Preparation and characterization of 3D hydroxyapatite/collagen scaffolds and its application in bone regeneration with bone morphogenetic protein-2.

Desirable bone engineering materials should have a conducive three-dimensional (3D) structure and bioactive mediators for guided bone regeneration. In the present study, hydroxyapatite (HA)/collagen (Col) scaffolds were prepared by an optimized freeze-drying process. The porosity, moisture content, and mechanical properties of the composite have been investigated. The micro-morphology and structure were analyzed with scanning electron microscopy (SEM) and transmission electron microscopy (TEM), confirmed that self-cross-linked HA/Col was evenly distributed and formed a 3D porous scaffold. The physicochemical/mechanical characterization was carried out by Fourier transform infrared spectroscopy (FT-IR) and X-ray diffraction (XRD). Morphological observation and CCK-8 assay of co-culture cells indicated that HA/Col scaffolds were biocompatible. Then HA/Col scaffolds coupled with recombinant human bone morphogenetic proteins 2 (rhBMP-2) were implanted in the mandibular critical size defect in rats, and histological staining was used to evaluate the bone reconstruction. The result showed that HA/Col coupled with rhBMP-2 could significantly improve the formation of new bone and angiogenesis within the scaffolds as well as the proliferation and differentiation of osteoblasts. Thanks to the encouraging osteogenesis effects, the well-defined 3D scaffolds (HA/Col) cooperating with bioactive agents (rhBMP-2) are expected to be a promising candidate for bone tissue engineering applied to regenerative medicine.

Prognostic Factors of Combined Periodontal and Endodontic Lesions: A Retrospective Study.

Objective: This study used a retrospective method to explore the relevant factors affecting the prognosis of periodontal-endodontic combined lesions. Methods: According to the changes of subjective feelings and clinical indicators of affected teeth, selected patients were divided into an effective group and an ineffective group. The natural conditions (age, gender, and smoking status) of the patients and various clinical indicators at the initial and follow-up visits were collected, including the periodontal clinical indicators of the whole mouth and the clinical indicators of the affected teeth. The full-mouth periodontal clinical indicators include periodontal probing depth (PD), clinical attachment loss (CAL), sulcus bleeding index (SBI), and simplified oral hygiene index (OHI.S); clinical indicators of affected teeth include PD, CAL, SBI, mobility (TM), clinical crown-to-root ratio (CR), periapical index (PAI), and number of root canals. Results: There were 74 cases of endodontic combined treatment, with a total of 86 teeth. There was no significant difference in age and gender ratio between the effective group and the ineffective group, and the proportion of smoking patients in the ineffective group was significantly higher than that in the effective group (P < 0.05). At the initial diagnosis, there was no significant difference in the clinical indicators of the whole mouth between the effective group and the ineffective group. After a combined endodontic treatment, the clinical indicators of the two groups were significantly improved (P < 0.01). There was no significant difference in other periodontal clinical indicators between the two groups. Conclusion: The prognosis of nonsurgical treatment of periodontal and periodontal combined lesions is mainly correlated to the patient's oral hygiene maintenance, as well as the loss of attachment, the degree of loosening, the clinical crown-to-root ratio, the periapical index, and the number of root canals.

Effect of a new modified polyamidoamine dendrimer biomimetic system on the mineralization of type I collagen fibrils: an in vitro study.

We evaluate the effects of the new Dentine matrix protein 1 (DMP-1) biomimetic system composed of phosphorylated polyamidoamine dendrimer (PAMAM-PO3H2) and carboxylated polyamidoamine dendrimer (PAMAM-COOH) on the mineralization of type I collagen fibrils. PAMAM-PO3H2 and PAMAM-COOH were observed to have the ability to induce internal and external mineralization of type I collagen fibrils in vitro through non-classical mineralization crystallization pathway, which has become a hopeful biomimetic system of biomimetic remineralization and demineralization of dentin type I collagen fibrils and has great potential in inducing biomimetic remineralization of demineralized dentin.

Remineralization of human dentin type I collagen fibrils induced by carboxylated polyamidoamine dendrimer/amorphous calcium phosphate nanocomposite: an in vitro study.

