Expert Revision of Key Elements for Clinical-Grade Production and Qualification of Perinatal Derivatives.

Perinatal derivatives have been proposed as adjunct therapeutic strategies or innovative treatments. Undoubtedly, perinatal derivatives can offer the opportunity and source material to isolate multipotent stem cells, but both maternal- and fetal-derived tissues can be processed and transformed into engineered tissues or advanced biomedical devices, whose potential remains to be fully elucidated. Promising preclinical and clinical results collected so far clearly foresee an escalation of such novel treatments.

The Role of Surface Complexes in Ketene Formation from Fatty Acids via Pyrolysis over Silica: from Platform Molecules to Waste Biomass.

Fatty acids (FA) are the main constituents of lipids and oil crop waste, considered to be a promising 2G biomass that can be converted into ketenes via catalytic pyrolysis. Ketenes are appraised as promising synthons for the pharmaceutical, polymer, and chemical industries. Progress in the thermal conversion of short- and long-chain fatty acids into ketenes requires a deep understanding of their interaction mechanisms with the nanoscale oxide catalysts.

Learning sequence, structure, and function representations of proteins with language models.

The sequence-structure-function relationships that ultimately generate the diversity of extant observed proteins is complex, as proteins bridge the gap between multiple informational and physical scales involved in nearly all cellular processes. One limitation of existing protein annotation databases such as UniProt is that less than 1% of proteins have experimentally verified functions, and computational methods are needed to fill in the missing information. Here, we demonstrate that a multi-aspect framework based on protein language models can learn sequence-structure-function representations of amino acid sequences, and can provide the foundation for sensitive sequence-structure-function aware protein sequence search and annotation.

Human mesenchymal stem cells increase LLC metastasis and stimulate or decelerate tumor development depending on injection method and cell amount.

Mesenchymal stem cells (MSCs) being injected into the body can stimulate or decelerate carcinogenesis. Here, the direction of influence of human placenta-derived MSCs (P-MSCs) on the Lewis lung carcinoma (LLC) tumor development and metastatic potential is investigated in C57BL/6 mice depending on the injection method. After intramuscular co-inoculation of LLC and P-MSCs (LLC + P-MSCs), the growth of primary tumor and angiogenesis are slowed down compared to the control LLC on the 15th day.

Recent progress in miRNA biogenesis and decay.

MicroRNAs are a class of small regulatory RNAs that mediate regulation of protein synthesis by recognizing sequence elements in mRNAs. MicroRNAs are processed through a series of steps starting from transcription and primary processing in the nucleus to precursor processing and mature function in the cytoplasm. It is also in the cytoplasm where levels of mature microRNAs can be modulated through decay mechanisms.

Comparative analysis of classification techniques for topic-based biomedical literature categorisation.

Scientific articles serve as vital sources of biomedical information, but with the yearly growth in publication volume, processing such vast amounts of information has become increasingly challenging. This difficulty is particularly pronounced when it requires the expertise of highly qualified professionals. Our research focused on the domain-specific articles classification to determine whether they contain information about drug-induced liver injury (DILI).

Femtosecond laser modified metal surfaces alter biofilm architecture and reduce bacterial biofilm formation.

Biofilm formation, or microfouling, is a basic strategy of bacteria to colonise a surface and may happen on surfaces of any nature whenever bacteria are present. Biofilms are hard to eradicate due to the matrix in which the bacteria reside, consisting of strong, adhesive and adaptive self-produced polymers such as eDNA and functional amyloids. Targeting a biofilm matrix may be a promising strategy to prevent biofilm formation.

On the wake of metformin: Do anti-diabetic SGLT2 inhibitors exert anti-aging effects?

Here we propose that SGLT2 inhibitors (SGLT2i), a class of drugs primarily used to treat type 2 diabetes, could also be repositioned as anti-aging senomorphic drugs (agents that prevent the extrinsic harmful effects of senescent cells). As observed for metformin, another anti-diabetic drug with established anti-aging potential, increasing evidence suggests that SGLT2i can modulate some relevant pathways associated with the aging process, such as free radical production, cellular energy regulation through AMP-activated protein kinase (AMPK), autophagy, and the activation of nuclear factor (NF)-kB/inflammasome. Some interesting pro-healthy effects were also observed on human microbiota.

Integrated workflow for the identification of new GABA R positive allosteric modulators based on the in silico screening with further in vitro validation. Case study using Enamine's stock chemical space.

Numerous studies reported an association between GABA R subunit genes and epilepsy, eating disorders, autism spectrum disorders, neurodevelopmental disorders, and bipolar disorders. This study was aimed to find some potential positive allosteric modulators and was performed by combining the in silico approach with further in vitro evaluation of its real activity. We started from the GABA R-diazepam complexes and assembled a lipid embedded protein ensemble to refine it via molecular dynamics (MD) simulation.

Telomeric repeat evolution in the phylum Nematoda revealed by high-quality genome assemblies and subtelomere structures.

Telomeres are composed of tandem arrays of telomeric-repeat motifs (TRMs) and telomere-binding proteins (TBPs), which are responsible for ensuring end-protection and end-replication of chromosomes. TRMs are highly conserved owing to the sequence specificity of TBPs, although significant alterations in TRM have been observed in several taxa, except Nematoda. We used public whole-genome sequencing data sets to analyze putative TRMs of 100 nematode species and determined that three distinct branches included specific novel TRMs, suggesting that evolutionary alterations in TRMs occurred in Nematoda.

