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1.
J Cell Physiol ; 235(1): 221-231, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31187497

RESUMO

The motility of mesenchymal stem cells (MSCs) is highly related to their homing in vivo, a critical issue in regenerative medicine. Our previous study indicated copper (Cu) might promote the recruitment of endogenous MSCs in canine esophagus defect model. In this study, we investigated the effect of Cu on the motility of bone marrow mesenchymal stem cells (BMSCs) and the underlying mechanism in vitro. Cu supplementation could enhance the motility of BMSCs, and upregulate the expression of hypoxia-inducible factor 1α (Hif1α) at the protein level, and upregulate the expression of rho family GTPase 3 (Rnd3) at messenger RNA and protein level. When Hif1α was silenced by small interfering RNA (siRNA), Cu-induced Rnd3 upregulation was blocked. When Rnd3 was silenced by siRNA, the motility of BMSCs was decreased with or without Cu supplementation, and Cu-induced cytoskeleton remodeling was neutralized. Furthermore, overexpression of Rnd3 also increased the motility of BMSCs and induced cytoskeleton remodeling. Overall, our results demonstrated that Cu enhanced BMSCs migration through, at least in part, cytoskeleton remodeling via Hif1α-dependent upregulation of Rnd3. This study provided an insight into the mechanism of the effect of Cu on the motility of BMSCs, and a theoretical foundation of applying Cu to improve the recruitment of BMSCs in tissue engineering and cytotherapy.

2.
AIDS Care ; 32(1): 12-20, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31142146

RESUMO

This study was to compare global and domain-specific neurocognitive performance between older people living with HIV (PLWH) taking/not taking efavirenz (EFV) and HIV-negative controls. A cross-sectional study was conducted in Yongzhou city, China. All PLWH older than 50 years listed on the registry of Centres for Disease Control and Prevention were invited to join the study. Frequency matching was used to sample HIV-negative controls according to the distribution of age, sex, and years of formal education of older PLWH. A total of 308 older PLWH and 350 HIV-negative controls completed the face-to-face interview and neurocognitive assessment using the comprehensive neuropsychological test battery. After adjusting for significant confounders, older PLWH taking EFV showed poorer performance in memory (p = 0.020), verbal fluency (p = 0.002), and poorer global neurocognitive performance (p = 0.032) than those without EFV use. Compared to HIV-negative controls, older PLWH taking EFV had poorer performance in all neurocognitive domains (p values: <0.001-0.003) and poorer global neurocognitive performance (p < 0.001). Similar trends were observed when comparing older PLWH without using EFV versus HIV-negative controls, with the exception of verbal fluency (p = 0.560). Health care workers should monitor the neuropsychological performance of older PLWH, epically those who were taking EFV. Longitudinal studies are warranted.

3.
Mater Sci Eng C Mater Biol Appl ; 106: 110286, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31753397

RESUMO

Autologous chondrocyte implantation (ACI) is a promising approach to repair cartilage defects; however, the cartilage trauma-induced inflammatory environment compromises its clinical outcomes. Cell-derived decellularized extracellular matrix (DECM) has been used as a culture substrate for mesenchymal stem cells (MSCs) to improve the cell proliferation and lineage-specific differentiation. In this study, DECM deposited by synovium-derived MSCs was used as an in vitro expansion system for rabbit articular chondrocytes and the response of DECM-expanded chondrocytes to pro-inflammatory cytokines such as interleukin-1ß (IL-1ß) and tumor necrosis factor-α (TNF-α) was evaluated. Compared with those grown on tissue culture polystyrene (TCPS), the proliferation rate was significantly improved in DECM-expanded chondrocytes. TCPS- and DECM-expanded chondrocytes were isolated and induced to redifferentiation in a high-density pellet culture. DECM-expanded chondrocytes exerted a stronger resistance to 1 ng/mL of IL-1ß than TCPS-expanded cells, but the production of cartilage matrix in both groups was inhibited by 5 ng/mL of IL-1ß. When exposed to 1 or 5 ng/mL of TNF-α, DECM-expanded chondrocytes showed higher levels of cartilage matrix synthesis than TCPS-expanded cells. In addition, the gene expression of IL-1ß- or TNF-α-induced matrix degrading enzymes (MMP3, MMP9, MMP13, and ADAMTS5) was significantly lower in DECM-expanded chondrocytes than TCPS-expanded cells. Furthermore, we found that SIRT1 inhibition by nicotinamide completely counteracted the protective effect of DECM on chondrocytes in the presence of IL-1ß or TNF-α, indicating that the SIRT1 signaling pathway was involved in the DECM-mediated enhancement of anti-inflammatory properties of chondrocytes. Taken together, this work suggests that stem cell-derived DECM is a superior culture substrate for in vitro chondrocyte expansion by improving proliferation and enhancing the anti-inflammatory properties of chondrocytes. DECM-expanded chondrocytes with enhanced anti-inflammatory properties hold great potential in clinically ACI-based cartilage repair.

