Bioinformatics analysis based on crucial genes of endothelial cells in rheumatoid.

Synovial neovascularization is an early and remarkable event that promotes the development of rheumatoid arthritis (RA) synovial hyperplasia. This study aimed to find potential diagnostic markers and molecular therapeutic targets for RA at the mRNA molecular level. We download the expression profile dataset GSE46687 from the gene expression ontology (GEO) microarray, and used R software to screen out the differentially expressed genes between the normal group and the disease group.

Engineering Extracellular Vesicles as Delivery Systems in Therapeutic Applications.

Extracellular vesicles (EVs) are transport vesicles secreted by living cells and released into the extracellular environment. Recent studies have shown that EVs serve as "messengers" in intercellular and inter-organismal communication, in both normal and pathological processes. EVs, as natural nanocarriers, can deliver bioactivators in therapy with their endogenous transport properties.

GSTP1-mediated S-glutathionylation of Pik3r1 is a redox hub that inhibits osteoclastogenesis through regulating autophagic flux.

Glutathione S-transferase P1(GSTP1) is known for its transferase and detoxification activity. Based on disease-phenotype genetic associations, we found that GSTP1 might be associated with bone mineral density through Mendelian randomization analysis. Therefore, this study was performed both in vitro cellular and in vivo mouse model to determine how GSTP1 affects bone homeostasis.

Nesfatin-1 suppresses autophagy of chondrocytes in osteoarthritis via remodeling of cytoskeleton and inhibiting RhoA/ROCK signal pathway.

Autophagy and cytoskeleton integrity of chondrocytes are a considered as major factors in the progression of osteoarthritis (OA) involving excessive chondrocyte apoptosis and senescence. Nesfatin-1, an adipokine, has been reported to be closely related to cell autophagy and cytoskeleton malfunction. Our previous study found that nesfatin-1 was highly correlated with OA progress in OA patient, and the expression of nesfatin-1 rises in knee articular tissue, serum and chondrocytes.

Cyclooxygenase-2-Prostaglandin E2 pathway: A key player in tumor-associated immune cells.

Cyclooxygenases-2 (COX-2) and Prostaglandin E2 (PGE2), which are important in chronic inflammatory diseases, can increase tumor incidence and promote tumor growth and metastasis. PGE2 binds to various prostaglandin E receptors to activate specific downstream signaling pathways such as PKA pathway, β-catenin pathway, NF-κB pathway and PI3K/AKT pathway, all of which play important roles in biological and pathological behavior. Nonsteroidal anti-inflammatory drugs (NSAIDs), which play as COX-2 inhibitors, and EP antagonists are important in anti-tumor immune evasion.

Enhancing the Management of Metastatic Tumors by Robust Co-Delivery of 5-Fluorouracil/MicroRNA-10b Inhibitor Using EGFR-Targeted Nanovehicles.

Invasion and metastasis are the leading causes of death of patients with CRC. 5-Fluorouracil is widely used in clinic practice as the basic chemotherapy drug for CRC. However, it is inefficient in inhibiting tumor metastasis.

Engineered Sensory Nerve Guides Self-Adaptive Bone Healing via NGF-TrkA Signaling Pathway.

The upstream role of sensory innervation during bone homeostasis is widely underestimated in bone repairing strategies. Herein, a neuromodulation approach is proposed to orchestrate bone defect healing by constructing engineered sensory nerves (eSN) in situ to leverage the adaptation feature of SN during tissue formation. NGF liberated from ECM-constructed eSN effectively promotes sensory neuron differentiation and enhances CGRP secretion, which lead to improved RAOECs mobility and osteogenic differentiation of BMSC.

Sandwich Biomimetic Scaffold Based Tendon Stem/Progenitor Cell Alignment in a 3D Microenvironment for Functional Tendon Regeneration.

Tendon injuries are some of the most commonly diagnosed musculoskeletal diseases. Tendon regeneration is sensitive to the topology of the substitute as it affects the cellular microenvironment and homeostasis. To bionic in vivo three-dimensional (3D) aligned microenvironment, an ordered 3D sandwich model was used to investigate the cell response in the tendon.

Nucleus pulposus cell-derived efficient microcarrier for intervertebral disc tissue engineering.

