Self-assembled Abietic acid encapsulated nanoparticles to improve the stability of Proanthocyanin B2.

Procyanidin B2 (Pac B2) has attracted much attention due to its strong antioxidant activity, but poor in vivo stability limits its wide application in food and medicine. In this paper, composite nanoparticles (NPs) were constructed using abietic acid (AA) as a carrier, which significantly enhanced Pac B2 stability. A spherical morphology and average diameter of 396.05 nm were observed in AA-Pac B2 NPs synthesized by solvent co-precipitation. Pac B2 encapsulation was 11.28 %, and thermal stability is improved. Infrared, Ultraviolet spectrum, and MD (molecular dynamics) spectroscopy revealed hydrogen bonding and hydrophobic interaction between AA and Pac B2. For up to 2 h at 37 °C, Pac B2 can be sustainably released in simulated gastric and intestinal fluids. In vitro, AA-Pac B2 NPs at the same concentration exhibited higher bioavailability and uptake efficiency than free Pac B2. The data demonstrate the potential of AA NPs for improving polyphenol thermal stability and bioavailability.

Unveiling intratumoral microbiota: An emerging force for colorectal cancer diagnosis and therapy.

Microbes, including bacteria, viruses, fungi, and other eukaryotic organisms, are commonly present in multiple organs of the human body and contribute significantly to both physiological and pathological processes. Nowadays, the development of sequencing technology has revealed the presence and composition of the intratumoral microbiota, which includes Fusobacterium, Bifidobacteria, and Bacteroides, and has shed light on the significant involvement in the progression of colorectal cancer (CRC). Here, we summarized the current understanding of the intratumoral microbiota in CRC and outline the potential translational and clinical applications in the diagnosis, prevention, and treatment of CRC. We focused on reviewing the development of microbial therapies targeting the intratumoral microbiota to improve the efficacy and safety of chemotherapy and immunotherapy for CRC and to identify biomarkers for the diagnosis and prognosis of CRC. Finally, we emphasized the obstacles and potential solutions to translating the knowledge of the intratumoral microbiota into clinical practice.

Application of Cyclodextrin for Cancer Immunotherapy.

Tumor immunotherapy, compared with other treatment strategies, has the notable advantage of a long-term therapeutic effect for preventing metastasis and the recurrence of tumors, thus holding great potential for the future of advanced tumor therapy. However, due to the poor water solubility of immune modulators and immune escape properties of tumor cells, the treatment efficiency of immunotherapy is usually significantly reduced. Cyclodextrin (CD) has been repeatedly highlighted to be probably one of the most investigated building units for cancer therapy due to its elegant integration of an internal hydrophobic hollow cavity and an external hydrophilic outer surface. The application of CD for immunotherapy provides new opportunities for overcoming the aforementioned obstacles. However, there are few published reviews, to our knowledge, summarizing the use of CD for cancer immunotherapy. For this purpose, this paper provides a comprehensive summary on the application of CD for immunotherapy with an emphasis on the role, function, and reported strategies of CD in mediating immunotherapy. This review summarizes the research progress made in using CD for tumor immunotherapy, which will facilitate the generation of various CD-based immunotherapeutic delivery systems with superior anticancer efficacy.

Fast, specific, and ultrasensitive antibiotic residue detection by monolayer WS2-based field-effect transistor sensor.

Antibiotic residues cause increasing concern in environmental ecology and public health, which needs efficient analysis strategy for monitoring and control. In this study, a fast, specific, and ultrasensitive sensor based on field-effect transistor (FET) has been proposed for the detection of ampicillin (AMP). The sensor involves monolayer tungsten disulfide (WS2) nanosheet as the sensing channel, single-stranded DNA (ssDNA) as the sensing probe, and gold nanoparticle (Au NP) as the linker. The WS2/Au/ssDNA FET sensor responds rapidly to AMP in a wide linear detection range (10-12-10-6 M) and has low limit of detection (0.556 pM), which meets the permissible standards of AMP in water and food. The sensing mechanism study suggests that the excellent sensor response results from the increased number of negative charges in the Debye length and the consequent accumulation of holes in WS2 channel after the addition of AMP. Moreover, satisfactory sensing performance was confirmed in real water samples, indicating the potential application of the proposed method in practical AMP detection. The reported FET sensing strategy provides new insights in antibiotic analysis for risk assessment and control.

