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Objectives: This study aimed to elucidate the connection between osteoclastic forkhead transcription factor O1 (FoxO1) and periodontitis and explore the underlying mechanism by which FoxO1 knockdown regulates osteoclast formation. Materials and Methods: A conventional ligature‐induced periodontitis model was constructed to reveal the alterations in the proportion of osteoclastic FoxO1 in periodontitis via immunofluorescence staining. Additionally, RNA sequencing (RNA‐seq) was performed to explore the underlying mechanisms of FoxO1 knockdown‐mediated osteoclastogenesis, followed by western blotting, quantitative polymerase chain reaction, and enzyme‐linked immunosorbent assay. Results: FoxO1+ osteoclasts were enriched in the alveolar bone in experimental periodontitis. Moreover, FoxO1 knockdown led to impaired osteoclastogenesis with low expression of osteoclast differentiation‐related genes, accompanied by an insufficient osteoclast maturation phenotype. Mechanistically, RNA‐seq revealed that the nuclear factor kappa B (NF‐κB) and nucleotide‐binding oligomerization domain‐like receptor family pyrin domain containing 3 (NLRP3) inflammasome signaling pathways were inhibited in FoxO1‐knockdown osteoclasts. Consistent with this, MCC950, an effective inhibitor of the NLRP3 inflammasome, substantially attenuated osteoclast formation. Conclusions: FoxO1 knockdown contributed to the inhibition of osteoclastogenesis by effectively suppressing NF‐κB signaling and NLRP3 inflammasome activation. This prospective study reveals the role of FoxO1 in mediating osteoclastogenesis and provides a viable therapeutic target for periodontitis treatment. [ABSTRACT FROM AUTHOR]

Litchi (Litchi chinensis Sonn.) is a famous fruit in south China, and it is also effective for chest tightness or chest pain, irritability, flatulence, epigastric pain and neuralgic pain, hernia pain and testicular swelling, cough, etc. It is valued because a great amount of polyphenol was found in litchi pericarp. In this paper, we got litchi pericarp pure extract by a simple purification method, then evaluated its activity to clear oxygen free radicals in vitro, and evaluated its myocardial protection effect in vivo through acute myocardial ischemia rat model. The results showed that the pure extract had protective effect on myocardial ischemia injury in a certain dose-effect relationship, which reflected in the electrocardiogram, myocardial pathological morphology and other indicators such as cardiac function enzymes, serum and myocardial antioxidant capacity, and eNOS, Bcl-2 and Bax gene expression. Furthermore, we analyzed the components of pure extract by UPLC-MS, ESI-MS and NMR. The main components of PLPE were procyanidin which were identified as procyanidin B2(1), (-)-epicatechin(2), epicatechin-(4β → 8,2β → O → 7)-epicatechin-(4β → 8)-epicatechin(3), A-type procyanidin trimer(4), B-type procyanidin dimer(5) and procyanidin A2(6).This study proved that litchi pericarp extract may have antioxidant activity and cardioprotection effect. It suggested that litchi pericarp may be good for cardiovascular disease. Copyright © 2017 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

A meta‐analysis was performed to assess the effects of different regenerative technologies and materials on wound healing after surgical endodontic therapy and provide a reference for surgical endodontic treatment. We searched for studies on the use of regenerative technologies and materials in surgical endodontic therapy via PubMed, MEDLINE, EMBASE, Web of Science, China National Knowledge Infrastructure (CNKI), and Wanfang Data from the time of database creation to December 2022. Two researchers independently screened the literature, extracted information based on the inclusion and exclusion criteria, and evaluated the quality of the included studies. A meta‐analysis was performed using Review Manager 5.4. The results showed that the use of regenerative technologies and materials significantly reduced wound healing failures (risk ratio [RR]: 0.30, 95% confidence intervals [CI]: 0.22–0.40, p < 0.001). Moreover, autologous platelet concentrations (APCs) (RR: 0.28, 95% CI: 0.15–0.53, p < 0.001) and collagen membrane plus bovine‐derived hydroxyapatite (RR: 0.27, 95% CI. 0.12–0.61, p = 0.002) were more effective in improving wound healing failure rates than collagen membrane alone (RR: 0.51, 95% CI: 0.20–1.25, p = 0.140). Our findings showed that APCs, as well as collagen membrane plus bovine‐derived hydroxyapatite, significantly improved wound healing after surgical endodontic therapy. In contrast, collagen membrane alone did not significantly improve wound healing outcomes. However, currently available studies vary significantly in sample size and methodologies. Hence, high‐quality randomised controlled studies with large sample sizes are necessary to validate our findings. [ABSTRACT FROM AUTHOR]

