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Telocytes (TCs) are a distinctive cell entity of the stromal microenvironment of multiple tumors; to date, their existence in infantile hemangioma (IH) remains almost unexplored. This study was therefore undertaken to characterize the immunophenotype, location, morphology, and ultrastructure of telocytes in the IH by means of immunohistochemistry, immunofluorescence confocal microscopy, and transmission electron microscopy. Telocytes were initially identified by CD34, PDGFR-α, Vimentin, and AQP-1 immunostaining. Analyzing the spatial relationship among telocytes, stem cells, endothelial cells, pericytes in the IH with AQP-1/CD31, AQP-1/Glut-1, AQP-1/α-SMA, AQP-1/CD146 and AQP-1/CD133 double immunofluorescence. TCs were immunonegative for CD31, Glut-1, CD146, α-SMA, CD133, and C-kit in the IH. The ultrastructural examination confirmed the presence of TCs, namely stromal cells with characteristic cytoplasmic processes (i.e. telopodes) forming labyrinthine networks around microvessels and releasing extracellular vesicles. Our study provides evidence that telocytes are present and PDGFR-α and AQP-1 are specific antigenic markers in the IH.

Objective: To evaluate the feasibility and accuracy of three-dimensional (3D)-printed individualised guiding templates in total hip arthroplasty (THA) for the treatment of developmental dysplasia of the hip (DDH)., Methods: 12 hips in 12 patients with Crowe type IV DDH were treated with THA. A 3D digital model of the pelvis and lower limbs was reconstructed using the computed tomography data of the patients. Preoperative surgical simulations were performed to determine the most suitable surgical planning, including femoral osteotomy and prosthesis placement. Based on the ideal surgical planning, individualised guiding templates were designed by software, manufactured using a 3D printer, and used in acetabulum reconstruction and femoral osteotomy during surgery., Results: 12 patients were followed up for an average of 72.42 months (range 38-135 months). During surgery, the guiding template for each case was matched to the bony markers of the acetabulum and proximal femur. Preoperative and follow-up Harris Hip Scores were 34.2 ± 3.7 and 85.2 ± 4.2; leg-length discrepancy, 51.5 ± 6.5 mm and 10.2 ± 1.5 mm; and visual analogue scale scores, 6.2 ± 0.8 and 1.3 ± 0.3, respectively, with statistical difference. Shortened deformity and claudication of the affected limb were obviously improved after surgery. However, 1 patient had artificial hip dislocation 2 weeks after surgery, and another patient had sciatic nerve traction injury, both of whom recovered after physical treatment., Conclusions: Preoperative surgical simulation and 3D-printed individualised guiding templates can fulfil surgeon-specific requirements for the treatment of Crowe type IV DDH. Accurate THA can be achieved using 3D-printed individualised templates, which provide a new personalised surgical plan for the precise positioning and orientation of acetabular reconstruction and femoral osteotomy.

Hepatocellular carcinoma (HCC) is an aggressive tumor with a poor prognosis that highly expresses phosphatidylinositol 3-kinase (PI3K) and mitogen-activated protein kinase (ERK). The PI3K/AKT/mTOR and MAPK/ERK signaling pathways play a crucial role in HCC tumor formation, cell cycle, apoptosis and survival. However, no effective targeted therapies against these pathways is available, mainly due to the extensive and complex negative feedback loops between them. Here we used CK-3, a dual blocker of the PI3K/AKT/mTOR and MAPK/ERK pathways, against HCC cell lines to verify its anti-tumor activity in vitro . CK-3 exhibited cytotoxic activity against HCC, as demonstrated with MTT and colony formation assays. The anti-metastatic potential of CK-3 was demonstrated with wound healing and cell invasion assays. The ability of CK-3 to block both the PI3K/AKT/mTOR and MAPK/ERK pathways was also confirmed. CK-3 induced the apoptosis of Hep3B cells, while Bel7402 cells died via mitotic catastrophe (MC). Oral administration of CK-3 also inhibited the subcutaneous growth of BEL7402 cells in nude mice. Simultaneous PI3K/AKT/mTOR and MAPK/ERK pathway inhibition with CK-3 may be superior to single pathway monotherapies by inhibiting their feedback-regulation, and represents a potential treatment for HCC., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Wu, Liu, Hu, Li, Wu, Sun, Jiang, Wang, Qin, Ding and Zhao.)