Intrafibrillar mineralization of type I collagen fibrils is of great significance in dental remineralization, which is the key of caries prevention and treatment. Herein, two substances that have the remineralization ability, carboxylated polyamidoamine dendrimer (PAMAM-COOH) and nano-sized amorphous calcium phosphate (n-ACP) were combined to synthesize a novel nanomaterial, carboxylated polyamidoamine dendrimer/amorphous calcium phosphate nanocomposite (PAMAM-COOH/ACP). This article aims to evaluate the remineralization effect of PAMAM-COOH/ACP of dentin type I collagen fibrils in vitro. Fluorescence labeling technique was innovatively used to observe and evaluate the remineralization effect. PAMAM-COOH/ACP showed superior remineralization ability of human dentin type I collagen fibrils, especially the intrafibrillar remineralization. Therefore, the novel nanomaterial PAMAM-COOH/ACP is promising to prevent and treat various diseases caused by dentin demineralization and to improve various dental materials.

A new PD-1-specific nanobody enhances the antitumor activity of T-cells in synergy with dendritic cell vaccine.

Despite the many successes and opportunities presented by PD-1 blockade in cancer therapies, anti-PD-1 monoclonal antibodies still face multiple challenges. Herein we report a strategy based on a nanobody (Nb) to circumvent these obstacles. A new PD-1-blocking Nb (PD-1 Nb20) in combination with tumor-specific dendritic cell (DC)/tumor-fusion cell (FC) vaccine that aims to improve the activation, proliferation, cytokine secretion, and tumor cell cytotoxicity of CD8+ T-cells. This combination was found to effectively enhance the in vitro cytotoxicity of CD8+ T-cells to kill human non-small cell lung cancer (NSCLC) HCC827 cells, hepatocellular carcinoma (HCC) HepG2 cells, and tongue squamous cell carcinoma (TSCC) Tca8113 cells. Moreover, CD8+ T-cells pre-treated with PD-1 Nb20 and tumor-specific DC/tumor-FCs significantly suppressed the growth of NSCLC-, HCC- and TSCC-derived xenograft tumors and prolonged the survival of tumor-bearing mice, through promoting T-cell infiltration to kill tumor cells and inhibiting tumor angiogenesis. These data demonstrate that PD-1 Nb20 in synergy with DC/tumor-FC vaccine augment the broad spectrum of antitumor activity of CD8+ T-cells, providing an alternative and promising immunotherapeutic strategy for tumor patients who are T-cell-dysfunctional or not sensitive to anti-PD-1 therapy.

A Single-Chain Variable Fragment Antibody/Chemokine Fusion Protein Targeting Human Endoglin to Enhance the Anti-Tumor Activity of Cytokine-Induced Killer Cells.

Cytokine-induced killer cell immunotherapy is an ideal candidate for adoptive cell transfer therapy. However, therapeutic approaches to enhance the anti-tumor activity of cytokine-induced killer cells remain to be explored. Here, we described the successful development of a novel antibody-chemokine fusion protein containing the anti-human Endoglin antibody in the single-chain variable fragment format and human interferon-gamma-induced protein 10 (hENG scFv/hIP-10). Its anti-Endoglin immunoreactivity and chemotactic activity against the cytokine-induced killer cells were characterized in vitro. To evaluate the anti-tumor effect in vivo, cytokine-induced killer cells were intravenously injected into human hepatocellular carcinoma-bearing nude mice, together with intratumoral administration of the fusion protein hENG scFv/hIP-10 as an enhancer. The tumor volume and survival time of the mice were monitored, whilst the tumor-infiltrating cytokine-induced killer cells, serum levels of interferon-gamma, tumor cell proliferation, apoptosis, and angiogenesis were measured. The results demonstrated that hENG scFv/hIP-10 and cytokine-induced killer cells synergistically inhibited tumor growth and prolonged survival of tumor-bearing mice. Moreover, the number of tumor-infiltrating cytokine-induced killer cells, serum levels of interferon-gamma, and tumor cell apoptosis were increased, accompanied with decreased tumor proliferation and angiogenesis. Thus, our study suggests that hENG scFv/hIP-10 could enhance the anti-tumor activity of cytokine-induced killer cells against human hepatocellular carcinoma.

Evaluation of the efficacy of casein phosphopeptide-amorphous calcium phosphate on remineralization of white spot lesions in vitro and clinical research: a systematic review and meta-analysis.