Background: The mortality of cervical cancer (CC) is quite high and advanced CC is hard to cure. Accordingly, to find the mechanism of CC progression at molecular level is imminent. Methods: The mRNA expression data were acquired from The Cancer Genome Atlas database, and squalene epoxidase (SQLE) level in the tumor and adjuvant tissues of CC was analyzed. The pathway enrichment analysis of target mRNAs was performed based on the GSEA database. The cancerous tissues and para‐cancerous tissues of CC patients were collected for immunohistochemistry. SQLE and p53 mRNA expression was ensured by qRT‐polymerase chain reaction. SQLE and p53 protein levels were determined by western blot. Cell functional assays focused on evaluating the malignant behaviors of cancer cells in each treatment group. Nude mouse xenograft models were constructed for tumorigenicity analysis. Results: Bioinformatics analysis revealed that SQLE expression was high in CC tissues, which was linked to the poor prognosis. SQLE could affect the p53 signaling pathway. Cell functional assays demonstrated that SQLE expression was promoted in CC cell lines, and overexpressing SQLE facilitated the malignant phenotypes of CC cells, whereas silencing SQLE suppressed CC progression in vitro and in vivo. Besides, the repressed p53 signaling pathway could reverse the effect caused by silenced SQLE. Conclusion: SQLE could promote CC progression by modulating the p53 signaling pathway. [ABSTRACT FROM AUTHOR]

Background: Circular RNAs (circRNAs) have been reported to play roles in lung cancer development. The purpose of this work was to explore the function and mechanism of circ_0043256 in lung cancer tumorigenesis. Methods: Quantitative real‐time polymerase chain reaction (qRT‐PCR) and western blot were used for the detection of the levels of genes and proteins. Cell growth, angiogenesis ability, migration, and invasion were analyzed by using 5‐ethynyl‐2′‐deoxyuridine (EdU) assay, flow cytometry, tube formation assay, transwell assay, and murine xenograft model, respectively. The target between miR‐1206 and circ_0043256 or Krüppel‐like factor 2 (KLF2) was verified by dual‐luciferase reporter assay. Results: Circ_0043256 was a stable circRNA, which was found to be decreased in lung cancer tissues and cells. Functionally, forced expression of circ_0043256 suppressed lung cancer cell growth, angiopoiesis, migration, and invasion. Mechanistically, circ_0043256 directly bound to miR‐1206 and miR‐1206 targeted KLF2, circ_0043256 could regulate KLF2 expression via absorbing miR‐1206. Rescue assay showed that miR‐1206 overexpression reversed the anticancer effects of circ_0043256 on lung cancer cells. Moreover, inhibition of miR‐1206 could suppress the malignant phenotypes of lung cancer cells, which was attenuated by KLF2 knockdown. Pre‐clinically, lentivirus‐mediated circ_0043256 overexpression impeded lung cancer growth in nude mice. Conclusion: Forced expression of circ_0043256 could impede the tumorigenesis of lung cancer via miR‐1206/KLF2 axis, indicating a potential therapeutic approach for lung cancer. [ABSTRACT FROM AUTHOR]

