Multiple Myeloma: Genetic and Epigenetic Biomarkers with Clinical Potential.

Multiple myeloma (MM) is characterized by the uncontrolled proliferation of monoclonal plasma cells and accounts for approximately 10% of all hematologic malignancies. The clinical outcomes of MM can exhibit considerable variability. Variability in both the genetic and epigenetic characteristics of MM undeniably contributes to tumor dynamics.

The Gene Related to the Family Genes: An Evolutionary View on Origin and Function.

has two paralogs, and , related to the evolutionarily conserved family genes. In mammals, the family consists of , encoding transcription co-factors involved in the regulation of development and cell fate determination. The function of and in remains unclear.

Novel Peptidomimetic Cyclo-{E(I)-E(W)}Na (CP-88) with Hematopoietic Activity Sustained in Invasive and Oral Administration: Experimental and Preclinical Evaluation.

Over the last decades, significant progress has been made in studying agonistic and antagonistic hematopoietic peptides. The main disadvantage of this class of peptides is their low stability with noninvasive administration methods, which limits the widespread use of hematopoiesis-regulated peptide drugs in medical practice. The aim of this work is to study novel peptidomimetics with hematopoietic activity sustained in invasive and oral administration.

Cellular and Molecular Effects of the Bruck Syndrome-Associated Mutation in the Gene.

Bruck syndrome is a rare autosomal recessive disorder characterized by increased bone fragility and joint contractures similar to those in arthrogryposis and is known to be associated with mutations in the () and () genes. These genes encode endoplasmic reticulum proteins that play an important role in the biosynthesis of type I collagen, which in turn affects the structure and strength of connective tissues and bones in the body. Mutations are associated with disturbances in both the primary collagen chain and its post-translational formation, but the mechanism by which mutations lead to Bruck syndrome phenotypes has not been determined, not only because of the small number of patients who come to the attention of researchers but also because of the lack of disease models.

Human Liver MSCs Retain Their Basic Cellular Properties in Chronically Inflamed Liver Tissue.

Every 25th death worldwide is associated with liver pathology. The development of novel approaches to liver diseases therapy and protocols for maintaining the vital functions of patients on the liver transplant waiting list are urgently needed. Resident mesenchymal stem cells (MSCs) play a significant role in supporting liver tissue integrity and improve the liver condition after infusion.

Transcription Factors ClrB and XlnR and Their Effect on the Transcription of Cellulase Genes in the Filamentous Fungus .

The filamentous fungus (anamorph ) has been shown to be an efficient producer of secreted cellulases, used in biorefinery processes. Understanding the mechanisms of regulation of cellulase gene expression in the fungus is a current task in industrial biotechnology, since it allows for targeted changes in the composition of the complex secreted by the fungus. Expression of cellulase genes in fungi is regulated mainly at the level of transcription via pathway-specific transcription factors (TF), the majority of which belong to the Zn(II)2Cys6 family of zinc binuclear cluster proteins.

Branched Linkers for Homogeneous Antibody-Drug Conjugates: How Long Is Long Enough?

Homogeneous antibody-drug conjugates (ADCs) exhibit significantly improved pharmacological properties compared to their heterogeneous counterparts. Site-specific conjugation of the payload to the IgG required for homogeneity can be achieved using enzymes. One example is microbial transglutaminase (MTGase), which can selectively perform transamidation on the Q295 residue of human Fc when N297 glycans are removed.

Comparative Analysis of the Effects of Maternal Hypoxia and Placental Ischemia on HIF1-Dependent Metabolism and the Glucocorticoid System in the Embryonic and Newborn Rat Brain.

Prenatal hypoxia, often accompanied by maternal glucocorticoid stress, can predispose offspring to neurological disorders in adulthood. If placental ischemia (PI) primarily reduces fetal oxygen supply, the maternal hypoxia (MH) model also elicits a pronounced fetal glucocorticoid exposure. Here, we compared MH and PI in rats to distinguish their unique and overlapping effects on embryonic and newborn brain development.

The Role of MicroRNAs in the Pathogenesis of Doxorubicin-Induced Vascular Remodeling.

