Synthesis of CF3-Containing 2-Imidazolines and Imidazoles via a Iodide-Promoted [3 + 2] Cyclization Reaction.

We report herein a general and effective system achieving cyclization of ß-trifluoromethyl enones with amidines in the presence of 1,3-diiodo-5,5-dimethylhydantoin (DIH), which affords a range of trifluoromethylated 2-imidazolines in synthetically useful yields with good diastereoselectivities (up to 95% yield, up to 98:2 dr) and good functional group tolerance. Furthermore, the one-pot synthesis of trifluoromethylated imidazoles via sequential cyclization and oxidation is demonstrated. More significantly, the reaction mechanism was verified by ESI-MS studies of possible intermediates, and a reasonable reaction mechanism was proposed.

Metal-free hydrosulfonylation of α,ß-unsaturated ketones: synthesis and application of γ-keto sulfones.

γ-Keto sulfones are versatile building blocks and valuable intermediates in organic synthesis and pharmaceutical chemistry. Motivated by their excellent properties, we herein report a green, convenient, metal-free hydrosulfonylation method for a variety of ynones, vinyl ketones, and sodium sulfinates in the absence of stoichiometric oxidants. This operationally simple protocol provides straightforward and practical access to a wide range of γ-keto sulfones with broad functional group tolerance from easily available starting materials. Moreover, the ß,γ-unsaturated keto sulfones could further react with 2,3-butadienoate to generate cyclopentenes in phosphine-mediated [3 + 2] cycloaddition.

Phosphine-Catalyzed Atroposelective Formal [3 + 2] Cycloaddition Desymmetrization of N-Arylmaleimides.

Herein, a new strategy for the enantioselective synthesis of axially chiral N-aryl succinimides was devised by [3 + 2] annulation of MBH carbonates and N-aryl maleimides under chiral phosphine. This desymmetrization process allows for quick construction of both two stereogenic carbon centers and a remote CAr-N atropisomeric chirality. A series of structurally diverse N-aryl succinimides were obtained with good to excellent yields, diastereoselectivities, and enantioselectivities. The process is mild, efficient, and scalable and features a broad substrate scope.

Controlled release of minocycline in hydroxyapatite/chitosan composite for periodontal bone defect repair.

The aim was to obtain bone repair materials with sustained release of minocycline and evaluate the effect in periodontal bone defect repair. Two complex material, hydroxyapatite/chitosan (HA/CS) and minocycline-hydroxyapatite/chitosan (Mino-HA/CS), were prepared by the co-precipitation method. The physical and chemical property, cytotoxicity, release of minocycline and the bacteriostasis examination of the materials were evaluated, they were applied to the rabbit model of mandible bone defect to evaluate their effects on the regeneration of periodontal bone defect. After minocycline was added to HA/CS, the setting time of the material was prolonged, the compressive strength was reduced and the pore size and porosity were increased significantly. The pH value did not change obviously and stayed in the neutral range. Mino-HA/CS could promote the growth of osteoblasts effectively compared with control medium. In vivo, Mino-HA/CS material showed better effect of promoting periodontal bone formation.

Disrupted metabolic pathways and potential human diseases induced by bisphenol S.

Although the toxicity of bisphenol S has been studied in some species, the global metabolic network disrupted by bisphenol S remains unclear. To this end, published datasets related to the genes, proteins, and metabolites disturbed by bisphenol S were investigated through omics methods. The dataset revealed that bisphenol S at high concentrations tended to downregulate biomolecules, while low concentrations of bisphenol S tended to enhance metabolic reactions. The results showed that exposure to bisphenol S upregulated estrogen and downregulated androgen metabolism in humans, mice, rats, and zebrafish. Fatty acid metabolism and phospholipid metabolism in mice were upregulated. Reactions in amino acid metabolism were upregulated, with the exception of the suppressive conversion of arginine to ornithine. In zebrafish, fatty acid synthesis was promoted, while nucleotide metabolism was primarily depressed through the downregulation of pyruvate 2-o-phosphotransferase. The interference in amino acid metabolism by bisphenol S could trigger Alzheimer's disease, while its disturbance of glucose metabolism was associated with type II diabetes. Disturbed glycolipid metabolism and vitamin metabolism could induce Alzheimer's disease and diabetes. These findings based on omics data provide scientific insight into the metabolic network regulated by bisphenol S and the diseases triggered by its metabolic disruption.

Suppression of the long non-coding RNA MALAT-1 impairs the growth and migration of human tongue squamous cell carcinoma SCC4 cells.

