Spinal cord regeneration after a spinal injury (SCI) remains difficult challenge due to the complicated inflammatory microenvironment and neuronal damage at sites. In this study, retinoic acid (RA) curcumin (Cur) were co-loaded with bovine serum albumin (BSA) self-assembly obtain RA@BSA@Cur nanoparticles (NPs) for SCI treatment. Cur, as an antioxidant drug, facilitated reactive oxygen species (ROS) scavenging, decreased amount of factors secreted by macrophages, while RA could enhance...

Prolonged or overdose glucocorticoids (GCs) usage is the common cause of osteoporosis. In present study, we studied cellular mechanism dexamethasone (Dex)-induce osteoblast cell death by focusing on role mitochondrial permeability transition pore (mPTP). cultured osteoblastic MC3T3-E1 cells, Dex-induced mPTP opening, which was demonstrated membrane potential (MPP) decrease, cyclophilin-D (CyPD)-adenine nucleotide translocator 1 (ANT-1) complexation and cytochrome C (cyto-C) release. The...

Biomimetic nanodecoys reconstruct the osteoclast/osteoblast balance to treat postmenopausal osteoporosis.

Osteoarthritis (OA) is a chronic degenerative disease featured by cartilage erosion and inflammation. Luteolin, member of the flavonoid family, has been shown to exert anti-inflammatory antioxidative activities. However, potential biological effects underlying mechanism luteolin on chondrocytes OA progression remain largely elusive. In this study, effect were investigated in vitro vivo. Our data revealed that inhibited H2O2-induced cell death, apoptosis, oxidative stress, programmed...

Signaling mediated by brain-derived neurotrophic factor (BDNF), which is supported the postsynaptic scaffolding protein PSD-95, has antidepressant effects. Conversely, clinical depression associated with reduced BDNF signaling. We found that peptidomimetic compounds bind to PSD-95 promoted signaling receptor TrkB in hippocampus and depression-like behaviors mice. The CN2097 Syn3 both PDZ3 domain of also binds an α-helical region protein. two mouse models stress-induced depression; had...

Abstract Monocyte-derived cells were shown to promote cartilage repair in osteoarthritis. The role of the long non-coding RNA (lncRNA) MM2P this function monocyte-derived remained unexplored. Treatment RAW264.7 murine macrophages and mouse bone marrow-derived with IL-4 or IL-13 upregulated expression, upstream STAT3 STAT6 phosphorylation. Specifically, blocked SHP2-mediated dephosphorylation at Try705 interacted RNA-binding protein FUS. In turn, p-STAT3 increased Sox9 gene expression. These...

Significance Heterotrimeric Gαi proteins are known to transduce G protein-coupled receptor signals. We have identified a role for in mediating brain-derived neurotrophic factor (BDNF)–tropomyosin-related kinase B (TrkB) signaling. BDNF dysfunction contributes the pathophysiology of depression. In stress model depression Gαi1 and Gαi3 downregulated hippocampus, limbic structure associated with major depressive disorder. show that Gαi1/Gαi3 required TrkB downstream signaling, knockout mice...

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 OGD/R accumulation of microRNA miR-422a, leading downregulation miR-422a targets myocyte enhancer factor-2D (MEF2D) mitogen-activated protein kinase 6 (MAPKK6). Ectopic inhibition attenuated OGD/R-induced cell death apoptosis, whereas overexpression induced significant apoptosis....

IL-4 induces Akt activation in macrophages, required for full M2 (alternative) polarization. We examined the roles of Gαi1 and Gαi3 polarization using multiple genetic methods. Methods Results: In MEFs primary murine BMDMs, Gαi1/3 shRNA, knockout or dominant negative mutations attenuated IL-4-induced IL4Rα endocytosis, Gab1 recruitment as well activation, leaving STAT6 signaling unaffected. Following stimulation, proteins associated with intracellular domain IL-4Rα APPL1 adaptor, to mediate...

Oxidative stress, due to the disruption of balance between reactive oxygen species (ROS) generation and antioxidant defense system, plays an important role in pathogenesis rheumatoid arthritis (RA). Excessive ROS leads loss biological molecules cellular functions, release many inflammatory mediators, stimulate polarization macrophages, aggravate response, thus promoting osteoclasts bone damage. Therefore, foreign antioxidants would effectively treat RA. Herein, ultrasmall iron-quercetin...

