Publications by authors named "Jiake Xu"

266 Publications

Targeted treatment for osteoarthritis: drugs and delivery system.

Drug Deliv 2021 Dec;28(1):1861-1876

School of Kinesiology, Shanghai University of Sport, Shanghai, China.

The management of osteoarthritis (OA) is a clinical challenge due to the particular avascular, dense, and occluded tissue structure. Despite numerous clinical reports and animal studies, the pathogenesis and progression of OA are still not fully understood. On the basis of traditional drugs, a large number of new drugs have been continuously developed. Intra-articular (IA) administration for OA hastens the development of targeted drug delivery systems (DDS). OA drugs modification and the synthesis of bioadaptive carriers contribute to a qualitative leap in the efficacy of IA treatment. Nanoparticles (NPs) are demonstrated credible improvement of drug penetration and retention in OA. Targeted nanomaterial delivery systems show the prominent biocompatibility and drug loading-release ability. This article reviews different drugs and nanomaterial delivery systems for IA treatment of OA, in an attempt to resolve the inconsonance between and release, and explore more interactions between drugs and nanocarriers, so as to open up new horizons for the treatment of OA.
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http://dx.doi.org/10.1080/10717544.2021.1971798DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8439249PMC
December 2021

Single-Cell RNA Sequencing Reveals the Migration of Osteoclasts in Giant Cell Tumor of Bone.

Front Oncol 2021 24;11:715552. Epub 2021 Aug 24.

Department of Trauma Orthopedic and Hand Surgery, First Affiliated Hospital of Guangxi Medical University, Nanning, China.

Giant cell tumor of bone (GCTB) is benign tumor that can cause significant osteolysis and bone destruction at the epiphysis of long bones. Osteoclasts are thought to be highly associated with osteolysis in GCTB. However, the migration of osteoclasts in GCTB remains unclear. A deeper understanding of the complex tumor microenvironment is required in order to delineate the migration of osteoclasts in GCTB. In this study, samples were isolated from one patient diagnosed with GCTB. Single-cell RNA sequencing (scRNA-seq) was used to detect the heterogeneity of GCTB. Multiplex immunofluorescence staining was used to evaluate the cell subtypes identified by scRNA-seq. A total of 8,033 cells were obtained from one patient diagnosed with GCTB, which were divided into eight major cell types as depicted by a single-cell transcriptional map. The osteoclasts were divided into three subsets, and their differentiation trajectory and migration status were further analyzed. Osteoclast migration may be regulated a series of genes associated with cell migration. Furthermore, four signaling pathways (RANKL, PARs, CD137 and SMEA3 signaling pathway) were found to be highly associated with osteoclast migration. This comprehensive single-cell transcriptome analysis of GCTB identified a series of genes associated with cell migration as well as four major signaling pathways that were highly related to the migration of osteoclasts in GCTB. Our findings broaden the understanding of GCTB bionetworks and provides a theoretical basis for anti-osteolysis therapy against GCTB in the future.
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http://dx.doi.org/10.3389/fonc.2021.715552DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8421549PMC
August 2021

Oroxylin A reduces osteoclast formation and bone resorption via suppressing RANKL-induced ROS and NFATc1 activation.

Biochem Pharmacol 2021 Sep 4;193:114761. Epub 2021 Sep 4.

Guangxi Key Laboratory of Regenerative Medicine, Research Centre for Regenerative Medicine, Guangxi Medical University, Nanning, Guangxi, China; Guangxi Collaborative Innovation Center for Biomedicine, Guangxi Medical University, Nanning, Guangxi, China. Electronic address:

Excessive bone erosion by osteoclasts is associated with osteoporosis, rheumatoid arthritis, and periprosthetic osteolysis. Targeting osteoclasts may serve as an effective treatment for osteolytic diseases. Although drugs are currently available for the treatment of these diseases, exploring potential anti-osteoclast natural compounds with safe and effective treatment remains needed. Oroxylin A (OA), a natural flavonoid isolated from the root of Scutellaria baicalensis Georgi, has numerous beneficial pharmacological characteristics, including anti-inflammatory and antioxidant activity. However, its effects and mechanisms on osteoclast formation and bone resorption have not yet been clarified. Our research showed that OA attenuated the formation and function of osteoclast induced by RANKL in a time- and concentration-dependent manner without any cytotoxicity. Mechanistically, OA suppressed intracellular reactive oxygen species (ROS) levels through the Nrf2-mediated antioxidant response. Moreover, OA inhibited the activity of NFATc1, the master transcriptional regulator of RANKL-induced osteoclastogenesis. OA exhibited protective effects in mouse models of post-ovariectomy (OVX)- and lipopolysaccharide (LPS)-induced bone loss, in accordance with its in vitro anti-osteoclastogenic effect. Collectively, our findings highlight the potential of OA as a pharmacological agent for the prevention of osteoclast-mediated osteolytic diseases.
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http://dx.doi.org/10.1016/j.bcp.2021.114761DOI Listing
September 2021

Upregulation of 15 Antisense Long Non-Coding RNAs in Osteosarcoma.

Genes (Basel) 2021 Jul 26;12(8). Epub 2021 Jul 26.

Perron Institute for Neurological and Translational Science, QEII Medical Centre, Nedlands, WA 6009, Australia.

The human genome encodes thousands of natural antisense long noncoding RNAs (lncRNAs); they play the essential role in regulation of gene expression at multiple levels, including replication, transcription and translation. Dysregulation of antisense lncRNAs plays indispensable roles in numerous biological progress, such as tumour progression, metastasis and resistance to therapeutic agents. To date, there have been several studies analysing antisense lncRNAs expression profiles in cancer, but not enough to highlight the complexity of the disease. In this study, we investigated the expression patterns of antisense lncRNAs from osteosarcoma and healthy bone samples (24 tumour-16 bone samples) using RNA sequencing. We identified 15 antisense lncRNAs (, , , , , , , , , , , , , and ) that were upregulated in tumour samples compared to bone sample controls. Further, we performed real-time polymerase chain reaction (RT-qPCR) to validate the expressions of the antisense lncRNAs in 8 different osteosarcoma cell lines (SaOS-2, G-292, HOS, U2-OS, 143B, SJSA-1, MG-63, and MNNG/HOS) compared to hFOB (human osteoblast cell line). These differentially expressed IncRNAs can be considered biomarkers and potential therapeutic targets for osteosarcoma.
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http://dx.doi.org/10.3390/genes12081132DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8394133PMC
July 2021

Morin attenuates osteoclast formation and function by suppressing the NF-κB, MAPK and calcium signalling pathways.