BACKGROUND: This systematic review with meta-analyses sought to answer whether casein phosphopeptide-amorphous calcium phosphate (CPP-ACP) provided a remineralizing benefit superior to that of nonintervention or placebo. METHODS: Following Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines, Cochrane databases, PubMed, EmBase, and Ovid up to May 20th, 2019, were scanned, only published in English. Study information extraction and methodological quality assessments were accomplished independently by two reviewers. The "Criteria for judging risk of bias in the 'Risk of bias' assessment tool" was used for methodological quality assessment. The continuous data was analyzed by mean difference (MD) or standardized mean difference (SMD) with a 95% confidence interval (CI). Review Manager 5.3 was used for statistical analysis. Outcome variables include quantitative light-induced fluorescence in clinical research, average surface roughness and surface microhardness in vitro. RESULTS: There were significant differences in the quantitative light-induced fluorescence (SMD = - 0.43, 95% CI: [- 0.79, - 0.07], P = 0.02), average surface roughness (SMD = - 8.21, 95% CI: [- 10.37, - 6.04], P < 0.01), Vickers microhardness (SMD = 1.19, 95% CI: [0.72, 1.66], P < 0.01), and Knoop microhardness (SMD = 3.52, 95% CI: [2.68, 4.36], P < 0.01) between the CPP-ACP and control groups or baseline. CONCLUSION: Within the limitations of this meta-analysis, CPP-ACP exhibited excellent remineralization effects evaluated in clinical research and in vitro, indicating outstanding restoration of form, aesthetics, and function in treating white spot lesions.

Association Between the Asp312Asn, Lys751Gln, and Arg156Arg Polymorphisms in XPD and the Risk of Prostate Cancer.

Prostate cancer is the most common solid cancer and genetic factors play important roles in its pathogenesis. XPD is one of the 8 core genes involved in the nucleotide excision repair pathway. The relationship between Asp312Asn, Lys751Gln, and Arg156Arg polymorphisms in XPD and prostate cancer risk is a controversial topic. Therefore, we conducted a meta-analysis to explore the relationship between these 3 polymorphisms and the risk of developing prostate cancer. We searched the electronic literature in PubMed and Google Scholar for all relevant studies (last updated January 1, 2017). The pooled odds ratios and 95% confidence intervals for the associations between the Asp312Asn, Lys751Gln, or Arg156Arg polymorphisms in XPD and prostate cancer risk were calculated. To evaluate the effects of specific study characteristics on the association of these 3 polymorphisms and prostate cancer risk, we performed subgroup analysis if 2 or more studies were available. After an extensive literature review, 7 publications regarding Asp312Asn genotype distribution with 8 case-controls, 9 publications regarding Lys751Gln genotype distribution with 10 case-controls, and 3 publications regarding Arg156Arg genotype distribution with 4 case-controls were selected. The results showed that Asp312Asn (odds ratio = 1.34, 95% confidence interval: 0.96-1.87, P = .000), Lys751Gln (odds ratio = 0.98, 95% confidence interval: 0.89-1.08, P = .986), and Arg156Arg (odds ratio = 1.05, 95% confidence interval: 0.91-1.22, P = .57) polymorphisms do not increase the risk of prostate cancer in the dominant model. Further, in the subgroup analysis by ethnicity, no relationships were observed between Lys751Gln and Arg156Arg polymorphisms and prostate cancer risk. However, stratified analysis by ethnicity revealed that Asp312Asn affects African (odds ratio = 1.57, 95% confidence interval: 1.06-2.33, P = .382) and Asian populations (odds ratio = 2.09, 95% confidence interval: 1.39-3.14, P = .396) in homozygote comparison. In conclusion, this meta-analysis suggests that there is no general association between the Asp312Asn, Lys751Gln, and Arg156Arg polymorphisms in XPD and prostate cancer susceptibility.

Synthesis and Characterization of Polyamidoamine Dendrimers/Nano-hydroxyapatite and Its Role in Dentin Tubule Occlusion.

