The Role of miR-486-5p on CSCs Phenotypes in Colorectal Cancer.

Background: Colorectal cancer (CRC) is the third diagnosed cancer worldwide. Forty-four percent of metastatic colorectal cancer patients were diagnosed at an early stage. Despite curative resection, approximately 40% of patients will develop metastases within a few years.

Cisplatin-Induced Hearing Loss, Oxidative Stress, and Antioxidants as a Therapeutic Strategy-A State-of-the-Art Review.

Cisplatin is an established component of treatment protocols for various solid malignancies but carries a significant potential for serious adverse effects. Ototoxicity from cisplatin treatment is an important dose-limiting toxicity that manifests as bilateral, progressive, irreversible, dose-dependent sensorineural hearing loss, ear pain, tinnitus, and vestibular dysfunction. Despite the recent approval of sodium thiosulphate for the prevention of cisplatin-induced hearing loss (CIHL) in pediatric patients, structured prevention programs are not routinely implemented in most hospitals, and reducing platinum-induced ototoxicity in adults remains an important clinical problem without established treatment options.

Erinacine A-Enriched Mycelium Ethanol Extract Lessens Cellular Damage in Cell and Models of Spinocerebellar Ataxia Type 3 by Improvement of Nrf2 Activation.

Spinocerebellar ataxia type 3 (SCA3), caused by the abnormal expansion of polyglutamine (polyQ) in the ataxin-3 protein, is one of the inherited polyQ neurodegenerative diseases that share similar genetic and molecular features. Mutant polyQ-expanded ataxin-3 protein is prone to aggregation in affected neurons and is predominantly degraded by autophagy, which is beneficial for neurodegenerative disease treatment. Not only does mutant polyQ-expanded ataxin-3 increase susceptibility to oxidative cytotoxicity, but it also hampers antioxidant potency in neuronal cells.

PTN secreted by cardiac fibroblasts promotes myocardial fibrosis and inflammation of pressure overload-induced hypertrophic cardiomyopathy through the PTN-SDC4 pathway.

Aims: Hypertrophic cardiomyopathy (HCM) is characterized by unexplained left ventricular hypertrophy (LVH) with key pathologic processes including myocardial necrosis, fibrosis, inflammation, and hypertrophy, which are involved in heart failure (HF), stroke, and even sudden death. Our aim was to explore the communication network among various cells in the heart of transverse aortic constriction (TAC) surgery induced HCM mice.

Materials And Methods: Single-cell RNA-seq data of GSE137167 was downloaded from the Gene Expression Omnibus (GEO) database.

Cell origin and microenvironment: The players of differentiation capacity in human mesenchymal stem cells.

Mesenchymal stem cells (MSCs) have several important properties that make them desirable for regenerative medicine. These properties include immunomodulatory ability, growth factor production, and differentiation into various cell types. Despite extensive research and promising results in clinical trials, our understanding of MSC biology, their mechanism of action, and their targeted and routine use in clinics is limited.

Protocol for evaluating the activity of R2 retrotransposons in mammalian cells.

R2 retrotransposons can be harnessed to insert genes at targeted sites by all-RNA delivery, presenting a new technology for next-generation biotherapeutics. Here, we report a protocol for evaluating the gene integration activity of R2 retrotransposons in mammalian cells. We describe the construction of vectors separately expressing R2 protein and donor, the process of liposome transfection, and flow cytometry.

Regulation of T Cell Glycosylation by MXene/β-TCP Nanocomposite for Enhanced Mandibular Bone Regeneration.

Immune-mediated bone regeneration driven by bone biomaterials offers a therapeutic strategy for repairing bone defects. Among 2D nanomaterials, TiCT MXenes have garnered substantial attention for their potential in tissue regeneration. This investigation concentrates on the role of MXene nanocomposites in modulating the immune microenvironment within bone defects to facilitate bone tissue restoration.

α-Cyclodextrin supplementation improves endurance exercise performance and reduces post-exercise fatigue in human males: a randomized, double-blind, placebo-controlled, parallel-group study.