Objective: This study aimed to explore the clinical application of three-dimensional (3D) printing technology in the surgical treatment of congenital scoliosis caused by hemivertebrae., Methods: Twenty-four patients (11 in the 3D-printing group and 13 in the conventional group) with scoliosis secondary to a single hemivertebra were retrospectively reviewed. All patients underwent hemivertebrectomy and short-segment fixation. Virtual preoperative planning, operation simulation, and intraoperative application of 3D-printed patient-specific templates were performed in the 3D-printing group. Hemorrhage volume, operation time, transfusion, and complications were noted. Radiographic parameters were evaluated preoperatively, postoperatively, and at final follow-up., Results: All patients had different degrees of successfully corrected scoliosis. There was a similar correction of the Cobb angle postoperatively between the 2 groups. The operation time, blood loss, transfusion, time for the insertion of each screw, accuracy of screw placement, and complication rate in the 3D-printing group were significantly superior to those in the control group. No patient experienced major complications. No significant correction loss or instrument dysfunction was observed during follow-up., Conclusions: As a viable and effective auxiliary technology, 3D printing makes it possible for surgery to meet both surgeon-specific and patient-specific requirements. 3D-printed individualized templates allow surgery for the correction of congenital scoliosis to enter a new stage of personalized precision surgery., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Objective: Parkinson's disease (PD) is characterized by the loss of dopaminergic neurons in substantia nigra (SN). Our previous study demonstrated kukoamine A (KuA) to exhibit strong neuroprotective effects through antioxidative stress, and autophagy in MPTP/MPP + -induced PD models in vivo and in vitro . It is necessary to evaluate the efficacy of the anti-PD effects under various models., Methods: In the present study, total chemical synthesis was used to obtain KuA, which performed low content in Lycii Cortex . Then, 6-OHDA-induced PD model of PC12 cells was used to investigate the effects of KuA on PD., Results: Our results demonstrated that KuA ameliorated cell loss and mitochondrial membrane potential (MMP) loss, and inhibited Bax/Bcl-2 ratio increase that were induced by 6-OHDA. Iron accumulation in SN is thought to participate in neuronal death in PD, which subsequently resulted in oxidative stress and overexpression of α-synuclein caused by iron metabolism protein disorder. In our study, KuA could chelate cellular iron content and decrease iron influx. Moreover, KuA could upregulate the expression of ferroportin1 and Hephaestin, downregulate the expression of DMT1, TfR, and Ferritin to maintain cellular iron homeostasis avoiding neuronal death from cellular iron deposition. Moreover, KuA could decrease the expression of a-synuclein in cells. All the results indicated that KuA protected against neurotoxin-induced PD due to the apoptosis inhibition and iron homeostasis maintaining., Conclusion: KuA treatment might represent a neuroprotective treatment for PD., Competing Interests: Neither any of the authors have anything to disclose regarding this manuscript nor do they have any potential conflicts of interest to report concerning this article., (© 2020 Tianjin Press of Chinese Herbal Medicines. Published by ELSEVIER B.V.)

EPHB6 is a metastasis inhibitory gene that is frequently decreased or deficiency in non-small cell lung cancer (NSCLC), which contributed to the subsequent development of distant metastasis. These suggested the possibility that reactivation of EPHB6 might prevent the metastasis of NSCLC. Nevertheless, EPHB6 expression might also promote cancer cell growth and inhibit cell apoptosis by activating Akt and ERK pathway, apart from inhibition of migration and invasion. In the present study, we developed a novel quinazolin-4(3H)-one analog (DFX24) as a potential PI3Kα inhibitor, which inhibited both cell proliferation and metastasis of NSCLC cell lines. Investigation to the molecular mechanisms revealed DFX24 inhibited the cell growth and metastasis via inhibition of PI3Kα and ERK activity, as well as the increase in EPHB6 expression. In addition, DFX24 also induced cell cycle arrest and tumor cell apoptosis by inhibiting PI3K/Akt pathway and activating mitochondria-dependent pathway, respectively. These findings suggested that DFX24 might be considered as a novel drug candidate and may provide a potential therapy for NSCLC., (Copyright © 2020. Published by Elsevier Ltd.)