4.
Methods Mol Biol ; 2084: 269-282, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31729667

RESUMO

Untargeted lipidomics aims to comprehensively measure and characterize all lipid species in biological systems. Ion mobility-mass spectrometry (IM-MS) has showed a great potential for untargeted lipidomic analysis. Coupling with liquid chromatography and data-independent tandem MS techniques, acquired IM-MS data set contains four-dimensional information for lipid identification, including m/z of MS1 ion, retention time (RT), collision cross section (CCS), and MS/MS spectra. In this protocol, we introduced a data processing workflow using an integrative web server, namely, LipidIMMS Analyzer, to support accurate lipid identification. The protocol demonstrated the integration of all four dimensional information to achieve unambiguous identifications of lipids in complex biological samples.

5.
Chemosphere ; 238: 124603, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31442773

RESUMO

Environmental pollution is a risk factor for kidney dysfunction. However, the combined toxicity of air pollutants on kidney function is scarce. We estimated the relationship between combined toxicity of air pollutants and kidney function among adult women (n = 7071, 18-65 years old) in Mianyang City, Southwest China. We measured serum concentrations of uric acid, urea, creatinine, and cystatin C, and we calculated the individual estimated glomerular filtration rate (eGFR) using a cystatin C-based equation developed specifically for Chinese patients with CKD equation. Air pollution data were collected to calculate the individual average daily dose (ADD) of pollutants based on the air quality complex index (AQCI). Mean AQCI was higher in winter and lower in summer, and followed the monthly and seasonal trends of air pollutants. Concomitantly, individual ADD was also higher in winter and lower in summer, and the seasonal differences were reflected in the levels of kidney biomarkers (including uric acid, urea, creatinine, cystatin C, and eGFR). With an interquartile range (IQR: 1.04-1.50 m3/day/kg) increases of ADD, the serum concentrations of uric acid, urea, creatinine, and cystatin C increase [B (95%CI): 1.774 (0.318, 3.231) umol/L, 0.218 (0.1888, 0.247) mmol/L, 1.501 (1.016, 1.986) umol/L, and 0.006 (0.003, 0.009) mg/L, respectively], whereas eGFR decreases [B (95%CI): -0.776 (-1.106, -0.446) mL/min/1.73 m2]. Totally, the relationship between combined toxicity of air pollutants and kidney function in Chinese adult women suggests that the toxicity of combined air pollutants inversely affects kidney function, which might accelerate the risk of CKD.

6.
Opt Express ; 27(19): 26295-26306, 2019 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-31674514

RESUMO

In this paper, by adaptively partitioning and precoding the subcarriers, we proposed a practical and effective entropy loading (EL) scheme for single sideband discrete multi-tone (SSB-DMT) systems. To reveal the practical performance, information bits per symbol (IBPS) is used to identify the optimal probabilistically shaped quadrature amplitude modulation (PS-QAM). Under the constraint of normalized generalized mutual information (NGMI) of the off-the-shelf forward error correction (FEC), we obtain the PS-QAMs that achieve the maximum IBPS using different constellations for different signal-to-noise ratio (SNR). Based on the result, we proposed two adaptively partitioning methods, equally partitioned precoding (EPP) and optimally partitioned precoding (OPP), to perform hybrid constellation entropy loading (HCEL). The HCEL with OPP significantly reduces the number of distribution matcher to 3 from generally several hundred of conventional EL with negligible loss of net data rate (NDR). As demonstrated by experiments, the HCEL with OPP achieves 4.4 dB receiver sensitivity gain compared to conventional bit and power loading, Levin-Campello (LC), and 1.2 dB receiver sensitivity gain compared to HCEL with EPP at the NDR of 60 Gb/s after 80 km standard single mode fiber transmission, making it a competitive and practical solution for EL in the short-to-medium reach transmission systems.

