Azvudine efficacy in reducing mortality in COVID-19 patients.

Background: Several therapeutic drugs have been authorized for the treatment of patients with Coronavirus disease 2019 (COVID-19). However, further research on the mechanisms of action, efficacy, and target populations of these novel therapeutic drugs are necessary. This study included mild, moderate, severe, and critical COVID-19 patients to evaluate azvudine's effectiveness across different severity levels.

Receptor Activator of Nuclear Factor Kappa-B-Expressing Mesenchymal Stem Cells-Derived Extracellular Vesicles for Osteoporosis Therapy.

The dynamic balance between bone resorption and formation is critical for maintaining healthy bone homeostasis. However, the receptor activator of the nuclear factor B ligand (RANKL) primarily stimulates mature osteoclasts to resorb bone, and its upregulation leads to osteoporosis in patients. Here, we designed RANK-expressing extracellular vesicles (EVs) derived from mesenchymal stem cells to maintain bone homeostasis in mice.

Amplification of Metalloregulatory Proteins in Macrophages by Bioactive ZnMn@SF Hydrogels for Spinal Cord Injury Repair.

Macrophages are rapidly activated and polarized toward the M1 phenotype after spinal cord injury (SCI), and inhibiting M1-like macrophages has emerged as a promising SCI treatment approach. Metalloregulatory proteins, which sense specific metal ions with high affinity and specificity, play a critical role in immune regulation. Here, we screened various bioactive metal ions associated with metalloregulatory proteins and discovered that Zn and Mn effectively suppressed M1 polarization.

Targeting NAMPT-OPA1 for treatment of senile osteoporosis.

Senescence of bone marrow mesenchymal stem cells (BMSCs) impairs their stemness and osteogenic differentiation, which is the principal cause of senile osteoporosis (SOP). Imbalances in nicotinamide phosphoribosyltransferase (NAMPT) homeostasis have been linked to aging and various diseases. Herein, reduction of NAMPT and impaired osteogenesis were observed in BMSCs from aged human and mouse.

Surgical outcomes of robotic-assisted percutaneous fixation for thoracolumbar fractures in patients with ankylosing spondylitis.

Background: Spinal fractures in patients with ankylosing spondylitis (AS) mainly present as instability, involving all three columns of the spine, and surgical intervention is often considered necessary. However, in AS patients, the significant alterations in bony structure and anatomy result in a lack of identifiable landmarks, which increases the difficulty of pedicle screw implantation. Therefore, we present the clinical outcomes of robotic-assisted percutaneous fixation for thoracolumbar fractures in patients with AS.

Targeting the postsynaptic scaffolding protein PSD-95 enhances BDNF signaling to mitigate depression-like behaviors in mice.

Signaling mediated by brain-derived neurotrophic factor (BDNF), which is supported by the postsynaptic scaffolding protein PSD-95, has antidepressant effects. Conversely, clinical depression is associated with reduced BDNF signaling. We found that peptidomimetic compounds that bind to PSD-95 promoted signaling by the BDNF receptor TrkB in the hippocampus and reduced depression-like behaviors in mice.

G protein subunit alpha i2's pivotal role in angiogenesis.

Here we explored the potential role of Gαi2 (G protein subunit alpha i2) in endothelial cell function and angiogenesis. Genetic methodologies such as shRNA, CRISPR/Cas9, dominant negative mutation, and overexpression were utilized to modify Gαi2 expression or regulate its function. Their effects on endothelial cell functions were assessed .

SCF/c-Kit-activated signaling and angiogenesis require Gαi1 and Gαi3.

The stem cell factor (SCF) binds to c-Kit in endothelial cells, thus activating downstream signaling and angiogenesis. Herein, we examined the role of G protein subunit alpha inhibitory (Gαi) proteins in this process. In MEFs and HUVECs, Gαi1/3 was associated with SCF-activated c-Kit, promoting c-Kit endocytosis, and binding of key adaptor proteins, subsequently transducing downstream signaling.

Size selection and placement of pedicle screws using robot-assisted versus fluoroscopy-guided techniques for thoracolumbar fractures: possible implications for the screw loosening rate.