Phosphatidylinositol 3-kinase (PI3K) pathway regulates various cellular processes, such as proliferation, growth, autophagy and apoptosis. Class I PI3K is frequently mutated and overexpressed in a lot of human cancers and PI3K was considered as a target for therapeutic treatment of cancer. In this study, we designed and synthesized a series of 1,6-disubstituted-1H-benzo[d]imidazoles derivatives and evaluated their anticancer activity and the compound 8i was identified as a lead compound. Compound 8i with the most potent antiproliferative activity was selected for further biological mechanism. The PI3K kinase assay have shown potent efficiency against four subtypes of PI3K with an IC 50 of 0.5-1.9 nM. Molecular docking showed a possible formation of H-bonding with essential amino acid residues. Meanwhile, western blot assay indicated that 8i inhibited cell proliferation via suppression of PI3K kinase activity and subsequently blocked PI3K/Akt pathway activation in HCT116 cells. In addition, 8i could inhibit the migration and invasion ability of HCT116 cells and could induce apoptosis of HCT116 cells., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Objective: To report the outcomes of severe kyphoscoliosis secondary to ankylosing spondylitis (AS) corrected with 3D-printed individualized guiding templates., Methods: Computed tomography (CT) data of patients with severe kyphoscoliosis secondary to AS were used to reconstruct 3D models of the spine and to develop a surgical plan. An asymmetric wedge pedicle subtraction osteotomy (PSO) was simulated using medical computer design software. Before the actual surgery, continual surgical simulations were performed until the most suitable one was obtained, and personalized guiding templates were manufactured for the anticipated PSO. During operation, the osteotomy plane and trajectories for the pedicle screws were positioned by the designed patient-specific 3D-printed guiding templates., Results: In this study, we reviewed 9 patients who underwent correction of kyphoscoliosis using a 3D-printed individualized guiding template and were followed for a median of 21.4 months (range, 9-36 months). The average correction at the site of osteotomy was 65.9°. No patient experienced severe complications, such as misplaced pedicle screws or neurologic complications. At the last follow-up, no patient exhibited implant dysfunction on radiography., Conclusions: Preoperative surgical simulation using 3D-printed templates is a viable technique that enables surgery to meet both patient- and surgeon-specific requirements for correction of severe thoracolumbar kyphoscoliosis. These 3D-printed templates can guide the performance of planned PSO to provide functional restoration of severe kyphoscoliosis secondary to AS., (Copyright © 2019. Published by Elsevier Inc.)

A series of 4-aminoquinazolines derivatives containing hydrophilic group were designed and identified as potent Pan-PI3K inhibitors in this study. The results of antiproliferative assays in vitro showed that this series of compounds had strong inhibition of tumor growth, especially compound 7b for MCF-7 cells but weak inhibition to normal cells. PI3K kinase assay showed that 7b had high activity for three PI3K isoforms with the IC 50 values of picomole. The western blot assay indicated that 7b could decrease the phospho-Akt (S473) in a dose-dependent manner. Further experiments showed that 7b could induce apoptosis in MCF-7 cells. Four key hydrogen bonding interactions were found in the docking of 7b with PI3K kinase. All these results suggested that 7b is a potent PI3K inhibitor and could be considered as a potential candidate for the development of anticancer agents., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

To provide molecular evidence on the thermogenic mechanism of primary brown adipocytes, western blot analysis was used to detect brown adipose tissue (BAT)-specific gene expressions. BAT protects the mammals from hypothermia injury with a large amount of mitochondria and high expression of uncoupling Protein 1 (UCP1), which is the vital protein to determine the heat production in BAT. In our previous study, the compound ZW290 (the structure shown in Fig. 1) was obtained by molecular docking with a UCP1 inducer. In the present study, ZW290 not only significantly upregulated the expression of UCP1 protein (p < 0.01) and its related signaling pathway in the primary brown adipocytes, but also remarkably decreased the mitochondrial membrane potential and the concentration of adenosine triphosphate (ATP) (p < 0.01). Kunming (KM) mice were kept under acute cold exposure (-20°C) to evaluate the preventive and protective effects of ZW290 on cold injury, and revealed its regulating mechanism in vitro. The rectal and body temperatures of ZW290-treated mice were significantly higher than those of the control (or model) group both at room temperature and at -20°C (p < 0.001). Hematoxylin-eosin (HE) staining and immunohistochemistry indicated that ZW290 notably decreased the size of lipid droplets in BAT and increased the content of mitochondria and the expression of UCP1 in BAT and white adipose tissue (WAT). Furthermore, the survival rate showed that ZW290 could prolong the overall survival of mice. Therefore, we obtained the conclusion that ZW290 might transform energy into heat by inhibiting ATP synthesis and increasing the expression of UCP1. Additionally, ZW290 may enhance cold tolerance by increasing heat production through increasing the content of mitochondria and the expression of UCP1 in BAT and WAT., (© 2019 AOCS.)

