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The illustration of the fabrication of nanoalloys by laser nanometallurgy using multivariate MOF as precursor.

This study is aimed to understand the pathogenesis of intracranial aneurysm (IA), which has a risk of rupture and is the primary cause of subarachnoid hemorrhage. From Gene Expression Omnibus (GEO) database, GSE75436 was extracted (15 IA tissues and 15 superficial temporal artery tissues). The differentially expressed genes (DEGs) was conducted through limma package, which followed by the enrichment analysis. Combining STRING database, protein-protein interaction (PPI) network was constructed. The modules in PPI network were performed utilizing molecular complex detection (MCODE) algorithm. With Cytoscape software, the transcription factor-miRNA-target regulatory network was constructed. Finally, microarray dataset GSE54083 was downloaded (13 IA tissues and 10 superficial temporal artery tissues) for the verification test. A total of 1332 DEGs were screened in IA tissues compared with superficial temporal artery tissues. Besides, the up-regulated TNF, IL10, IL1B, and CTSS, as well as down-regulated IL6 were included in the top 20 nodes in the PPI networks. Furthermore, in the module A of up-regulated PPI network, TNF, IL10, IL1B, and VCAM1 were interact with each other. In the regulatory network, miR-29A/B/C targeted up-regulated genes. Besides, VCAM1 was implicated in the pathway of leukocyte transendothelial migration. In the verification analysis, between GSE75436 and GSE54083, there were 444 up-regulated and 543 down-regulated co-existence DEGs and 11 co-existence genes involved the Leukocyte transendothelial migration pathway. VCAM1, TNF, CTSS, IL10, IL1B, IL6, and miR-29A/B/C might be the potential biomarkers for the formation and development of IA.

Traumatic brain injury (TBI) is one of the most devastating nervous injuries. Neural tissue engineering based on stem cells and bioactive scaffold is a promising but challenging approach for neural repair. A cutting-edge system with capability to control the fate of encapsulated stem cells is attractive to enhance neural regeneration after TBI. Herein, an injectable gelatin hydrogel dual-enzymatically cross-linked by horse radish peroxidase (HRP) and choline oxidase (ChOx) was performed as the neural scaffold to load murine bone marrow-derived mesenchymal stem cells (BMSC) for TBI treatment. The results of in vitro cellular experiments showed that low cross-linked gelatin hydrogel could obviously promote cellular viability, neural differentiation, and neurotrophins secretion of the loaded BMSC. In vivo tests on a TBI model of C57BL/6 mouse demonstrated that BMSC-laden gelatin hydrogel implants could significantly reduce the damaged area, ameliorate inflammation, attenuate neuronal apoptosis, facilitate survival and proliferation of endogenous neural cells, and promote the neurological function recovery of TBI mice. All data suggest that establishment of this three-dimensional (3D) gelatin hydrogel stem cell-loaded system is a promising therapeutic strategy for TBI or other neurological rehabilitation.

Temozolomide is a first line anti-tumor drug used for the treatment of patients with Glioblastoma multiforme (GBM). However, the drug resistance to temozolomide limits its clinical application. Therefore, novel strategies to overcome chemoresistance are desperately needed for improved treatment of human GBM. Recent studies have demonstrated that miRNAs are closely related to resistance to cancer chemotherapy. This study aimed to further validate the biological role of miR-128-3p and to investigate whether miR-128-3p can enhance the chemosensitivity of glioblastoma to temozolomide (TMZ) and the underlying mechanisms. The effects of miR-128-3p and TMZ on the proliferation of glioblastoma cells were investigated by cell counting kit-8 (cck8). Transwell and intracerebral invasion assays were applied to determine the effects of the combination of miR-128-3p and TMZ on the invasion and migration of glioblastoma in vitro and in vivo. Flow cytometry was used to detect apoptosis in each group, and immunofluorescence was used to determine the expression levels of EMT-related proteins. RT-PCR and Western-blot were applied to detect EMT-transformed proteins (c-Met, PDGFRα, Notch1, and Slug) and EMT phenotype-associated proteins (Vim, CD44, and E-cadherin) at both mRNA and protein levels. Based on the microRNA.org database, we predicted the target genes of miR-128-3p. The target-relationship between miR-128-3p and c-Met and PDGFRα was verified by dual luciferase reporter gene. The tumor volume, weight and the expression levels of the proteins described above were measured in subcutaneously transplanted tumor model in nude mice. We found that the expression of miR-128-3p was down-regulated in glioblastoma tissue samples and cell lines. miR-128-3p suppressed the proliferation, migration, and invasion of GBM both in vitro and in vivo; miR-128-3p enhanced the therapeutic effect of TMZ via inhibition of proliferation, invasion and migration of glioblastoma cells and induction of apoptosis. Overexpression of miR-128-3p down-regulated the expression levels of EMT-transformed proteins (c-Met, PDGFRα, Notch1 and Slug) to enhance the effect of TMZ. In addition, we found that miR-128-3p targeted and bound c-Met. More importantly, the upregulation of c‐Met significantly prompted U87 and U251 cell proliferation. This effect could be abolished when c‐Met was silenced. The investigation in tumor bearing nude mice showed that miR-128-3p in combination with TMZ reduced tumor volume and the invasion extent, and increased the sensitivity of glioblastoma to TMZ. miR-128-3p is capable of enhancing the sensitivity of glioblastoma to TMZ through regulating c-Met/EMT.

