Gradient gyroid Ti6Al4V scaffolds with TiO2 surface modification: Promising approach for large bone defect repair.

Large bone defects, particularly those exceeding the critical size, present a clinical challenge due to the limited regenerative capacity of bone tissue. Traditional treatments like autografts and allografts are constrained by donor availability, immune rejection, and mechanical performance. This study aimed to develop an effective solution by designing gradient gyroid scaffolds with titania (TiO2) surface modification for the repair of large segmental bone defects. The scaffolds were engineered to balance mechanical strength with the necessary internal space to promote new bone formation and nutrient exchange. A gradient design of the scaffold was optimized through Finite Element Analysis (FEA) and Computational Fluid Dynamics (CFD) simulations to enhance fluid flow and cell adhesion. In vivo studies in rabbits demonstrated that the G@TiO2 scaffold, featuring a gradient structure and TiO2 surface modification, exhibited superior healing capabilities compared to the homogeneous structure and TiO2 surface modification (H@TiO2) and gradient structure (G) scaffolds. At 12 weeks post-operation, in a bone defect representing nearly 30 % of the total length of the radius, the implantation of the G@TiO2 scaffold achieved a 27 % bone volume to tissue volume (BV/TV) ratio, demonstrating excellent osseointegration. The TiO2 surface modification provided photothermal antibacterial effects, enhancing the scaffold's biocompatibility and potential for infection prevention. These findings suggest that the gradient gyroid scaffold with TiO2 surface modification is a promising candidate for treating large segmental bone defects, offering a combination of mechanical strength, bioactivity, and infection resistance.

Identification of key miRNAs in unilateral mastication-induced disruption of cartilage homeostasis.

OBJECTIVE: The present study identified potentially pivotal miRNAs contributing to chondrogenic differentiation in temporomandibular joint suffering abnormal stress. MATERIALS AND METHODS: Sprague-Dawley rats were randomly divided into control and experimental unilateral mastication (EUM) group. Bone micro-structure parameters was detected by micro-CT, and FGF-1 and MMP-1 expression was examined by immunohistochemistry. Differentially expressed miRNAs of bilateral condyle cartilage were screened via miRNA microarray at 4- and 8-week EUM, then further verified using quantitative reverse-transcription PCR. Over-expression of five differentially expressed miRNAs in chondrocytes was triggered by transfecting miRNA mimics. The expression of MMP-13, Col-II, OPN, and Runx2 was verified by western blotting. RESULTS: Expressions of FGF-1 and MMP-1 in right condyles gradually increased from 2 to 6 weeks after EUM. A total of 20 differentially expressed miRNAs were regulated by EUM, which related to cell proliferation, invasion, and osteoblast differentiation pathways. The over-expression of miR-148a-3p and miR-1-3p led to down-regulation of Col-II, while MMP-13 and Runx2 were up-regulated by induction of hypotrophic differentiation or IL-1ß stimulation. These findings suggested that miR-148a-3p and miR-1-3p promote chondrogenic differentiation. CONCLUSIONS: Several pivotal miRNAs were found to be related to chondrogenic differentiation, which provides novel insight into pathogenic mechanisms of cartilage homeostasis.

Lactiplantibacillus plantarum LPJZ-658 Improves Non-Alcoholic Steatohepatitis by Modulating Bile Acid Metabolism and Gut Microbiota in Mice.

Non-alcoholic steatohepatitis (NASH) is one of the most prevalent diseases worldwide; it is characterized by hepatic lipid accumulation, inflammation, and progressive fibrosis. Here, a Western diet combined with low-dose weekly carbon tetrachloride was fed to C57BL/6J mice for 12 weeks to build a NASH model to investigate the attenuating effects and possible mechanisms of Lactiplantibacillus plantarum LPJZ-658. Hepatic pathology, lipid profiles, and gene expression were assessed. The metabolomic profiling of the serum was performed. The composition structure of gut microbiota was profiled using 16s rRNA sequencing. The results show that LPJZ-658 treatment significantly attenuated liver injury, steatosis, fibrosis, and inflammation in NASH mice. Metabolic pathway analysis revealed that several pathways, such as purine metabolism, glycerophospholipid metabolism, linoleic acid metabolism, and primary bile acid biosynthesis, were associated with NASH. Notably, we found that treatment with LPJZ-658 regulated the levels of bile acids (BAs) in the serum. Moreover, LPJZ-658 restored NASH-induced gut microbiota dysbiosis. The correlation analysis deduced obvious interactions between BAs and gut microbiota. The current study indicates that LPJZ-658 supplementation protects against NASH progression, which is accompanied by alternating BA metabolic and modulating gut microbiota.

