Enhanced anti-melanoma efficacy through a combination of the armed oncolytic adenovirus ZD55-IL-24 and immune checkpoint blockade in B16-bearing immunocompetent mouse model.

Although the recent treatment in melanoma through the use of anti-PD-1 immunotherapy is successful, the efficacy of this approach remains to be improved. Here, we explore the feasibility of combination strategy with the armed oncolytic adenovirus ZD55-IL-24 and PD-1 blockade. We find that combination therapy with localized ZD55-IL-24 and systemic PD-1 blockade leads to synergistic inhibition of both local and distant established tumors in B16-bearing immunocompetent mouse model. Our further mechanism investigation reveals that synergistic therapeutic effect is associated with marked promotion of tumor immune infiltration and recognition in both local and distant tumors as well as spleens. PD-1 blockade has no obvious effect on promotion of tumor immune infiltration and recognition. Localized therapy with ZD55-IL-24, however, can help PD-1 blockade to overcome the limitation of relatively low tumor immune infiltration and recognition. This study provides a rationale for investigation of such combination therapy in the clinic.

[Effect of zero-balanced ultrafiltration and modified ultrafiltration on pulmonary function after cardiac surgery in infants].

OBJECTIVE: To determine the protective effect of zero-balanced ultrafiltration and modified ultrafiltration on infants' pulmonary function after cardiac surgery. METHODS: Sixty infants with congenital heart diseases were randomly divided into 3 groups: a zero-balanced ultrafiltration group (Z group), a modified ultrafiltration group (M group) and a zero-balanced ultrafiltration with modified ultrafiltration group (Z+M group). Oxygenation index (OI), difference of alveoli-arterial oxygen pressure (P(A-α)O2), static lung compliance (Cstat), and airway resistance (Raw) were measured before caridopulmonary bypass (CPB, T1), 20 minutes after the CPB (T2), 2 h after the operation (T3), 6 h after the operation (T4) and 12 h after the operation (T5). The time of mechanical ventilation was also monitored. RESULTS: After the CPB, OI and Cstat in all groups decreased significantly, while Raw and P(A-α)O2 increased significantly. At T3, T4 and T5, OI and Cstat in the Z+M group were significantly higher than those in the Z group and the M group (P<0.05), Raw and P(A-α)O2 in the Z+M group were significantly lower than those in the Z group and the M group (P<0.05). The ventilation time in the Z+M group was significantly shorter than that in the Z group and the M group (P<0.05). CONCLUSION: Zero-balanced ultrafiltration and modified ultrafiltration can effectively promote the pulmonary function after cardiac surgery in infants.

Synthesis, in vitro antimycobacterial and antibacterial evaluation of IMB-070593 derivatives containing a substituted benzyloxime moiety.

A series of novel IMB-070593 derivatives containing a substituted benzyloxime moiety and displaying a remarkable improvement in lipophilicity were synthesized and evaluated for their in vitro antimycobacterial and antibacterial activity. Our results reveal that the target compounds 19a-m have considerable Gram-positive activity (MIC: <0.008-32 µg/mL), although they are generally less active than the reference drugs against the Gram-negative strains. In particular, compounds 19h, 19j, 19k and 19m show good activity (MICs: <0.008-4 µg/mL) against all of the tested Gram-positive strains, including ciprofloxacin (CPFX)- and/or levofloxacin (LVFX)-resistant MSSA, MRSA and MSSE. Moreover, compound 19l (MIC: 0.125 µg/mL) is found to be 2-4 fold more active than the parent IMB070593, CPFX and LVFX against M. tuberculosis H37Rv ATCC 27294.

Does low-intensity pulsed ultrasound accelerate phasic calcium phosphate ceramic-induced bone formation?