Inhibition of bone regeneration by wear debris is the main cause of peri-prosthetic osteolysis. Here, we investigated the effect of icariin on cell proliferation, apoptosis, osteogenic differentiation and matrix mineralization of osteoblasts in an in vitro model of titanium (Ti) particle-induced osteolysis. In the present study, MC3T3-E1 cells were pretreated with 10-8 M icariin for 4 h and then incubated with Ti particles (0.1 mg/mL). The results showed that Ti particles inhibited cell proliferation and promoted cell apoptosis of MC3T3-E1 cells, whereas icariin pretreatment blocked the effect of Ti particles. In addition, we found that icariin stimulation alone increased ALP activity, accelerated matrix mineralization and upregulated the levels of bone morphogenetic protein 2 (BMP2), Runt-related transcription factor 2 (Runx2), osteocalcin (OCN) and miR-21-5p; whereas, Ti particles alone exerted the opposite effects. Icariin partly reversed the effect of Ti particles on cell differentiation and mineralization. Twenty hours after transfection with antagomiR-21-5p or antagomiR-NC, the cells were pretreated with icariin for 4 h and then incubated with Ti particles. Further studies showed that partial knockdown of miR-21-5p abolished the promotion effect of icariin on osteoblast differentiation and matrix mineralization in Ti particle-stimulated MC3T3-E1 cells. In conclusion, miR-21-5p may be a potential pro-osteogenesis regulator and icariin may protect against Ti particle-induced inhibition of osteogenic differentiation and mineralization through upregulation of miR-21-5p.

Temozolomide is a first line anti-tumor drug used for the treatment of patients with Glioblastoma multiforme (GBM). However, the drug resistance to temozolomide limits its clinical application. Therefore, novel strategies to overcome chemoresistance are desperately needed for improved treatment of human GBM. Here, we simultaneously detected, for the first time, the expression profiles of mRNAs, lncRNAs, and circRNAs in three pairs of secondary temozolomide-resistant glioblastoma (STRG) and matched primary glioblastoma tissues by microarrays. Using these data, we discovered a total of 92 mRNA, 299 lncRNAs and 53 circRNAs were altered in human glioma tissue after chemotherapy with temozolomide. The functions of differentially expressed lncRNAs, circRNAs were annotated by analysis of Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). The results showed that the highest enriched GO terms of the upregulated lncRNAs were embryonic forelimb morphogenesis (BP), extracellular space (CC), and serine-type endopeptidase activity (MF). Meanwhile, GO:0035360(BP), PRC1 complex (CC), and ubiquitin-protein transferase activity (MF) were the highest enriched GO terms targeted by downregulated lncRNAs. The NF-kappa B signaling pathway were significantly enriched in the STRG. However, circRNAs highest enriched GO term was viral process, chromosome, and protein transporter activity, respectively. KEGG pathway analysis showed that circRNAs in the network were enriched in ErbB signaling pathway. Furthermore, we also predicted the potential role of these differentially expressed ncRNAs and constructed a network of lncRNAs-mRNAs and circRNAs-miRNAs to show their interactions. After a series of bioinformatics analyses, we found that low expression of NONHSAT163779 and high expression of circ_0043949 are closely related to the chemoresistance of STRG. Our findings revealed the alteration of expression patterns of mRNAs, lncRNAs, and circRNAs in the secondary temozolomide-resistant glioblastoma for the first time. NONHSAT163779 and hsa_circ_0043949 might be potential therapeutic targets and prognostic biomarkers for the treatment of glioblastoma.

