Variations in ECM Topography, Fiber Alignment, Mechanical Stiffness, and Cellular Composition Between Ventral and Dorsal Ligamentum Flavum Layers: Insights Into Hypertrophy Pathogenesis.

Background: Previous studies have suggested that changes in the composition of the extracellular matrix (ECM) play a significant role in the development of ligamentum flavum hypertrophy (LFH) and the histological differences between the ventral and dorsal layers of the hypertrophied ligamentum flavum. Although LFH is associated with increased fibrosis in the dorsal layer, comprehensive research exploring the characteristics of the ECM and its mechanical properties in both regions is limited. Furthermore, the distribution of fibrosis-associated myofibroblasts within LFH remains poorly understood.

3D bioprinted dynamic bioactive living construct enhances mechanotransduction-assisted rapid neural network self-organization for spinal cord injury repair.

Biomimetic neural substitutes, constructed through the bottom-up assembly of cell-matrix modulus via 3D bioprinting, hold great promise for neural regeneration. However, achieving precise control over the fate of neural stem cells (NSCs) to ensure biological functionality remains challenging. Cell behaviors are closely linked to cellular dynamics and cell-matrix mechanotransduction within a 3D microenvironment.

An extracellular vesicle based hypothesis for the genesis of the polycystic kidney diseases.

Autosomal dominant polycystic kidney (ADPKD) disease is the commonest genetic cause of kidney failure (affecting 1:800 individuals) and is due to heterozygous germline mutations in either of two genes, and . Homozygous germline mutations in are responsible for autosomal recessive polycystic kidney (ARPKD) disease a rare (1:20,000) but severe neonatal disease. The products of these three genes, (polycystin-1 (PC1 4302(3)aa)), (polycystin-2 (PC2 968aa)) and (fibrocystin (4074aa)) are all present on extracellular vesicles (EVs) termed, PKD-exosome-like vesicles (PKD-ELVs).

Proteome differences of dental stem cells between permanent and deciduous teeth by data-independent acquisition proteomics.

Dental pulp stem cells hold significant prospects for tooth regeneration and repair. However, a comprehensive understanding of the molecular differences between dental pulp stem cells (DPSC, from permanent teeth) and stem cells from human exfoliated deciduous teeth (SHED, from deciduous teeth) remains elusive, which is crucial for optimizing their therapeutic potential. To address this gap, we employed a novel data-independent acquisition (DIA) proteomics approach to compare the protein expression profiles of DPSC and SHED.

Assessing patient risk, benefit and outcomes in drug development: an observational study of regorafenib clinical trials.

Objective: Our objective of this study was to analyse all oncological clinical trials using regorafenib to create a complete risk/benefit profile for the drug.

Background: Creating a novel chemotherapy is costly both in time and capital spent for drug manufacturers. To regenerate what they've spent, drug manufacturers may attempt to repurpose their medications for new indications via clinical trials.

Potential implications of granzyme B in keloids and hypertrophic scars through extracellular matrix remodeling and latent TGF-β activation.

Keloid scars (KS) and hypertrophic scars (HS) are fibroproliferative wound healing defects characterized by excessive accumulation of extracellular matrix (ECM) in the dermis of affected individuals. Although transforming growth factor (TGF)-β is known to be involved in the formation of KS and HS, the molecular mechanisms responsible for its activation remain unclear. In this study we investigated Granzyme B (GzmB), a serine protease with established roles in fibrosis and scarring through the cleavage of ECM proteins, as a potential new mediator of TGF-β activation in KS and HS.

The next generation of regenerative dentistry: From tooth development biology to periodontal tissue, dental pulp, and whole tooth reconstruction in the clinical setting.

In modern dentistry, prosthetic approaches such as implants and dentures have been developed as symptomatic solutions for tooth loss. However, the complete regeneration of teeth and periodontal tissue, an ultimate aspiration of humanity, remains unachieved. Recent advancements in fundamental scientific technologies, including single-cell RNA sequencing and spatial transcriptomics, have significantly advanced our molecular understanding of tooth development, paving the way toward achieving this goal.

Simultaneous Guidance of Intraoperative Tumor Resection by Near-Infrared-II Imaging Combined with Complementary Surface-Enhanced Raman Imaging via Janus Au-PbS Nanoparticles.

