Search Results (10,048)

Compounds with rigid planar structures can insert into tumor cell DNA, thereby inducing DNA damage in tumor cells. In this study, quinazoline, a compound with a planar structure, was used as the core scaffold. A rigid planar 1,2,3-triazole moiety was introduced into its structure, and its activity was tested on HepG2 liver cancer cells. The results showed that most compounds exhibc± 0.37 μM and 3.60 ± 0.53 μM. We found that the designed compounds significantly upregulated the expression of γ-H2AX in tumor cells, inducing DNA damage while reducing PARP levels, thereby weakening the DNA damage repair capacity of tumor cells and leading to apoptosis. Additionally, these compounds inhibited the migration and invasion of HepG2 cells. One of the compounds was found to be low in toxicity in mice, suggesting its potential as a targeted DNA anti-tumor drug. Full article

Tissue regeneration can be achieved by providing endogenous cells with a biomaterial scaffold that supports their adhesion and proliferation, as well as the synthesis and deposition of an extracellular matrix (ECM). In this work, silk fibroin protein foams were formed by lyophilization to generate tissue engineering scaffolds. Three types of medically relevant nanoparticles (NPs) (iron oxide, gold and silver) were added to this biomaterial to assess the ability of silk foams to be functionalized with these NPs. The structural and mechanical properties of the foams with and without the NPs were suitable for tissue support. The in vitro cytocompatibility of the scaffolds was confirmed according to the ISO 10993 guidelines. The biocompatibility of the scaffolds was investigated by assessing inflammation and endogenous cell colonization in a mouse subcutaneous model These in vivo experiments demonstrated a loss of acute inflammation and the absence of chronic inflammation in the grafted animals. The obtained results show that silk foams are good candidates for supporting soft tissue regeneration with the additional possibility of functionalization with NPs. Full article

This study evaluates the effects of two decellularization protocols, enzyme-detergent (ED) and detergent-detergent (DD), on the structural and biomechanical properties of human urethral tissue. Urethral samples from 18 individuals were divided into ED (n = 7) and DD (n = 11) groups, with native samples (n = 3) serving as controls. Histological and ultrastructural analyses confirmed that both protocols effectively removed cellular content while preserving essential extracellular matrix (ECM) elements, such as collagen and elastic fibers. Immunohistochemical staining for collagen IV and fibronectin revealed no significant differences between decellularized and native tissues, indicating intact ECM structure. Biomechanical testing demonstrated that DD-treated tissues had significantly lower Cauchy stress (1494.8 ± 518.4 kPa) when compared to native tissues (2439.7 ± 578.7 kPa, p = 0.013), while ED-treated tissues were similar to both groups. Both decellularized groups exhibited reduced stretch at failure and elastic modulus compared to native tissues. Cytotoxicity assays using adipose-derived stem cells demonstrated no signs of toxicity in either protocol. Overall, both ED and DD protocols effectively preserved the urethral ECM structure and mechanical properties, making them suitable for potential use in tissue-engineered grafts and for biobanking purposes. Further research is needed to refine and optimize decellularization methods to improve scaffold recellularization and ensure clinical safety and efficacy. Full article

The disorder and heterogeneity of low-molecular-weight amyloid-beta oligomers (AβOs) underlie their participation in multiple modes of cellular dysfunction associated with the etiology of Alzheimer’s disease (AD). The lack of specified conformational states in these species complicates efforts to select or design small molecules to targeting discrete pathogenic states. Furthermore, targeting AβOs alone may be therapeutically insufficient, as AD progresses as a multifactorial, self-amplifying cascade. To address these challenges, we have screened the activity of seven new candidates that serve as Paramagnetic Amyloid Ligand (PAL) candidates. PALs are bifunctional small molecules that both remodel the AβO structure and localize a potent antioxidant that mimics the activity of SOD within live cells. The candidates are built from either a stilbene or curcumin scaffold with nitroxyl moiety to serve as catalytic antioxidants. Measurements of PAL AβO binding and remolding along with assessments of bioactivity allow for the extraction of useful SAR information from screening data. One candidate (HO-4450; PMT-307), with a six-membered nitroxyl ring attached to a stilbene ring, displays the highest potency in protecting against cell-derived Aβ. A preliminary low-dose evaluation in AD model mice provides evidence of modest treatment effects by HO-4450. The results for the curcumin PALs demonstrate that the retention of the native curcumin phenolic groups is advantageous to the design of the hybrid PAL candidates. Finally, the PAL remodeling of AβO secondary structures shows a reasonable correlation between a candidate’s bioactivity and its ability to reduce the fraction of antiparallel β-strand. Full article

