Core-shell ZnO@CoO nitrogen doped nano-composites as highly sensitive electrochemical sensor for organophosphate pesticides detection.

Core-shell ZIF-8@ZIF-67 was synthesized by growing a cobalt-based ZIF-67 on a ZIF-8 seed particle. Herein, through selective etching of the ZIF-8@ZIF-67 core and subsequent direct carbonization, core-shell hollow ZnO@CoO nitrogen-doped nanoporous carbon (HZnO@CoO-NPC) nanocomposites were prepared. HZnO@CoO-NPCs possessed a high nitrogen content, large surface area, high degree of graphitization and excellent electrical conductivity, all of which were attributed to successfully integrating the unique advantages of ZIF-8 and ZIF-67. HZnO@CoO-NPCs were used to assemble acetylcholinesterase (AChE) biosensors for organophosphorus pesticides (OPs) detection. The low detection limit of 2.74 × 10-13 M for chlorpyrifos and 7.6 × 10-15 M for parathion-methyl demonstrated the superior sensing performance. The results showed that the electrochemical biosensor constructed by HZnO@CoO-NPC provided a sensitive and efficient electrochemical strategy for OPs detection.

Doublecortin-like kinase 1 activates NF-κB to induce inflammatory responses by binding directly to IKKß.

Doublecortin-like kinase 1 (DCLK1), a microtubule-associated protein kinase, is involved in neurogenesis, and its levels are elevated in various human cancers. Recent studies suggest that DCLK1 may relate to inflammatory responses in the mouse model of colitis. However, cellular pathways engaged by DCLK1, and potential substrates of the kinase remain undefined. To understand how DCLK1 regulates inflammatory responses, we utilized the well-established lipopolysaccharide (LPS)-stimulated macrophages and mouse model. Through a range of macrophage-based and cell-free platforms, we discovered that DCLK1 binds directly with the inhibitor of κB kinase ß (IKKß) and induces IKKß phosphorylation on Ser177/181 to initiate nuclear factor-κB (NF-κB) pathway. Deficiency in DCLK1, achieved by silencing or through pharmacological inhibition, prevented LPS-induced NF-κB activation and cytokine production in macrophages. We further show that mice with myeloid-specific DCLK1 knockout or DCLK1 inhibitor treatment are protected against LPS-induced acute lung injury and septic death. Our studies report a novel functional role of macrophage DCLK1 as a direct IKKß regulator in inflammatory signaling and suggest targeted therapy against DCLK1 for inflammatory diseases.

Amphiphilic Aminated Derivatives of [60]Fullerene as Potent Inhibitors of Tumor Growth and Metastasis.

Malignant proliferation and metastasis are the hallmarks of cancer cells. Aminated [70]fullerene exhibits notable antineoplastic effects, promoting it a candidate for multi-targeted cancer drugs. It is an urgent need to reveal the structure-activity relationship for antineoplastic aminated fullerenes. Herein, three amphiphilic derivatives of [60]fullerene with clarified molecular structures are synthesized: TAPC-4, TAPC-3, and TCPC-4. TAPC-4 inhibits the proliferation of diverse tumor cells via G0/G1 cell cycle arrest, reverses the epithelial-mesenchymal transition, and abrogates the high mobility of tumor cells. TAPC-4 can be excreted from the organism and achieves an in vivo inhibition index of 75.5% in tumor proliferation and 87.5% in metastatic melanoma with a wide safety margin. Molecular dynamics simulations reveal that the amphiphilic molecular structure and the ending amino groups promote the targeting of TAPC-4 to heat shock protein Hsp90-beta, vimentin, and myosin heavy chain 9 (MYH9), probably resulting in the alteration of cyclin D1 translation, vimentin expression, and MYH9 location, respectively. This work initially emphasizes the dominant role of the amphiphilic structure and the terminal amino moieties in the antineoplastic effects of aminated fullerenes, providing fundamental support for their anti-tumor drug development.

Enhancing anaerobic digestion of pharmaceutical industries wastewater with the composite addition of zero valent iron (ZVI) and granular activated carbon (GAC).