α-Cyclodextrin (αCD), a cyclic hexasaccharide composed of six glucose units, is not digested in the small intestine but is completely fermented by gut microbes. Recently, we have reported that αCD supplementation for nonathlete men improved their 10 km biking times. However, the beneficial effects of αCD on exercise are not yet fully understood.

sc-SPLASH provides ultra-efficient reference-free discovery in barcoded single-cell sequencing.

Typical high-throughput single-cell RNA-sequencing (scRNA-seq) analyses are primarily conducted by (pseudo)alignment, through the lens of annotated gene models, and aimed at detecting differential gene expression. This misses diversity generated by other mechanisms that diversify the transcriptome such as splicing and V(D)J recombination, and is blind to sequences missing from imperfect reference genomes. Here, we present sc-SPLASH, a highly efficient pipeline that extends our SPLASH framework for statistics-first, reference-free discovery to barcoded scRNA-seq (10x Chromium) and spatial transcriptomics (10x Visium); we also provide its optimized module for preprocessing and -mer counting in barcoded data, BKC, as a standalone tool.

Genetically Labeled Premyelinating Oligodendrocytes: Bridging Oligodendrogenesis and Neuronal Activity.

To myelinate axons, oligodendrocyte precursor cells (OPCs) must stop dividing and differentiate into premyelinating oligodendrocytes (preOLs). PreOLs are thought to survey and begin ensheathing nearby axons, and their maturation is often stalled at human demyelinating lesions. Lack of genetic tools to visualize and manipulate preOLs has left this critical differentiation stage woefully understudied.

U-shaped relationship between serum uric acid and gastric cancer risk: a large prospective cohort study.

Objective: We conducted this study to investigate the relationship between serum uric acid (SUA) levels and the risk of upper gastrointestinal cancer.

Methods: We conducted a prospective cohort study with 475659 cancer-free participants from the UK Biobank. All subjects were grouped into quartiles, and we used a Cox proportional hazards model to analyze the association between SUA levels and the risk of upper gastrointestinal cancer and explore the potential sex-specific relationship.

Nanoparticles for the Delivery of Pro-regenerative Cardiac Progenitor Secretory Proteins Targeting Cellular Senescence and Vasculogenesis.

Contemporary therapies following heart failure center on regenerative approaches to account for the loss of cardiomyocytes and limited regenerative capacity of the adult heart. While the delivery of cardiac progenitor cells has been shown to improve cardiac function and repair following injury, recent evidence has suggested that their paracrine effects (or secretome) provides a significant contribution towards modulating regeneration, rather than the progenitor cells intrinsically. The direct delivery of secretory biomolecules, however, remains a challenge due to their lack of stability and tissue retention, limiting their prolonged therapeutic efficacy.

Effect of Hyaluronan Molecular Weight on the Stability and Biofunctionality of Microfibers Assembled by Interfacial Polyelectrolyte Complexation.

Nervous system disorders are characterized by a progressive loss of function and structure of neurons that ultimately leads to a decline in cognitive and motor functions. In this study, we used interfacial polyelectrolyte complexation (IPC) to produce fibers for neural tissue regeneration. IPC is a processing method that allows spinning of sensitive biopolymers.

Whole-genome sequencing identifies novel loci for keratoconus and facilitates risk stratification in a Han Chinese population.

Background: Keratoconus (KC) is a prevalent corneal condition with a modest genetic basis. Recent studies have reported significant genetic associations in multi-ethnic cohorts. However, the situation in the Chinese population remains unknown.

Construction and Behavioral Comparison of Two Mouse Models of Cerebral Palsy.

Cerebral palsy (CP) is the most common neuromuscular disorder in children with no effective therapeutic methods. To examine CP, a large variety of methods and animal models was developed, the most popular are the hypoxic-ischemic (HI) injury and/or LPS injection in mice. In the presented work, HI and LPS were applied on the postnatal day 9 to humanized immunodeficiency mouse pups, thereupon 3 behavioral tests were performed in 8 weeks later.

Consequences of Reprogrammed CD8 T-Cell Therapy for Lewis Lung Carcinoma Cells and Neovasculogenesis in C57BL/6 Mice.