Non-small cell lung cancer (NSCLC) is one of the most common malignancies, and Taxol is a cornerstone in the treatment. However, taxol-resistance eventually limits the clinical effects and applications. Daurinoline could restore the sensitivity of resistant MCF-7/adr and KBv200 cells. Whereas, the effect of daurinoline on the chemo-resistant NSCLC cells and the mechanism has not been elucidated. In this study, daurinoline was firstly demonstrated that inhibited the proliferation, migration, invasion and EMT phenotype of chemo-resistant NSCLC cells. And these effects were associated with EMT and Notch-1 reversal. Moreover, daurinoline could significantly enhance the anti-tumor effect of Taxol rather than epirubicin, adriamycin and cisplatin. And the reverse fold (RF) value of daurinoline was greater than terfenadine reported before. There are little cytotoxic effects of daurinoline and its derivatives reported by L.W. Fu, et al. (2001). Therefore, daurinoline may be a potential anti-tumor agent or chemosensitizer for chemo-resistant NSCLC patients., (Copyright © 2018. Published by Elsevier B.V.)

Objectives: Colorectal cancer is one of the most common malignancies both in men and women. Owing to metastasis and resistance, the prognosis of colorectal cancerCRC patients remains extremely poor with chemotherapy. A disintegrin and metalloproteinase 17 (ADAM17) induces the activation of Notch pathway and contributes to the chemoresistance. This study aimed to discover a novel ADAM17 inhibitor and investigate the chemosensitization effect., Materials and Methods: Pharmacophore model, western blot and enzymatic assay were used to discover ZLDI-8. Cell proliferation was determined by MTT and colony formation assay. Cell migratory and invasive ability were determined by wound healing scratch and transwell assay. Immunofluorescence images and western blot analysed the expression of Notch or epithelial-mesenchymal transition (EMT) pathway markers. Xenografts were employed to evaluate the chemosensitization effect of ZLDI-8 in vivo., Results: We found that ZLDI-8 cell-specifically inhibited the proliferation of CRC, and this effect was due to abrogation of ADAM17 and Notch pathway. Meanwhile, we reported for the first time that ZLDI-8 synergistically improved the anti-tumour and anti-metastasis activity of 5-fluorouracil or irinotecan by reversing Notch and EMT pathways. Interestingly, in vivo studies further demonstrated that ZLDI-8 promoted the anti-tumour effect of 5-fluorouracil through Notch and EMT reversal., Conclusions: A novel ADAM17 inhibitor ZLDI-8 may be a potential chemosensitizer which sensitized CRC cells to 5-fluorouracil or irinotecan by reversing Notch and EMT pathways., (© 2018 John Wiley & Sons Ltd.)

The abnormal activation of PI3K signaling pathway leads to the occurrence of various cancers. The PI3Kα is frequently mutated and overexpressed in many human cancers. Therefore, the PI3Kα was considered as a promising target in therapeutic treatment of cancer. In this study, two series of compounds containing 2H-benzo[b][1,4]oxazin-3(4H)-one and 2H-benzo[b][1,4]oxazine scaffold were synthesized and evaluated antiproliferative activities against three cancer cell lines, including HCT-116, MDA-MB-231 and SNU638. Compound 7f with the most potent antiproliferative activity was selected for further evaluation on normal cells and PI3K kinase. Studies indicated that compound 7f could decrease the phospho-Akt (T308) in a dose-dependent manner. Four key hydrogen bonding interactions were found in the docking of 7f with PI3K enzyme. All the results suggested that 7f was a potent PI3Kα inhibitor., (Copyright © 2018. Published by Elsevier Ltd.)