Anaerobic digestion of pharmaceutical wastewater is challenged by its contained toxic compounds which limits the stability and efficiency of methane production and organic degradation. In this study, zero valent iron (ZVI) and granular activated carbon (GAC) were added with different strategies to improve anaerobic digestion of pharmaceutical wastewater. The results confirmed synergy effects of ZVI + GAC for both COD removal (increased by 13.4%) and methane production (increased by 11.0%). Furthermore, ZVI + GAC improved the removal of pharmaceutical intermediates, in particular, the residues (%) of dehydroepiandrosterone (DHEA) and 2,2'-methylenebis(6-tert-butyl-4-methylphenol) were only 30.48 ± 6.53 and 39.92 ± 4.50, and effectively reduced biotoxicity. The promoted results were attributed to the establishment of direct interspecies electron transfer (DIET). Microbial community analysis revealed that ZVI + GAC decreased species evenness and richness in bacterial whereas increased in archaeal. The relative abundance of acetotrophic methanogens decreased but hydrogenotrophic and methylotrophic methanogens increased, which broadening the pathway of methane production.

Lipoxin A4 protects primary spinal cord neurons from Erastin-induced ferroptosis by activating the Akt/Nrf2/HO-1 signaling pathway.

Ferroptosis is an iron-dependent programmed cell death, which participates in the pathogenesis of spinal cord injury (SCI). Our previous study has revealed that Lipoxin A4 (LXA4) exerts a protective role in SCI. Here, we investigated whether LXA4 can protect SCI through inhibiting neuronal ferroptosis. We treated primary spinal cord neurons with Erastin (ferroptosis activator) to induce ferroptosis. Erastin treatment reduced cell viability and enhanced cell death of primary spinal cord neurons, which was rescued by ferrostatin-1 (ferroptosis inhibitor). Moreover, Erastin repressed glutathione peroxidase 4 (GPX4) expression and the levels of glutathione and cysteine in primary spinal cord neurons. Erastin also enhanced the expression of ferroptosis biomarkers (PTGS2 and ACSL4) and the levels of reactive oxygen species (ROS) in primary spinal cord neurons. The influence conferred by Erastin was effectively abolished by LXA4 treatment. Furthermore, LXA4 enhanced the protein expression of p-AKT, nuclear factor (erythroid-derived 2)-like 2 (Nrf2) and haem-oxygenase-1 (HO-1) in primary spinal cord neurons. LXA4-mediated inhibition of ferroptosis of primary spinal cord neurons was prohibited by LY294002 (AKT inhibitor), brusatol (Nrf2 inhibitor) or zinc protoporphyrin (HO-1 inhibitor). In conclusion, this work demonstrated that LXA4 exerted a neuroprotective effect in Erastin-induced ferroptosis of primary spinal cord neurons by activating the Akt/Nrf2/HO-1 signaling pathway. Thus, this work provides novel insights into the mechanisms of action of LXA4 in ferroptosis of primary spinal cord neurons and indicates that LXA4 may be a potential therapeutic agent for SCI.

Impact of phosphorus fertilizer level on the yield and metabolome of goji fruit.

Goji (Lycium barbarum L.) is a highly medicinal value tree species. The yield and nutritional contents of goji fruit are significant affected by fertilizer level. In this study, we analyzed the yield and nutritional contents change of goji fruit, which planted in pot (vermiculite:perlite, 1:2, v:v) in growth chamber under P0 (32.5 g/per tree), P1 (65 g/per tree), and P2 (97.5 g/per tree). Meanwhile, we utilized an integrated Ultra Performance Liquid Chromatography-Electrospray Ionization-Tandem Mass Spectrometry (UPLC-ESI-MS/MS) to analysis of the response of the metabolome in goji fruit to phosphorus level. The results show that the yield of goji fruits had strongly negative correlation with phosphorus level, especially in the third harvest time. The amino acids, flavonoids, polysaccharides, and betaine contents of goji fruits in the first harvest time had obvious correlated with the level of phosphorus level. The Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment results indicated that the impact of different phosphorus fertilizer levels on each group mainly involved the biosynthesis of flavonoids. The results provide new insights into the theoretical basis of the relationship between the nutritional contents of goji fruits and phosphorus fertilizer level.