Modulating adult neurogenesis affects synaptic plasticity and cognitive functions in mouse models of Alzheimer's disease.

New neurons are abnormal in the adult hippocampus of Alzheimer's disease (AD) mouse models. The effects of modulating adult neurogenesis on AD pathogenesis differ from study to study. We reported recently that ablation of adult neural stem cells (aNSCs) was associated with improved memory in AD models. Here, we found that long-term potentiation (LTP) was improved in the hippocampus of APP/PS1 mice after ablation of aNSCs. This effect was confirmed in hAPP-J20 mice, a second AD mouse model. On the other hand, we found that exposure to enriched environment (EE) dramatically increased the number of DCX+ neurons, promoted dendritic growth, and affected the location of newborn neurons in the dentate gyrus of APP/PS1 mice, and EE exposure significantly ameliorated memory deficits in APP/PS1 mice. Together, our data suggest that both inhibiting abnormal adult neurogenesis and enhancing healthy adult neurogenesis could be beneficial for AD, and they are not mutually exclusive.

Spider Toxin Peptide-Induced NIR Gold Nanocluster Fabrication for GSH-Responsive Cancer Cell Imaging and Nuclei Translocation.

Goldnanoclusters (GNCs) have become a promising nanomaterial for bioimaging because of their unique optical properties and biocompatibility. In this study, lycosin-I peptide, which possesses a highly selective anticancer activity by affecting the permeability of cancer cell membrane, was firstly modified for constructing fluorescent GNCs (LGNCs) for bioimaging of tumor cells. The obtained LGNCs exhibited strong near-infrared (NIR) fluorescence, which can be further enhanced by the peptide-induced aggregation and selectively stained three cancerous cell lines over normal cell lines with low intrinsic toxicity. After uptake by tumor cells, LGNC aggregates can be depolymerized into ultrasmall nanoclusters by high-level glutathione (GSH) and realize the nuclear targeting translocation. Collectively, our work suggests the potential of natural active biomolecules in designing NIR fluorescent GNCs for bioimaging.

Synergistic Effect of Ni/W/Cu on MgAl2O4 for One-Pot Hydrogenolysis of Cellulose to Ethylene Glycol at a Low H2 Pressure.

Nickel and tungsten, combined with copper, were incorporated into a magnesium aluminum spinel to form a multifunctional catalyst (Ni-W-Cu/MgAl2O4). Characterization results suggested that the adjacent Cu not only facilitated the reduction of W6+ to W5+ with substantial oxygen vacancies but also promoted the reducibility of the Ni species. Besides, the incorporation of Ni, W, and Cu into the support enhanced the catalytic acidity, as well as the L acid sites. The catalyst exhibited a strong synergistic effect between the three metals and the support, resulting in higher catalytic activity for the one-pot hydrogenolysis of cellulose to ethylene glycol. High cellulose conversion (100%) and ethylene glycol yield (52.8%) were obtained, even under a low H2 pressure of 3 MPa.

Protective effect of 2-dodecyl-6-methoxycyclohexa-2, 5-diene-1, 4-dione, isolated from Averrhoa carambola L., against Aß1-42-induced apoptosis in SH-SY5Y cells by reversing Bcl-2/Bax ratio.

BACKGROUND AND PURPOSE: Aß1-42-induced neurotoxicity has been considered as a possible mechanism to aggravate the onset and progression of Alzheimer's disease (AD). In this study, we aim to determine the protective effect of DMDD on the apoptosis of SH-SY5Y cells induced by Aß1-42 and elucidate potential mechanism of DMDD's protective function in apoptosis. EXPERIMENTAL APPROACH: CCK-8, AnnexinV-FITC/PI flow cytometry, and transmission electron microscopy analysis were used to determine the protection of DMDD on Aß1-42-evoked apoptosis of SH-SY5Y cells. Cytochrome c release, JC-1 staining, and measuring the protein of Bcl-2 family by Western blot were applied to elucidate the mechanism of DMDD's protective function in apoptosis. KEY RESULTS: Three concentration of DMDD (5 µmol/L, 10 µmol/L, and 20 µmol/L) rescues the cell viability loss and apoptosis of SH-SY5Y cells cultivated in Aß1-42. The expressions of cleaved Caspase-3, -8, -9, the cytochrome c release, and mitochondrial membrane potential loss were inhibited by DMDD in Aß1-42-insulted SH-SY5Y cells. The Western blot analysis showed that DMDD pretreatment clearly downregulated the protein of Bax and upregulated Bcl-2. Moreover, the Bcl-2/Bax ratio was obviously decreased in cells only exposed to Aß1-42, but, which was suppressed by treated with DMDD. CONCLUSION AND IMPLICATIONS: DMDD attenuated the apoptosis of SH-SY5Y cells induced by Aß1-42 through reversing the Bcl-2/Bax ratio.