PURPOSE: Low-intensity pulsed ultrasound (LIPUS) has been used to stimulate the healing of the fresh fracture, delayed union, and non-union in both animal and clinical studies. Besides, biphasic calcium phosphate ceramic (BCP) is a promising biomaterial for bone repair as it shows favorable biocompatibility, osteoinduction, and osteoconduction. However, scarcity is known about the combined effect of LIPUS and BCP on bone formation. METHODS: The combined effect of LIPUS and BCP was studied in a beagle model. Twelve dogs were used. BCP granules without any additions were implanted into bilateral erector spinae muscles. One side is the BCP group, while the counterlateral side is LIPUS + BCP group. Histological and histomorphometric analyses, and quantitative real-time polymerase chain reaction were evaluated. RESULTS: Compared with BCP alone, the LIPUS + BCP showed no advantages in early bone formation. Furthermore, the Notch signaling pathway-related mRNA has no significant difference between the two groups. CONCLUSIONS: The preliminary results showed that the BCP, which has intrinsic osteoinduction nature, was an effective and promising material. However, LIPUS has no enhanced effect in BCP induced ectopic bone formation. Furthermore, LIPUS has no effect on the Notch signaling pathway. Whether costly LIPUS could be used in combination with BCP should be a rethink.

Comprehensive Evaluation of 24 Red Raspberry Varieties in Northeast China Based on Nutrition and Taste.

Red raspberry is a kind of fruit with high nutritional values. To evaluate the comprehensive quality of 24 red raspberry varieties in Northeast China, physicochemical properties, bioactive compounds and sensory characteristics were measured, followed by principal component analysis (PCA) and cluster analysis (CA). Altogether, eight important property indexes for processing attributes were selected out using PCA, including titratable acidity (TAC), sugar-acid ratio (SAR), pH, length, diameter, weight, sucrose and citric acid. Six individual sugars, including l-rhamnose monohydrate, fructose, glucose, sucrose, maltose and d-trehalose anhydrous, as well as eight organic acids, including oxalic acid, tartaric acid, malic acid, α-ketoglutaric acid, lactic acid, citric acid, fumaric acid and succinic acid, were identified in red raspberry. The two main clusters according to individual sugar, organic acids and SAR indicated that varieties including 'European red', 'DNS9', 'Bulgaskc', 'Canby' and 'Samodiva' were suitable for fresh-eating or processing to juice or other products directly because they had suitable SAR; other varieties with relatively low SAR were unsuitable for fresh-eating and need to adjust their excessive sour taste during processing.

Zinc-Doping Induces Evolution of Biocompatible Strontium-Calcium-Phosphate Conversion Coating on Titanium to Improve Antibacterial Property.

Implant-associated infections (IAI) remains a common and devastating complication in orthopedic surgery. To reduce the incidence of IAI, implants with intrinsic antibacterial activity have been proposed. The surface functionalization and structure optimization of metallic implants can be achieved by surface modification using the phosphate chemical conversion (PCC) technique. Zinc (Zn) has strong antibacterial behavior toward a broad-spectrum of bacteria. Herein, Zn was incorporated into strontium-calcium-phosphate (SrCaP) coatings on titanium (Ti) via PCC method, and the influence of its doping amount on the phase, microstructure, antibacterial activity, and biocompatibility of the composite coating was researched. The results indicated that traces of Zn doping produced grain refinement of SrCaP coating with no significant effect on its phase and surface properties, while a higher Zn content induced its phase and microstructure transformed into zinc-strontium-phosphate (SrZn2(PO4)2). SrCaP-Zn1 and SrCaP-Zn4 represented trace and high content Zn-doped coatings, respectively, which exhibited a similar bacterial attachment for a short time but showed inhibition of biofilm formation after continuous incubation up to 24 h. The killing rates of SrCaP-Zn1 coating for Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli) reached 61.25% and 55.38%, respectively. While that data increased to 83.01% and 71.28% on SrCaP-Zn4 coating due to the more-releasing Zn2+. Furthermore, in vitro culture of MC3T3-E1 cells proved that the Zn-doped coatings also possessed excellent biocompatibility. This study provides a new perception for the phase and microstructural optimization of phosphate coatings on implant surfaces, as well as fabricating promising coatings with excellent biocompatibility and antimicrobial properties against IAI.