Phytother Res 2021 Aug 22. Epub 2021 Aug 22.

Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, China.

Morin is a natural compound isolated from moraceae family members and has been reported to possess a range of pharmacological activities. However, the effects of morin on bone-associated disorders and the potential mechanism remain unknown. In this study, we investigated the anti-osteoclastogenic effect of morin in vitro and the potential therapeutic effects on ovariectomy (OVX)-induced osteoporosis in vivo. In vitro, by using a bone marrow macrophage-derived osteoclast culture system, we determined that morin attenuated receptor activator of nuclear factor (NF)-κB ligand (RANKL)-induced osteoclast formation via the inhibition of the mitogen-activated protein kinase (MAPK), NF-κB and calcium pathways. In addition, the subsequent expression of nuclear factor of activated T cells c1 (NFATc1) and c-fos was significantly suppressed by morin. In addition, NFATc1 downregulation led to the reduced expression of osteoclastogenesis-related marker genes, such as V-ATPase-d2 and Integrin β3. In vivo, results provided that morin could effectively attenuate OVX-induced bone loss in C57BL/6 mice. In conclusion, our results demonstrated that morin suppressed RANKL-induced osteoclastogenesis via the NF-κB, MAPK and calcium pathways, in addition, its function of preventing OVX-induced bone loss in vivo, which suggested that morin may be a potential therapeutic agent for postmenopausal osteoporosis treatment.
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http://dx.doi.org/10.1002/ptr.7229DOI Listing
August 2021

Single-Cell Transcriptomics Reveals the Complexity of the Tumor Microenvironment of Treatment-Naive Osteosarcoma.

Front Oncol 2021 21;11:709210. Epub 2021 Jul 21.

Center for Genomic and Personalized Medicine, School of Preclinical Medicine, Guangxi Medical University, Nanning, China.

Osteosarcoma (OS), which occurs most commonly in adolescents, is associated with a high degree of malignancy and poor prognosis. In order to develop an accurate treatment for OS, a deeper understanding of its complex tumor microenvironment (TME) is required. In the present study, tissues were isolated from six patients with OS, and then subjected to single-cell RNA sequencing (scRNA-seq) using a 10× Genomics platform. Multiplex immunofluorescence staining was subsequently used to validate the subsets identified by scRNA-seq. ScRNA-seq of six patients with OS was performed prior to neoadjuvant chemotherapy, and data were obtained on 29,278 cells. A total of nine major cell types were identified, and the single-cell transcriptional map of OS was subsequently revealed. Identified osteoblastic OS cells were divided into five subsets, and the subsets of those osteoblastic OS cells with significant prognostic correlation were determined using a deconvolution algorithm. Thereby, different transcription patterns in the cellular subtypes of osteoblastic OS cells were reported, and key transcription factors associated with survival prognosis were identified. Furthermore, the regulation of osteolysis by osteoblastic OS cells receptor activator of nuclear factor kappa-B ligand was revealed. Furthermore, the role of osteoblastic OS cells in regulating angiogenesis through vascular endothelial growth factor-A was revealed. C3_TXNIP macrophages and C5_IFIT1 macrophages were found to regulate regulatory T cells and participate in CD8 T cell exhaustion, illustrating the possibility of immunotherapy that could target CD8 T cells and macrophages. Our findings here show that the role of C1_osteoblastic OS cells in OS is to promote osteolysis and angiogenesis, and this is associated with survival prognosis. In addition, T cell depletion is an important feature of OS. More importantly, the present study provided a valuable resource for the in-depth study of the heterogeneity of the OS TME.
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http://dx.doi.org/10.3389/fonc.2021.709210DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8335545PMC
July 2021

Type II Collagen Sponges Facilitate Tendon Stem/Progenitor Cells to Adopt More Chondrogenic Phenotypes and Promote the Regeneration of Fibrocartilage-Like Tissues in a Rabbit Partial Patellectomy Model.

Front Cell Dev Biol 2021 16;9:682719. Epub 2021 Jul 16.

School of Biomedical Sciences, The University of Western Australia, Perth, WA, Australia.

Objective: Fibrocartilage transition zone (FC) is difficult to regenerate after surgical re-attachment of tendon to bone. Here, we investigated whether type II collagen-sponges (CII-sponges) facilitated tendon stem/progenitor cells (TSPCs) to adopt chondrogenic phenotypes and further observed if this material could increase the FC areas in bone-tendon junction (BTJ) injury model.

Methods: CII-sponges were made as we previously described. The appearance and pore structure of CII-sponges were photographed by camera and microscopies. The viability, proliferation, and differentiation of TSPCs were examined by LIVE/DEAD assay, alamarBlue, and PKH67 tracking. Subsequently, TSPCs were seeded in CII-sponges, Matrigel or monolayer, and induced under chondrogenic medium for 7 or 14 days before being harvested for qPCR or being transplanted into nude mice to examine the chondrogenesis of TSPCs. Lastly, partial patellectomy (PP) was applied to establish the BTJ injury model. CII-sponges were interposed between the patellar fragment and tendon, and histological examination was used to assess the FC regeneration at BTJ after surgery at 8 weeks.

Results: CII-sponges were like sponges with interconnected pores. TSPCs could adhere, proliferate, and differentiate in this CII-sponge up to 14 days at least. Both qPCR and immunostaining data showed that compared with TSPCs cultured in monolayer or Matrigel, cells in CII-sponges group adopted more chondrogenic phenotypes with an overall increase of chondrocyte-related genes and proteins. Furthermore, in PP injured model, much more new formed cartilage-like tissues could be observed in CII-sponges group, evidenced by a large amount of positive proteoglycan expression and typical oval or round chondrocytes in this area.