7.
Comput Biol Med ; 116: 103519, 2019 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-31710870

RESUMO

BACKGROUND: Understanding the biomechanical effects of cervical disc degeneration (CDD) on the cervical spine is fundamental for understanding the mechanisms of spinal disorders and improving clinical treatment. While the biomechanical effects of CDD on segmental flexibility and the posterior facets have been reported, a clear understanding of the effect of the motion loading method on facet joint forces after CDD is still lacking. Therefore, the objective of this study was to determine the effect of the motion loading method on facet joint forces after CDD. METHODS: A three-dimensional nonlinear finite element (FE) model of the cervical spine (C3-C7) was developed and validated to represent normal conditions. This normal model was modified to create six degenerative models simulating mild, moderate, and severe grades of disc degeneration at C5-C6. While under a follower compressive preload (73.6 N), a 1-Nm moment was applied to all models to determine range of motion (ROM). A displacement load was applied to all degenerative models under the same follower load, making the C5-C6 degeneration segment motion same to the ROM of C5-C6 in normal model, and facet joint forces were computed. RESULTS: Compared with the normal model, ROM of the C5-C6 degenerative segments dramatically declined in all postures with increasing degenerative pathologies in the disc. The ROM in the adjacent normal segments of the degenerative segments also declined, with the exception of C4-C5 during extension. Under a 1-Nm moment load, there were not obvious changes in facet joint forces in the C5-C6 degenerative segment with increasing grades of degeneration, but facet joint forces in the adjacent normal segments did increase. Under a displacement load, the facet joint forces of the C5-C6 degenerative segment increased with increasing grades of degeneration. CONCLUSIONS: Facet joint forces were positively correlated with the ROM of the degenerative segment, demonstrating that the motion loading method had a significant effect on facet joint forces after CDD. Loading conditions must be strictly controlled in future finite element analysis studies to improve the comparability between models built by different units.

8.
J Inorg Biochem ; 203: 110909, 2019 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-31689591

RESUMO

Glioma stem cells (GSCs) are thought to be responsible for the recurrence and invasion of glioblastoma multiform (GBM), which have been evaluated and exploited as the therapeutic target for GBM. Cyclometalated iridium(III) complexes have been demonstrated as the potential anticancer agents, however, their antitumor efficacies against GSCs are still unknown. Herein, we investigated the antitumor activity of two cyclometalated iridium(III) complexes [Ir(ppy)2L](PF6) (Ir1) and [Ir(thpy)2L](PF6) (Ir2) (ppy = 2-phenylpyridine, thpy = 2-(2-thienyl)pyridine and L = 4,4'-Bis(hydroxymethyl)-2,2'-bipyridine) against GSCs. The results clearly indicate that Ir1 and Ir2 kill GSCs selectively with IC50 values ranging from 5.26-9.05 µM. Further mechanism research display that Ir1 and Ir2 can suppress the proliferation of GSCs, penetrate into GSCs efficiently, localize to mitochondria, and induce mitochondria-mediated apoptosis, including the loss of mitochondrial membrane (MMP), elevation of intracellular reactive oxygen species (ROS) and caspases activation. Moreover, Ir1 and Ir2 can destroy the GSCs self-renewal and unlimited proliferation capacity by affecting the GSCs colony formation. According our knowledge, this is the first study to investigate the anti-GSCs properties of cyclometalated iridium(III) complexes.

9.
Cancer Sci ; 2019 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-31691433

RESUMO

Capn4, also known as CapnS1, is a member of the calpain family, which plays a crucial role in maintaining the activity and function of calpain. We previously reported that Capn4 also plays an essential role in the migration of nasopharyngeal carcinoma (NPC) cells through regulation of (MMP-2) by nuclear factor-kappa B activation. Epstein-Barr virus latent membrane protein 1 (LMP1) is closely related to the malignant functions of NPC; however, the relationship between LMP1 and Capn4 in NPC remain unclear. Immunohistochemical studies showed that the level of LMP1 and Capn4 expression was high in both primary and metastatic NPC tissues, with a significantly positive correlation. We further found that LMP1 was able to upregulate the Capn4 promoter in a dose-dependent way through the C-terminal activation region (CTAR)1 and CTAR2 domains to activate AP-1. Moreover, we also found that LMP1 activated AP-1 through ERK/JNK phosphorylation. These findings indicate that Capn4 coordination with LMP1 promotes actin rearrangement and, ultimately, cellular migration. These results show that Capn4 coordination with LMP1 enhances NPC migration by increasing actin rearrangement involving ERK/JNK/AP-1 signaling. Therapeutically, additional and more specific LMP1 and Capn4 targeted inhibitors could be exploited to treat NPC.