Investigation and influencing factors about well-being level of elderly chronic patients during COVID-19 postpandemic period in Beijing.

ABSTRACT: The Corona Virus Disease 2019 (COVID-19) pandemic has huge impacts on the world, including human health and economic decline. The COVID-19 has severe infectivity, especially the elderly with chronic diseases will cause various complications after infection and accelerate the disease process. In addition, COVID-19 will also affect their mental health. Therefore, the mental health of elderly patients with chronic diseases cannot be ignored. The aim of this study was to investigate the well-being level of elderly people with chronic disease during COVID-19 postpandemic period in Beijing and analysis related influencing factors, so as to provide a basis for improving the well-being level of elderly chronic patients during the postpandemic period.Elderly patients with chronic diseases who met the inclusion criteria in 5 different administrative regions in Beijing were selected to carry out a questionnaire survey. The contents of the questionnaire included general data, the Memorial University of Newfoundland Happiness scale and the awareness situation of the COVID-19 pandemic. A total of 500 questionnaires were distributed by WeChat and 486 valid questionnaires were collected. The t test and one-way analysis of variance were used to compare Memorial University of Newfoundland Happiness scores between 2 or more groups, multiple linear regression analysis was used to conduct multiple factor analysis to explore the related factors about well-being level of elderly chronic patients.A total of 109 cases (22.43%) were evaluated high well-being level, 319 cases (65.64%) were evaluated moderate well-being level and 58 cases (11.93%) were evaluated low well-being according to the Memorial University of Newfoundland Happiness (MUNSH) scores rating. The multiple linear regression indicated that the education level, number of chronic diseases, medical expenses, frequency of children's visits, taking care of grandchildren or not, and group activity frequency significantly affected the well-being of patients with chronic diseases during COVID-19 postpandemic period in Beijing (P < .05).Most elderly patients with chronic diseases had moderate or above sense of well-being during postpandemic period, but we should still pay attention to the mental health of those elderly chronic patients with low education level, much comorbidity, more medical expenses, less visits by children, not take care of grandchildren and never participate in group activities.

HCCS1-armed, quadruple-regulated oncolytic adenovirus specific for liver cancer as a cancer targeting gene-viro-therapy strategy.

BACKGROUND: In previously published studies, oncolytic adenovirus-mediated gene therapy has produced good results in targeting cancer cells. However, safety and efficacy, the two most important aspects in cancer therapy, remain serious challenges. The specific expression or deletion of replication related genes in an adenovirus has been frequently utilized to regulate the cancer cell specificity of a virus. Accordingly, in this study, we deleted 24 bp in E1A (bp924-bp947) and the entirety of E1B, including those genes encoding E1B 55kDa and E1B19kDa. We used the survivin promoter (SP) to control E1A in order to construct a new adenovirus vector named Ad.SP.E1A(Δ24).ΔE1B (briefly Ad.SPDD). HCCS1 (hepatocellular carcinoma suppressor 1) is a novel tumor suppressor gene that is able to specifically induce apoptosis in cancer cells. The expression cassette AFP-HCCS1-WPRE-SV40 was inserted into Ad.SPDD to form Ad.SPDD-HCCS1, enabling us to improve the safety and efficacy of oncolytic-mediated gene therapy for liver cancer. RESULTS: Ad.SPDD showed a decreased viral yield and less toxicity in normal cells but enhanced toxicity in liver cancer cells, compared with the cancer-specific adenovirus ZD55 (E1B55K deletion). Ad.SPDD-HCCS1 exhibited a potent anti-liver-cancer ability and decreased toxicity in vitro. Ad.SPDD-HCCS1 also showed a measurable capacity to inhibit Huh-7 xenograft tumor growth on nude mice. The underlying mechanism of Ad.SPDD-HCCS1-induced liver cancer cell death was found to be via the mitochondrial apoptosis pathway. CONCLUSIONS: These results demonstrate that Ad.SPDD-HCCS1 was able to elicit reduced toxicity and enhanced efficacy both in vitro and in vivo compared to a previously constructed oncolytic adenovirus. Ad.SPDD-HCCS1 could be a promising candidate for liver cancer therapy.