Genome Sequence and Evaluation of Safety and Probiotic Potential of Lactiplantibacillus plantarum LPJZ-658.

This study aims to systematically evaluate the safety of a novel L. plantarum LPJZ-658 explored on whole-genome sequence analysis, safety, and probiotic properties assessment. Whole genome sequencing results demonstrated that L. plantarum LPJZ-658 consists of 3.26 Mbp with a GC content of 44.83%. A total of 3254 putative ORFs were identified. Of note, a putative bile saline hydrolase (BSH) (identity 70.4%) was found in its genome. In addition, the secondary metabolites were analyzed, and one secondary metabolite gene cluster was predicted to consist of 51 genes, which verified its safety and probiotic properties at the genome level. Additionally, L. plantarum LPJZ-658 exhibited non-toxic and non-hemolytic activity and was susceptible to various tested antibiotics, indicating that L. plantarum LPJZ-658 was safe for consumption. Moreover, the probiotic properties tests confirm that L. plantarum LPJZ-658 also exhibits tolerance to acid and bile salts, preferably hydrophobicity and auto-aggregation, and excellent antimicrobial activity against both Gram-positive and Gram-negative gastrointestinal pathogens. In conclusion, this study confirmed the safety and probiotic properties of L. plantarum LPJZ-658, suggesting it can be used as a potential probiotic candidate for human and animal applications.

Lignocellulosic-Based Nanoparticles with Photoluminescent Properties for Bioimaging.

Natural and renewable resources from plants or animals are an important source of biomaterials due to their biocompatibility and high availability. Lignin is a biopolymer present in the biomass of plants, where it is intertwined and cross-linked with other polymers and macromolecules in the cell walls, generating a lignocellulosic material with potential applications. We have prepared lignocellulosic-based nanoparticles with an average size of 156 nm that exhibit a high photoluminescence signal when excited at 500 nm with emission in the near-infrared (NIR) region at 800 nm. The advantage of these lignocellulosic-based nanoparticles is their natural luminescent properties and their origin from rose biomass waste, which eliminates the need for encapsulation or functionalization of imaging agents. Moreover, the in vitro cell growth inhibition (IC50) of lignocellulosic-based nanoparticles is about 3 mg/mL, and no in vivo toxicity was registered up to 57 mg/kg, which suggests that they are suitable for bioimaging applications. In addition, these nanoparticles can circulate in the blood and are excreted in urine. The combined high luminescence signal in NIR, small size, low in vitro toxicity, low in vivo toxicity, and blood circulation support the potential of lignin-based nanoparticles as a novel bioimaging agent.

Icariin Has a Synergistic Effect on the Osteoinductivity of Bone Morphogenetic Protein 2 at Ectopic Sites.

OBJECTIVE: Establishing biocompatible, biodegradable, osteoconductive, and osteoinductive bone materials remains a challenging subject in the research of bone healing and bone regeneration. Previously, we demonstrated the osteogenic and osteoconductive effects of biomimetic calcium phosphate (BioCaP) incorporating with Icariin and/or bone morphogenetic protein 2 (BMP-2) at orthotopic sites. METHODS: By implanting the BioCaP granules incorporated Icariin and/or BMP-2 into the dorsal subcutaneous pockets of adult male Sprague-Dawley (S-D) rats (6-7 weeks old), we investigated the osteoinductive efficacy of the samples. Micro-computed tomography(micro-CT) observations and histological slices were used to verify the osteoinduction of this system on the 2nd and 5th week. Statistical significances was evaluated using Turkey's post hoc test of one-way analysis of variance. RESULTS: The osteoinduction of the BioCaP incorporated with BMP-2 or both agents was confirmed as expected. BioCaP with Icariin alone could not generate bone formation at an ectopic sites. Nevertheless, co-administration of Icariin increased bone mineral density (BMD; p < 0.01) (628mg HA/cm3 vs 570mg HA/cm3 ) and completely changed the distribution of newly formed bone when compared with the granules with BMP-2 alone, even though there was no significant difference in the volume of newly formed bone. In contrast, the BioCaP with both agents (37.86%) had significantly fewer remaining materials than the other groups by the end of the fifth week (53.22%, 53.62% and 48.22%) (p < 0.01). CONCLUSION: The co-administration of Icariin and BMP-2 increased BMD changed the distribution of newly formed bone, and reduced the amount of remaining materials. Therefore, Icariin can stimulate BMP-2 when incorporated into BioCaP granules at ectopic sites, which makes it useful for bone tissue engineering.