10.
Artigo em Inglês | MEDLINE | ID: mdl-31702835

RESUMO

In this study, a halotolerant strain was isolated from high salinity leachate and identified as Bacillus cereus NT-3. It can produce a high concentration of polyhydroxyalkanoates (PHAs) with no significant changes when NaCl concentration is up to 50 g/L. FTIR and NMR spectra of PHAs synthesized by Bacillus cereus NT-3 were similar to the standard or previous results. Effluent from acidogenic fermentation of food waste and pure volatile fatty acids (VFAs) mixture was used as carbon source to check the effect of non-VFAs compounds of the effluent on PHAs production. The maximum PHAs production was 0.42 g/L for effluent fermentation, whereas it was 0.34 g/L for pure VFAs fermentation, indicating that bacteria could use actual effluent in a better way. Furthermore, a mathematical model was established for describing kinetic behavior of bacteria using different carbon sources. These results provided a promising approach for PHAs biosynthesis with a low-cost carbon source.

11.
Sci Rep ; 9(1): 17600, 2019 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-31772224

RESUMO

Epidemiological studies have shown that female smokers are at higher risk of chronic obstructive pulmonary disease (COPD). Female patients have worse symptoms and health status and increased risk of exacerbations. We determined the differences in the transcriptome of the airway epithelium between males and females, as well the sex-by-smoking interaction. We processed public gene expression data of human airway epithelium into a discovery cohort of 211 subjects (never smokers n = 68; current smokers n = 143) and two replication cohorts of 104 subjects (21 never, 52 current, and 31 former smokers) and 238 subjects (99 current and 139 former smokers. We analyzed gene differential expression with smoking status, sex, and smoking-by-sex interaction and used network approaches for modules' level analyses. We identified and replicated two differentially expressed modules between the sexes in response to smoking with genes located throughout the autosomes and not restricted to sex chromosomes. The two modules were enriched in autophagy (up-regulated in female smokers) and response to virus and type 1 interferon signaling pathways which were down-regulated in female smokers compared to males. The results offer insights into the molecular mechanisms of the sexually dimorphic effect of smoking, potentially enabling a precision medicine approach to smoking related lung diseases.

12.
Ann Dyslexia ; 2019 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-31773486

RESUMO

The purpose of the present study was to examine the predictive value of a dynamic test of English and French lexical specificity on at-risk reading classification in 13 at-risk and 44 not at-risk emerging English (L1)-French (L2) bilingual Grade 1 children (M = 75.87 months, SD = 3.18) enrolled in an early French immersion program in Canada. Lexical specificity was assessed with a computerized word learning game in which children were taught new English (e.g., "foal" and "sole") and French (e.g., bac "bin" and bague "ring") word pairs contrasted by minimal phonological differences. The results indicated that the dynamic test of lexical specificity in English contributed significantly to the prediction of children's French at-risk reading status at the end of Grade 1 after controlling for French phonological awareness and nonverbal reasoning skills. However, French lexical specificity did not predict children's reading risk classification in French after controlling for French phonological awareness. Thus, it may be feasible to identify at-risk status in emerging bilinguals using dynamic measures in their stronger language.