Design, synthesis and in vitro antibacterial activity of 7-(4-alkoxyimino-3-aminomethylpiperidin-1-yl)fluoroquinolone derivatives.

We report herein the design and synthesis of novel 7-(4-alkoxyimino-3-aminomethylpiperidin-1-yl) fluoroquinolone derivatives. The antibacterial activity of the newly synthesized compounds was evaluated and compared with gemifloxacin, levofloxacin and ciprofloxacin. Results reveal that compounds 10, 16, and 17 have good activity against all of the tested gram-positive organisms including drug-resistance strains (MICs: 0.125-4 µg/mL). In addition, compounds 16 and 17 (MICs: 4 µg/mL) were 2- to 8-fold more potent than the reference drugs against Pseudomonas aeruginosa.

Optimization of the Administration Strategy for the Armed Oncolytic Adenovirus ZD55-IL-24 in Both Immunocompromised and Immunocompetent Mouse Models.

ZD55-IL-24 is an armed oncolytic adenovirus similar but superior to ONYX-015. Virotherapeutic strategies using ZD55-IL-24 have been demonstrated to be effective against several cancer types. However, it is unclear whether the traditional administration strategy is able to exert the maximal antitumor efficacy of ZD55-IL-24. In this study, we sought to optimize the administration strategy of ZD55-IL-24 in both A375-bearing immunocompromised mouse model and B16-bearing immunocompetent mouse model. Although the underlying antitumor mechanisms are quite different, the obtained results are similar in these two mouse tumor models. We find that the antitumor efficacy of ZD55-IL-24 increases as injection times increase in both of these two models. However, no obvious increase of efficacy is observed as the dose of each injection increases. Our further investigation reveals that the administration strategy of sustained ZD55-IL-24 therapy can achieve a better therapeutic effect than the traditional administration strategy of short-term ZD55-IL-24 therapy. Furthermore, there is no need to inject every day; every 2 or 3 days of injection achieves an equivalent therapeutic efficacy. Finally, we find that the sustained rather than the traditional short-term ZD55-IL-24 therapy can synergize with anti-PD-1 therapy to reject tumors in B16-bearing immunocompetent mouse model. These findings suggest that the past administration strategy of ZD55-IL-24 is in fact suboptimal and the antitumor efficacy can be further enhanced through administration strategy optimization. This study might shed some light on the development of clinically applicable administration regimens for ZD55-IL-24 therapy.

Synthesis and in vitro antibacterial activity of 7-(4-alkoxyimino-3-methyl-3-methylaminopiperidin-1-yl)quinolones.

To explore new agents of quinolone derivatives with high antibacterial activity, 7-(4-alkoxyimino-3-methyl-3-methylaminopiperidin-1-yl)quinolones were designed and synthesized, and their activity against gram-positive and gram-negative strains was tested in vitro. Sixteen target compounds were obtained. Their structures were established by 1H NMR, HRMS and X-ray crystallographic analysis. Compounds 14k and 14m-14o show good antibacterial activity against the tested five gram-positive strains and five gram-negative strains (MIC: 0.25-16 micromg x mL(-1)), of which the most active compound 14o is 8-fold more potent than levofloxacin against S. pneumoniae (MIC: 4 microg x mL(-1)), and comparable to levofloxacin against S. aureus, S. epidermidis, E. faecalis and E. coli (MIC: 0.25-1 microg x mL(-1)), but generally less potent than gemifloxacin.

The armed oncolytic adenovirus ZD55-IL-24 eradicates melanoma by turning the tumor cells from the self-state into the nonself-state besides direct killing.

