IGFBP6 regulates extracellular vesicles formation via cholesterol abundance in MDA-MB-231 cells.

Breast cancer recurrence is associated with the growth of disseminated cancer cells that separate from the primary tumor before surgical treatment and hormonal therapy and form a metastatic niche in distant organs. We previously demonstrated that IGFBP6 expression is associated with the risk of early relapse of luminal breast cancer. Knockdown of IGFBP6 in MDA-MB-231 breast cancer cells increased their invasiveness, proliferation, and metastatic potential.

α-Latrotoxin Tetramers Spontaneously Form Two-Dimensional Crystals in Solution and Coordinated Multi-Pore Assemblies in Biological Membranes.

α-Latrotoxin (α-LTX) was found to form two-dimensional (2D) monolayer arrays in solution at relatively low concentrations (0.1 mg/mL), with the toxin tetramer constituting a unit cell. The crystals were imaged using cryogenic electron microscopy (cryoEM), and image analysis yielded a ~12 Å projection map.

Modulators of the Nrf2 Signaling Pathway Enhance the Cytotoxic Effect of Standard Chemotherapeutic Drugs on Organoids of Metastatic Colorectal Cancer.

The activity of known modulators of the Nrf2 signaling pathway (bardoxolone and brusatol) was studied on cultures of tumor organoids of metastatic colorectal cancer previously obtained from three patients. The effect of modulators was studied both as monotherapy and in combination with standard chemotherapy drugs used to treat colorectal cancer. The Nrf2 inhibitor brusatol and the Nrf2 activator bardoxolone have antitumor activity.

Mathematical model explains differences in Omicron and Delta SARS-CoV-2 dynamics in Caco-2 and Calu-3 cells.

Within-host infection dynamics of Omicron dramatically differs from previous variants of SARS-CoV-2. However, little is still known about which parameters of virus-cell interplay contribute to the observed attenuated replication and pathogenicity of Omicron. Mathematical models, often expressed as systems of differential equations, are frequently employed to study the infection dynamics of various viruses.

Assessing the Efficacy of Anti-Cancer Drugs on Organoid Models Derived from Prostate Cancer.

It was proven that tumor organoids effectively mirror the phenotypic and genetic traits of the original biomaterial. It was reported that outcomes from drug testing in organoid cultures can accurately represent the clinical response observed in patients. In this study, an organoid culture was derived from biopsy material of prostate cancer (PC).

Viral and host small RNA transcriptome analysis of SARS-CoV-1 and SARS-CoV-2-infected human cells reveals novel viral short RNAs.

RNA viruses have been shown to express various short RNAs, some of which have regulatory roles during replication, transcription, and translation of viral genomes. However, short viral RNAs generated from SARS-CoV-1 and SARS-CoV-2 genomic RNAs remained largely unexplored, possibly due limitations of the widely used library preparation methods for small RNA deep sequencing and corresponding data processing. By analyzing publicly available small RNA sequencing datasets, we observed that human Calu-3 cells infected by SARS-CoV-1 or SARS-CoV-2 accumulate multiple previously unreported short viral RNAs.

Challenges in characterization of transcriptomes of extracellular vesicles and non-vesicular extracellular RNA carriers.

Since its original discovery over a decade ago, extracellular RNA (exRNA) has been found in all biological fluids. Furthermore, extracellular microRNA has been shown to be involved in communication between various cell types. Importantly, the exRNA is protected from RNases degradation by certain carriers including membrane vesicles and non-vesicular protein nanoparticles.

RNA-binding proteins regulating the CD44 alternative splicing.

Alternative splicing is often deregulated in cancer, and cancer-specific isoform switches are part of the oncogenic transformation of cells. Accumulating evidence indicates that isoforms of the multifunctional cell-surface glycoprotein CD44 play different roles in cancer cells as compared to normal cells. In particular, the shift of CD44 isoforms is required for epithelial to mesenchymal transition (EMT) and is crucial for the maintenance of pluripotency in normal human cells and the acquisition of cancer stem cells phenotype for malignant cells.

Spontaneous metastasis xenograft models link CD44 isoform 4 to angiogenesis, hypoxia, EMT and mitochondria-related pathways in colorectal cancer.

Hematogenous metastasis limits the survival of colorectal cancer (CRC) patients. Here, we illuminated the roles of CD44 isoforms in this process. Isoforms 3 and 4 were predominantly expressed in CRC patients.

Metabolic effects of vasopressin in pathophysiology of diabetic kidney disease.

The diabetic kidney disease (DKD) is the major cause of the chronic kidney disease (CKD). Enhanced plasma vasopressin (VP) levels have been associated with the pathophysiology of DKD and CKD. Stimulation of VP release in DKD is caused by glucose-dependent reset of the osmostat leading to secondary pathophysiologic effects mediated by distinct VP receptor types.

The signature of SARS-CoV-2 evolution reflects selective pressures within human guts.

In somatic cells, microRNAs (miRNAs) bind to the genomes of RNA viruses and influence their translation and replication. In London and Berlin samples represented in GISAID database, we traced severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) lineages and divided these sequenced in two groups, "Ancestral variants" and "Omicrons," and analyzed them through the prism of the tissue-specific binding between host miRNAs and viral messenger RNAs. We demonstrate a significant number of miRNA-binding sites in the NSP4 region of the SARS-CoV-2 genome, with evidence of evolutionary pressure within this region exerted by human intestinal miRNAs.

Immunomodulatory Effect and Biological Significance of β-Glucans.

