In-situ Sprayed platelet-derived small extracellular vesicles for the skin flap survival by reducing PANoptosis.

Necrosis at the distal end of random skin flaps remains a significant challenge, limiting the clinical application of these flaps in plastic and reconstructive surgery. Inhibiting ischemia/reperfusion (I/R) injury and promoting the formation of neovascular networks are critical preventive strategies. Platelet-derived small extracellular vesicles (PL-sEV) are nanocarriers of growth factors that provide an alternative to clinically used platelet-rich plasma and platelet lysates, offering higher growth factor concentrations and lower immunogenicity.

Platelet-derived exosomes alleviate tendon stem/progenitor cell senescence and ferroptosis by regulating AMPK/Nrf2/GPX4 signaling and improve tendon-bone junction regeneration in rats.

Background: Tendon stem/progenitor cell (TSPC) senescence contributes to tendon degeneration and impaired tendon repair, resulting in age-related tendon disorders. Ferroptosis, a unique iron-dependent form of programmed cell death, might participate in the process of senescence. However, whether ferroptosis plays a role in TSPC senescence and tendon regeneration remains unclear.

Scellseg: A style-aware deep learning tool for adaptive cell instance segmentation by contrastive fine-tuning.

Deep learning-based cell segmentation is increasingly utilized in cell biology due to the massive accumulation of large-scale datasets and excellent progress in model architecture and instance representation. However, the development of specialist algorithms has long been hampered by a paucity of annotated training data, whereas the performance of generalist algorithms is limited without experiment-specific calibration. Here, we present Scellseg, an adaptive pipeline that utilizes a style-aware pre-trained model coupled to a contrastive fine-tuning strategy that also learns from unlabeled data.

CY-09 attenuates the progression of osteoarthritis via inhibiting NLRP3 inflammasome-mediated pyroptosis.

Excessive activation of inflammation in chondrocyte has been considered to be a major reason cause of cellular death and degeneration in osteoarthritis (OA) development. The NLRP3 inflammasome-mediated pyroptosis pathway is closely related to inflammation regulation. This research was conducted to confirm whether NLRP3 expression and activity are impacted in the development of OA and to detect the role of CY-09, a selective and direct inhibitor of NLRP3 in the in vitro and in vivo models of OA.

Oroxylin A attenuates osteoarthritis progression by dual inhibition of cell inflammation and hypertrophy.

The imbalance between the anabolism and catabolism of the extracellular matrix (ECM) is of great importance to osteoarthritis (OA) development. Aberrant inflammatory responses and hypertrophic changes of chondrocytes are the main contributors to these metabolic disorders. In the present study, we found that Oroxylin A (ORA), a flavonoid compound derived from Oroxylum indicum, maintained ECM hemostasis of chondrocytes by Interleukin-1β (IL-1β) stimulation.

Advances in applying of multi-omics approaches in the research of systemic lupus erythematosus.

Systemic lupus erythematosus (SLE), an autoimmune disease that causes multiorgan injury, has an unclear etiology and complex pathogenesis. Numerous studies have found abnormal alterations in mRNAs, proteins and/or metabolites in SLE patients. These findings have extended our understanding of the pathogenesis of SLE.

Pharmacological blockade of PCAF ameliorates osteoarthritis development via dual inhibition of TNF-α-driven inflammation and ER stress.

Background: Epigenetic mechanisms have been reported to play key roles in osteoarthritis (OA) development. P300/CBP-associated factor (PCAF) is a member of the histone acetyltransferases, which exhibits a strong relationship with endoplasmic reticulum (ER) stress and transcription factor nuclear factor kappa B (NF-κB) signals. Salidroside, a natural histone acetylation inhibitor, showed its anti-inflammatory and anti-apoptotic effects in lipopolysaccharide (LPS)-stimulated microglia cells in our previous study.

Discovery, structural insight, and bioactivities of BY27 as a selective inhibitor of the second bromodomains of BET proteins.

Recently, selective inhibition of BET BD2 is emerging as a promising strategy for drug discovery. Despite significant progress in this area, systematic studies of selective BET BD2 inhibitors are still few. In this study, we report the discovery of a potent and selective BET BD2 inhibitor BY27 (47).