ZD55-IL-24 is similar but superior to the oncolytic adenovirus ONYX-015, yet the exact mechanism underlying the observed therapeutic effect is still not well understood. Here we sought to elucidate the underlying antitumor mechanism of ZD55-IL-24 in both immunocompetent and immunocompromised mouse model. We find that ZD55-IL-24 eradicates established melanoma in B16-bearing immunocompetent mouse model not through the classic direct killing pathway, but mainly through the indirect pathway of inducing systemic antitumor immunity. Inconsistent with the current prevailing view, our further results suggest that ZD55-IL-24 can induce antitumor immunity in B16-bearing immunocompetent mouse model in fact not due to its ability to lyse tumor cells and release the essential elements, such as tumor-associated antigens (TAAs), but due to its ability to put a "nonself" label in tumor cells and then turn the tumor cells from the "self" state into the "nonself" state without tumor cell death. The observed anti-melanoma efficacy of ZD55-IL-24 in B16-bearing immunocompetent mouse model was practically caused only by the viral vector. In addition, we also notice that ZD55-IL-24 can inhibit tumor growth in B16-bearing immunocompetent mouse model through inhibiting angiogenesis, despite it plays only a minor role. In contrast to B16-bearing immunocompetent mouse model, ZD55-IL-24 eliminates established melanoma in A375-bearing immunocompromised mouse model mainly through the classic direct killing pathway, but not through the antitumor immunity pathway and anti-angiogenesis pathway. These findings let us know ZD55-IL-24 more comprehensive and profound, and provide a sounder theoretical foundation for its future modification and drug development.

4-Ethoxy-imino-N'-methoxy-pyrrolidin-1-ium-3-carboximidamidium dichloride.

The title compound, C(8)H(18)N(4)O(2) (2+)·2Cl(-), contains two oxime groups. The methyl oxime group has a Z configuration, and the ethyl oxime group is disordered, with both Z and E configurations in occupancies of 0.840 (8) and 0.160 (8), respectively. In the crystal structure, there are a number of N-H⋯Cl hydrogen bonds.

Improving Cycling Behaviors of Dockless Bike-Sharing Users Based on an Extended Theory of Planned Behavior and Credit-Based Supervision Policies in China.

Motivating users' civilized cycling plays a significant role in alleviating the troubles of dockless bike-sharing programs (DBSPs) and promoting the sustainable development of bike-sharing organizations. Based on the theory of planned behavior (TPB) and observed practices in China, this study develops a theoretical framework to examine how attitudes (ATT), subjective norms (SN), perceived behavioral control (PBC), and personal norms (PN) motivate users' civilized cycling behavior through civilized cycling intentions. Furthermore, the moderating effect of perceived policy effectiveness (PPE) between users' civilized cycling intention and their actual behavior is tested. Using structural equation model-multiple group analysis (SEM-MGA) for a sample of 874 valid questionnaire responses in Beijing and Shanghai, China, our results reveal that (1) ATT, PBC, and PN are positively related to both users' civilized cycling intentions and their actual behavior, while SN positively affect users' civilized cycling intention only; (2) users' civilized cycling intentions mediate the relationship between the four influencing factors and their actual behavior; and (3) PPE plays a moderating role for the effect of users' civilized cycling intentions on their actual civilized cycling behavior. Our results indicate that the four influencing factors can encourage users' civilized cycling behavior, especially when civilized cycling intention exists. Policies like credit-based supervision mechanisms could promote users' civilized-cycling intentions, which could then be transformed into actual behavior.

[Synthesis and antibacterial activity of 7-(3-amino-4-alkoxyimino-1 -piperidyl) -quinolones].

To explore new agents of quinolone derivatives with high activity against Gram-positive and Gram-negative microorganisms, 7-(3-amino-4-alkoxyimino-1-piperidyl) quinolones were designed and synthesized, and their activity against Gram-positive and Gram- negative microorganisms were tested in vivo and in vitro. Twenty one target compounds were obtained. Their structures were established by 1H NMR, HRMS and X-ray crystallographic analysis. The target compounds possess different antimicrobial activities against both Gram-negative and Gram-positive microorganisms. Compounds 14a and 14m have broad spectral antibacterial activities. They show better antibacterial activities against 12 strains Gram-positive bacteria than three references. In particular, their activities against S. aureus and S. epidermidis (including MRSA and MRSE) were 4 - 16 times than that of gemifloxacin and balofloxacin, and 8 - 64 times than that of levofloxacin. The MIC values to S. aureus strains of compounds 14a and 14m were 0.25 - 1 mg x L(-1) and 0.125 - 1 mg x L(-1), to S. epidermidis strains were 0.5 - 4 mg x L(-1) and 1 - 8 mg x L(-1) respectively. The in vivo results showed that they have as good internal protection as gemifloxacin and moxifloxacin against systemic infection model in mice (P > 0.05).