Metatranscriptomics Reveals the RNA Virome of Ixodes Persulcatus in the China-North Korea Border, 2017.

In recent years, numerous viruses have been identified from ticks, and some have been linked to clinical cases of emerging tick-borne diseases. Chinese northeast frontier is tick infested. However, there is a notable lack of systematic monitoring efforts to assess the viral composition in the area, leaving the ecological landscape of viruses carried by ticks not clear enough. Between April and June 2017, 7101 ticks were collected to perform virus surveillance on the China-North Korea border, specifically in Tonghua, Baishan, and Yanbian. A total of 2127 Ixodes persulcatus were identified. Further investigation revealed the diversity of tick-borne viruses by transcriptome sequencing of Ixodes persulcatus. All ticks tested negative for tick-borne encephalitis virus. Transcriptome sequencing expanded 121 genomic sequence data of 12 different virus species from Ixodes persulcatus. Notably, a new segmented flavivirus, named Baishan Forest Tick Virus, were identified, closely related to Alongshan virus and Harz mountain virus. Therefore, this new virus may pose a potential threat to humans. Furthermore, the study revealed the existence of seven emerging tick-borne viruses dating back to 2017. These previously identified viruses included Mudanjiang phlebovirus, Onega tick phlebovirus, Sara tick phlebovirus, Yichun mivirus, and three unnamed viruses (one belonging to the Peribunyaviridae family and the other two belonging to the Phenuiviridae family). The existence of these emerging tick-borne viruses in tick samples collected in 2017 suggests that their history may extend further than previously recognized. This study provides invaluable insights into the virome of Ixodes persulcatus in the China-North Korea border region, enhancing our ongoing efforts to manage the risks associated with tick-borne viruses.

Dose Effects of Slow-Released Bone Morphogenetic Protein-2 Functionalized ß-Tricalcium Phosphate in Repairing Critical-Sized Bone Defects.

The aim of this study is to investigate the efficacy and the effect of the dosage of the slow-released Escherichia coli-derived recombinant human bone morphogenetic protein 2 (ErhBMP-2) functionalized ß-tricalcium phosphate (ß-TCP) in repairing critical-sized bone defects. The functionalization was implemented by modifying the surface of ß-TCP with biomimetic calcium phosphate coating with or without ErhBMP-2. Critical-sized calvarial defects were created in rats and filled with ErhBMP-2 functionalized ß-TCP loaded with gradient doses of ErhBMP-2 (0, 50, 100, 150, 200, and 300 µg/g). The blank control group and the autologous bone group were also included. The systemic toxicity was evaluated using routine blood and histopathological examination. The efficiency in bone healing was evaluated using microcomputed tomography, histology, and histometric analyses. Neither local nor systemic adverse effects were found following the implantation of the ErhBMP-2 functionalized ß-TCP. The new bone formation was significantly increased in the ErhBMP-2 functionalized ß-TCP groups compared with the blank group and the ß-TCP with coating only group. The efficacy of the ErhBMP-2 functionalized ß-TCP in bone healing was comparable to that of the autologous bone. There was no significant difference in bone formation among all concentrations of ErhBMP-2 (0-300 µg/g). Increased bone maturation was found in the higher concentration groups (150, 200, and 300 µg/g) when compared with the lower concentration groups (50, and 100 µg/g). Our results demonstrated that the ErhBMP-2 functionalized ß-TCP could significantly promote bone repairing in critical-sized defects, and it could clinically be a promising substitute for autologous bone. Besides, our results demonstrated that there was a dosage-dependent effect of ErhBMP-2 functionalized ß-TCP on bone maturation rather than bone formation. The optimized concentrations of ErhBMP-2 recommended for this kind of model should be in the range of 150-300 µg/g. Impact Statement Bone substitutes functionalized by mammalian-derived recombinant human bone morphogenetic protein 2 (rhBMP-2) have demonstrated to be comparable to the autologous bone in repairing the critical-sized bone defects. To develop a commercial product with more effective cost, Escherichia coli-derived rhBMP-2 (ErhBMP-2) has been produced and evaluated as an alternative to the mammalian-derived rhBMP-2. In this study, we prepared gradient ErhBMP-2 functionalized ß-tricalcium phosphate (ß-TCP) with biomimetic calcium phosphate coating and investigate their efficacy and dose effects. We revealed the dose effects of the slow-released ErhBMP-2 and demonstrated that ErhBMP-2 functionalized ß-TCP could be a promising bone substitute for bone regeneration in clinical settings.