Glycated conjugates were prepared by heating aqueous dispersions of soy protein isolate (SPI) and maltodextrin (MD) after ultrasonic treatment (138 W/cm2, 20 kHz) for 5, 15, and 25 min. The effect of the ultrasonic pretreatment on the structure, physicochemical characteristics, and acid-induced gelation properties of the resulting SPI–MD conjugates was investigated. The analyses of free amino groups, degree of graft, intermediates, and browning intensity confirmed the formation of SPI–MD conjugates. The ultrasonic treatment promoted the glycation reaction, which led to the increase in the β-type ordered secondary structure and less compact tertiary conformation of conjugates. The ultrasonic treatment for 5 min increased the isoelectric point, surface hydrophobicity (H0), free sulfhydryl (-SH) groups, and particle size of the conjugates. These changes in the structural and physicochemical properties of the conjugates affected their acid-induced gelation. Glucono-δ-lactone was used to form acid gels at 25 °C. Although the glycation with MD deteriorated the acid-induced gelation properties of SPI, the 5 min ultrasonic conjugates formed gels faster than the untreated conjugate, and their gels exhibited higher storage modulus (G′), gel strength, and water holding capacity (WHC), as well as denser microstructure, than the untreated conjugate gels. However, prolonged ultrasonic treatment (15 or 25 min) weakened the gelation properties of the conjugates by promoting the glycation reaction and reducing the H0. Thus, an optimum ultrasonic pretreatment can be used to modify the structure of soy protein glycation conjugates to control their gelation properties.

Background This study aimed to investigate the effect of deep hypothermic circulatory arrest (DHCA) on rat hippocampal mitochondrial protein expression and its differential proteomics, and explore the potential mechanisms behind the effect. Methods We used internal jugular vein reflux and tail artery perfusion methods to establish the rat cardiopulmonary bypass (CPB) model. Rats were dissected to obtain the hippocampus, and the hippocampal mitochondria were purified. The mitochondrial morphology and the mitochondrial marker cytochrome C oxidase (COX) qualitatively examined via transmission electron microscopy and western-blot analysis, respectively. The qualified samples were subjected to isobaric tags for relative and absolute quantification (iTRAQ); we then established the CPB model again to obtain the rat hippocampus for cryoultramicrotomy, and used immunofluorescent double staining technique to qualitatively and semi-quantitatively verify two representative differentially expressed proteins. Results By searching the Mascot 2.2 database, 29 differentially expressed proteins were obtained with statistical significance, including 21 known proteins and 8 unknowns. The expression level of COX and monoacylglycerol lipase did not change significantly (P>0.05) during the hyperacute phase; however, their intracellular localizations were altered. Conclusions DHCA induced the differential expression of 29 rat hippocampal mitochondrial proteins, some of which had altered intracellular localization. We speculated that the localized alteration of these proteins is one of the neuroprotection mechanisms that occurs during DHCA.

The study aims to investigate the intestinal (small and large intestine) clinical features and treatment of hamartoma. Nowadays, with the rapid development of new technologies, digestive system endoscopy has been proven to be an effective device for treatment, rather than just a diagnostic tool. Such development plays a revolutionary role in diagnosis and treatment for digestive diseases. And endoscopic treatment was used in this study (LED light source, wavelength 580 ∼ 595 nm, power 200 W). A retrospective analysis of 20 cases of intestinal hamartomas performed from January 2012 to January 2016 to summarize its clinical characteristics and follow-up study on the therapeutic effect of the patients. There were 8 cases for endoscopic operation, and 12 cases for surgical operation. Comparison of tumor size between endoscopic and surgical estimated by using Wilcoxon rank sum test for tumor length (Z = -3.134, p = 0.001), and for tumor diameter (Z = -2.920, p = 0.002). The results of this study showed that intestinal hamartomas and gender have no significant relationship. The incidence of the disease is concentrated under 60 years, the incidence of the small intestine is significantly higher than that of the large intestine, and the rate of misdiagnosis is high. Endoscopic and surgical treatment are the main treatment, the prognosis is good, and after the radical resection, the recurrence was less.

Cell proliferation was inhibited following forced over-expression of miR-30a in the ovary cancer cell line A2780DX5 and the gastric cancer cell line SGC7901R. Interestingly, miR-30a targets the DNA replication protein RPA1, hinders the replication of DNA and induces DNA fragmentation. Furthermore, ataxia telangiectasia mutated (ATM) and checkpoint kinase 2 (CHK2) were phosphorylated after DNA damage, which induced p53 expression, thus triggering the S-phase checkpoint, arresting cell cycle progression and ultimately initiating cancer cell apoptosis. Therefore, forced miR-30a over-expression in cancer cells can be a potential way to inhibit tumour development.