Background: There has been increased development of robotic technologies for the accuracy of percutaneous pedicle screw placement. However, it remains unclear whether the robot really optimize the selection of screw sizes and enhance screw stability. The purpose of this study is to compare the sizes (diameter and length), placement accuracy and the loosening rate of pedicle screws using robotic-assisted versus conventional fluoroscopy approaches for thoracolumbar fractures.

Development and biomechanical test of a new pedicle screw for thoracolumbar spinal surgery.

Rupture of the medial pedicle wall often occurs during pedicle screw insertion. This allows the pedicle screw to compress or cut the nerve root and/or spinal cord. In this paper, we designed a new double-threaded pedicle screw that has a cylindrical outer diameter and a conical core diameter, with a wide thread at the front, no thread in the middle, and a narrow thread at the rear, according to an analysis of the shortcomings of the conventional pedicle screw and anatomical parameters in 300 healthy adult volunteers.

Prophylactic Effects of NFκB Essential Modulator-Binding Domain Peptides on Bone Infection: An Experimental Study in a Rabbit Model.

Introduction: Osteomyelitis is characterized by intensive inflammatory bone disease and remains a clinical challenge in orthopedic surgery, despite the advances made in medical and surgical therapies. is a major causative agent of osteomyelitis, causing the progressive inflammatory destruction of bone. Prophylaxis of osteomyelitis during orthopedic surgery is necessary.

Identification of Gαi3 as a promising target for osteosarcoma treatment.

Sustained activation of multiple receptor tyrosine kinases (RTKs) simultaneously is vital for tumorigenesis and progression of osteosarcoma (OS). Gαi proteins recruitment to various RTKs mediates downstream oncogenic signaling activation. The expression, functions and underlying mechanisms of Gαi3 in human OS were examined.

Type I collagen scaffold with WNT5A plasmid for in situ cartilage tissue engineering.

Background: Cartilage tissue lacks the ability to heal. Cartilage tissue engineering using cell-free scaffolds has been increasingly used in recent years.

Objective: This study describes the use of a type I collagen scaffold combined with WNT5A plasmid to promote chondrocyte proliferation and differentiation in a rabbit osteochondral defect model.

MAFG-driven osteosarcoma cell progression is inhibited by a novel miRNA miR-4660.

Osteosarcoma (OS) is the most common primary bone malignancy in the adolescent population. MAFG (v-maf avian musculoaponeurotic fibrosarcoma oncogene homolog G) forms a heterodimer with Nrf2 (NF-E2-related factor 2), binding to antioxidant response element (ARE), which is required for Nrf2 signaling activation. We found that mRNA and protein expression is significantly elevated in human OS tissues as well as in established and primary human OS cells.

Requirement of Gαi1 and Gαi3 in interleukin-4-induced signaling, macrophage M2 polarization and allergic asthma response.

IL-4 induces Akt activation in macrophages, required for full M2 (alternative) polarization. We examined the roles of Gαi1 and Gαi3 in M2 polarization using multiple genetic methods. In MEFs and primary murine BMDMs, Gαi1/3 shRNA, knockout or dominant negative mutations attenuated IL-4-induced IL4Rα endocytosis, Gab1 recruitment as well as Akt activation, leaving STAT6 signaling unaffected.

Functional reconstruction of severe hand injuries using allogeneic tendons: a retrospective study.

Objective: To evaluate the effectiveness and safety of allogeneic tendons for functional reconstruction of severe hand injuries.

Methods: From August 2007 to July 2014, we performed functional reconstruction with tendon allografts for severe hand injuries affecting two or more tendons. At the final follow-up, we assessed total active motion (TAM); pincer pinch strength; grip strength; Disabilities of the Arm, Shoulder, and Hand (DASH) score; degree of satisfaction; and adhesion.

Oxygen glucose deprivation/re-oxygenation-induced neuronal cell death is associated with Lnc-D63785 m6A methylation and miR-422a accumulation.

Oxygen glucose deprivation/re-oxygenation (OGD/R) induces neuronal injury via mechanisms that are believed to mimic the pathways associated with brain ischemia. In SH-SY5Y cells and primary murine neurons, we report that OGD/R induces the accumulation of the microRNA miR-422a, leading to downregulation of miR-422a targets myocyte enhancer factor-2D (MEF2D) and mitogen-activated protein kinase kinase 6 (MAPKK6). Ectopic miR-422a inhibition attenuated OGD/R-induced cell death and apoptosis, whereas overexpression of miR-422a induced significant neuronal cell apoptosis.

p38γ overexpression promotes osteosarcoma cell progression.