Head-to-head comparative pharmacokinetic and biodistribution (PK/BD) study of two dexamethasone prodrug nanomedicines on lupus-prone NZB/WF1 mice.

HPMA copolymer-based dexamethasone prodrug (P-Dex) and PEG-based dexamethasone prodrug (PEG-Dex, ZSJ-0228) were previously found to passively target the inflamed kidney and provide potent and sustained resolution of nephritis in NZB/WF1 lupus-prone mice. While both prodrug nanomedicines effectively ameliorate lupus nephritis, they have demonstrated distinctively different safety profiles. To explore the underlining mechanisms of these differences, we conducted a head-to-head comparative PK/BD study of P-Dex and PEG-Dex on NZB/WF1 mice. Overall, the systemic organ/tissue exposures to P-Dex and Dex released from P-Dex were found to be significantly higher than those of PEG-Dex. The high prodrug concentrations were sustained in kidney for only 24 h, which cannot explain their lasting therapeutic efficacy (>1 month). P-Dex showed sustained presence in liver, spleen and adrenal gland, while the presence of PEG-Dex in these organs was transient. This difference in PK/BD profiles may explain PEG-Dex' superior safety than P-Dex.

Ultrasensitive SERS detection of antitumor drug methotrexate based on modified Ag substrate.

Methotrexate (MTX) is a drug with broad-spectrum antitumor activity that is of great importance in therapeutic drug monitoring applications. In this essay, the two-step modified concentrated Ag colloid with the assistance of KF and MgSO4 was used as the SERS active substrate for the ultrasensitive detection of MTX and its commercial formulations (tablets). It can be found that the two-step modification of the samples is a crucial procedure to remove the by-products in the synthesis of Ag colloid and further concentrate the Ag colloid. Under the optimal detection conditions, the minimum detection concentration of MTX is 1 × 10-16 mol/L. And, there is a good linear relationship over a wide concentration range of 1 × 10-16-1 × 10-6 mol/L. The labelled amounts of the two manufacturers of MTX commercial tablets are in the range of 96.4-104.3% with the RSDs between 1.8% and 3.5% by this method, which are in accordance with the methodological requirements. These results prove that the proposed SERS method exhibits a good reproducibility and ultra-high sensitivity for the detection of the antitumor drug MTX.

Benign and malignant skull-involved lesions: discriminative value of conventional CT and MRI combined with diffusion-weighted MRI.

BACKGROUND: Little is known about the value of computed tomography (CT) and magnetic resonance imaging (MRI) combined with diffusion-weighted imaging (DWI) in distinguishing malignant from benign skull-involved lesions. PURPOSE: To evaluate the discriminative value of DWI combined with conventional CT and MRI for differentiating between benign and malignant skull-involved lesions. MATERIAL AND METHODS: CT and MRI findings of 58 patients with pathologically proven skull-involved lesions (43 benign and 15 malignant) were retrospectively reviewed. Conventional CT and MRI characteristics and apparent diffusion coefficient (ADC) value of the two groups were evaluated and compared. Multivariate logistic regression and receiver operating characteristic (ROC) curve analyses were performed to assess the differential performance of each parameter separately and together. RESULTS: The presence of cortical defects or break-through and ill-defined margins were associated with malignant skull-involved lesions (both P < 0.05). Malignant skull-involved lesions demonstrated a significantly lower ADC (P = 0.016) than benign lesions. ROC curve analyses indicated that a combination of CT, MRI, and DWI with an ADC ≤ 0.703 × 10-3 mm2/s showed optimal sensitivity, while DWI along showed optimal specificity of 88.4% in differentiating between benign and malignant skull-involved lesions. CONCLUSION: The combination of CT, MRI, and DWI can help to differentiate malignant from benign skull-involved lesions. CT + MRI + DWI offers optimal sensitivity, while DWI offers optimal specificity.

Juvenile hormone-dependent Kazal-type serine protease inhibitor Greglin safeguards insect vitellogenesis and egg production.