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 this process. In MEFs HUVECs, Gαi1/3 was associated with SCF-activated c-Kit, promoting endocytosis, binding key adaptor proteins, subsequently transducing signaling. SCF-induced Akt-mTOR Erk activation robustly attenuated by silencing or knockout (KO), due dominant negative mutations but...

Abstract Keloids are one of the common refractory conditions in dermatology and aesthetic plastic surgery. The most effective treatment is superficial radiotherapy followed by surgical removal. rate recurrence strongly associated with total dose ionizing irradiation, underlying mechanism remains unclear. In this study, we used primary keloid fibroblasts ( KF b) isolated from patient samples to investigate effects X ‐ray radiation on cell proliferation, toxicity cycle, as detected CCK ‐8...

Abstract Spinal cord injury (SCI) is lead to locomotor impairment because of neurological damage after following trauma. Quercetin (Que) has been confirmed have a neuro‐protective effect during nerve processes. The purpose this study was determine the roles Que in functional recovery, cavity formation, astrocyte activation, and regeneration SCI. Sprague‐Dawley rats were randomly divided into three groups: Sham group, SCI + group. A rat model made at T10 using modified Allen's method. In...

Excessive osteoclast activation is an important cause of imbalanced bone remodeling that leads to pathological destruction. This a clear feature many osteolytic diseases such as rheumatoid arthritis, osteoporosis, and osteolysis around prostheses. Because natural compounds have therapeutic potential for treating these by suppressing formation function, we hypothesized α-mangostin, compound isolated from mangosteen, might be promising treatment it exhibits anti-inflammatory, anticancer,...

Sustained activation of multiple receptor tyrosine kinases (RTKs) simultaneously is vital for tumorigenesis and progression osteosarcoma (OS). Gαi proteins recruitment to various RTKs mediates downstream oncogenic signaling activation. The expression, functions underlying mechanisms Gαi3 in human OS were examined. Expression robustly elevated tissues correlated with a poor overall survival. In patient-derived primary cells immortalized lines (MG63 U2OS), depletion, by shRNA CRISPR/Cas9...

In the present study, we investigated activity of XL388, a novel mammalian target rapamycin (mTOR) complex 1/2 (mTORC1/2) dual inhibitor, in preclinical osteosarcoma (OS) models. XL388 was cytotoxic, cytostatic and pro-apoptotic to multiple established OS cell lines primary human cells. blocked mTORC1/2 activation downregulated cyclin D1/B1 expressions cells, leaving AKT Thr-308 phosphorylation un-affected. Intriguingly, AKT1 T308A mutation potentiated XL388-induced cytotoxicity activated...

// Min-Bin Chen 1, * , Zhen-Tao Zhou 2, Lan Yang 3, Mu-Xin Wei 4 Min Tang 1 Ting-Yan Ruan 5 Jun-Ying Xu Xiao-zhong 2 Gang 6 Pei-Hua Lu Department of Oncology, Kunshan First People's Hospital Affiliated to Jiangsu University, 215300, China Orthopedics, the Second Soochow Suzhou 215000, 3 Breast Surgery, Third Changzhou 213003, Traditional Chinese Medicine, Nanjing Medical 210029, Wuxi 214023, Neurosurgery, 215006, These authors have contributed equally this work Correspondence to: Lu, e-mail:...

Abstract During rheumatoid arthritis (RA) development, over‐produced proinflammatory cytokines represented by tumor necrosis factor‐α (TNF‐α) and reactive oxygen species (ROS) H 2 O form a self‐promoted cycle to exacerbate the synovial inflammation tissue damage. Herein, biomimetic nanocomplexes (NCs) reversibly cloaked with macrophage membrane (RM) are developed for effective RA management via dual scavenging of TNF‐α ROS. To construct NCs, membrane‐penetrating, helical polypeptide first...

Improved chondrogenic differentiation of mesenchymal stem cells (MSCs) by genetic regulation is a potential method for regenerating articular cartilage. MiR-127-5p has been reported to promote cartilage rat bone marrow MSCs (rMSCs); however, the regulatory mechanisms underlying hypoxia-stimulated remain unknown.rMSCs were induced undergo under normoxic or hypoxic conditions. Expression lncRNA DNM3OS, miR-127-5p, and GREM2 was detected quantitative real-time PCR. Proteoglycans Alcian blue...