We studied the effect of reprogrammed CD8 T cells (rT cells) from the bone marrow of intact mice on tumor cells and neovasculogenesis in mice with orthotopic Lewis lung carcinoma (LLC). Reprogramming of T cells was carried out using a MEK inhibitor and a PD-1 blocker; the targeting of rT cells to tumor cells was achieved by preincubation with LLC cell lysate. It was shown that the antitumor effect of rT cells was based on apoptosis of tumor cells.

Hypoxia-Preconditioned Adipose Stem Cell Exosomes Promote Adipose Graft Vascular Regeneration via miRNA-126.

Background And Objective: Adipose-derived mesenchymal stem cell-derived extracellular vesicles (ASCs-Exos) possess angiogenic potential, which can enhance the retention rate of fat grafts. Hypoxic preconditioning can augment their functionality. However, the optimal conditions for hypoxic preconditioning and the specific mechanisms by which it exerts its effects are not well defined.

Innovative Mechanical Processing of Adipose Tissue: A Comparative Evaluation of Microfat and Concentrated Micronized Fat for Superficial Fat Grafting.

Background: Superficial autologous fat grafting is widely used for facial rejuvenation and regenerative treatments, yet its retention rate remains unpredictable. Enhancing the concentration of adipose-derived stem cells (ASCs) has been shown to improve graft retention. Mechanical fat processing techniques can reduce fat granules size for superficial injection as well as elevate the concentration of ASCs.

DNA-damage orchestrates self-renewal and differentiation via reciprocal p53 family and Hippo/Wnt/TGF-β pathway activation in embryonic stem cells.

The mechanism by which DNA-damage affects self-renewal and pluripotency remains unclear. DNA damage and repair mechanisms have been largely elucidated in mutated cancer cells or simple eukaryotes, making valid interpretations on early development difficult. Here we show the impact of ionizing irradiation on the maintenance and early differentiation of mouse embryonic stem cells (ESCs).

METTL3 modulates colonic epithelium integrity via maintaining the self-renewal and differentiation of Lgr5+ stem cell.

The development and homeostasis of intestinal epithelium are mediated by actively proliferating Lgr5+ stem cells, which possess a remarkable self-renewal and differentiation capacity. Recently, our study demonstrated that m6A methylation was essential for the survival of colonic stem cells. Here, we show that METTL3 expression is downregulated in the colon mucosa in ulcerative colitis (UC) patients and strongly associated with the differentiation and maturation of goblet cells during inflammation.

The effect of conditioned medium from human amniotic membrane-derived mesenchymal stem cells on thymus involution.

Aims: The development and selection of T cells occur within the thymus. This organ involutes throughout life, compromising the generation of T cells and, consequently, the efficacy of the immune system. Mesenchymal stem cells (MSC) have beneficial effects on the immune system.

Omega-3 Polyunsaturated Fatty Acids in Chronic Obstructive Pulmonary Disease Patients with COVID-19: A Review.

Purpose Of The Review: Mounting evidence indicates that individuals with chronic obstructive pulmonary disease (COPD) face a heightened risk of severe outcomes upon contracting coronavirus disease 2019 (COVID-19). Current medications for COVID-19 often carry side effects, necessitating alternative therapies with improved tolerance. This review explores the biological mechanisms rendering COPD patients more susceptible to severe COVID-19 and investigates the potential of omega-3 polyunsaturated fatty acids (n-3 PUFAs) in mitigating the severity of COVID-19 in COPD patients.

Cell-type specific epigenetic clocks to quantify biological age at cell-type resolution.

The ability to accurately quantify biological age could help monitor and control healthy aging. Epigenetic clocks have emerged as promising tools for estimating biological age, yet they have been developed from heterogeneous bulk tissues, and are thus composites of two aging processes, one reflecting the change of cell-type composition with age and another reflecting the aging of individual cell-types. There is thus a need to dissect and quantify these two components of epigenetic clocks, and to develop epigenetic clocks that can yield biological age estimates at cell-type resolution.