In addition to preventing insect metamorphosis, juvenile hormone (JH) is known to stimulate aspects of insect reproduction. However, the molecular mechanisms of JH action in insect reproduction remain largely unknown. By reanalyzing the transcriptomic data from adults and other developmental stages of the migratory locust Locusta migratoria, we identified a gene coding for Kazal-type protease inhibitor, previously named Greglin. Greglin is specifically expressed in adult females and most abundant in the fat body and ovaries. Interestingly, Greglin is among the top 3 of highly expressed genes in adult female locusts, after 2 vitellogenin ( Vg) genes. Greglin is induced by JH and expressed at remarkably high levels in the vitellogenic stage. Knockdown of Greglin in adult female locusts results in accelerated degradation of serine protease substrate and significantly reduced levels of Greglin protein in hemolymph and ovaries. The consequent phenotypes include blocked oocyte maturation, arrested ovarian growth and shrunken follicular epithelium, as well as declines in egg number and hatchability. The data provide the first evidence, to our knowledge, that JH-dependent Greglin is involved in locust vitellogenesis and oocyte maturation likely by protecting vitellogenesis and other forms of yolk precursors from proteolysis. The result offers new insights into the regulation of JH and function of protease inhibitors in insect vitellogenesis, oocyte maturation and fecundity.-Guo, W., Wu, Z., Yang, L., Cai, Z., Zhao, L., Zhou, S. Juvenile hormone-dependent Kazal-type serine protease inhibitor Greglin safeguards insect vitellogenesis and egg production.

Juvenile hormone promotes locust fat body cell polyploidization and vitellogenesis by activating the transcription of Cdk6 and E2f1.

Juvenile hormone (JH) is known to promote cell polyploidization for insect vitellogenesis and egg production, but the underlying mechanisms remain poorly understood. Using the migratory locust Locusta migratoria as a model system, we report here that the expression of cyclin-dependent kinase 6 (Cdk6) and adenovirus E2 factor-1 (E2f1), the core mediators in cell cycle progression is regulated by JH and its receptor Methoprene-tolerant (Met). JH acts through its receptor complex comprised of Met and Taiman to directly activate the transcription of Cdk6 and E2f1. Depletion of Cdk6 or E2f1 results in significantly decreased ploidy, precocious mitotic entry and increased cell numbers in the fat body, accompanied by substantial reduction of Vitellogenin gene expression, blocked ovarian growth and arrested oocyte maturation. These findings indicate a crucial role of Cdk6 and E2f1 in JH-regulated polyploidization and vitellogenesis as well as a novel regulatory machinery for endocycling in insects.

An Optimized and Feasible Preparation Technique for the Industrial Production of Hydrogel Patches.

For hydrogel patches, the laboratory tests could not fully reveal the existing problems of full scale of industrial production, and there are few studies about the preparation technique for the industrial manufacturing process of hydrogel patches. So, the purpose of this work was to elucidate the effects of mainly technological operation and its parameters on the performance of hydrogel patches at the industrial-scale production. The results revealed the following: (1) the aqueous phase was obtained by polyvinylpyrrolidone (PVP) along with tartaric acid dissolved in purified water, then feeding this into a vacuum mixer as a whole in one batch, thus extended the crosslinking reaction time of hydrogel paste (matrix) and allowed the operation of coating/cutting-off to be carried out easily, and there was no permeation of backing layer; (2) the gel strength of the hydrogel patches increased with the increase of working temperature, however, once the temperature exceeded 35 ± 2 °C, the hydrogel paste would lose water severely and the resultant physical crosslinking structure which has lower gel/cohesive strength would easily bring gelatinization/residues during application; (3) the relative humidity (RH) of the standing-workshop was dynamically controlled (namely at 35 ± 2 °C, keeping the RH at 55 ± 5% for 4 days, then 65 ± 5% for 2 days), which would make patches with satisfactory characteristics such as better flexibility, higher adhesive force, smooth flat matrix surface, and without gelatinization/residues and warped edge during the using process; (4) the aging of the packaged hydrogel patches was very sensitive to storage temperature, higher temperature, higher gel strength and lower adhesiveness. The storage temperature of 10 ± 2 °C could effectively prevent matrix aging and adhesion losing, which would also facilitate the expiration date of patches extended obviously. In conclusion, this work provides an optimized and feasible preparation technique for the industrial production of the hydrogel patches and establishes the hydrogel patches as a novel carrier for transdermal drug delivery.