The development of sophisticated nanomaterials with synergistically enhanced functionalities and applications has been greatly promoted via the construction of Janus nanoparticles with controlled compositions. In this work, we described and demonstrated the formation of Janus Au-PbS nanoparticles (NPs) by Au NPs-mediated spontaneous epitaxial nucleation and growth. The mechanism of formation of Janus Au-PbS NPs was investigated in detail.

Electroacupuncture for the treatment of ischemic stroke: a preclinical meta-analysis and systematic review.

Stroke remains a leading cause of death and disability worldwide, and electroacupuncture has a long history of use in stroke treatment. This meta-analysis and systematic review aimed to evaluate the efficacy of electroacupuncture and explore its potential mechanisms in animal models of ischemic stroke. The PubMed, EMBASE, Web of Science, CENTRAL, and CINAHL databases were comprehensively searched up to May 1, 2024.

Enhancing neural stem cell integration in the injured spinal cord through targeted PTEN modulation.

Spinal cord injury results in permanent loss of neurological functions due to severance of neural networks. Transplantation of neural stem cells holds promise to repair disrupted connections. Yet, ensuring the survival and integration of neural stem cells into the host neural circuit remains a formidable challenge.

Multi-target neural circuit reconstruction and enhancement in spinal cord injury.

After spinal cord injury, impairment of the sensorimotor circuit can lead to dysfunction in the motor, sensory, proprioceptive, and autonomic nervous systems. Functional recovery is often hindered by constraints on the timing of interventions, combined with the limitations of current methods. To address these challenges, various techniques have been developed to aid in the repair and reconstruction of neural circuits at different stages of injury.

NLRP3 inflammasome and gut microbiota-brain axis: a new perspective on white matter injury after intracerebral hemorrhage.

Intracerebral hemorrhage is the most dangerous subtype of stroke, characterized by high mortality and morbidity rates, and frequently leads to significant secondary white matter injury. In recent decades, studies have revealed that gut microbiota can communicate bidirectionally with the brain through the gut microbiota-brain axis. This axis indicates that gut microbiota is closely related to the development and prognosis of intracerebral hemorrhage and its associated secondary white matter injury.

Probiotic active gel promotes diabetic wound healing through continuous local glucose consumption and antioxidant.

Background: Diabetic foot ulcers (DFU) are severe complications of diabetes, posing significant health and societal challenges. Accumulation of reactive oxygen species (ROS) and elevated glucose levels are primary factors affecting diabetic wound healing. Achieving effective treatment by reducing ROS alone is challenging, as high glucose levels continuously drive ROS production.

Women and birth partners' experiences of cervical ripening at home and in hospital.

Background: In the United Kingdom, induction of labour rates are rapidly rising, and around a third of pregnant women undergo the procedure. The first stage, cervical ripening, traditionally carried out in hospital, is increasingly offered outpatient - or 'at home'. The current induction of labour rates place considerable demand on maternity services and impact women's experiences of care, and at home cervical ripening has been suggested as potential solution for alleviating these.

Peripheral nerve regeneration using a bioresorbable silk fibroin-based artificial nerve conduit fabricated via a novel freeze-thaw process.

While silk fibroin (SF) obtained from silkworm cocoons is expected to become a next-generation natural polymer, a fabrication method for SF-based artificial nerve conduits (SFCs) has not yet been established. Here, we report a bioresorbable SFC, fabricated using a novel freeze-thaw process, which ensures biosafety by avoiding any harmful chemical additives. The SFC demonstrated favorable biocompatibility (high hydrophilicity and porosity with a water content of > 90%), structural stability (stiffness, toughness, and elasticity), and biodegradability, making it an ideal candidate for nerve regeneration.

Genes related to neural tube defects and glioblastoma.

There are many similarities between early embryonic development and tumorigenesis. The occurrence of neural tube defects (NTDs) and glioblastoma (GBM) are both related to the abnormal development of neuroectodermal cells. To obtain genes related to both NTDs and GBM, as well as small molecule drugs with potential clinical application value.

EZH2 serves as a viable therapeutic target for myeloma-induced osteolytic bone destruction.

Myelomatous bone disease is a complication characterized by lytic bone lesions, reduced bone formation, bone pain, and increased fracture risk. Understanding these underlying mechanisms is crucial for developing effective therapeutic approaches. Here we show the role of enhancer of zeste homolog 2 (EZH2) in bone lesions induced by myeloma cells.