Conclusion: Our study showed that CII-sponges facilitated the TSPCs to differentiate toward chondrocytes and increased the area of FCs, which suggests that CII-sponges are meaningful for the reconstruction of FC at bone tendon junction. However, the link between the two phenomena requires further research and validation.
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http://dx.doi.org/10.3389/fcell.2021.682719DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8322758PMC
July 2021

Current research progress in targeted anti-angiogenesis therapy for osteosarcoma.

Cell Prolif 2021 Jul 26:e13102. Epub 2021 Jul 26.

Division of Regenerative Biology, School of Biomedical Sciences, University of Western Australia, Perth, WA, Australia.

Osteosarcoma (OS) is the most common primary malignant bone tumour with a peak in incidence during adolescence. Delayed patient presentation and diagnosis is common with approximately 15% of OS patients presenting with metastatic disease at initial diagnosis. With the introduction of neoadjuvant chemotherapy in the 1970s, disease prognosis improved from 17% to 60%-70% 5-year survival, but outcomes have not significantly improved since then. Novel and innovative therapeutic strategies are urgently needed as an adjunct to conventional treatment modalities to improve outcomes for OS patients. Angiogenesis is crucial for tumour growth, metastasis and invasion, and its prevention will ultimately inhibit tumour growth and metastasis. Dysregulation of angiogenesis in bone microenvironment involving osteoblasts and osteoclasts might contribute to OS development. This review summarizes existing knowledge regarding pre-clinical and developmental research of targeted anti-angiogenic therapy for OS with the aim of highlighting the limitations associated with this application. Targeted anti-angiogenic therapies include monoclonal antibody to VEGF (bevacizumab), tyrosine kinase inhibitors (Sorafenib, Apatinib, Pazopanib and Regorafenib) and human recombinant endostatin (Endostar). However, considering the safety and efficacy of these targeted anti-angiogenesis therapies in clinical trials cannot be guaranteed at this point, further research is needed to completely understand and characterize targeted anti-angiogenesis therapy in OS.
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http://dx.doi.org/10.1111/cpr.13102DOI Listing
July 2021

Sesamolin Protects Mice From Ovariectomized Bone Loss by Inhibiting Osteoclastogenesis and RANKL-Mediated NF-κB and MAPK Signaling Pathways.

Front Pharmacol 2021 14;12:664697. Epub 2021 Jun 14.

Guangxi Key Laboratory of Regenerative Medicine, Guangxi-ASEAN Collaborative Innovation Center for Major Disease Prevention and Treatment, Guangxi Medical University, Guangxi, China.

This article was submitted to Experimental Pharmacology and Drug Discovery, a section of the journal Frontiers in Pharmacology. Postmenopausal osteoporosis (PMOP), which increases the risk of fracture, is the most common bone disease in women. PMOP not only increases the risk of death but also imposes a financial burden on countless families. At present, most of the drugs used to treat osteoporosis have significant side effects, so it is important to find effective anti-osteoporosis medications without major side effects. Sesamolin (Ses) is a kind of natural lignan extracted from sesame oil. Many researches have shown that Ses has anti-inflammatory, antioxidative, and anticancer effects, however it is still unknown whether it has any effect on osteoporosis. In this research, we explored the therapeutic effect of Ses in the process of osteoclast formation and bone resorption and found that Ses effectively inhibited osteoclast formation through TRAcP staining and hydroxyapatite resorption assays. Through Western blot analysis of the NF-κB pathway, MAPK pathway, c-Fos and NFATc1, it was found that Ses not only effectively inhibited the activation of NF-κB and MAPK signaling pathways induced by RANKL but also significantly reduced the protein expression of c-Fos and NFATc1. Several genes specifically expressed in osteoclasts were determined by qPCR, and Ses was also found to play a significant inhibitory role on the expression of these genes. Besides, an osteoporosis model induced in ovariectomized (OVX) mice was employed to verify that Ses could effectively reduce bone loss caused by estrogen deficiency . In conclusion, Ses showed promise as a new treatment for postmenopausal osteoporosis.
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http://dx.doi.org/10.3389/fphar.2021.664697DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8237092PMC
June 2021

Patchouli Alcohol Modulates the Pregnancy X Receptor/Toll-like Receptor 4/Nuclear Factor Kappa B Axis to Suppress Osteoclastogenesis.

Front Pharmacol 2021 8;12:684976. Epub 2021 Jun 8.

Department of Orthopaedic Surgery, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China.

The incidence of osteoporosis, which is primarily characterized by plethoric osteoclast (OC) formation and severe bone loss, has increased in recent years. Millions of people worldwide, especially postmenopausal women, suffer from osteoporosis. The drugs commonly used to treat osteoporosis still exist many disadvantages, but natural extracts provide options for the treatment of osteoporosis. Therefore, the identification of cost-effective natural compounds is important. Patchouli alcohol (PA), a natural compound extracted from that exerts anti-inflammatory effects, is used as a treatment for gastroenteritis. However, no research on the use of Patchouli alcohol in osteoporosis has been reported. We found that PA dose-dependently inhibited the receptor activator of nuclear factor kappa-B ligand (RANKL)-induced formation and function of OCs without cytotoxicity. Furthermore, these inhibitory effects were reflected in the significant effect of PA on the NF-κB signaling pathway, as PA suppressed the transcription factors NFATc1 and c-Fos. We also determined that PA activated expression of the nuclear receptor pregnane X receptor (PXR) and promoted the PXR/Toll-like receptor 4 (TLR4) axis to inhibit the nuclear import of NF-κB (p50 and p65). Additionally, PA exerted therapeutic effects against osteoporosis in ovariectomized (OVX) mice, supporting the use of PA as a treatment for osteoporosis in the future.
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http://dx.doi.org/10.3389/fphar.2021.684976DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8227438PMC
June 2021

Biological insights into the rapid tissue regeneration of freshwater crayfish and crustaceans.

Cell Biochem Funct 2021 Aug 24;39(6):740-753. Epub 2021 Jun 24.

Division of Regenerative Biology, School of Biomedical Sciences, University of Western Australia, Perth, Western Australia, Australia.