INTRODUCTION: Aberrant expression of long non-coding RNAs (lncRNAs) is associated with metastasis and poor prognosis in patients with various cancer types. However, few studies have assessed lncRNAs in oral squamous cell carcinoma (OSCC). This study aimed to investigate the expression and impact of lncRNAs in OSCC. MATERIAL AND METHODS: Real-time PCR analysis was used to examine the expression of four lncRNAs, MALAT-1, UCA1, BC200 and SRA, in 14 OSCC and adjacent normal tissue pairs. The impact of MALAT-1 suppression by siRNA on the proliferation, apoptosis, anchorage-independent growth and migration of the human tongue carcinoma cell line SSC4 was also determined. RESULTS: MALAT-1 levels were significantly higher in the OSCC tissue than in the normal tissues (p < 0.004); no significant differences in UCA1, BC200 or SRA RNA levels were observed. Knockdown of MALAT-1 by siRNA significantly suppressed proliferation of SSC4 cells (p < 0.004) and enhanced their apoptosis (p < 0.001). In addition, siRNA-mediated suppression of MALAT-1 inhibited SSC4 cell colony formation (p < 0.001) and migration (p < 0.004). CONCLUSIONS: Elevated expression of MALAT-1 in OSCC may play a role in tumorigenesis and/or metastasis. Further studies are necessary to identify the mechanism by which MALAT-1 influences SCC4 growth and migration and validate its increased expression in OSCC patients.

Low-Intensity Pulsed Ultrasound Treatment Accelerates Angiogenesis by Activating YAP/TAZ in Human Umbilical Vein Endothelial Cells.

As a non-invasive method, low-intensity pulsed ultrasound (LIPUS) can accelerate fracture healing. The mechanisms responsible for the enhanced fracture healing need to be studied further. Activation of YAP/TAZ, key mediators of the Hippo signaling pathway, could promote angiogenesis and vascular remodeling. The purpose of this study was to determine whether LIPUS treatment can activate YAP/TAZ. Human umbilical vein endothelial cells (HUVEC) were used. After LIPUS treatment, Western blot and immunofluorescence staining were used for YAP/TAZ activation. Small interfering RNA (siRNA) of YAP and short hairpin LATS1/2 (shLATS1/2) were used to check whether there is cross-talk with the Hippo pathway. The phosphorylated YAP (p-127 and p-397) protein increased more than 3-fold 0.5 h after LIPUS treatment (p < 0.05). TAZ protein increased 3.0-, 2.0- and 1.5-fold 0.5, 6 and 12 h after LIPUS treatment. We found that LIPUS treatment activates YAP/TAZ, which is translocated into the cell nucleus to activate target genes. This process can be inactivated by siYAP and activated by shLATS1/2. The cross-talk with the Hippo pathway can initiate angiogenesis so as to accelerate fracture healing by LIPUS.

Bone Morphogenetic Protein-9 Enhances Osteogenic Differentiation of Human Periodontal Ligament Stem Cells via the JNK Pathway.

Bone morphogenetic protein-9 (BMP9) shows great osteoinductive potential in bone regeneration. Periodontal ligament stem cells (PDLSCs) with multi-differentiation capability and low immunogenicity are increasingly used as seed cells for periodontal regenerative therapies. In the present study, we investigated the potent osteogenic activity of BMP9 on human PDLSCs (hPDLSCs), in which the c-Jun N-terminal kinase (JNK) pathway is possibly involved. Our results showed that JNK inhibition by the specific inhibitor SP600125 or adenovirus expressing small interfering RNA (siRNA) targeting JNK (AdR-si-JNK) significantly decreased BMP9-induced gene and protein expression of early and late osteogenic markers, such as runt-related transcription factor 2 (Runx2), alkaline phosphatase (ALP), osteopontin (OPN), and osteocalcin (OCN), in hPDLSCs. We also confirmed the in-vivo positive effect of JNKs on ectopic bone formation induced by hPDLSCs injected into the musculature of athymic nude mice and BMP9 ex vivo gene delivery. For the cellular mechanism, we found that BMP9 activated the phosphorylation of JNKs and Smad2/3, and that JNKs may engage in cross-talk with the Smad2/3 pathway in BMP9-mediated osteogenesis.

Calcitonin induces collagen synthesis and osteoblastic differentiation in human periodontal ligament fibroblasts.