Preparation and Structural Analysis of Nano-Silver Loaded Poly(styrene-co-acrylic acid) Core-Shell Nanospheres with Defined Shape and Composition.

A systematic study for the preparation and structural analysis of poly(styrene-co-acrylic acid) composite nanospheres (PSA) and silver nanoparticles loaded poly(styrene-co-acrylic acid) composite nanospheres (nAg@PSA) is reported. Poly(styrene-co-acrylic acid) nanospheres were synthesized by soap-free emulsion polymerization of styrene (St) and acrylic acid (AA) in water. Ag nanoparticles (Ag-NPs) were well-dispersed on the surfaces of poly(styrene-co-acrylic acid) composite nanospheres by in situ chemical reduction of AgNO3 using NaBH4 as a reducing agent in water. The particle size of PSA nanospheres was uniform. The surfaces of PSA nanospheres were distributed by highly uniform half-sphere arrays. Those half-sphere protruded more with the increase of the feeding amount of AA or the feed ratios of AA and St. The carboxyl groups content of nanospheres was directly proportional to the nanosphere surface area. This relationship and X-ray photoelectron spectroscopy and transmission electron microscopy images of the PSA nanospheres indicate that the acrylic acid was mainly distributed on the surface of the polystyrene spheres with unnegligible thickness. The number of Ag-NPs depends on immobilized carboxyl groups on the surface of PSA, according to thermogravimetry, ultraviolet-visible, X-ray diffraction and transmission electron microscopy results.

Impact of interaction between the G870A and EFEMP1 gene polymorphism on glioma risk in Chinese Han population.

AIMS: To investigate the impact of CCND1 and EFEMP1 gene polymorphism, and additional their gene-gene interactions and haplotype within EFEMP1 gene on glioma risk based on Chinese population. METHODS: Logistic regression was performed to investigate association between single-nucleotide polymorphisms (SNP) and glioma risk and generalized multifactor dimensionality reduction (GMDR) was used to analyze the gene-gene interaction. RESULTS: Glioma risks were higher in carriers of homozygous mutant of rs603965 within CCND1 gene, rs1346787 and rs3791679 in EFEMP1 gene than those with wild-type homozygotes, OR (95%CI) were 1.67 (1.23-2.02), 1.59 (1.25-2.01) and 1.42 (1.15-1.82), respectively. GMDR analysis indicated a significant two-locus model (p=0.0010) involving rs603965 within CCND1 gene and rs1346787 within EFEMP1 gene. Overall, the cross-validation consistency of the two- locus models was 10\ 10, and the testing accuracy is 60.17%. Participants with rs603965 - GA or AA and rs1346787- AG or GG genotype have the highest glioma risk, compared to participants with rs603965 - GG and rs1346787- AA genotype, OR (95%CI) was 3.65 (1.81-5.22). We conducted haplotype analysis for rs1346787 and rs3791679, because D' value between rs1346787 and rs3791679 was more than 0.8. The most common haplotype was rs1346787 - A and rs3791679- G haplotype, the frequency of which was 0.4905 and 0.4428 in case and control group. CONCLUSIONS: Polymorphism in rs603965 within CCND1 gene and rs1346787 within EFEMP1 gene and its gene- gene interaction were associated with increased glioma risk.

Impact of Heat Shock Protein A 12B Overexpression on Spinal Astrocyte Survival Against Oxygen-Glucose-Serum Deprivation/Restoration in Primary Cultured Astrocytes.