13.
JAMA Ophthalmol ; 2019 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-31774474

RESUMO

Importance: Progression of retinopathy of prematurity (ROP) to stage 4 may require surgical intervention. The partial retinal detachment of stage 4 ROP may involve the fovea (stage 4B ROP) or may not (stage 4A ROP). This determination has heretofore been based on indirect ophthalmoscopy and documented with color fundus photography. Objective: To investigate optical coherence tomography (OCT) features of eyes with stage 4 ROP and compare them with indirect ophthalmoscopy findings and grading of photographs. Design, Setting, and Participants: In this study, research and clinical medical records of 15 infants with clinically diagnosed stage 4 ROP were retrospectively reviewed. Infants were treated at an academic center from May 2011 to January 2018. Main Outcomes and Measures: Review of OCT images for the presence and foveal involvement of retinoschisis, retinal detachment, and/or vitreomacular traction masked to indirect ophthalmoscopy findings. Results: Of the 15 included infants, 9 (60%) were male, the mean (SD) gestational age at birth was 23.9 (1.1) weeks, and the mean (SD) postmenstrual age at surgery was 42.4 (4.9) weeks. A total of 21 eyes were analyzed, of which 19 had adequate OCT imaging. Optical coherence tomography imaging extended to the retinal midperiphery but did not cover the entire region of possible detachment in each eye. Among these eyes, 7 eyes had peripheral retinoschisis without retinal detachment or foveal involvement, 5 eyes had peripheral retinoschisis and retinal detachment without foveal involvement, 7 eyes had either retinoschisis or retinal detachment involving the fovea, and 2 eyes had poor OCT signal owing to high retinal detachment. Conclusions and Relevance: Handheld OCT imaging is useful in clinical evaluation of stage 4 ROP to determine foveal involvement and differentiate retinal detachment and retinoschisis. Many infants diagnosed as having stage 4A ROP had retinoschisis without OCT evidence of retinal detachment. This group of infants may represent a substage of stage 4A ROP, ie, stage 4A-schisis by OCT. These findings suggest handheld OCT imaging may be useful in the clinical evaluation of stage 4 ROP. Further investigations are needed to determine if this subgroup portends a different prognosis and if this observation should alter future clinical practice.

14.
J Hazard Mater ; : 121685, 2019 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-31776088

RESUMO

Disinfection by-products (DBPs) are generated during chlorination of drinking water. Previous studies demonstrate that DBPs are cytotoxic, genotoxic and associated with an increased risk of human cancer. However, the molecular basis of DBPs-induced toxic effects remains unclear. Here, we chlorinated samples of algal-derived organic matter (AOM) and sediment organic matter (SOM) from a local drinking water reservoir. Chemical properties, toxicities and transcriptomic profiles of human Caco-2 cell exposed to AOM and SOM were compared before and after chlorination. We analyzed chlorination-caused distinct gene expression patterns between AOM and SOM, and identified a set of 22 differentially expressed genes under chlorination of AOM that are different from chlorinated SOM. Consequent network analysis indicates that differential CYP1A1, CYP1B1, ID1 and ID2 are common targets of the upstream regulators predicted in the AOM group, but not the SOM group. Through experimental validation and data integration from previous reports related to DBPs or environmental stressors, we found that CYP1A1 and CYP1B1 are specifically up-regulated after chlorinating AOM. Our study demonstrates that the two CYP1 genes likely act as novel biomarkers of AOM derived DBPs, and this would be helpful for testing drinking water DBPs toxicity and further monitoring drinking water safety.

15.
Mol Carcinog ; 2019 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-31777985

RESUMO

The discovery of epidermal growth factor receptor (EGFR) mutations has made EGFR tyrosine kinase inhibitors (EGFR-TKIs) a milestone in the treatment for advanced non-small cell lung cancer (NSCLC). However, patients lacking EGFR mutations are not sensitive to EGFR-TKI treatment and the emergence of secondary resistance poses new challenges for the targeted therapy of lung cancer. In this study, we identified that the expression of membrane progesterone receptor α (mPRα) was associated with EGFR mutations in lung adenocarcinoma patients and subsequently affected the efficacy of EGFR-TKIs. Progesterone (P4) or its derivative Org OD02-0 (Org), which is mediated by mPRα, increases the function of EGFR-TKIs to suppress the proliferation, migration, and invasion of lung adenocarcinoma cells in vitro and in vivo. In addition, the mPRα pathway triggers delayed resistance to EGFR-TKIs. Mechanistic investigations demonstrated that the mPRα pathway can crosstalk with the EGFR pathway by activating nongenomic effects to inhibit the EGFR-SRC-ERK1/2 pathway, thereby promoting antitumorigenic effects. In conclusion, our data describe an essential role for mPRα in improving sensitivity to EGFR-TKIs, thus rationalizing its potential as a therapeutic target for lung adenocarcinomas.