Safety and efficacy of filgotinib in patients with rheumatoid arthritis: final results of the DARWIN 3 long-term extension study.

Objectives: DARWIN 3 (ClinicalTrials.gov: NCT02065700) assessed the safety and efficacy of filgotinib in a long-term extension (LTE) of two phase II randomised controlled rheumatoid arthritis (RA) trials.

Methods: Eligible patients completing the 24-week DARWIN 1 (filgotinib plus methotrexate) and DARWIN 2 (filgotinib monotherapy) trials could enrol.

Modification-based Pinus pumila polysaccharides and their effects on osteoblast MC3T3-E1.

In this study, a polysaccharide component was extracted from Pinus pumila using biomimetic-microwave assisted alkali tandem extraction and then purified by DEAE-52 and Sephadex G-200. A new purified polysaccharide (PSP c-a) was determined through in vitro tracking. The structural features were characterized using a HPGP, FTIR, IC and NMR spectroscopy.

Cluster Analysis of HCC Prognosis Using Preoperative AFP and DCP Levels: A Multi-Institutional Study.

Background: Hepatocellular carcinoma (HCC) remains a leading cause of cancer-related mortality worldwide, characterized by high recurrence rates post-curative resection. Tumor markers des-gamma-carboxy prothrombin (DCP) and alpha-fetoprotein (AFP) are crucial for HCC diagnosis and prognosis, yet their roles in the modern era of HCC epidemiology require reevaluation.

Methods: This multi-institutional retrospective study analyzed 1,515 patients who underwent hepatectomy for primary HCC.

Endothelial Colony-Forming Cells (ECFCs) in Cerebrovascular Aging: Focus on the Pathogenesis of Vascular Cognitive Impairment and Dementia (VCID), and Treatment Prospects.

Endothelial colony-forming cells (ECFCs), a unique endothelial progenitor subset, are essential for vascular integrity and repair, providing significant regenerative potential. Recent studies highlight their role in cerebrovascular aging, particularly in the pathogenesis of vascular cognitive impairment and dementia (VCID). Aging disrupts ECFC functionality through mechanisms such as oxidative stress, chronic inflammation, and cellular senescence, leading to compromised vascular repair and reduced neurovascular resilience.

Casz1 is required for both inner hair cell fate stabilization and outer hair cell survival.

Cochlear inner hair cells (IHCs) and outer hair cells (OHCs) require different transcription factors for their cell fate stabilization and survival, suggesting separate mechanisms are involved. Here, we found that the transcription factor Casz1 was crucial for early IHC fate consolidation and for OHC survival during mouse development. Loss of Casz1 resulted in transdifferentiation of IHCs into OHCs, without affecting OHC production.

PRC2 promotes canalisation during endodermal differentiation.

The genetic circuitry that encodes the developmental programme of mammals is regulated by transcription factors and chromatin modifiers. During early gestation, the three embryonic germ layers are established in a process termed gastrulation. The impact of deleterious mutations in chromatin modifiers such as the polycomb proteins manifests during gastrulation, leading to early developmental failure and lethality in mouse models.

Aerobic exercise prevents renal osteodystrophy via irisin-activated osteoblasts.

Renal osteodystrophy is commonly seen in patients with chronic kidney disease (CKD) due to disrupted mineral homeostasis. Given the impaired renal function in these patients, common anti-resorptive agents, including bisphosphonates, must be used with caution or even contraindicated. Therefore, an alternative therapy without renal burden to combat renal osteodystrophy is urgently needed.

In vivo bone regeneration performance of hydroxypropyl methylcellulose hydrogel-based composite bone cements in ovariectomized and ovary-intact rats: a preliminary investigation.

The objective of this study is to fabricate and develop hydroxypropyl methylcellulose (HPMC) hydrogel (HG)-based composite bone cements with incorporation of hydroxyapatite (HA), beta-tricalcium phosphate (β-TCP), and with/without polymethylmethacrylate (PMMA) for vertebroplasty. For animal study, twenty female Wister rats (250-300 g, 12 weeks of age) were divided into four groups including a two non-ovariectomy (NOVX) groups and two ovariectomy (OVX)-induced osteoporosis groups. Two prepared biocomposites including HG/β-TCP/HA and HG/β-TCP/HA/PMMA were injected into the tibial defects of both OVX and NOVX rats for evaluating in vivo osteogenesis after 12 weeks.