BACKGROUND: Extracellular matrix (ECM) secretion and osteogenic differentiation in periodontal ligament fibroblasts (PDLF) facilitate the neogenesis of alveolar bone, which is the cellular basis for alveolar bone repair. Calcitonin (CT) has been reported to play an important role in promoting ECM expression and inducing osteogenic differentiation in osteoblast, but its effects on PDLFs remain obscure. METHODS: The expression of CT, transforming growth factor-beta 1(TGF-ß1) and bone morphogenetic protein (BMP) in gingival crevicular fluid (GCF) was measured by ELISA. The effects of CT on collagen synthesis and osteogenic differentiation in hPDLFs were investigated by using the primarily cultured hPDLFs infected with adenovirus carrying the CT gene. Gene expression was measured by quantitative PCR and western blot. RESULTS: The expression of CT in gingival crevicular fluid (GCF) of patients with periodontitis was significantly higher than that of healthy subjects. In addition, CT expression correlated with the clinical indexes including probing pocket depth (PPD), clinical attachment level (CAL), and gingival index (GI). The in vitro study demonstrated that overexpression of CT by adenovirus infection increased the expression of TGF-ß1, collagen type I and III, and osteoblastic markers including BMP-2/-4, alkaline phosphatase and osteocalcin in human PDLFs. Moreover, CT-enhanced collagen synthesis was abrogated in hPDLFs transfected with TGF-ß1 siRNA, and CT-induced osteoblastic differentiation was blocked in hPDLFs by BMPs inhibitor noggin. CONCLUSIONS: These results suggest that CT promotes collagen synthesis and osteogenic differentiation in hPDLFs via the TGF-ß1 and BMPs signaling pathways, respectively.

Validation of a Chinese version of the Chronic Pain Acceptance Questionnaire (CAPQ) and CPAQ-8 in chronic pain patients.

Acceptance of chronic pain has increasingly become a significant issue in the field of pain management. Many researchers have suggested that patients with better acceptance of pain are more likely to have better functioning both in physical and psychological status. In many countries, the Chronic Pain Acceptance Questionnaire (CPAQ) and CPAQ-8 have been validated and utilized frequently to measure the pain acceptance of patients with chronic pain. However, the CPAQ and CPAQ-8 yet have not been introduced and validated in Mainland China.In this study, we aimed to translate the English version of the CPAQ into simplified Chinese, make proper cross-cultural adaptations, and validate the psychometric properties of the Chinese version of the CPAQ and the CPAQ-8.The English version of the CPAQ was first linguistically translated and cross-culturally adapted to formulate a Chinese version. Then, we recruited 224 patients from a pain clinic and every participant was asked to finish a series of questionnaires. Finally, statistical analysis was performed to test the psychometric properties of the CPAQ and the CPAQ-8.Both confirmatory factor analysis (CFA) and principal component analysis (PCA) confirmed a 2-factor structure for the CPAQ and the CPAQ-8. Nine out of 10 of the hypotheses were validated for construct validity. The overall intraclass correlation coefficient (ICC) value for the CPAQ and CPAQ-8 were 0.92 and 0.89, respectively. In addition, the Cronbach α values for both the CPAQ and the CPAQ-8 showed excellent test-retest reliability.In conclusion, the original CPAQ was successfully developed into the Chinese version of the CPAQ and CPAQ-8 with excellent validity and reliability. The scores of the CPAQ or CPAQ-8 might be a strong predictor for the physical and psychological function of chronic pain patients. In addition, to improve the satisfaction of surgery patients, we recommend measuring patients' pain acceptance using the CPAQ or CPAQ-8 before and after the surgery. For patients with lower acceptance, psychological interventions may be more effective than treatment that simply reduces symptoms. Finally, we suggest that the Chinese version of the CPAQ and CPAQ-8 are appropriate for use in clinical settings or fundamental research in Mainland China.

[Management of apicectomy and root canal obturation completed one time under direct vision].

PURPOSE: To evaluate the clinical effect of apicectomy and root canal obturation completed one time under direct vision on chronic periapical periodontitis of anterior teeth. METHODS: 34 cases(40 teeth) with RCT failing or larger periodontal lesion, which couldn't be cured depending on RCT only, were chosen for this clinical study. They were randomly divided into two groups with 20 teeth in each group. Root canal obturation was done after apicectomy under direct vision(group A),or apicectomy was done after RCT(group B).The time of filling process, the ratio of postobturation pain, the obturation quality and short-term efficiency of the treatment were assessed. The data were separately subjected to t test, Chi-square test, Mann-Whitney U test with SPSS12.0 software package. RESULTS: The time of filling process in group A was significantly less than group B (P<0.05); No statistically significant difference was found between group A and group B in the ratio of postobturation pain, obturation quality and clinical therapeutic efficiency. CONCLUSIONS: The method of apicectomy and root canal obturation completed one time under direct vision is rapid, simple and effective in treating chronic periapical periodontitis of anterior teeth.The short-term clinical therapeutic efficiency is similar to that of apicectomy done after RCT.