The freshwater crayfish is capable of regenerating limbs, following autotomy, injury and predation. In arthropod species, regeneration and moulting are two processes linked and strongly regulated by ecdysone. The regeneration of crayfish limbs is divided into wound healing, blastema formation, cellular reprogramming and tissue patterning. Limb blastema cells undergo proliferation, dedifferentiation and redifferentiation. A limb bud, containing folded segments of the regenerating limb, is encased within a cuticular sheath. The functional limb regenerates, in proecdysis, in two to three consecutive moults. Rapid tissue growth is regulated by hormones, limb nerves and local cells. The TGF-β/activin signalling pathway has been determined in the crayfish, P. fallax f. virginalis, and is suggested as a potential regulator of tissue regeneration. In this review article, we discuss current understanding of tissue regeneration in the crayfish and various crustaceans. A thorough understanding of the cellular, genetic and molecular pathways of these biological processes is promising for the development of therapeutic applications for a wide array of diseases in regenerative medicine.
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http://dx.doi.org/10.1002/cbf.3653DOI Listing
August 2021

Notopterol Attenuates Estrogen Deficiency-Induced Osteoporosis Repressing RANKL Signaling and Reactive Oxygen Species.

Front Pharmacol 2021 3;12:664836. Epub 2021 Jun 3.

Department of Orthopaedic Surgery, First Affiliated Hospital, Guangzhou University of Chinese Medicine, Guangzhou, China.

Integrity of the skeleton is sustained through the balanced activities of osteoblasts and osteoclasts in bone remodeling unit. The balance can be disrupted by excessive osteoclasts activation commonly seen in osteoporosis. Notopterol (NOT) is a main component of Notopterygium incisum which exerts a wide spectrum effect on biomedical pharmacology. In our study, we found NOT serves as an inhibitor in regulating RANKL-activated osteoclasts formation and bone resorption function by calculating tartrate resistant acid phosphatase (TRAcP) staining and hydroxyapatite resorption assays. Furthermore, RANKL-mediated signaling pathways including MAPK, NF-κB and calcium ossification were hampered, whereas ROS scavenging enzymes in Nrf2/Keap1/ARE signaling pathways were promoted by NOT. In addition, the activation of the essential transcription factor NFATc1 in RANKL-mediated osteoclastogenesis was almost totally suppressed by NOT. What is more, NOT diminished the loss of bone mass in preclinical model of OVX mice by blocking osteoclastogenesis determined by bone histomorphometry, TRAcP staining and H&E staining. Conclusively, our findings demonstrated that NOT could arrest osteoclastogenesis and bone resorptive activity by attenuating RANKL-mediated MAPK, NF-κB, calcium and NFATc1 signaling transduction pathways and enhancing ROS scavenging enzymes in Nrf2/Keap1/ARE pathways , and prohibit bone loss induced by OVX . Taken together, NOT may be identified to be a natural and novel treatment for osteolytic diseases.
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http://dx.doi.org/10.3389/fphar.2021.664836DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8210423PMC
June 2021

An emerging role of Prevotella histicola on estrogen deficiency-induced bone loss through the gut microbiota-bone axis in postmenopausal women and in ovariectomized mice.

Am J Clin Nutr 2021 Jun 10. Epub 2021 Jun 10.

Department of Orthopaedics, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.

Background: The gut microbiota (GM)-bone axis has emerged as a crucial mediator of bone homeostasis. Estrogen deficiency-induced bone loss is closely associated with an altered GM. However, the underlying mechanisms remain unclear.

Objectives: We sought to explore the putative effects of GM on estrogen deficiency-induced bone loss and determine a potential mechanism.

Methods: Fecal samples collected from postmenopausal women with osteoporosis (PMO) and with normal bone mass (PMN) were examined by 16S ribosomal RNA (rRNA) gene sequencing and analysis. Prevotella histicola, a typical species of Prevotella, was orally given to female C57BL6/J mice after ovariectomy [ovariectomized (OVX)]. The primary outcomes were changes in bone microstructures as measured by micro-computed tomography scanning and bone histomorphometry analysis. Secondary outcomes included changes in osteoclast activity, the expression of osteoclastogenic cytokines, and gut permeability, which were measured by ELISA, qRT-PCR, western blot, and immunofluorescence.

Results: As demonstrated through 16S rRNA gene sequencing and analysis, the GM in the PMO group featured a significantly decreased proportion of the genus Prevotella in comparison with that in the PMN group (∼60%, P < 0.05). In animal experiments, P. histicola-treated OVX mice maintained a relatively higher bone volume than OVX controls. Mechanistically, the protective effects of P. histicola on bone mass were found to be associated with its modulation of gut permeability as well as its inhibitory effects on osteoclast activity which function by attenuating osteoclastogenic cytokine expression.

Conclusions: The GM diversity and composition between the PMN and PMO groups were significantly different. In particular, the proportion of the genus Prevotella was notably higher in the PMN group, demonstrating its potential bone-protective effects on osteoporosis. Further animal study using osteoporotic mice showed P. histicola could prevent estrogen deficiency-induced bone loss through the GM-bone axis. Thus, P. histicola may serve as a therapeutic agent or target for osteoporosis treatment.
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http://dx.doi.org/10.1093/ajcn/nqab194DOI Listing
June 2021

The effects of biophysical stimulation on osteogenic differentiation and the mechanisms from ncRNAs.

Cell Biochem Funct 2021 Aug 26;39(6):727-739. Epub 2021 May 26.

School of Kinesiology, Shanghai University of Sport, Shanghai, China.

Ample proof showed that non-coding RNAs (ncRNAs) play a crucial role in proliferation and differentiation of osteoblasts and bone marrow stromal cells (BMSCs). Varied forms of biophysical stimuli like mechanical strain, fluid shear stress (FSS), microgravity and vibration are verified to regulate ncRNAs expression in osteogenic differentiation and influence the expression of target genes associated with osteogenic differentiation and ultimately regulate bone formation. The consequences of biophysical stimulation on osteogenic differentiation validate the prospect of exercise for the prevention and treatment of osteoporosis. In this review, we tend to summarize the studies on regulation of osteogenic differentiation by ncRNAs beneath biophysical stimulation and facilitate to reveal the regulatory mechanism of biophysical stimulation on ncRNAs, and provide an update for the prevention of bone metabolism diseases by exercise.
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http://dx.doi.org/10.1002/cbf.3650DOI Listing
August 2021

The Role of Irisin in Exercise-Mediated Bone Health.