Common Juniper (Juniperus communis L.) is a gymnosperm that stands out through its fleshy, spherical female cones, often termed simply “berries”. The cone berries and various vegetative parts (leaves, twigs and even roots) are used in traditional phytotherapy, based on the beneficial effects exerted by a variety of secondary metabolites. While the volatile compounds of Juniperus communis are known for their aromatic properties and have been well-researched for their antimicrobial effects, this review shifts focus to non-volatile secondary metabolites—specifically diterpenes, lignans, and biflavonoids. These compounds are of significant biomedical interest due to their notable pharmacological activities, including antioxidant, anti-inflammatory, antimicrobial, and anticancer effects. The aim of this review is to offer an up-to-date account of chemical composition of Juniperus communis and related species, with a primary emphasis on the bioactivities of diterpenes, lignans, and biflavonoids. By examining recent preclinical and clinical data, this work assesses the therapeutic potential of these metabolites and their mechanisms of action, underscoring their value in developing new therapeutic options. Additionally, this review addresses the pharmacological efficacy and possible therapeutic applications of Juniperus communis in treating various human diseases, thus supporting its potential role in evidence-based phytotherapy. Full article

Three-dimensional (3D) printing is a highly effective scaffold manufacturing technique that may revolutionize tissue engineering and regenerative medicine. The use of scaffolds, along with growth factors and cells, remains among the most promising approaches to organ regeneration. However, the applications of hard 3D-printed scaffolds may be limited by their poor surface properties, which play a crucial role in cell recruitment and infiltration, tissue–scaffold integration, and anti-inflammatory properties. However, various prerequisites must be met before 3D-printed scaffolds can be applied clinically to the human body. Consequently, various attempts have been made to modify the surfaces, porosities, and mechanical properties of these scaffolds. Techniques that involve the chemical and material modification of surfaces can also be applied to enhance scaffold efficacy. This review summarizes the characteristics and discusses the developmental directions of the latest 3D-printing technologies according to its intended application in unmet clinical needs. Full article

Regenerated cellulose fibers are a highly adaptable biomaterial with numerous medical applications owing to their inherent biocompatibility, biodegradability, and robust mechanical properties. In the domain of wound care, regenerated cellulose fibers facilitate a moist environment conducive to healing, minimize infection risk, and adapt to wound topographies, making it ideal for different types of dressings. In tissue engineering, cellulose scaffolds provide a matrix for cell attachment and proliferation, supporting the development of artificial skin, cartilage, and other tissues. Furthermore, regenerated cellulose fibers, used as absorbable sutures, degrade within the body, eliminating the need for removal and proving advantageous for internal suturing. The medical textile industry relies heavily on regenerated cellulose fibers because of their unique properties that make them suitable for various applications, including wound care, surgical garments, and diagnostic materials. Regenerated cellulose fibers are produced by dissolving cellulose from natural sources and reconstituting it into fiber form, which can be customized for specific medical uses. This paper will explore the various types, properties, and applications of regenerated cellulose fibers in medical contexts, alongside an examination of its manufacturing processes and technologies, as well as associated challenges. Full article

For feedback to be productive, it relies on the interactions of participants, design elements, and resources. Yet, complexities in clinical education pose challenges for feedback practices in students and teachers, and efforts to improve feedback often ignore the influence of culture and context. A recent sociocultural approach to feedback practices recognized three layers to understand the complexity of productive feedback: the encounter layer, the design layer, and the knowledge layer. This study explores the sociocultural factors that influence productive feedback practices in clinical settings from the clinical teacher–student dyad perspective. A cross-sectional qualitative study in a physiotherapy clerkship involved semi-structured interviews with ten students and eight clinical educators. Convenience sampling was used, and participation was voluntary. Employing thematic analysis from a sociocultural perspective, this study examined feedback practices across the three layers of feedback practices. The analysis yielded different elements along the three layers that enable productive feedback practices in the clinical workplace: (1) the feedback encounter layer: dyadic relationships, mutual trust, continuity of supervision, and dialogue; (2) the feedback design layer: enabled learning opportunities and feedback scaffolding; (3) the knowledge domain layer in the clinical culture: Growing clinical experience and accountability. In the context of undergraduate clinical education, productive feedback practices are shaped by social–cultural factors. Designing feedback practices should consciously integrate these components, such as cultivating relationships, fostering guidance, enhancing feedback agency, and enabling supervised autonomy to promote productive feedback. Full article