Hesperetin has been known to exert several activities such as anti-oxidant, antitumor and anti-inflammatory. To find hesperetin derivatives showing better activity, sixteen novel hesperetin derivatives were designed and synthesized. The new obtained compounds were investigated for their anti-inflammatory activity by inhibiting interleukin-1β (IL-1β), interleukin-6 (IL-6) and production of nitric oxide (NO) in mouse RAW264.7 macrophages, and the structure-activity relationship of them was discussed. Among them, the compound 1l, 2c demonstrated more effective inhibitory activity of IL-1β and IL-6, meanwhile, the compound 1l showed the best inhibition of NO production. The results of NO inhibition study were basically accord with the molecular docking results of inducible nitric oxide synthase (iNOS). Furthermore, the expression of LPS-induced iNOS and components of NF-κB signaling pathway were reduced by compound 1l. Our results suggest that the inhibitory effect of compound 1l on LPS-stimulated inflammatory mediator production in RAW 264.7 cells is associated with the suppression of NF-κB signaling pathway and inhibition of iNOS protein and iNOS activity. From in vivo study, it was also observed that compound 1l had hepato-protective and anti-inflammatory effects in CCl 4 -induced acute liver injury mouse models., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Melanoma is an extremely aggressive malignant skin tumor with a high mortality. Various long noncoding RNAs (lncRNAs) have been reported to be associated with the oncogenesis of melanoma. The purposes of this study were to investigate the potential role of lncRNA PVT1 in melanoma progression and to explore its possible mechanisms. A total of 35 patients who were diagnosed with malignant melanoma were enrolled in this study. Expression of PVT1 was significantly upregulated in melanoma tissue and was associated with a poor prognosis. Loss-of-function experiments showed that PVT1 knockdown markedly suppressed the proliferation activity, induced cell cycle arrest at the G0/G1 phase, and enhanced the apoptosis of melanoma cell lines. Bioinformatics analysis and dual-luciferase reporter assay revealed that PVT1 directly bound to miR-26b, which had been verified to be a tumor suppressor in melanoma. Moreover, further functional rescue experiments revealed that PVT1 knockdown could observably reverse the tumor-promoting role of the miR-26b inhibitor. Overall, our study demonstrates the oncogenic role of PVT1 as a miR-26b sponge, possibly providing a novel therapeutic target for melanoma.

Phosphatidylinositol 3-kinase (PI3K) signaling pathway has diverse functions, including the regulation of cellular survival, proliferation, cell cycle, migration, angiogenesis and apoptosis. Among class I PI3Ks (PI3Kα, β, γ, δ), the PIK3CA gene encoding PI3K p110α is frequently mutated and overexpressed in a large portion of human cancers. Therefore, the inhibition of PI3Kα has been considered as a promising target for the development of a therapeutic treatment of cancer. In this study, we designed and synthesized a series of 4-aminoquinazoline derivatives and evaluated their antiproliferative activities against six cancer cell lines, including HCT-116, SK-HEP-1, MDA-MB-231, SNU638, A549 and MCF-7. Compound 6b with the most potent antiproliferative activity and without obvious cytotoxicity to human normal cells was selected for further biological evaluation. PI3K kinase assay showed that 6b has selectivity for PI3Kα distinguished from other isoforms. The western blot assay and PI3K kinase assay indicated that 6b effectively inhibited cell proliferation via suppression of PI3Kα kinase activity with an IC 50 of 13.6 nM and subsequently blocked PI3K/Akt pathway activation in HCT116 cells. In addition, 6b caused G1 cell cycle arrest owing to the inhibition of PI3K signaling and induced apoptosis via mitochondrial dependent apoptotic pathway. Our findings suggested that 6b has a therapeutic value as an anticancer agent via PI3Kα inhibition., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

The overexpression of EGFR correlates with rapidly progressive disease, resistance to chemotherapy and poor prognosis. In certain human cancers, PI3K works synergistically with EGFR to promote proliferation, survival, invasion and metastasis. Development of dual-target drugs against EGFR and PI3K has therapeutic advantage and was an attractive approach against tumors. In this work, based on the molecular docking and previous studies, a series of 4-aminoquinazolines derivatives containing 6-sulfonamide substituted pyridyl group were rationally designed and identified as potent EGFR and PI3K dual inhibitors. The cytotoxicity experiment results showed that this series of compounds could effectively inhibit cell growth. The kinase assay demonstrated that 6c and 6i had high inhibition for EGFR and selectivity for PI3Kα distinguished from other isoforms. Further experiments showed that 6c could induce cell cycle arrest in G1 phase and apoptosis in BT549 cells. The western blot assay indicated that 6c inhibited the proliferation of BT549 cell through EGFR and PI3Kα/Akt signaling pathway. Our study suggested that compound 6c was a potential dual inhibitors of EGFR and PI3Kα., (Copyright © 2018 Elsevier Masson SAS. All rights reserved.)

