508) at the plasma membrane (PM), promoting Cl secretion across human bronchial epithelial (HBE) cells.

IL-36β Promotes CD8 T Cell Activation and Antitumor Immune Responses by Activating mTORC1.

Cytokine-amplified functional CD8 T cells ensure effective eradication of tumors. Interleukin 36α (IL-36α), IL-36β, and IL-36γ share the same receptor complex, composed of the IL-36 receptor (IL-36R), and IL-1RAcP. Recently, we revealed that IL-36γ greatly promoted CD8 T cell activation, contributing to antitumor immune responses.

[Development of drugs on the basis of high-polymeric double-stranded RNA for antiviral and antitumor therapy].

The review summarizes literature data on the development of drugs based on natural and synthetic high-polymeric double-stranded RNA, and their antiviral, immunoadjuvant and antitumor properties. Special attention is paid to cell receptors responding to exogenous dsRNA, the paths of dsRNA-dependent antiviral reaction, ability of dsRNA to inhibit growth and induce apoptosis ofmalignant cells. It has been shown that enhancing the innate immune response with dsRNA can be an effective component in improving methods for treating and preventing infectious and cancer diseases.

3D Printed Lab-on-a-Chip Platform for Chemical Stimulation and Parallel Analysis of Ion Channel Function.

Functional imaging has been a widely established method for the assessment of ion channel function in vitro. Conventional infrastructure used for in vitro functional analysis of ion channels is typically proprietary, non-customizable, expensive, and requires a high level of skill to use and maintain. 3D desktop printing, which is employed in the rapid prototyping field, allows for quick engineering of alternatives to conventional imaging infrastructure that are customizable, low cost, and user friendly.

Ultra-Low-Cost 3D Bioprinting: Modification and Application of an Off-the-Shelf Desktop 3D-Printer for Biofabrication.

3D bioprinting has become a versatile and powerful method in tissue engineering and regenerative medicine and is increasingly adapted by other disciplines due to its tremendous potential beyond its typical applications. However, commercially available 3D bioprinting systems are typically expensive circumventing the broad implementation, including laboratories in low-resource settings. To address the limitations of conventional and commercially available technology, we developed a 3D bioprinter by modification of an off-the-shelf 3D desktop printer, that can be installed within a single day, is of handy size to fit into a standard laminar flow hood, customizable, ultra-low cost and thus, affordable to a broad range of research labs, or educational institutions.

Deletion of INMAP postpones mitotic exit and induces apoptosis by disabling the formation of mitotic spindle.

INMAP was first identified as a spindle protein that plays important roles in cell-cycle progression, and previous studies have revealed that its abnormal expression leads to mitotic disorder and the growth inhibition of human tumor xenografts, but the underlying mechanism is still unclear. In this study, we knocked out INMAP in HEK293T cells, a strain of human embryonic renal cells, through CRISPR-Cas9 gene editing technology, resulting in obvious cell growth inhibition. In this system, the deletion of INMAP caused obviously apoptosis.

Enhanced cytotoxic and genotoxic effects of gadolinium-doped ZnO nanoparticles on irradiated lung cancer cells at megavoltage radiation energies.

The purpose of this study was to investigate the radiation dose enhancement effects of gadolinium-doped zinc oxide nanoparticles (Gd-doped ZnO NPs) under the megavoltage (MV) X-ray irradiation. ZnO NPs have preferred photocatalytic properties under UV light for cancer killing. UV light has limited applications in cancer treatment and it is necessary to use X-ray photons with MV energies.

The MyoRobot technology discloses a premature biomechanical decay of skeletal muscle fiber bundles derived from R349P desminopathy mice.

Mutations in the Des gene coding for the muscle-specific intermediate filament protein desmin lead to myopathies and cardiomyopathies. We previously generated a R349P desmin knock-in mouse strain as a patient-mimicking model for the corresponding most frequent human desmin mutation R350P. Since nothing is known about the age-dependent changes in the biomechanics of affected muscles, we investigated the passive and active biomechanics of small fiber bundles from young (17-23 wks), adult (25-45 wks) and aged (>60 wks) heterozygous and homozygous R349P desmin knock-in mice in comparison to wild-type littermates.

Synergistic effects of polyaniline and pulsed electromagnetic field to stem cells osteogenic differentiation on polyvinylidene fluoride scaffold.

Repairing the lost or damaged mandible is very difficult and time-consuming, so there is a great hope for tissue engineering to accelerate it. At the present study, electrospinning was applied to fabricate polyvinylidene fluoride (PVDF) and PVDF-polyaniline (PANI) composite scaffolds. In addition, extremely low frequency pulsed electromagnetic field (PEMF) was applied for treating the stem cells derived from dental pulp (DPSCs) when cultured on the nanofibrous scaffolds.

Inhibiting PGGT1B Disrupts Function of RHOA, Resulting in T-cell Expression of Integrin α4β7 and Development of Colitis in Mice.