Background: Oncolytic viral therapy is a promising method for tumor treatment. Currently, several oncolytic viruses (OVs) have been used as tumor therapy at different phases of research and clinical trials. OVs not only directly lyse tumor cells due to viral replication but also initiate host antitumor immune responses. Previous studies have primarily focused on how OVs activate adaptive immune responses in immune cells. However, the role of innate immune responses in tumors induced by OVs remains unclear. Methods: To determine the innate immune responses induced by vesicular stomatitis virus (VSV), the mutant VSVΔM51 strain was used for the infection and quantitative polymerase chain reaction (qPCR) was employed to measure the transcriptional levels of antiviral genes. The knockdown efficiency of RIG‐I was examined by qPCR. Viral titers were measured by plaque assays. Tumor models were established by intradermally implanting RIG‐I‐knockdown and control LLC cells into the flank of wild type C57BL/6J mice. When the tumors reached approximately 50mm3, they were infected with VSVΔM51 via intratumoral injections to examine its therapeutic effect. Results: Infection with VSVΔM51 triggered remarkable innate immune responses in several tumor cell lines through the cytoplasmic RIG‐I sensing pathway. Moreover, we found that intratumoral injection of VSVΔM51 effectively reduced tumor growth in murine LCC lung cancer model. Importantly, VSVΔM51‐induced antitumor therapy was more effective in murine LLC tumor model established using Rig‐I‐knockdown cells compared with the tumor model established using control cells. Conclusion: RIG‐I‐mediated innate immune signaling in tumor cells plays a negative role in regulating antitumor therapy with VSVΔM51 virus. [ABSTRACT FROM AUTHOR]

Cholestasis causes hepatic accumulation of bile acids leading to liver injury, fibrosis and liver failure. Paeoniflorin, the major active compound isolated from the roots of Paeonia lactiflora pall and Paeonia veitchii Lynch, is extensively used for liver diseases treatment in China. However, the mechanism of paeoniflorin's hepatoprotective effect on cholestasis has not been investigated yet. In this study, we administered paeoniflorin to rats for 3 days prior to alpha-naphthylisothiocyanate (ANIT) administration for once, then went on administering paeoniflorin to rats for 3 days. The data demonstrated that paeoniflorin significantly prevented ANIT-induced change in serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphates (ALP), serum total bilirubin (TBIL), direct bilirubin (DBIL), total bile acid (TBA) and gamma-glutamyl transpeptidase (γ-GT). Histology examination revealed that paeoniflorin treatment rats relieved more liver injury and bile duct proliferation than ANIT-administered rats. Moreover, our data indicated that paeoniflorin could restore glutathione (GSH) and its related synthase glutamate-cysteine ligase catalytic subunit (GCLc) and glutamate-cysteine ligase modifier subunit (GCLm) in ANIT-treated group. In addition, the RNA and protein expression of Akt and nuclear factor-E2-related factor-2 (Nrf2) were also activated by paeoniflorin in ANIT-induced rats. These findings indicated that paeoniflorin protected ANIT-induced cholestasis and increased GSH synthesis by activating Nrf2 through PI3K/Akt-dependent pathway. Therefore, paeoniflorin might be a potential therapeutic agent for cholestasis. [ABSTRACT FROM AUTHOR]

Objective The objective of this study was to investigate the effects of osteoprotegerin ( OPG) gene therapy on alveolar bone resorption caused by experimental periodontitis in rats, thus forming a foundation for potential clinical applications of OPG gene therapy in the treatment of periodontitis and peri-implantitis. Material and Methods To study the effects of OPG on alveolar bone protection, an experimental periodontitis model was used by placing a bacterial plaque retentive silk ligature in the gingival sulcus around the maxillary second molar tooth, injection of Porphyromonas gingivalis and high carbohydrate diet. A total of 30 Sprague-Dawley rats were randomly divided into three groups, with 10 rats in each group: group I (control) was treated with 10 μL normal saline injection; group II with 10 μL mock vector; and group III with 10 μL local OPG gene transfer by transfection with in vitro constructed pcDNA3.1- human OPG (pcDNA3.1-hOPG). A subperiosteal injection was done adjacent to the second molars on days 0, 7, 14 and 21. Four weeks later, all animals were killed and radiographic, histological and immunohistochemical examinations were performed. Statistical analysis included ANOVA and LSD-Bonferroni test. Results Group III ( OPG gene therapy) had significantly enhanced ( p < 0.05) integrated optical density of OPG, had significantly decreased alveolar bone resorption volume and active osteoclast number ( p < 0.05) through descriptive histological examination when compared with the other two groups at week 4. Conclusion Local recombinant OPG plasmid-mediated gene therapy suppresses osteoclastogenesis in vivo and inhibits alveolar bone height reduction caused by experimental periodontitis in rats. OPG gene therapy may be beneficial in preventing progressive periodontal bone loss. [ABSTRACT FROM AUTHOR]