Adipose-derived stem cells (ADSCs) show great potential for the treatment of intervertebral disc (IVD) degeneration. An ideal carrier is necessary to transplant ADSCs into degenerated IVDs without influencing cell function. Nucleus pulposus cells (NPCs) can synthesize and deposit chondroitin sulfate and type II collagen which are NP-specific extracellular matrix (ECM) and can also regulate the NP-specific differentiation of stem cells.

Therapeutic potential and mechanisms of mesenchymal stem cell-derived exosomes as bioactive materials in tendon-bone healing.

Tendon-bone insertion (TBI) injuries, such as anterior cruciate ligament injury and rotator cuff injury, are the most common soft tissue injuries. In most situations, surgical tendon/ligament reconstruction is necessary for treating such injuries. However, a significant number of cases failed because healing of the enthesis occurs through scar tissue formation rather than the regeneration of transitional tissue.

The regulation of N6-methyladenosine modification in PD-L1-induced anti-tumor immunity.

There is growing evidence that programmed death ligand-1 (PD-L1) has exciting therapeutic efficacy in hematological malignancy and partial solid tumors. However, many patients still face failure with the treatment of immune checkpoint blockade because of PD-L1 expression regulation during transcription and post-transcription processes, including N6-methyladenosine (m6A). Similar to the epigenetic regulation in DNA and histones, recent research has revealed the essential regulation of m6A modification in RNA nuclear export, metabolism and translation.

EGFL7 Secreted By Human Bone Mesenchymal Stem Cells Promotes Osteoblast Differentiation Partly Via Downregulation Of Notch1-Hes1 Signaling Pathway.

Background: Epidermal growth factor-like domain protein 7 (EGFL7) is a secreted protein that is differentially expressed in the bone microenvironment; however, the effect of EGFL7 on the osteogenesis of human bone marrow mesenchymal stem cells (hBMSCs) is largely unknown.

Methods: EGFL7 expression in the fracture microenvironment was analyzed based on the Gene Expression Omnibus (GEO) database. Knockdown of EGFL7 by small interfering RNA (siRNA) and in vitro stimulation with recombinant human EGFL7 (rhEGFL7) protein were used to assess alterations in downstream signaling and changes in the osteogenic differentiation and proliferation of hBMSCs.

Norcantharidin ameliorates estrogen deficient-mediated bone loss by attenuating the activation of extracellular signal-regulated kinase/ROS/NLRP3 inflammasome signaling.

Osteoporosis, characterized by reduced bone mass, aberrant bone architecture, and elevated bone fragility, is driven by a disruption of bone homeostasis between bone resorption and bone formation. However, up to now, no drugs are perfect for osteoporosis treatment due to different defects. In this study, we demonstrated that norcantharidin (NCTD) could inhibit osteoclast formation and bone resorption by attenuating the ERK, ROS and NLRP3 inflammasomes pathways .

Synergistic Effect of Reverse Drilling and Bone Dust on Femoral Tendon-Bone Healing After Anterior Cruciate Ligament Reconstruction in a Rabbit Model.

Background: Anterior cruciate ligament (ACL) injuries and bone tunnel enlargement (BTE) after ACL reconstruction (ACLR) remain frequent issues. Bone dust (BD) produced by tunnel preparation with osteogenic ability and reverse drilling (RD), an easy compaction technique, make it accessible to enhance tendon-bone healing in the clinic.

Hypothesis: RD and BD synergistically promote tendon-bone healing by improving peritunnel bone and preventing BTE in femurs.

Remote Eradication of Bacteria on Orthopedic Implants via Delayed Delivery of Polycaprolactone Stabilized Polyvinylpyrrolidone Iodine.

Bacteria-associated late infection of the orthopedic devices would further lead to the failure of the implantation. However, present ordinary antimicrobial strategies usually deal with early infection but fail to combat the late infection of the implants due to the burst release of the antibiotics. Thus, to fabricate long-term antimicrobial (early antibacterial, late antibacterial) orthopedic implants is essential to address this issue.

Metabolic control of CD47 expression through LAT2-mediated amino acid uptake promotes tumor immune evasion.

Chemotherapy elicits tumor immune evasion with poorly characterized mechanisms. Here, we demonstrate that chemotherapy markedly enhances the expression levels of CD47 in osteosarcoma tissues, which are positively associated with patient mortality. We reveal that macrophages in response to chemotherapy secrete interleukin-18, which in turn upregulates expression of L-amino acid transporter 2 (LAT2) in tumor cells for substantially enhanced uptakes of leucine and glutamine, two potent stimulators of mTORC1.