Osteochondral (OC) tissue plays a crucial role due to its ability to connect bone and cartilage tissues. To address the complexity of structure and functionality at the bone–cartilage interface, relevant to the presence of the tidemark as a critical element at the bone–cartilage boundary, we fabricated graded scaffolds through sequential 3D printing. The scaffold’s bottom layer was based on a gelatin/oxidized alginate mixture enriched with hydroxyapatite (HAp) to create a rougher surface and larger pores to promote osteogenesis. In contrast, the upper layer was engineered to have smaller pores and aimed to promote cartilage tissue formation and mimic the physical properties of the cartilage. An electrospun ε-polycaprolactone (PCL) membrane with micrometer-range pores was incorporated between the layers to replicate the function of tidemark—a barrier to prevent vascularization of cartilage from subchondral bone tissue. In vitro cell studies confirmed the viability of the cells on the layers of the scaffolds and the ability of PCL mesh to prevent cellular migration. The fabricated scaffolds were thoroughly characterized, and their mechanical properties were compared to native OC tissue, demonstrating suitability for OC tissue engineering and graft modeling. The distance of gradient of mineral concentration was found to be 151 µm for grafts and the native OC interface. Full article

Tuberculosis (TB) caused by Mycobacterium tuberculosis is a leading infectious cause of death globally. The treatment of patients becomes much more difficult for the increasingly common multi-drug resistant TB. Topoisomerase I is essential for the viability of M. tuberculosis and has been validated as a new target for the discovery of novel treatment against TB resistant to the currently available drugs. Virtual high-throughput screening based on machine learning was used in this study to identify small molecules that target the binding site of divalent ion near the catalytic tyrosine of M. tuberculosis topoisomerase I. From the virtual screening of more than 2 million commercially available compounds, 96 compounds were selected for testing in topoisomerase I relaxation activity assay. The top hit that has IC₅₀ of 7 µM was further investigated. Commercially available analogs of the top hit were purchased and tested with the in vitro enzyme assay to gain further insights into the molecular scaffold required for topoisomerase inhibition. Results from this project demonstrated that novel small molecule inhibitors of bacterial topoisomerase I can be identified starting with the machine-learning-based virtual screening approach. Full article

Tissue engineering is an interdisciplinary field that combines materials, methods, and biological molecules to engineer newly formed tissues to replace or restore functional organs. Biomaterials-based scaffolds play a crucial role in developing new tissue by interacting with human cells. Tissue engineering scaffolds with ideal characteristics, namely, nontoxicity, biodegradability, and appropriate mechanical and surface properties, are vital for tissue regeneration applications. However, current biocomposite scaffolds face significant limitations, particularly in achieving structural durability, controlled degradation rates, and effective cellular integration. These qualities are essential for maintaining long-term functionality in vivo. Although commonly utilized biomaterials can provide physical and chemical properties needed for tissue regeneration, inadequate biomimetic properties, as well as insufficient interactions of cells-scaffolds interaction, still need to be improved for the application of tissue engineering in vivo. It is impossible to achieve some essential features using a single material, so combining two or more materials may accomplish the requirements. In order to achieve a proper scaffold design, a suitable fabrication technique and combination of biomaterials with controlled micro or nanostructures are needed to achieve the proper biological responses. This review emphasizes advancements in scaffold durability, biocompatibility, and cellular responsiveness. It focuses on natural and synthetic polymer combinations and innovative fabrication techniques. Developing stimulus-responsive 3D scaffolds is critical, as these scaffolds enhance cell adhesion and promote functional tissue formation while maintaining structural integrity over time. This review also highlights the natural polymers, smart materials, and recent advanced techniques currently used to create emerging scaffolds for tissue regeneration applications. Full article