C9 Petroleum Resin Hydrogenation over a PEG1000-Modified Nickel Catalyst Supported on a Recyclable Fluid Catalytic Cracking Catalyst Residue.

A PEG1000-modified nickel-based catalyst (Ni-PEG1000/FC3R) supported on an activated fluid catalytic cracking catalyst residue (FC3R) was synthesized and applied to C9 petroleum resin (C9PR) hydrogenation. The results of the Brunauer-Emmett-Teller method, X-ray diffraction, H2 temperature-programmed reduction, and scanning electron microscopy-energy-dispersive X-ray spectroscopy show that the Ni-PEG1000/FC3R catalyst had a smaller crystallite size and higher Ni dispersion than those of a Ni/FC3R catalyst. The prepared Ni-PEG1000/FC3R catalyst was applied in a hydrogenation of C9PR at 270 °C and 6 MPa H2 pressure for 3 h. Under these conditions, the bromine value of C9PR was decreased from 46.1 g Br/100 g (Gardner color grade no. 11) to 0.72 g Br/100 g (Gardner color grade no. 1), and the sulfur content was reduced from 25.7 to 1.66 mg kg-1. Experimental results show that the Ni-PEG1000/FC3R catalyst exhibited high activity and stability for C9PR hydrogenation.

Association between cytokine profiles and lung injury in COVID-19 pneumonia.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is a new respiratory and systemic disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. The purpose of the present study was to investigate the association between cytokine profiles and lung injury in COVID-19 pneumonia. METHODS: This retrospective study was conducted in COVID-19 patients. Demographic characteristics, symptoms, signs, underlying diseases, and laboratory data were collected. The patients were divided into COVID-19 with pneumonia and without pneumonia. CT severity score and PaO2/FiO2 ratio were used to assess lung injury. RESULTS: 106 patients with 12 COVID-19 without pneumonia and 94 COVID-19 with pneumonia were included. Compared with COVID-19 without pneumonia, COVID-19 with pneumonia had significantly higher serum interleukin (IL)-2R, IL-6, and tumor necrosis factor (TNF)-α. Correlation analysis showed that CT severity score and PaO2/FiO2 were significantly correlated with age, presence of any coexisting disorder, lymphocyte count, procalcitonin, IL-2R, and IL-6. In multivariate analysis, log IL6 was the only independent explanatory variables for CT severity score (ß = 0.397, p < 0.001) and PaO2/FiO2 (ß = - 0.434, p = 0.003). CONCLUSIONS: Elevation of circulating cytokines was significantly associated with presence of pneumonia in COVID-19 and the severity of lung injury in COVID-19 pneumonia. Circulating IL-6 independently predicted the severity of lung injury in COVID-19 pneumonia.

Protective Effect of Benzoquinone Isolated from the Roots of Averrhoa carambola L. on Streptozotocin-Induced Diabetic Mice by Inhibiting the TLR4/NF-κB Signaling Pathway.

BACKGROUND: Studies have demonstrated that the roots of Averrhoa carambola L. (Oxalidaceae), a traditional Chinese medicine, can be used to treat diabetes and diabetes-related diseases. Nevertheless, the potential beneficial effects and mechanism of benzoquinone isolated from the roots of Averrhoa carambola L. (BACR) on diabetes remain unclear. METHODS: Diabetic Kunming mice were injected with STZ (120 mgkg-1) in the tail vein. Fasting blood glucose (FBG) and the change of body weight were measured after oral administration of BACR (120, 60, 30 mg/kg/d) every week. The levels of the total cholesterol (TC), triglyceride (TG), free fatty acids (FFA), glucosylated hemoglobin (GHb), fasting insulin (FINS), tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) were measured. The histological examination of pancreatic tissues and the TLR4/NF-κB pathway was analyzed by RT-PCR, immunohistochemistry and Western blot. RESULTS: The study found that clearly the BACR obviously reduced the blood glucose, serum lipids, GHb and FINS. In addition, BACR treatment markedly reduced the release of inflammatory factors, including IL-6 and TNF-α, and down-regulated the expression of the TLR4/NF-κB pathway. CONCLUSION: BACR has potential benefits for the treatment of diabetes by ameliorating metabolic functions and attenuating the inflammatory response via inhibition of the activation of theTLR4/NF-κB pathway.