Front Cell Dev Biol 2021 4;9:668759. Epub 2021 May 4.

School of Kinesiology, Shanghai University of Sport, Shanghai, China.

Exercise training promotes physical and bone health, and is the first choice of non-drug strategies that help to improve the prognosis and complications of many chronic diseases. Irisin is a newly discovered peptide hormone that modulates energy metabolism and skeletal muscle mass. Here, we discuss the role of irisin in bone metabolism via exercise-induced mechanical forces regulation. In addition, the role of irisin in pathological bone loss and other chronic diseases is also reviewed. Notably, irisin appears to be a key determinant of bone mineral status and thus may serve as a novel biomarker for bone metabolism. Interestingly, the secretion of irisin appears to be mediated by different forms of exercise and pathological conditions such as diabetes, obesity, and inflammation. Understanding the mechanism by which irisin is regulated and how it regulates skeletal metabolism via osteoclast and osteoblast activities will be an important step toward applying new knowledge of irisin to the treatment and prevention of bone diseases such as osteolysis and other chronic disorders.
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http://dx.doi.org/10.3389/fcell.2021.668759DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8129548PMC
May 2021

Novel vertebrate- and brain-specific driver of neuronal outgrowth.

Prog Neurobiol 2021 Jul 29;202:102069. Epub 2021 Apr 29.

Department of Molecular Animal Physiology, Donders Institute for Brain, Cognition and Behaviour, Centre for Neuroscience, Radboud University, Geert Grooteplein Zuid 26-28, 6525 GA, Nijmegen, the Netherlands. Electronic address:

During the process of neuronal outgrowth, developing neurons produce new projections, neurites, that are essential for brain wiring. Here, we discover a relatively late-evolved protein that we denote Ac45-related protein (Ac45RP) and that, surprisingly, drives neuronal outgrowth. Ac45RP is a paralog of the Ac45 protein that is a component of the vacuolar proton ATPase (V-ATPase), the main pH regulator in eukaryotic cells. Ac45RP mRNA expression is brain specific and coincides with the peak of neurogenesis and the onset of synaptogenesis. Furthermore, Ac45RP physically interacts with the V-ATPase V-sector and colocalizes with V in unconventional, but not synaptic, secretory vesicles of extending neurites. Excess Ac45RP enhances the expression of V-subunits, causes a more elaborate Golgi, and increases the number of cytoplasmic vesicular structures, plasma membrane formation and outgrowth of actin-containing neurites devoid of synaptic markers. CRISPR-cas9n-mediated Ac45RP knockdown reduces neurite outgrowth. We conclude that the novel vertebrate- and brain-specific Ac45RP is a V-interacting constituent of unconventional vesicular structures that drives membrane expansion during neurite outgrowth and as such may furnish a tool for future neuroregenerative treatment strategies.
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http://dx.doi.org/10.1016/j.pneurobio.2021.102069DOI Listing
July 2021

12 Survival-related differentially expressed genes based on the TARGET-osteosarcoma database.

Exp Biol Med (Maywood) 2021 Apr 29:15353702211007410. Epub 2021 Apr 29.

Perron Institute for Neurological and Translational Science, QEII Medical Centre, Nedlands, WA 6009, Australia.

The Therapeutically Applicable Research to Generate Effective Treatments (TARGET) project aims to determine molecular changes that drive childhood cancers, including osteosarcoma. The main purpose of the program is to use the open-source database to develop novel, effective, and less toxic therapies. We downloaded TARGET-OS RNA-Sequencing data through R studio and merged the mRNA expression of genes with clinical information (vital status, survival time and gender). Further, we analyzed differential gene expressions between dead and alive patients based on TARGET-OS project. By this study, we found 5758 differentially expressed genes between deceased and alive patients with a false discovery rate below 0.05; 4469 genes were upregulated in deceased patients compared to alive, whereas 1289 genes were downregulated. The survival-related genes were obtained using Kaplan-Meier survival analysis and Cox univariate regression (KM < 0.05 and Cox -value < 0.05). Out of 5758 differentially expressed genes, only 217 have been associated with overall survival. Eight survival-related downregulated genes (, , , , , , , and ) and four survival-related upregulated genes (, , and ) were selected for further analysis as potential independent prognostic candidate genes. This study may help to discover novel prognostic markers and potential therapeutic targets for osteosarcoma.
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http://dx.doi.org/10.1177/15353702211007410DOI Listing
April 2021

Rosuvastatin Nanomicelles Target Neuroinflammation and Improve Neurological Deficit in a Mouse Model of Intracerebral Hemorrhage.

Int J Nanomedicine 2021 20;16:2933-2947. Epub 2021 Apr 20.

Neurosurgery Research Laboratory, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, Sichuan, People's Republic of China.

Background: Intracerebral hemorrhage (ICH), a devastating subtype of stroke, has a poor prognosis. However, there is no effective therapy currently available due to its complex pathological progression, in which neuroinflammation plays a pivotal role in secondary brain injury. In this work, the use of statin-loaded nanomicelles to target the neuroinflammation and improve the efficacy was studied in a mouse model of ICH.

Methods: Rosuvastatin-loaded nanomicelles were prepared by a co-solvent evaporation method using polyethylene glycol-poly(ε-caprolactone) (PEG-PCL) copolymer as a carrier. The prepared nanomicelles were characterized by transmission electron microscopy (TEM) and dynamic light scattering (DLS), and then in vitro and in vivo studies were performed.

Results: TEM shows that the nanomicelles are spherical with a diameter of about 19.41 nm, and DLS shows that the size, zeta potential, and polymer dispersity index of the nanomicelles were 23.37 nm, -19.2 mV, and 0.221, respectively. The drug loading content is 8.28%. The in vivo study showed that the nanomicelles significantly reduced neuron degeneration, inhibited the inflammatory cell infiltration, reduced the brain edema, and improved neurological deficit. Furthermore, it was observed that the nanomicelles promoted the polarization of microglia/macrophages to M2 phenotype, and also the expression of the proinflammatory cytokines, such as IL-1β and TNF-α, was significantly down-regulated, while the expression of the anti-inflammatory cytokine IL-10 was significantly up-regulated. The related mechanism was proposed and discussed.