Vertical bone augmentation with simultaneous implantation using deproteinized bovine bone block functionalized with a slow delivery of BMP-2.

OBJECTIVE: We hypothesized that a biomimetic calcium phosphate (CaP) coating which incorporates morphogenetic protein 2 (BMP-2) on the deproteinized bovine bone (DBB) blocks could be used to enhance the vertical alveolar ridge augmentation for the one-stage onlay surgery with simultaneous implants insertion. We aimed to test this hypothesis in vivo. MATERIAL AND METHODS: Beagles dogs were used for the study (n = 6 specimens per group). One month after building the edentulous animal model, 4 mm vertical alveolar bone loss were surgically created and four groups of blocks (W × L × H: 7 mm × 10 mm × 4 mm) were randomly fixed onto the reduced alveolar ridge by implants: (a) DBB blocks alone (negative control group); (b) DBB blocks with superficial adsorption of 50 µg BMP-2 (ad.BMP-2 group); (c) DBB blocks coated by biomimetic CaP coating which incorporates 50 µg BMP-2 (inc.BMP-2 group); and (d) autologous bone blocks (positive control group). After 3 months of healing, samples were harvested for micro-CT and histomorphometric analyses. RESULTS: In histomorphometry, the inc.BMP-2 group showed a significantly thicker (coronal-apically) and wider (buccal-lingually) augmented bone area, better bone-to-implant contact than the negative control group. In both the micro-CT and histomorphometry, the inc.BMP-2 group showed more mineralized tissue than the negative control group and the inc.BMP-2 group also showed significantly more newly formed bone and residual grafts than the negative control group in the upper half of the blocks. In micro-CT, the inc.BMP-2 group showed significantly more bone-to-graft contact percentage than the ad.BMP-2 group. In both micro-CT and histomorphometry, the inc.BMP-2 group showed significantly more percentage of mineralized tissue than the ad.BMP-2 group. No significant differences were found between the inc.BMP-2 group and the positive control group either in micro-CT or in histomorphometry. CONCLUSIONS: The DBB blocks with coating-delivered BMP-2 significantly enhanced the efficacy of vertical alveolar bone augmentation, compared with the unloaded blocks and blocks with adsorbed BMP-2, in the one-stage onlay surgery with simultaneous implant insertion.

HMGB2 is associated with pressure loading in chondrocytes of temporomandibular joint: In vitro and in vivo study.