The rotor of the locomotive turbocharger is prone to malfunction of the turbocharger, and it is also the most important part of the turbocharger. The reasonable establishment of rotor dynamics model is very important in the study. It determines the accuracy of analysis. The influence of the shaft quality on the turbine and impeller was not considered in the process of analyzing the dynamic model in the passed research. But the quality of locomotive turbocharger rotor shaft is relatively large, it cannot be ignored because it will have a large bending moment in the model simplified. So the rotor dynamic equation was deduced in the case of considered the quality of the rotor axis. The rotor of the turbocharger rotor was simplified firstly, the various parts of the simplified rotor were analyzed, and the dynamic model of the rotor was established. And the dynamic model was verified by the hammer experiment. The factors considered in the dynamic model were more comprehensive, so the model would be more practical for the future research.

Interleukin-6 (IL-6), a central proinflammatory cytokine, may be involved in both development and progression of many human malignancies. Therefore, we aimed to evaluate any associations of IL-6 gene polymorphisms with susceptibility and overall survival of osteosarcoma in a Chinese population. A total of 412 subjects, including 206 patients with osteosarcoma and 206 healthy controls, were recruited and were assessed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) in this study. Significant differences of genotype distribution were observed between osteosarcoma cases and controls at the IL-6 -174 G/C genotypes. Compared with the homozygote GG, the heterozygous GC genotype was associated with significantly increased risk for osteosarcoma (odds ratio [OR] = 1.58, 95 % confidence interval [CI] = 1.13-3.05, p = 0.028); the CC genotype was associated with increased risk for osteosarcoma (OR = 1.57, 95 % CI = 1.21-3.26, p = 0.022). Moreover, the genotype CC of IL-6 -174 G/C carried a higher risk of osteosarcoma metastasis and later Enneking stages, compared with the GG genotype. The IL-6 -174 G/C genotype was associated with risk for development and metastasis of osteosarcoma in Chinese Han population.

Inhibition of bone regeneration by wear debris is the main cause of peri-prosthetic osteolysis. Here, we investigated the effect of icariin on cell proliferation, apoptosis, osteogenic differentiation and matrix mineralization of osteoblasts in an in vitro model of titanium (Ti) particle-induced osteolysis. In the present study, MC3T3-E1 cells were pretreated with 10

Background: Acute spinal cord injury (SCI) leads to permanent disabilities. This study evaluated the neuroprotective effect of puerarin, a natural extract, in a rat model of SCI. Methods: Acute SCI models were established in rats using a modified Allen's method. Locomotor function was evaluated using the BBB test. The histological changes in the spinal cord were observed by H&E staining. Neuron survival and glial cells activation were evaluated by immunostaining. ELISA and realtime PCR were used to measure secretion and gene expression of cytokines. TUNEL staining was used to examine cell apoptosis and western blot analysis was used to detect protein expression. Results: Puerarin significantly increased BBB score in SCI rats, attenuated histological injury of spinal cord, decreased neuron loss, inhibited glial cells activation, alleviated inflammation, and inhibited cell apoptosis in the injured spinal cords. In addition, the downregulated PI3K and phospho-Akt protein expression were restored by puerarin. Conclusion: Puerarin accelerated locomotor function recovery and tissue repair of SCI rats, which is associated with its neuroprotection, glial cell activation suppression, anti-inflammatory and anti-apoptosis effects. These effects may be associated with the activation of PI3K/Akt signaling pathway.

SRCIN1 (SRC kinase signalling inhibitor 1) is a new tumor suppressor gene. Previous studies showed that SRCIN1 played a tumor suppressor role in the development of lung cancer and breast cancer. However, the role of SRCIN1 in osteosarcoma is still unknown. In this study, we demonstrated that SRCIN1 was downregulated in osteosarcoma cell lines compared with osteoblastic cell line. Moreover, SRCIN1 was downregulated in osteosarcoma tissues compared with the adjacent tissues. Further investigation revealed that overexpression of SRCIN1 inhibited the osteosarcoma cell line MG-63 proliferation. This effect was confirmed by measuring the ki-67 and PCNA expression. SRCIN1 overexpression promoted E-cadherin expression and suppressed N-cadherin, Vimentin and Snail expression, suggesting that SRCIN1 overexpression inhibited EMT of the osteosarcoma cell. In addition, ectopic expression of SRCIN1 inhibited the MG-63 cell colony formation and invasion. These data suggested that SRCIN1 acted as a tumor suppressor gene in the development of osteosarcoma.