[Expression of BMP4 mRNA in the in-vivo tissue engineering bone].

This study was aimed to compare the expression of BMP4 mRNA in the in-vivo tissue engineering bone constructed with Ca/P ceramics against the expression of BMP4 mRNA in the naturally healing bone. 20 porous Ca/P ceramics cylinders with Phi 5 mm x 8 mm were made and implanted into the dorsal muscles of 5 dogs. As control, one molar tooth was pulled out from each dog to create bone defect for the naturally healing bone at the same time. The specimens and the naturally healing bone were harvested at 1, 2, 4, 12 and 24 weeks post-implantation. After RNA extraction and reverse transcription, bone morphogenetic protein 4 (BMP4) and GAPDH mRNA were detected by real-time quantitative polymerase chain reaction (PCR) method. The results showed that the expression level of BMP4 mRNA of the in-vivo tissue engineering bone constructed with Ca/P ceramics was higher than that of the naturally healing bone in the period of experiment. However, the in-vivo tissue engineering bone had the same chronological order of BMP mRNA expression that the naturally healing bone did. As a bone substitute analogous to autologous bone, the in-vivo tissue engineering bone constructed with Ca/P ceramics has the potential for clinical application.

Does low-intensity pulsed ultrasound accelerate phasic calcium phosphate ceramic-induced bone formation?

Purpose: Low-intensity pulsed ultrasound (LIPUS) has been used to stimulate the healing of the fresh fracture, delayed union, and non-union in both animal and clinical studies. Besides, biphasic calcium phosphate ceramic (BCP) is a promising biomaterial for bone repair as it shows favorable biocompatibility, osteoinduction, and osteoconduction. However, scarcity is known about the combined effect of LIPUS and BCP on bone formation. Methods: The combined effect of LIPUS and BCP was studied in a beagle model. Twelve dogs were used. BCP granules without any additions were implanted into bilateral erector spinae muscles. One side is the BCP group, while the counterlateral side is LIPUS + BCP group. Histological and histomorphometric analyses, and quantitative real-time polymerase chain reaction were evaluated. Results: Compared with BCP alone, the LIPUS + BCP showed no advantages in early bone formation. Furthermore, the Notch signaling pathway-related mRNA has no significant difference between the two groups. Conclusions: The preliminary results showed that the BCP, which has intrinsic osteoinduction nature, was an effective and promising material. However, LIPUS has no enhanced effect in BCP induced ectopic bone formation. Furthermore, LIPUS has no effect on the Notch signaling pathway. Whether costly LIPUS could be used in combination with BCP should be a rethink.

MicroRNA-802 plays a tumour suppressive role in tongue squamous cell carcinoma through directly targeting MAP2K4.