LncRNA EPB41L4A-AS1 regulates glycolysis and glutaminolysis by mediating nucleolar translocation of HDAC2.

Background: LncRNAs have been found to be involved in various aspects of biological processes. In this study, we aimed to uncover the molecular mechanisms of lncRNA EPB41L4A-AS1 in regulating glycolysis and glutaminolysis in cancer cells.

Methods: The expression of EPB41L4A-AS1 in cancer patients was analyzed in TCGA and GEO datasets.

A new technique for medial-end comminuted clavicle fractures.

Fractures of the medial comminuted clavicle are rare injuries but are associated with significant morbidity and mortality. Although rare, such injuries deserve rapid diagnosis and effective treatment to avoid future complications. An optimal, standardized operative treatment has not yet been established.

Small molecule natural compound agonist of SIRT3 as a therapeutic target for the treatment of intervertebral disc degeneration.

Oxidative stress-induced mitochondrial dysfunction is implicated in the pathogenesis of intervertebral disc degeneration (IVDD). Sirtuin 3 (SIRT3), a sirtuin family protein located in mitochondria, is essential for mitochondrial homeostasis; however, the role of SIRT3 in the process of IVDD has remained elusive. Here, we explored the expression of SIRT3 in IVDD in vivo and in vitro; we also explored the role of SIRT3 in senescence, apoptosis, and mitochondrial homeostasis under oxidative stress.

TFEB protects nucleus pulposus cells against apoptosis and senescence via restoring autophagic flux.

Objective: Excessive apoptosis and senescence of nucleus pulposus (NP) cells are major pathological changes in intervertebral disc degeneration (IVDD) development; previous studies demonstrated pharmacologically or genetically stimulation of autophagy may inhibit apoptosis and senescence in NP cells. Transcription factor EB (TFEB) is a master regulator of autophagic flux via initiating autophagy-related genes and lysosomal biogenesis. This study was performed to confirm whether TFEB was involved in IVDD development and its mechanism.

Allenamide as a bioisostere of acrylamide in the design and synthesis of targeted covalent inhibitors.

The success of acrylamide-containing drugs in treating cancers has spurred a passion to search for acrylamide bioisosteres. In our endeavour, we have identified that an allenamide group can be a reactive bioisostere of the acrylamide group. In our development of allenamide-containing compounds, we found that the most potent compound, , inhibited the kinase activities of both T790M/L858R double mutant and wild type EGFR in a low nM range.

Wogonoside inhibits IL-1β induced catabolism and hypertrophy in mouse chondrocyte and ameliorates murine osteoarthritis.

The inflammatory environment is correlated with extracellular matrix (ECM) degradation and chondrocyte hypertrophy in the development of osteoarthritis (OA). Previous studies have reported the anti-inflammatory effects of wogonoside in several diseases. In the present study, we investigated the protective effects of wogonoside in relation to the development of OA and delineated the potential mechanism.

Zero-Profile Spacer Versus Cage-Plate Construct in Anterior Cervical Diskectomy and Fusion for Multilevel Cervical Spondylotic Myelopathy: Systematic Review and Meta-Analysis.

Background: Anterior cervical diskectomy and fusion with plate-screw construct has been gradually applied for multilevel cervical spondylotic myelopathy in recent years. However, long cervical plate was associated with complications including breakage or loosening of plate and screws, trachea-esophageal injury, neurovascular injury, and postoperative dysphagia. To reduce these complications, the zero-profile spacer has been introduced.

Hydrogen sulfide protects against endoplasmic reticulum stress and mitochondrial injury in nucleus pulposus cells and ameliorates intervertebral disc degeneration.

It has been suggested that excessive apoptosis in intervertebral disc cells induced by inflammatory cytokines, such as interleukin (IL)-1β, is related to the process of intervertebral disc degeneration (IVDD). Hydrogen sulfide (HS), a gaseous signaling molecule, has drawn attention for its anti-apoptosis role in various pathophysiological processes in degenerative diseases. To date, there has been no investigation of the correlation of HS production and IVDD or of the effects of HS on IL-1β-induced apoptosis in nucleus pulposus (NP) cells.

