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.

Risk Factors for Surgical Site Infection After Cardiac Surgery in Neonates: A Case-Control Study.

This study was undertaken to determine the incidence and risk factors associated with the development of sternal wound infection in neonates after surgery for congenital heart disease. A case-control study was conducted to examine the influence of perioperative risk factors on the development of sternal infection. In total, 253 neonates with CHD underwent a complete median sternotomy.

Availability of the Great Saphenous Veins as Conduits for Arterial Bypass Surgery in Patients with Varicose Veins.

The great saphenous vein (GSV) has long been recognized as the best conduit for vascular bypass procedures. Concomitant varicose veins disease may be a reason for GSV unavailability either due to dilatation and tortuosity of the vein or due to its destruction during invasive venous treatment. -to assess the rate of varicose vein patients with concomitant lower extremity arterial disease (LEAD) who have previously lost their GSV due to venous ablation.

Effectiveness of Telemedicine in Inflammatory Bowel Disease in Russia: TIGE-Rus (Telemonitoring for IBD Goodness Examination in Russia) Study Protocol of a Randomized Controlled Trial.

: Inflammatory bowel diseases (IBD), associated with a significant burden on patients' lives, are becoming increasingly common. Patients with IBD need continuous treatment and lifelong monitoring, which could be achieved by telemonitoring. Telemonitoring has been shown to be effective in improving outcomes for patients with IBD, and can provide a more convenient and accessible way for patients to receive care.

Pancreatic Neuroendocrine Tumor: The Case Report of a Patient with Germline Mutation and Tumor Analysis Using Single-Cell RNA Sequencing.

Unlabelled: Neuroendocrine neoplasms are a rare and heterogeneous group of neoplasms. Small-sized (≤2 cm) pancreatic neuroendocrine tumors (PanNETs) are of particular interest as they are often associated with aggressive behavior, with no specific prognostic or progression markers.

Methods: This article describes a clinical case characterized by a progressive growth of nonfunctional PanNET requiring surgical treatment in a patient with a germline mutation, previously not reported in PanNETs.

Advancements in Minimally Invasive Techniques and Biomarkers for the Early Detection of Endometrial Cancer: A Comprehensive Review of Novel Diagnostic Approaches and Clinical Implications.

This review evaluates the advances in the early detection and diagnosis of endometrial cancer (EC), emphasizing the growing importance of minimally invasive techniques and novel biomarkers. Current diagnostic protocols for EC rely heavily on invasive procedures such as transvaginal ultrasound (TVU), hysteroscopy, and endometrial biopsy, which, although effective, can be overly burdensome for patients and inefficient for asymptomatic or low-risk populations. As there is no consensus on EC screening in high-risk or general populations, recent studies have explored alternative methods using biofluids and genomic biomarkers to improve sensitivity and specificity and facilitate access for patients.

Localization of Secondary Metabolites in Relict Gymnosperms of the Genus In Vivo and in Cell Cultures In Vitro, and the Biological Activity of Their Extracts.

In order to scientifically search for new sources of secondary metabolites with valuable qualities for phytopharmacognosy, tasks requiring a step-by-step solution were set. The primary task is the development of technologies for obtaining in vitro highly productive biomass of cells of relict gymnosperms of the genus , capable of accumulating various classes of secondary metabolites. The study of the accumulation and localization of secondary metabolites allowed us to evaluate the biological activity and cytotoxicity of in vitro cultures.