What is central to renal nutrition: protein or sodium intake?

Historically, nutrition intervention has been primarily focused on limiting kidney injury, reducing generation of uraemic metabolites, as well as maintaining nutrition status and preventing protein-energy wasting in patients with chronic kidney disease (CKD). This forms an important rationale for prescribing restricted protein diet and restricted salt diet in patients with CKD. However, evidence supporting a specific protein intake threshold or salt intake threshold remains far from compelling.

The SGLT2 inhibitor dapagliflozin improves kidney function in glycogen storage disease XI.

Glycogen storage disease XI, also known as Fanconi-Bickel syndrome (FBS), is a rare autosomal recessive disorder caused by mutations in the gene that encodes the glucose-facilitated transporter type 2 (GLUT2). Patients develop a life-threatening renal proximal tubule dysfunction for which no treatment is available apart from electrolyte replacement. To investigate the renal pathogenesis of FBS, expression was ablated in mouse kidney and HK-2 proximal tubule cells.

CHESS 3: an improved, comprehensive catalog of human genes and transcripts based on large-scale expression data, phylogenetic analysis, and protein structure.

CHESS 3 represents an improved human gene catalog based on nearly 10,000 RNA-seq experiments across 54 body sites. It significantly improves current genome annotation by integrating the latest reference data and algorithms, machine learning techniques for noise filtering, and new protein structure prediction methods. CHESS 3 contains 41,356 genes, including 19,839 protein-coding genes and 158,377 transcripts, with 14,863 protein-coding transcripts not in other catalogs.

From Cardiorenal Syndrome to Chronic Cardiovascular and Kidney Disorder: A Conceptual Transition.

The association between cardiac and kidney dysfunction has received attention over the past two decades. A putatively unique syndrome, the cardiorenal syndrome, distinguishing five subtypes on the basis of the chronology of cardiac and kidney events, has been widely adopted. This review discusses the methodologic and practical problems inherent to the current classification of cardiorenal syndrome.

Current State of Human Gene Therapy: Approved Products and Vectors.

In the realm of gene therapy, a pivotal moment arrived with Paul Berg's groundbreaking identification of the first recombinant DNA in 1972. This achievement set the stage for future breakthroughs. Conditions once considered undefeatable, like melanoma, pancreatic cancer, and a host of other ailments, are now being addressed at their root cause-the genetic level.

Structure of human TRPM8 channel.

TRPM8 is a non-selective cation channel permeable to both monovalent and divalent cations that is activated by multiple factors, such as temperature, voltage, pressure, and changes in osmolality. It is a therapeutic target for anticancer drug development, and its modulators can be utilized for several pathological conditions. Here, we present a cryo-electron microscopy structure of a human TRPM8 channel in the closed state that was solved at 2.

Interplay between BMP2 and Notch signaling in endothelial-mesenchymal transition: implications for cardiac fibrosis.

Background: The endothelial-to-mesenchymal transition (EndoMT) is a crucial process in cardiovascular development and disorders. Cardiac fibrosis, characterized by excessive collagen deposition, occurs in heart failure, leading to the organ remodeling. Embryonic signaling pathways such as bone morphogenetic protein 2 (BMP2) and Notch are involved in its regulation.

Case report: Azithromycin-meropenem combination therapy as a low-cost approach to combat PDR gram-negative infections of war wounds in Ukraine.

Antimicrobial resistance recognised as a major global health problem and it poses a significant challenge in conflict zones, such as the Russia-Ukraine war. This case study focuses on a 32-year-old soldier who sustained combat-related injuries, including extensive wound infections caused by multidrug-resistant and pan-resistant bacteria and was successfully treated with azithromycin-meropenem combination therapy. The emergence of pan-resistant bacteria, particularly a pandrug-resistant strain of , highlights the severity of the problem and the limited treatment options available.

CLINICAL SIGNIFICANCE OF BRCA1 GENE SEQUENCING AND ITS PROMOTER METHYLATION TESTING IN THE SEARCH STRATEGY FOR THERAPEUTIC TARGETS IN BREAST CANCER TREATMENT.

Background: Currently, there is a great interest in the genetic testing of BRCA1 and BRCA2 due to the fact that for patients with breast cancer (BC) with pathogenic variants of these genes, the use of the PARP inhibitors could be also provided in addition to implemented treatment protocols. The aim of this study was to characterize the molecular genetic structure of the BRCA1 gene in BC patients without progenitor germline mutations taking into account the methylation state of the promoter region.

Materials And Methods: The study involved 210 patients with newly diagnosed BC.

Physical exercise in kidney disease: A commonly undervalued treatment modality.

Background: Physical inactivity has been identified as a risk factor for multiple disorders and a strong association exists between chronic kidney disease (CKD) and a sedentary lifestyle. Even though physical activity is crucial in the development and progression of disease, the general focus of the current medical practice is the pharmacological perspective of diseases with inadequate emphasis on lifestyle intervention.

Methods: In this narrative review we explain the pathophysiological mechanisms underlying the beneficial effects of physical exercise on CKD in addition to discussing the clinical studies and trials centred on physical exercise in patients with CKD.