Heat shock protein A 12B (HSPA12B) is a newly discovered member of the heat shock protein 70 family. Preclinical evidence indicates that HSPA12B helps protect the brain from ischemic injury, although its specific function remains unclear. The aim of this study is to investigate whether HSPA12B overexpression can protect astrocytes from oxygen-glucose-serum deprivation/restoration (OGD/R) injury. We analyzed the effects of HSPA12B overexpression on spinal cord ischemia-reperfusion injury and spinal astrocyte survival. After ischemia-reperfusion injury, we found that HSPA12B overexpression decreased spinal cord water content and infarct volume. MTT assay showed that HSPA12B overexpression increased astrocyte survival after OGD/R treatment. Flow cytometry results showed a marked inhibition of OGD/R-induced astrocyte apoptosis. Western blot assay showed that HSPA12B overexpression significantly increased regulatory protein B-cell lymphocyte 2 (Bcl-2) levels, whereas it decreased expression of the Bax protein, which forms a heterodimer with Bcl-2. Measurements of the level of activation of caspase-3 by Caspase-Glo®3/7 Assay kit showed that HSPA12B overexpression markedly inhibited caspase-3 activation. Notably, we demonstrated that the effects of HSPA12B on spinal astrocyte survival depended on activation of the PI3K/Akt signal pathway. These findings indicate that HSPA12B protects against spinal cord ischemia-reperfusion injury and may represent a potential treatment target.

Antitumor effects of recombinant human adenovirus-p53 against human cutaneous squamous cell carcinoma in mice.

The present study was conducted to identify the anti-tumor effects of rAd/p53, which is a recombinant human serotype 5 adenovirus, in cutaneous squamous cell carcinoma (cSCC). Mouse models of human cSCC were constructed by injecting human cutaneous squamous cell carcinoma cells into both flanks of nude mice. Subsequently, the 75 nude mice with cSCC xenograft tumors were randomly divided into recombinant human serotype 5 adenovirus (rAd)/p53, rAd/p53 + 5-fluorouracil (5-Fu) and 5-Fu groups. One side of the tumors was administered the therapeutic agents as the therapeutic group, whereas the remaining side was treated with medical saline as the control. At 24, 48, 72, 120 and 168 h post-intratumoral injection, alterations in tumor volume, tumor necrosis and the expression of several tumor-associated genes, including Smad4, Brca1 and matrix metalloproteinase (MMP-2), were analyzed. Compared with its control group, the rAd/P53 group exhibited a significantly increased tumor necrosis ratio. In addition, Smad4 and Brca1 expression levels increased significantly at various time points (P<0.05), and MMP-2 expression decreased significantly (P<0.05). In the rAd/p53 + 5-Fu group, the tumor necrosis ratio, and Smad4 and Brca1 expression levels also significantly increased at various time points (P<0.05). MMP-2 gene transcription gradually decreased, high expression of Smad4 was prolonged, and high expression of Brca1 was observed in the early period following treatment compared with the rAd/P53 group. In addition, p53 expression exhibited a positive correlation with the tumor necrosis ratio and Smad4 expression, and showed a negative correlation with MMP-2 gene transcription (P<0.05). These findings indicate that rAd/p53 has a potent anti-tumor effect in cSCC via the promotion of tumor necrosis and regulating the expression of various tumor-associated genes.

Association between XRCC3 Thr241Met polymorphism and risk of osteosarcoma in a Chinese population.

The aim of this study was to investigate whether XRCC3 Thr241Met polymorphism could affect the development of osteosarcoma in a Chinese population. A total of 152 osteosarcoma patients and 304 health control subjects were included in our study. Polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) assay was applied to assess the XRCC3 Thr241Met gene polymorphism. By conditional logistic regression analysis, we found that TT genotype of XRCC3 Thr241Met was associated with increased risk of osteosarcoma in codominant model (OR = 2.53, 95% CI = 1.28-5.39). Moreover, XRCC3 Thr241Met gene polymorphism was correlated with an elevated increased risk of osteosarcoma in dominant (OR = 1.55, 95% CI = 1.03-2.34) and recessive models (OR = 2.30, 95% CI = 1.16-4.56). In conclusion, we found that XRCC3 Thr241Met gene polymorphism was associated with increased risk of osteosarcoma in codominant, dominant and recessive models.