Phosphatidylinositol 3-kinase (PI3K) is a pivotal regulator of intracellular signaling pathways and considered as a promising target in the development of a therapeutic treatment of cancer. Among the different PI3K subtypes, the PIK3CA gene encoding PI3K p110α is frequently mutated and overexpressed in majority of human cancers. Therefore, the inhibition of PI3Kα has been considered to be an efficient approach for the treatment of cancer. In this study, two series compounds containing hydrophilic group in imidazo[1,2-a]pyridine and quinazolin-4(3H)-one were synthesized and their antiproliferative activities against five cancer cell lines, including HCT-116, SK-HEP-1, MDA-MB-231, SNU638 and A549, were evaluated. Compound 1i with most potent antiproliferative activity was selected for further biological evaluation. PI3K kinase assay showed that 1i has selectivity for PI3Kα distinguished from other isoforms. The western blot assay indicated that 1i is more effective than HS-173, an imidazopyridine-based PI3Ka inhibitor, in reducing the levels of phospho-Akt. All these results suggested that 1i is a potent PI3Kα inhibitor and could be considered as a potential candidate for the development of anticancer agents., (Copyright © 2017. Published by Elsevier Masson SAS.)

A flavonoid hesperetin is reported to have a variety of biological activities, including anticancer, antiviral, antioxidant, neuroprotective and anti-inflammatory properties. Thirty-one novel hesperetin derivatives were designed, synthesized and evaluated for anti-inflammatory activity using RAW264.7 cells and CCl4-induced acute liver injury model. Among these compounds, 5b displayed the excellent anti-inflammatory activity on decreasing NO, IL-6 and TNF-α both in vitro and vivo. In addition, 5b could also reduce the release of NO, IL-6 and TNF-α production by LPS stimulated RAW 264.7 cell through MAPK and NF-κB signaling pathway in a concentration dependent manner. From in vivo study, it was also observed that 5b attenuated liver histopathologic changes in mouse models., (Copyright © 2017. Published by Elsevier B.V.)

In this study we designed and synthesized a series of new hesperetin derivatives on the basis of the structural characteristics of acetylcholinesterase (AChE) dual-site inhibitors. The activity of the novel derivatives was also evaluated. Results showed that the synthesized hesperetin derivatives displayed stronger inhibitory activity against AChE and higher selectivity than butyrylcholine esterase (BuChE) (selectivity index values from 68 to 305). The Lineweaver-Burk plot and molecular docking study showed that these compounds targeted both the peripheral anionic site (PAS) and catalytic active site (CAS) of AChE. The derivatives also showed a potent self-induced β-amyloid (Aβ) aggregation inhibition and a peroxyl radical absorbance activity. Moreover, compound 4f significantly protected PC12 neurons against H₂O₂-induced cell death at low concentrations. Cytotoxicity assay showed that the low concentration of the derivatives does not affect the viability of the SH-SY5Y neurons. Thus, these hesperetin derivatives are potential multifunctional agents for further development for the treatment of Alzheimer's disease.