16.
Sci Total Environ ; 703: 134706, 2019 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-31731156

RESUMO

BACKGROUND: Although the adverse health effects of ambient air pollution are well documented, evidence on the depression effects of household air pollution (HAP) are scarce. OBJECTIVES: We investigated the effects of HAP exposure from the use of solid fuel on depression using a nationally representative dataset of middle-aged and older population in China. METHODS: By employing the propensity score matching method, we first matched the type of household fuel based on background information, including demographic characteristics, lifestyles, health status, and household economic levels. Based on the matched data, we conducted OLS and logistic regressions with cluster standard error at community level to examine the effects of household solid fuel use on depression and adjusted for potential confounders. Heterogeneous effects for vulnerable population were also considered. RESULTS: We found a significantly higher Center for Epidemiologic Studies Depression Scale (CES-D) score and depression risk among current household solid fuel users. After matching and adjusting for potential confounders, current solid fuel users had a higher CES-D score of 0.59 (95% confidence interval [CI]: 0.31, 0.89) than clean fuel users. The OR of depression risk were 1.26 (95% CI: 1.14, 1.41). Solid fuel users had the highest CES-D scores (ß = 0.99, 95% CI: 0.62, 1.36) and depression risk (OR = 1.49, 95% CI: 1.30, 1.73) for over five years. These associations were generally higher in females, participants aged 65 years and older, with a BMI ≥ 25, with low education, with low household economic levels, and those suffer from chronic diseases, including diabetes, chronic lung diseases, and cardiovascular diseases. CONCLUSIONS: Exposure to HAP from solid fuel combustion was linked with strong depression outcomes. Findings suggested a need to strengthen public health efforts, such as controlling the social, health, and economic costs of depression by taking the physical environment, including HAP exposure, into account.

17.
J Mech Behav Biomed Mater ; 103: 103530, 2019 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-31756564

RESUMO

OBJECTIVES: Mechanical complications play a key role in failure of dental implants. Retaining screw loosening was one of the most commonly encountered. This study investigated the effect of PEEK and PTFE coatings on dental implant screw thread joint. METHODS: Retaining screws were coated with PEEK and PTFE in thickness of 30 µm and 60 µm. Friction coefficient and clamping force of screw thread pair were measured, single load-to-fracture (SLF) test and dynamic fatigue life (DFL) test were done to test the stability of implant thread connection. After that, screw fracture mode and erosion morphology of screw surface and implant internal thread were observed. RESULTS: The results showed that both PEEK and PTFE coatings could reduce friction coefficient, and consequently increase clamping force, especially PTFE coatings. PEEK coatings had no significant effect on fracture load, while 30 µm PTFE coating reduced fracture load. PEEK coatings also elongated fatigue life and improved the anti-loosening property under dynamic load, while 30 µm PTFE coating shortened fatigue life. Most of the screw fracture happened at the first thread of the retaining screws. The fracture-end of PEEK coated screws were loosed and could easily remove, but fracture-end of PTFE screws could not. Internal thread observation showed that both PEEK and PTFE coatings could reduce wear of implant internal thread. CONCLUSION: PEEK coatings could effectively improve the stability of implant threaded connection, and reduce wear of implant internal thread. PEEK coating may be a suitable way to prevent screw loosening.

18.
J Med Chem ; 2019 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-31774672

RESUMO

The importance of upregulated Wnt signaling in colorectal cancers led to efforts to develop inhibitors that target ß-catenin in this pathway. We now report that several "Wnt inhibitors" that allegedly target ß-catenin actually function as mitochondrial proton uncouplers that independently activate AMPK and concomitantly inhibit Wnt signaling. As expected for a process in which mitochondrial uncoupling diminishes ATP production, a mitochondrial proton uncoupler, FCCP, and a glucose metabolic inhibitor, 2-DG, activated AMPK and inhibited Wnt signaling. Also consistent with these findings, a well-known "Wnt inhibitor", FH535, functioned as a proton uncoupler, and in support of this finding, the N-methylated analog, 2,5-dichloro-N-methyl-N-(2-methyl-4-nitrophenyl)benzenesulfonamide (FH535-M) was inactive as an uncoupler and Wnt inhibitor. Apart from suggesting an opportunity to develop dual Wnt inhibitors and AMPK activators, these findings provide a cautionary tale that claims for Wnt inhibition alone require scrutiny as possible mitochondrial proton uncouplers or inhibitors of the electron transport chain.