Rocaglamide-A Potentiates Osteoblast Differentiation by Inhibiting NF-κB Signaling.

Rheumatoid arthritis is a chronic inflammatory disease that leads to bone and cartilage erosion. The inhibition of osteoblast differentiation by the inflammatory factor TNF-α is critical for the pathogenesis of rheumatoid arthritis. To modulate TNF-α mediated inhibition of osteoblast differentiation is required to improve therapeutic efficacy of rheumatoid arthritis. Here, we explored the potential role of rocaglamide-A, a component of Aglaia plant, in osteoblast differentiation. Rocaglamide-A prevented TNF-α mediated inhibition of osteoblast differentiation, and promoted osteoblast differentiation directly, in both C2C12 and primary mesenchymal stromal cells. Mechanistically, Rocaglamide-A inhibited the phosphorylation of NF-κB component p65 protein and the accumulation of p65 in nucleus, which resulted in the diminished NF-κB responsible transcriptional activity. Oppositely, overexpression of p65 reversed rocaglamide-A's protective effects on osteoblast differentiation. Collectively, rocaglamide-A protected and stimulated osteoblast differentiation via blocking NF-κB pathway. It suggests that rocaglamide-A may be a good candidate to develop as therapeutic drug for rheumatoid arthritis associated bone loss diseases.

Increased expression of lncRNA HULC indicates a poor prognosis and promotes cell metastasis in osteosarcoma.

INTRODUCTION: Long non-coding RNAs (lncRNAs) are aberrantly expressed in many diseases including cancer. LncRNA HULC (highly up-regulated in liver cancer) has recently been revealed to be involved in hepatocellular carcinoma development and progression. However, the role and function of HULC in human osteosarcoma remains unknown. METHODS: LncRNA HULC expression in osteosarcoma tissues and cell lines was detected by quantitative real-time PCR. Then, the association of HULC level with survival of osteosarcoma patients was performed by the Kaplan-Meier and Cox proportional regression analyses. Furthermore, the effects of HULC on tumorigenicity of osteosarcoma cells were evaluated by in vitro assays. RESULTS: In the present study, we demonstrated that HULC was significantly up-regulated in osteosarcoma tissues and cell lines compared with normal controls, and over-expression of HULC was correlated with clinical stage and distant metastasis. Moreover, higher HULC expression was associated with shorter overall survival of osteosarcoma patients. Furthermore, decreased expression of HULC markedly suppressed osteosarcoma cell proliferation, migration, and invasion. CONCLUSIONS: Our results indicated that HULC is a novel molecule involved in osteosarcoma progression, which may provide a new marker of poor prognosis and a potential therapeutic target for osteosarcoma intervention.

Rescue effect of lipid emulsion on bupivacaine-induced cardiac toxicity in cardiomyocytes.

The aim of the present study was to investigate the mechanism underlying the rescue effect of lipid emulsion on bupivacaine (BPV)­induced cardiomyocyte toxicity. The inhibitory effects of BPV on H9c2 myoblast cell proliferation were investigated using an MTT assay. The H9c2 myoblast cells were treated with either 1 mM BPV or 1% lipid emulsion (LE) alone, or co­treated with both of the drugs. Cell apoptosis was detected using both Annexin V/propidium iodide staining and a terminal deoxynucleotidyl transferase dUTP assay. The protein expression levels of apoptosis-associated proteins were quantified using western blot analysis, and the mRNA expression levels were quantified by reverse transcription­quantitative polymerase chain reaction. The expression levels of reactive oxidative species, malondialdehyde, superoxide dismutase, and catalase were quantified using the optical density values obtained from a spectrophotometer. In addition, the mechanism underlying the mitochondrial function of the H9c2 myoblast cells was investigated using both JC­1 staining, and cyclosporin A and atractyloside treatment. The results indicated that the H9c2 myoblast cells treated with BPV exhibited significantly higher levels of apoptosis. Furthermore, BPV treatment increased the levels of oxidative stress, and caused mitochondrial dysfunction within the H9c2 myoblast cells. LE treatment reversed the effects of BPV treatment in the H9c2 myoblast cells.