Background & Aims: It is not clear how regulation of T-cell function is altered during development of inflammatory bowel diseases (IBD). We studied the mechanisms by which geranylgeranyltransferase-mediated prenylation controls T-cell localization to the intestine and chronic inflammation.

Methods: We generated mice with T-cell-specific disruption of the geranylgeranyltransferase type I, beta subunit gene (Pggt1b), called Pggt1b mice, or the ras homolog family member A gene (Rhoa), called Rhoa mice.

Artemisinin-(Iso)quinoline Hybrids by C-H Activation and Click Chemistry: Combating Multidrug-Resistant Malaria.

A substantial challenge worldwide is emergent drug resistance in malaria parasites against approved drugs, such as chloroquine (CQ). To address these unsolved CQ resistance issues, only rare examples of artemisinin (ART)-based hybrids have been reported. Moreover, protein targets of such hybrids have not been identified yet, and the reason for the superior efficacy of these hybrids is still not known.

Single muscle fibre biomechanics and biomechatronics - The challenges, the pitfalls and the future.

Interest in muscle biomechanics is growing with availabilities of patient biopsies and animal models related to muscle diseases, muscle wasting (sarcopenia, cachexia), exercise and drug effects. However, development of technologies or facilitated systems required to measure biomechanical and contractile properties of single fibres has not kept pace with this demand. Most studies use manual mechatronics systems that have not changed in decades and are confined to a few labs worldwide.

Preparation of brushite cements with improved properties by adding graphene oxide.

Brushite (dicalcium phosphate dihydrate, DCPD) cement as a promising bioactive material for bone tissue engineering is widely used to treat defects. However, relatively poor mechanical properties of brushite cement limit its application in loadbearing conditions. The aim of this study is to investigate the effect of graphene oxide (GO) addition to the physical-mechanical-biological properties of brushite cement.

MyoRobot 2.0: An advanced biomechatronics platform for automated, environmentally controlled skeletal muscle single fiber biomechanics assessment employing inbuilt real-time optical imaging.

We present an enhanced version of our previously engineered MyoRobot system for reliable, versatile and automated investigations of skeletal muscle or linear polymer material (bio)mechanics. That previous version already replaced strenuous manual protocols to characterize muscle biomechanics properties and offered automated data analysis. Here, the system was further improved for precise control over experimental temperature and muscle single fiber sarcomere length.

[SELECTIVE EFFICACY OF GEORGIAN LEGUME EXTRACTS ON JURKAT AND MDCK CELLS].

The goal of our study was to establish the anti- proapoptotic activity of the common in Georgia crops on the Jurkat and MDCK cells. Extracts of various varieties of beans (Tirkmela, Batumi meadow, Shulavera, Udelebi, as well as green peas, Lens Culinaris lentils, soy beans) were added to the intact or incubated under oxidative stress conditions Jurkat and MDCK cells. Cell viability (apoptosis intensity) was determined by a cell proliferative activity test (MTT test).

Camptothecin activates SIRT1 to promote lipid catabolism through AMPK/FoxO1/ATGL pathway in CC myogenic cells.

Caloric restriction activates sirtuin 1 (SIRT1) and induces a variety of metabolic effects that are beneficial for preventing age-related disease. The present study screened a commercially available used drug library to develop small molecule activators of SIRT1 as therapeutics for treatment of metabolic disorders. Using an in vitro fluorescence assay, the cancer therapeutic camptothecin increased SIRT1 enzymatic activity by 5.

Label-Free Multiphoton Endomicroscopy for Minimally Invasive In Vivo Imaging.

Multiphoton microscopy of cellular autofluorescence and second harmonic generation from collagen facilitates imaging of living cells and tissues without the need for additional fluorescent labels. Here, a compact multiphoton endomicroscope for label-free in vivo imaging in small animals via side-viewing needle objectives is presented. Minimal invasive imaging at cellular resolution is performed in colonoscopy of mice without surgical measures and without fluorescent dyes as a contrast agent.

Investigating the diagnostic performance of HOTTIP, PVT1, and UCA1 long noncoding RNAs as a predictive panel for the screening of colorectal cancer patients with lymph node metastasis.

Like other noncoding RNAs (ncRNAs), dysregulation of long ncRNAs (lncRNAs) has been associated with various clinicopathological features of colorectal cancer (CRC) patients such as lymph node metastasis (LNM). Recently, three aberrant expressed oncogenic lncRNA (onco-lncRNAs), including HOXA transcript at the distal tip (HOTTIP), plasmacytoma variant translocation 1 (PVT1), and urothelial carcinoma associated 1 (UCA1) have been reported in LNM. Herein, we compared the diagnostic performance of these lncRNAs as individual biomarkers and as a discriminating panel between LNM CRC patients, nonmetastatic lymph nodes (NLN) and normal healthy subjects.