Yulangsan polysaccharide inhibits 4T1 breast cancer cell proliferation and induces apoptosis in vitro and in vivo.

Yulangsan polysaccharide (YLSPS) is derived from the root of Millettia pulchra (Benth.) Kurz var. Recent studies have postulated YLSPS as a regimen for cancer treatment. However, the underlying mechanism anti-breast cancer is still poorly unknown. The aim of this study was to examine the suppressive and apoptosis effect of YLSPS on the growth of breast cancer cell 4T1 and its possible underlying mechanism. In this study, breast cancer cell 4T1 viability and apoptosis were assessed by CCK-8 and flow cytometry, relative quantitative real-time PCR and western blot after treated with drug-serum of YLSPS. Furthermore, therapy experiments were conducted using a Balb/c mouse transplanted tumor model of breast cancer. The number of apoptotic cells and microvascular density (MVD) in the tumor tissues were assessed by TUNEL and CD34 immunostaining. Immunohistochemical assays and ELISA were used to detect the expression of VEGF, Bcl-2, Bax and Caspase-3 in the tissues. The in vitro studies showed that the drug-serum of YLSPS significantly inhibition of proliferation and effectively induced apoptosis of 4T1 cells. Oral administration of YLSPS in the breast cancer models significantly reduced the tumor volume and weight. The enhanced antitumor efficacy was associated with decreased angiogenesis, an enhanced antioxidant capacity, an increased induction of apoptosis and an inhibition of lung metastasis. These findings indicate that YLSPS significantly inhibited mouse breast cancer growth in vitro and in vivo. These data suggest that YLSPS may serve as a potential therapeutic agent for breast cancer.

The conversion of α-pinene to cis-pinane using a nickel catalyst supported on a discarded fluid catalytic cracking catalyst with an ionic liquid layer.

The concept of a solid catalyst coated with a thin ionic liquid layer (SCILL) was applied to the stereoselective hydrogenation of α-pinene. Nickel, a non-noble metal, was supported on a discarded fluid catalytic cracking catalyst (DF3C) and then modified with different loadings of the ionic liquid 1-ethanol-3-methylimidazolium tetrafluoroborate ([C2OHmim][BF4]). The resulting catalysts showed a range of conversions and selectivities for the hydrogenation of α-pinene. The SCILL catalysts afforded cis-pinane with high selectivity and their activity depended on the ionic liquid loading. For an ionic liquid loading of 10 wt%, although the catalytic activity was suppressed, the selectivity and conversion could reach above 98% and 99%, respectively. In addition, the catalyst remained stable after 13 runs and the activity was almost unchanged with the conversion maintained at approximately 99%. Thus, the ionic liquid layer not only improved the selectivity for cis-pinane but also protected the active site of the catalyst and prolonged the service lifetime of the catalyst. The SCILL catalytic system provides an example of an ionic liquid catalytic system which eliminates organic solvents from the catalytic process.

Protective Effects of 2-Dodecyl-6-Methoxycyclohexa-2,5 -Diene-1,4-Dione Isolated from Averrhoa Carambola L. (Oxalidaceae) Roots on Neuron Apoptosis and Memory Deficits in Alzheimer's Disease.