High mobility group protein B2 (HMGB2) is an important protein attributed to tissue function and homeostasis in osteoarthritis (OA), however, its roles in the temporomandibular joint with mechanical pressure are unclear. This study investigated the expression patterns of HMGB2 in chondrocytes of TMJ on OA-related cellular and animal models. The transcriptional level and protein expression of HMGB2 as well as Col- II, MMP-13 and ß-catenin were examined in primary cultured chondrocytes from TMJs with hydrostatic pressures (HP). The immunohistochemistry of HMGB2, Col- II, MMP13 and ß-catenin in rabbits with surgical anterior disc displacement (ADD) were analyzed. The results indicated that HP decreased the mRNA expression of HMGB2, MMP-13, and ß-catenin. HMGB2 knockdown attenuated the sensitivity of chondrocytes response to pressure loading. Immunohistochemical results showed that the rabbits with ADD exhibited thinner condylar cartilage with disordered cell arrangement. The distribution of HMGB2 was chiefly in the fibrous layer and the proliferative layer of the condylar cartilage. In rabbit cartilage with ADD, the expression of HMGB2 and ß-catenin were elevated at 1 week followed by sustained decrease at 2 and 4 weeks. Our findings suggested that HMGB2 is necessary for TMJ chondrocytes to sense pressure loading, which plays an important role in the pathogenesis of chondrogenesis and TMJOA following mechanical loading.

Periodontal regeneration using bone morphogenetic protein 2 incorporated biomimetic calcium phosphate in conjunction with barrier membrane: A pre-clinical study in dogs.

AIM: To evaluate the effect of bone morphogenetic protein 2 (BMP-2) incorporated biomimetic calcium phosphate (BMP-2/BioCaP) in conjunction with barrier membrane on periodontal regeneration in chronic periodontitis experimental model. MATERIAL AND METHODS: Chronic periodontitis experimental model with critical-sized supra-alveolar defects was created in 15 dogs' mandibles. After the initial periodontal therapy, the defects were randomly assigned to the following groups: (a) control; (b) barrier membrane; (c) deproteinized bovine bone mineral + barrier membrane; (d) BioCaP + barrier membrane and (e) BMP-2/BioCaP + barrier membrane (6 quadrants with 18 teeth per group). Eight weeks later, clinical examinations, micro-CT, and histomorphometric analyses were performed. RESULTS: Clinical examinations, including plaque index, bleeding index, and probing depth, were similar for all groups. In contrast, the clinical attachment loss was significantly lower in defects grafted with BMP-2/BioCaP and barrier membrane. The micro-CT results showed that the height of mineralized tissue in defects grafted with BMP-2/BioCaP and barrier membrane was significantly higher. For histometric analysis, the defects grafted with BMP-2/BioCaP and barrier membrane exhibited significantly more connective tissue height, new cementum height, new bone height and area, as well as less down-growth of junctional epithelium. CONCLUSION: BMP-2/BioCaP could be a promising bone substitute for periodontal regeneration.

Osteogenic Enhancement Between Icariin and Bone Morphogenetic Protein 2: A Potential Osteogenic Compound for Bone Tissue Engineering.

Icariin, a typical flavonol glycoside, is the main active component of Herba Epimedii, which was used to cure bone-related diseases in China for centuries. It has been reported that Icariin can be delivered locally by biomaterials and it has an osteogenic potential for bone tissue engineering. Biomimetic calcium phosphate (BioCaP) bone substitute is a novel drug delivery carrier system. Our study aimed to evaluate the osteogenic potential when Icariin was internally incorporated into the BioCaP granules. The BioCaP combined with Icariin and bone morphogenetic protein 2 (BMP-2) was investigated in vitro using an MC3T3-E1 cell line. We also investigated its efficacy to repair 8 mm diameter critical size bone defects in the skull of SD male rats. BioCaP was fabricated according to a well-established biomimetic mineralization process. In vitro, the effects of BioCaP alone or BioCaP with Icariin and/or BMP-2 on cell proliferation and osteogenic differentiation of MC3T3-E1 cells were systematically evaluated. In vivo, BioCaP alone or BioCaP with Icariin and/or BMP-2 were used to study the bone formation in a critical-sized bone defect created in a rat skull. Samples were retrieved for Micro-CT and histological analysis 12 weeks after surgery. The results indicated that BioCaP with or without the incorporation of Icariin had a positive effect on the osteogenic differentiation of MC3T3-E1. BioCaP with Icariin had better osteogenic efficiency, but had no influence on cell proliferation. BioCap + Icariin + BMP-2 showed better osteogenic potential compared with BioCaP with BMP-2 alone. The protein and mRNA expression of alkaline phosphatase and osteocalcin and mineralization were higher as well. In vivo, BioCaP incorporate internally with both Icariin and BMP-2 induced significantly more newly formed bone than the control group and BioCaP with either Icariin or BMP-2 did. Micro-CT analysis revealed that no significant differences were found between the bone mineral density induced by BioCaP with icariin and that induced by BioCaP with BMP-2. Therefore, co-administration of Icariin and BMP-2 was helpful for bone tissue engineering.