Doxorubicin (DOX), a cornerstone chemotherapeutic agent, effectively combats various malignancies but is marred by significant cardiovascular toxicity, including endothelial damage, chronic heart failure, and vascular remodeling. These adverse effects, mediated by oxidative stress, mitochondrial dysfunction, inflammatory pathways, and dysregulated autophagy, underscore the need for precise therapeutic strategies. Emerging research highlights the critical role of microRNAs (miRNAs) in DOX-induced vascular remodeling and cardiotoxicity.

Novel Selectable Marker Sesquiterpenoid Antibiotic Pentalenolactone.

Antibiotic resistance has been and remains a major problem in our society. The main solution to this problem is to search and study the mechanisms of antibiotic action. Many groups of secondary metabolites, including antimicrobial ones, are produced by the phylum.

Expanding Horizons of CRISPR/Cas Technology: Clinical Advancements, Therapeutic Applications, and Challenges in Gene Therapy.

CRISPR-Cas technology has transformed the field of gene editing, opening new possibilities for treatment of various genetic disorders. Recent years have seen a surge in clinical trials using CRISPR-Cas-based therapies. This review examines the current landscape of CRISPR-Cas implementation in clinical trials, with data from key registries, including the Australian New Zealand Clinical Trials Registry, the Chinese Clinical Trial Register, and ClinicalTrials.

Interaction of Cyclosporin C with Dy Ions in Acetonitrile and in Complex with Dodecylphosphocholine Micelles Determined by NMR Spectroscopy.

The spectral characteristics of cyclosporin C (CsC) with the addition of Dy ions in acetonitrile (CDCN) and CsC with Dy incorporated into dodecylphosphocholine (DPC) micelle in deuterated water were investigated by high-resolution NMR spectroscopy. The study was focused on the interaction between Dy ions and CsC molecules in different environments. Using a combination of one-dimensional and two-dimensional NMR techniques, we obtained information on the spatial features of the peptide molecule and the interaction between CsC and the metal ion.

Increased Levels of hsa-miR-199a-3p and hsa-miR-382-5p in Maternal and Neonatal Blood Plasma in the Case of Placenta Accreta Spectrum.

Despite the increasing number of placenta accreta spectrum (PAS) cases in recent years, its impact on neonatal outcomes and respiratory morbidity, as well as the underlying pathogenetic mechanism, has not yet been extensively studied. Moreover, no study has yet demonstrated the effectiveness of antenatal corticosteroid therapy (CT) for the prevention of respiratory distress syndrome (RDS) in newborns of mothers with PAS at the molecular level. In this regard, microRNA (miRNA) profiling by small RNA deep sequencing and quantitative real-time PCR was performed on 160 blood plasma samples from preterm infants (gestational age: 33-36 weeks) and their mothers who had been diagnosed with or without PAS depending on the timing of the antenatal RDS prophylaxis.

The Role of the Serotonergic System in Time Perception: A Systematic Review.

Time perception is a fundamental cognitive function essential for adaptive behavior and shared across species. The neural mechanisms underlying time perception, particularly its neuromodulation, remain debated. In this review, we examined the role of the serotonergic system in time perception (at the scale of seconds and minutes), building a translational bridge between human and non-human animal studies.

Brown and Beige Adipose Tissue: One or Different Targets for Treatment of Obesity and Obesity-Related Metabolic Disorders?

The failure of the fight against obesity makes us turn to new goals in its treatment. Now, brown adipose tissue has attracted attention as a promising target for the treatment of obesity and associated metabolic disorders such as insulin resistance, dyslipidemia, and glucose tolerance disorders. Meanwhile, the expansion of our knowledge has led to awareness about two rather different subtypes: classic brown and beige (inducible brown) adipose tissue.

Antisolvent 3D Printing of Gene-Activated Scaffolds for Bone Regeneration.

The use of 3D-printed gene-activated bone grafts represents a highly promising approach in the fields of dentistry and orthopedics. Bioresorbable poly-lactic-co-glycolic acid (PLGA) scaffolds, infused with adenoviral constructs that carry osteoinductive factor genes, may provide an effective alternative to existing bone grafts for the reconstruction of extensive bone defects. This study aims to develop and investigate the properties of 3D scaffolds composed of PLGA and adenoviral constructs carrying the BMP2 gene (Ad-BMP2), both in vitro and in vivo.