19.
Inflamm Bowel Dis ; 2019 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-31750910

RESUMO

BACKGROUND: Interleukin (IL)-6/signal transducers and activators of transcription 3 (STAT3) signaling plays an important role in the development of colitis-associated colorectal cancer (CAC). The mechanism of CAC formation remains unclear, and the relationship between miRNAs and the IL-6/STAT3 signaling pathway in the development of CAC is not well understood. In this study, we investigated the relationship between miR-29a-5p and the IL-6/STAT3 signaling pathway in the development of CAC and alterations in 10-11 translocations (TETs) regulated by this network. METHODS: miR-29a-5p was screened in a CAC mouse model by high-throughput microarray analysis and investigated in human colorectal cancer tissue samples and colon cell lines by quantitative reverse transcription polymerase chain reaction (Q-RTPCR). The expression of miR-29a and TETs was detected by Q-RTPCR, and the expression of STAT3/P-STAT3 and TET3 was detected via Western blot assay. The expression of TET1 and 5-hydroxymethylcytosine (5hmC) was detected through immunofluorescence. RESULTS: Our results showed that miR-29a-5p was significantly upregulated and was accompanied by STAT3 activation in the colon tissues of CAC mouse and human colorectal cancer tissues, as compared with normal colon tissues. In contrast, the levels of TETs and 5hmC were decreased. In vitro, overexpression of miR-29a-5p in colonic cell lines (HCT-116 and IEC-6) and RAW264.7 cells increased STAT3 expression, but decreased that of TET3, TET1, and 5hmC. miR-29a-5p downregulation in HCT-116 and IEC-6 cell lines could rescue the expression of STAT3 and TET3. Notably, STAT3 activation induced by IL-6 upregulated miR-29a-5p expression and reduced TET expression in vitro, although STAT3 inhibitor treatment downregulated miR-29a-5p expression, which was induced by IL-6. CONCLUSIONS: Our studies showed that tumor development occurred with inflammation. The miR-29a-5p/STAT3 signaling axis could play an important role in the development of CAC, and the miR-29a-5p/STAT3 positive feedback loop may amplify the effects of inflammation, lead to decreased levels of TET and 5hmC, and eventually lead to the development of CAC.

20.
BMC Genomics ; 20(1): 856, 2019 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-31726968

RESUMO

BACKGROUND: Non-coding RNAs (ncRNAs), including microRNAs (miRNAs), long ncRNAs (lncRNAs) and circular RNAs (circRNAs), accomplish remarkable variety of biological functions. However, the composition of ncRNAs and their interactions with coding RNAs in modulating and controlling of cellular process in plants is largely unknown. Using a diverse group of high-throughput sequencing strategies, the mRNA, miRNA, lncRNA and circRNA compositions of tobacco (Nicotiana tabacum) roots determined and their alteration and potential biological functions in response to topping treatment analyzed. RESULTS: A total of 688 miRNAs, 7423 non-redundant lncRNAs and 12,414 circRNAs were identified, among which, some selected differentially expressed RNAs were verified by quantitative real-time PCR. Using the differentially expressed RNAs, a co-expression network was established that included all four types of RNAs. The number of circRNAs identified were higher than that of miRNAs and lncRNAs, but only two circRNAs were present in the co-expression network. LncRNAs appear to be the most active ncRNAs based on their numbers presented in the co-expression network, but none of them seems to be an eTM (endogenous Target Mimicry) of miRNAs. Integrated with analyses of sequence interaction, several mRNA-circRNA-miRNA interaction networks with a potential role in the regulation of nicotine biosynthesis were uncovered, including a QS-circQS-miR6024 interaction network. In this network miR6024 was significantly down-regulated, while the expression levels of its two targets, circQS and its host gene QS, were sharply increased following the topping treatment. CONCLUSIONS: These results illustrated the transcriptomic profiles of tobacco roots, the organ responsible for nicotine biosynthesis. mRNAs always play the most important roles, while ncRNAs are also expressed extensively for topping treatment response, especially circRNAs are the most activated in the ncRNA pool. These studies also provided insights on the coordinated regulation module of coding and non-coding RNAs in a single plant biological sample. The findings reported here indicate that ncRNAs appear to form interaction complex for the regulation of stress response forming regulation networks with transcripts involved in nicotine biosynthesis in tobacco.

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