Objective To synthesis and characterization nano-composite biomaterials-polyamidoamine dendrimers/nano-hydroxyapatite (PAMAM/n-HAP),which has the properties of both organic and inorganic materials,and then evaluate its role in dentin tubule occlusion. Methods PAMAM/n-HAP was characterized and validated by Fourier transform infrared spectrometry and transmission electron microscopy after its preparation via the Pramanik aqueous-based chemical method. Scanning electron microscope was used to evaluate its role in dentin tublule occlusion. Results The peak absorption bands were found at 1244 cm-1 and 1650 cm-1 in Fourier transform infrared spectroscopy. A relatively low-density coating (about 10 nm) appeared on the n-HAP. The results of Fourier transform infrared spectrometry and transmission electron microscopy confirmed the successful synthesis of PAMAM/n-HAP. The scanning electron microscope showed that PAMAM/n-HAP could effectively reduce the diameter of the dentin tubule and close dentin tubule. Conclusion PAMAM/n-HAP,as a newly synthesized biomaterial,has a good binding capacity with collagen fibers with the help of superficial carboxyl. It can induce effective dentinal tubule occlusion,indicating that PAMAM/n-HAP have great potential in clinical practice for dentin hypersensitivity.

Fabrication and characterization of dendrimer-functionalized nano-hydroxyapatite and its application in dentin tubule occlusion.

The occlusion of dentinal tubules is an effective method to alleviate the symptoms of dentin hypersensitivity. In this paper, we successfully modified nano-hydroxyapatite (n-HAP) with carboxyl-terminated polyamidoamine dendrimers by an aqueous-based chemical method and verified by fourier transform infrared spectroscopy (FTIR) and transmission electron microscope (TEM). Then the demineralization dentin discs were randomly divided into 4 groups, corresponding to subsequent brushing experiments: deionized water and kept in artificial saliva (AS), dendrimer-functionalized n-HAP and stored in AS, n-HAP and saved in AS, dendrimer-functionalized n-HAP and stored in deionized water. After 7 days of simulated brushing, dentin discs followed the in vitro characterization using scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy and microhardness test. These data suggested that dendrimer-functionalized n-HAP could crosslink with collagen fibers and resulted in effective dentinal tubule occlusion. Moreover, the new material can induce the HAP formation with the help of superficial carboxyl and fill the spaces in dentinal tubules furtherly. The microhardness of dendrimer-functionalized n-HAP-treated specimens was significantly higher than others. In summary, dendrimer-functionalized n-HAP can be a new therapeutic material for the treatment of dentin hypersensitivity.

The HLA-DRB1 allele polymorphisms and nasopharyngeal carcinoma.

Human leukocyte antigen (HLA)-DRB1 has been reported to influence individual's susceptibility to nasopharyngeal carcinoma (NPC) by many studies in recent years; however, these studies provided controversial results. The meta-analysis was thus conducted here to estimate the relationship between HLA-DRB1 polymorphisms and NPC. After an extensive review of journals from various databases (PubMed, the Web of Science, Embase, China National Knowledge Internet (CNKI), and Wanfang Database), 8 out of 69 case-control studies, including 778 cases and 1148 controls, were extracted. The results showed that 4 of 13 polymorphisms allele are statistically significantly associated with NPC, among them, HLA-DRB1*3, HLA-DRB1*9, and HLA-DRB1*10 may increase the risk of NPC while HLA-DRB1*01 has the opposite effect. The pooled odds ratio and 95 % confidence interval (CI) were 1.702 [95 % CI (1.047, 2.765)], 1.363 [95 % CI (1.029, 1.806)], 1.989 [95 % CI (1.042, 3.799)], and 0.461 [95 % CI (0.315, 0.676)], respectively. In a further ethnicity-based subgroup analysis, HLA-DRB1*08, HLA-DRB1*11, and HLA-DRB1*16 were found to be linked with NPC in Asian, Tunisian, and Caucasian, respectively. In Asian, HLA-DRB1*03, 08, and 10 may elevate the risk whereas HLA-DRB1*09 could lower it. In Tunisian, HLA-DRB1*01 and 11 are the protective factors while HLA-DRB1*03 is the only risk factor. In Caucasian, HLA-DRB1*01 and 03 increase the risk and HLA-DRB1*16 lowers it. The most frequent statistically associated gene is found to be HLA-DRB1*03 which has protective influence on Asian and Tunisian. In conclusion, HLA-DRB1*01, DRB1*03, DRB1*09, and DRB1*10 are related with NPC susceptibility, and the association of HLA-DRB1*08, DRB1*11, and DRB1*16 with NPC risk are significantly different in different ethnicities.