Osteosarcoma (OS) is the most common primary bone malignancy in the adolescent population. Recent studies demonstrate that p38 gamma (p38γ) phosphorylates retinoblastoma (Rb) to promote cyclin expression, cell-cycle entry and tumorigenesis. Studying the potential function of p38γ in human OS, we show that γ mRNA and protein expression are significantly elevated in OS tissues and OS cells, whereas its expression is relatively low in normal bone tissue and in human osteoblasts/osteoblastic cells.

Dexamethasone-induced cytotoxicity in human osteoblasts is associated with circular RNA HIPK3 downregulation.

Dexamethasone (DEX) exerts potent cytotoxicity against cultured human osteoblasts. The current study examined the role of the circular RNA HIPK3 (circHIPK3) in the mechanism of cell death. We found that circHIPK3 expression was downregulated in DEX-treated human osteoblasts and circHIPK3 levels decreased in human necrotic femoral head tissues.

The GDF11-FTO-PPARγ axis controls the shift of osteoporotic MSC fate to adipocyte and inhibits bone formation during osteoporosis.

During osteoporosis, the shift of bone mesenchymal stem cell (BMSC) lineage commitment to adipocyte leads to the imbalance between bone mass and fat, which increases the risk of fracture. The mechanism underlying this process is not fully understood. Fat mass and obesity-associated protein (FTO) is an RNA demethylase that demethylates various methylated nucleic acids and participates in various physiological and pathological processes.

LncRNA EPIC1 protects human osteoblasts from dexamethasone-induced cell death.

Dexamethasone (Dex) can induce injury to human osteoblasts. Long non-coding RNA (LncRNA) EPIC1 (Lnc-EPIC1) is a novel Myc-interacting LncRNA. Its effect on Dex-treated human osteoblasts is studied here.

microRNA-29a inhibition induces Gab1 upregulation to protect OB-6 human osteoblasts from hydrogen peroxide.

The present study determines the role of the Gab1 in hydrogen peroxide (HO)-induced death of human osteoblasts. We show that Gab1 is required for HO-induced Akt activation to promote osteoblast survival. In OB-6 human osteoblasts, Gab1 silencing (by targeted-shRNA) or complete knockout (by CRISPR-Cas9 KO plasmid) largely attenuated Akt activation by HO.

Antidepression action of BDNF requires and is mimicked by Gαi1/3 expression in the hippocampus.

Stress-related alterations in brain-derived neurotrophic factor (BDNF) expression, a neurotrophin that plays a key role in synaptic plasticity, are believed to contribute to the pathophysiology of depression. Here, we show that in a chronic mild stress (CMS) model of depression the Gαi1 and Gαi3 subunits of heterotrimeric G proteins are down-regulated in the hippocampus, a key limbic structure associated with major depressive disorder. We provide evidence that Gαi1 and Gαi3 (Gαi1/3) are required for the activation of TrkB downstream signaling pathways.

Bromodomain protein BRD4 promotes cell proliferation in skin squamous cell carcinoma.

The present study examined the expression and biological functions of bromodomain-containing protein 4 (BRD4) in skin squamous cell carcinoma (SCC) cells. Our results show that BRD4 mRNA and protein expression was upregulated in human skin SCC cells, as compared to its level in the normal skin keratinocytes and fibroblasts. Treatment with BRD4 inhibitors, JQ1 and CPI203, resulted in proliferation inhibition, apoptosis and cell cycle arrest in both established (A431 cell line) and primary skin SCC cells.

microRNA-135b expression silences Ppm1e to provoke AMPK activation and inhibit osteoblastoma cell proliferation.

Forced-activation of AMP-activated protein kinase (AMPK) can possibly inhibit osteoblastoma cells. Here, we aim to provoke AMPK activation via microRNA silencing its phosphatase Ppm1e (protein phosphatase Mg2+/Mn2+-dependent 1e). We showed that microRNA-135b-5p ("miR-135b-5p"), the anti-Ppm1e microRNA, was significantly downregulated in human osteoblastoma tissues.