BACKGROUND/AIMS: The roots of Averrhoa carambola L. (Oxalidaceae) have long been used as a traditional Chinese medicine for the treatment of headaches, vomiting, coughing and hangovers. 2-dodecyl-6-methoxycyclohexa-2, 5-1, 4-dione (DMDD) has been isolated from A. carambola L. roots, and this study was carried out to investigate the potential beneficial effects of DMDD on neuron apoptosis and memory deficits in Alzheimer's disease. METHODS: The effects of a DMDD on learning and memory in APP/PS1 transgenic AD mice in vivo were investigated via Morris water maze and Y-type electric maze tests. In vitro, Cell viability was assessed by CCK-8. Apoptosis was assessed by Annexin V-FITC/PI flow cytometry assay, and transmission electron microscopy assay. Relative quantitative real-time PCR and Western blot were used to determine the expressions of genes and proteins. RESULTS: The spatial learning and memory deficit, fear memory deficit, as well as apoptosis and loss of neuron in hippocampal area of APP/PS1 mice were reversed by DMDD in APP/PS1 transgenic AD mice. DMDD protected against the Aß1-42-induced apoptosis, loss of mitochondria membrane potential, induction of pro-apoptotic Bcl-2 family protein Bax, reduction of anti-apoptotic Bcl-2 family proteins Bcl-2, and activation of Caspase-3, and -9 in PC-12 cells. The Bcl-2/Bax ratio was also increased in DMDD-pretreated PC-12 cells in vitro and APP/PS1 mice in vivo. CONCLUSION: DMDD has potential benefit on treating learning and memory deficit in APP/PS1 transgenic AD mice, and its effects may be associated with reversing the apoptosis of neuron via inhibiting Bax/Bcl-2 mediated mitochondrial membrane potential loss.

NaHS restores mitochondrial function and inhibits autophagy by activating the PI3K/Akt/mTOR signalling pathway to improve functional recovery after traumatic brain injury.

Traumatic brain injury (TBI) is one of the most serious public health problems in the world. TBI causes neurological deficits by triggering secondary injuries. Hydrogen sulfide (H2S), a gaseous mediator, has been reported to exert neuroprotective effects in central nervous system diseases, such as TBI. However, the molecular mechanisms involved in this effect are still unclear. The present study was designed to explore the ability of NaHS, a H2S donor, to provide neuroprotection in a mouse model of TBI and to discover the associated molecular mechanisms of these protective effects. Here, we found that administration of NaHS not only maintained the integrity of the blood brain barrier (BBB), protected neurons from apoptosis, and promoted remyelination and axonal reparation but also protected mitochondrial function. In addition, we found that autophagy was inhibited after treatment with NaHS following TBI, an effect that was induced by activation of the PI3K/AKT/mTOR signalling pathway. Our study indicated that H2S treatment is beneficial for TBI, pointing to H2S as a potential therapeutic target for treating TBI.

The release and transmission of amyloid precursor protein via exosomes.

Amyloid precursor protein (APP) processing is central in Alzheimer's disease (AD) pathogenesis. The healthy unaffected neurons suffer the transmission of amyloid protein from pathologically affected neurons, which may play an important role in the anatomical spread of the disease. Exosomes are appropriate candidates for transmission of amyloid species, because of their potential role as "intercellular transportation". To address a role of secreted exosomes in neuronal homeostasis in AD, we harvested exosomes from the conditioned medium of HEK293-APP Swe/Ind cells. We have demonstrated that these exosomes contained APP and were capable of efficiently transferring APP to normal primary neurons. Moreover, these exosomes had dose-dependent detrimental effect on cultured neurons. Our results suggest a key mechanism underlying the spread of amyloid protein in the brain and the acceleration of pathology in AD; exosomes secretion serves to amplify and propagate Alzheimer's disease related pathology.

Transplantation of bFGF-expressing neural stem cells promotes cell migration and functional recovery in rat brain after transient ischemic stroke.

Cerebrovascular disease such as stroke is one of the most common diseases in the aging population, and neural stem cells (NSCs) transplantation may provide an alternative therapy for cerebral ischemia. However, a hostile microenvironment in the ischemic brain offers is challenging for the survival of the transplanted cells. Considering the neuroprotective role of basic fibroblast growth factor (bFGF), the present study investigated whether bFGF gene-modified NSCs could improve the neurological function deficit after transient middle cerebral artery occlusion (MCAO) in adult male Sprague-Dawley rats. These rats were intravenously injected with modified NSCs (5×106/200 µL) or vehicle 24 h after MCAO. Histological analysis was performed on days 7 and 28 after tMCAO. The survival, migration, proliferation, and differentiation of the transplanted modified C17.2 cells in the brain were improved. In addition, the intravenous infusion of NSCs and bFGF gene-modified C17.2 cells improved the functional recovery as compared to the control. Furthermore, bFGF promoted the C17.2 cell growth, survival, and differentiation into mature neurons within the infarct region. These data suggested that bFGF gene-modified NSCs have the potential to be a therapeutic agent in brain ischemia.