Sero-epidemiologic study of influenza A(H7N9) infection among exposed populations, China 2013-2014.

BACKGROUND: The first human infections of novel avian influenza A(H7N9) virus were identified in China in March 2013. Sentinel surveillance systems and contact tracing may not identify mild and asymptomatic human infections of influenza A(H7N9) virus. OBJECTIVES: We assessed the seroprevalence of antibodies to influenza A(H7N9) virus in three populations during the early stages of the epidemic. PATIENTS/METHODS: From March 2013 to May 2014, we collected sera from the general population, poultry workers, and contacts of confirmed infections in nine Chinese provinces reporting human A(H7N9) infections and, for contacts, second sera 2-3 weeks later. We screened for A(H7N9) antibodies by advanced hemagglutination inhibition (HI) assay and tested sera with HI titers ≥20 by modified microneutralization (MN) assay. MN titers ≥20 or fourfold increases in paired sera were considered seropositive. RESULTS: Among general population sera (n=1480), none were seropositive. Among poultry worker sera (n=1866), 28 had HI titers ≥20; two (0.11%, 95% CI: 0.02-0.44) were positive by MN. Among 61 healthcare and 117 non-healthcare contacts' sera, five had HI titers ≥20, and all were negative by MN. There was no seroconversion among 131 paired sera. CONCLUSIONS: There was no evidence of widespread transmission of influenza A(H7N9) virus during March 2013 to May 2014, although A(H7N9) may have caused rare, previously unrecognized infections among poultry workers. Although the findings suggest that there were few undetected cases of influenza A(H7N9) early in the epidemic, it is important to continue monitoring transmission as virus and epidemic evolve.

Differential gene expression in the condylar cartilage of growing rabbits with temporomandibular joint anterior disk displacement-A transcriptomic study.

Internal derangement (ID) in the temporomandibular joint (TMJ) comprises a group of clinical problems with relatively high prevalence. However, the temporal changes in gene expression of condylar cartilage during continuous ID remain unclear. The aim of the current study is to investigate by microarray analysis, the differentially-expressed gene pattern in condylar cartilage of rabbits with ID from one to eight weeks of ID progression. Histological results (hematoxylin and eosin staining) indicated that abnormal collagen fiber arrangements, fragmentation of fibrils, and inflammatory cell-infiltration were detected from one to four weeks in joint disc specimens, while newly formed vessels, mucoid degeneration, meniscal tears, and the presence of osteoclasts and osteoblasts were observed at later time points. The microarray analysis revealed 6478 genes among all tested transcripts, to have a greater than two-fold expression change compared to controls. The inflammation-associated gene group including ace and il1ß increased rapidly in the early stage of disease and decreased later. In contrast, bone construction-related genes showed low expression levels at first and increased at later period in the ID progression. The current study also found some genes such as hla2g, which have not been previously reported, to be potentially relevant within ID. Our findings provide useful insights into the pathological mechanism of ID in TMJ.

Hydrostatic Compress Force Enhances the Viability and Decreases the Apoptosis of Condylar Chondrocytes through Integrin-FAK-ERK/PI3K Pathway.