NK1.1+ natural killer (NK)-T cells reactive to CD1 appear to be involved in spontaneous autoimmune disease, but their role in induced autoimmune disease remains unclear. While we previously reported a regulatory role of NK cells in experimental autoimmune encephalomyelitis (EAE), we demonstrate here that NK-T cells would also play a pivotal role in the control of EAE. C57BL/6 (B6) mice selectively depleted for NK-T cells were generated by antibody-depended protocols or knocking out TCRJα281 gene. Regardless of the method for NK-T cell deletion, these NK-T depleted mice developed unusually early onset of EAE (5–8 days after challenge) after immunization with an encephalitogenic peptide myelin oligodendrocyte glycoprotein (MOG) 35–55 . The early EAE onset was associated with early induction of T helper cell type 1 (Th1) cells and marked elevation of Th1 cytokines in the serum. It was of note that, although the NK-T deficient mice spontaneously recovered from EAE, mice selectively depleted for NK cells developed a later onset of non-remitting EAE. These data establish differential roles played by NK-T and NK cells in the protection against EAE.

The reasonable establishment of rotor dynamics model is very important in the study. This paper establishes a dynamic model of the rotor, and gets the numerical calculation of the frequencies and mode shapes of the rotor under the free condition. The modal of the rotor bearing system is analyzed by using software. Compared to the above two kinds of results, the test of turbocharger rotor mechanics correctly modeled is to prove that this method has practical significance.

OBJECTIVE: The aim of the present study was to explore the potential for hematoporphyrin monomethyl ether-Sonodynamic Therapy (HMME-SDT) treatment of hypertrophic scars within rabbit ears. METHODS: 60 white rabbits were randomly divided into five groups: (1) untreated controls, (2) lesioned, (3) lesioned + HMME, (4) lesioned + US (Ultrasound), and (5) lesioned +HMME-SDT. After induction of a lesion upon the ears of the rabbits, hypertrophic scars were assessed at 14, 28, 42 and 56 days post-lesion +/- treatment. Assessments consisted of visual inspection in the change of the skin, scar formation pathological morphology by hematoxylin and eosin (HE) staining technique with optical microscopy, calculation of a hypertrophic index, fibroblastic density measures, and observation of collagen changes in the scar tissue by Van Gieson's (VG)Stain along with calculation of collagen area density. RESULTS: With continued HMME-SDT treatment there was a gradual improvement in all parameters over the duration of the experiment. The lesion-induced scars of rabbits receiving HMME-SDT treatment were soft, the size was reduced, hyperplasia was flat and the color pale. The fibroblasts and collagens were reduced and the collagens were light red, sparse and orderly. The hypertrophic index was reduced, since the fibroblastic density was lowered and collagen area density was decreased. CONCLUSION: HMME is an effective sonosensitizer and the combination of HMME-SDT treatment can exert significant benefits in reducing the formation of hypertrophic scars.

The aim of this study was to explore the mechanism underlying the promotive effect of morroniside on rat mesenchymal stem cell (RMSC) proliferation and to provide an experimental basis for the development of potential new drugs. RMSCs were obtained from the bone marrow of Sprague-Dawley rats aged 3-4 months. The proliferation of primary and subcultured RMSCs in the high‑, medium‑ and low‑concentration morroniside intervention and blank control groups was observed using light microscopy. Cell proliferation and survival conditions were detected using methyl thiazolyl tetrazolium (MTT) colorimetric tests. Light microscopy and the MTT assay revealed that RMSC adherence time in the morroniside groups was shorter compared with that of the control group. Twelve hours after the media of primary RMSCs were changed, the number of adherent cells in the morroniside groups increased and an elongated cell morphology was observed. The cells at the fourth passage in the morroniside groups fused completely 12‑16 h after inoculation and then rapidly entered into the logarithmic phase. The primary RMSCs of the morroniside intervention groups grew into typical bone marrow mesenchymal stem cell (BMSC) colonies after 4 days of morroniside treatment and their fusion rate had reached 80% after 9‑11 days. By contrast, the cell fusion rate of the control group only reached 75-80% after 14 days of morroniside treatment. Morroniside exhibited a similar promotive effect on proliferation in primary and subcultured RMSCs. Morroniside may promote RMSC proliferation through secreted factors, cell-to-cell interactions and/or the interactions between cellular adhesion molecules and extracellular matrices (ECMs). However, the specific mechanism underlying this effect remains to be fully elucidated.