OBJECTIVES: Tongue squamous cell carcinoma (TSCC) is the most common oral tumours. MicroRNAs play crucial roles in many cell processes including cell viability, development, apoptosis, migration and invasion. The role of miR-802 in the TSCC is still unknown. MATERIALS AND METHODS: The miR-802 expression in TSCC tissues and cell lines was determined by quantitative real-time polymerase chain reaction. CCK-8 assay was performed to measure the cell viability, while the cell invasion assay was used to determine the cell invasion. Dual-luciferase reporter and western blot were used to confirm the potential target gene of miR-802. RESULTS: In our study, we demonstrated that miR-802 expression was downregulated in TSCC tissues and cell lines. Elevated expression of miR-802 suppressed the TSCC cell viability and invasion. Moreover, enforced expression of miR-802 increased the expression of E-cadherin, while suppressed the expression of N-cadherin, Snail and Vimentin in the TSCC cell. In addition, we identified the mitogen-activated protein kinase 4 (MAP2K4) as a direct target gene of miR-802 in the TSCC cell. We also demonstrated that the expression of MAP2K4 was higher in the TSCC tissues than that in the adjacent normal tissues. Furthermore, the expression level of MAP2K4 was inversely associated with the expression of miR-802 in TSCC tissues. We also demonstrated that the MAP2K4 expression was upregulated in TSCC cell lines. Elevated expression of miR-802 inhibited TSCC cell viability and invasion through inhibiting MAP2K4 expression. CONCLUSIONS: Our data revealed that miR-802 played as a tumour suppressor gene and might act as a therapeutic target in TSCC patients.

Cells responding to surface structure of calcium phosphate ceramics for bone regeneration.

Surface structure largely affects the inductive bone-forming potential of calcium phosphate (CaP) ceramics in ectopic sites and bone regeneration in critical-sized bone defects. Surface-dependent osteogenic differentiation of bone marrow stromal cells (BMSCs) partially explained the improved bone-forming ability of submicron surface structured CaP ceramics. In this study, we investigated the possible influence of surface structure on different bone-related cells, which may potentially participate in the process of improved bone formation in CaP ceramics. Besides BMSCs, the response of human brain vascular pericytes (HBVP), C2C12 (osteogenic inducible cells), MC3T3-E1 (osteogenic precursors), SV-HFO (pre-osteoblasts), MG63 (osteoblasts) and SAOS-2 (mature osteoblasts) to the surface structure was evaluated in terms of cell proliferation, osteogenic differentiation and gene expression. The cells were cultured on tricalcium phosphate (TCP) ceramics with either micron-scaled surface structure (TCP-B) or submicron-scaled surface structure (TCP-S) for up to 14 days, followed by DNA, alkaline phosphatase (ALP) and quantitative polymerase chain reaction gene assays. HBVP were not sensitive to surface structure with respect to cell proliferation and osteogenic differentiation, but had downregulated angiogenesis-related gene expression (i.e. vascular endothelial growth factor) on TCP-S. Without additional osteogenic inducing factors, submicron-scaled surface structure enhanced ALP activity and osteocalcin gene expression of human (h)BMSCs and C2C12 cells, favoured the proliferation of MC3T3-E1, MG63 and SAOS-2, and increased ALP activity of MC3T3-E1 and SV-HFO. The results herein indicate that cells with osteogenic potency (either osteogenic inducible cells or osteogenic cells) could be sensitive to surface structure and responded to osteoinductive submicron-structured CaP ceramics in cell proliferation, ALP production or osteogenic gene expression, which favour bone regeneration. Copyright © 2017 John Wiley & Sons, Ltd.

Veratric Acid Inhibits LPS-Induced IL-6 and IL-8 Production in Human Gingival Fibroblasts.

Veratric acid, one of the major benzoic acid isolated from vegetables and fruits, has been reported to have anti-inflammatory activity. The purpose of this study was to investigate the anti-inflammatory effects of veratric acid on lipopolysaccharide (LPS)-induced inflammatory response in human gingival fibroblasts (HGFs). HGFs were pretreated with veratric acid 1 h before LPS stimulation. The productions of IL-6 and IL-8 were detected by ELISA. The expression of iNOS, COX-2, PI3K, AKT, and NF-κB were detected by western blotting. The results showed that veratric acid inhibited LPS-induced IL-6 and IL-8 production, as well as iNOS and COX-2 expression. Veratric acid also inhibited LPS-induced NF-κB activation. In addition, veratric acid was found to suppress LPS-induced PI3K and AKT phosphorylation. In conclusion, the anti-inflammatory mechanism of veratric acid is due to its ability to inhibit PI3K/Akt/NF-κB signaling pathway.