Conclusion: The nanomicelles treatment suppressed the neuroinflammation that might contribute to the promoted nerve functional recovery of the ICH mouse, making it potential to be applied in clinic.
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http://dx.doi.org/10.2147/IJN.S294916DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8068519PMC
June 2021

The molecular structure and role of CCL2 (MCP-1) and C-C chemokine receptor CCR2 in skeletal biology and diseases.

J Cell Physiol 2021 Oct 30;236(10):7211-7222. Epub 2021 Mar 30.

Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.

Monocyte chemoattractant protein-1, also called chemokine (C-C motif) ligand 2 (CCL2) or small inducible cytokine A2, is an inflammatory mediator capable of recruiting monocytes, memory T cells, and dendritic cells. CCL2 is a member of the CC chemokine superfamily, which binds to its receptor, C-C motif chemokine receptor-2 (CCR2), for the induction of chemotactic activity and an increase of calcium influx. It exerts multiple effects on a variety of cells, including monocytes, macrophages, osteoclasts, basophils, and endothelial cells, and is involved in a diverse range of diseases. This review discusses the molecular structure and role of CCL2 and CCR2 in skeletal biology and disease. Molecular structure analyses reveal that CCL2 shares a conserved C-C motif; however, it has only limited sequence homology with other CCL family members. Likewise, CCR2, as a member of the G-protein-coupled seven-transmembrane receptor superfamily, shares conserved cysteine residues, but exhibits very limited sequence homology with other CCR family members. In the skeletal system, the expression of CCL2 is regulated by a variety of factors, such as parathyroid hormone/parathyroid hormone-related peptide, interleukin 1b, tumor necrosis factor-α and transforming growth factor-beta, RANKL, and mechanical forces. The interaction of CCL2 and CCR2 activates several signaling cascades, including PI3K/Akt/ERK/NF-κB, PI3K/MAPKs, and JAK/STAT-1/STAT-3. Understanding the role of CCL2 and CCR2 will facilitate the development of novel therapies for skeletal disorders, including rheumatoid arthritis, osteolysis and other inflammatory diseases related to abnormal chemotaxis.
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http://dx.doi.org/10.1002/jcp.30375DOI Listing
October 2021

AAV2-mediated and hypoxia response element-directed expression of bFGF in neural stem cells showed therapeutic effects on spinal cord injury in rats.

Cell Death Dis 2021 03 15;12(3):274. Epub 2021 Mar 15.

School of Biomedical Sciences, The University of Western Australia, Perth, WA, 6009, Australia.

Neural stem cell (NSCs) transplantation has been one of the hot topics in the repair of spinal cord injury (SCI). Fibroblast growth factor (FGF) is considered a promising nerve injury therapy after SCI. However, owing to a hostile hypoxia condition in SCI, there remains a challenging issue in implementing these tactics to repair SCI. In this report, we used adeno-associated virus 2 (AAV2), a prototype AAV used in clinical trials for human neuron disorders, basic FGF (bFGF) gene under the regulation of hypoxia response element (HRE) was constructed and transduced into NSCs to yield AAV2-5HRE-bFGF-NSCs. Our results showed that its treatment yielded temporally increased expression of bFGF in SCI, and improved scores of functional recovery after SCI compared to vehicle control (AAV2-5HRE-NSCs) based on the analyses of the inclined plane test, Basso-Beattie-Bresnahan (BBB) scale and footprint analysis. Mechanistic studies showed that AAV2-5HRE-bFGF-NSCs treatment increased the expression of neuron-specific neuronal nuclei protein (NeuN), neuromodulin GAP43, and neurofilament protein NF200 while decreased the expression of glial fibrillary acidic protein (GFAP) as compared to the control group. Further, the expressions of autophagy-associated proteins LC3-II and Beclin 1 were decreased, whereas the expression of P62 protein was increased in AAV2-5HRE-bFGF-NSCs treatment group. Taken together, our data indicate that AAV2-5HRE-bFGF-NSCs treatment improved the recovery of SCI rats, which is accompanied by evidence of nerve regeneration, and inhibition of SCI-induced glial scar formation and cell autophagy. Thus, this study represents a step forward towards the potential use of AAV2-5HRE-bFGF-NSCs for future clinical trials of SCI repair.
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http://dx.doi.org/10.1038/s41419-021-03546-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7960741PMC
March 2021

Molecular structure, gene expression and functional role of WFDC1 in angiogenesis and cancer.

Cell Biochem Funct 2021 Jul 21;39(5):588-595. Epub 2021 Feb 21.

Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, China.

Whey acidic proteins (WAP) perform a diverse range of important biological functions, including proteinase activity, calcium transport and bacterial growth. The WAP four-disulphide core domain protein 1 (WFDC1) gene (also called PS20), encodes the 20 kDa prostate stromal protein (ps20), which is a member of the WAP-type four-disulphide core domain family of proteins, and exhibits characteristics of serine protease inhibitors, such as elafin and secretory leukocyte protease inhibitor. Molecular structural analysis reveals that ps20 consists of four-disulphide bonds formed by eight cysteine residues located at the carboxyl terminus of the protein. Wfdc1-null mice were found to display no overt developmental phenotype, suggesting a dispensable role in organ growth and development. However, WFDC1 was able to mediate endothelial cell migration and pericyte stabilization, which are vital for the formation of functional vascular structures. WFDC1 was also found to be downregulated in cancers and exhibited a regulatory effect on cell proliferation. In addition, it was involved in the modulation of memory T cells during human immunodeficiency virus infection. Gaining a solid understanding of the mechanisms by which WFDC1 regulates tissue homeostasis and disease processes, in a tissue specific manner, will be an important move towards the development of WFDC1/ps20 as potential therapeutic targets.
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http://dx.doi.org/10.1002/cbf.3624DOI Listing
July 2021

Systemic Administration of Fibroblast Growth Factor 21 Improves the Recovery of Spinal Cord Injury (SCI) in Rats and Attenuates SCI-Induced Autophagy.

Front Pharmacol 2020 27;11:628369. Epub 2021 Jan 27.

Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, China.

Protecting the death of nerve cells is an essential tactic for spinal cord injury (SCI) repair. Recent studies show that nerve growth factors can reduce the death of nerve cells and promote the healing of nerve injury. To investigate the conducive effect of fibroblast growth factor 21 (FGF21) on SCI repair. FGF21 proteins were systemically delivered into rat model of SCI via tail vein injection. We found that administration of FGF21 significantly promoted the functional recovery of SCI as assessed by BBB scale and inclined plane test, and attenuated cell death in the injured area by histopathological examination with Nissl staining. This was accompanied with increased expression of NeuN, GAP43 and NF200, and deceased expression of GFAP. Interestingly, FGF21 was found to attenuate the elevated expression level of the autophagy marker LC3-II (microtubules associated protein 1 light chain 3-II) induced by SCI in a dose-dependent manner. These data show that FGF21 promotes the functional recovery of SCI via restraining injury-induced cell autophagy, suggesting that systemic administration of FGF21 could have a therapeutic potential for SCI repair.
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http://dx.doi.org/10.3389/fphar.2020.628369DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7873052PMC
January 2021

Osteoimmunological insights into the pathogenesis of ankylosing spondylitis.

J Cell Physiol 2021 Sep 8;236(9):6090-6100. Epub 2021 Feb 8.

School of Kinesiology, Shanghai University of Sport, Shanghai, China.

Ankylosing spondylitis (AS) is inflammatory arthritis predominantly affecting the spine, which is involved in the disorders of both immune and skeletal systems. The exact pathogenesis of AS is not fully understood. Osteoimmunology is a new subject of study in inflammatory arthritis, in particular the pathogenic events involved in the cross-regulation of both skeletal and immune systems. In this review, we discuss osteoimmunological and pathological changes of AS in the spine that are characterized by altered osteogenesis and osteolytic bone destruction, accompanied by the changes of the immune system. It was revealed that bone cells like mesenchymal stem cells, osteoblast, and osteoclast in crossing talking with immune cells such as T cells, B cells coregulate to the pathogenesis of AS. Further, an array of cytokines and molecules expressed by both skeletal and immune systems contribute to these complex interplays. Understanding the cellular and molecular mechanisms underlying the pathogenesis of AS will lay a foundation for the exploration of the potential new treatment to AS.
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http://dx.doi.org/10.1002/jcp.30313DOI Listing
September 2021

Enhanced BMP signalling causes growth plate cartilage dysrepair in rats.

Bone 2021 04 4;145:115874. Epub 2021 Feb 4.

University of South Australia, UniSA Clinical and Health Sciences, Adelaide, SA 5001, Australia; Department of Orthopedics, Tongji Hospital, Tongji University, Shanghai 200065, China; Ningbo No. 6 Hospital, Ningbo University, Ningbo 315040, China. Electronic address:

Growth plate cartilage injuries often result in bony repair at the injury site and premature mineralisation at the uninjured region causing bone growth defects, for which underlying mechanisms are unclear. With the prior microarray study showing upregulated bone morphogenetic protein (BMP) signalling during the injury site bony repair and with the known roles of BMP signalling in bone healing and growth plate endochondral ossification, this study used a rat tibial growth plate drill-hole injury model with or without systemic infusion of BMP antagonist noggin to investigate roles of BMP signalling in injury repair responses within the injury site and in the adjacent "uninjured" cartilage. At days 8, 14 and 35 post-injury, increased expression of BMP members and receptors and enhanced BMP signalling (increased levels of phosphorylated (p)-Smad1/5/8) were found during injury site bony repair. After noggin treatment, injury site bony repair at days 8 and 14 was reduced as shown by micro-CT and histological analyses and lower mRNA expression of osteogenesis-related genes Runx2 and osteocalcin (by RT-PCR). At the adjacent uninjured cartilage, the injury caused increases in the hypertrophic zone/proliferative zone height ratio and in mRNA expression of hypertrophy marker collagen-10, but a decrease in chondrogenesis marker Sox9 at days 14 and/or 35, which were accompanied by increased BMP signalling (increased levels of pSmad1/5/8 protein and BMP7, BMPR1a and target gene Dlx5 mRNA). Noggin treatment reduced the hypertrophic zone/proliferative zone height ratio and collagen-10 mRNA expression, but increased collagen-2 mRNA levels at the adjacent growth plate. This study has identified critical roles of BMP signalling in the injury site bony repair and in the hypertrophic degeneration of the adjacent growth plate in a growth plate drill-hole repair model. Moreover, suppressing BMP signalling can potentially attenuate the undesirable bony repair at injury site and suppress the premature hypertrophy but potentially rescue chondrogenesis at the adjacent growth plate.
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http://dx.doi.org/10.1016/j.bone.2021.115874DOI Listing
April 2021

New physiological insights into the phenomena of deer antler: A unique model for skeletal tissue regeneration.

J Orthop Translat 2021 Mar 24;27:57-66. Epub 2020 Dec 24.

Division of Regenerative Biology, School of Biomedical Sciences, University of Western Australia, Perth, 6009, Australia.

Generally, mammals are unable to regenerate complex tissues and organs however the deer antler provides a rare anomaly to this rule. This osseous cranial appendage which is located on the frontal bone of male deer is capable of stem cell-based organogenesis, annual casting, and cyclic de novo regeneration. A series of recent studies have classified this form of regeneration as epimorphic stem cell based. Antler renewal is initiated by the activation of neural crest derived pedicle periosteal cells (PPCs) found residing within the pedicle periosteum (PP), these PPCs have the potential to differentiate into multiple lineages. Other antler stem cells (ASCs) are the reserve mesenchymal cells (RMCs) located in the antlers tip, which develop into cartilage tissue. Antlerogenic periosteal cells (APCs) found within the antlerogenic periosteum (AP) form the tissues of both the pedicle and first set of antlers. Antler stem cells (ASCs) further appear to progress through various stages of activation, this coordinated transition is considered imperative for stem cell-based mammalian regeneration. The latest developments have shown that the rapid elongation of the main beam and antler branches are a controlled form of tumour growth, regulated by the tumour suppressing genes TP73 and ADAMTS18. Both osteoclastogenesis, as well as osteogenic and chondrogenic differentiation are also involved. While there remains much to uncover this review both summarises and comprehensively evaluates our existing knowledge of tissue regeneration in the deer antler. This will assist in achieving the goal of in vitro organ regeneration in humans by furthering the field of modern regenerative medicine.