Swelling-Mediated Mechanical Stimulation Regulates Differentiation of Adipose-Derived Mesenchymal Stem Cells for Intervertebral Disc Repair Using Injectable UCST Microgels.

Mechanical stimulation is an effective approach for controlling stem cell differentiation in tissue engineering. However, its realization in in vivo tissue repair remains challenging since this type of stimulation can hardly be applied to injectable seeding systems. Here, it is presented that swelling of injectable microgels can be transformed to in situ mechanical stimulation via stretching the cells adhered on their surface.

Prominin 1 Significantly Correlated with Bone Metastasis of Breast Cancer and Influenced the Patient's Prognosis.

Background: This study is aimed at identifying the important biomarkers associated with bone metastasis (BM) in breast cancer (BRCA).

Methods: The GSE175692 dataset was used to detect significant differential expressed genes (DEGs) between BRCA samples with or without BM, and DEG-related pathways were then explored. Further, we constructed the protein-protein interaction (PPI) network on GEGs and filtered 5 vital nodes.

Collagen Niches Affect Direct Transcriptional Conversion toward Human Nucleus Pulposus Cells via Actomyosin Contractility.

Cellular niches play fundamental roles in regulating cellular behaviors. However, the effect of niches on direct converted cells remains unexplored. In the present study, the specific combination of transcription factors is first identified to directly acquire induced nucleus pulposus-like cells (iNPLCs).

A Novel Suture-Preset Spring Plate System (SSPS) for Comminuted Coronoid Process Fracture in the Elbow.

Objective: This study is aimed to investigate the clinical outcomes of a novel SSPS for fixation of the comminuted coronoid fracture.

Methods: A retrospective study was carried out in the patients with comminuted fractures of the coronoid treated by SPSS fixation between January 2014 and December 2018. A total of 17 patients (17 sides) was included in our study, including 11 male and six female, with a mean age range from 18 to 60.

Knockdown of FOXA1 enhances the osteogenic differentiation of human bone marrow mesenchymal stem cells partly via activation of the ERK1/2 signalling pathway.

Background: The available therapeutic options for large bone defects remain extremely limited, requiring new strategies to accelerate bone healing. Genetically modified bone mesenchymal stem cells (BMSCs) with enhanced osteogenic capacity are recognised as one of the most promising treatments for bone defects.

Methods: We performed differential expression analysis of miRNAs between human BMSCs (hBMSCs) and human dental pulp stem cells (hDPSCs) to identify osteogenic differentiation-related microRNAs (miRNAs).

LONP1 downregulation with ageing contributes to osteoarthritis via mitochondrial dysfunction.

Osteoarthritis (OA) is an age-related disorder and an important cause of disability that is characterized by a senescence-associated secretory phenotype and matrix degradation leading to a gradual loss of articular cartilage integrity. Mitochondria, as widespread organelles, are involved in regulation of complex biological processes such as energy synthesis and cell metabolism, which also have bidirectional communication with the nucleus to help maintain cellular homeostasis and regulate adaptation to a broad range of stressors. In light of the evidence that OA is strongly associated with mitochondrial dysfunction.

Remotely Temporal Scheduled Macrophage Phenotypic Transition Enables Optimized Immunomodulatory Bone Regeneration.

Precise timing of macrophage polarization plays a pivotal role in immunomodulation of tissue regeneration, yet most studies mainly focus on M2 macrophages for their anti-inflammatory and regenerative effects while the essential proinflammatory role of the M1 phenotype on the early inflammation stage is largely underestimated. Herein, a superparamagnetic hydrogel capable of timely controlling macrophage polarization is constructed by grafting superparamagnetic nanoparticles on collagen nanofibers. The magnetic responsive hydrogel network enables efficient polarization of encapsulated macrophage to the M2 phenotype through the podosome/Rho/ROCK mechanical pathway in response to static magnetic field (MF) as needed.

Effect of C Single-door Laminoplasty on Symptomatic Atlas Canal Stenosis.

Objective: To verify the effect of single-door laminoplasty combined with atlantoaxial fusion in the treatment of symptomatic atlas canal stenosis.

Methods: This is a single-center retrospective analysis. From February 2014 to January 2019, 16 patients (five were females) with an average age of 63.