Tissue engineering of nervous tissue is a promising direction in the treatment of neurological diseases such as spinal cord injuries or neuropathies. Thanks to technological progress and scientific achievements; the use of cells; artificial scaffolds; and growth factors are becoming increasingly common. Despite challenges such as the complex structure of this tissue, regenerative medicine appears as a promising future approach to improve the quality of life of patients with nervous injuries. Until now; most functional biomaterials used for this purpose were based on decellularized extra cellular matrix (ECM) or nanofibrous materials, whereas current clinically verified ones in most cases do not exhibit bioactivity or the possibility for external stimulation. The aim of this research was to develop a new type of bioactive, chitosan-based 3D materials applicable as nerve guide conduits (NGCs) modified with poly(dopamine), Au/Pt coated with PVP nanoparticles, and cannabidiol. The NGCs were prepared under microwave-assisted conditions and their chemical structure was studied using the FT-IR method. Next, this study will discuss novel biomaterials for morphology and swelling abilities as well as susceptibility to biodegradation in the presence of collagenase and lysozyme. Finally, their potential in the field of nervous tissue engineering has been verified via a cytotoxicity study using the 1321N1 human astrocytoma cell line, which confirmed their biocompatibility in direct contact studies. Full article

Secondary intention healing offers an alternative when surgical options are infeasible. This study analyzed the effect of micronized acellular dermal matrices (mADMs; CGderm Matrix^®, CG Bio, Seoul, Republic of Korea) on secondary intention healing in patients with complex soft-tissue defects and assessed mADMs’ efficacy in promoting secondary healing and improving clinical outcomes in these challenging cases. This retrospective study included 26 patients treated with sheet-type reprocessed mADMs between August 2022 and December 2022 at Soonchunhyang University Cheonan Hospital. Patients with full-thickness skin defects classified as complex wounds were included. Data on demographics, wound characteristics, and treatment outcomes were collected and analyzed. Wound area was measured using ImageJ software, and statistical analyses were conducted using SPSS. The application of mADMs resulted in a median wound area reduction of 81.35%, demonstrating its significant efficacy in wound healing. Most patients presented with compromised vascular supply, significant tissue loss, or infections that precluded conventional surgical interventions. No significant correlations were observed between patient variables and wound-healing outcomes, indicating the complex nature of wound healing. mADMs effectively promote secondary intention healing by providing a supportive extracellular matrix scaffold that enhances epithelialization and angiogenesis. Their rapid absorption, ease of handling, and ability to improve wound tensile strength make them particularly suitable for complex wounds. Full article

Among eukaryotes, there are many examples of partial genome elimination during ontogenesis. A striking example of this phenomenon is the loss of entire avian chromosomes during meiosis, called a germline-restricted chromosome (GRC). The GRC is absent in somatic tissues but present in germ cells. It has been established that a prophase I male GRC is usually represented by a univalent surrounded by heterochromatin. In the present study, an immunocytochemical analysis of zebra finch spermatocytes was performed to focus on some details of this chromosome’s organization. For the first time, it was shown that a prophase I GRC contains the HORMAD1 protein, which participates in the formation of a full axial element. This GRC axial element has signs of a delay of core protein loading, probably owing to peculiarities of meiotic silencing of chromatin. The presence of repressive marks (H3K9me3 and H3K27me3) and the lack of RNA polymerase II, typically associated with active transcription, indicate transcriptional inactivation in the GRC body, despite the known activity of some genes of the GRC. Nevertheless, RPA and RAD51 proteins were found at some GRC sites, indicating the formation and repair of double-strand breaks on this chromosome. Our results provide new insights into the meiotic behavior and structure of a GRC. Full article

The “architectural suitability” of scaffolds for bone tissue engineering is commonly evaluated by assessing the pore volume and the mean pore size (or pore size distribution, if possible) and comparing these values with the reference ranges of human cancellous bone. However, these two parameters cannot precisely describe the complex architecture of bone scaffolds and just provide a preliminary comparative criterion. Permeability is suggested as a more comprehensive and significant parameter to characterize scaffold architecture and mass transport capability, being also related to bone in-growth and, thus, functional properties. However, assessing the permeability of bioactive ceramics and glass scaffolds is a complex task from both methodological and experimental viewpoints. After providing an overview of the fundamentals about porosity in scaffolds, this review explores the different experimental and numerical approaches used to determine the permeability of porous bioceramics, describing the methodologies used (pump-based, gravity-based, acoustic and computational methods) and highlighting advantages and limitations to overcome (e.g., reliability issues and need for better standardization of the experimental procedures). Full article