Reduced mechanical stimuli in many pathological cases, such as hemimastication and limited masticatory movements, can significantly affect the metabolic activity of mandibular condylar chondrocytes and the growth of mandibles. However, the molecular mechanisms for these phenomena remain unclear. In this study, we hypothesized that integrin-focal adhesion kinase (FAK)-ERK (extracellular signal-regulated kinase)/PI3K (phosphatidylinositol-3-kinase) signaling pathway mediated the cellular response of condylar chondrocytes to mechanical loading. Primary condylar chondrocytes were exposed to hydrostatic compressive forces (HCFs) of different magnitudes (0, 50, 100, 150, 200, and 250 kPa) for 2 h. We measured the viability, morphology, and apoptosis of the chondrocytes with different treatments as well as the gene, protein expression, and phosphorylation of mechanosensitivity-related molecules, such as integrin α2, integrin α5, integrin ß1, FAK, ERK, and PI3K. HCFs could significantly increase the viability and surface area of condylar chondrocytes and decrease their apoptosis in a dose-dependent manner. HCF of 250 kPa resulted in a 1.51 ± 0.02-fold increase of cell viability and reduced the ratio of apoptotic cells from 18.10% ± 0.56% to 7.30% ± 1.43%. HCFs could significantly enhance the mRNA and protein expression of integrin α2, integrin α5, and integrin ß1 in a dose-dependent manner, but not ERK1, ERK2, or PI3K. Instead, HCF could significantly increase phosphorylation levels of FAK, ERK1/2, and PI3K in a dose-dependent manner. Cilengitide, the potent integrin inhibitor, could dose-dependently block such effects of HCFs. HCFs enhances the viability and decreases the apoptosis of condylar chondrocytes through the integrin-FAK-ERK/PI3K pathway.

A practical community-based response strategy to interrupt Ebola transmission in sierra Leone, 2014-2015.

BACKGROUND: The Ebola virus disease spread rapidly in West Africa in 2014, leading to the loss of thousands of lives. Community engagement was one of the key strategies to interrupt Ebola transmission, and practical community level measures needed to be explored in the field and tailored to the specific context of communities. METHODS: First, community-level education on Ebola virus disease (EVD) prevention was launched for the community's social mobilizers in six districts in Sierra Leone beginning in November 2014. Then, from January to May of 2015, in three pilot communities, local trained community members were organized to engage in implementation of EVD prevention and transmission interruption measures, by involving them in alert case report, contact tracing, and social mobilization. The epidemiological indicators of transmission interruption in three study communities were evaluated. RESULTS: A total of 6 016 community social mobilizers from 185 wards were trained by holding 279 workshops in the six districts, and EVD message reached an estimated 631 680 residents. In three pilot communities, 72 EVD alert cases were reported, with 70.8 % of them detected by trained local community members, and 14 EVD cases were finally identified. Contact tracing detected 64.3 % of EVD cases. The median duration of community infectivity for the cases was 1 day. The secondary attack rate was 4.2 %, and no third generation of infection was triggered. No health worker was infected, and no unsafe burial and noncompliance to EVD control measures were recorded. The community-based measures were modeled to reduce 77 EVD cases, and the EVD-free goal was achieved four months earlier in study communities than whole country of Sierra Leone. CONCLUSIONS: The community-based strategy of social mobilization and community engagement was effective in case detection and reducing the extent of Ebola transmission in a country with weak health system. The successfully practical experience to reduce the risk of Ebola transmission in the community with poor resources would potentially be helpful for the global community to fight against the EVD and the other diseases in the future.

Rapid assessment of knowledge, attitudes, practices, and risk perception related to the prevention and control of Ebola virus disease in three communities of Sierra Leone.

BACKGROUND: The recent outbreak of the Ebola virus disease (EVD) in Sierra Leone has been characterized by the World Health Organization as one of the most challenging EVD outbreaks to date. The first confirmed case in Sierra Leone was a young woman who was admitted to a government hospital in Kenema following a miscarriage on 24 May 2014. On 5 January 2015, intensified training for an EVD response project was initiated at the medical university of Sierra Leone in Jui. To understand the knowledge, attitudes, practices, and perceived risk of EVD among the public, especially after this training, a rapid assessment was conducted from 10 to 16 March 2015. METHODS: Interviews were conducted with 466 participants based on questionnaires that were distributed from 10 to 16 March 2015 by cluster sampling in three adjacent communities, namely Jui, Grafton, and Kossoh Town, in the Western Area Rural District of Sierra Leone. RESULTS: It was found that knowledge about EVD was comprehensive and high. Positive attitude towards prevention was found to be satisfactory. Nearly all participants knew the reporting phone number 117 and had reported some change in behavior since learning about Ebola. More than half (62 %) of the participants had a history of travelling to urban areas, which increases the risk of infection. The multivariable logistic regression analysis showed that community and occupation were variables associated with perceived risk of EVD. CONCLUSIONS: Our study showed that community level social mobilization and community engagement were an effective strategy in the special context.