The Translational Potential Of This Article: As a unique stem cell-based organ regeneration process in mammals, the deer antler represents a prime model system for investigating mechanisms of regeneration in mammalian tissues. Novel ASCs could provide cell-based therapies for regenerative medicine and bone remodelling for clinical application. A greater understanding of this process and a more in-depth defining of ASCs will potentiate improved clinical outcomes.
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http://dx.doi.org/10.1016/j.jot.2020.10.012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7773678PMC
March 2021

The investigation of bone fracture healing under intramembranous and endochondral ossification.

Bone Rep 2021 Jun 15;14:100740. Epub 2020 Dec 15.

Department of Infrastructure Engineering, The University of Melbourne, Victoria 3010, Australia.

After trauma, fractured bone starts healing directly through bone union or indirectly through callus formation process. Intramembranous and endochondral ossification are two commonly known mechanisms of indirect healing. The present study investigated the bone fracture healing under intramembranous and endochondral ossification by developing theoretical models in conjunction with performing a series of animal experiments. Using experimentally determined mean bone densities in sheep tibia stabilized by the Locking Compression Plate (LCP) fixation system, the research outcomes showed that intramembranous and endochondral ossification can be described by Hill Function with two unique sets of function parameters in mechanical stimuli mediated fracture healing. Two different thresholds exist within the range of mechanical simulation index which could trigger significant intramembranous and endochondral ossification, with a relatively higher bone formation rate of endochondral ossification than that of intramembranous ossification. Furthermore, the increase of flexibility of the LCP system and the use of titanium LCP could potentially promote uniform bone formation across the fracture gap, ultimately better healing outcomes.
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http://dx.doi.org/10.1016/j.bonr.2020.100740DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7772545PMC
June 2021

STAT3 and its targeting inhibitors in osteosarcoma.

Cell Prolif 2021 Feb 31;54(2):e12974. Epub 2020 Dec 31.

Division of Regenerative Biology, School of Biomedical Sciences, University of Western Australia, Perth, WA, Australia.

Signal transducer and activator of transcription 3 (STAT3) is one of seven STAT family members involved with the regulation of cellular growth, differentiation and survival. STAT proteins are conserved among eukaryotes and are important for biological functions of embryogenesis, immunity, haematopoiesis and cell migration. STAT3 is widely expressed and located in the cytoplasm in an inactive form. STAT3 is rapidly and transiently activated by tyrosine phosphorylation by a range of signalling pathways, including cytokines from the IL-6 family and growth factors, such as EGF and PDGF. STAT3 activation and subsequent dimer formation initiates nuclear translocation of STAT3 for the regulation of target gene transcription. Four STAT3 isoforms have been identified, which have distinct biological functions. STAT3 is considered a proto-oncogene and constitutive activation of STAT3 is implicated in the development of various cancers, including multiple myeloma, leukaemia and lymphomas. In this review, we focus on recent progress on STAT3 and osteosarcoma (OS). Notably, STAT3 is overexpressed and associated with the poor prognosis of OS. Constitutive activation of STAT3 in OS appears to upregulate the expression of target oncogenes, leading to OS cell transformation, proliferation, tumour formation, invasion, metastasis, immune evasion and drug resistance. Taken together, STAT3 is a target for cancer therapy, and STAT3 inhibitors represent potential therapeutic candidates for the treatment of OS.
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http://dx.doi.org/10.1111/cpr.12974DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7848963PMC
February 2021

Circular RNAs in childhood-related diseases and cancers: A review.

Cell Biochem Funct 2021 Jun 23;39(4):458-467. Epub 2020 Dec 23.

School of Kinesiology, Shanghai University of Sport, Shanghai, China.

Research into the diagnosis, treatment and prevention of childhood-related diseases is the key to reducing their morbidity and mortality. Circular RNAs (circRNAs) play critical roles, both in physiology and pathology, and there is ample evidence to show that they play varying roles in tissue development and gene regulation. Studies on circRNAs in different childhood-related diseases have confirmed their great potential for disease prevention and treatment. These breakthroughs highlight the pathological role of circRNAs in cancers, as well as cardiovascular and hereditary childhood illnesses. In this review, we summarize the role of circRNAs in childhood-related diseases and cancer, and provide an update of the possible diagnostic and therapeutic application of circRNAs.
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http://dx.doi.org/10.1002/cbf.3611DOI Listing
June 2021

Highly Selective Gas Sensor Based on Hydrophobic Silica Decorated with Trimethoxyoctadecylsilane.

ACS Appl Mater Interfaces 2021 Jan 22;13(1):1956-1966. Epub 2020 Dec 22.

School of New Energy and Materials, Southwest Petroleum University (SWPU), Chengdu 610500, China.

Trimethoxyoctadecylsilane (OTMS) was successfully used to decorate mesoporous silica with a self-assembly method to enhance the relative gas selectivity. A quartz crystal microbalance was employed to measure the gas-sensing properties. The content of OTMS was the crucial factor that greatly affected the adsorption capacity () of silica, which could be converted to relative selectivity () to study the sensing mechanism. With increasing OTMS content, was far higher for small-molecule gases compared to volatile organic compounds (VOCs), which could be explained by the polarity of the bonding objects, and reached a maximum value of 45.71%. When exposed to VOCs, was always greater than 0 among the three alcohols. The sensing mechanisms of undecorated silica and OTMS-decorated silica were quite different; the three-state mechanism was proposed to explain the sensing mechanism of OTMS-decorated silica. When exposed to small-molecule gases, the atoms that bonded with carbon atoms on OTMS greatly influenced . With increasing OTMS content, the bonding energy of OTMS with CO was far less than that with other molecules, resulting in a relative selectivity as high as 38.69%. Furthermore, macroperformance and microproperties were combined in three-dimensional coordinates, which could be applied to predict the sensing performance of silica.
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http://dx.doi.org/10.1021/acsami.0c18582DOI Listing
January 2021
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