Hesperetin is a flavanone glycoside compound naturally occurring in the fruit peel of Citrusaurantium L. (Rutaceae). Previous studies revealed that hesperetin possesses various pharmacological effects, including anti-inflammation, anti-tumor, anti-oxidant and neuroprotective properties. Hesperetin derivative-14 (HD-14) is a derivative of hesperetin improved in water solubility and bioavailability. In this study, we indicated that HD-14 (2μM) significantly attenuated inflammation in LPS-treated RAW264.7 cells, besides, HD-14 (100mg/kg) exhibited hepato-protective effects and anti-inflammatory effects on C57BL/6J mice with CCl 4 -induced acute liver injury. In addition, it was demonstrated that HD-14 dramatically up-regulated the expression of PPAR-γ in vivo and in vitro. Interestingly, over-expression of PPAR-γ had anti-inflammatory effects on the expressions of TNF-α, IL-6, and IL-1β, whereas, knockdown of PPAR-γ with small interfering RNA had pro-inflammatory effects in LPS-treated RAW264.7 cells. Thus, our findings demonstrated that HD-14 alleviated inflammation by activating PPAR-γ expression at least in part. Further studies founded that HD-14 remarkably inhibited the expression of p-JAK1 and p-STAT1 through up-regulating PPAR-γ. Together, these results suggested that HD-14 served as an activator of PPAR-γ and the JAK1/STAT1 signaling pathway may be involved in the progress of inflammation. Collectively, HD-14 may be utilized as a potential anti-inflammation monomeric compound in the treatment of acute liver injury., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Adjacent vertebral fractures are common in patients with osteoporotic vertebral compression fractures (OVCFs) after kyphoplasty. This finite element study was to examine whether short segment pedicle screw fixation (PSF) with kyphoplasty may decrease the fracture risk of the treated and adjacent non-treated vertebrae after kyphoplasty for OVCFs. By simulating cement augmentation with or without short segment pedicle screw fixation (PSF), two tridimensional, anatomically detailed finite element models of the T10-L2 functional spinal junction were developed. The insertion of pedicle screws into the intact vertebra apparently decreased the stress distribution of the treated vertebra in vertical compression and other load situations. The stress distribution in the bone structures of the intact vertebra adjacent to the intact-screwed vertebra was much less than that in the one adjacent to the treated vertebra. The insertion of pedicle screws into the intact vertebra greatly decreased the maximum displacement of the cortical bones and cancellous bones of the vertebrae. Our results indicated that short segment PSF with kyphoplasty may decrease the fracture risk of the treated and adjacent non-treated vertebrae in the management of OVCFs.

Background: To report the outcomes of computer-aided resection and endoprosthesis design for the management of malignant bone tumors around the knee., Methods: Computed tomography (CT) and magnetic resonance imaging (MRI) data were input into computer software to produce three-dimensional (3D) models of the tumor extent. Imaging data was then used to create a template for surgical resection, and development of an individualized combined allogeneic bone/endoprosthesis. Surgical simulations were performed prior to the actual surgery., Results: This study included 9 males and 3 females with a mean age of 25.3 years (range, 13 to 40 years). There were 9 tumors in the distal femur and 3 in the proximal tibia. There were no surgical complications. In all cases pathologically confirmed clear surgical margins were obtained. Postoperative radiographs showed the range of tumor resection was in accordance with the preoperative design, and the morphological reconstruction of the bone defect was satisfactory with complete bilateral symmetry. The mean follow-up time was 26.5 months. Two patients died of their disease and the remaining are alive and well without evidence of recurrence. All patients are able to ambulate freely without restrictions. At the last follow-up, the average International Society of Limb Salvage score was 25.8 (range, 18 to 27), and was excellent in 8 cases and good in 4 cases., Conclusions: Computer-aided design and modeling for the surgical management of bone tumors and subsequent limb reconstruction provides accurate tumor removal with the salvage of a maximal amount of unaffected bone and precise endoprosthesis reconstruction.

Objective: To prepare a cisplatin-impregnated coral-derived hydroxyapatite (CCHA) drug delivery system (DDS), and evaluate its inhibitory effect on human osteosarcoma cells U-2 OS, human breast cancer and prostatic carcinoma cells PC-3 in vitro., Methods: The coral-derived hydroxyapatite (CHA) was manufactured by hydrothermal exchange and impregnated with cisplatin by vacuum freeze-drying techniques. The leaching solutions of this DDS was collected at different intervals in a course of 8 weeks and their inhibitory effect on the cells was tested in vitro by MTT assay., Results: Electron microscope showed that cisplatin was distributed homogeneously in the pores of CHA. The inhibition rates of the leaching solution on all the tumor cells exceeded 50% except for PC-3 cells, whose inhibition rate was 29.92% when treated with the solution collected at the eighth week., Conclusion: CCHA allows sustained drug release and maintains excellent inhibitory effect on human bone tumor cells within 8 weeks in vitro.

Cytochrome P 450 2C19 (CYP2C19) is involved in the metabolism of a number of clinically used drugs. Individuals can be characterized as extensive metabolizers (EMs) or poor metabolizers (PMs) , according to the drugs-metabolized ability of CYP2C19 in population studies. The incidence of poor metabolizer phenotype shows marked interracial differences. In this article we report the gene polymorphism of CYP2C19 in Zang population. There were 49 wild-type homozygotes (wt/wt) , 46 were heterozygotes (wt/m1) and 9 were homozygotes (m1/m1) among 104 unrelated Zang subjects. The frequency of CYP2C19(m1) allele was 0.308, which was in agreement with that in other published data.