Knowledge and attitudes about Ebola vaccine among the general population in Sierra Leone.

BACKGROUND: Clinical trials of Ebola vaccine are ongoing. Before it becomes commercially available, understanding the Ebola vaccine-related knowledge and attitude of the general population is imperative to developing an effective vaccine coverage strategy. METHODS: We conducted a survey including 400 participants from general communities of the West Area Rural District, Sierra Leone. Knowledge and attitudes about Ebola vaccine were investigated, and the determinants of having knowledge and a positive attitude toward accepting vaccination were identified. RESULTS: Over half (55.8%) of the participants were aware of Ebola vaccine. About 60% of the participants were willing to be study subjects if the Ebola vaccine clinical trial were conducted in their communities. Most of the participants (72.5%) were willing to take Ebola vaccination if it was free of charge. Given that the vaccination was not free, the proportion willing to pay a fee to take the vaccination declined dramatically to 26.6%. Using a forward step-wise logistic model, monthly salary was identified as the single determinant (OR for every 100,000 Leones increase: 1.17, 95%CI: 1.04-1.31) for awareness of Ebola vaccine, which was identified as the determinant (OR: 1.88, 95%CI: 1.17-3.02) for free vaccination uptake willingness. The combination of monthly salary, monthly average income of family members and their interaction was found to be associated with charged vaccination uptake willingness. DISCUSSION: Measures are still needed to promote the Ebola vaccine awareness and knowledge updating. Free or low-priced vaccine could increase the vaccination acceptability of the general community population significantly.

Transcriptomic study on the impact of temporomandibular joint internal derangement in the condylar cartilage of rabbits.

Internal derangement (ID) in the temporomandibular joint (TMJ) compromises a group of clinical problems, and holds a relative high prevalence in populations. However, the temporal genomic change in gene expression of condylar cartilage during continuous ID remains unclear. Here we reported the differentially expressed gene pattern in condylar cartilage of rabbits with ID from 1 to 8 weeks by microarray analysis. The whole genome project was deposited at GenBank under the accession PRJNA278127. The microarray analysis showed that 6478 genes have more than two-fold changes among all the tested transcripts. Many inflammation gene increased rapidly in the early stage while decrease later. On the contrary, the bone construction related genes showed a low level at first and increased at later period in the ID progression. Besides, the current study found some genes such as HLA2G, which had never been reported, might be relevant with ID.

The Features of Genetic Prion Diseases Based on Chinese Surveillance Program.

OBJECTIVE: To identify the features of Chinese genetic prion diseases. METHODS: Suspected Creutzfeldt-Jakob disease (CJD) cases that were reported under CJD surveillance were diagnosed and subtyped using the diagnostic criteria issued by the WHO. The general information concerning the patient, their clinical, MRI and EEG data, and the results of CSF 14-3-3 and PRNP sequencing were carefully collected from the database of the national CJD surveillance program and analyzed using the SPSS 11.5 statistical software program. RESULTS: Since 2006, 69 patients were diagnosed with genetic prion diseases and as having 15 different mutations. The median age of the 69 patients at disease onset was 53.5 years, varying from 19 to 80 years. The majority of patients displaying clinical symptoms were in the 50-59 years of age. FFI, T188K gCJD and E200K were the three most common subtypes. The disease appeared in the family histories of 43.48% of the patients. The clinical manifestations varied considerably among the various diseases. Patients who carried mutations in the N-terminus displayed a younger age of onset, were CSF 14-3-3 negative, had a family history of the condition, and experienced a longer duration of the condition. The clinical courses of T188K were significantly shorter than those of FFI and E200K gCJD, while the symptoms in the FFI group appeared at a younger age and for a longer duration. Moreover, the time intervals between the initial neurologist visit to the final diagnosis were similar among patients with FFI, T188K gCJD, E200K gCJD and other diseases. CONCLUSION: The features of Chinese genetic prion diseases are different from those seen in Europe and other Asian countries.