β-glucan, one of the homopolysaccharides composed of D-glucose, exists widely in cereals and microorganisms and possesses various biological activities, including anti-inflammatory, antioxidant, and anti-tumor properties. More recently, there has been mounting proof that β-glucan functions as a physiologically active "biological response modulator (BRM)", promoting dendritic cell maturation, cytokine secretion, and regulating adaptive immune responses-all of which are directly connected with β-glucan-regulated glucan receptors. This review focuses on the sources, structures, immune regulation, and receptor recognition mechanisms of β-glucan.

Differences in Presentation of SARS-CoV-2 Omicron Strain Variant BA.1-BA.5 Peptides by HLA Molecules.

In this work, we analyzed the binding affinities of mutated peptides of Omicron strain variants BA.1-BA.5 and the worldwide prevalent HLA alleles.

Development of a novel mathematical model that explains SARS-CoV-2 infection dynamics in Caco-2 cells.

Mathematical modeling is widely used to study within-host viral dynamics. However, to the best of our knowledge, for the case of SARS-CoV-2 such analyses were mainly conducted with the use of viral load data and for the wild type (WT) variant of the virus. In addition, only few studies analyzed models for data, which are less noisy and more reproducible.

and genes modulate sensitivity of breast cancer cells to ferroptosis.

Relapse of breast cancer is one of the key obstacles to successful treatment. Previously we have shown that low expression of and genes in breast cancer tissue corresponded to poor prognosis. participates directly in the elongation of polyunsaturated fatty acids (PUFAs) that are considered to play an important role in cancer cell metabolism.

allele diminishing in COVID-19 patients population associated with non-structural epitope abundance in CD8+ T-cell repertoire.

In mid-2021, the SARS-CoV-2 Delta variant caused the third wave of the COVID-19 pandemic in several countries worldwide. The pivotal studies were aimed at studying changes in the efficiency of neutralizing antibodies to the spike protein. However, much less attention was paid to the T-cell response and the presentation of virus peptides by MHC-I molecules.

Differential co-expression network analysis with DCoNA reveals isomiR targeting aberrations in prostate cancer.

Motivation: One of the standard methods of high-throughput RNA sequencing analysis is differential expression. However, it does not detect changes in molecular regulation. In contrast to the standard differential expression analysis, differential co-expression one aims to detect pairs or clusters whose mutual expression changes between two conditions.

A novel approach for a joint analysis of isomiR and mRNA expression data reveals features of isomiR targeting in breast cancer.

A widely used procedure for selecting significant miRNA-mRNA or isomiR-mRNA pairs out of predicted interactions involves calculating the correlation between expression levels of miRNAs/isomiRs and mRNAs in a series of samples. In this manuscript, we aimed to assess the validity of this procedure by comparing isomiR-mRNA correlation profiles in sets of sequence-based predicted target mRNAs and non-target mRNAs (negative controls). Target prediction was carried out using RNA22 and TargetScan algorithms.

On the peptide binding affinity changes in population-specific HLA repertoires to the SARS-CoV-2 variants Delta and Omicron.

Objective: To investigate the changes of Spike protein-HLA binding affinity profiles between the Wuhan strain and two dominant variants, the Delta and the Omicron strains, among the Taiwanese, the British and the Russian populations.

Methods: The HLA frequencies and the HLA-peptide binding affinity profiles in the T-CoV database were combined to conduct the study. We focused on the public alleles in the three populations (HLA-A, HLA-B, HLA-C, HLA-DRB1, and/or HLA-DPA1/DPB1 alleles) and the altered peptides of the spike protein (compared to the Wuhan strain) in the Delta G/478K·V1 (B.

Specificity of viscumin revised. As probed with a printed glycan array.

Viscumin, a lectin used in anti-cancer therapy, was originally considered as βGal recognizing protein; later, an ability to bind 6'-sialyl N-acetyllactosamine (6'SLN) terminated gangliosides was found. Here we probed viscumin with a printed glycan array (PGA) containing a large number of mammalian sulfated glycans, and found a strong binding to glycans with 6-O-SuGal moiety as lactose, N-acetyllactosamine (LN), di-N-acetyllactosamine (LacdiNAc), and even 6-O-SuGalNAcα (but not SiaTn). Also, the ability to bind some of αGal terminated glycans, including Galα1-3Galβ1-4GlcNAc, was observed.

ADGRL1 haploinsufficiency causes a variable spectrum of neurodevelopmental disorders in humans and alters synaptic activity and behavior in a mouse model.

ADGRL1 (latrophilin 1), a well-characterized adhesion G protein-coupled receptor, has been implicated in synaptic development, maturation, and activity. However, the role of ADGRL1 in human disease has been elusive. Here, we describe ten individuals with variable neurodevelopmental features including developmental delay, intellectual disability, attention deficit hyperactivity and autism spectrum disorders, and epilepsy, all heterozygous for variants in ADGRL1.

Alterations in SARS-CoV-2 Omicron and Delta peptides presentation by HLA molecules.

The T-cell immune response is a major determinant of effective SARS-CoV-2 clearance. Here, using the recently developed T-CoV bioinformatics pipeline (https://t-cov.hse.

Immunogenic epitope panel for accurate detection of non-cross-reactive T cell response to SARS-CoV-2.

The ongoing COVID-19 pandemic calls for more effective diagnostic tools. T cell response assessment serves as an independent indicator of prior COVID-19 exposure while also contributing to a more comprehensive characterization of SARS-CoV-2 immunity. In this study, we systematically assessed the immunogenicity of 118 epitopes with immune cells collected from multiple cohorts of vaccinated, convalescent, healthy unexposed, and SARS-CoV-2-exposed donors.