Background Kirsten rat sarcoma ( KRAS) mutations are widespread in lung adenocarcinoma patients. The combined utilization of KRAS antisense oligodeoxynucleotide ( ASODN) and insulin-like growth factor- I receptor ( IGF-IR) may inhibit the proliferation of A549 cell lines of lung adenocarcinoma. Methods Point mutations of the KRAS gene in A549 cells were detected by polymerase chain reaction with special sequence primers ( PCR-SSP) and gene sequence analysis; ASODN was designed and synthesized according to the mutation specialty of KRAS; and the correlation of gene mutations and clinicopathological features were analyzed. Inhibition on the proliferation and morphostructure change were measured by methyl thiazolyl tetrazolium and colony-forming unit assays. Flow cytometry was used to evaluate the expression of KRAS and IGF-IR proteins and cell apoptosis and reverse transcriptase-polymerase chain reaction were used to detect the expression of KRAS and IGF-IR messenger ribonucleic acid ( mRNA). Male nude mice were used to form the mice-human lung cancer model and show the inhibition of KRAS ASODN on A549 cells. Results PCR-SSP and gene sequence analysis results showed that the codon 12 of KRAS had changed from GGT to GTT. KRAS ASODN or IGF-IR ASODN could inhibit cell proliferation and promote apoptosis of A549 cells. However, the combined utilization of KRAS ASODN and IGF-IR ASODN could inhibit cell proliferation and promote apoptosis more powerfully than exclusive use of KRAS ASODN or IGF-IR ASODN. Conclusion The two ASODNs can inhibit the proliferation of lung adenocarcinoma cells through decreasing the expression of KRAS and IGF-IR mRNA and protein. [ABSTRACT FROM AUTHOR]

Aim To evaluate the effects of non-equilibrium plasma in the treatment of ligature-induced peri-implantitis in beagle dogs. Materials and Methods Six beagles received 12 implants installed in the position of the fourth mandibular premolars. Ligature-induced peri-implantitis was initiated at 3 months post-implantation. When approximately 40% of the supporting bone was lost, the ligatures were removed. The implants were subjected to the muco-periosteal scaling and chlorhexidine irrigation with or without plasma irrigation. Three months later, clinical, radiographic and microbiological analyses were performed. Block biopsies were prepared for micro- CT and histomorphometric analysis. The primary outcome was the difference in bone healing of peri-implant sites, and the secondary outcomes included changes in clinical parameters ( SBI, PD) and bacterial detection. Results At baseline, no significant differences were observed between the two groups. At 3 months post-treatment, the plasma group showed a significantly higher bone level than the control group ( p < 0.05), a significantly decreased detection of bacteria ( Porphyromonas gingivalis and Tannerella forsythia) ( p < 0.05), and a significant improvement in clinical examination ( p < 0.05). Conclusions Within the limits of this study, non-equilibrium plasma treatment as an adjunct to the conventional therapy is a feasible approach for the treatment of peri-implantitis. [ABSTRACT FROM AUTHOR]

Background: The optimal chemotherapy route for non-small cell lung cancers involving the phrenic nerve and diaphragmis unclear.The pharmacokinetic properties of paclitaxel following intravenous (IV) or intrapleural (IP) administrationwere analyzed in the plasma, lung, and diaphragm in a rat model. The purpose of this study was to determine whether IP injection increased paclitaxel concentration in the diaphragm. Methods: Paclitaxel was administered by IV or IP to male Sprague-Dawley rats. The concentration of drug in the plasma, lung, and diaphragm was determined using liquid chromatography-tandem mass spectrometry (LC-MS/MS).The pharmacokinetic parameters area under the curve (AUC), mean residence time (MRT), peak plasma concentration (Cmax), and half-life (t1/2) were analyzed. Results: Paclitaxel concentration in the plasma, lung, and diaphragm decreased quickly following IV administration.However, after IP injection, paclitaxel reached a high concentration in the plasma, lung, and diaphragmthat declined gradually. Significant differences in all parameters, except Cmax in the lung,were observed between the two routes of administration (all P < 0.05). Plasma exposure to paclitaxel IP was 41.1% of that observed after IV in the first 24 hours (P < 0.05). IP also significantly increased exposure of paclitaxel in comparison with IV administration to 267.3% and 905.7% of IV administration in the lung and diaphragm, respectively (P < 0.05). Conclusion: These results suggest that IP administration may reduce systemic distribution of paclitaxel and increase the concentration in the lung and diaphragm. This could increase therapeutic efficacy by increasing the available drug and reduce systemic toxicity. [ABSTRACT FROM AUTHOR]