Artificial Tertiary Lymphoid Structures: Exploring Mesenchymal Stromal Cells as a Platform for Immune Niche Formation.

Constructing artificial tertiary lymphoid structures (TLSs) opens new avenues for advancing cancer immunotherapy and personalized medicine by creating controllable immune niches. Mesenchymal stromal cells (MSCs) offer an ideal stromal source for such constructs, given their potent immunomodulatory abilities and accessibility. In this study, we explored the potential of adipose-derived MSCs to adopt TLS-supportive phenotypes and facilitate lymphocyte organization.

Damage of the Bone Marrow Stromal Precursors in Patients with Acute Leukemia at the Onset of the Disease and During Treatment.

In patients with acute leukemia (AL), malignant cells and therapy modify the properties of multipotent mesenchymal stromal cells (MSCs) and their descendants, reducing their ability to maintain normal hematopoiesis. The aim of this work was to elucidate the alterations in MSCs at the onset and after therapy in patients with AL. The study included MSCs obtained from the bone marrow of 78 AL patients (42 AML and 36 ALL) and healthy donors.

MicroRNA-Based Liquid Biopsy for Cervical Cancer Diagnostics and Treatment Monitoring.

Despite prevention strategies, cervical cancer remains a significant public health issue. Human papillomavirus plays a critical role in its development, and early detection is vital to improve patient outcomes. The incidence of cervical cancer is projected to rise, necessitating better diagnostic tools.

Alterations in the Rice Coleoptile Metabolome During Elongation Under Submergence Stress.

Plants known as obligate aerobes developed different mechanisms to overcome the damage incurred under oxygen limitation. One of the survival strategies to have commonly appeared in hydrophytic plants is the escape strategy, which accelerates plant axial organs' growth in order to escape hypoxic conditions as soon as possible. The present study aimed to distinguish the alterations in coleoptile elongation, viability and metabolic profiles in coleoptiles of slow- and fast-growing rice varieties.

Establishment of Novel High-Grade Serous Ovarian Carcinoma Cell Line OVAR79.

High-grade serous ovarian carcinoma (HGSOC) remains the most common and deadly form of ovarian cancer. However, available cell lines usually fail to appropriately represent its complex molecular and histological features. To overcome this drawback, we established OVAR79, a new cell line derived from the ascitic fluid of a patient with a diagnosis of HGSOC, which adds a unique set of properties to the study of ovarian cancer.

An Approach to Identifying Single-Nucleotide Mutations Using Noncovalent Associates of Gold Nanoparticles with Fluorescently Labeled Oligonucleotides.

Globally, widespread tuberculosis is one of the acute problems of healthcare. Drug-resistant forms of tuberculosis require a personalized approach to treatment. Currently, rapid methods for detecting drug resistance of (MTB) to some antituberculosis drugs are often used and involve optical, electrochemical, or PCR-based assays.

The Influence of Craniometric Variation on the Position of Mandibular Foramen: A Cadaveric Cross-Sectional Study.

: the mandibular foramen is an essential anatomic landmark in performing various dental and surgical procedures, including inferior alveolar nerve block (IANB). However, its position may vary based on the individual morpho-functional features of the skull and face. This study aims to conduct a personalized assessment of the location of the mandibular foramen in various shapes of skulls, faces, and mandibles.

Real-World Effectiveness and Safety of Selective JAK Inhibitors in Ulcerative Colitis and Crohn's Disease: A Retrospective, Multicentre Study.

: Data on the real-world effectiveness and safety of selective JAK inhibitors (JAKis) in ulcerative colitis (UC) and Crohn's disease (CD) are limited. : We conducted a multicentre, retrospective study to assess clinical, biochemical, and endoscopic outcomes of selective JAKis in bio-experienced UC and CD. : A total of 246 patients (mean age: 40.

Exploring the Link Between Interoception and Symptom Severity in Premature Ventricular Contractions.

: The physiological basis underlying symptomatic versus asymptomatic premature ventricular contractions (PVCs) remains poorly understood. However, symptomatic PVCs can significantly impair quality of life. In patients without structural heart disease, symptom intensity is crucial for guiding management strategies and determining the need for medical or surgical intervention.