A small-molecule inhibitor of NF-κB-inducing kinase (NIK) protects liver from toxin-induced inflammation, oxidative stress, and injury.

Potent and selective chemical probes are valuable tools for discovery of novel treatments for human diseases. NF-κB-inducing kinase (NIK) is a key trigger in the development of liver injury and fibrosis. Whether inhibition of NIK activity by chemical probes ameliorates liver inflammation and injury is largely unknown.

Metformin protects against apoptosis and senescence in nucleus pulposus cells and ameliorates disc degeneration in vivo.

Intervertebral disc degeneration (IDD) is a complicated process that involves both cellular apoptosis and senescence. Metformin has been reported to stimulate autophagy, whereas autophagy is shown to protect against apoptosis and senescence. Therefore, we hypothesize that metformin may have therapeutic effect on IDD through autophagy stimulation.

Menopause is associated with articular cartilage degeneration: a clinical study of knee joint in 860 women.

Objective: The purpose of this study was to investigate the association between menopause and severity of knee joint cartilage degeneration using a magnetic resonance imaging-based six-level grading system, with six cartilage surfaces, the medial and lateral femoral condyle, the femoral trochlea, the medial and lateral tibia plateau, and the patella.

Methods: The study cohort comprised 860 healthy women (age 36-83 y), and 5,160 cartilage surfaces were analyzed. Age, weight, height, age at natural menopause, and years since menopause (YSM) were obtained.

Proliferation of rabbit chondrocyte and inhibition of IL-1β-induced apoptosis through MEK/ERK signaling by statins.

Chondrocyte plays a critical role in endochondral ossification and cartilage repair by maintaining the cartilaginous matrix. Statins have been widely used to lower the cholesterol level in patients with cardiovascular disorders. Previous research has demonstrated potential role of statins in chondrocyte proliferation.

Salidroside Promotes Random Skin Flap Survival in Rats by Enhancing Angiogenesis and Inhibiting Apoptosis.

 Flap necrosis is frequently observed in flap transfer operations. Salidroside has been reported to reduce cell apoptosis by alleviating inflammation and oxidative stress. We investigated the effects of salidroside on the survival of random skin flaps.

Stabilization of HIF-1α by FG-4592 promotes functional recovery and neural protection in experimental spinal cord injury.

Previous studies have shown that inhibition of prolyl hydroxylase(PHD) stabilizes Hypoxia-inducible factor 1, alpha subunit(HIF-1α), increases tolerance to hypoxia, and improves the prognosis of many diseases. However, the role of PHD inhibitor (PHDI) in the recovery of spinal cord injury remains controversial. In this study, we investigated the protective role of a novel PHDI FG-4592 both in vivo and in vitro.

Stimulation of autophagy promotes functional recovery in diabetic rats with spinal cord injury.

In this study we examined the relationship between autophagy and apoptosis in diabetic rats after spinal cord injury (SCI), also we determined the role of autophagy in diabetes-aggravated neurological injury in vivo and in vitro. Our results showed that diabetes decreased the survival of neurons, promoted astrocytes proliferation, increased inflammatory cells infiltration and inhibited functional recovery after SCI. Diabetes was shown to confer increased activation of apoptotic pathways, along with an increase in autophagy; similar effects were also observed in vitro in neuronal PC12 cells.

Characterization of the microRNA pool and the factors affecting its regulatory potential.

The regulation of gene expression by microRNAs (miRNAs) is complex due to a number of variables involved. The potential for one miRNA to target many genes, the presence of multiple miRNA response elements (MREs) in one mRNA molecule and the interplay between RNAs that share common MREs each add a layer of complexity to the process; making it difficult to determine how regulation of gene expression by miRNAs works within the context of the system as a whole. In this study, we used luciferase report vectors inserted with different 3'UTR fragments as probes to detect the repressive effect of the miRNA pool on gene expression and uncovered some essential characteristics of gene regulation mediated by the miRNA pool, such as the nonlinear correlative relationship between the regulatory potential of a miRNA pool and the number of potential MREs, the buffering effect and the saturating effect of the miRNA pool, and the restrictive effect caused by the density of MREs.