Objective This study was designed to investigate the effects of mineral trioxide aggregate (MTA) on the osteo/odontogenic differentiation of inflammatory dental pulp stem cells (i DPSCs). Materials and Methods inflammatory DPSCs were isolated from the inflammatory pulps of rat incisors and cocultured with MTA-conditioned medium. MTT assay and flow cytometry were performed to evaluate the proliferation of i DPSCs. Alkaline phosphatase ( ALP) activity, alizarin red staining, real-time RT- PCR, and Western blot assay were used to investigate the differentiation capacity as well as the involvement of NF-κB pathway in i DPSCs. Results Mineral trioxide aggregate-treated i DPSCs demonstrated the higher ALP activity and formed more mineralized nodules than the untreated group. The odonto/osteoblastic markers ( Alp, Runx2/RUNX2, Osx/OSX, Ocn/OCN, and Dspp/DSP, respectively) in MTA-treated i DPSCs were significantly upregulated as compared with untreated i DPSCs. Mechanistically, cytoplastic phos-P65 and nuclear P65 in MTA-treated i DPSCs were significantly increased in a time-dependent manner. Moreover, the inhibition of NF-κB pathway suppressed the MTA-induced odonto/osteoblastic differentiation of i DPSCs, as indicated by decreased ALP levels, weakened mineralization capacity and downregulated levels of odonto/osteoblastic genes ( Osx, Ocn, and Dspp). Conclusions Mineral trioxide aggregate enhances the odonto/osteogenic capacity of DPSCs from inflammatory sites via activating the NF-κB pathway. [ABSTRACT FROM AUTHOR]

1. Plateau pikas Ochotona curzoniae are considered a pest species on the Tibetan Plateau because they compete with livestock for forage and their burrowing could contribute to soil erosion. The effectiveness of pest control programmes in Tibet has not been measured, and it is not known whether changes in livestock management have exacerbated problems with plateau pikas or compromised their control. This study measured the impact of control programmes and livestock management for forage conservation on populations of plateau pikas in alpine meadow in Naqu District, central Tibet, during 2004 and 2005. 2. Current techniques for controlling plateau pikas in spring cause large reductions in abundance, but high density-dependent rates of increase result in no differences between treated and untreated populations by the following autumn. Rates of increase from spring to autumn are not influenced by standing plant biomass or concurrent grazing by yaks Bos grunniens and Tibetan sheep Ovis aries. 3. In autumn there was significantly lower biomass outside fenced areas with year-round livestock grazing compared with inside fenced areas with equivalent or higher numbers of plateau pikas but predominantly winter grazing by livestock. Inside fenced areas, control of plateau pikas in spring produced no detectable effect on standing plant biomass at the end of the following summer compared with uncontrolled populations of plateau pikas. 4. Regardless of their initial density, populations of plateau pikas declined rapidly over winter outside fenced areas where there was very low standing plant biomass in autumn. However, inside fenced areas with higher plant biomass in autumn, low-density populations of plateau pikas declined more slowly than high-density populations. 5. Synthesis and applications. Current control programmes have limited effect because populations of plateau pikas can recover in one breeding season. There was no apparent increase in forage production in areas where plateau pikas were controlled. However, plateau pikas appear to benefit from changes in grazing management, with low-density populations declining less over winter inside fenced areas than elsewhere. It was not evident that control programmes are warranted or that they will improve the livelihoods of Tibetan herders. [ABSTRACT FROM AUTHOR]