Protective Effects of 2-Dodecyl-6-Methoxycyclohexa-2,5 -Diene-1,4-Dione Isolated from Averrhoa Carambola L. (Oxalidaceae) Roots on High-Fat Diet-Induced Obesity and Insulin Resistance in Mice.

BACKGROUND/AIMS: The roots of Averrhoa carambola L. (Oxalidaceae) have long been used as a traditional Chinese medicine for the treatment of diabetes and diabetes-related diseases. 2-dodecyl-6-methoxycycyclohexa-2,5-1,4-dione (DMDD) has been isolated from A. carambola L. roots, and this study was carried out to investigate the potential beneficial effects of DMDD on obesity and insulin resistance induced by a high-fat diet (HFD) in mice. METHODS: C57BL/6J mice were fed a HFD for 16 weeks and orally administered DMDD (12.5, 25, or 50 mg/kg of body weight per day) and metformin (280 mg/kg of body weight per day) for the last 4 weeks. RESULTS: The body weights and adipose tissue weights as well as the serum levels of blood glucose, total cholesterol, triglycerides, free fatty acids, insulin, interleukin-6, and tumor necrosis factor-α were significantly decreased by DMDD, and the expression of Toll-like receptor 4 (TLR4) and myeloid differentiation factor (Myd88) in the epididymal adipose tissue was downregulated by DMDD. In contrast, insulin sensitivity was enhanced. The results of the glucose tolerance tests, insulin tolerance tests, and insulin release tests indicated that there was a marked improvement in insulin secretion, and the areas under the curve corresponding to the three tests were also significantly decreased by DMDD. The activities of superoxide dismutase and glutathione peroxidase were simultaneously enhanced, whereas the content of malondialdehyde was decreased by DMDD in the liver homogenates of the C57BL/6J mice. In addition, hepatic steatosis and adipocyte hypertrophy, as assessed by H&E staining of liver and adipose tissues, were significantly improved by DMDD. CONCLUSION: These data suggest that MDD has potential benefits for the treatment of HFD-induced obesity and insulin resistance, and its effects may be associated with improvements in lipid metabolism and inhibition of the expression of TLR4 in adipose tissues.

Protection of endothelial cells against Ang II-induced impairment: Involvement of both PPARα and PPARγ via PI3K/Akt pathway.

The aim of our study is to explore the involvement of PPARα and PPARγ in Ang II-induced endothelial injury. We found that Ang II significantly elevated the oxidative stress in HUVECs, causing apoptosis and cellular impairment in a time-dependent pattern. Activation of either PPARα by docosahexaenoic acid (DHA) or PPARγ by rosiglitazone protected the endothelial cells. Interestingly, a more significant effect was observed when DHA and rosiglitazone were administrated together. Moreover, we found that this protection was mediated through the PI3K/Akt pathway. Our study may help to understand the mechanism of endothelial dysfunction, contributing to the treatment of hypertension and other endothelial-related diseases.

The predictive potential and oncogenic effects of HOXC8 expression on osteosarcoma.

Homeobox C8 (HOXC8) has been implicated in cell growth, migration, and metastasis of various cancers, yet its role in osteosarcoma remains to be explored. In the present study, resected osteosarcoma specimens from 50 patients were enrolled to evaluate the expression of HOXC8 protein by immunohistochemistry (IHC). In vitro and in vivo assays were used to determine the effect of HOXC8 on cell growth, migration, and tumor growth. HOXC8 expression was observed in 31 (62.0 %) of the 50 primary tumors and significantly associated with poorly or un-differentiated specimens (P = 0.031) and larger tumor size (P = 0.049). Survival analysis demonstrated that HOXC8 is a candidate predictive factor in predicting patients' outcome and chemotherapeutic effect. HOXC8 knockdown led to inhibition of tumor cell proliferation and migration in vitro by inhibiting MMP-9 expression and tumor growth in vivo. Our results strongly suggest that HOXC8 is involved in the tumorigenesis of osteosarcoma and might serve as a novel predictor for patients' outcome.